1.Efficacy Mechanism of Xianlian Jiedu Prescription Against Colorectal Cancer Recurrence vias Regulating Angiogenesis
Yanru XU ; Lihuiping TAO ; Jingyang QIAN ; Weixing SHEN ; Jiani TAN ; Chengtao YU ; Minmin FAN ; Changliang XU ; Yueyang LAI ; Liu LI ; Dongdong SUN ; Haibo CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):79-87
ObjectiveTo explore effect of Xianlian Jiedu prescription on the recurrence of colorectal cancer (CRC) and investigate the related mechanisms. MethodsA postoperative recurrence model was established in 25 Balb/c mice by injecting CT26 cells subcutaneously into the armpit, followed by surgical removal of 99% of the subcutaneous tumor. The mice were randomly divided into model group, low-dose Xianlian Jiedu prescription (XLJDP-L) group (6.45 g·kg-1·d-1), medium-dose Xianlian Jiedu prescription (XLJDP-M) group (12.9 g·kg-1·d-1), high-dose Xianlian Jiedu prescription (XLJDP-H) group (25.8 g·kg-1·d-1), and 5-fluorouracil (5-FU) group (1×10-3 g·kg-1·d-1). The mice were euthanized after 14 days of continuous intervention, and recurrent tumor tissue was harvested. Hematoxylin and eosin (HE) staining was used to observe pathological and morphological changes in the recurrent tumor tissue. Immunohistochemistry (IHC) was employed to assess the expression of proliferating cell nuclear antigen (Ki67), vascular endothelial growth factor (VEGF), and platelet-endothelial cell adhesion molecule (CD31) in recurrent tumor tissue. The Western blot was used to detect the protein expression levels of angiopoietin-2 (ANG-2), VEGF, phosphorylated-protein kinase B (p-Akt), protein kinase B (Akt), phosphorylated-phosphatidylinositol 3-kinase (p-PI3K), and phosphatidylinositol 3-kinase (PI3K) in recurrent tumor tissue. ResultsBefore treatment, there were no statistical differences in tumor volume, tumor weight, and body mass among the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group compared to the model group, indicating model stability. After treatment, compared with those in the model group, the tumor volume and tumor weight in the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly reduced (P<0.01), showing dose dependency. Meanwhile, there were no significant differences in body weight among the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group compared to the model group. HE staining showed that compared with that in the model group, tumor tissue in the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group had loosely arranged cells, increased intercellular spaces, small and shriveled nuclei, light staining, fewer mitotic figures and atypical nuclei, and increased necrotic areas. IHC showed that compared with those of the model group, the positive rates of Ki67, VEGF, and CD31 in the recurrent tumor tissue of the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly reduced (P<0.01) in a dose-dependent manner. Western blot results showed that compared with those of the model group, the protein expression levels of ANG-2 and VEGF in the recurrent tumor tissue of the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly downregulated (P<0.05, P<0.01), and the p-Akt/Akt and p-PI3K/PI3K ratios were significantly decreased in a dose-dependent manner (P<0.05, P<0.01). ConclusionXianlian Jiedu prescription significantly inhibits the recurrence of CRC in mice after subcutaneous tumor surgery. The mechanism may involve regulating the PI3K/Akt pathway and downregulating key angiogenic proteins such as ANG-2, VEGF, and CD31.
2.Effect of polystyrene microplastics combined with high-fat treatment on vascular endothelial cells
Jing WANG ; Jiani DIAO ; Jing LONG ; Yuguang HE ; Lipin TAN ; Xuemei CHEN ; Fangfang LI ; Junlin HE ; Yingxiong WANG ; Rufei GAO ; Weike LI
Journal of Chongqing Medical University 2025;50(7):969-976
Objective:To investigate the effect of polystyrene microplastics(PS-MPs)combined with high-fat treatment on vascular endothelial cells.Methods:Human umbilical vein endothelial cells(HUVECs)were cultured in the DMEM medium containing 5%fe-tal bovine serum.HUVECs were treated with conventional culture,high-fat treatment,and PS-MPs combined with high-fat treatment.The experiment was conducted in the three groups of control group,high-fat treatment group and PS-MPs+high-fat treatment group.CCK-8 assay was used to measure cell viability,F-actin staining was used to observe cell morphological changes,and flow cytometry,scratch assay,and tube formation assay were used to measure the apoptosis,migration,and tube-forming ability of cells.Results:After HUVECs were exposed to the high-fat environment,there was a significant reduction in cell viability,shrinkage of cells,a signifi-cant increase in cell apoptosis,and significant reductions in cell migration and tube-forming ability.Compared with the high-fat treat-ment group,there were no significant changes in cell viability,cell morphology,cell apoptosis,and cell migration ability after PS-MPs combined with high-fat treatment,but the tube-forming ability of cells was further impaired.Conclusion:High-fat treatment will affect cell viability,change cell morphology,and damage vascular endothelial cell function,and PS-MPs combined with high-fat treat-ment can aggravate the damage of vascular endothelial cell function.
3.Establishment of a prediction model for capecitabine chemotherapy-related hepatotoxicity in colorectal cancer patients based on metabonomics
Zeshuai LIN ; Jiani CHEN ; Houshan YAO ; Mingming LI ; Jia YAO
Academic Journal of Naval Medical University 2025;46(1):40-47
Objective To identify potential biomarkers and establish a prediction model for chemotherapy-related hepatotoxicity susceptibility based on plasma endogenous metabolites of colorectal cancer(CRC)patients before chemotherapy.Methods The plasma samples of 50 CRC patients before capecitabine chemotherapy and the records of their chemotherapy-related hepatotoxicity during the follow-up were collected.An ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)was used to perform untargeted metabolomic analysis.Based on bioinformatics analysis,differential analysis,correlation analysis,and random forest were used to screen for hepatotoxicity-related plasma endogenous metabolites.All samples were randomly assigned(7∶3)to training set or test set.A multivariate logistic regression model was established to predict the hepatotoxicity of capecitabine chemotherapy based on the training set data.The prediction effects of the model in the training,test and entire sets were evaluated by receiver operating characteristic(ROC)curve analysis.Results The endogenous metabolites related to hepatotoxicity in the plasma of CRC patients before chemotherapy were mainly lipid endogenous metabolites.A series of potentially important predictive biomarkers for hepatotoxicity susceptibility were identified,including sphingamine-1-phosphate,ceramide,galactose,arachidonic acid,tyrosine,biliverdin,myristic acid,phosphatidylcholine(35∶1),phosphatidylethanolamine(36∶1),and hexadecanoic acid.The area under curve values of the prediction model based on the above biomarkers in the training,test and entire sets were 0.946(95%confidence interval[CI]0.842-1.000),0.920(95%CI 0.720-1.000),and 0.912(95%CI 0.810-0.982),respectively.Conclusion The endogenous metabolites in the plasma of CRC patients before chemotherapy can effectively predict the hepatotoxicity of capecitabine chemotherapy.These hepatotoxicity biomarkers indicate that susceptible patients have characteristics related to lipid metabolism disorders.
4.Medication preparation for self-aid and buddy-aid in naval combat injuries
Shiqing LI ; Jingwen ZHAI ; Jiani CHEN ; Ruidong WANG ; Jie WU ; Suiyi LIU ; Hua WEI
Academic Journal of Naval Medical University 2025;46(2):258-262
Self-aid and buddy-aid are primary steps in battlefield first aid,offering the timeliest treatment effectiveness.Medications are indispensable key supplies in battlefield first aid,playing a crucial role in the timely treatment of the injured.This review provides an overview of medication preparation for battlefield first aid both domestically and internationally,aiming to provide reference for the medication preparation for self-aid and buddy-aid of naval combat injuries,so as to enhance the Navy's first-aid capability and medical support capability.
5.Clinical Experience Applying the "Kidney-supplementing and Blood-invigorating" Method to Treat Infertility of Repeated Implantation Failure
Kun MA ; Guanlan ZHONG ; Han ZHANG ; Dandan HE ; Jiani LI ; Qian LI ; Shanfeng GAO
Journal of Traditional Chinese Medicine 2024;65(24):2593-2597
kidney deficiency and blood stasis are believed to be the key pathogenesis of recurrent implantation failure (RIF), and therefore, it is proposed to take kidney-supplementing and blood-invigorating as the basic treatment method, and use it by stages to assist the controlled superovulation program of in vitro fertilization-embryo transfer (IVF-ET). The focus should be put on nourishing kidney yin, soothing the liver and invigorating blood during down-regulation period, using kidney yin-nourishing medicinals and modified Qinghao Biejia Decoction (青蒿鳖甲汤). During the ovulation induction period, the focus should be put on nourishing kidney yang, replenishing blood, and promoting blood circulation, with self-made Bushen Culuan Formula (补肾促卵方) in modifications. After transplantation, it is suggested to put focus on tonifying the kidneys and replenishing essence, and self-made Wuzi Yanzong Guchong Decoction (五子衍宗固冲汤) in modifications can be used. At the same time, fetal protection treatment should be carried out for pregnant women, and modified Shou Tai Pill (寿胎丸) can be used to tonify the kidneys and calm the fetus.
6.Influencing factors for chronic pancreatitis complicated by pancreatogenic portal hypertension and establishment of a predictive model
Jiani YANG ; Zhini MA ; Yingxia HU ; Zongshuai LI ; Yan LIU ; Hairong ZHANG ; Yinglei MIAO
Journal of Clinical Hepatology 2024;40(7):1438-1445
Objective To investigate the influencing factors for chronic pancreatitis(CP)complicated by pancreatogenic portal hypertension(PPH),and to establish a predictive model.Methods A retrospective analysis was performed for the clinical data of 99 patients with CP complicated by PPH who were hospitalized in The First Affiliated Hospital of Kunming Medical University,Chuxiong Yi Autonomous Prefecture People's Hospital,Wenshan People's Hospital,and Puer People's Hospital from January 2017 to December 2022,and these patients were enrolled as PPH group.The incidence density sampling method was used to select 198 CP patients from databases as control group.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.The Least Absolute Shrinkage and Selection Operator(LASSO)regression model was used to identify the potential predictive factors for CP complicated by PPH,and the predictive factors obtained were included in the multivariate Logistic regression analysis to obtain independent risk factors,which were used to establish a nomogram prediction model.The receiver operating characteristic(ROC)curve,the calibration curve,and the Hosmer-Lemeshow goodness-of-fit test were used to perform internal validation of the model,and the clinical decision curve was used to assess the clinical practicability of the model.Results There were significant differences between the two groups in sex,history of recurrent acute pancreatitis attacks,acute exacerbation of CP,bile duct stones,peripancreatic fluid accumulation,pseudocysts,pulmonary infection,elevated C-reactive protein(CRP),elevated procalcitonin,fibrinogen(FIB),neutrophil-lymphocyte ratio(NLR),gamma-glutamyl transpeptidase,total bilirubin,direct bilirubin,low-density lipoprotein(LDL),serum amylase,D-dimer,and serum albumin(all P<0.05).The predictive variables obtained by the LASSO regression analysis included sex,recurrent acute pancreatitis attacks,bile duct stones,peripancreatic fluid accumulation,pulmonary infection,pseudocysts,CRP,NLR,FIB,and LDL.The multivariate Logistic regression analysis showed that sex(odds ratio[OR]=2.716,P<0.05),recurrent acute pancreatitis attacks(OR=2.138,P<0.05),peripancreatic fluid accumulation(OR=2.297,P<0.05),pseudocysts(OR=2.805,P<0.05),and FIB(OR=1.313,P<0.05)were independent risk factors for CP complicated by PPH.The above factors were fitted into the model,and the Bootstrap internal validation showed that the nomogram model had an area under the ROC curve of 0.787(95%confidence interval:0.730—0.844),and the calibration curve was close to the reference curve.The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good degree of fitting(χ2=7.469,P=0.487).The clinical decision curve analysis showed that the prediction model had good clinical practicability.Conclusion Male sex,recurrent acute pancreatitis attacks,peripancreatic fluid accumulation,pseudocysts,and FIB are independent risk factors for CP complicated by PPH,and the nomogram model established has good discriminatory ability,calibration,and clinical practicability.
7.Efficacy Evaluation of Qishen Yizhi Formula in Improving the Learning and Memory Ability of D-Galactose Induced Suba-cute Aging Mice
Yang CHEN ; Ziqiang ZHU ; Yunqing LU ; Jiani ZHENG ; Cheng CAO ; Jiaxiang TONG ; Xuan LI ; Sheng GUO ; Hongjie KANG ; Jinao DUAN ; Yue ZHU
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(2):145-152
OBJECTIVE To evaluate the effect of Qishen Yizhi formula on improving learning and memory ability in D-galactose subcutaneous injection induced subacute aging mice.METHODS Subacute aging mice model mice were developed by D-galactose subcutaneous injection and then treated with positive drug donepezil(2 mg·kg-1·d-1)and Qishen Yizhi formula water extracts in low(1.33 g·kg-1·d-1)and high dose group(2.67 g·kg-1·d-1).The learning and memory abilities of mice were evaluated using Morris water maze and Y maze tests;HE staining was used to examine hippocampal damage in model mice;TUNEL was used to detect apoptosis of mouse hippocampal tissue;ELISA was used to detect the expression levels of oxidative stress factors and inflammatory fac-tors in the mouse hippocampus tissue;Western blot was used to detect the expression of signaling pathway proteins related to apoptosis,oxidative stress and inflammatory stress in the hippocampus of mice.RESULTS The water extract of Qishen Yizhi formula signifi-cantly shortened the latency and distance of model mice for reaching the platform in the water maze test(P<0.01),and significantly increased the number of crossing the platform(P<0.01);increased the exploration time and number of the Y maze new arm in model mice(P<0.05);inhibited the TUNEL fluorescence expression in the hippocampus of model mice(P<0.01);upregulated the activity of the oxidative stress factor superoxide dismutase(SOD)(P<0.05)and glutathione(GSH)content(P<0.05),and downregulated malondialdehyde(MDA)content(P<0.05);reduced interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF-α)expression levels(P<0.05,P<0.01);decreased the expression of apoptosis signaling pathway proteins Cleaved Caspase-3 and Caspase-3(P<0.05),upregulated the expression of oxidative stress signaling pathway proteins Nrf2 and HO-1(P<0.05),and downregulated the expression of inflammatory stress signaling pathway proteins p-NF-κB and NF-κB(P<0.05).CONCLUSION Qishen Yizhi for-mula can improve the learning and memory ability of subacute aging model mice injected with D-galactose,which may be related to its inhibitory effect on hippocampal oxidative stress and inflammatory stress.
8.Progression of Tripterygium wilfordii polyglycoside in mice with premature ovarian insufficiency at various time points
Linna MA ; Kun MA ; Xiaodi FAN ; Jie LUO ; Shanfeng GAO ; Jiani LI ; Han ZHANG
Chinese Journal of Comparative Medicine 2024;34(2):35-44,153
Objective Changes in relevant indexes in the mouse model of early-onset ovarian insufficiency caused by Tripterygium wilfordii polyglycoside were analyzed,and the optimal time point for intervention was determined.Methods Forty female ICR mice were randomly divided into control and A,B,C,and D model groups with eight mice in each group.The control group was gavaged with purified water for 14 days(0.01 mL/10 g),and the remaining groups were administered a Tripterygium wilfordii polyglycoside suspension(80 mg/kg,0.01 mL/10 g)for 1 day(A model group),3 days(B model group),7 days(C model group),or 14 days(D model group),and samples were collected.Body weight and wet weights of the uterus and bilateral ovaries of mice were determined in each group.Serum FSH,LH,E2,P,AMH,INH-B,and T contents were measured using enzyme-linked immunoassays.HE staining was used to observe the number and developmental status of follicles and corpus luteum at all levels in mice of each group.TUNEL staining was used to detect the apoptosis in the ovaries of mice in each group.IHC detected expression of VEGFA,CD34,and EPO proteins in the ovaries of mice in each group.mRNA expression of HIF-1α,SDF-1,and CXCR4 in each group of mice was detected by PCR.Results Compared with the control group,changes in indicators in model A mice did not meet the POI modeling standard.The ovarian index,uterine index,and body weight of mice in the B model group were decreased significantly(P<0.01),the weight of the C model group was decreased significantly(P<0.01),and the ovarian index of the D model group was decreased significantly(P<0.05).Serum contents of FSH and LH in B,C,and D model groups were increased(P<0.05,P<0.01),the E2,PROG,AMH,INH-B,and T contents were decreased(P<0.01).The numbers of basal follicles,pre-sinus follicles,sinusoidal follicles,antral follicles,preovulatory follicles,and corpus luteum were decreased significantly(P<0.05,P<0.01)and the number of atresia follicles was increased significantly(P<0.01)in B,C,and D model groups.The apoptotic area of TUNEL staining in A,B,C,and D model groups was increased significantly(P<0.05,P<0.01).Expression of CD34,VEGFA,and EPO in B,C,and D model groups was decreased significantly(P<0.05,P<0.01).mRNA expression of HIF-1α,SDF-1,and CXCR4 in A and B model groups was significantly increased(P<0.05,P<0.01).Compared with the B model group,the relevant indexes of C and D model groups were changed significantly,indicating that C and D models were more serious and tended to develop POF.Conclusions The B model group is the turning point of ovarian function from impaired POI to irreversible POF,suggesting that 3 days of administrating Tripterygium wilfordii polyglycoside is optimal to induce a POI disease model for effective drug intervention.
9.Investigation and study of factors related to NCD health management of basic public health services in Chongqing and Guizhou Province
Shili LIU ; Jiani ZHOU ; Quan YUAN ; Geng WANG ; Yong CHEN ; Qingning HUANG ; Ying LI
Chongqing Medicine 2024;53(2):276-280,285
Objective To analyze the health management situation of non-communicable chronic disease(NCD)in Chongqing City and Guizhou Province and its influencing factors.Methods A stratified random sampling method was used to select 16 representative primary medical and health institutions from Chongqing City and Guizhou Province as the research sites,and the data were collected through the combination method of qualitative and quantitative research.Results A total of 760 patients with NCD were surveyed,and the awareness rate,utilization rate and satisfaction rate of the NCD health management program all exceeded 84.2%,while the awareness rate,utilization rate and satisfaction rate of follow-up and categorical intervention were the lowest.The awareness rate of hypertension physical examination in the patients with<60 years old was lower than that in the patients with 60-<70 years old(OR=4.28,95%CI:1.43-12.81)and the pa-tients with ≥70 year sold(OR=3.16,95%CI:1.12-8.91);the utilization rate of diabetes screening in the patients with<60 years-old was lower than that in the patients with ≥70 years old(OR=2.70,95%CI:1.08-6.76)and the awareness rate of hypertension physical examination was lower than that of the patients with 60-<70 years old(OR=4.24,95%CI:1.01-17.75);the awareness rate of hypertension physical ex-amination in the patients in Chongqing City was higher than that in Guizhou Province(OR=0.15,95%CI:0.04-0.54)and the utilization situation was better than that in Guizhou Province(OR=0.13,95%CI:0.05-0.34).Conclusion The overall situation of NCD management services in Chongqing City and Guizhou Province is good,but the service quality of follow-up and classified intervention projects needs to be further improved.
10.Exploration of Anti-depression Mechanism of Kai-Xin-San via Regulation of Neurogenesis of Hippocampus on Chronic Unpredictable Mild Stress Induced Mice
Jiani ZHENG ; Lingxin HUANG ; Yunqing LU ; Xuan LI ; Yang CHEN ; Jiaxiang TONG ; Ziqiang ZHU ; Jinao DUAN ; Lejun LI ; Yue ZHU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):19-30
Objective To explore the anti-depression mechanism of Kai-Xin-San(KXS)via regulation of neurogenesis in hippocampus of depression-like mice.Methods The extracts of KXS were prepared and the anti-depression effects of KXS were evaluated by behavioral tests on chronic unpredictable mild stress(CUMS)induced depression-like mice.Evaluating depression-like behavior in CUMS mice through sucrose preference test,forced swimming test,tail suspension test,and other methods.Neurogenesis in hippocampus were determined by immunofluorescence assay.In addition,effects of KXS on regulating nestin expression and Wnt/b-catenin signaling pathway were explored by western blotting analysis.Amounts of cortisol,corticotropin-releasing factor(CRF),adrenocorticotropic hormone(ACTH),brain-derived neurotrophic factor(BDNF)and nerve growth factor(NGF)were determined by ELISA tests.Mouse primary neural stem cells(NSC)was used to evaluate the effect of KXS on promoting its proliferation by immunofluorescence assay.In addition,effects of KXS on regulating nestin and Wnt/β-catenin signaling pathway were also explored by Western blotting analysis.Results KXS significantly ameliorated the depression-like behaviors in presence of increased sucrose preference rate and decreased immobile time of tail suspension and forced swimming.KXS significantly promoted the neurogenesis in the hippocampus and expressions of nestin,reduced the expressions of cortisol,CRF,ACTH,increased the expressions of BDNF,NGF,and regulated Wnt/β-catenin signaling pathway.KXS also promoted the proliferation of NSCs and expressions of nestin,enhanced the translocation of b-catenin into nucleus,and regulated the expressions of proteins of Wnt/β-catenin signaling pathway.Conclusion KXS promoted neurogenesis in hippocampus and regulated Wnt/β-catenin pathway,which might contribute to its antidepressant effect.

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