Table of Content

Volume 29 Issue 7
26 July 2024

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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

2024, 29(7):  722-734.  doi:10.12092/j.issn.1009-2501.2024.07.001

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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.

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

2024, 29(7):  735-743.  doi:10.12092/j.issn.1009-2501.2024.07.002

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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.

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

2024, 29(7):  744-751.  doi:10.12092/j.issn.1009-2501.2024.07.003

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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.

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

2024, 29(7):  752-761.  doi:10.12092/j.issn.1009-2501.2024.07.004

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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.

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

2024, 29(7):  762-767.  doi:10.12092/j.issn.1009-2501.2024.07.005

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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.

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

2024, 29(7):  768-774.  doi:10.12092/j.issn.1009-2501.2024.07.006

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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.

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

2024, 29(7):  775-784.  doi:10.12092/j.issn.1009-2501.2024.07.007

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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.

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

2024, 29(7):  785-791.  doi:10.12092/j.issn.1009-2501.2024.07.008

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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.

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

2024, 29(7):  792-799.  doi:10.12092/j.issn.1009-2501.2024.07.009

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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.

Caragana sinica root inhibits Erastin-induced chondrocyte ferroptosis by blocking TRPM7

ZHU Rendi, QU Biao, ZHOU Renpeng, HU Wei

2024, 29(7):  800-808.  doi:10.12092/j.issn.1009-2501.2024.07.010

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AIM: To investigate the effect of Caragana sinica root (CSR) on ferroptosis in the Erastin-induced chondrocyte ferroptosis model and possible mechanisms. METHODS: The C28/I2 chondrocyte cell line was cultured to construct a cell model of Erastin-induced ferroptosis. Cell viability was detected by MTT assay; cell death was observed by Calcein/PI staining; cell lactate dehydrogenase (LDH) and total glutathione (GSH) levels were detected by the kit; reactive oxygen species (ROS) levels were detected by fluorescent probe BODIPY 581/591 C11 labeling; mitochondrial membrane potential (ΔΨm) changes were observed by Rh123 and JC-1 staining; Western blot was used to detect the expression of ferroptosis-related proteins (ACSL4, GPX4) and TRPM7 proteins. RESULTS: Erastin treatment decreased chondrocyte viability, increased cytotoxicity, induced oxidative stress, disrupted ΔΨm, and up-regulated ACSL4 protein expression, while down-regulating GPX4 protein expression and inducing chondrocyte ferroptosis. In contrast, CSR restored cell viability and reduced oxidative stress, thereby inhibiting chondrocyte ferroptosis. In addition, CSR reduced the Erastin-induced increase in TRPM7 protein expression level. CONCLUSION: Erastin induced lipid peroxidation in C28/I2 chondrocytes, causing mitochondrial damage and ferroptosis; CSR may inhibit chondrocyte ferroptosis by blocking TRPM7, thus exerting a protective effect on chondrocytes.

Protective efficacy of epalrestat on mitochondrial oxidative stress damage for radiation pneumonitis in mice

LI Zepeng, GU Wenqiang, CHEN Xiao, WANG Yinhua, LI Xianwei

2024, 29(7):  809-818.  doi:10.12092/j.issn.1009-2501.2024.07.011

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AIM: To investigate the effects of epalrestat (Epa) on the mitochondrial oxidative stress damage of radiation pneumonitis (RP) mice and to explore its possible mechanism. METHODS: C57BL/6 mice were randomly divided into control (CON), Irradiation (IR), IR combined with Epa (10 mg/kg) and IR combined with Epa (20 mg/kg) group, 16 mice in each group. Mouse models of RP were established by whole thorax irradiation at a dose of 15Gy using a 6?MV linear accelerator. Continuous intragastric administration after IR for 6 or 8 weeks. Lung histopathology was analyzed by HE staining. The expression of aldose reductase (AR) was determined by immunohistochemistry. Mitochondrial morphology of lung tissues was observed by transmission electron microscopy. The levels of inflammatory cytokines (IL-6, TNF-α and TGF-β1) in plasma were detected by ELISA. The contents of Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) in lung tissues were determined by colorimetry. Single cell suspension of lung tissues was prepared and reactive oxygen species (ROS) levels in the cells was examined using a DCFH-DA fluorescent probe. Real-time quantitative PCR was used to determine the expression of AR, IL-6, TNF-α and TGF-β1. The protein levels of AR, IL-6, TNF-α, TGF-β1, BAX, Bcl2, Cleaved Caspase-3,8-oxoguanine DNA glycosylase 1 (OGG1) and silent information regulator 3 (SIRT3) were detected by Western blot analysis. RESULTS: Compared with the CON group, the alveolar hyperplasia, alveolar septum thickening and inflammatory cell infiltration were observed in the IR group. Moreover, the content of inflammatory factors such as IL-6, TNF-α and TGF-β1 and the expression of BAX and Cleaved Caspase-3 were significantly increased, and the expression of Bcl2 was obviously decreased after irradiation. Compared with the IR group, Epa robustly alleviated RP. Meanwhile, Epa down-regulated inflammatory cells infiltration and the expression of inflammatory cytokines, such as IL-6, TNF-α and TGF-β1. In addition, Epa could down-regulate the expression of BAX and Cleaved Caspase-3, and up-regulate Bcl2 in lung tissues. Compared with the CON group, the expression of AR, the levels of ROS, MDA and 4-HNE were significantly increased, the expression of OGG1 and SIRT3 were significantly decreased, and mitochondrial damage was aggravated in the IR group. Compared with IR group, the expression of AR was significantly down-regulated, the levels of ROS, MDA and 4-HNE were significantly decreased, the expressions of OGG1 and SIRT3 were significantly increased, and the mitochondrial damage was significantly alleviated in IR group after 6 to 8 weeks of Epa administration. CONCLUSION: Epa has a protective effect on RP, which may be related to the inhibition of AR expression, the reduction of mitochondrial oxidative stress injury, and the inhibition of inflammatory response and cell apoptosis.

Analysis of clinical characteristics of tramadol induced hypoglycemia

LIU Wei, HE Qin, HE Yiran

2024, 29(7):  819-825.  doi:10.12092/j.issn.1009-2501.2024.07.012

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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.

Clinical research progress of esketamine application within the spinal canal

SUN Yufeng, YANG Xiaolin, DING Ying, LV Yanrong, WU Hongwei, YANG Chun

2024, 29(7):  826-830.  doi:10.12092/j.issn.1009-2501.2024.07.013

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Esketamine, which was recently introduced in China, is a type of intravenous general anesthetic that is widely used in clinical practice for general anesthesia and anti-depression therapy. Studies have found that esketamine can be safely used to intrathecally produce analgesic, sedative, and anti-depressive effects at subanesthetic doses. This review summarizes the mechanism of action, safety, adverse reactions, and various clinical applications of esketamine intrathecally, so as to provide relevant references for further research.

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

2024, 29(7):  831-840.  doi:10.12092/j.issn.1009-2501.2024.07.014

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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.