1.SIRT5 Potentiates Hepatocarcinogenesis by Modulating Protein Acylation in Mice
Yu ZHANG ; Feng-Rui REN ; Jia-Yun LI ; Xiang-Yu CHEN ; Zi-Yi WANG ; Qi SUN ; Jun-Cheng ZHAO ; Ye ZHANG ; Zhen HUANG ; Hao HU ; Tao-Tao WEI ; Min XIAO
Progress in Biochemistry and Biophysics 2026;53(6):1712-1722
ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.
2.Study on the functions of ERG3 in Candida albicans
Zi YE ; Ruina WANG ; Jiacun LIU ; Shiyun YANG ; Chan LIANG ; Lan YAN
Journal of Pharmaceutical Practice and Service 2025;43(9):431-435
Objective To investigate the biological functions of the ERG3 gene in Candida albicans and its potential value in antifungal therapy. Methods The ERG3 null mutant was constructed by the CRISPR/Cas9 technology. Gas chromatography-mass spectrometry, microbroth dilution method, hyphal induction and mouse systemic infection models were carried out to evaluate sterol metabolism, drug susceptibility, hyphal formation ability and pathogenicity in C. albicans. Results The disruption of the ERG3 gene led to disordered sterol metabolism in C. albicans with a significant increased level of episterol, 14α-methylfecosterol and ergosta-7,22-dienol. The ERG3 null mutant exhibited significantly reduced susceptibility to antifungal azole and polyene drugs, which suggested that ERG3 involve in regulating drug resistance. Although the disruption of ERG3 inhibited hyphal growth and biofilm formation, it did not significantly alter the pathogenicity of the strain in a mouse model of systemic fungal infection. Conclusion The ERG3 gene was a key regulator in the ergosterol synthesis pathway in C. albicans. Its deletion induced multi-drug resistance by reshaping sterol metabolism, while pathogenicity maintenance depended on compensatory mechanisms. This study provided critical insights for developing antifungal drugs targeting sterol metabolism and overcoming drug resistance.
3.Design of intelligent airborne soldier physical training system based on human body composition analysis
Lin YANG ; Zheng LIU ; Yu-shan YE ; Jian-fei PANG ; Jing HE ; Xuan-zi ZHOU ; Qiong WANG ; Xin-sheng CAO ; Tao LIU
Chinese Medical Equipment Journal 2025;46(2):16-23
Objective To design an intelligent airborne soldier physical training system based on human body composition analysis to solve the problems in diversity of training mode,targeted training plan and high incidence of military training-related injuries.Methods The intelligent airborne military physical training system was designed with B/S architecture and developed with Python language,which was composed of four functional modules for airborne soldier information acquisition,trainee physical fitness state assessment,physical fitness training program recommendation and airborne soldier physical fitness training program evaluation.The airborne soldier information acquisition module collected and analyzed the trainee physiological parameter information with a human body composition analyzer,clarified the parameter characteristics related to physical training with considerations on military physical training requirements and constructed a trainee physical fitness assessment parameter model;the trainee physical fitness state assessment module established an evaluation model based on machine learning to realize stage-by-stage physical fitness evaluation for airborne soldiers;the physical fitness training program recommendation module was constructed based on the physical training feature similarity algorithm and graph embedding theory to provide decision making assistance for program development of airborne military physical training;the airborne soldier physical fitness training program evaluation module compared the physical fitness and evaluation results before and after training by means of list and chart,and updated the training program based on the evaluation results by calling the physical training program recommendation module.Results The intelligent airborne soldier physical training system contributed to forming an individualized physical fitness training recommendation mechanism after trainee body evaluation,modifying training program based on comparison and feedback for stage-by-stage training evaluation,so as to decrease the incidence of military training-related injuries while increasing the training efficiency.Conclusion The system developed improves airborne soldier physical training in rationality and reliability,and provides references for intelligent military training of the PLA.[Chinese Medical Equipment Journal,2025,46(2):16-23]
4.Integrating Internet Search Data and Surveillance Data to Construct Influenza Epidemic Thresholds in Hubei Province: A Moving Epidemic Method Approach.
Cai Xia DANG ; Feng LIU ; Heng Liang LYU ; Zi Qian ZHAO ; Si Jin ZHU ; Yang WANG ; Yuan Yong XU ; Ye Qing TONG ; Hui CHEN
Biomedical and Environmental Sciences 2025;38(9):1150-1154
5.Expert consensus on evaluation index system construction for new traditional Chinese medicine(TCM) from TCM clinical practice in medical institutions.
Li LIU ; Lei ZHANG ; Wei-An YUAN ; Zhong-Qi YANG ; Jun-Hua ZHANG ; Bao-He WANG ; Si-Yuan HU ; Zu-Guang YE ; Ling HAN ; Yue-Hua ZHOU ; Zi-Feng YANG ; Rui GAO ; Ming YANG ; Ting WANG ; Jie-Lai XIA ; Shi-Shan YU ; Xiao-Hui FAN ; Hua HUA ; Jia HE ; Yin LU ; Zhong WANG ; Jin-Hui DOU ; Geng LI ; Yu DONG ; Hao YU ; Li-Ping QU ; Jian-Yuan TANG
China Journal of Chinese Materia Medica 2025;50(12):3474-3482
Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards*
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Humans
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Consensus
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Drugs, Chinese Herbal/therapeutic use*
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Surveys and Questionnaires
6.Influencing factors in patients with cervical cancer during chemoradiotherapy
Zepeng WANG ; Zi YE ; Shanshan YUAN
Journal of Clinical Medicine in Practice 2025;29(10):68-72
Objective To analyze the influencing factors of symptom clusters during chemoradio-therapy in patients with cervical cancer.Methods A retrospective analysis was conducted on the clini-cal data of 776 patients diagnosed with cervical cancer during chemoradiotherapy.The M.D.Anderson Symptom Inventory(MDASI-D)was used to assess common symptoms and their severity in cancer pa-tients.Exploratory factor analysis was employed to extract symptom clusters.Univariate and multiple linear regression analyses were performed to screen for influencing factors of the major symptom clus-ters.Results Among 776 cervical cancer patients undergoing chemoradiotherapy,the five most prevalentsymptoms were fatigue,nausea,dry mouth,disturbed sleep and vomiting.Through explora-tory factor analysis,a total of four symptom clusters,namely the digestive tract symptom cluster,the somatic symptom cluster,the side effect symptom cluster and the emotional symptom cluster were ex-tracted.Multiple linear regression analysis revealed that age and Eastern Cooperative Oncology Group(ECOG)score were influencing factors for gastrointestinal symptom cluster(P<0.05);age,educa-tional level,disease stage and ECOG performance status were influencing factors for physical symptom cluster(P<0.05);age,educational level,monthly household income per capita,ECOG performance status and disease stage were influencing factors for the emotional symptom cluster(P<0.05);the ECOG performance status,disease stage and comorbid chronic diseases were influencing factors for the side effect symptom cluster(P<0.05).Conclusion Patients with cervical cancer frequently experi-ence gastrointestinal,emotional,physical and side effect symptom clusters during chemoradiotherapy.
7.MAGED4 activates the PI3K/AKT signaling pathway through SIRT7 to promote glioma cell proliferation
Ai Ye ; Ziliang Zhong ; Feng Li ; Huan Xie ; Xiaoqiong Zou ; Guojian Wang ; Zi Wang ; Bin Luo ; Qingmei Zhang ; Xiaoxun Xie
Acta Universitatis Medicinalis Anhui 2025;60(12):2235-2246
Objective:
To determine the expression of melanoma-associated antigens D4(MAGED4) and SIRT7 in human glioma, and to analyze the potential effects of MAGED4 and SIRT7 on glioma cell proliferation.
Methods:
The MAGED4 and SIRT7 expression levels and their correlation were compared by the China glioma genome atlas(CGGA), human protein atlas(HPA), and UALCAN databases. Survival analysis, ROC curve analysis, and Cox regression analysis were used to predict the outcome of MAGED4 and SIRT 7 in glioma patients. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) signaling pathway enrichment analysis were used to explore the biological functions of MAGED4 and SIRT7 in glioma. Western blot experiment was used to investigate whether MAGED4 protein exerted its regulatory effects on the activity of the PI3K/AKT signaling pathway via SIRT7. The effect of MAGED4 on cell proliferation in glioma through SIRT7 was explored by CCK-8.
Results:
The analysis results of CGGA, UALCAN, and HPA databases showed that the expression levels of MAGED4 and SIRT7 in glioma tissues were higher than those in normal brain tissue, and the expression were positively correlated. Results of survival, ROC, and Cox analysis showed that high expression of MAGED4 and SIRT7 mRNA were risk factors for poor prognosis in glioma. Results of KEGG enrichment analysis showed that MAGED4 and SIRT7 were associated with the PI3K/AKT signaling in glioma, and Western blot results showed that MAGED4 activated the PI3K/AKT signaling pathway by regulating SIRT7. The CCK-8 results showed that MAGED4 promotes the proliferation of glioma cells through SIRT7.
Conclusion
MAGED4 and SIRT7 are highly expressed in glioma and associated with poor prognosis, and MAGED4 promotes glioma cell proliferation through activation of the PI3K/AKT signaling pathway by SIRT7.
8.Feasibility study of using clinical trial individual-level data sample bank as external control to support drug and device development:taking transcatheter aortic valve replacement device as an example
Xiao-ying LIN ; Chi-lie DANZENG ; Duo-er WANG ; Ying-xuan ZHU ; Ye LU ; Fan GAO ; Yuan-xin LI ; Meng-zhu SU ; Zi-long ZHANG ; Min CHEN ; Qi-ze LI ; Ru JIANG ; Yan-yan ZHAO ; Yang WANG
Chinese Journal of Interventional Cardiology 2025;33(8):459-466
Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.
9.Evaluation of Hemolytic Performance of Cellulose Hemostatic Products
Qing-qing HOU ; Qin-lian JIAO ; Chun-xia QIAO ; Zi-ye WANG ; Xiao-yan WANG ; Wen-qian MA ; Zeng-xiang LIU ; Xiao-xia SUN
Progress in Modern Biomedicine 2025;25(9):1488-1495
Objective:To compare the differences in the evaluation of hemolysis performance of cellulose hemostatic materials using different detection methods and test media,and to explore a m ore reasonable testing plan for such products.Methods:Hemolysis tests were conducted on cellulose hemostatic materials using the absorbance measurement hemolysis method and hemoglobin concentration measurement hemolysis method in accordance with YY/T 1651.1-2019 standard.We compared the changes in hemolysis rate,pH value,and osmotic pressure under different experimental media.Results:Under the same experimental method,compared to SC,the hemolysis results using PBS as the extraction medium are smaller,and the changes in pH and osmotic pressure are closer to the normal range of human body changes.Conclusions:The changes in pH and osmotic pressure may be one of the reasons for the high hemolysis rate of cellulose hemostatic materials.Choosing PBS with buffering effect as the leaching medium may be more suitable for evaluating the hemolysis performance of cellulose hemostatic materials.
10.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.


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