1.Rehmanniae Radix Iridoid Glycosides Protect Kidneys of Diabetic Mice by Regulating TGF-β1/Smads Signaling Pathway
Hongwei ZHANG ; Ming LIU ; Huisen WANG ; Wenjing GE ; Xuexia ZHANG ; Qian ZHOU ; Huani LI ; Suqin TANG ; Gengsheng LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):56-66
ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides (RIG) on the kidney tissue of streptozotocin (STZ)-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group, and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model, metformin (250 mg·kg-1), catalpol (100 mg·kg-1), low-dose RIG (RIG-L, 200 mg·kg-1) and high-dose RIG (RIG-H, 400 mg·kg-1) groups (n=11). Mice in each group were administrated with corresponding drugs, while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention, an oral glucose tolerance test (OGTT) was performed, and the area under the curve (AUC) was calculated. After mice were sacrificed, both kidneys were collected. The body weight, kidney weight, and fasting blood glucose (FBG) were measured. Biochemical assays were performed to measure the serum levels of triglycerides (TG), total cholesterol (TC), serum creatinine (SCr), and blood urea nitrogen (BUN). Enzyme-linked immunosorbent assay (ELISA) was employed to determine the serum level of fasting insulin (FINS), and the insulin sensitivity index (ISI) and homeostatic model assessment for insulin resistance (HOMA-IR) were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method (IHC) was employed to assess the expression of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), transforming growth factor-β1 (TGF-β1), and collagen-3 (ColⅢ) in the kidney tissue. The protein levels of TGF-β1, cell signal transduction molecule 3 (Smad3), matrix metalloproteinase-9 (MMP-9), and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group, the model group showcased decreased body weight and ISI (P<0.01), increased kidney weight, FBG, AUC, FINS, HOMA-IR, TC, TG, SCr, and BUN (P<0.01), glomerular hypertrophy, capsular space narrowing, and collagen deposition in the kidney, up-regulated protein levels of IL-1, IL-6, TNF-α, TGF-β1, ColⅢ, and Smad3 (P<0.01), and down-regulated protein level of MMP-9 (P<0.01) in the kidney tissue. Compared with the model group, the treatment groups had no significant difference in the body weight and decreased kidney weight (P<0.05, P<0.01). The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin, catalpol, and RIG-L groups after treatment for 6-8 weeks (P<0.01). The AUC in the RIG-L, RIG-H, and metformin groups decreased (P<0.05, P<0.01). The levels of TC, SCr, and BUN in the serum of mice in each treatment group became lowered (P<0.05, P<0.01). The level of TG declined in the RIG-L, RIG-H, and metformin groups (P<0.05, P<0.01). The serum level of FINS declined in the catalpol, RIG-L, and metformin groups (P<0.01). Compared with the model group, the treatment groups showed decreased HOMA-IR (P<0.01), increased ISI (P<0.01), alleviated pathological changes in the kidney tissue, and down-regulated expression of IL-1 and TGF-β1. In addition, the protein levels of IL-6, TNF-α, and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated (P<0.05, P<0.01), and the protein levels of IL-6, TNF-α, and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β1, Smad3, and ColⅢ in the RIG-H and metformin groups were down-regulated (P<0.01). Compared with that in the model group, the protein level of MMP-9 was up-regulated in each treatment group (P<0.01). ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β1/Smads signaling pathway.
2.Effects and mechanism of persimmon leaf extract on IEC-6 cell ferroptosis induced by H2O2
Xuexia ZHANG ; Min ZHOU ; Hongyan ZHOU ; Lifei WANG ; Huani LI ; Changhe LIU ; Hongde XU ; Mingli ZHANG
China Pharmacy 2025;36(1):64-70
OBJECTIVE To investigate the effects and potential mechanism of persimmon leaf (PL) extract against ferroptosis induced by H2O2 in IEC-6 cells. METHODS Using IEC-6 cells as object, the effects of ferroptosis inhibitor ferrostatin-1 on IEC-6 cell viability induced by H2O2 were investigated; IEC-6 cells were divided into control group, H2O2 group, H2O2+PL 25 μg/mL group and H2O2+PL 50 μg/mL group. The levels of oxidant stress indexes [content of malondialdehyde (MDA), activity of superoxide dismutase (SOD), and levels of reactive oxygen species (ROS)], mitochondrial membrane potential (MMP) as well as mRNA and protein expressions of nuclear factor-erythroid-2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH/quinone oxidoreductase-1 (NQO-1), cystine/glutamate anti-porter (xCT), glutathione peroxidase 4 (GPX4) and ferritin heavy chain (FTH) were detected. RESULTS Ferroptosis inhibitor ferrostatin-1 could significantly increase the survival rate of H2O2-induced cells (P< 0.01). Compared with the control group, MDA content, ROS level, mRNA expressions of Nrf2 and NQO-1 as well as protein expressions of Nrf2 and HO-1 were increased or up-regulated significantly, while SOD activity, MMP, mRNA expressions of xCT, GPX4 and FTH as well as protein expressions of GPX4 and FTH were decreased or down-regulated significantly (P<0.01 or P<0.05). Compared with the H2O2 group, oxidative stress Δ indexes of H2O2+PL 25, 50 μg/mL groups were reversed to different extents, MMP level was increased significantly, as well as mRNA and protein expressions of Nrf2, HO-1, NQO-1,xCT, GPX4 and FTH were up-regulated to different extents;there were statistical significances in some indexes between groups (P<0.01 or P<0.05). CONCLUSIONS PL extract can alleviate mitochondrial membrane damage and abnormal accumulation of ROS caused by H2O2, which may be related to the inhibition of ferroptosis by activating the Nrf2/HO-1 signaling pathway.
3.Discovery and investigation of six polio vaccine derived viruses in Guangzhou City
Min CUI ; Chunhuan ZHANG ; Wei ZHANG ; Jun LIU ; Jialing LI ; Jianxiong XU ; Wenji WANG ; Qing HE ; Lihong NI ; Xuexia YUN ; Huanying ZHENG
Journal of Public Health and Preventive Medicine 2025;36(2):22-25
Objective To understand the surveillance situation of poliovirus in Guangzhou from 2011 to 2024, and to further strengthen polio surveillance and ensure the continued maintenance of a polio-free status. Methods An analysis was conducted on the discovery and investigation results of six cases of vaccine-derived poliovirus (VDPV) detected in Guangzhou. Results A total of 6 VDPV incidents were reported in Guangzhou from 2011 to June 2024, among which 5 incidents were from sewage sample testing in the Liede Sewage Treatment Plant in Guangzhou, all of which were confirmed as VDPV, with 1 for type I, 1 for type II, and 3 for type III. In addition, one confirmed HFMD case was identified as a type VDPV II carrier. No presence of any wild poliovirus (WPV), VDPV cases, or circulating VDPV (cVDPV) was reported. Conclusion Guangzhou City has maintained a high level of vigilance and effectiveness in the monitoring and prevention of polio. Continuously strengthening the construction of the polio monitoring network, optimizing vaccination strategies, and comprehensively improving public health awareness are still the focus of the prevention and control work in the future.
4.SRSF2 promotes glioblastoma cell proliferation by inducing alternative splicing of FSP1 and inhibiting ferroptosis
Dan HUA ; Xuexia ZHOU ; Qian WANG ; Cuiyun SUN ; Cuijuan SHI ; Wenjun LUO ; Zhendong JIANG ; Shizhu YU
Chinese Journal of Pathology 2024;53(5):430-438
Objective:To investigate the effect of serine/arginine-rich splicing factor 2 (SRSF2) on ferroptosis and its possible mechanism in glioblastoma cells.Methods:The online database of gene expression profiling interactive analysis 2 (GEPIA 2) and Chinese Glioma Genome Atlas were used to analyze the expression of SRSF2 in glioblastoma tissue and its association with patients prognosis. To validate the findings of the online databases, the pathological sections of glioblastoma and non-tumor brain tissues from Tianjin Medical University General Hospital, Tianjin, China were collected and analyzed by using immunohistochemistry. Silencing SRSF2 gene expression in glioblastoma cells by siRNA was analyzed with Western blot. The proliferation index was detected by using CCK8 assay. The rescued experiment was conducted by using expression plasmid of pcDNA3.1(+)-SRSF2. The activity of ferroptosis was assessed by using the levels of iron ions and malondialdehyde in glioblastoma cells and the changes in the ratio of glutathione to oxidized glutathione. The changes of gene expression and differential pre-mRNA alternative splicing (PMAS) induced by SRSF2 were monitored by using the third-generation sequencing technology analysis, namely Oxford nanopore technologies (ONT) sequencing analysis.Results:SRSF2 expression was higher in glioblastoma tissues than non-tumor brain tissues. Immunohistochemistry also showed a positive rate of 88.48%±4.60% in glioblastoma tissue which was much higher than the 9.97%±4.57% in non-tumor brain tissue. The expression of SRSF2 was inversely correlated with overall and disease-free disease survivals ( P<0.01). The proliferation index of glioblastoma cells was significantly reduced by silencing with SRSF2 siRNA ( P<0.01) and could be reversed with transfection of exogenous SRSF2. The levels of intracellulariron ions and malondialdehyde increased ( P<0.05), but the glutathione/oxidized glutathione ratio and the expression of key proteins in the glutathione pathway remained unchanged ( P>0.05). ONT sequencing results showed that silencing SRSF2 in glioblastoma cells could induce a significant alternative 3' splice site change on ferroptosis suppressor protein 1 (FSP1). Conclusion:SRSF2 inhibits the ferroptosis in glioblastoma cells and promotes their proliferation, which may be achieved by regulating FSP1 PMAS.
5.Analysis of issues in quality control test results of linear accelerators in China
Hongbo WANG ; Xuexia LIU ; Songhui ZHANG ; Chenxu HUANG ; Yuexin GUO ; Quanfu SUN
Chinese Journal of Radiological Health 2024;33(6):675-680
Objective To study the unqualified items in the reported quality control tests of linear accelerators, analyze the issues in quality control tests, and propose the key points and development directions for accelerator quality control test in China. Methods A literature review was conducted using the CNKI database to analyze the qualified rates of test items and the issues in quality control tests. Results In the literature on the quality control tests of linear accelerators, except for a few provinces where the qualified rates of all test items were 100%, unqualified items were reported in most of the literature. There were unqualified items related to X-ray and electron beam in different reports. Error of dose indication was the unqualified item with the highest occurrence rate in X-ray test, and the item with the lowest qualified rates in X-ray and electron beam tests. The lowest qualified rate of X-ray dose indication error was 73.5% in 2016, and the lowest qualified rate of electron beam dose indication error was 46.2% in 2017. Conclusion Tests should be carried out strictly according to the items and intervals specified by the quality control test standards. Hospitals, radiation health technology service institutions, and health administrative departments should each fulfill their respective responsibilities, work together, and place emphasis on ensuring effective quality control tests of linear accelerators to further enhance the overall quality control standards for these devices.
6.Prenatal diagnosis of a case with Congenital myasthenic syndrome due to compound heterozygous variants of SCN4A gene
Fanrong MENG ; Yunfang SHI ; Duan JU ; Xiuyan WANG ; Haiwei DONG ; Xuebing LI ; Xiaozhou LI ; Xuexia ZHOU
Chinese Journal of Medical Genetics 2024;41(4):450-455
Objective:To explore the clinical and genetic characteristics of a fetus diagnosed with Congenital myasthenic syndrome type 16 (CMS16).Methods:A couple who had visited Tianjin Medical University General Hospital in February 2018 due to "adverse outcome of two pregnancies" was selected as the study subject. Clinical data was gathered. Peripheral blood and amniotic fluid samples were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Low-depth whole-genome sequencing was carried out to detect copy number variation (CNV) in the fetus.Results:The couple′s first pregnancy had resulted in a miscarriage at 27 + 5 weeks, when ultrasound had revealed pleural effusion and polyhydramnios in the fetus. Their second pregnancy was terminated at 30 + 5 weeks due to fetal hand malformations, polyhydramnios and pleural fluid. Both couple had denied family history of genetic conditions. For their third pregnancy, no CNV abnormality was detected, whilst a compound heterozygous variants, including a maternally derived c. 3172C>T (p.R1058W) and paternal c. 1431delG (p.K477fs*89) in the SCN4A gene were detected. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 3172C>T (p.R1058W) was predicted as a likely pathogenic variant (PM1+ PM2_supporting+ PP3+ PP4), whilst the c. 1431delG (p.K477fs*89) was predicted as a pathogenic variant (PVS1+ PM2_supporting+ PP4). Conclusion:The c. 3172C>T (p.R1058W) and c. 1431delG (p.K477fs*89) compound heterozygous variants of the SCN4A gene probably underlay the CMS16 in the third fetus.
7.Genetic analysis and prenatal diagnosis of a Chinese pedigree affected with Complete androgen insensitivity syndrome due to a novel variant of AR gene
Fanrong MENG ; Xiaozhou LI ; Yunfang SHI ; Duan JU ; Xiuyan WANG ; Chunying WANG ; Xuebing LI ; Wenjun YU ; Yingmei WANG ; Xuexia ZHOU
Chinese Journal of Medical Genetics 2024;41(10):1206-1212
Objective:To explore the clinical and molecular basis for a Chinese pedigree affected with Complete androgen insensitivity syndrome (CAIS).Methods:A CAIS pedigree presented at Tianjin Medical University General Hospital between 2019 and 2021 was selected as the study subject. Clinical data of the proband was collected, along with peripheral blood samples from the proband and her family members. Chromosomal karyotyping, sex-determining region of the Y chromosome ( SRY) testing, and next-generation sequencing (NGS) were carried out for the proband, and candidate variant was verified by Sanger sequencing of her family members. Prenatal diagnosis was provided for the sister of the proband. This study was approved by Medical Ethics Committee of the Tianjin Medical University General Hospital (Ethics No. IRB2023-WZ-070). Results:The 18-year-old proband, who has a social gender of female, underwent laparoscopic examination, which showed no presence of uterus and ovaries. The karyotype of peripheral blood sample was 46, XY, with SRY gene detected. NGS indicated that the proband has harbored a heterozygous c. 1988C>G (p.Ser663Ter) variant of the AR gene. Sanger sequencing confirmed that her mother and sister had both harbored the same variant, whilst her father and younger sister were of the wild-type. Prenatal diagnosis revealed that her sister′s first fetus had harbored carried the same variant, which had led to termination of pregnancy. Her second fetus did not carry the variant, and a healthy boy was born. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+ PM4+ PP3_Moderate+ PP4). Conclusion:The c. 1988C>G (p.Ser663Ter) variant of the AR gene probably underlay the CAIS in the proband. The accurate diagnosis of sex development disorders will rely on the physicians′ thorough understanding of the clinical symptoms and pathogenic genes. Genetic testing and counseling can enable precise diagnosis, prenatal diagnosis, and guidance for reproduction
8.Effect of comprehensive intervention on the incidence of lactation galactostasis during breasefeeding of pregnant and delivery women
Feng WANG ; Jiandong WANG ; Baofeng GUO ; Xuexia GU ; Ping LI ; Guanrong GAO ; Chunying ZHAO
Shanghai Journal of Preventive Medicine 2023;35(5):448-452
ObjectiveTo observe the effect of comprehensive intervention on the incidence of lactation galactostasis in communities from the perspective of preventive medicine, so as to prevent the occurrence of the mammary ducts obstruction disease. MethodsA total of 400 women in the early stage of pregnancy were selected from four communities. Those in two communities were set up as the intervention group. Comprehensive intervention for the prevention and treatment of mammary ducts obstruction disease during pregnancy and "Six-step recanalization manual therapy" practical guidance were conducted on the intervention group. The pregnant women from the other two communities were the control group, who received no intervention or guidance training. The two groups were followed up at 1 month, 3 months and 5 months postpartum, and the occurrence of mammary ducts obstruction disease was investigated and interventions were carried out. ResultsThe incidence of galactostasis in the intervention group was 26.0%, 10.6% and 5.1%, respectively at 1, 3 and 5 months after delivery, and the incidence of galactostasis in the control group was 38.0%, 22.2% and 8.3%, respectively. The incidence of galactostasis at 1 month and3 months after delivery was statistically different (P<0.05), while the incidence of galactostasis 5 months after delivery was not statistically different (P>0.05). The protection rates of comprehensive intervention on galactostasis were 31.58%, 52.25% and 38.55%, respectively. ConclusionPublicity and education work of prevention and control of the mammary ducts obstruction disease and "Six-step recanalization manual therapy" practical guidance can effectively reduce the occurrence of plugged mammary ducts, and therefore should be promoted.
9.The correlation between lipid peroxide, total oxidation state, apolipoprotein(a) and pregnancy outcome of polycystic ovary syndrome in vitro fertilization-embryo transfer
Jiao WANG ; Hairu SUN ; Xuexia JI
Chinese Journal of Postgraduates of Medicine 2022;45(12):1071-1075
Objective:To investigate the relationship of lipid peroxide (LPO), total oxidation state (TOS), apolipoprotein (a) [apolipoprotein(a), Apo(a)] and pregnancy outcome in patients with polycystic ovarian syndrome (PCOS) treated by ovulation induction-in vitro fertilization-embryo transfer (IVF-ET).Methods:The clinical of 215 patients with PCOS treated by IVF-ET who were admitted to Hengshui People′s Hospitalfrom May 2017 to February 2020 were collected and they were divided into clinical pregnancy group (155 cases) and biochemical pregnancy group (60 cases) according to pregnancy outcome. The levels of LPO, TOS, and Apo(a) in the peripheral blood of the two groups were detected and the data were analyzed.Results:The levels of LPO and TOS before ovulation induction and human chorionic gonadotropin (HCG) dayin the biochemical pregnancy group were higher than those in the clinical pregnancy group: (10.35 ± 3.67) μmol/L vs. (7.16 ± 1.59) μmol/L, (17.98 ± 3.15) mmol H 2O 2 equiv/L vs. (15.03 ± 3.21) mmol H 2O 2 equiv/L; (12.81 ± 4.09) μmol/L vs. (7.38 ± 2.14) μmol/L, (19.66 ± 3.02) mmol H 2O 2 equiv/L vs. (15.19 ± 3.34) mmol H 2O 2 equiv/L; and the level of Apo(a) was lower than that in the clinical pregnancy group: (379.8 ± 95.9) mg/L vs. (486.5 ± 100.3) mg/L, (335.8 ± 84.7) mg/L vs. (473.5 ± 112.9) mg/L, the differences were statistically significant ( P<0.05). LPO and TOS before ovulation induction and HCG day were negatively correlated with the number of high-quality embryos ( P<0.01), and Apo(a) was positively correlated with the number of high-quality embryos ( P<0.01). The risk of non-clinical pregnancy for those with LPO, TOS, Apo(a) higher than the average before ovulation induction was 1.435, 1.233, 0.678 times of those with lower than the average ( P<0.05). The risk of non-clinical pregnancy for those with LPO, TOS, and Apo(a) higher than the average on HCG day was 1.443, 1.689, 0.762 times of those with lower than average ( P<0.05). After receiver operating characteristic (ROC) curve analysis, the area under the curve(AUC) of all indicators before ovulation induction combined to predict clinical pregnancy was 0.844. The AUC of all indicators on HCG day combined to predict clinical pregnancy was 0.894. Conclusions:Peripheral blood LPO, TOS, Apo(a) levels are closely related to the number of high-quality embryos, and are the main influencing factors of pregnancy outcome. Therefore, dynamic monitoring of the above-mentioned index levels can provide a reference for the clinical improvement of the treatment plan.
10.Effect of emergency "zero channel" process on improving efficiency of intravenous thrombolysis in stroke
Yiyu HONG ; Qun WANG ; Qian WANG ; Shuo WANG ; Hua XIE ; Xuexia MAI ; Yucun ZHU ; Qiangjun XU ; Rongrong LIAO
Chinese Journal of Neuromedicine 2022;21(2):176-179
Objective:To explore the effect of emergency "zero channel" process on improving the efficiency of intravenous thrombolysis in stroke.Methods:Fifty-eight acute ischemic stroke patients admitted to our hospital from January 2020 to December 2020 were enrolled into experimental group; another 58 acute ischemic stroke patients admitted to our hospital from January 2019 to December 2019 and matched with age and gender were selected as control group. "Green channel" process was adopted for patients in the control group, and optimized "zero channel" process (moving the working passageway forward to the ambulance) was implemented for patients in the experimental group. Door to rescue room time (DRRT), door to consultation time (DCT), door to laboratory examination completion time (DLECT), door to CT report time (DCRT), and door to needle time (DNT) were used to evaluate the times of emergency treatment. The thrombolytic effect of the two groups was compared by evaluating the recanalization rate of occluded vessels and thrombolytic efficiency. Modified Rankin scale (mRS) was used to evaluate the prognoses 6 months after treatment in both groups, and mRS scores≤2 was defined as good prognosis.Results:The DCRT, DCT and DNT in the experimental group were significantly shorter than those in the control group ( P<0.05); the compliance rate of DNT≤60 min in the experimental group was significantly higher as compared with that in the control group ( P<0.05). The immediate recanalization rate of occluded vessels in the experimental group and control group was 60.3% and 27.6%, and the thrombolytic efficiency was94.83% and 82.76%; significant differences were noted between the two groups ( χ2=12.633, P<0.001; χ2=4.245, P=0.039). The good prognosis rate of the experimental group and control group was 36.2% and 15.5%, respectively, after 6 months of follow-up ( χ2=4.016, P=0.041). Conclusion:Emergency "zero channel" can further shorten DCT, DCRT, and DNT, and improve the efficiency of thrombolysis and prognoses of acute ischemic stroke patients.


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