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.

AIM To improve the quality standard for Dahuang Sodium Bicarbonate Tablets.METHODS TLC was adopted in the qualitative identification of rhein,emodin,chrysophanol,aloe-emodin,physcion and rhapontin,after which UPLC fingerprints were established,content determination of aloe emodin-8-O-β-D-glucoside,rhein-8-O-β-D-glucoside,emodin-8-O-β-D-glucoside,chrysophanol-8-O-β-D-glucoside,physcion-8-O-β-D-glucoside,aloe-emodin,rhein,emodin,chrysophanol,physcion were performed.RESULTS The clear TLC plots demonstrated good specificity.There were 20 common peaks in the fingerprints for 8 batches of samples with the similarities of more than 0.535.Ten constituents showed good linear relationships within their own ranges(r≥0.997 0),whose average recoveries were 98.7％-104.1％with the RSDs of 0.59％-2.13％,whose content ranges were 0.274 1-2.005 9,0.547 8-5.192 2,1.209 2-3.936 3,1.039 3-3.330 2,0.307 0-1.248 1,0.118 2-0.674 7,0.115 1-0.970 3,0.224 5-1.789 3,0.881 4-4.882 6,0.801 4-5.099 1 mg/g,respectively.CONCLUSION This simple and stable method can effectively control the quality of Rhei Radix et Rhizoma in Dahuang Sodium Bicarbonate Tablets.

Chronic kidney disease(CKD)is a chronic disease characterized by renal structural damage and dysfunction.At present,there is still a lack of effective therapeutic drugs and prevention and treatment methods for CKD in clinical practice.More and more studies have shown that necroptosis,as a new type of programmed cell death,plays a vital role in the onset and progression of CKD.Targeting key molecules in the necroptosis pathway,such as RIPK1,RIPK3 and MLKL,the development of small molecule inhibitors has become an emerging strategy for the treatment of CKD,and has shown significant potential to pro-tect the kidneys and alleviate renal fibrosis in a variety of in vitro and in vivo models.Therefore,this article summarizes the re-search progress of the mechanism of necroptosis in recent years,and focuses on the potential role of necroptosis in the pathogene-sis of CKD and the therapeutic potential of targeting this path-way,providing a new perspective and research direction for the prevention and treatment of CKD in the future.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Chronic kidney disease(CKD)is a chronic disease characterized by renal structural damage and dysfunction.At present,there is still a lack of effective therapeutic drugs and prevention and treatment methods for CKD in clinical practice.More and more studies have shown that necroptosis,as a new type of programmed cell death,plays a vital role in the onset and progression of CKD.Targeting key molecules in the necroptosis pathway,such as RIPK1,RIPK3 and MLKL,the development of small molecule inhibitors has become an emerging strategy for the treatment of CKD,and has shown significant potential to pro-tect the kidneys and alleviate renal fibrosis in a variety of in vitro and in vivo models.Therefore,this article summarizes the re-search progress of the mechanism of necroptosis in recent years,and focuses on the potential role of necroptosis in the pathogene-sis of CKD and the therapeutic potential of targeting this path-way,providing a new perspective and research direction for the prevention and treatment of CKD in the future.

Aim To investigate the neuroprotective effect of dioscin(DIO)on hippocampal neurons(HT22)after oxygen glucose deprivation/reoxygen-ation(OGD/R)and its possible mechanism.Methods HT22 cells were treated with 0,2.5,5,10,20,40,80,160,and 320 mg·L-1DIO for 24 h,and the cell proliferation rate was detected by CCK-8 method.The concentration that was non-toxic to HT 2 2 cells was se-lected for subsequent experiments.After OGD for 2 h,HT22 cells were randomly divided into the OGD/R group,1.25,2.5,and 5 mg·L-1DIO group,and posi-tive control group.HT22 cells were taken as the con-trol group.After drug intervention for 24 h,the cell proliferation rate was detected by CCK-8 method;the LDH release was detected by colorimetry;the cell ap-optosis rate was detected by TUNEL method;the ex-pression of proteins related to PARP-1/AIF pathway and caspase pathway was detected by Western blot.Results DIO intervention significantly upregulated the expression of AIF protein in mitochondria and PAR protein in nucleus of HT22 cells after OGD/R,and sig-nificantly downregulated the release of LDH,neuronal apoptosis rate,total protein expression of AIF and PAR,PARP-1,AIF in nucleus and protein expression of PAR protein in mitochondria,while the expression of Bax and caspase-3 proteins was not significantly differ-ent from that in the OGD/R group.Conclusion DIO can alleviate the apoptosis of HT22 cells induced by OGD/R by regulating the expression and translocation of proteins related to the PARP-1/AIF pathway,thus playing a neuroprotective role.

AIM To improve the quality standard for Dahuang Sodium Bicarbonate Tablets.METHODS TLC was adopted in the qualitative identification of rhein,emodin,chrysophanol,aloe-emodin,physcion and rhapontin,after which UPLC fingerprints were established,content determination of aloe emodin-8-O-β-D-glucoside,rhein-8-O-β-D-glucoside,emodin-8-O-β-D-glucoside,chrysophanol-8-O-β-D-glucoside,physcion-8-O-β-D-glucoside,aloe-emodin,rhein,emodin,chrysophanol,physcion were performed.RESULTS The clear TLC plots demonstrated good specificity.There were 20 common peaks in the fingerprints for 8 batches of samples with the similarities of more than 0.535.Ten constituents showed good linear relationships within their own ranges(r≥0.997 0),whose average recoveries were 98.7％-104.1％with the RSDs of 0.59％-2.13％,whose content ranges were 0.274 1-2.005 9,0.547 8-5.192 2,1.209 2-3.936 3,1.039 3-3.330 2,0.307 0-1.248 1,0.118 2-0.674 7,0.115 1-0.970 3,0.224 5-1.789 3,0.881 4-4.882 6,0.801 4-5.099 1 mg/g,respectively.CONCLUSION This simple and stable method can effectively control the quality of Rhei Radix et Rhizoma in Dahuang Sodium Bicarbonate Tablets.

Objective:To improve the teaching effect and promote the cultivation of medical talents by innovation of teaching design and learning methods for the "medical ethics" course.Methods:The "medical ethics" course in fall semester of 2021 was reformed, and 779 undergraduate students participated in the course. The course reform included the following elements: "clinical application" was set as the teaching goal and senior clinicians served as the main faculty; a "student-centered" learning format was developed based on social cognitive theory and the case-based learning (CBL) + clinical-scenario-deduction teaching method; formative assessment was conducted for individuals and groups, and essays, reviews, or reports of thoughts and experiences were used as the primary method of summative assessment. Questionnaires were used to evaluate students' satisfaction with the course reform. SPSS 24.0 software was used for statistical analysis. The results of the satisfaction survey were reported as percentage (number of specific cases/total cases).Results:A total of 770 valid questionnaires were collected. The results showed that 98.83% (761/770) students were satisfied with the course, the average score of teachers was 9.5 (0-10) points, the overall satisfaction of the teaching arrangement was 80.52% (620/770), and 96.10% (740/770) students reported that the course had a positive impact on their future career planning and facilitated multiple improvements in learning outcomes.Conclusions:Through the application of appropriate education and teaching methods in the reform of "medical ethics" course, the comprehensive quality and humanistic quality of students have been significantly improved, the teaching purpose has been achieved, and high levels of student satisfaction and teaching effect have been obtained.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.