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.

Objective To explore the effectiveness of the generative large language model MedGo in nursing decision-making for elderly patients with multimorbidity. Methods A quasi-randomized controlled trial study was conducted involving 6 junior nurses, 6 senior nurses and the MedGo model from January 1, 2025 to March 31, 2025 at the Emergency Internal Medicine Ward of Shanghai East Hospital Affiliated to Tongji University. Clinical data of 120 elderly patients with multimorbidity were analyzed to compare the performance of the three groups in four tasks (nursing diagnosis assessment, nursing intervention formulation, complication identification, and complication prevention) from three evaluation dimensions: decision-making time consumption, decision accuracy, and decision-making quality. Results In terms of decision-making time, the senior nurse group completed all four tasks faster than the junior nurse group (P＜0.01), and the MedGo group completed all four tasks faster than the junior nurse group (P＜0.001) and the senior nurse group (P＜0.001). In terms of decision-making accuracy, senior nurse group scored higher than junior nurse group in all four tasks (P＜0.001), while the MedGo group outperformed the senior nurse group only in complication identification (P＜0.001). In terms of decision-making quality, the MedGo group scored higher than junior nurse group (P＜0.001) and senior nurse group (P＜0.001) in all four tasks. Conclusions The MedGo model demonstrates advantages of high efficiency, accuracy, and quality in nursing decision-making for elderly patients with multimorbidity; senior nurses outperform junior nurses in decision-making, providing diverse references for clinical nursing decision-making.

Jianghuanglian is one of the representative processed products of Coptidis Rhizoma for treating cold syndrome with drugs of heat nature， and ginger is used to restrict the bitter cold of Coptidis Rhizoma， which can be traced back to Bojifang， and it is suitable for stagnation of damp-heat in middle-jiao， cold-heat mutual knots and other symptoms. Jianghuanglian retains the alkaloids， phenylpropanoids and flavonoids of Coptidis Rhizoma， and also introduces gingerol components such as 6-gingerol in ginger， which has pharmacological activities such as anti-inflammatory， antibacterial， anti-tumor， and improving gastrointestinal function. The 2020 edition of Chinese Pharmacopoeia and many local processing specifications have included the traditional processing process and quality standards of Jianghuanglian， but the specific process parameters and quality standards are incomplete， which limits the production and clinical application of this processed product. By summarizing the processing history， process research， quality evaluation， pharmacodynamic and medicinal property changes and application of Jianghuanglian in the past 20 years， there are differences in the processing methods and standards in various provinces and cities， which are mainly reflected in the preparation method， dosage， processing process and quantitative standards of ginger juice. In addition， there are also certain differences in the changes of the main components of Jianghuanglian prepared from ginger or dried ginger， as well as their efficacy and medicinal properties. The research on the processing process of Jianghuanglian plays an important role in improving its quality standards， and this review can provide a reference for improving the quality evaluation system of Jianghuanglian.

Objective:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

Objective To systematically evaluate the clinical efficacy of thyroid surgery via the sternocleidomastoid muscle approach with lateral cervical incision.Methods A total of 286 patients undergoing thyroid surgery in Yuncheng Central Hospital Affiliated to Shanxi Medical University and the First Hospital of Shanxi Medical University from June 2022 to June 2023 were enrolled,and were divided into the lateral incision group(102 cases)and the median incision group(184 cases)according to the surgical approach.The clinical data including intraoperative bleeding volume,postoperative recovery time,intraoperative neuromonitoring signal changes,postoperative pain visual analogue scale(VAS)score,quality of life score,and postoperative complications of patients were compared between the two groups.Results The intraoperative bleeding volume of patients in the lateral incision group was significantly lower than that in the median incision group(P=0.03),and the postoperative recovery time was significantly shorter than that in the median incision group(P=0.01).Intraoperative monitoring of the recurrent laryngeal nerve showed that the residual amplitude of nerve signals in the lateral incision group was significantly greater than that in the median incision group(P<0.05),and the change in nerve signals latency was significantly smaller than that in the median incision group(P<0.05).The VAS scores of patients in the lateral incision group 3 days and 7 days after surgery were significantly lower than those in the median incision group(P<0.05).The quality of life scores of patients in the lateral incision group 3 months and 1 year after surgery were significantly higher than those in the median incision group(P<0.05).There was no statistically significant difference in the incidence of postoperative complications of patients between the two groups(P=0.15).Conclusion Thyroid surgery via the sternocleidomastoid muscle approach with lateral cervical incision has definite therapeutic effects,which can reduce intraoperative bleeding,shorten the postoperative recovery time,alleviate postoperative pain,and improve the quality of life of patients.

Deep medullary veins(DMVs)are critical components of the cerebral medullary venous system,responsible for venous drainage of the deep cerebral white matter.Recent research indicates that DMVs are closely related to cerebral small vessel disease(CSVD)and associated cognitive disorders.The morphological structure of DMVs can be clearly visualized on susceptibility weighted imaging and quantitative susceptibility mapping,which could potentially serve as markers for assessing the severity of CSVD.This article reviewed the anatomical characteristics and physiological functions of DMVs,as well as the mechanistic correlations between DMVs and various CSVD imaging markers,aiming to provide novel theoretical insights for early diagnosis and clinical management of CSVD.

Objective To assess the dietary quality of preschool children and explore the relationship between feeding practices and dietary quality.Methods Relying on the Shanghai Maternal-Child Pairs Cohort,3 177 preschool children were selected as the subjects for this study,and questionnaire were surveyed on their dietary intake and feeding practice.The diet balance index was used to evaluate dietary quality among preschool children.High bound score(HBS),the low bound score(LBS),and the dietary quality distance(DQD)were calculated to respectively reflect overall dietary overconsumption,insufficiency,and imbalance.Logistic regression was utilized to analyze the association between feeding practice and dietary quality in preschool children.Results The HBS,LBS,and DQD of the subjects were 2(0,8),22.19±10.80,and 26.78±9.57,respectively.Only 7.68%of the children had a balanced dietary intake,with 74.73%and 33.99%of overall dietary intake being inadequate and excessive,respectively.Parental perceived weight were negatively associated with the risk of moderate to high over intake among children(aOR=0.79,95%CI:0.63-0.98).The higher the perceived responsibility(aOR=1.19,95%CI:1.03-1.37)score,the lower the monitoring score(aOR=0.83,95%CI:0.74-0.93),and the higher the likelihood that the child had a moderate to high under intake.The scores of pressure to eat were also positively correlated with the risks of under intake and moderate to high overall unbalance in preschool children(aOR=1.15-1.39,95%CI:1.02-1.63).Conclusion Preschool children commonly experience dietary imbalance,with inadequate and excessive intake coexisting.Parental perceived weight and monitoring were positively associated with preschoolers'dietary quality,whereas perceived responsibility and pressure to eat were negatively associated with it.

Objective To investigate the correlation between enlarged perivascular spaces(EPVS)in different regions and glymphatic system(GS)function with cognitive function in patients with recent subcortical small infarction(RSSI).Methods A retrospective study was conducted by consecutively enrolling patients with RSSI who were hospitalized in the Department of Neurology at the Third Affiliated Hospital of Nanjing Medical University(Changzhou Second People's Hospital)from December 2023 to December 2024.Baseline and clinical data were collected,including age,sex,body mass index(BMI),history of smoking and alcohol consumption,hypertension,diabetes mellitus,atrial fibrillation,coronary heart disease,and laboratory indicators(including homocysteine,total cholesterol,triglycerides,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,glycated hemoglobin,uric acid,and creatinine).Cognitive function was assessed within 7 d of onset using the mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)scale,which covers seven cognitive domains:visuospatial and executive functioning,naming,attention,language,abstraction,memory,and orientation.All patients underwent brain MRI within 3 d of admission,including diffusion tensor imaging(DTI)sequences.The DTI along the perivascular space(DTI-ALPS)post-processing tool was used to calculate the DTI-ALPS index on both sides,and the mean value was taken as an indicator to evaluate overall GS function.The volumes of EPVS in the basal ganglia(BG)and centrum semiovale(CSO)were measured.EPVS severity was visually rated based on Potter's method(on a scale range from 0 to 4)and categorized into a none-to-mild(grades 0-1)and a moderate-to-severe(grades 2-4)group.Patients were further classified by region into a BG-EPVS and a CSO-EPVS subgroups under each severity group.(1)Univariate analyses were performed to compare baseline characteristics,DTI-ALPS index,and cognitive assessment scores between groups.Variables with P＜0.05 in univariate analyses were tested for multicollinearity using variance inflation factor.Variables without multicollinearity were included in multivariate Logistic regression to identify independent factors associated with BG-EPVS.To assess the robustness of the predictive value of the DTI-ALPS index,outlier diagnostics and exclusion were performed,followed by re-estimation of the Logistic regression model.Spearman's correlation analysis was used to examine the associations of BG-EPVS volume with the DTI-ALPS index,MMSE scale score,MoCA scale score,and each cognitive domain score.Mediation analysis was conducted to evaluate whether the DTI-ALPS index mediated the relationship between BG-EPVS volume and MoCA scale score.Results A total of 65 RSSI patients were included in the study,comprising 34 males and 3 1 females,aged 37 to 78 years,with a mean age of(53±15)years.Among them,30 patients were classified into the none-to-mild EPVS group and 35 into the moderate-to-severe EPVS group.For regional classification,34 were in the none-to-mild BG-EPVS group and 31 in the moderate-to-severe BG-EPVS group;36 were in the none-to-mild CSO-EPVS group and 29 in the moderate-to-severe CSO-EPVS group.(1)Univariate analysis showed,in both overall EPVS and BG-EPVS subgroup,the none-to-mild groups had lower age,lower proportions of male and hypertensive patients,and higher DTI-ALPS indices,MMSE scale scores,and MoCA scale scores than the moderate-to-severe groups(all P＜0.05).No significant differences were found in other baseline or clinical characteristics(all P＞0.05).In the CSO-EPVS subgroup,age was the only variable differed significantly between the none-to-mild group(significantly younger)and the moderate-to-severe group(P＜0.05),no other variables showed significant differences between the groups(all P＞0.05).(2)No multicollinearity was found among age,sex,hypertension,and the DTI-ALPS index through the multicollinearity analysis.Multivariate Logistic regression identified older age(OR,4.410,95％CI 1.211-16.025,P=0.024),male(OR,1.076,95％CI 1.001-1.156,P=0.048),and hypertension(OR,6.287,95％CI 1.635-24.167,P=0.007)as independent risk factors for moderate-to-severe BG-EPVS in RSSI patients,while a higher DTI-ALPS index was an independent protective factor(OR,0.002,95％CI 0.000-0.904,P=0.046).To assess the robustness of this model,six outlier cases were identified and excluded.After reanalysis,the negative association between the DTI-ALPS index and BG-EPVS risk remained significant(OR,0.050,95％CI 0.003-0.974,P=0.048).(3)Spearman correlation analysis revealed that the BG-EPVS volume in RSSI patients was negatively correlated with the DTI-ALPS index(rs=-0.842,P=0.007),MMSE scale score(rs=-0.491,P=0.033),MoCA scale score(rs=-0.563,P=0.018),and visuospatial/executive function score(rs=-0.596,P=0.001).No significant correlations were found between BG-EPVS volume and other cognitive domains,including naming,attention,language,abstraction,memory,and orientation(all P＞0.05).(4)Mediation analysis showed that the total effect size of BG-EPVS volume on MoCA scale score was-0.673,with a direct effect size of-0.537(account for 79.79％of the total effect size)and an indirect effect size via the DTI-ALPS index of-0.136(account for 20.21％).Conclusions In RSSI patients,age,sex,hypertension,and the DTI-ALPS index were identified as independent factors associated with the severity of BG-EPVS.BG-EPVS volume was negatively correlated with the DTI-ALPS index and cognitive function scores in RSSI patients.Moreover,the DTI-ALPS index mediated the relationship between BG-EPVS volume and cognitive function in RSSI patients.

With the increasing demand for dynamic,real-time and rapid qualitative analysis of chemical composition in areas such as emergency response and space exploration,chip-scale mass spectrometers have attracted significant attention.These devices are expected to drive the integration of mass spectrometry with micro/nano-fabrication and intelligent sensing technologies,fostering profound innovation and breakthroughs in analytical chemistry.As an excellent mass analyzer,the ion trap exhibits numerous advantages,and its miniaturization creates favorable conditions for the high-density integration of miniature mass spectrometers.However,the reduction in ion storage capacity may compromise its sensitivity and dynamic range,rendering the study of ion unidirectional ejection in highly miniaturized ion traps of significant practical importance.In this work,a research was conducted on achieving efficient ion unidirectional ejection while maintaining high mass resolution in the extremely miniature hyperbolic linear ion trap(M-HLIT)with a field radius of 1 mm,and an electric field compensation method was proposed,which combined asymmetric electrode stretching and unbalanced RF voltage to achieve high-precision optimization of the electric field composition.Simulations showed that in an ideal structure,this method achieved 100％unidirectional ejection efficiency with the mass resolution of 518,significantly outperforming traditional asymmetric structure method(365)and unbalanced voltage method(321).Following the introduction of ion ejection slots,further optimization through bidirectional stretching and electrical parameters improved the resolution to 790 while maintaining a unidirectional ejection efficiency of 93％.This method eliminated the requirement for additional excitation voltage,offering an ideal solution for the miniature mass analyzer with high detection performance of chip-level mass spectrometers.