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.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver disorder worldwide, characterized by complex molecular regulatory networks driving its pathogenesis. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), serve as critical regulators of gene expression and have been increasingly recognized for their pivotal roles in MASLD development. Rather than functioning in isolation, these ncRNAs form intricate regulatory networks that integrate and amplify disease signals across multiple cellular compartments and pathological stages. This review provides a comprehensive overview of how these ncRNA networks orchestrate MASLD progression, focusing on their roles in metabolic dysregulation, inflammation, and fibrosis. We further evaluate the diagnostic potential of circulating ncRNAs as stable, non-invasive biomarkers for disease stratification and monitoring, and discuss emerging therapeutic strategies targeting ncRNAs, including antisense oligonucleotides, synthetic mimics, and advanced delivery platforms such as lipid nanoparticles and engineered exosomes. Despite significant progress, challenges related to delivery efficiency, tissue specificity, and safety remain barriers to clinical translation. By synthesizing current knowledge of ncRNA networks in MASLD and highlighting opportunities for therapeutic intervention, this review provides a roadmap for translating ncRNAs into clinical applications for this increasingly prevalent metabolic liver disease.

Objectives:To explore the relationship between carboxymethyl lysine (CML) and type 2 diabetes (T2DM) with myopenia, so as to provide some clinical reference for clinical prevention and early intervention of myopenia.Methods:A case-control study was conducted, selecting 142 T2DM patients admitted to the Endocrinology Department of the Affiliated Hospital of North China University of Science and Technology from November 2022 to November 2023. According to the diagnostic criteria of the 2019 consensus of experts on the diagnosis and treatment of sarcopenia, the patients were divided into a case group (T2DM with sarcopenia, 58 cases) and a control group (T2DM without sarcopenia, 84 cases). Collect and compare general information, serological data, and body composition data of two groups of patients. Two independent sample t-test is used for inter group comparison of metric data that conforms to normal distribution; Non parametric tests are used for inter group comparisons of non normally distributed quantitative data; The comparison of count data between groups is conducted using χ2 test. Multivariate logistic regression analysis was used to analyze the relationship between carboxymethyl lysine and type 2 diabetes with myopenia. Draw receiver operating characteristic (ROC) curves and analyze the efficacy of carboxymethyllysine in diagnosing T2DM with muscle atrophy. Results:Univariate analysis showed the BMI ((21.59±3.04) kg/m 2), FINS (4.49 (1.85,9.03) U/L), and FCP ((1.45±0.96) mg/L) levels of the patients in the case group were lower than those in the control group(27.32±3.74) kg/m 2, 6.91 (3.74, 11.99) U/L, (2.64±1.23) mg/L), while age, ((64.67±6.75) years old) of disease duration(12.16±6.69) years, and CML (5.70±2.14 μg/L) were higher than those in the control group ((62.23±7.33) years old, (8.70±8.01) years, (2.38±0.73) μg/L), and the differences were statistically significant (Statistical values were t=9.66, Z=2.86, t=6.46, t=2.02, t=2.70, t=13.17; P values were <0.001, 0.004, <0.001, 0.046, 0.008, <0.001). Multifactorial binary logistic regression analysis showed that CML ( OR(95%CI):3.242 (1.933-5.437)) and BMI ( OR(95%CI):0.636 (0.505-0.801)) were associated with T2DM combined with sarcopenia (all P<0.001). The results of the ROC curve showed that the area under the curve (AUC) of CML was 0.934, and the corresponding optimal cut-off value was 3.038 μg/L. The diagnostic efficacy of CML for the diagnosis of T2DM combined with myasthenia gravis was high, and the diagnostic results were in good agreement with the actual results. Conclusions:Carboxymethyl lysine is associated with T2DM combined with muscle atrophy. CML has a high diagnostic efficacy in diagnosing T2DM combined with muscle atrophy, and it has certain practical value in diagnosing T2DM combined with muscle atrophy.

OBJECTIVE To construct a predictive tool for surgical site infections(SSIs)in spinal surgery for Chi-nese population to provide evidence support for reducing SSIs.METHODS A systematic review of Chinese and English database literature was conducted for Meta-analysis to obtain pooled risk values for influencing factors,and a risk prediction scoring tool was constructed based on the logistic regression model.Patients who underwent spinal surgery and completed postoperative follow-up in a tertiary hospital in Beijing from Jan.to Dec.2021 were selected to validate the predictive effect of the tool.RESULTS The predictive model for SSIs in Chinese spinal sur-gery patients was Logit(P)=—3.47+0.63(age 60 years)+0.31 ×(patient with cardiovascular disease)+0.69 ×(rheumatoid arthritis)+1.07 ×(diabetes)+1.06 ×(operation duration＞3 h)+1.17 ×(preopera-tive albumin＜35 g/L)+0.71 ×(history of spinal surgery)+0.67 ×(carrying internal implants)+0.73 ×(blood transfusion).The total score of the predictive tool was 92,with a cutoff score of≥24.50 indicating high-risk individuals.The area under the curve was 0.733,with the sensitivity 58.30％and the specificity 79.60％.CONCLUSION The established predictive model for SSIs in Chinese spine surgery demonstrates good predictive performance and can be used as a reference assessment tool in clinical practice.

As a new generation of time-of-flight mass spectrometry,multiple-reflection time-of-flight mass spectrometry(MR-TOF-MS)has been increasingly applied in the fields such as nuclear physics,chemistry,and biology due to its ultra-high resolution and rapid analysis capabilities.However,the analytical performance of MR-TOF-MS largely depends on the ion bunch state entering the mass analyzer.In this study,a rectangular ion trap(RIT)was developed,designed and processed using printed circuit board technology,as an ion accumulating and focusing device for MR-TOF mass analyzer.Compared to traditional ion traps composed of two sets of planar electrodes,this RIT had higher voltage utilization efficiency,resulting in more efficient ion collection and focusing.The ions were cooled to a sufficiently small bunch for precise mass measurement with MR-TOF-MS mass spectrometry in only 1 ms of cooling time in the RIT,then orthogonally ejected to the MR-TOF mass spectrometer for mass analysis.Experimental results indicated that the working cycle,ion flux,and ion focusing state of the RIT fully met the requirements of the MR-TOF mass analyzer.When coupled with the MR-TOF mass analyzer,the RIT enabled MR-TOF-MS to achieve a mass resolution of 1.5×105.

Objective To analyze differences of purified water,softened water,and concentrated softened water on the decontamination effects for surgical instruments,so as to provide a reliable reference for the selection of cleaning water for surgical instruments.Methods The physical and chemical indexes and components of concentrated softened water,softened water,and purified water were detected,and their cleaning effects for instrument were compared.The decontamination cleaning experiment was conducted in three hospitals with different types of cleaning water using mini cleaning machines,and the differences in the decontamination time were analyzed.The cleaning and decontamination experiments on contaminated instruments was performed using a spray cleaning and disinfection device,and the cleaning effects of instruments with different types of cleaning water were analyzed.Results Calcium content and hardness of the three types of cleaning water were all at a low level,which can avoid scale adhesion for cleaning surgical instruments.There were statistically significant differences in the pH value,conductivity,and contents of calcium,sodium and chloride among the three cleaning waters(P<0.05).The purified water was weakly acidic,and its conductivity,hardness,and contents of calcium,sodium and chloride were all at low levels.The softened water and concentrated softened water were weakly alkaline,with high levels of conductivity and sodium content and low level of chloride.There were statistically significant differences in the decontamination time of the purified water,softened water and concentrated softened water among hospitals(P<0.05).Under the same contamination condition of surgical instruments,there was a statistically significant difference in the qualified rate of instruments cleaning in the upper and lower cleaning baskets with different cleaning waters(P<0.05).Conclusion Concentrated softened water and softened water have high sodium content,and their decontamination and cleaning abilities are significantly stronger than those of the purified water.Purified water has poorer effects in instruments cleaning for its deionized property.Using concentrated softened water or softened water in the surgical instrument cleaning process can achieve effects of reducing consumption and increasing efficiency,which is conducive to improving cleaning efficiency and quality.

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult