1.Zuogui Wan Improve Ovarian Inflammatory Microenvironment and Stemness of Ovarian Germline Stem Cells in Ovarian Aging via cGAS/STING Signaling Pathway
Yunling ZHENG ; Xinyi PAN ; Zuang LI ; Yixuan WANG ; Junyi AN ; Yuxin ZOU ; Mengting XIAO ; Zheng CHEN ; Ling ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):1-10
ObjectiveTo investigate the mechanism of Zuogui Wan (ZGW) in improving ovarian inflammatory microenvironment and stemness of ovarian germline stem cells (OSCs) for treating ovarian aging via the cyclic guanosine monophosphate/adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. MethodsForty C57BL/6 female mice were randomly divided into a blank group, a model group, a low-dose ZGW group (2.7 g·kg-1), a high-dose ZGW group (5.4 g·kg-1), and an estradiol valerate group (0.15 mg·kg-1), with 8 mice in each group. Except the blank group, all other groups received a single intraperitoneal injection of cyclophosphamide at 120 mg·kg-1 to establish an ovarian aging mouse model. After successful modeling, each group was continuously administered for 4 weeks, once daily. The physiological status of the mice was observed, and the ovarian index was calculated. The estrus cycle of the mice was monitored. Hematoxylin-eosin (HE) staining was used to observe pathological changes in ovarian tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum sex hormone levels. Serum inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and mouse interleukin-6 (IL-6) levels were detected using kits. Western blot was used to detect the protein expression of ovarian cGAS, STING, p-STING, TANK-binding kinase 1 (TBK1), p-TBK1, interferon-induced transmembrane protein 3 (Fragilis), and Vasa homolog protein (MVH). Quantitative real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of inflammatory factors in ovarian tissue. Immunofluorescence double labeling was performed to locate OSCs in ovarian tissues, and fluorescence intensities of OSCs markers MVH and octamer binding transcription factor 4 (Oct4) were calculated. ResultsCompared with the blank group, the model group showed reduced body weight, ovarian wet weight, and ovarian index (P<0.01) and a disordered estrus cycle (P<0.01). In addition, the levels of serum follicle-stimulating hormone (FSH), TNF-α, IL-6, and IL-1β were increased (P<0.01), while anti-Müllerian hormone (AMH) and estradiol (E2) levels were decreased (P<0.01). The protein expression of cGAS, p-STING/STING, and p-TBK1/TBK1 in ovarian tissue was increased (P<0.05, P<0.01), while that of OSCs stemness factors MVH and Fragilis was reduced (P<0.01). Immunofluorescence indicated a reduction in MVH and Oct4 expression in OSCs (P<0.01). The mRNA expression of inflammatory factors TNF-α, IL-6, and IL-1β in ovarian tissue was increased (P<0.05, P<0.01). Compared with the model group, the treatment groups exhibited improved body weight, ovarian wet weight, and ovarian index (P<0.05) and a reduced rate of estrus cycle disorder (P<0.05, P<0.01). The levels of serum FSH, TNF-α, IL-6, and IL-1β were decreased (P<0.05, P<0.01), while AMH and E2 levels were increased (P<0.01). The protein expression levels of cGAS, p-STING/STING, and p-TBK1/TBK1 in ovarian tissue were decreased (P<0.05), while the protein expression of MVH and Fragilis was increased (P<0.05), and the fluorescence intensities of MVH and Oct4 were increased (P<0.05, P<0.01). The mRNA expression of inflammatory factors in ovarian tissue was decreased (P<0.05). ConclusionZGW alleviate ovarian inflammatory response, regulate ovarian microenvironment homeostasis, and maintain stemness of OSCs in ovarian aging mice probably by modulating the cGAS-STING signaling pathway, thereby improving ovarian function and delaying ovarian aging.
2.Optimization Study of Rat Models for Sequelae of Pelvic Inflammatory Disease
Zhen LIU ; Wei-ling WANG ; Yun-cheng MA ; Yu-xi WANG ; Yuan TIAN ; Qian LI ; Xiao-zhu WANG ; Xiao-yao LIU ; Mei JIANG ; Wen-hui XU ; Jian GAO ; Ting WANG
Progress in Modern Biomedicine 2025;25(12):1921-1930
Objective:To establish a stable rat model of sequelae of pelvic inflammatory disease(SPID)with clinical characteristics,and to provide a reliable experimental model for the study of the pharmcological effect and mechanism of SPID.Methods:Twenty-four 7-week-old SD rats were divided into sham operation group,model-A(108 cfu/mL mixed bacterial solution,0.2 mL),model-B(109 cfu/mL mixed bacterial solution 0.2 mL),and model-C(108 cfu/mL E.coli 0.2 mL).The weight of the rat's uterine was weighed and the uterine index was calculated.The automatic hematology analyzer was used to detect the blood routine;hematoxylin-eosin staining(HE)and masson staining were used to detect uterine pathlogical changes in rats.Enzyme-linked immunosorbent assay(ELISA)was used to detect interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in rat uterine tissue homogenates.Western blot was used to detect the expression of proteins related to NF-κB signaling pathway.Results:Compared with the sham operation group,the uterine index of model-A,model-B,and model-C were significantly increased(P<0.05,P<0.01).The levels of WBC and NE in the model-A increased significantly(P<0.01).The level of LY in model-B decreased significantly(P<0.01).The levels of IL-1β,TNF-α in model-A,model-B,and model-C were significantly increased(P<0.01).The levels of IL-6 in model-A and model-B were significantly increased(P<0.05,P<0.01).The collagen volume fraction of model-A and model-B were significantly increased(P<0.01).Mechanism study indicates that the expression levels of p-IKKβ/IKKβ,p-IκBα/IκBα and p-p65/p65 in model-A were significantly increased(P<0.01),and the expression levels of IκBα/β-actin were significantly decreased(P<0.01).The expression level of p-IKKβ/IKKβ in model-B was significantly increased(P<0.01).Conclusions:A stable rat model of SPID that conforms to clinical characteristics can be successfully constructed by combining 0.2 mL of mixed bacterial solution with a concentration of 108 cfu/mL and mechanical injury.This modeling method intervened in the expression of the NF-κB inflammatory signaling pathway.
3.Selection of exosomal microRNA biomarkers for brucellosis diagnosis and construction of a potential miRNA-mRNA regulation network
Jin ZHAO ; Zhi-qiang CHEN ; Bing-Li WANG ; Shu-ling LI ; Xiao-yu ZHU ; Jin-tong JIA ; Ye-zi LIU ; Zhi-wei LI
Chinese Journal of Zoonoses 2025;41(3):269-277
This study was aimed at exploring novel auxiliary diagnostic biomarkers for brucellosis and their potential miR-NA-mRNA regulatory networks.High-throughput sequencing was used to compare miRNA expression differences in serum ex-osomes between patients with brucellosis and healthy controls.Subsequently,RT-qPCR was used to validate the expression of significantly upregulated exosomal miRNAs.The diagnostic value of these miRNAs was assessed with ROC curves,and bioin-formatics analyses were performed to investigate the potential roles of the miRNAs in brucellosis infection.The ROC curve a-nalysis indicated that the area under the curve for exosomal hsa-miR-11400(P<0.05),hsa-miR-199a-5p(P<0.05),and hsa-miR-148a-5p(P<0.05)was 0.79,0.81,and 0.74,respectively.A total of 465 differentially expressed miRNAs and their tar-get genes were predicted,including 25 immune-related target genes,most of which were closely associated with cancer-related proteoglycans,NF-kappa B signaling pathways,and IL-17 signaling pathways.The constructed differentially expressed gene network indicated that the immune genes PLXNA2,IL17RA,PRKCA,CD22,ACVR1B,and CBL might be regulated by hsa-miR-199a-5p and hsa-miR-148a-5p.These findings suggest that exosomal miRNAs might serve as auxiliary diagnostic indicators for brucellosis.Our exosomal miRNA-mRNA regulatory network provides new insights into the pathogenesis and treatment of brucellosis.
4.Optimization Study of Rat Models for Sequelae of Pelvic Inflammatory Disease
Zhen LIU ; Wei-ling WANG ; Yun-cheng MA ; Yu-xi WANG ; Yuan TIAN ; Qian LI ; Xiao-zhu WANG ; Xiao-yao LIU ; Mei JIANG ; Wen-hui XU ; Jian GAO ; Ting WANG
Progress in Modern Biomedicine 2025;25(12):1921-1930
Objective:To establish a stable rat model of sequelae of pelvic inflammatory disease(SPID)with clinical characteristics,and to provide a reliable experimental model for the study of the pharmcological effect and mechanism of SPID.Methods:Twenty-four 7-week-old SD rats were divided into sham operation group,model-A(108 cfu/mL mixed bacterial solution,0.2 mL),model-B(109 cfu/mL mixed bacterial solution 0.2 mL),and model-C(108 cfu/mL E.coli 0.2 mL).The weight of the rat's uterine was weighed and the uterine index was calculated.The automatic hematology analyzer was used to detect the blood routine;hematoxylin-eosin staining(HE)and masson staining were used to detect uterine pathlogical changes in rats.Enzyme-linked immunosorbent assay(ELISA)was used to detect interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in rat uterine tissue homogenates.Western blot was used to detect the expression of proteins related to NF-κB signaling pathway.Results:Compared with the sham operation group,the uterine index of model-A,model-B,and model-C were significantly increased(P<0.05,P<0.01).The levels of WBC and NE in the model-A increased significantly(P<0.01).The level of LY in model-B decreased significantly(P<0.01).The levels of IL-1β,TNF-α in model-A,model-B,and model-C were significantly increased(P<0.01).The levels of IL-6 in model-A and model-B were significantly increased(P<0.05,P<0.01).The collagen volume fraction of model-A and model-B were significantly increased(P<0.01).Mechanism study indicates that the expression levels of p-IKKβ/IKKβ,p-IκBα/IκBα and p-p65/p65 in model-A were significantly increased(P<0.01),and the expression levels of IκBα/β-actin were significantly decreased(P<0.01).The expression level of p-IKKβ/IKKβ in model-B was significantly increased(P<0.01).Conclusions:A stable rat model of SPID that conforms to clinical characteristics can be successfully constructed by combining 0.2 mL of mixed bacterial solution with a concentration of 108 cfu/mL and mechanical injury.This modeling method intervened in the expression of the NF-κB inflammatory signaling pathway.
5.Selection of exosomal microRNA biomarkers for brucellosis diagnosis and construction of a potential miRNA-mRNA regulation network
Jin ZHAO ; Zhi-qiang CHEN ; Bing-Li WANG ; Shu-ling LI ; Xiao-yu ZHU ; Jin-tong JIA ; Ye-zi LIU ; Zhi-wei LI
Chinese Journal of Zoonoses 2025;41(3):269-277
This study was aimed at exploring novel auxiliary diagnostic biomarkers for brucellosis and their potential miR-NA-mRNA regulatory networks.High-throughput sequencing was used to compare miRNA expression differences in serum ex-osomes between patients with brucellosis and healthy controls.Subsequently,RT-qPCR was used to validate the expression of significantly upregulated exosomal miRNAs.The diagnostic value of these miRNAs was assessed with ROC curves,and bioin-formatics analyses were performed to investigate the potential roles of the miRNAs in brucellosis infection.The ROC curve a-nalysis indicated that the area under the curve for exosomal hsa-miR-11400(P<0.05),hsa-miR-199a-5p(P<0.05),and hsa-miR-148a-5p(P<0.05)was 0.79,0.81,and 0.74,respectively.A total of 465 differentially expressed miRNAs and their tar-get genes were predicted,including 25 immune-related target genes,most of which were closely associated with cancer-related proteoglycans,NF-kappa B signaling pathways,and IL-17 signaling pathways.The constructed differentially expressed gene network indicated that the immune genes PLXNA2,IL17RA,PRKCA,CD22,ACVR1B,and CBL might be regulated by hsa-miR-199a-5p and hsa-miR-148a-5p.These findings suggest that exosomal miRNAs might serve as auxiliary diagnostic indicators for brucellosis.Our exosomal miRNA-mRNA regulatory network provides new insights into the pathogenesis and treatment of brucellosis.
6.Subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets
Qiu-jin QU ; Ling-xiao SUN ; Xiao-fei WANG ; Fu-yu ZHU ; Guo-xi CHE ; Jing XU ; Xiao-yan WANG ; Nai-shui HAN ; Xiao-xia SUN ; Chun-xia QIAO
Chinese Medical Equipment Journal 2025;46(10):29-35
Objective To evaluate the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets using hydroxyethyl starch(HES)130/0.4 sodium chloride injection as an extraction medium.Methods Firstly,40 Sprague Dawley(SD)rats including 20 male and 20 female ones were seleted and randomly enrolled into a sample group and a control group by sex,with 20 ones in each group.Secondly,instead of plasma HES 130/0.4 sodium chloride injection was used to leach disposable plasma virus-inactivated blood transfusion sets to prepare the test solution by simulating clinical application such as lighting,adsorption and filtration and storage.Finally,the test solution and HES 130/0.4 sodium chloride injection were injected into the tail vein of the SD rats at a dose of 20 mL/kg for 28 d in the sample group and in the control group respectively,and the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets and the feasibility of using HES 130/0.4 sodium chloride injection as the extraction medium to assess their subchronic systemic toxicity were evaluated with clinical observation,body mass monitoring,clinical pathology examination,gross necropsy and histopathology examination.Results The sample group and control group had no significant differences in mortality rates,clinical observation results,body mass,gross necropsy results,hematological and coagulation examination results and organ weight(all P>0.05);blood biochemical examinations showed the male rats in the sample group had the cholesterol(CHO)values higher while the creatinine(CR)values lower than those in the control group,with the differences being statistically significant(both P<0.05)and the two indexes within the range of the laboratory's historical reference data,and other blood biochemical indexes were not significantly different(all P>0.05);the sample group had the spleen weight-to-body mass ratios of the female rates lower significantly than those in the control group(P<0.05),and the ratios of other organ weight to body mass had significant differences(all P>0.05);histopathology examination showed slight pathological changes in liver,spleen and kidney of female rats and in spleen and kidney of male rats in the sample group,and the female and male rats in the control group had similar pathological changes found in the sample group,which might be caused by HES metabolites.Conclusion Disposable plasma virus-inactivated blood transfusion sets prove to have no significant subchronic systemic toxicity,and its feasible to use HES 130/0.4 sodium chloride injection as the extraction medium to evaluate the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets.[Chinese Medical Equipment Journal,2025,46(10):29-35]
7.Expert Consensus on the Ethical Requirements for Generative AI-Assisted Academic Writing
You-Quan BU ; Yong-Fu CAO ; Zeng-Yi CHANG ; Hong-Yu CHEN ; Xiao-Wei CHEN ; Yuan-Yuan CHEN ; Zhu-Cheng CHEN ; Rui DENG ; Jie DING ; Zhong-Kai FAN ; Guo-Quan GAO ; Xu GAO ; Lan HU ; Xiao-Qing HU ; Hong-Ti JIA ; Ying KONG ; En-Min LI ; Ling LI ; Yu-Hua LI ; Jun-Rong LIU ; Zhi-Qiang LIU ; Ya-Ping LUO ; Xue-Mei LV ; Yan-Xi PEI ; Xiao-Zhong PENG ; Qi-Qun TANG ; You WAN ; Yong WANG ; Ming-Xu WANG ; Xian WANG ; Guang-Kuan XIE ; Jun XIE ; Xiao-Hua YAN ; Mei YIN ; Zhong-Shan YU ; Chun-Yan ZHOU ; Rui-Fang ZHU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):826-832
With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.
8.The synergistic effect and mechanism verification of effective components of Biejia-Ezhu against triple-negative breast cancer based on network pharmacology and component compatibility theory
Dou-dou FENG ; Xiao-shan LUO ; Yan-yun MENG ; Jing-zhe ZHAO ; Jiu-long ZHU ; Ya-zhen HUANG ; Qing XIE ; Xiang-Li LING ; Su XIE
Chinese Pharmacological Bulletin 2025;41(5):950-959
Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P<0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P<0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.
9.Subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets
Qiu-jin QU ; Ling-xiao SUN ; Xiao-fei WANG ; Fu-yu ZHU ; Guo-xi CHE ; Jing XU ; Xiao-yan WANG ; Nai-shui HAN ; Xiao-xia SUN ; Chun-xia QIAO
Chinese Medical Equipment Journal 2025;46(10):29-35
Objective To evaluate the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets using hydroxyethyl starch(HES)130/0.4 sodium chloride injection as an extraction medium.Methods Firstly,40 Sprague Dawley(SD)rats including 20 male and 20 female ones were seleted and randomly enrolled into a sample group and a control group by sex,with 20 ones in each group.Secondly,instead of plasma HES 130/0.4 sodium chloride injection was used to leach disposable plasma virus-inactivated blood transfusion sets to prepare the test solution by simulating clinical application such as lighting,adsorption and filtration and storage.Finally,the test solution and HES 130/0.4 sodium chloride injection were injected into the tail vein of the SD rats at a dose of 20 mL/kg for 28 d in the sample group and in the control group respectively,and the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets and the feasibility of using HES 130/0.4 sodium chloride injection as the extraction medium to assess their subchronic systemic toxicity were evaluated with clinical observation,body mass monitoring,clinical pathology examination,gross necropsy and histopathology examination.Results The sample group and control group had no significant differences in mortality rates,clinical observation results,body mass,gross necropsy results,hematological and coagulation examination results and organ weight(all P>0.05);blood biochemical examinations showed the male rats in the sample group had the cholesterol(CHO)values higher while the creatinine(CR)values lower than those in the control group,with the differences being statistically significant(both P<0.05)and the two indexes within the range of the laboratory's historical reference data,and other blood biochemical indexes were not significantly different(all P>0.05);the sample group had the spleen weight-to-body mass ratios of the female rates lower significantly than those in the control group(P<0.05),and the ratios of other organ weight to body mass had significant differences(all P>0.05);histopathology examination showed slight pathological changes in liver,spleen and kidney of female rats and in spleen and kidney of male rats in the sample group,and the female and male rats in the control group had similar pathological changes found in the sample group,which might be caused by HES metabolites.Conclusion Disposable plasma virus-inactivated blood transfusion sets prove to have no significant subchronic systemic toxicity,and its feasible to use HES 130/0.4 sodium chloride injection as the extraction medium to evaluate the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets.[Chinese Medical Equipment Journal,2025,46(10):29-35]
10.The trajectory of depressive symptoms and its risk factors in the middle-aged and elderly population
Xiao CUI ; Song CHANG ; Heqing HUANG ; Ling ZHU
Journal of Army Medical University 2025;47(4):369-377
Objective To identify and delineate the developmental trajectories of depressive symptoms in the middle-aged and elderly population in China,and to explore the risk factors for depressive symptom trajectories in China's middle-aged and elderly population.Methods According to our inclusion and exclusion criteria,7 600 participants were subjected based on the data from the China Health and Aged Care Tracking Survey(CHARLS)published by Peking University.The data from 5 waves of the survey from 2011 to 2023 were collected and analyzed with latent growth curve model(LGCM),latent class growth model(LGCM)to identify the developmental trajectories of depressive symptoms in the participants.Multicategorical logistic regression analyses were conducted to analyze whether gender,marital status,educational level,urban/rural residence,annual income,self-rated health status,and childhood bullying experience were risk factors for different trajectories of depressive symptoms.Results Two developmental trajectories of depressive symptoms were identified and classified in this study,that is,low-level stable(n=5 545,72.96%)and high-level ascending(n=2 055,27.04%).With the low-level stable group as a reference,multicategorical logistic regression analysis revealed that female(OR=1.373,95CI%:1.191~1.584,P<0.001),residence of rural area(OR=1.634,95CI%:1.410~1.895,P<0.001),and poor self-rated health status(OR=2.059,95%CI:1.890~2.243,P<0.001),and experience of childhood bullying(OR=1.76,95%CI:1.489~2.080,P<0.001)were associated with an increased risk of high-level ascending trajectory of depression.Conclusion There are 2 different trajectories of depressive mood in Chinese middle-aged and elderly population.And poor self-rated health status,history of childhood bullying,being female,and residence of rural area are risk factors for a high-level ascending trajectory of depressive symptoms.

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