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.

BackgroundSuicide and self-injury risk in patients with depression disorder is associated with pain symptoms， but the relationships between specific pain types and their severity and distinct self-injury/suicide risk phenotypes remain controversial. ObjectiveTo explore whether somatic pain can reflect different self-injury/suicide risk phenotypes， and to provide references for the clinical identification of suicide and self-injury risk in patients with depression. MethodsBased on data from the National Survey on Symptomatology of Depression （NSSD）， 3 275 patients who met the diagnostic criteria for major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders， fourth edition， text revision （DSM-IV-TR） were recruited. According to previous suicidal behavior， suicidal ideation and self-injury behavior in the past two weeks， patients were divided into the no self-injury/suicide risk group， self-injury group， and high suicide-risk group. The occurrence of headache， muscle soreness， trunk pain， limb pain， and other pain symptoms was assessed using the structured symptom assessment instrument of the NSSD. With the no self-injury/suicide risk group as the reference， an ordinal Logistic regression model was used to analyze the associations between the risk groups and the occurrence frequency of pain， with demographic and clinical characteristics entered into the model as covariates for adjustment. ResultsA total of 3 211 patients （98.05%） were included in the analysis， including 1 329 cases （41.39%） in the no self-injury/suicide risk group， 415 cases （12.92%） in the self-injury group， and 1 467 cases （45.69%） in the high suicide-risk group. Compared with the no self-injury/suicide risk group， the occurrence frequencies of headache （OR=1.526， 95% CI： 1.221–1.894） and muscle soreness （OR=1.287， 95% CI： 1.034–1.597） were higher in the self-injury group， and the occurrence frequencies of headache （OR=0.583， 95% CI： 0.504–0.672）， muscle soreness （OR=0.682， 95% CI： 0.597–0.780）， trunk pain （OR=0.557， 95% CI： 0.475–0.634）， limb pain （OR=0.454， 95% CI： 0.384–0.522）， and other pain difficult to localize （OR=0.542， 95% CI： 0.472–0.631） were all lower in the high suicide-risk group. ConclusionPatients with depression disorder across different self-injury and suicide risk phenotypes exhibit distinct pain characteristics， and these differences may provide a reference for the clinical identification of suicide and self-injury risk in patients with depression disorder. ［Funded by The National Key Research and Development Program of China during the "13th Five-Year Plan" period （number， 2016YFC1307100）； Shanghai Key Clinical Specialties Construction Project］

Aim To explore the relation between the protective effect of hyperoside(Hyp)on energy metab-olism and apoptosis in cardiomyocytes after myocardial infarction(MI)and the regulation of peroxisome pro-life rator-activated receptor α(PPARα)pathway.Methods Mouse myocardial infarction injury model was established by ligation of left anterior descending coronary artery.The mice that were successfully liga-ted were randomly divided into the following groups:MI group,Hyp(9,18 and 36 mg·kg-1)group,posi-tive fenofibrate group(120 mg·kg-1)and Hyp(36 mg·kg-1)+PPARα inhibitor GW6471 group.In addition,a sham group was set up,only threading with-out ligature.The mice were administered different kinds of drugs by gavage for seven days,once daily.ECG changes were recorded in mice 5 min before,5 min after surgery,and 1 hour after day 7 using the BL-420F biofunction system.The diagnostic ultrasound in-strument was used to examine the heart structure and function of each group of mice.The influence of myo-cardial histology was observed by hematoxylin and eo-sin (HE) staining and Sirius red(Sirius Red)stai-ning.The changes of creatine kinase isozymin-MB(CK-MB),cardiac troponin Ⅰ(cTnⅠ)and lactate de-hydrogenase(LDH)in mouse serum were assessed by ELISA kit.The expressions of PPARα signaling related proteins and apoptosis-related proteins were detected by immunofluorescence and Western blot.Results Compared with MI mice,Hyp could significantly im-prove the ECG abnormality of MI mice,increase the left ventricular ejection fraction(LVEF)and left ventricu-lar short axis shortening rate(LVFS),reduce serum cTnⅠ content,CK-MB and LDH activity,and reduce myocardial fibrosis,infarct area and cardiomyocyte ap-optosis in the MI area.Meanwhile,this research found that Hyp could activate PPARα signaling pathway and regulate apoptosis-related proteins.However,the car-dioprotective effect of hyperoside was reversed by the combination with the treatment of the PPARα signaling inhibitor,GW6471.Conclusions Hyp has an impro-ving effect on energy metabolism and apoptosis in mice after MI,and the mechanism may be related to its acti-vation of PPARα signaling pathway.

Aim To explore the relation between the protective effect of hyperoside(Hyp)on energy metab-olism and apoptosis in cardiomyocytes after myocardial infarction(MI)and the regulation of peroxisome pro-life rator-activated receptor α(PPARα)pathway.Methods Mouse myocardial infarction injury model was established by ligation of left anterior descending coronary artery.The mice that were successfully liga-ted were randomly divided into the following groups:MI group,Hyp(9,18 and 36 mg·kg-1)group,posi-tive fenofibrate group(120 mg·kg-1)and Hyp(36 mg·kg-1)+PPARα inhibitor GW6471 group.In addition,a sham group was set up,only threading with-out ligature.The mice were administered different kinds of drugs by gavage for seven days,once daily.ECG changes were recorded in mice 5 min before,5 min after surgery,and 1 hour after day 7 using the BL-420F biofunction system.The diagnostic ultrasound in-strument was used to examine the heart structure and function of each group of mice.The influence of myo-cardial histology was observed by hematoxylin and eo-sin (HE) staining and Sirius red(Sirius Red)stai-ning.The changes of creatine kinase isozymin-MB(CK-MB),cardiac troponin Ⅰ(cTnⅠ)and lactate de-hydrogenase(LDH)in mouse serum were assessed by ELISA kit.The expressions of PPARα signaling related proteins and apoptosis-related proteins were detected by immunofluorescence and Western blot.Results Compared with MI mice,Hyp could significantly im-prove the ECG abnormality of MI mice,increase the left ventricular ejection fraction(LVEF)and left ventricu-lar short axis shortening rate(LVFS),reduce serum cTnⅠ content,CK-MB and LDH activity,and reduce myocardial fibrosis,infarct area and cardiomyocyte ap-optosis in the MI area.Meanwhile,this research found that Hyp could activate PPARα signaling pathway and regulate apoptosis-related proteins.However,the car-dioprotective effect of hyperoside was reversed by the combination with the treatment of the PPARα signaling inhibitor,GW6471.Conclusions Hyp has an impro-ving effect on energy metabolism and apoptosis in mice after MI,and the mechanism may be related to its acti-vation of PPARα signaling pathway.

Objective:To investigate the related factors of cognitive impairment in middle-aged and old-aged patients with type 2 diabetes mellitus(T2DM).Methods:A total of 970 patients with T2DM(585 middle-aged group and 385 old-aged group)were selected from residents of a large community in Beijing from September to December 2018.The Mini-Mental State Examination(MMSE)was used to assess the cognitive func-tion.Multivariate logistic regression was used to analyze the related factors.Results:The detection rates of cognitive impairment were 12.0％and 13.5％in middle-aged and old-aged patients with T2DM,respectively.Among mid-dle-aged patients with T2DM,work(OR=0.22,95％CI:0.03-0.77)and education at the junior college or un-dergraduate level and above(OR=0.18,95％CI:0.04-0.55)were protective factors for cognitive impair-ment.Myocardial infarction(OR=4.13,95％CI:1.26-13.63)was a risk factor for cognitive impairment.Among old-aged patients with T2DM,drinking tea 1-2 times a week(OR=0.11,95％CI:0.01-0.58)and education at the junior college or undergraduate level and above(OR=0.19,95％CI:0.05-0.54)were protective factors for cognitive impairment.Stroke(OR=3.64,95％CI:1.55-8.39)and good sleep self-assessment(OR=2.75,95％CI:1.13-7.35)were risk factors for cognitive impairment.Conclusion:Cognitive impairment in middle-aged pa-tients with T2DM is related to work,education level and myocardial infarction,and cognitive impairment in old-aged patients with T2DM is related to lifestyle,education level and stroke.

Objective:To investigate the structural changes in the spinal cord in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) and their relationship with clinical disability.Methods:This study was cross-sectional. A retrospective analysis of clinical and imaging data from 124 patients with MS (MS group), 101 patients with aquaporin-4 antibody-positive NMOSD (NMOSD group), and 110 healthy controls (HC group) from seven medical centers were conducted from January 2018 to October 2021. All subjects underwent 3D T 1WI, and the upper cervical spinal cord cross-sectional area (MUCCA) was segmented and measured. All patients completed the expanded disability status scale (EDSS) assessments at baseline and during follow-up, as well as the baseline 25-foot walk test (T25FW) and the nine-hole peg test (NHPT). Patients were classified into EDSS progression and non-progression groups based on follow-up EDSS scores. Comparisons of MUCCA among the three groups were conducted using analysis of covariance, controlling for age and sex as covariates. Pairwise comparisons between groups were performed using the HSD test. Univariate linear regression and logistic models were employed to identify candidate predictors of baseline clinical disability status or EDSS progression in the MS and NMOSD groups. L1 regularized multivariable linear regression analysis was used to determine independent predictors of baseline clinical disability status or EDSS progression. Independent predictors were then combined to establish a logistic regression model, and the model′s performance in predicting EDSS progression was evaluated using receiver operating characteristic analysis and the area under the curve (AUC). Results:A total of 144 patients completed follow-up EDSS assessments, with a follow-up duration of 3.30 (1.10, 6.42) years, including 82 patients in the MS group and 62 patients in the NMOSD group. Controlling for sex and age as covariates, the overall difference in MUCCA among the MS, NMOSD, and HC groups was statistically significant ( P=0.001). The MUCCA in the MS group was lower than that in the HC group, with a significant difference ( t=-2.54, P=0.007); the MUCCA in the NMOSD group was also lower than that in the HC group, with a significant difference ( t=-2.80, P=0.002). However, the difference in MUCCA between the MS and NMOSD groups was not statistically significant ( t=-0.40, P=0.882). In the MS group, MUCCA was an independent predictor of baseline EDSS score (β=-0.03), baseline T25FW score (β=-0.09), and baseline NHPT score (β=-0.30). In the NMOSD group, MUCCA (β=-0.08), age (β=0.06), and baseline EDSS score (β=-0.43) were independent predictors of EDSS progression, and the logistic regression model incorporating these three factors predicted EDSS progression with an AUC of 0.82. Conclusions:Significant spinal cord atrophy occurs in patients with both MS and NMOSD. Atrophy of the upper cervical spinal cord can predict the degree of disability in MS patients and the progression of clinical disability in NMOSD patients.

Magnesium(Mg)-based bone implants have emerged as a promising candidate in bone regeneration due to their elastic modulus matching natural bone,favorable biodegradability,and biocompatibility.The degradation-derived magnesium ions(Mg2+)promote angiogenesis through multifaceted molecular mechanisms,thereby accelerating bone healing.This review systematically elucidates key pathways by which Mg2+regulates vascularization:① Activation of the CGRP-FAK-VEGF signaling axis via dorsal root ganglia-mediated neurovascular coupling;② Stabilization of HIF-1α through inhibiting VHL-mediated ubiquitination degradation and activating MagT1/TRPM7 ion channels,thereby enhancing VEGF transcription;③ Modulation of Notch signaling to drive vascular endothelial differentiation of bone marrow mesenchymal stem cells(BMSCs);④The activation of PI3K/AKT signaling pathway enhances endothelial nitric oxide synthase(eNOS)activity,leading to increased nitric oxide(NO)production which subsequently promotes endothelial cell proliferation and migration;⑤Immunomodulatory effects via macrophage M2 polarization and subsequent secretion of angiogenic factors;⑥stimulation of PDGF-BB secretion from MC3T3-E1 pre-osteoblasts.Notably,Mg2+exhibits concentration-dependent pro-angiogenic effects(optimal range:1-10 mM)and specifically enhances type H vessel formation,which critically couples angiogenesis with osteogenesis to boost bone regeneration efficiency.

Aim To study the therapeutic effect of al-licin on senna-induced diarrhea in mice and to explore the underlying mechanism.Methods Forty-eight C57BL/6J mice were randomly divided into six groups:control,model,loperamide positive control group(2 mg·kg-1),allicin low-dose group(6 mg·kg-1),allicin medium-dose group(12 mg·kg-1)and allicin high-dose group(18 mg·kg-1).Except for the con-trol group,the diarrhea model was induced in the other groups by intragastric administration of senna leaf ex-tract.After drug administration,several diarrhea indi-ces were measured:the rate of loose stools,diarrhea index,accumulated frequency of loose stools at differ-ent time points within 5 hours,and small intestine pro-pelling rate.Serum levels of TNF-α and IL-6 were de-tected by ELISA.Serum NO content was determined u-sing the Griess method.The activities of SOD and CAT,as well as MDA content in the ileum and colon,were measured.The pathological changes and the ex-pression of mRNA related to intestinal barrier proteins in the ileum and colon were evaluated using HE stai-ning and RT-qPCR.Results Allicin improved diar-rhea symptoms in mice induced by senna leaf.It re-duced the rate of loose stools,diarrhea index,cumula-tive number of loose stools in five hours,and the intes-tinal propulsion rate.Allicin also protected the intesti-nal mucosa,decreased serum TNF-α and IL-6 levels,and lowered MDA content in the intestines.It in-creased serum NO levels and enhanced SOD and CAT activities in the intestines.Additionally,allicin upreg-ulated the mRNA expression of AQP1,AQP4,and ZO-1 in intestinal tissues.Conclusions Allicin has a significant therapeutic effect on senna-induced diarrhea in mice.The underlying molecular mechanisms may involve anti-inflammatory and antioxidant effects,in-creased NO content,and upregulation of mRNA ex-pression of aquaporins and tight-junction proteins.

In order to understand the genetic variation and whole genome characteristics of goose as-trovirus(GoAstV)in Jiangxi Province,a strain of GoAstV was successfully isolated from a typical gosling gout case sample and the whole genome sequencing and genetic characteristics of the isola-ted strain were analyzed.The results showed that the JXNC1 strain could be stably passaged on LMH cells and could cause mild cytopathic effects in LMH cells.Sequencing and analysis showed that the full-length genome of the strain was 7 173 bp,and its genetic relationship was the closest to the GZ2301(PP966939)reference strain,belonging to the GoAstV-Ⅱ genotype.The complete genome of JXNC1 strain shared 98.1％-98.8％nucleotide similarity with 22 GoAstV-Ⅱ reference strains,and the amino acid similarity of ORF2 gene was 97.6％-99.6％.At the same time,the analysis results showed that the mutation of the strain mainly occurred in the ORF2 gene,and there were 13 amino acid site mutations,of which T630I was a unique mutation.Animal regression experiments showed that the inoculation of JXNC1 strain could cause urate deposition in the or-gans of goslings,congestion and dilatation of hepatic sinusoids,and small focal necrosis of some hepatocytes.Renal tissue tubular dilatation,renal interstitial connective tissue hyperplasia.The re-sults of this study laid a foundation for accurate prevention and control of the disease.

Objective:To construct a key item checklist for the Mini-HTA report specification,providing scientific guidance for drafting each section of Mini-HTA research reports,enhancing their standardization,scientific rigor,and completeness,thereby improving the efficiency and quality of health decision-making.Methods:Based on preliminary literature review and qualitative systematic review,a pool of problem items for the Mini-HTA report specification was formed.Delphi questionnaires were distributed,and the Delphi technique was employed through two rounds of expert consultation to optimize and select key items.Results:Through two rounds of Delphi expert consultation,the initial Mini-HTA report specification item checklist was screened,integrated,and supplemented.A finalized key item checklist was constructed,comprising 8 first-level items(Title,Abstract,Introduction,Methods,Results,Discussion,Conclusion,and Other Relevant Information)and 48 second-level items.Conclusion:The constructed key item checklist for the Mini-HTA report specification provides scientific guidance for drafting Mini-HTA research reports.It helps enhance the standardization and transparency of the assessment process and the reliability of results,thereby optimizing the efficiency and quality of health decision-making.