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.Validation and Forensic Application of a Domestic Human DNA Quantitative De-tection Kit
Jing CHEN ; Ya-Ping WANG ; Yun-Peng FENG ; Xiao-Xin HU ; Zhen-Jun JIA ; Hong-Di LIU ; An-Xin YAN ; Yong-Jiu LI ; Zhu PENG ; Zhi-Fang LIU ; Jian-Gang CHEN
Journal of Forensic Medicine 2025;41(3):252-259
Objective To verify the efficacy of a domestic human DNA quantification kit based on real-time fluorescence quantitative PCR in detecting the total human DNA concentration,male DNA concen-tration in mixed male/female DNA samples,the degree of DNA degradation and inhibitor tolerance.Methods Samples with different concentrations,different male/female ratios,different concentrations of inhibitors,and different degradation degrees were tested using the domestic human DNA quantification kit based on real-time fluorescence quantitative PCR.This kit was compared with a similar product on the market and was applied to the detection of DNA from real cases.Results This human DNA quan-tification kit can effectively detect human DNA as low as 0.001 65 ng/μL,and 6.25 pg/μL of male DNA in mixed samples with a male-to-female ratio of 1∶15 000.Even when the sample contains as high as 400 ng/μL of humic acid or 1 000 μmol/L of hemin alone,the DNA concentration can still be accurately detected.The degradation index can effectively characterize the degradation degree of the sample.This kit has been successfully applied in forensic practice.Conclusion This human DNA quan-tification kit is accurate and reliable in detection.It can accurately reflect the degradation of DNA and inhibitor tolerance.It has good performance in quantitative accuracy,determination of the male/female ratio in mixed samples,and inhibitor tolerance.It has application potential in forensic case examination.
3.Development of a machine learning-based risk prediction model for mild cognitive impairment with spleen-kidney deficiency syndrome in the elderly.
Ya-Ting AI ; Shi ZHOU ; Ming WANG ; Tao-Yun ZHENG ; Hui HU ; Yun-Cui WANG ; Yu-Can LI ; Xiao-Tong WANG ; Peng-Jun ZHOU
Journal of Integrative Medicine 2025;23(4):390-397
OBJECTIVE:
As an age-related neurodegenerative disease, the prevalence of mild cognitive impairment (MCI) increases with age. Within the framework of traditional Chinese medicine, spleen-kidney deficiency syndrome (SKDS) is recognized as the most frequent MCI subtype. Due to the covert and gradual onset of MCI, in community settings it poses a significant challenge for patients and their families to discern between typical aging and pathological changes. There exists an urgent need to devise a preliminary diagnostic tool designed for community-residing older adults with MCI attributed to SKDS (MCI-SKDS).
METHODS:
This investigation enrolled 312 elderly individuals diagnosed with MCI, who were randomly distributed into training and test datasets at a 3:1 ratio. Five machine learning methods, including logistic regression (LR), decision tree (DT), naive Bayes (NB), support vector machine (SVM), and gradient boosting (GB), were used to build a diagnostic prediction model for MCI-SKDS. Accuracy, sensitivity, specificity, precision, F1 score, and area under the curve were used to evaluate model performance. Furthermore, the clinical applicability of the model was evaluated through decision curve analysis (DCA).
RESULTS:
The accuracy, precision, specificity and F1 score of the DT model performed best in the training set (test set), with scores of 0.904 (0.845), 0.875 (0.795), 0.973 (0.875) and 0.973 (0.875). The sensitivity of the training set (test set) of the SVM model performed best among the five models with a score of 0.865 (0.821). The area under the curve of all five models was greater than 0.9 for the training dataset and greater than 0.8 for the test dataset. The DCA of all models showed good clinical application value. The study identified ten indicators that were significant predictors of MCI-SKDS.
CONCLUSION
The risk prediction index derived from machine learning for the MCI-SKDS prediction model is simple and practical; the model demonstrates good predictive value and clinical applicability, and the DT model had the best performance. Please cite this article as: Ai YT, Zhou S, Wang M, Zheng TY, Hu H, Wang YC, Li YC, Wang XT, Zhou PJ. Development of a machine learning-based risk prediction model for mild cognitive impairment with spleen-kidney deficiency syndrome in the elderly. J Integr Med. 2025; 23(4): 390-397.
Humans
;
Cognitive Dysfunction/diagnosis*
;
Aged
;
Male
;
Female
;
Machine Learning
;
Spleen
;
Aged, 80 and over
;
Kidney
;
Medicine, Chinese Traditional
4.Predicting Postoperative Circulatory Complications in Older Patients: A Machine Learning Approach.
Xiao Yun HU ; Wei Xuan SHENG ; Kang YU ; Jie Tai DUO ; Peng Fei LIU ; Ya Wei LI ; Dong Xin WANG ; Hui Hui MIAO
Biomedical and Environmental Sciences 2025;38(3):328-340
OBJECTIVE:
This study examines utilizes the advantages of machine learning algorithms to discern key determinants in prognosticate postoperative circulatory complications (PCCs) for older patients.
METHODS:
This secondary analysis of data from a randomized controlled trial involved 1,720 elderly participants in five tertiary hospitals in Beijing, China. Participants aged 60-90 years undergoing major non-cardiac surgery under general anesthesia. The primary outcome metric of the study was the occurrence of PCCs, according to the European Society of Cardiology and the European Society of Anaesthesiology diagnostic criteria. The analysis metrics contained 67 candidate variables, including baseline characteristics, laboratory tests, and scale assessments.
RESULTS:
Our feature selection process identified key variables that significantly impact patient outcomes, including the duration of ICU stay, surgery, and anesthesia; APACHE-II score; intraoperative average heart rate and blood loss; cumulative opioid use during surgery; patient age; VAS-Move-Median score on the 1st to 3rd day; Charlson comorbidity score; volumes of intraoperative plasma, crystalloid, and colloid fluids; cumulative red blood cell transfusion during surgery; and endotracheal intubation duration. Notably, our Random Forest model demonstrated exceptional performance with an accuracy of 0.9872.
CONCLUSION
We have developed and validated an algorithm for predicting PCCs in elderly patients by identifying key risk factors.
Aged
;
Aged, 80 and over
;
Female
;
Humans
;
Male
;
Middle Aged
;
Cardiovascular Diseases/etiology*
;
Machine Learning
;
Postoperative Complications/etiology*
;
Risk Factors
;
Randomized Controlled Trials as Topic
;
Secondary Data Analysis
5.Threshold-Effect Associations of Serum 25-hydroxyvitamin D on Bone Turnover Markers and GC rs2282679 Variants in Chinese Women of Childbearing Age.
Xiao Yun SHAN ; Yu Ting LI ; Xia Yu ZHAO ; Yi Chun HU ; Si Ran LI ; Hui di ZHANG ; Yang CAO ; Rui WANG ; Li Chen YANG
Biomedical and Environmental Sciences 2025;38(4):433-446
OBJECTIVE:
This study aimed to investigate possible serum 25-hydroxyvitamin D [25(OH)D] cutoffs for the associations between 25(OH)D and Bone turnover markers (BTMs), and how GC gene variation influences such cutoffs in Chinese women of childbearing age.
METHODS:
In total, 1,505 non-pregnant or non-lactating women (18-45 years) were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Serum 25(OH)D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and single nucleotide polymorphisms were determined. Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds.
RESULTS:
The median serum 25(OH)D was 16.63 (11.96-22.55) ng/mL and the prevalence of low serum 25(OH)D (< 12 ng/mL) was 25.2%. Women with the lowest 25(OH)D had the highest β-CTX. After adjustment for the confounders, 25(OH)D cutoffs for OC [14.04 (12.84-15.23) ng/mL], β-CTX [13.94 (12.49-15.39) ng/mL], and P1NP [13.87 (12.37-15.37) ng/mL] in the whole population, cutoffs for OC [12.30 (10.68-13.91) ng/mL], β-CTX [12.23 (10.22-14.23) ng/mL], and P1NP [11.85 (10.40-13.31) ng/mL] in women with the GC rs2282679 G allele, and cutoffs for OC [12.75 (11.81-13.68) ng/mL], β-CTX [13.05 (11.78-14.32) ng/mL], and P1NP [12.81 (11.57-14.06) ng/mL] in women with the GC rs2282679 T allele, were observed. Below these cutoffs, BTMs were negatively associated with 25(OH)D, while above these cutoffs, BTMs plateaued.
CONCLUSION
In Chinese women of childbearing age, there were thresholds effect of serum 25(OH)D concentrations on BTMs. The results indicated that serum 25(OH)D concentrations < 13.87 ng/mL in this population had adverse influences on maintaining bone remodeling. BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
Humans
;
Female
;
Vitamin D/blood*
;
Adult
;
Middle Aged
;
Polymorphism, Single Nucleotide
;
Adolescent
;
Young Adult
;
China
;
Biomarkers/blood*
;
Bone Remodeling/genetics*
;
Vitamin D-Binding Protein/genetics*
;
Procollagen/blood*
;
Osteocalcin/blood*
;
Peptide Fragments/blood*
;
East Asian People
6.Application of mindfulness-based stress reduction on the patients treated with image fusion-guided prostate biopsy
Qiang JI ; Jun HU ; Xiao-hong WANG ; Yun LI ; Fan WANG ; Jie LIU ; Hui-xian WEI ; Ying-chun HUANG ; Ying LI
National Journal of Andrology 2025;31(9):812-817
Objective:To evaluate the application effect of mindfulness-based stress reduction(MBSR)therapy on the patients treated with image fusion-guided transperineal prostate biopsy.Methods:A total of 160 patients who underwent image fusion-guided transperineal prostate biopsy in the Urology Department from April 2023 to April 2024 were included.Patients were randomly assigned to a control group and an observation group,with 80 cases in each group.The control group received routine care,while the observa-tion group received combined MBSR on the basis of routine care.The surgical indicators,pain levels,psychological states,nursing satisfaction,and postoperative complication rates of both groups were compared.Results:There was no statistically significant differ-ence in general personal information and clinical data between the two groups(P>0.05).The surgery duration,secondary fusion rate,and postoperative complication rate in the observation group were all lower than those in the control group([23.54±2.07]min vs[26.25±1.69]min,P<0.05;8.75%vs 22.50%,P=0.017;17%vs 29%,P=0.036),and nursing satisfaction was higher in the observation group than in the control group(77%vs 69%,P=0.025).The VAS scores biopsy(5.11±0.93 vs 6.27±1.32,P=0.041),discharge(0.74±0.67 vs 1.85±0.95,P=0.004),and scores of SDS(47.76±2.06 vs 50.46±2.07,P=0.009)and SAS(46.89±2.68 vs 49.75±2.83,P=0.031)in the observation group were all lower than those in the control group.Conclusion:The application of MBSR in image fusion-guided prostate biopsy can synergistically utilize the advantages of minimally in-vasive technology,significantly optimize surgical indicators,and improve patients' psychological experiences,which is worthy of clinical application and promotion.
7.Development of dynamic multi-time-point clinical prediction models for bronchopulmonary dysplasia in preterm infants with gestational age<32 weeks
Wen LI ; Xue-Fei ZHANG ; Xiao-Ri HE ; Tao WANG ; Jing-Tao HU ; Wen LI ; Qing-Yi DONG ; Xiao-Yun GONG ; Yong-Hui YANG ; Ping-Yang CHEN
Chinese Journal of Contemporary Pediatrics 2025;27(12):1464-1474
Objective To develop dynamic prediction models based on multiple postnatal time points to support early diagnosis and individualized intervention for bronchopulmonary dysplasia(BPD)in preterm infants with gestational age<32 weeks.Methods Clinical data of 472 preterm infants with gestational age<32 weeks admitted to the Second Xiangya Hospital of Central South University between January 2016 and November 2020 were retrospectively analyzed.Multivariable logistic regression was applied to develop five independent prediction models at postnatal days 1,7,14,21,and 28.The performance of the models was assessed using the area under the receiver operating characteristic curve(AUC)and the Hosmer-Lemeshow test.Results Baseline characteristics such as gestational age and birth weight differed significantly between the BPD group(n=147)and the non-BPD group(n=325)(P<0.05).Predictors of BPD evolved across time points:on day 1,key predictors included gestational age,birth weight,Score for Neonatal Acute Physiology II(SNAP-II),invasive mechanical ventilation,and fraction of inspired oxygen>30%;by day 7,additional variables emerged,including fasting duration>2 days,mean feeding advancement rate<8.5 mL/(kg·d),neonatal respiratory distress syndrome,apnea of prematurity,and positive sputum culture;from day 14 onward,nutrition-and treatment-related indicators were incorporated additionally.The models demonstrated good discrimination at postnatal days 1,7,14,21,and 28,with AUCs of 0.917,0.927,0.939,0.944,and 0.968,respectively,and good calibration(Hosmer-Lemeshow P>0.05).Internal validation showed AUCs ranging from 0.899 to 0.958,indicating robust performance.Conclusions Dynamic postnatal prediction models incorporating indicators spanning perinatal factors,respiratory support,nutritional management,and therapeutic interventions demonstrate high predictive performance and facilitate dynamic risk assessment for BPD in preterm infants with gestational age<32 weeks.
8.Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in anterior mediastinal masses
Junmin ZHU ; Junjie WANG ; Jianming YUE ; Yixin SUN ; Yichen LIU ; Lei WANG ; Lin LIN ; Jie LI ; Jinlan ZHAO ; Xuehua TU ; Ningying DING ; Jianrong HU ; Chunmei HE ; Leilei TIAN ; Hongtao TANG ; Jiasheng ZHAO ; Cheng CHEN ; Yongxiang SONG ; Yunwei TIAN ; Yong XIAO ; Kaidi LI ; Lin MA ; Yun WANG ; Longqi CHEN ; Dong TIAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(11):1603-1609
Objective To assess the clinical value of a novel surgical technique—Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in the resection of anterior mediastinal masses. Methods Patients who underwent tubeless subxiphoid uniportal video-assisted thoracoscopic surgery via balance-shaped sternal elevation device in anterior mediastinal masses process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to April 2025 were included, and their clinical data were analyzed. Results A total of 4 patients were included, with 2 males and 2 females, aged 58-75 years. The diameter of the tumor was 2.5-3.0 cm. The operation time was 60.0-150.0 min, intraoperative blood loss was 5-10 mL, pain score on the 3rd day after surgery was 0 points, and postoperative hospital stay was 2-3 days. All patients achieved complete resection of the masses and thymus without perioperative complications. Conclusion The tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device technique optimizes surgical visualization and instrument maneuverability while avoiding complications related to conventional anesthesia and tubing, thereby markedly enhancing the minimally invasive profile of anterior mediastinal masses resections. In addition to maintaining procedural safety, this approach effectively reduces postoperative pain and accelerates patient recovery, highlighting its potential for widespread clinical adoption.
9.Consensus on the use of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for cancer pain management
Yi LU ; Cunzhi LIU ; Wujun GENG ; Xiaozhen ZHENG ; Jingdun XIE ; Guangfang ZHANG ; Chao LIU ; Yun LI ; Yan QU ; Lei CHEN ; Xizhao HUANG ; Hang TIAN ; Yuhui LI ; Hongxin LI ; Heying ZHONG ; Ronggui TAO ; Jie ZHONG ; Yue ZHUANG ; Junyang MA ; Yan HU ; Jian FANG ; Gaofeng ZHAO ; Jianbin XIAO ; Weifeng TU ; Jiaze SUN ; Yuting DUAN ; Bao WANG
Journal of Southern Medical University 2025;45(8):1800-1808
Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
10.Effectiveness and safety of augmentative plating technique in managing nonunion following intramedullary nailing of long bones in the lower extremity: A systematic review and meta-analysis.
Cong-Xiao FU ; Hao GAO ; Jun REN ; Hu WANG ; Shuai-Kun LU ; Guo-Liang WANG ; Zhen-Feng ZHU ; Yun-Yan LIU ; Wen LUO ; Yong ZHANG ; Yun-Fei ZHANG
Chinese Journal of Traumatology 2025;28(3):164-174
PURPOSE:
To methodically assess the effectiveness of augmentative plating (AP) and exchange nailing (EN) in managing nonunion following intramedullary nailing for long bone fractures of the lower extremity.
METHODS:
PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to gather clinical studies regarding the use of AP and EN techniques in the treatment of nonunion following intramedullary nailing of lower extremity long bones. The search was conducted up until May 2023. The original studies underwent an independent assessment of their quality, a process conducted utilizing the Newcastle-Ottawa scale. Data were retrieved from these studies, and meta-analysis was executed utilizing Review Manager 5.3.
RESULTS:
This meta-analysis included 8 studies involving 661 participants, with 305 in the AP group and 356 in the EN group. The results of the meta-analysis demonstrated that the AP group exhibited a higher rate of union (odds ratio: 8.61, 95% confidence intervals (CI): 4.12 - 17.99, p < 0.001), shorter union time (standardized mean difference (SMD): -1.08, 95% CI: -1.79 - -0.37, p = 0.003), reduced duration of the surgical procedure (SMD: -0.56, 95% CI: -0.93 - -0.19, p = 0.003), less bleeding (SMD: -1.5, 95% CI: -2.81 - -0.18, p = 0.03), and a lower incidence of complications (relative risk: -0.17, 95% CI: -0.27 - -0.06, p = 0.001). In the subgroup analysis, the time for union in the AP group in nonisthmal and isthmal nonunion of lower extremity long bones was shorter compared to the EN group (nonisthmal SMD: -1.94, 95% CI: -3.28 - -0.61, p < 0.001; isthmal SMD: -1.08, 95% CI: -1.64 - -0.52, p = 0.002).
CONCLUSION
In the treatment of nonunion in diaphyseal fractures of the long bones in the lower extremity, the AP approach is superior to EN, both intraoperatively (with reduced duration of the surgical procedure and diminished blood loss) and postoperatively (with an elevated union rate, shorter union time, and lower incidence of complications). Specifically, in the management of nonunion of lower extremity long bones with non-isthmal and isthmal intramedullary nails, AP demonstrated shorter union time in comparison to EN.
Humans
;
Bone Nails/adverse effects*
;
Bone Plates/adverse effects*
;
Femoral Fractures/surgery*
;
Fracture Fixation, Intramedullary/methods*
;
Fractures, Ununited/surgery*
;
Lower Extremity/injuries*

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