Table of Content

Volume 30 Issue 2
26 February 2025

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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

2025, 30(2):  146-158.  doi:10.12092/j.issn.1009-2501.2025.02.001

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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.

Advances in precision diagnosis and treatment of cholangiocarcinoma

CHEN Zhenmei, CHEN Jinhong

2025, 30(2):  159-170.  doi:10.12092/j.issn.1009-2501.2025.02.002

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Cholangiocarcinoma (CCA) is a highly aggressive and heterogeneous biliary malignancy characterized by challenges in early diagnosis, limited efficacy of traditional chemotherapy, and poor prognosis. Due to its significant heterogeneity at the genomic, epigenetic, and molecular levels, molecular testing and targeted therapy have become increasingly important in CCA management, forming an integral part of the era of precision oncology. The development of next-generation sequencing (NGS) has advanced research into the molecular subtypes and therapeutic targets of CCA, including FGFR2 fusions/rearrangements, IDH1 mutations, and BRAF mutations. Recently, two phase III clinical trials, TOPAZ-1 and KEYNOTE-966, have established the pivotal role of immunotherapy combined with chemotherapy in advanced CCA. While precision diagnosis and treatment in CCA have shown promising progress, this field remains in its exploratory phase and faces numerous challenges. This review summarizes recent advancements in the diagnosis, molecular targeted therapy, immunotherapy, resistance mechanisms, and the development of novel strategies for CCA. 

Current status and progress of targeted therapy for hepatocellular carcinoma

CHEN Zhiwen, WANG Longrong, WANG Lu

2025, 30(2):  171-182.  doi:10.12092/j.issn.1009-2501.2025.02.003

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Hepatocellular carcinoma, as a common malignant tumor, remains a serious global health problem. Traditional methods such as surgical resection and chemotherapy have limited effects in improving the prognosis of advanced hepatocellular carcinoma. With the deepening of research into molecular mechanisms, targeted therapy has become an important direction for the treatment of hepatocellular carcinoma. In this review, we summarize the main targeted drugs and associated therapeutic strategies for hepatocellular carcinoma, aiming to provide references and evidence for future related research.

Advancements and frontiers in targeted therapy for pancreatic cancer

DU Nan, WEI Miaoyan, XU Jin

2025, 30(2):  183-192.  doi:10.12092/j.issn.1009-2501.2025.02.004

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The incidence of pancreatic cancer has been increasing each year, and the 5-year survival rate is still around 10%. Diagnosis and treatment strategies are major concerns in the industry. Gene sequencing and multi-omics research have revealed more signal pathways and actionable targets, offering the potential for new targeted therapeutic drugs. However, current drug treatment for pancreatic cancer still relies mainly on chemotherapy, and targeted therapy strategies are not yet fully developed and require further discussion. As basic and translational research in pancreatic cancer advances and precision medicine develops, it is expected that targeted treatment for pancreatic cancer will become more precise and individualized in the future. This article discusses the current progress and frontiers of targeted treatment for pancreatic cancer.

Research progress on the resistance mechanism of anti-angiogenesis targeted drugs in the treatment of colorectal cancer 

JIANG Haitao, XU Yangxian

2025, 30(2):  193-199.  doi:10.12092/j.issn.1009-2501.2025.02.005

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Colorectal cancer (CRC) is one of the most common malignancies worldwide, although anti-angiogenic targeted agents such as bevacizumab have shown significant efficacy in the treatment of metastatic CRC, however, the emergence of drug resistance is still a key obstacle affecting the success rate of treatment and survival of patients. This article reviews the progress of anti-angiogenesis targeted drugs in the treatment of CRC, the mechanism of drug resistance and how to solve the problem of drug resistance. 

Research on the application of machine learning algorithms in anticancer drug response prediction

TAN Yanchen, WANG Wenwen, XIA Jielai, LI Chen

2025, 30(2):  200-208.  doi:10.12092/j.issn.1009-2501.2025.02.006

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With the continuous development of genomics and precision medicine, targeted therapy and immunotherapy targeting biomarkers have ushered in a new era of anti-tumor therapy. However, due to the heterogeneity of tumor cells and the variability of tumor microenvironment, there are still significant differences in response to the same drug even in patient populations with the same biomarker enrichment. By combining omics data with drug sensitivity algorithms, the response of anti-tumor drugs can be predicted and transformed into personalized diagnosis and treatment strategies required for precision medicine, which is expected to improve the effectiveness of anti-tumor drugs in clinical treatment. Currently, machine learning is one of the commonly used modeling algorithms for predicting the response of anti-tumor drugs. However, due to differences in input data and algorithm construction methods, there is currently a lack of comprehensive literature review in this field. Therefore, this article provides a review of machine learning algorithms for predicting anti-tumor drug responses, summarizing publicly available cell genome characterization datasets, machine learning algorithms, and evaluation indicators in drug response prediction, as well as the current situation and challenges faced in clinical applications, in order to provide methodological references for the main research problems and potential solutions of machine learning algorithms in the field of drug response prediction.

Radix angelica sinensis and astragalus mongholicus extract mediating the Jagged1/Notch1 pathway to inhibit fibroblast transdifferentiation and resist radiation induced myocardial fibrosis

LI Wen, JIANG Hugang, WANG Xinqiang, LI Yingdong, LIU Kai, ZHAO Xinke

2025, 30(2):  209-215.  doi:10.12092/j.issn.1009-2501.2025.02.007

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AIM: To study the mechanism of action of radix angelica sinensis and astragalus mongholicus extract (RAS-AM) in inhibiting fibroblast transdifferentiation (CMT) and preventing radiation-induced myocardial fibrosis (RIMF) via the Jagged1/Notch1 pathway. METHODS: Sixty male Wistar rats were randomly divided into blank group, model group, benazepril hydrochloride group, low dose RAS-AM group, medium dose RAS-AM group, and high dose RAS-AM group, with 10 rats in each group. Except for the blank group, all other groups were induced with high-energy radiation at a dose of 38 Gy to establish RIMF models. The blank group and the model group received sterile distilled water by gavage, and the other groups received medication for 4 weeks of intervention: benazepril hydrochloride group (1.0 mg·kg-1·d-1), low dose RAS-AM group (150 mg·kg-1·d-1), medium dose RAS-AM group (300 mg·kg-1·d-1), and high dose RAS-AM group (600 mg·kg-1·d-1). The general condition of rats, the ultrastructure of myocardial tissue were observed using electron microscopy, changes in myocardial tissue fibers using Masson staining, and  CMT related protein Vimentin and α-SMA expression using immunohistochemical staining techniques. ELISA was used to detect serum inflammatory factors IL-6 and TNF-α in rats. The levels of cTnI and ST2, and the expression of Jagged1 and Notch1 were detected by Western blot. RESULTS: Compared with the blank group, the model group rats exhibited symptoms such as mental fatiguem anorexiam and loose stools; The arrangement of some myofibrils in the myocardium is disordered, with dissolution and breakage of myofibrilsm abnormal Z-line structure in some partsm disordered mitochondrial arrangement, rupture of mitochondrial membranem, and rupture or disappearance of mitochondrial ridge structure in some parts. A large amount of collagen fibers proliferate and deposit in the myocardium, and the fibrotic area significantly increases (P<0.01); The expression of myocardial tissue Vimentin α-SMA protein increased (P<0.05), while the expression of Jagged1 and Notch1 proteins decreased (P<0.05); serum IL-6 and TNF-α, the expression of inflammatory factors such as cTnI and ST2 increased (P<0.05). compared with the model group, the RAS-AM and benazepril hydrochloride groups showed varying degrees of improvement in general conditions; the pathological changes of myocardial ultrastructure have been improved, and myocardial fibrosis has been alleviated; The area of collagen fibers significantly decreased (P<0.01); Myocardial tissue Vimentin α-SMA protein expression decreased (P<0.05), while Jagged1 and Notch1 expression increased (P<0.05); Serum IL-6 and TNF-α, The expression of inflammatory factors such as cTnI and ST2 decreased (P<0.05). CONCLUSION: RAS-AM may alleviate RIMF by intervening in the Jagged1/Notch1 pathway to inhibit CMT. The specific mechanism still needs further investigation. 

Ameliorating effect of total flavonoids of rhododendron on brain oxidative stress injury in cerebral ischemia-reperfusion rats

YU Xiaohai, JIN Yu, SUN Minqiong, CONG Hui, GUO Qianying

2025, 30(2):  216-221.  doi:10.12092/j.issn.1009-2501.2025.02.008

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AIM: To explore the protective effect of total flavonoids from rhododendron (TFR) on oxidative stress injury in the brain of rats subjected to cerebral ischemia/reperfusion (I/R). METHODS: Forty male SD rats were randomly divided into 5 groups: sham operation group ( Sham group ), cerebral ischemia-reperfusion group (MCAO group), and Cerebral Ischemia/Reperfusion with TFR treatment groups (TFR 50, 100, 200 mg/kg groups). The MCAO group and TFR-treated groups underwent ischemia/reperfusion surgery, and the TFR-treated groups received TFR intragastrically for 14 consecutive days following the ischemia/reperfusion injury. After 14 days, comparisons were made in terms of neurological function scores, serum inflammatory factors, oxidative stress indicators, and brain injury markers. Additionally, histological examination of brain tissue morphology using Hematoxylin and Eosin (HE) staining, observation of cerebral blood flow through cerebral blood flow imaging, and measurement of lactate dehydrogenase (LDH), neuron-specific enolase (NSE) activity in serum, interleukin-1 (IL-1), interleukin-6 (IL-6) levels, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, nitric oxide (NO) content, and nitric oxide synthase (NOS) activity were performed. RESULTS: Compared to the Sham group, MCAO rats exhibited abnormal neurological function scores, severe damage to the microstructure of brain tissue, noticeable changes in brain morphology, elevated activities of LDH and NSE, increased levels of IL-1 and IL-6, elevated MDA content, and decreased SOD, NOS activity, and NO content. In comparison to the MCAO group, rats treated with TFR at doses of 50, 100, and 200 mg/kg showed recovery of abnormal neurological function scores, reduced damage to the microstructure of brain tissue, decreased activities of LDH and NSE, lowered levels of IL-1 and IL-6, reduced MDA content, and increased SOD, NOS activity, and NO content. CONCLUSION: Total flavonoids from Rhododendron can protect against cerebral ischemia/reperfusion injury, reducing oxidative stress levels.

Evidence map on the treatment of heart failure with Yiqifumai injection

LYU Shichao, WANG Yunjiao, ZUO Yiming, SHANG Hongcai

2025, 30(2):  222-231.  doi:10.12092/j.issn.1009-2501.2025.02.009

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AIM: To display the distribution of evidence in the field of Yiqifumai injection treatment for heart failure. METHODS: To retrieve relevant databases such as CBM, CNKI, Wanfang, VIP, Cochrane Library, PubMed, Embase, and Web of Science, and search for the China Clinical Trial Registry, ClinicalTrials.gov and collect clinical studies, systematic evaluations, and guideline studies on the treatment of heart failure with Yiqifumai injection. The evidence map research method use a table to display the proportion of literature, sample size, comorbidities, and quality evaluations of systematic evaluations. Use a pie chart to display the proportion distribution of research types, a line chart to describe publication trends, and a bubble chart to display the distribution of evidence. RESULTS: The overall number of articles on the treatment of heart failure with Yiqifumai injection is in a steady development stage. Clinical studies are mainly small sample, single center, short-term randomized controlled trials, with a sample size of 60-100 cases and an intervention duration of mostly 14 days. The underlying disease is mainly coronary heart disease. Clinical research evidence tends to support the therapeutic effect of Yiqifumai injection combined with conventional Western medicine in improving heart failure patients' heart function and quality of life. However, there are also issues such as low overall quality of research, unreasonable clinical trial design, small sample size, incomplete selection of outcome indicators, low international recognition of certain outcome indicators, and lack of reporting on long-term outcomes The overall quality of randomized controlled trials andsystematic evaluation methodology is low. CONCLUSION: In the future, more large sample, multicenter clinical randomized controlled trials should be conducted to obtain higher-level evidence-based medicine evidence to fully demonstrate the advantages of traditional Chinese medicine treatment, and promote the common development of traditional Chinese medicine cardiology and evidence-based medicine.

Analysis of risk factors for intolerance of valsartan with Sakubatrol in patients with heart failure

WANG Jia, WANG Lei, XU Binfa, LIU Feng, WEN Xin, CHEN Min, GAO Yinsi

2025, 30(2):  232-237.  doi:10.12092/j.issn.1009-2501.2025.02.010

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AIM: To investigate the risk factors for intolerance to sacubitril/valsartan in the treatment of heart failure. METHODS: A total of 124 heart failure patients hospitalized in our hospital from May 2023 to May 2024 were collected. Logistic regression analysis and nomogram analysis were used to identify the risk factors for drug tolerance. RESULTS: 22 patients exhibited intolerance, with low blood pressure being the primary cause (P<0.05). Multivariate regression analysis found that patients with a low BMI (OR 95%CI 1.814(1.385-2.525)) and those without concomitant right heart failure (OR 95%CI 4.998(1.552-17.301)) were more likely to experience drug intolerance. The model had a stable C-index of 0.923 (95%CI=0.863-0.975). CONCLUSION: Low BMI and absence of right heart failure are risk factors affecting the tolerance to sacubitril/valsartan, which has certain value for guiding clinical treatment. Large-sample clinical studies are still needed to confirm these findings.

Effects of different frequencies 0.01% atropine eye drops on the ocular surface in adolescent myopia control

XU Qibin, LI Qiushi, WEI Jiamin, DAI Hongmei

2025, 30(2):  238-243.  doi:10.12092/j.issn.1009-2501.2025.02.011

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AIM: To evaluate the effect of different frequencies 0.01% atropine eye drops on the ocular surface in adolescent myopia control. METHODS: A total of 84 adolescent patients with myopia were recruited for this study. They were randomly assigned to receive 0.01% atropine eye drops at different frequencies (morning group, evening group, morning and evening group). During the treatment period, ocular and systemic adverse reactions were observed, spherical equivalent refraction (SER) and axial length (AX) were examined. Additionally, ocular surface disease index (OSDI) questionnaire was obtained, tear meniscus height (TMH) ,non-invasive first tear film break-up time (NifBUT), non-invasive average tear film break-up time (NiaBUT), and meibomian gland atrophy score (MaS) were measured by Keratograph 5M. RESULTS: During the 6-month treatment with 0.01% atropine eye drops, all adverse reaction  symptoms were relatively mild and infrequent. Only one case of systemic reaction was reported, with temporary xerostomia. Six patients reported discomfort such as ocular itching and dryness. The ocular reactions of photophobia and blurred near vision were slightly more common in the morning and combined morning-evening groups compared to the evening group, but there were no significant differences among the three groups (P>0.05). Compared to baseline, there were significant differences in SER and AX among the three groups after six months of treatment (P<0.05). Compared to baseline, no significant differences were observed in the Morning group after six months of treatment in terms of OSDI score (P=0.656), TMH value (P=0.362), NifBUT (P=0.510), NiaBUT (P=0.700), and MaS (P=0.846). Similarly, no significant changes were found in the Evening group regarding OSDI score (P=0.429), TMH value (P=0.462), NifBUT (P=0.462), NiaBUT (P=0.598), and MaS (P=0.351). Additionally, in the Morning and evening group, no significant changes were detected in OSDI score (P=0.457), TMH value (P=0.748), NifBUT (P=0.197), NiaBUT (P=0.070), and MaS (P=0.802) after six months of treatment. CONCLUSION: After six months of using 0.01% atropine eye drops with different frequencies in adolescent myopia control, there was no significant impact on the ocular surface.

Characteristics and applications in bioequivalence of physiologically based on pharmacokinetic model

WANG Jianxiong, HU Xiao, MIAO Beibei, ZHANG Lan

2025, 30(2):  244-250.  doi:10.12092/j.issn.1009-2501.2025.02.012

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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.

Research progress of Pinellia ternata and its active ingredients in cardiovascular diseases

SONG Min, DIAO Tingting, WANG Yichao, LIU Luyi, QI Qiqi, BI Jingjing, ZHU Nailiang, QIAO Xinrong

2025, 30(2):  251-264.  doi:10.12092/j.issn.1009-2501.2025.02.013

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Cardiovascular diseases (CVD) are chronic disease with high morbidity and mortality in the world. Pinellia ternata is a traditional Chinese medicinal herb and has the effects on drying dampness, resolving phlegm, lowering symptoms, stopping vomiting and relieving swelling. In recent years, researches showed that Pinellia ternata and its active ingredients (β- sitosterol, baicalin, baicalein, quercetin) had significant effects in the treatment of cardiovascular diseases. This review summarized and analyzed the role and mechanism of Pinellia ternata and its active ingredients in cardiovascular diseases, which provided a theoretical basis for its clinical application.

Research progress on the effect of hippocampal FXR regulation of CREB-BDNF signaling pathway on depression

HE Hui, GUO Mingliang, RAN Licheng, WANG Yajun

2025, 30(2):  265-271.  doi:10.12092/j.issn.1009-2501.2025.02.014

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Depression is a mental disorder characterized by mood disturbances that pose a significant threat to human mental and physical health. In recent years, the farnesoid X receptor (FXR) has been found to be expressed in brain regions such as the hippocampus and is closely related to the onset of depression. It can also affect the downstream target cAMP response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling pathway, holding promise as a new target for the treatment of depression. This article analyzes how hippocampal FXR regulates the CREB-BDNF signaling pathway and summarizes the latest research progress related to the pathogenesis of depression, with the aim of providing precise targeted ideas for the drug development and clinical treatment of depression.

Progress in the pharmacological effects of naringin on cardiovascular diseases

LIU Dan, MIAO Jiawei, TAN Zihao, HE Chunyao, ZHAO Mingzhu, HE Xiuzhen

2025, 30(2):  272-281.  doi:10.12092/j.issn.1009-2501.2025.02.015

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Naringin is a flavonoid compound with a wide range of biological and pharmacological activities, which can be used in treating tumor, diabetes, neurodegenerative diseases, cardiovascular diseases, metabolic syndrome, etc. Among them, the application of naringin in cardiovascular diseases has attracted the attention of many researchers. This article mainly reviews the role of naringin in cardiovascular disease (regulating blood lipids, anti atherosclerosis, lowering blood pressure, inhibiting myocardial hypertrophy, anti myocardial infarction, protecting myocardial ischemia/reperfusion injury, reducing myocardial ischemia/reperfusion injury and improving pulmonary arterial hypertension), the protective effect on cardiotoxicity, and the signal pathways in cardiovascular disease (PI3K-Akt-mTOR, p-eNOS/p-Akt/p-ERK, miR-126/GSK-3 β/β-Catenin), clinical trials, etc. This paper is expected to review the current research status of naringin in cells and animal models so as to reveal its clinical application prospects and provide reference for further research in related fields.

The mechanism and application prospects of mitochondrial quality control in osteoarthritis

WANG Liang, DENG Yinshuan, QU Tao, DA Chaoming, HE Yunfei, LIU Rui, NIU Weimin, YAN Weishun, CHEN Zhen, LI Shuo, YANG Zhiyun, GUO Binbin, LAI Xueqian

2025, 30(2):  282-288.  doi:10.12092/j.issn.1009-2501.2025.02.016

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Osteoarthritis (OA) is a common joint disease in clinical practice, and cartilage damage is a typical pathological change. The pathogenesis of OA is complex, and various adverse factors can lead to the occurrence of OA. Mitochondria are important organelles within cells and play important roles in cellular physiological and pathological activities. Mitochondrial quality control is an important regulatory mechanism in the body to maintain normal mitochondrial structure and function, mainly including mitochondrial biogenesis, mitochondrial dynamics, mitochondrial autophagy, mitochondrial oxidative stress, and other forms. The imbalance of mitochondrial quality control in chondrocytes is closely related to the occurrence and development of osteoarthritis, and regulating the balance of mitochondrial quality control is a potential therapeutic point for osteoarthritis. The author reviewed relevant research literature in recent years to provide a review of the relationship between mitochondrial quality control and the occurrence and development of osteoarthritis, in order to provide new ideas and directions for the research and diagnosis and treatment strategies of osteoarthritis.