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Mechanism of action and research progress of vaccine adjuvants ZHANG Li, LU Chang, AN Minghui, WANG Mengmeng, ZONG Xiaoyu, YU Lin, RAN Zhuo-ling, SONG Jing, LI Huijie, GONG Jian Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (7): 785-791.   DOI: 10.12092/j.issn.1009-2501.2024.07.008 Abstract （485）      PDF （831KB）（1114）       Knowledge map    Save Vaccines are among the most effective measures for preventing infectious diseases and play a crucial role in controlling the spread of these diseases. Adjuvants, serving as auxiliary components in vaccines, are indispensable in the vaccine development process. Ideal adjuvants not only enhance the immune response, enabling the body to achieve optimal protective immunity but also play important roles in reducing the dosage of immunogens and lowering vaccine production costs. To meet the demands of novel vaccines, many new types of adjuvants have been developed. However, there is still a lack of adjuvants that are safe, effective, easy to prepare, highly pure, and suitable for a variety of vaccines in clinical settings. This article categorizes adjuvants and summarizes their mechanisms of action and characteristics, focusing on traditional aluminum salt adjuvants and more modern lipid-based and nucleic acid-based adjuvants. The summary is based on a computer search of databases including PubMed, Embase, The Cochrane Library, CNKI (China National Knowledge Infrastructure), VIP Database, and Wanfang Database, using English search keywords such as Adjuvants, Vaccine, Vaccine Adjuvant, aluminum salts, MF59, AS03, Toll-like receptor agonist, etc., and corresponding Chinese search terms. The aim is to provide references for the development and application of adjuvants. Related Articles | Metrics

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Progress in the clinical application of the biased μ-opioid agonist oliceridine ZHU Changmao, XIE Li, WU Zifeng, WANG Sen, ZHANG Qi, XU Xiangqing, YANG Chun Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (9): 1057-1061.   DOI: 10.12092/j.issn.1009-2501.2024.09.012 Abstract （430）      PDF （596KB）（849）       Knowledge map    Save Opioid receptors μOR, δOR, κOR and NOPR are all G protein-coupled receptors (GPCRs), which mainly function through G protein and β-arrestin. Recent studies have found that G protein mediates analgesia, while β-arrestin reduces analgesia and is related to the side effects of opioids. Oliceridine is the first biased μOR agonist approved for commerce. It mainly exerts analgesic effect by activating G protein. It has rapid onset of action and reliable analgesic effect. Due to its low activity on β-arrestin, the incidence of side effects is low, comparing to the classic opioid morphine. Oliceridine can be safely used in patients with liver or kidney insufficiency and its metabolite is inactive. This article summarizes the current progress of pharmacological research and clinical application of oliceridine, aiming to provide reference for the clinical practice of oliceridine. Related Articles | Metrics

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Expert consensus on the diagnosis and treatment of insomnia in specified populations CHEN Guihai, DENG Liying, DU Yijie, HUANG Zhili, JIANG Fan, JIN Furui, LI Yanpeng, LIU Chunfeng, PAN Jiyang, PENG Yanhui, SU Changjun, TANG Jiyou, WANG Tao, WANG Zan, WU Huijuan, XUE Rong, YANG Yuechang, YU Fengchun, YU Huan, ZHAN Shuqin, ZHANG Hongju, ZHANG Lin, ZHAO Zhengqing, ZHAO Zhongxin Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 841-852.   DOI: 10.12092/j.issn.1009-2501.2024.08.001 Abstract （425）      PDF （795KB）（651）       Knowledge map    Save Clinicians need to focus on various points in the diagnosis and treatment of insomnia. This article prescribed the treatment protocol based on the unique features, such as insomnia in the elderly, women experiencing specific physiological periods, children insomnia, insomnia in sleep-breathing disorder patients, insomnia in patients with chronic liver and kidney dysfunction. It provides some reference for clinicians while they make decision on diagnosis, differentiation and treatment methods. Related Articles | Metrics

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Progress on anti-tumor mechanisms of Ganoderma lucidum active ingredients LV Yujiao, ZHOU Shuting, WANG Lina, SHEN Mingmei, LIU Yongchao Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 947-954.   DOI: 10.12092/j.issn.1009-2501.2024.08.012 Abstract （397）      PDF （712KB）（989）       Knowledge map    Save Malignant tumors are one of the main causes of death from chronic diseases in China, and their incidence and mortality rates show an increasing trend year by year. Advanced non-surgical treatment of malignant tumors is an important means of improving patients' prognosis and enhancing their quality of life. The traditional Chinese medicine Ganoderma lucidum has anti-tumor effects and plays a role in the treatment of many malignant tumors. In this paper, a systematic review of the effects of Ganoderma lucidum active ingredients on tumors has been conducted at home and abroad in the past five years to explore the anti-tumor mechanism of Ganoderma lucidum active ingredients and to lay a theoretical foundation for the application of Ganoderma lucidum active ingredients in clinical practice. Related Articles | Metrics

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Application of single-cell multi-omics sequencing technology in the study of ischemic stroke MENG Qian, WANG Yiwen, CUI Na, BAI Min, YANG Le, DING Yi Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (6): 690-699.   DOI: 10.12092/j.issn.1009-2501.2024.06.011 Abstract （353）      PDF （810KB）（708）       Knowledge map    Save Ischemic stroke is an acute cerebrovascular disease with high disability and mortality, is the most common cause of death in China. Despite years of research, there are still no biomarkers for stroke, and the molecular mechanisms remain largely unknown. In the past decade, single-cell sequencing technology, as a rapidly developing emerging technology, can conduct high-throughput sequencing of multiple omics including genome, transcriptome, epigenome and proteome at the level of a single cell, providing a new way to discover biomarkers and analyze pathological mechanisms. In this paper, the progress of single-cell multi-omics sequencing technology and its application in the discovery of biomarkers, pathological mechanisms and drug development of ischemic stroke are introduced in detail, in order to provide valuable reference for precision medicine of ischemic stroke. Related Articles | Metrics

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Analysis of clinical characteristics of tramadol induced hypoglycemia LIU Wei, HE Qin, HE Yiran Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (7): 819-825.   DOI: 10.12092/j.issn.1009-2501.2024.07.012 Abstract （327）      PDF （556KB）（193）       Knowledge map    Save AIM: To investigate the clinical characteristics of tramadol-induced hypoglycemia. METHODS: Case reports of tramadol-induced hypoglycemia were collected by searching Chinese and English data from the database establishment to April 28, 2023. RESULTS: Twenty patients were included, with a median age of 50 years (4, 88). Hypoglycemia occurred 1 h-23 d after tramadol administration, with a median blood glucose of 2.25 mmol/L  (0.22, 3.3) and a median daily dose of 300 mg (1.53, 14 000). The main clinical manifestations were unconscious (12 cases), multiple organ failure (7 cases), asystole and/or apnea (7 cases), seizures (4 cases), somnolence (3 cases) and sweating (3 cases).Tramadol concentrations were reported in 6 patients, with a median of 3.56 mg/L (0.47, 9.4). After stopping tramadol in 20 patients and giving symptomatic supportive treatment, 16 patients recovered, 1 patient had moderate brain dysfunction, and 3 patients died. CONCLUSION: Tramadol induced hypoglycemia can occur from 1 h to 23 d after administration, and can be clinically manifested as autonomic nervous system symptoms and neurohypoglycemia symptoms, mainly neurohypoglycemia symptoms. After stopping tramadol, most patients with hypoglycemia returned to normal, and severe patients can die. Related Articles | Metrics

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Can adalimumab biosimilars be clinically interchanged: evidence based on a systematic review and Meta-analysis HU Yang, SONG Zaiwei, GAO Yuan, RAN Yiwen, JIANG Dan, ZHAO Rongsheng Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (7): 722-734.   DOI: 10.12092/j.issn.1009-2501.2024.07.001 Abstract （325）      PDF （1571KB）（241）       Knowledge map    Save AIM: To systematically evaluate the clinical interchangeability of adalimumab biosimilars in terms of efficacy, safety, and immunogenicity, and to provide evidence-based reference for clinical interchangeability. METHODS: Randomized Controlled Trials (RCTs) on the interchangeability of adalimumab biosimilars were systematically searched in PubMed, Embase, Cochrane Library, CNKI, WANFANG and SinoMed from inceptions to October 2023. Data were extracted from the literature that met the inclusion criteria, risk of bias was assessed using the Cochrane Handbook for Systematic Reviews of Interventions 5.0 bias risk assessment tool. Meta-analysis was performed using Revman 5.4 software. The certainty of evidence was graded using the GRADE tool recommended by the Cochrane Collaboration. This study was conducted according to the PRISMA guideline. RESULTS: Eighteen studies were included, with 7 focusing on psoriasis and 11 on rheumatoid arthritis. Regarding efficacy, for psoriasis, there were no statistical differences in PASI 75 response rates and sPGA scores of ≤1 after 1-4 switches between biosimilars and the reference drug (P>0.05, moderate-quality evidence). For rheumatoid arthritis, there were no statistical differences in ACR 20/50/70 response rates after 1-3 switches (P>0.05, moderate-quality evidence). Regarding safety, there were no statistical differences in the risk of adverse events after single or multiple switches for both diseases (P>0.05, moderate-quality evidence). Regarding immunogenicity, there were no statistical differences in the rate of anti-drug antibody production after single or multiple switches (P>0.05, moderate-quality evidence). High-quality evidence is still lacking for the interchangeability of adalimumab biosimilars in other indications.CONCLUSION:The switches between adalimumab biosimilars and the reference drug have no significant impact on clinical efficacy, safety and immunogenicity for psoriasis and rheumatoid arthritis patients. Related Articles | Metrics

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Research progress on material basis and mechanism of Hedyotis Diffusa-Scutellaria Barbata Herb Pair in the treatment of gastric cancer ZHANG Xiaowei, WANG Nan, DAI Mengge, LIU Ruijuan, MA Ting Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (7): 831-840.   DOI: 10.12092/j.issn.1009-2501.2024.07.014 Abstract （312）      PDF （1074KB）（376）       Knowledge map    Save Gastric cancer is one of the most common malignant tumors in the digestive system, which often occurs in middle-aged and elderly people. Traditional Chinese medicine recognizes gastric cancer as a kind of tumor characterized by fluid deficiency, heat accumulation and the growing binding of toxins in the stomach. It is commonly treated with heat-clearing and detoxifying drugs in clinical practice. Hedyotis diffusa-Scutellaria barbata herb pair (HS) has the effects of clearing heat and detoxifying, promoting blood circulation, resolving carbuncle and expulsing boil, anti-inflammatory and analgesic, which are consistent with the etiology and pathogenesis of gastric cancer, therefore, it can be used for the treatment of gastric cancer. Modern pharmacological researches have confirmed that HS can play an anti-gastric cancer role by inducing cell apoptosis, inhibiting cell proliferation, inhibiting angiogenesis, improving immune microenvironment and down-regulating telomerase activity. Herein, this review summarizes the active ingredients and related mechanism responsible for the anti-gastric cancer effect of HS, which will provide the theoretical basis for its clinical use and the development of new drugs against gastric cancers. Related Articles | Metrics

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A novel antibody-drug conjugate: disitamab vedotin YIN Xiaoyu, LU Ming, YU Zefang, PANG Guoxun Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (11): 1315-1320.   DOI: 10.12092/j.issn.1009-2501.2024.11.015 Abstract （306）      PDF （673KB）（396）       Knowledge map    Save Antibody drug conjugates (ADCs) are a new class of anti-tumor drugs in which linkers in the structure link cytotoxic drugs to monoclonal antibodies and release cytotoxic drugs to tumors. Disitamab vedotin (RC48) is a new antibody-drug conjugate independently developed in China. It targets the HER2 protein on the surface of tumors, it has both antibody targeting and small molecule drug killing, and can accurately recognize and kill tumor cells. Compared with traditional HER2-targeted drugs, disitamab vedotin has a wider therapeutic window and less toxicity to normal tissues. Currently, disitamab vedotin for injection has been approved by the National Medical Products Administration (NMPA) for use in patients with HER2 overexpression (HER2 immunohistochemical results of 2+ or 3+) who have locally advanced or metastatic gastric cancer (including gastroesophageal junction adenocarcinoma) and have received at least two types of systemic chemotherapy. Additionally, it is indicated for patients with locally advanced or metastatic urothelial carcinoma who have previously undergone platinum-containing chemotherapy and exhibit HER2 overexpression, specifically 2+ or 3+ immunohistochemical results. In this paper, we will review the structural characteristics, mechanism of action and clinical trials of disitamab vedotin and look forward to the clinical application prospects of this drug. Related Articles | Metrics

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Research progresses of nonsense-mediated mRNA decay in tumorigenesis and cancer therapy WANG Yuhui, WANG Jingpeng, CHEN Bei, WANG Yaru, LI Tangliang Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 930-936.   DOI: 10.12092/j.issn.1009-2501.2024.08.010 Abstract （297）      PDF （815KB）（359）       Knowledge map    Save Nonsense-mediated mRNA decay (NMD) is a highly conserved post-transcriptional regulatory mechanism in eukaryotic cells. NMD can recognize and degrade abnormal transcripts containing premature termination codons (PTC) to prevent the translation of C-terminal truncated proteins. Furthermore, NMD could degrade a subset of normal gene transcripts and thus fine-tune gene expression. NMD is essential for cell fate determination, stress response, as well as animal development. In this review, we briefly discussed the functional and molecular mechanisms of NMD pathway activation and inhibition in tumorigenesis, cancer progression and therapy. Current studies indicate that NMD factor mutations can lead to a variety of human tumors. Interestingly, inhibition of NMD factors can activate DNA damage response and inhibit the expression of oncogenic factors, thereby killing cancer cells. This review may provide new perspectives for the biological mechanism and therapeutic strategy of human tumors. Related Articles | Metrics

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Research progress on targeted therapy combined with immune-activating strategies in CLDN18.2-positive gastric cancer NIE Yang, WANG Yue, WEI Jia Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (2): 146-158.   DOI: 10.12092/j.issn.1009-2501.2025.02.001 Abstract （290）      PDF （1213KB）（176）       Knowledge map    Save Claudin 18 isoform 2 (Claudin18.2, CLDN18.2) is a crucial structural protein involved in cell-cell tight junctions. While its expression is limited in normal tissues, it is specifically overexpressed in malignant tumors such as gastric cancer, pancreatic cancer, and esophageal cancer, making it a promising therapeutic target for cancer treatment. Recent advances in CLDN18.2-targeted therapies have been encouraging, and studies suggest that CLDN18.2-positive gastric cancer may possess a unique immune microenvironment. This raises the potential for combining targeted therapies with immune activation to achieve synergistic effects, potentially improving treatment outcomes for patients with advanced gastric cancer. This review will focus on the immune microenvironment characteristics of CLDN18.2-positive gastric cancer and summarize the current research and clinical trial progress in targeted therapies combined with immune activation for this specific cancer type. Related Articles | Metrics

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Analysis of hyperglycaemia adverse drug reactions of PCSK9 inhibitors and statins based on FAERS database Analysis of hyperglycaemia adverse drug reactions of PCSK inhibitors and statins based on FAERS database Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (7): 762-767.   DOI: 10.12092/j.issn.1009-2501.2024.07.005 Abstract （289）      PDF （554KB）（200）       Knowledge map    Save AIM: To compare the risk of hyperglycaemia with PCSK9 inhibitors versus statins, based on U.S. Food and Drug Administration Adverse Events Reporting System (FAERS). METHODS: The hyperglycaemia reports induced by "alirocumab", "evolocumab", "atorvastatin" and "rosuvastatin" were utilized as the first suspected drugs from the database of FAERS from 2016 to the third quarter of 2023. The report odd ratio (ROR) method was employed. RESULTS: Based on the FAERS database, the ROR (95% CI) for hyperglycaemia due to Alirocumab versus Atorvastatin and Rosuvastatin were 0.628(0.545, 0.724) and 0.307 (0.263, 0.357) , the ROR (95% CI) for hyperglycaemia due to Evolocumab were 0.817 (0.750, 0.889) and 0.399 (0.361, 0.441) , all generated no adverse reaction signals. The ROR (95% CI) for hyperglycaemia due to Alirocumab and Evolocumab versus all other drugs in FAERS were 1.488(1.315,1.682) and 1.934(1.845, 2.027), all generated adverse reaction signals, respectively. CONCLUSION: Based on the FAERS database, PCSK9 inhibitors have a lower risk of hyperglycemia than statins and deserve clinical attention. Related Articles | Metrics

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Low-dose rituximab improves progression in early-stage medium-to-high-risk membranous nephropathy: an exploratory study XU Qiuyu, AI Sanxi, WANG Gangan, JIA Chunyu, WANG Jiahui, ZHENG Ke, QIN Yan, CHEN Gang, LI Xuemei Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (7): 744-751.   DOI: 10.12092/j.issn.1009-2501.2024.07.003 Abstract （276）      PDF （1117KB）（152）       Knowledge map    Save Membranous nephropathy (MN) is the predominant cause of primary nephrotic syndrome (NS) among adults. The identification of PLA2R as target antigen has brought about a profound transformation in the management of MN, offering a basis for the utilization of B-cell depleting agents such as rituximab (RTX). The question of whether early intervention targeting antibodies can effectively impede the progression of MN, contributing to enhanced disease control and long-term renal outcomes for patients, remains further exploration. We analyzed demographic data, laboratory parameters, and renal involvement in 13 patients with PLA2R antibody-related MN who received at least one RTX treatment at our center from October 2019 to March 2023. Early-stage medium-to-high-risk MN was defined as baseline or admission anti-PLA2R antibody levels exceeding 50 RU/mL, excluding patients who already presented with nephrotic syndrome at baseline. The median duration of MN at the initiation of the first RTX treatment was 4.1 months (IQR 1-7.7), and the median follow-up time after RTX therapy was 27 months (IQR 23-45). All patients had commenced renin-angiotensin system inhibitors before receiving RTX. Following RTX therapy, none of the 13 patients progressed to NS during the follow-up period, and 12 patients achieved complete or partial remission at the 2-year follow-up or the last visit. No deaths, severe infections, or other serious adverse reactions occurred during the follow-up period. In conclusion, RTX demonstrates favorable efficacy and safety in early-stage, medium-to-high-risk MN patients. Initiating antibody clearance therapy in these patients may be beneficial for long-term disease control and distant renal outcomes. Related Articles | Metrics

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Advances in clinical research of CAR-T immunotherapy for systemic rheumatic diseases LI Zhi, ZHANG Mengying, ZHU Chuanmiao, MAO Li, PENG Hui Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 937-946.   DOI: 10.12092/j.issn.1009-2501.2024.08.011 Abstract （275）      PDF （743KB）（398）       Knowledge map    Save Systemic rheumatic disease is a kind of autoimmune disease which is caused by the dysfunction of autoimmune cells and the damage of multiple systems and organs. Traditional immunosuppressants play an important role in the treatment of systemic rheumatic diseases, but there are still a considerable number of refractory systemic rheumatic diseases that do not respond well to traditional immunosuppressant therapy, and new therapeutic methods need to be explored. Chimeric antigen receptor T cell therapy (CAR-T) immunotherapy was initially used for the treatment of malignant hematological diseases and has shown good efficacy. Recently,CAR-T immunotherapy has also achieved remarkable efficacy in refractory systemic lupus erythematosus. It brings new hope for the treatment of systemic rheumatic diseases. This article summarizes the progress of clinical application of CAR-T immunotherapy in systemic rheumatic diseases in recent years, aiming to enhance clinicians' cognition of CAR-T immunotherapy and promote the further development of CAR-T immunotherapy in systemic rheumatic diseases. Related Articles | Metrics

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Umbrella review of the efficacy and safety of monoclonal antibodies in the treatment of thyroid-associated ophthalmopathy LIU Shuang, JIANG Hanchun, WU Jingjing, ZHAO Rongsheng Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (7): 735-743.   DOI: 10.12092/j.issn.1009-2501.2024.07.002 Abstract （274）      PDF （623KB）（252）       Knowledge map    Save AIM：To comprehensively evaluate the efficacy and safety of rituximab (RTX), tocilizumab (TCZ), and teprotumumab (TMB) in the treatment of thyroid-associated ophthalmopathy (TAO). METHODS: A systematic search was conducted in PubMed, Embase and Cochrane Library databases for systematic reviews/meta-analyses on TAO treatment, with the search time limited to January 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, Assessment of Multiple Systematic Reviews (AMSTAR) 2 tool, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) were used to assess the reporting quality, methodological quality, and evidence quality of the included studies. RESULTS: The current systematic reviews on the three monoclonal antibodies in TAO treatment exhibited deficiencies in reporting quality, methodological quality, and evidence quality. Direct comparative evidence between the three monoclonal antibodies is still lacking. Based on indirect comparative evidence, TCZ appears to be the most promising treatment option, followed by TMB and RTX. In terms of efficacy, TCZ and TMB significantly reduced the Clinical Activity Score (CAS), proptosis, and improved quality of life. TCZ also significantly reduced the incidence of diplopia. RTX significantly reduced disease response, while RTX and TCZ both significantly improved disease inactivation rates. RTX showed no significant difference in diplopia, lid fissure changes, NOSPECS score and quality of life. The conclusions regarding safety are inconsistent, with TCZ and TMB potentially increasing the incidence of adverse events, while RTX showed no significant difference in safety compared to glucocorticoids or placebo.CONCLUSION: This study provides evidence-based insights for the selection of three monoclonal antibodies in the treatment of TAO. While TCZ may have advantages in efficacy, considering the limitations of existing evidence, more high-quality studies are needed to further verify and compare the efficacy and safety of different monoclonal antibodies in TAO treatment. Related Articles | Metrics

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Lymphoma risk in the treatment of Crohn's disease with four biological agents: a real world analysis of post-marketing surveillance data  SONG Yao, PAN Chen, ZHAO Xiaohong, YANG Hongge, LI Ze, CUI Xiangli Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (7): 768-774.   DOI: 10.12092/j.issn.1009-2501.2024.07.006 Abstract （272）      PDF （626KB）（121）       Knowledge map    Save AIM：To determine the link between infliximab, adalimumab, vedolizumab, ustekinumab and risk of lymphoma in order to provide reference for the safety of clinical application. METHODS: Disproportionality analysis and Bayesian analysis were used in data mining to screen the suspected lymphoma after the use of four biological agents based on the FAERS data from October 2012 to June 2023. The fatality and hospitalization rates of this four biological agents associated lymphoma were also investigated. RESULTS: Totally 705 cases of four biological agents associated lymphoma were collected. Four biological agents associated lymphoma appeared to influent more young patients and middle-aged patients than elderly patients (25.11% vs. 22.41% vs. 12.2%). There were slightly more male than females (42.84% vs. 35.60%). Infliximab has the highest reporting odds ratio ［ROR3.40, 95%CI=(3.03, 3.82)］, proportional ratio ［PRR3.38, 95%CI=(3.01, 3.79)］, information component (IC1.14, IC-2SD=1.02) and empirical Bayes geometric mean (EBGM2.21, EBGM05=2.01). Significant difference in the fatality rate and hospitalization rate among four biological agents were not found. CONCLUSION: Infliximab showed a strongest lymphoma association than the other three biological agents. Lymphoma risk should be vigilant when using infliximab. Related Articles | Metrics

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A rapid health technology assessment of camrelizumab in combination with chemotherapy for the first-line treatment of locally advanced/metastatic non-small cell lung cancer CUI Yanjun, MA Tian, LIU Yi, JIAO Ling, CHAI Aijun, FAN Rongrong, LIU Yanguo, LUO Xing-xian, HUANG Lin, ZHANG Xiaohong Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (7): 775-784.   DOI: 10.12092/j.issn.1009-2501.2024.07.007 Abstract （265）      PDF （710KB）（174）       Knowledge map    Save AIM: To evaluate the efficacy, safety, and economy of camrelizumab (CAM) combined with platinum-containing chemotherapy (CT) for the first-line treatment of locally advanced/metastatic non-small cell lung cancer (NSCLC). METHODS: Chinese and English databases such as Pubmed, the Cochrane Library, China Knowledge Network, Wanfang Data, and other related websites were systematically searched. After literature screening, quality assessment, and data extraction of the literature according to the inclusion and exclusion criteria, two researchers conducted a rapid health technology assessment (HTA). RESULTS: A total of 7 systematic evaluations/Meta-analyses and 17 economics evaluations were included. In terms of effectiveness, compared to docetaxel chemotherapy, CAM + CT significantly prolonged the overall survival (OS), progression-free survival (PFS), and improved the objective remission rate (ORR) of mutation-negative patients with locally advanced/metastatic NSCLC. Compared with CT and pembrolizumab (PEM), CAM + CT significantly prolonged the PFS, and improved the ORR of mutation-negative patients with locally advanced/metastatic NSCLC. Subgroup analysis showed that CAM + CT significantly prolonged PFS in patients with PD-L1 ≥ 1% and PD-L1 ≥ 50% compared with CT. Compared with CT, CAM + CT significantly prolonged the OS and PFS of mutation-negative patients with locally advanced/metastatic squamous NSCLC. Compared with sintilimab (SIN), CAM + CT significantly prolonged the PFS of mutation-negative patients with locally advanced/metastatic squamous NSCLC. Subgroup analysis showed that CAM + CT significantly prolonged OS in patients with PD-L1 <1% compared with CT. In terms of safety, CAM + CT was comparable in terms of the occurrence of all grades of adverse events, but the incidence of grade 3 or higher treatment-related adverse events was significantly increased compared with CT and PEM for mutation-negative locally advanced/metastatic NSCLC patients. CAM + CT was significantly increased the occurrence of all grades of adverse events compared with CT, but was comparable in terms of the occurrence of grade 3 or higher treatment-related adverse events. In terms of economy, CAM + CT has a cost-effectiveness advantage over CT for patients with mutation-negative advanced/metastatic squamous NSCLC. CAM + CT has a cost-effectiveness advantage over CT and PEM + CT; and CAM + CT does not have a cost-effectiveness advantage over SIN + CT for patients with mutation-negative locally advanced/metastatic non-squamous NSCLC. CONCLUSION: CAM + CT has good efficacy and cost-effectiveness for the first-line treatment of locally advanced/metastatic NSCLC, and the safety aspect is compared with CT, PEM or slightly worse. Related Articles | Metrics

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Current clinical application and research progress of antiplatelet drugs PAN Guanxing, HUANG Pinfang, CHAI Dajun, ZHANG Jing Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (1): 91-99.   DOI: 10.12092/j.issn.1009-2501.2025.01.011 Abstract （258）      PDF （934KB）（204）       Knowledge map    Save Arterial thrombosis is a major cause of death in several cardiovascular diseases (CVDs), including coronary heart disease and stroke. Since platelets play a pivotal role in arterial thrombosis, antiplatelet drug is an important part of the clinical therapy of CVD patients. Currently, the long-term antithrombotic effect of the dual antiplatelet therapy of P2Y12 antagonists combined with aspirin are showed to be effective. And αΙIbβ3 antagonists represented by tirofiban are widely used for antiplatelet therapy in emergency surgery. However, the bleeding risk caused by antiplatelet therapy is a clinical issue that cannot be ignored. In order to provide a reference for further research on antiplatelet drugs, this article reviews the major targets of antiplatelet drugs and the drugs that have been under clinical research in recent years. Related Articles | Metrics

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Research progress in clinical trials of new drugs and candidate drugs for type 2 diabetes mellitus ZHOU Xin, WANG Zhi, DU Wenyu, LIU Zihan, LI Ying, DONG Zhanjun Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (10): 1185-1193.   DOI: 10.12092/j.issn.1009-2501.2024.10.012 Abstract （252）      PDF （641KB）（328）       Knowledge map    Save A number of drugs for the treatment of type 2 diabetes mellitus (T2DM) are currently under clinical investigation, including the sodium-dependent glucose transporters 2 (SGLT2) inhibitor rongliflozin, the SGLT1/2 inhibitor LIK066, the dipeptidyl peptidase-4 (DPP-4) inhibitor DBPR108, the glucagon-likepeptide-1 receptor (GLP-1R) agonist CJC-1134-PC, the G-protein-coupled receptor 40 (GRP40) agonist SCO-267 and the Glucokinase (GK) agonist PB201. This article briefly reviews the clinical research progress of drugs targeting the above targets in the field of T2DM treatment, in order to provide reference for the treatment of T2DM patients. Related Articles | Metrics

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Research progress of molecular docking in screening anti-cervical cancer drugs WANG Dan, ZHANG Wenyan, LUO Renjie, CHEN Yuanjing, HAN Xue, QU Bo, FENG Shifang, NIE Xiazi, LIU Huiling Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 955-960.   DOI: 10.12092/j.issn.1009-2501.2024.08.018 Abstract （251）      PDF （568KB）（402）       Knowledge map    Save Cervical cancer is one of the most common gynecological malignant tumors,the five-year survival rate decreased significantly in the case of lymph node metastasis and distant metastasis,so the development of new anti-cervical cancer drugs is of great significance for the treatment of cervical cancer.Molecular docking technology is one of the most commonly used research methods in computer aided drug design,which is widely used in screening the effective components of drugs, finding the targets of drugs acting on tumors and exploring the mechanism of antineoplastic drugs. This paper reviews the molecular docking technology in the screening of anti-cervical cancer drugs,the determination of anti-tumor targets and the mechanism of anti-cervical cancer,in order to provide more sufficient theoretical basis for the screening of anti-cervical cancer drugs and new drug research and development. Related Articles | Metrics

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Advances of VEGF signalling pathway in hepatocellular carcinomar invasion and metastasis and therapy LAN Xueling, HUANG Yanni, ZHU Minmin, MA Ping, DONG Min Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (6): 707-714.   DOI: 10.12092/j.issn.1009-2501.2024.05.013 Abstract （250）      PDF （664KB）（616）       Knowledge map    Save The development of hepatocellular carcinoma (HCC) is closely related to the formation of tumour blood vessels. VEGF-mediated angiogenesis is a major driver of the immune escape response in tumours. VEGF binds to vascular endothelial growth factor receptor2 (VEGFR2) on endothelial cells, promoting endothelial cell proliferation and migration, inducing vascular changes in HCC, and thus promote the growth of hepatocellular carcinoma cells. Anti-VEGF and its receptor-targeted molecular drugs are currently effective new treatments for HCC. Monoclonal antibodies against VEGF and small-molecule tyrosine kinase inhibitors targeting VEGF have been shown to block its angiogenic activity, alleviate the inhibitory effect of the tumour microenvironment, and ultimately achieve tumour regression. This article provides a review of the research progress of VEGF/VEGFR inhibitors in HCC treatment. Related Articles | Metrics

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Analysis of the efficacy and influencing factors after the First 131I treatment after surgery for differentiated thyroid cancer TAO Shaoneng, GE Junliang, YANG Jiwen, CHEN Xiaolei, YIN Weili, WANG Yingying, LIU Xiaocen Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (12): 1435-1440.   DOI: 10.12092/j.issn.1009-2501.2024.12.014 Abstract （244）      PDF （718KB）（54）       Knowledge map    Save AIM: To explore the therapeutic efficacy and influencing factors of differentiated thyroid cancer (DTC) after the first postoperative 131I treatment. METHODS: We retrospectively analyzed the clinical data of 116 DTC patients treated with 131I　for the first time after thyroid cancer surgery in the Department of Nuclear Medicine of the First Affiliated Hospital of Wannan Medical College, analysed their therapeutic efficacy, and Univariate and multivariate Logistic analyses were performed for the factors that may affect the efficacy of the treatment, respectively, and established ROC curves to analyse the diagnostic and ER efficacy of those with psTg and TTR that had a significant effect on the multifactorial Logistic analyses. RESULTS: In DTC patients who were followed up 3-9 months after the first postoperative 131I treatment, 69.0% (80/116) achieved ER. Univariate analysis revealed no statistical significance between ER and NER groups in terms of age, gender, TSH, TgVR, maximum tumour diameter, presence of lymph node metastasis, bilaterality of tumour, multifocality and clinical stage (P>0.05). While 131I dose, nsTg, psTg, TgV and TTR（Tg/TSH ratio） were statistically significant (P<0.05). The results of multifactorial Logistic analysis showed that psTg and TTR were independent risk factors for the first 131I treatment after DTC, with a psTg OR of 5.950 (95% CI 1.437-24.639, P<0.05) and a TTR OR of 4.137 (95%CI 1.073-15.947, P<0.05). The best threshold value of psTg for ROC curve analysis to predict the efficacy of the first postoperative 131I treatment for DTC was 8.935 μg/L, with a sensitivity of 80.6%, a specificity of 83.6%, and a Yuden's index of 0.64. And the best threshold value of TTR for predicting the efficacy of the first postoperative 131I treatment for DTC was 125.72 ng/mIU, with a sensitivity, specificity of 80.6% and 91.2%, and the Yuden index was 0.618. psTg and TTR areas under the curve were 0.839 and 0.833, respectively. psTg<8.935 μg/L patients achieved ER after 3-9 months of follow-up in DTC patients (67/74, 90.5%). psTg>8.935 μg/L patients achieved ER (13/42, 30.95%). Correspondingly TTR<125.72 ng/mIU achieved ER (65/72, 90.2%). psTg>125.72 ng/mIU achieved ER (15/44, 34.1%). CONCLUSION: The efficacy of the first 131I treatment after surgery for differentiated thyroid cancer is significant. psTg and TTR are independent risk factors for the first 131I treatment after DTC and have an important predictive value of efficacy. Related Articles | Metrics

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Characteristics and applications in bioequivalence of physiologically based on pharmacokinetic model WANG Jianxiong, HU Xiao, MIAO Beibei, ZHANG Lan Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (2): 244-250.   DOI: 10.12092/j.issn.1009-2501.2025.02.012 Abstract （240）      PDF （623KB）（96）       Knowledge map    Save Physiologically based pharmacokinetics (PBPK) model is a tool to simulate the process of drug absorption, distribution, metabolism and excretion in vivo. It is widely used in drug research and regulation. In the bioequivalence evaluation of generic drug consistency evaluation and drug production process change,the PBPK model can provide a certain reference and theoretical support for the drug bioequivalence, thereby promoting safer and more economic drug clinical trials. In this paper, the application progress of PBPK model in bioequivalence study will be reviewed in order to provide support for clinical research on drugs in China. Related Articles | Metrics

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Icariin improves hypertensive renal fibrosis and injury through Cx32-Nox4 signaling pathway WU Xiaoxue, YE Yiping, LEI Zhendong, ZHANG Zunjing, CHEN Wenling Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 870-878.   DOI: 10.12092/j.issn.1009-2501.2024.08.004 Abstract （235）      PDF （1794KB）（125）       Knowledge map    Save AIM: To investigate the effect of icariin on renal fibrosis and injury in hypertension through Cx32-Nox4 signaling pathway. METHODS: Models of hypertensive nephropathy (HN) were established in spontaneously hypertensive rats (SHRs). The experiment was divided into 4 groups: normal control group (WKY rats), model group (SHR), icariin 10 mg·kg-1·d-1 group (icariin once daily), icariin 30 mg·kg-1·d-1 group (icariin once daily), n=10. The expression of fibrosis-related proteins was detected in vivo. NRK-52E cells exposed to AngII were selected to observe the effects of icariin on kidney injury. Extracellular matrix (ECM) levels, including α-smooth muscle actin (α-SMA), collagen I (Col-I) and fibronectin (FN) expression were measured by Western blot and immunohistochemistry. The expressions of oxidative stress markers including superoxide dismutase (SOD) and malondialdehyde (MDA) were determined by the test kit. RESULTS: Icariin reduced renal fibrosis in SHR rats in vivo. Icariin down-regulated the expression of α-SMA, FN, and Col-I and protected hypertension-damaged kidney tissue from progressive fibrosis (P<0.05). Icariin increased the total SOD activity and decrease the MDA level in kidney and serum of SHR rats (P<0.05). In addition, icariin increased the expression of Cx32 and decreased the expression of Nox4 in the kidneys of SHR rats (P<0.05). Icariin had a protective effect on AngII-mediated NRK-52E cell damage and fibrosis. CONCLUSION: Icariin can improve renal tubulointerstitial fibrosis and delay the progression of HN. Renal protection may be attributed to the regulation of oxidative stress mediated by the Cx32-Nox4 signaling pathway. Related Articles | Metrics

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Improvement of insulin sensitivity in T2DM patients by glucagon-like peptide fusion protein LIU Huan, LIU Yang, LUO Dan, GUO Lixin, LIU Dongyang Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 879-886.   DOI: 10.12092/j.issn.1009-2501.2024.08.005 Abstract （228）      PDF （1195KB）（130）       Knowledge map    Save AIM: In order to quantitatively examine the improvement of insulin sensitivity (IS) in patients with type 2 diabetes mellitus (T2DM) when exendin-4-IgG4-Fc (E4F4) was given for 12 weeks, the present study was conducted to establish E4F4 population oral glucose minimal models based on the meal tolerance test (MTT) data of E4F4 pre- and post-dosing, and to analyze whether low-dose (2.7 mg) administration for 12 weeks significantly improved insulin sensitivity in patients with T2DM. METHODS: Blood glucose and insulin concentrations were collected among 16 subjects in the study who completed MTT before or after dosing. Nonlinear mixed-effects model construction for the population oral glucose minimal models was performed using NONMEN 7.2 software using pre- and post-dosing data, respectively. The insulin sensitivity parameters obtained from the models before and after the administration of the drug were statistically analyzed using GraphPad Prism 8.0. RESULTS: Nonparametric test of IS before and after dosing showed statistical difference (P=0.02), and insulin sensitivity after dosing was significantly higher than the baseline value before dosing. CONCLUSION: 12 weeks of low-dose E4F4 treatment in patients with type 2 diabetes mellitus resulted in an improvement in insulin sensitivity. This study provides a pharmacodynamic basis for the efficacy of this novel biologic. Related Articles | Metrics

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Signal mining and analysis of adverse drug reactions for polatuzumab vedotin based on FAERS database SONG Zaiwei, LI Xinya, MEN Peng, JIANG Dan, DONG Fei, ZHAO Rongsheng, YANG Jun Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (7): 752-761.   DOI: 10.12092/j.issn.1009-2501.2024.07.004 Abstract （225）      PDF （709KB）（236）       Knowledge map    Save AIM: To evaluate and analyze the post-marketing adverse drug reaction (ADR) signals of polatuzumab vedotin, so as to provide reference for clinical safety management. METHODS: Using the FDA adverse drug event reporting system (FAERS) database and OpenVigil data platform, the ADR reports of polatuzumab vedotin were collected from June 10, 2019 (FDA approval for marketing) to the March 31, 2023. The ADR signals were detected by using the reporting odds ratio (ROR) and proportional reporting ratio (PRR) in the proportional imbalance method. To increase the threshold and obtain stronger and more frequently occurring ADRs, a second screening of signals was performed. RESULTS: A total of 2 408 ADR reports related to polatuzumab vedotin were collected, and 83 ADR signals were detected after secondary screening. 26 ADR signals were not mentioned in the drug instructions such as abnormal spinal magnetic resonance imaging, increased bone resorption, osteolysis, decreased aspartate aminotransferase, decreased alanine aminotransferase, hypofibrinogenemia, and pulmonary embolism. The system organ classes with a high signal counts or cumulative number of cases included infections and invasive diseases (24 signals, 632 cases), various examinations (17 signals, 675 cases), blood and lymphatic system diseases (11 signals, 734 cases), various nervous system diseases (7 signals, 153 cases), immune system diseases (3 signals, 95 cases), systemic diseases and various reactions at the site of administration (2 signals, 145 cases), and systemic diseases and various reactions at the site of administration (2 signals, 87 cases), etc. CONCLUSION: In addition to the common ADRs suggested by the instructions, this study identified new ADR risk signals for polatuzumab vedotin. In the clinical application of polatuzumab vedotin, in addition to the ADR mentioned in the instructions such as infections, myelosuppression, peripheral neuropathies, infusion-related reactions, and abnormal liver function, attention should also be paid to the risk signals not mentioned such as abnormal spinal magnetic resonance imaging, and increased bone resorption. Related Articles | Metrics

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Influence of hepatitis B combined with hepatic fibrosis on endogenous and exogenous metabolism and therapeutic implications NI Jie, HONG Xiaodan, JI Ke, JIA Yuanwei, WANG Guangji, ZHANG Jingwei Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 853-860.   DOI: 10.12092/j.issn.1009-2501.2024.08.002 Abstract （224）      PDF （1714KB）（132）       Knowledge map    Save AIM: To study the effect of hepatitis B combined with hepatic fibrosis on endogenous and exogenous metabolism of liver and the effect of glycyrrhizic acid combined with tenofovir (TFV) ester on anti-HBV efficacy. METHODS: Hepatitis B mouse was induced by chronic CCl4 to form a model of hepatitis B with hepatic fibrosis. H&E staining, Sirius Red Staining, α-SMA immunohistochemistry were used to detect pathological changes in liver tissue. The changes of liver endogenous metabolism in mice with hepatitis B and hepatic fibrosis were detected by metabolomics. LC-MS/MS was used to investigate the plasma and liver concentrations of TFV and its active metabolite (TFV-DP), for investigating the changes of exogenous metabolism. RESULTS: HBV+CCl4 mice showed fibrosis symptoms such as liver injury and collagen deposition. Hepatitis B combined with hepatic fibrosis affected nucleotide metabolism, amino acid metabolism, tricarboxylic acid cycle, pentose phosphate pathway and other endogenous metabolism, lowered the hepatic level of TFV-DP, and decreased the antiviral efficacy. By combining with glycyrrhizic acid or forming a self-assembled preparation, the hepatic level of TFV-DP was improved, and the antiviral efficacy was enhanced. CONCLUSIONS: Hepatitis B combined with hepatic fibrosis affected both endogenous and exogenous metabolism of liver. Different forms of combination of glycyrrhizic acid and TFV could elevate the level of TFV-DP in liver and improve the antiviral efficacy in HBV+CCl4 mice.  Related Articles | Metrics

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Exploring the mechanism of Radix Angelica sinensis and Astragalus mongholicus extract therapy for radiationinduced myocardial fibrosis based on network pharmacology and experimental validation LI Wen, JIANG Hugang, WANG Xinqiang, LI Yingdong, LIU Kai, ZHAO Xinke Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (6): 601-611.   DOI: 10.12092/j.issn.1009-2501.2024.06.001 Abstract （221）      PDF （2822KB）（299）       Knowledge map    Save AIM: To explore the potential targets and mechanisms of Angelica sinensis and Astragalus membranaceus ultrafiltration (RAS-AM) in the treatment of radiation induced myocardial fibrosis (RIMF) through network pharmacology combined experimental validation. METHODS: Using the TCMSP database TCM@TAIWAN The Taiwan Traditional Chinese Medicine Database and TCMID Traditional Chinese Medicine Database screen the components and targets of RAS-AM, and use the Swiss Target Prediction database for target prediction. Obtain RIMF disease targets from Gene Cards and OMIM databases, obtain intersection targets of diseases and drugs through Wayne's online tool, obtain protein interaction relationships (PPIs) through STRING database, and use Cytoscape 3.9.1 software to construct a visualized network topology diagram of "drug component target disease". Conduct GO and KEGG enrichment analysis on core targets through the David database, and use the microbiome platform for mapping. Experimental verification: Sixty Wistar rats were randomly divided into a blank group, a model group, a positive drug group, a RAS-AM low-dose group, a RAS-AM medium dose group, and a RAS-AM high-dose group. A RIMF model was established using a 38Gy dose of radiation induction, and was administered orally for 4 weeks. The general condition of the rats was also observed. After blood and heart collection in rats, HE staining was used to observe the morphological changes of myocardial tissue, and ELISA and Western blot methods were used to detect key targets for network pharmacology prediction. RESULTS: Network pharmacology analysis revealed 34 active components and 705 targets of Angelica sinensis and Astragalus membranaceus ultrafiltration, with a total of 154 targets, with IL-6, VEGFA, MMP2, MMP9, and ACE as the top five core targets; GO enrichment analysis screened a total of 153 entries, and KEGG enrichment had 25 pathways. Experimental part: HE staining results showed that the degeneration and necrosis of myocardial cells improved in each medication group, the infiltration of inflammatory cells in the myocardial interstitium decreased, and the proliferation of fibrous connective tissue in the myocardial interstitium decreased. ELISA and Western blot results showed that compared with the normal group, the expression of IL-6, VEGFA, and MMP-9 in the model group increased. Compared with the model groupthe expression of IL-6, VEGFA, and MMP-9 in each medication group decreased to varying degrees, in a dose-dependent manner. CONCLUSION: RAS-AM may inhibit RIMF by downregulating core targets such as IL-6, VEGFA protein, MMP-9 protein, and regulating inflammatory pathways, collagen degradation, and other processes. Related Articles | Metrics

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Research progress of dalpiciclib in treatment of breast cancer DU Caiying, QUAN Xianghua, SUN Caihong, YUAN Haidan Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (6): 715-720.   DOI: 10.12092/j.issn.1009-2501.2024.06.014 Abstract （219）      PDF （632KB）（500）       Knowledge map    Save As the first domestically originated cell cycle protein-dependent kinase 4/6 inhibitor, dalpiciclib has been approved by the State Drug Administration for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer in combination with fulvestrant or aromatase inhibitors. This article focuses on the progress of dalpiciclib research in breast cancer, summarizing the drug's mechanism of action, phase I-III clinical trials, and drug safety issues. Related Articles | Metrics

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Enhancement of anti-tumor effect of immune checkpoint inhibitor anti-PD-L1 by shenqifuzheng injection and the mechanism study ZHOU Zhihua, CHANG Jingwen, YAN Yuanyuan, QI Yanan, HAN Jingjing, ZHU Xinyi, YU Chen, WU Hongyan, FAN Fangtian Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (7): 792-799.   DOI: 10.12092/j.issn.1009-2501.2024.07.009 Abstract （219）      PDF （3747KB）（201）       Knowledge map    Save AIM: To investigate of the effect of Shenqifuzheng injection (SFI) combined with PD-L1 antibody on tumor immune microenvironment and its efficacy. METHODS: A subcutaneous transplantation tumor model for B16F10-LUC melanoma was created. The expression of Ki67, CD31, CD8, CD16, CD163, FOXP3, LY6C, LY6G with labeling antibodies was used to detect CD8+T cells, Treg cells, NK cells, MDSCs cells, centrocytes, and granulocytes in the tumor tissues via immunohistochemistry. Flow cytometry was used to measure the ratios of CD11c+, IA/IE+, and CD80+ cells in splenic tissue, as well as the ratios of CD8+T, CD4+T, and Treg cells in tumor tissue. Additionally, granulocyte count and NK cell expression were analyzed. RESULTS: The immunohistochemistry results indicate that the drug administration group effectively suppressed tumor angiogenesis and cell proliferation, while decreasing the expression level of immunosuppressive cytokines CD4+T cells, Treg cells, MDSCs and centroblasts. Additionally, CD8 and NK cell infiltration was promoted compared to the control group. The results of the flow analysis demonstrated a significant increase in the expression level of CD8+T cells within tumor tissues, as well as inhibition of CD4+T, Treg, and DC cell infiltration within the spleen in the drug administration group. Additionally, the tumor volume analysis indicated that the drug administration group effectively inhibited tumor growth. The flow results illustrate that the group administering treatment exhibited significant increases in CD8+T cell expression levels in tumor tissue and DC cells in the spleen. Furthermore, the treatment effectively inhibited the infiltration of CD4+T and Treg cells. The results also indicate that the treatment significantly reduced tumor growth, with the tumor inhibition rate being better with PD-L1 antibody alone than with the SFI group. Additionally, combining drugs resulted in superior results compared to the PD-L1 antibody group alone. CONCLUSION: SFI combined with a PD-L1 antibody can have synergistic anti-tumor effects, potentially enhancing DC cell infiltration and promoting T cell activation. Immunohistochemistry results indicate a positive impact on the tumor immune microenvironment. Related Articles | Metrics

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Network pharmacology-molecular docking analysis and experimental validation to explore the protective mechanism of Mongolian medicine Gaoyou on renal function Celimuge, Hudeligen, XU Liang Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (9): 968-978.   DOI: 10.12092/j.issn.1009-2501.2024.09.002 Abstract （216）      PDF （2207KB）（449）       Knowledge map    Save AIM: To explore the protective mechanism of Mongolian medicine Gaoyou on renal function through network pharmacology molecular docking and animal experiments. METHODS: The effective active components and targets of Gao you acting on acute kidney injury (AKI) and the related targets of AKI disease were obtained by using the relevant database of traditional Chinese medicine. The targets and components were mutually constructed to act on the network, and the signal pathways of drugs and diseases were enriched and analyzed. And the molecular docking validation study was carried out on the pharmacodynamic components with high moderate value in the network and the core action target. On this basis, after establishing the rat model of acute renal injury and giving Gaoyou intervention, the contents of creatinine (CR), urea nitrogen (BUN) and tumor necrosis factor-A (TNF-α), Kidney damage molecule-1 (Kim-1), cystatin C (Cys-C), neutrophil gelatinase related lipid transporter (NGAL) in serum of rats were detected, and renal tissue sections were observed with HE staining to verify the protective effect of Mongolian medicine Gaoyou on renal function of rats with acute renal injury. The predicted signal pathway was verified by Western blot. RESULTS: 40 key targets were obtained by network pharmacology and molecular docking analysis. KEGG and go enrichment analysis were carried out on the key targets. ALB, AKT1, VEGFA, IL-6, CASP3 and other key targets were predicted, and cancer signal pathway, TNF signal pathway, PI3K/AKT signal pathway and other key pathways were predicted. The results of molecular docking showed that the main active components of Gaoyou had good binding activity with related targets. The results of animal experiments showed that Gao you had a good protective effect on renal function, and Cr and BUN were significantly lower than those in the model group (P<0.05). The content of TNF-α decreased significantly (P<0.05). Kim-1, Cys-C and NGAL decreased significantly (P<0.05). HE staining showed that Gao can obviously improve the pathological state of acute renal damage. The expression of AKT1, p-AKT1 and CASP3 in renal tissue of rats with acute renal injury increased (P<0.05). Compared with the model group, the expression of AKT1, p-AKT1 and CASP3 in renal tissue of rats in Gaoyou group decreased significantly (P<0.05). CONCLUSION: Gaoyou can protect the renal function of rats with renal injury through multiple pathways such as anti-inflammatory, antioxidant, antithrombotic, anti apoptotic and so on through the characteristics of multi-component, multi target. Intervention of PKA3/AKT signal pathway and apoptosis factor may be one of its main mechanisms. Related Articles | Metrics

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Effect of antithrombotic therapy selection on stroke recurrence based on drug gene polymorphism and thromboelastography SONG Qiuying, TAO Chenjuan, WU Zhihao, XIE Zhefeng, LIU Haijun, CHEN Binbin Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (9): 1035-1041.   DOI: 10.12092/j.issn.1009-2501.2024.09.009 Abstract （213）      PDF （662KB）（181）       Knowledge map    Save AIM: Clopidogrel and aspirin are commonly used drugs for the secondary prevention of cerebrovascular disease. Due to drug resistance, their preventive effect is often affected. This article explores the clinical value of clopidogrel and aspirin pharmacogenetic genetic testing in the secondary prevention of ischemic stroke. METHODS: 220 patients with mild ischemic stroke or TIA admitted to our hospital from 2021.7 to 2022.9 were included and randomly divided into individualized treatment group and clopidogrel conventional treatment group (control group). The patients were followed up for one year to observe stroke recurrence and hemorrhagic events. RESULTS: (1) Compared with the control group, the recurrence rate of ischemic stroke in the individualized treatment group after 1-year follow-up was slightly lower (5.82% vs. 7.92%, P>0.05), the risk of cerebral hemorrhage was similar, but the risk of other occurrences was increased (6.79% vs. 0.99%, P<0.05). (2) COX regression analysis showed that ESRS (HR 2.576, 95%CI 1.226-5.413, P=0.013) and history of hypertension (HR 5.517, 95%CI 1.624-18.737, P=0.006) were associated with recurrence of ischemic stroke, independent of antithrombotic regimen (HR 0.918, 95%CI 0.291-2.894, P=0.883). CONCLUSION: Aspirin GPIBA, PTGS1, and ITGB3 gene polymorphisms have limited significance in guiding antiplatelet medication. Selecting aspirin maintenance therapy for clopidogrel CYP2C19*2*3 allele carriers cannot significantly reduce the risk of recurrence of minor ischemic stroke and may increase other bleeding risks. COX regression analysis shows that ESRS and history of hypertension are independent risk factors for stroke recurrence. Related Articles | Metrics

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Research progress on physiological and pathological functions of salt-inducible kinase and its inhibitors LIN Xinyue, WANG Yanyan, BIAN Hongsheng, YU Shuang, HUANG Lili Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (11): 1306-1314.   DOI: 10.12092/j.issn.1009-2501.2024.11.014 Abstract （213）      PDF （743KB）（393）       Knowledge map    Save The salt-inducible kinase (SIK) family includes three isoforms, SIK1, SIK2 and SIK3, which are the main regulators of physiological and pathological processes and participate in the regulation of glucose and lipid metabolism, tumor, inflammation, depression, sleep-wake and circadian rhythm. SIK inhibitor has become a candidate drug for the treatment of a variety of diseases, and is especially expected to become a potential new drug for the treatment of nervous system diseases, such as sleep disorders, circadian rhythm disorders, and depression. This review summarizes the regulation and mechanism of three isoforms of SIK and their upstream and downstream signaling pathways in the above physiological and pathological processes. It also reviews the recentstudies of SIK inhibitors.  Related Articles | Metrics

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Research progress of miRNA in ulcerative colitis LIU Xuan, FENG Cuijuan, WANG Yiqiang, LI Fang Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 917-929.   DOI: 10.12092/j.issn.1009-2501.2024.08.009 Abstract （212）      PDF （977KB）（388）       Knowledge map    Save Ulcerative colitis (UC) is a chronic immune-mediated disease characterized by diffuse mucosal inflammation and clinical symptoms of abdominal pain, diarrhea, mucopurulent bloody stool and tenesmus. Due to its complex etiology, difficult treatment and poor prognosis, UC has been listed as one of the modern refractory diseases by the World Health Organization. MicroRNAs (microRNAs) regulate various biological processes such as cell growth, differentiation, and development by regulating gene expression. Studies have shown that miRNA is involved in the pathogenesis of UC through various pathways such as intestinal mucosal barrier homeostasis disorder, intestinal flora imbalance and excessive differentiation of immune cells, and is expected to become a new target for clinical treatment of UC. In order to better understand the role of miRNA in the pathogenesis of UC and provide new research directions for the treatment of UC, this article reviews the correlation between miRNA and the pathogenesis of UC, the potential of miRNA as a biomarker of UC, and the treatment strategies of miRNA in UC in recent years. Related Articles | Metrics

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Retrospective study of the efficacy of vedolizumab in patients with inflammatory bowel disease LI Peipei, WU Yue, ZHANG Xianzheng, ZHANG Lingling Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 899-906.   DOI: 10.12092/j.issn.1009-2501.2024.08.007 Abstract （211）      PDF （1023KB）（130）       Knowledge map    Save AIM: To evaluate the efficacy and safety of vedolizumab in the treatment of inflammatory bowel disease. METHODS: The clinical data of 25 patients with inflammatory bowel disease (IBD) (13 ulcerative colitis (UC) and 12 Crohn's disease (CD)) treated with vedolizumab (VDZ) in the Anorectal department of our hospital from July 2020 to August 2023 were retrospectively collected. VDZ 300 mg was given intravenously at weeks 0, 2 and 6 to induce remission, and 300 mg was given intravenously every 8 weeks to maintain remission. The evaluation was carried out after 30 weeks of treatment. The primary efficacy indicators included clinical response rate, clinical remission rate, and endoscopic remission rate. The secondary efficacy indicators included nutritional status indicators (body weight (Wt), hemoglobin (HGB), albumin (ALB), hematocrit (HCT)), inflammation degree indicators (high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR)). All adverse reactions that occurred during VDZ treatment were recorded. RESULTS: The total clinical response rate of IBD patients treated with VDZ for 6 weeks and 14 weeks was 32% and 60%, respectively. The total clinical remission rate of IBD patients treated with VDZ for 14 weeks and 30 weeks was 16% and 36%, respectively. There was no significant difference in clinical response rate and clinical remission rate between UC and CD treated with VDZ (P>0.05). After 30 weeks of treatment, the body weight of UC patients was significantly increased, the levels of HCT%, ALB and HGB were significantly improved, and the level of ESR was significantly decreased. After 30 weeks of treatment, the body weight of CD patients increased significantly, and the inflammatory index hs-CRP, nutritional index HCT%, ALB and HGB levels were significantly improved. One patient had an increase in white blood cell count after the third infusion of VDZ, and no other adverse reactions occurred. CONCLUSION: As an induction and maintenance therapy for IBD patients, VDZ can alleviate intestinal inflammation, relieve clinical symptoms, improve nutritional status and improve quality of life of patients, with high safety. Related Articles | Metrics

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Pharmacokinetics, pharmacodynamics of esomeprazole in critically ill patients ZHA Xian, SUN Luning, CHEN Chao, WANG Yongqing Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (10): 1152-1160.   DOI: 10.12092/j.issn.1009-2501.2024.10.008 Abstract （211）      PDF （814KB）（239）       Knowledge map    Save AIM: To investigate the pharmacokinetic/pharmacodynamic (PK/PD) profile of esomeprazole for injection in critically ill patients. METHODS: This was a prospective, single-center, open-label study, all patients received intravenous infused esomeprazole 40 mg q12h for stress ulcer prophylaxis, treatment duration is determined by clinicians based on patients condition. Forty critically ill patients were enrolled and were divided into single and multiple dose groups according to the timing of blood sample collection. Twenty-one patients in the single-dose group had their blood samples collected at 1, 3, 6, 8, and 12 h after the first dose, and 34 patients in the multiple-dose group had their blood samples collected at 0 h before the fifth dose and 1, 3, 6, and 8, and 12 h after the fifth dose, of which 14 patients had their blood samples collected at both the first dose and the repeated doses. The concentration of esomeprazole was measured by HPLC-MS/MS, and PK parameters were analyzed using noncompartmental analysis. Gastric aspirates were collected for pH measurement in fasted patients with gastric tube before the first dose (0 h), and 1, 2, 4, 8, 12, 14, 16, 20, 24 h after the initiation of drug administration, and the percentage of time with pH≥4 was calculated. All adverse events and serious adverse events during treatment were recorded. RESULTS: Patients in the single-dose group were 67.75 years old (45-69 years) with a BMI (24.05 ± 3.35) kg/m2, and patients in the multiple-dose group were 63.35 years old (24-87 years) with a BMI (24.08 ± 3.29) kg/m2. PK parameters after the first dose were AUC0-t (11.26 ± 6.58) mg·h·L-1, Cmax (3.08 ± 2.06) mg/L, CL (4.13 ± 3.68) L/h, Vd (17.12 ± 6.13) L, t1/2 (4.80 ± 3.06) h; PK parameters after multiple doses were AUC0-t (16.70 ± 11.20) mg·h/L, Cmax (3.37 ± 2.59) mg/L, CL (3.94 ± 2.94) L/h, Vd (22.71 ± 17.26) L, t1/2 (5.23 ± 3.34) h. Percentage of time with pH≥4 within 0 h-24 h after administration was 61.69%, and percentage of time with pH≥4 within 12 h-24 h was up to 100%. Esomeprazole was well tolerated by all patients with no serious adverse events. CONCLUSION: Compared with healthy volunteers, injectable esomeprazole showed increased Vd, decreased CL, increased drug exposure and accumulation after repeated administration in critically ill patients. The drug had a favorable safety profile in critically ill patients. Related Articles | Metrics

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Research and application of personalized treatment of severe infection patients with Meropenem based on TDM WANG Wenjuan, LU Peiyuan, YANG Xiaotong, CHEN Li, ZHAO Yinzhi, YUAN Yuan Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (12): 1329-1336.   DOI: 10.12092/j.issn.1009-2501.2024.12.002 Abstract （210）      PDF （634KB）（190）       Knowledge map    Save Severe infection is a significant threat to patient safety and survival. As the main treatment for hospital acquired infections, meropenem is limited in its effectiveness due to the emergence of drug resistance, especially after long-term use of antibiotics. Therefore, optimizing the efficacy of antibiotics such as meropenem and avoiding microbial resistance has become an urgent issue to be addressed. Therapeutic drug monitoring (TDM), as an important tool for achieving personalized drug administration, is increasingly recognized as an important strategy for optimizing antibiotic concentration, avoiding treatment failure and toxicity in critically ill patients and patients with renal insufficiency. By reviewing the current application status, pharmacokinetics, and TDM guidance of meropenem, clinical references are provided for the treatment of critically ill patients and patients with renal insufficiency, and guidance and support are provided for optimizing antibiotic treatment. Related Articles | Metrics

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Retrospective analysis on adverse drug reactions of four PD-1 inhibitors reported in literature YU Xiao, ZHOU Yan, LI Qin, CHENG Xuefang Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 887-898.   Abstract （209）      PDF （704KB）（210）       Knowledge map    Save AIM: To analyze the occurrence and clinical characteristics of adverse drug reactions (ADR) induced by four programmed cell death protein 1 (PD-1) inhibitors according to literature reports, and to provide reference for clinical safe medication. METHODS: PubMed, CNKI, and Wanfang, and other databases were searched to collect case reports of adverse reactions caused by four PD-1 inhibitors, including camrelizumab, sintilimab, toripalimab, and tislelizumab. RESULTS: A total of 105 eligible literature reports were retrieved from the databases at home and abroad (as of June 1, 2022), including 42 reports on camrelizumab with 47 patients, 29 reports on sintilimab with 30 patients, 21 reports on toripalimab with 24 patients and 13 reports on tislelizumab with 15 patients. Among them, there were 76 males (65.5%) and 40 females (34.5%), with a gender ratio of 1.9:1.0. The age range was between 29 to 84 years old, and the onset of ADR mainly occurred within 4 months after the first use of PD-1 inhibitors. Immune-related adverse reactions were mainly manifested as skin and its attachment (41 cases, 34.5%), endocrine system (25 cases, 21.0%), and cardiovascular system (22 cases, 18.5%). Most patients improved after symptomatic and?supportive?treatment. CONCLUSION: Immune-related adverse effects (irAEs) may occur at any time during treatment with the four PD-1 inhibitors, among these the skin system is most frequently affected, followed by the cardiovascular and endocrine systems. This suggests the importance of individualized drug administration and stringent control over indications in clinical practice. Close monitoring throughout immunotherapy is essential to minimize or prevent irAEs, thus ensuring patient safety in medication usage. Related Articles | Metrics

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Molecular mechanism of NEDD8-conjugating enzyme UBE2F regulating lung adenocarcinoma metastasis LIN Xiongzhi, ZHANG Luyi, HE Lianping, LIANG Yong, ZHOU Lisha Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (6): 612-620.   DOI: 10.12092/j.issn.1009-2501.2024.06.002 Abstract （209）      PDF （1853KB）（159）       Knowledge map    Save AIM: To study the effect of NEDD8-conjugating enzyme UBE2F on lung adenocarcinoma metastasis. METHODS: The expression of UBE2F in lung adenocarcinoma was analyzed using TIMER2.0, UALCAN and HPA databases. Kaplan-Meier Plotter database was used to analyze the relationship between UBE2F expression and survival rate of lung adenocarcinoma. A UBE2F-knockout lung adenocarcinoma cell line was constructed using CRISPR/Cas9 technology, and a UBE2F-knockout lung adenocarcinoma metastasis model was constructed in nude mice to verify the effect of UBE2F knockout on lung adenocarcinoma metastasis. The effects of UBE2F knockout on invasion and migration of lung adenocarcinoma cells were examined by cell scratch assay and Transwell invasion and migration assays. The effect of down-regulated UBE2F expression on snail expression, a key marker of epithelial-mesenchymal transition (EMT), was detected by Western blot and Real time PCR. RESULTS: Multiple database analysis showed that UBE2F was highly expressed in lung cancer, and Kaplan-Meier Plotter analysis showed that high expression of UBE2F in lung adenocarcinoma had better prognosis than low expression. In vivo experiments showed that compared with control group, the number of nodules metastasized on the lung surface of nude mice after UBE2F knockout was significantly increased (P<0.05). Cell scratch assay and Transwell assay showed that UBE2F enhanced the migration and invasion ability of lung cancer cells after knockout, and the difference were statistically significant (P<0.05). Western blot and Real time PCR results indicated that the level of EMT transcription factor snail protein and mRNA increased after UBE2F knockout. CONCLUSION: In lung adenocarcinoma cells, UBE2F down-regulation leads to Snail accumulation and promotes invasion and metastasis of lung adenocarcinoma cells. Related Articles | Metrics

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Correlation between type 2 diabetic kidney disease and trimethylamine-N-oxide WANG Mengke, GAN Chao, YUAN Yue, ZOU Jingyi, WANG Zhen, LI Shuyun, LV Haihong Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (6): 661-670.   DOI: 10.12092/j.issn.1009-2501.2024.06.008 Abstract （206）      PDF （1178KB）（100）       Knowledge map    Save AIM: To explore the correlation between trimethylamine-N-oxide (TMAO) and type 2 diabetic kidney disease (DKD), and to provide new ideas for the early clinical diagnosis of DKD. METHODS: A total 246 patients with type 2 diabetes mellitus (T2DM) admitted to the Department of Endocrinology of the First Hospital of Lanzhou University from January 1, 2020 to May 31, 2020 were divided into diabetic kidney disease group (DKD group) and simple diabetes mellitus group (NDKD group). According to urinary albumin/creatinine ratio (UACR), the patients were divided into A1, A2 and A3 subgroups. According to the estimated glomerular filtration rate (eGFR), the patients were divided into G1, G2, G3 and G4-5 subgroups. According to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, the risk of progression of DKD was assessed (low, medium, high or very high risk). General clinical data and laboratory indicators were collected. TMAO level was measured by euzymelinked immunosorbent assay. SPSS 25.0 software was used for statistical analysis. RESULTS: In T2DM patients, TMAO level was positively correlated with UACR (r=0.515, P<0.01) and negatively correlated with eGFR (r=-0.409, P<0.01). TMAO is an independent risk factor for the onset and progression of DKD. In diagnostic model, the AUROC was 0.745 with optimal cut-off value was 5.37 μmol/L. CONCLUSION: TMAO is closely related to the occurrence and development of DKD, and it has certain clinical predictive value for DKD. Therefore, TMAO may become a potential target for the early diagnosis and treatment of DKD.  Related Articles | Metrics