1.Research progress on the mechanism and clinical application of the effective ingredients from Sijunzi decoction in the treatment of gastric cancer
Hongwei ZHANG ; Wenfei DANG ; Xin SUO ; Ru ZHANG ; Yan ZHANG ; Ziming JIN ; Xia DOU
China Pharmacy 2025;36(5):624-629
Gastric cancer is a common malignant tumor of the digestive tract and can be classified as “fullness of the stomach”, “epigastric pain”, “noise” and other categories in the field of traditional Chinese medicine. Sijunzi decoction is composed of Panax ginseng, Poria cocos, Atractylodes macrocephala, and honey-fried Glycyrrhiza uralensis, and it has the effect of tonifying qi and strengthening the spleen. This article summarizes the active ingredients, mechanism of action, and clinical application research progress of Sijunzi decoction in treating gastric cancer. The results show that the main active ingredients of Sijunzi decoction include ginsenosides, atractylenolide, pachymic acid, glycyrrhizic acid, etc.; Sijunzi decoction and its effective ingredients can play an anti-gastric cancer role by inhibiting the proliferation of gastric cancer cell, inducing apoptosis of gastric cancer cell, enhancing gastric cancer cell chemotherapy sensitivity, and inhibiting invasion and metastasis of gastric cancer cell. In addition, Sijunzi decoction can enhance the efficacy of chemotherapy drugs, strengthen the immune function of the body and lower serum cancer marker levels during the clinical treatment of gastric cancer.
2.Improvement effects and mechanism of Xiangsha yiwei tang on gastric mucosal injury in rats with chronic atrophic gastritis
Pengfei XIA ; Di JIN ; Jin LIANG ; Yi YU ; Jinjun DU ; Zhanyong JIN ; Jun FANG ; Xia YANG ; Huiwu LIU
China Pharmacy 2025;36(11):1311-1316
OBJECTIVE To investigate the improvement effects and mechanism of Xiangsha yiwei tang on gastric mucosal injury in rats with chronic atrophic gastritis (CAG). METHODS Rats were randomly assigned into normal control group, model group, Xiangsha yiwei tang low-, medium- and high-dose groups (6, 12, 18 g/kg, calculated by crude drug), and high-dose group of Xiangsha yiwei tang+740 Y-P [Xiangsha yiwei tang 18 g/kg+transforming growth factor β1/phosphatidyl inositol 3 kinase/ protein kinase B(TGF-β1/PI3K/Akt) pathway activator group 740 Y-P 10 mg/kg], with 18 rats in each group. Rats in each group were administered the corresponding drugs via oral gavage or injection, once daily, for 4 consecutive weeks. Gastric mucosal blood flow, the levels of serum gastrointestinal hormones [including motilin (MTL), gastrin (GAS), and pepsinogen (PP)], as well as inflammatory cytokines [including tumor necrosis factor- α (TNF- α), interleukin-1β (IL-1β), IL-6] in rats were measured. Pathological damage to gastric mucosal tissue was observed in rats; the apoptotic rate of gastric mucosal cells was detected. The expressions of TGF-β1/PI3K/Akt signaling pathway-related proteins and apoptosis-related proteins [including B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax)] in the gastric mucosal tissues of rats were assessed. RESULTS Compared with normal control group, model group had abnormal gastric mucosal tissue structure, with shedding of gastric mucosal epithelial cells, and prominent infiltration of inflammatory cells. Gastric mucosal blood flow, the serum levels of MTL, GAS, PP, and Bcl-2 protein expression were lowered significantly, while serum levels of TNF-α, IL-1β and IL-6, apoptosis rate, protein expressions of Bax and TGF-β1, the phosphorylations of PI3K and Akt were increased significantly (P<0.05). Compared with model group, Xiangsha yiwei decoction groups exhibited attenuated histopathological injuries in gastric mucosal tissues, reduced inflammatory cell infiltration, and significant improvements in the aforementioned quantitative parameters (P<0.05). Compared with high-dose group of Xiangsha yiwei tang, high-dose group of Xiangsha yiwei decoction combined with 740 Y-P exhibited significantly aggravated histopathological injuries in gastric mucosal tissues, and the aforementioned quantitative parameters were markedly reversed (P<0.05). CONCLUSIONS Xiangsha yiwei tang can alleviate gastric mucosal damage in CAG rats, and its mechanism of action is related to the inhibition of TGF-β1/PI3K/Akt signaling pathway.
3.Effect of Highly Expressed lysophosphatidyllecithin acyltransferase 4 on Proliferation of Pancreatic Cancer
Haoming LU ; Jin HUANG ; Yixi WU ; Jiayin LU ; Zhenpei LI ; Xiuying XIONG ; Jiawen YE ; Xia YANG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):401-409
ObjectiveTo investigate the expression level of lysophosphatidyllecithin acyltransferase 4 (LPCAT4) in pancreatic cancer and its effect on the proliferation of pancreatic cancer cells. MethodsIn this study, the differentially expressed genes of patients with KRAS mutant and wild-type pancreatic cancer were analyzed by online database LinkedOmics. The LPCAT4 expression in pancreatic cancer tissues was analyzed online by the University of Alabama at Birmingham Cancer Data Analysis (UALCAN), Sangerbox and gene expression profile interaction analysis 2 (GEPIA2). Kaplan-Meier Plotter database was used to explore the correlation between LPCAT4 and the prognosis of patients with pancreatic cancer. The expression of LPCAT4 in human pancreatic cancer cells were detected by quantitative real-time PCR and Western blot analysis. LPCAT4 was knocked down in the high-expressing SW1990 cell line and overexpressed in the low-expressing MIA PaCa-2 cell line. The effects of LPCAT4 expression on cell proliferation were assessed using CCK-8 and EdU assays. STRING and GEPIA2 databases were used to obtain LPCAT4 binding and coexpressed genes in tumors, which were then analyzed by GO and KEGG. ResultsAnalysis of the LinkedOmics online database revealed a significant upregulation of LPCAT4 in patients with KRAS mutant pancreatic cancer compared to patients with KRAS wild-type pancreatic cancer. The online analysis of GEPIA2, UALCAN and Sangerbox 3.0 showed that the expression of LPCAT4 was higher in pancreatic cancer than in normal tissues. Analysis of the Kaplan-Meier Plotter database revealed that high LPCAT4 expression was associated with poorer prognosis in pancreatic cancer patients.Western blot and qPCR results showed that expression of LPCAT4 in pancreatic cancer cell lines was significantly higher than in normal pancreatic ductal epithelial cells. Knockdown of LPCAT4 in SW1990 cells inhibited proliferation, while overexpression in MIA PaCa-2 cells promoted proliferation. Enrichment analysis indicated that LPCAT4 was closely related to sulfur metabolism. ConclusionsLPCAT4 is highly expressed in pancreatic cancer and is associated with poor prognosis of patients. It plays a significant regulatory role in the proliferation of pancreatic cancer cells, with its expression level closely correlated with cell proliferation capacity. These findings reveal the critical role of LPCAT4 in the malignant progression of pancreatic cancer and provide important evidence for its potential as a therapeutic target.
4.Research progress on impacts of air pollutants, gut microbiota, and seminal microbiota on semen quality
Wenchao XIA ; Jiahua SUN ; Yuya JIN ; Ruixin LUO ; Ruyan YAN ; Yuming GUI ; Yongbin WANG ; Fengquan ZHANG ; Wei WU ; Weidong WU ; Huijun LI
Journal of Environmental and Occupational Medicine 2025;42(8):1003-1008
In recent years, China has been facing the dual challenges of declining fertility rates and births, with male reproductive health issues, especially the decline in semen quality, identified as a pivotal contributor to this phenomenon. Meanwhile, accumulating evidence indicates that air pollutants, an increasingly severe environmental problem, can damage semen quality not only directly through their biological toxicity but also indirectly by disrupting the composition of microbial communities in the gut and semen, thereby dysregulating immune function, endocrine homeostasis, and oxidative stress responses. The gut microbiota and semen microbiota, as important components of the human microecosystem, play crucial roles in maintaining reproductive health. This article comprehensively reviewed the research progress on the potential effects of air pollutants (particulate matter and gaseous pollutants), gut microbiota, and semen microbiota on semen quality. Specifically, it elucidated the mechanisms of interaction between these factors and explored how they affect male fertility.
5.A prediction model for diabetic peripheral neuropathy among patients with type 2 diabetes mellitus
LIU Mingkun ; ZHANG Fengxiang ; HAN Caijing ; WANG Xia ; CHEN Shikun ; JIN Mei ; SUN Jinyue
Journal of Preventive Medicine 2025;37(7):692-696
Objective:
To establish a risk prediction model for diabetic peripheral neuropathy (DPN) among patients with type 2 diabetes mellitus (T2DM), so as to provide a basis for DPN prevention and control.
Methods:
T2DM inpatients aged 18-65 years admitted to the department of endocrinology and metabolism at Affiliated Hospital Shandong Second Medical University from April to December 2024 were selected as study subjects. Age, T2DM duration, hypertension history, 25-hydroxyvitamin D, serum C-peptide, and high density lipoprotein cholesterol (HDL-C) were collected through electronic medical records. Risk predictors of DPN among T2DM patients were screened using multivariable logistic regression model, and a nomogram was established. The receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis were employed to evaluate the discrimination, calibration and clinical utility of the nomogram, respectively.
Results:
A total of 598 T2DM patients were enrolled, including 359 (60.03%) males and 239 (39.97%) females. The median age was 54.50 (interquartile range, 15.00) years, the median T2DM duration was 6.00 (interquartile range, 9.00) years. There were 262 cases of T2DM patients with DPN, accounting for 43.81%. Multivariable logistic regression identified hypertension history (OR=3.260, 95%CI: 2.220-4.790), alcohol use history (OR=2.150, 95%CI: 1.390-3.310), diabetes complications (OR=0.430, 95%CI: 0.270-0.680), T2DM duration (OR=1.040, 95%CI: 1.010-1.070), body mass index (OR=1.130, 95%CI: 1.070-1.200), 25-hydroxyvitamin D (OR=0.930, 95%CI: 0.910-0.960), and HDL-C (OR=0.400, 95%CI: 0.230-0.720) as risk predictors for DPN among T2DM patients. The area under the ROC curve of the established risk prediction model was 0.774 (95%CI: 0.737-0.812), with a sensitivity of 0.710 and a specificity of 0.723. The calibration curve after repeated sampling calibration approached the standard curve. Decision curve analysis showed that when the risk threshold probability was 0.2 to 0.4, the model demonstrates favorable clinical applicability.
Conclusion
The risk prediction model established in this study has favorable discrimination, calibration, and clinical utility, can effectively predict the risk of DPN among T2DM patients aged 18-65 years.
6.Association between overweight, obesity, central obesity and hypertension
YE Zhenmiao ; ZHANG Mohan ; FAN Lihui ; XIE Yimin ; JIANG Xuexia ; ZHENG Yuhang ; LUO Yongyuan ; XIA Zhezheng ; JIN Xi ; SUN Qian
Journal of Preventive Medicine 2025;37(11):1113-1118
Objective:
To investigate the association between overweight, obesity, central obesity and hypertension, so as to provide the basis for formulating targeted hypertension prevention and control strategies.
Methods:
Permanent residents aged ≥18 years were selected in Wenzhou City, Zhejiang Province from June 2023 to August 2024 by a multistage cluster random sampling method. Data on demographic information, lifestyle, height, weight, waist circumference (WC), blood pressure, and blood biochemical indicators were collected through questionnaire surveys, physical examinations, and laboratory tests. The prevalence of hypertension was calculated and standardized using the data of the Sixth National Population Census in 2010. Body mass index (BMI) was calculated to determine overweight and obesity, while WC was used to identify central obesity. The association between overweight, obesity, central obesity and hypertension were analyzed using multivariable logistic regression models.
Results:
A total of 38 593 residents were surveyed, including 19 481 (50.48%) males and 19 112 (49.52%) females. The median age was 46.00 (interquartile range, 26.00) years. The rates of overweight, obesity, and central obesity were 32.74% (12 634 individuals), 10.27% (3 963 individuals), and 27.87% (10 755 individuals), respectively. There were 11 813 cases of hypertension, with a prevalence and standardized prevalence of 30.61% and 24.41%, respectively. Multivariable logistic regression analysis showed that after adjusting for demographic information, lifestyle, diabetes and dyslipidemia, the likelihood of hypertension in the overweight and obesity groups was 1.927 (95%CI: 1.815-2.045) times and 3.724 (95%CI: 3.404-4.073) times that of the normal BMI group, respectively. The likelihood of hypertension in the central obesity group was 2.346 (95%CI: 2.214-2.486) times that of the normal WC group. The likelihood of hypertension in the central obesity only, overweight only, overweight with central obesity, obesity only and obesity with central obesity groups was 1.586 (95%CI: 1.391-1.809), 1.704 (95%CI: 1.582-1.835), 2.433 (95%CI: 2.254-2.626), 1.768 (95%CI: 1.424-2.194), and 4.466 (95%CI: 4.053-4.921) times that of the normal BMI and WC group, respectively.
Conclusions
Overweight, obesity and central obesity were all associated with hypertension among adult residents. The highest likelihood of hypertension was observed among adult residents with both general obesity and central obesity.
7.Protective Effect of Liuwei Dihuangwan on Mitochondrial Damage in AD Model of Caenorhabditis Elegans
Jinfeng ZHANG ; Yuliang TONG ; Jiapeng WANG ; Ting SU ; Deping ZHAO ; Hao YU ; Kun ZUO ; Ziyue ZHU ; Meiling JIN ; Ning ZHANG ; Xia LEI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):18-25
ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan (LW) on mitochondrial damage in the Alzheimer's disease (AD) model of Caenorhabditis elegans (C. elegans). MethodC. elegans transfected with human β-amyloid protein (Aβ) 1-42 gene was used as an AD model. The rats were divided into blank group, model group, metformin group (50 mmol·L-1), and low, medium, and high dose (1.04, 2.08, 4.16 g·kg-1) LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine (5-HT) in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate (ATP) kit, and mitochondrial membrane potential was detected by the JC-1 method. In addition, the mRNA expression of Aβ expression gene (Amy-1), superoxide dismutase-1 (SOD-1), mitochondrial transcription factor A homologous gene-5 (HMG-5), mitochondrial power-associated protein 1 (DRP1), and mitochondrial mitoprotein 1 (FIS1) was detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT (P<0.05) and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group, in the model group, the mRNA expression of Aβ protein and Amy-1 increased (P<0.01), and the mRNA expression of SOD-1 and HMG-5 decreased (P<0.01). The mRNA expression of DRP1 and FIS1 increased (P<0.01), and the level of mitochondrial membrane potential decreased (P<0.05). The content of ATP decreased (P<0.01). Compared with the model group, in the positive medicine group and medium and high dose LW groups, the mRNA expression of Aβ protein and Amy-1 decreased (P<0.05,P<0.01), and the mRNA expression of SOD-1 and HMG-5 increased (P<0.01). The mRNA expression of DRP1 decreased (P<0.05,P<0.01), and that of FIS1 decreased (P<0.01). The level of mitochondrial membrane potential increased (P<0.01), and the content of ATP increased (P<0.05,P<0.01). ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria, protect mitochondrial DNA, reduce the fragmentation of mitochondrial division, repair the damaged mitochondria, adjust the mitochondrial membrane potential, restore the level of neuronal ATP, and reduce the neuronal damage caused by Aβ deposition.
8.Clinical significance of immunotherapy-associated oxidative stress gene expression in lung adenocarcinoma and its relationship with immune cell infiltration and drug sensitivity
JIN Shan1,2 ; LI Xin1,2 ; WANG Ruolan1,2 ; XIA Wei2 ; HE Juan2
Chinese Journal of Cancer Biotherapy 2024;31(1):62-74
[摘 要] 目的:探究肺腺癌中与免疫治疗相关氧化应激基因(IROSG)及其与肿瘤组织免疫浸润和患者预后的关系。方法:从TCGA数据库和GEO数据库下载肺腺癌患者IROSG表达数据及相关临床信息。对非小细胞肺癌免疫治疗队列进行差异基因表达分析以获取免疫治疗相关基因,然后与从GeneCards数据库筛选的氧化应激相关基因取交集得到IROSG。基于得到的IROSG对肺腺癌患者进行分型,对亚型的差异表达基因进行单因素COX、LASSO和多因素COX回归分析以构建预后模型。使用模型公式计算每个患者的风险评分,并将患者划分为高、低风险组。从多个层面验证模型的预测效能,并进行肿瘤微环境(TME)分析、免疫治疗反应预测和药物敏感性分析。结果:通过数据库分析获取82个IROSG,IROSG高表达的肺腺癌患者预后较好(P<0.05)。基于IROSG表达水平分型和风险评分构建的肺腺癌患者预后模型预测能力好,基于风险评分和病例特征等预后因子构建的列线图和校正曲线能较好地预测肺腺癌患者的总生存率。低风险组主要富集于同种异体移植物排斥和自身免疫性疾病等通路,而高风险组主要富集在细胞周期和DNA复制等通路上,且低风险组肺腺癌组织中免疫细胞浸润水平较高。高、低风险评分结合肿瘤突变负荷(TMB)、TME、肿瘤免疫功能障碍和排斥(TIDE)评分和免疫检查点分子表达水平能较好地预测肺腺癌患者预后、免疫治疗反应和对化疗药物的敏感性。结论:本研究构建了一个可以预测肺腺癌患者预后和免疫治疗反应的模型,可为肺腺癌患者个体化治疗提供了理论依据。
9.Prognostic Value and Immune Infiltration of Anoikis-related LncRNAs in Lung Adenocarcinoma
Xin LI ; Juan HE ; Shan JIN ; Ruolan WANG ; Qibiao LUO ; Wei XIA
Cancer Research on Prevention and Treatment 2024;51(1):34-42
Objective To explore the prognostic value and immune infiltration landscape of anoikis-related long noncoding RNAs (arlncRNAs) in lung adenocarcinoma. Methods RNA-seq and clinical data of lung adenocarcinoma were downloaded from the TCGA database, and anoikis-related genes were obtained from the GeneCards and Harmonizome databases. Coexpression, differential, and WGCNA analyses were performed to screen differentially expressed arlncRNAs closely related to the occurrence of lung adenocarcinoma. A prognostic risk model was then constructed based on the arlncRNAs, and its predictive efficacy was further validated. Finally, consensus clustering was used to identify the molecular subtypes associated with anoikis in lung adenocarcinoma. Results Seven prognostic arlncRNAs were identified, and the prognostic risk models established based on them had AUC values of ROC curves greater than 0.7. Survival and immune infiltration analyses revealed that low-risk patients had high overall survival and immune infiltration, implying that they experienced good immune treatment effects. Drug sensitivity analysis showed that the high-risk patients were more sensitive to commonly used chemotherapeutic agents than the low-risk patients. According to the expression of model genes, subtypes C1 and C2 were identified through consensus clustering, and C1 showed a good prognosis. Conclusion The prognostic risk model based on the seven arlncRNAs can effectively predict the prognosis of lung adenocarcinoma patients. The results of immune-related and drug sensitivity analyses provide a reference for the precise individualized treatment of patients with lung adenocarcinoma.
10.Neuroprotective effect of 7,8-dihydroxyflavone on cerebral hemorrhage in mice by regulating the TrkB/BDNF signal pathway
Kun WANG ; Li-Bo WEN ; Jin-Xia FU ; He-Nan ZHANG ; Li-Jun HAN
The Chinese Journal of Clinical Pharmacology 2024;40(1):52-56
Objective To investigate the neuroprotective effect of 7,8-dihydroxyflavone(7,8-DHF)on cerebral hemorrhage in mice by regulating the tyrosine kinase receptor B(TrkB)/brain derived neurotrophic factor(BDNF)signal pathway.Methods C57BL/6 mice were injected with bacterial collagenase V Ⅱ to establish cerebral hemorrhage model.The mice were randomly grouped into model group,control group(5 mg·kg-1 7,8-DHF),experimental group(1 mg·kg-1 K252a),and combined group(5 mg·kg-1 7,8-DHF+1 mg·kg-1 K252a),mice injected with normal saline were used as sham-operation group,with 10 mice in each group.After the treatment,the mice were scored for neurological function by Garcia method,brain water contents of the brain tissue were detected by the dry and wet weight method,the blood brain barrier permeability was examined using the Evans blue method,the neuronal apoptosis was detected by TUNEL method,and the protein expression levels of TrkB,phosphorylated TrkB(p-TrkB)and BDNF were detected by Western blot.Results The neurological function scores of control,experimental,combined,model and sham-operation groups were(15.47±1.55),(7.23±0.73),(10.55±1.06),(10.45±1.05)and(16.12±1.62)points;the brain water contents were(62.88±2.19)%,(83.77±3.11)%,(72.71±2.59)%,(72.88±2.61)%and(59.64±2.06)%;the Evans blue contents were(3.26±0.36),(16.23±1.63),(8.78±0.88),(9.47±0.95)and(1.02±0.11)μg·g-1;neuronal apoptosis rates were(9.82±0.99)%,(39.88±3.99)%,(22.15±2.24)%,(25.71±2.58)%and(6.46±0.65)%;p-TrkB/TrkB ratios were 1.01±0.11,0.21±0.03,0.48±0.05,0.49±0.05 and 1.03±0.11;the protein expression levels of BDNF were 1.15±0.12,0.18±0.02,0.46±0.05,0.42±0.05 and 1.18±0.12,respectively.The above indexes of sham-operation,control and experimental groups were compared with those of model group,and the above indexes of control and experimental groups were compared with those of combined group,the differences were statistically significant(all P<0.05).Conclusion 7,8-DHF has neuroprotective effect on mice with intracerebral hemorrhage,and its mechanism may be related to the activation of TrkB/BDNF signal pathway.


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