OBJECTIVE To investigate the risk factors for sodium valproate （VPA）-induced hyperammonemia in neurocritical patients， and to construct a risk prediction model. METHODS Clinical data were retrospectively collected from 172 neurocritical patients who received VPA treatment in the Department of Critical Care Medicine， the Fourth Affiliated Hospital of Soochow University from January 2022 to June 2025. Patients were divided into the hyperammonemia group （73 cases） and the normal group （99 cases） based on their blood ammonia levels. Univariate analysis and LASSO regression analysis were used to screen for predictive variables. Independent factors were identified through multivariate Logistic regression analysis， and a nomogram was constructed accordingly. The performance of the model was evaluated using receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis （DCA）. RESULTS Combination of univariate analysis and LASSO regression analysis screened out seven predictive variables： body mass index （BMI）≥24.0 kg/m 2 ， concomitant use of benzodiazepines， VPA blood concentration， hemoglobin， serum urea， average daily VPA dose， and albumin. Multivariate Logistic regression analysis showed that concomitant use of benzodiazepines， BMI≥24.0 kg/m 2 ， VPA blood concentration， albumin and serum urea level （with odds ratios of 1.615， 1.538， 1.623， 1.942 and 0.637， respectively； 95% confidence intervals of 1.128-2.359， 1.059-2.251， 1.112-2.431， 1.106-3.598 and 0.402-0.980， respectively） were all significantly associated with VPA-induced hyperammonemia in neurocritical patients （ P ＜0.05）. The nomogram prediction model constructed based on these variables was evaluated， showing that the area under the ROC curve was 0.810 for the test set and 0.844 for the validation set. The calibration curves closely approximated t he actual curves， and the application of this model could improve the clinical net benefit. CONCLUSIONS Concomitant use of benzodiazepines， BMI≥24.0 kg/m 2 ， high VPA blood concentration and high albumin level are independent risk factors for VPA-induced hyperammonemia in neurocritical patients， while high serum urea level is an independent protective factor. The risk prediction model constructed based on these factors exhibits good discrimination， consistency， and clinical applicability， making it applicable for predicting the risk of VPA-induced hyperammonemia in neurocritical patients.

Great revolutionary practice nurtures great revolutionary spirits. During the period of the New Democratic Revolution， under the leadership of the Communist Party of China （CPC）， the vast red medical workers relied on the masses， overcame numerous difficulties， worked self-reliantly， and struggled hard， achieving tremendous accomplishments in the healthcare industry. In this great practice， red doctor spirit with connotations of “political firmness， technical excellence， selfless dedication， healing the wounded and rescuing the dying， working hard， and daring to innovate” has been nurtured. It is the profound embodiment of the political position， value orientation， moral sentiment， willpower， and work style of the vast red medical workers， condensing the fine qualities of CPC members. Inheriting and promoting red doctor spirit in the new era is of great significance for advancing governance in the healthcare field， enhancing the medical ethics of medical personnel， and cultivating the humanistic spirit of medical students.

Objective To investigate the effects and mechanisms of high-fat diet(HFD)-induced obesity on male ze-brafish reproductive function.Methods Adult male zebrafish were divided into normal diet(ND)group and HFD group.Growth and metabolic conditions were evaluated by measuring body weight,body length,BMI,organ index,and glucose/lipid lev-els.Reproductive capacity was assessed via sperm concentration,motility,fertilization rate,and testosterone levels.Testicular tissues from both of groups were subjected to transeriptomic sequencing(RNA-seq).And qRT-PCR was used to validate the expression of genes.Results Compared to male zebrafish in ND group,the ones in HFD group exhibited hepatic steatosis and glucose/lipid meta-bolic disorders(P＜0.05).Testicular structural disorganization,along with reduced testosterone levels,decreased gonadosomatic in-dex,and impaired sperm concentration and motility occurred in HFD group(P＜0.05).GO analysis revealed that differentially ex-pressed genes were enriched in spermatogenesis and ciliary system,while KEGG analysis highlighted metabolic related pathways(pu-rine metabolism,thyroid hormone synthesis,mTOR signaling)and cell adhesion molecules.Twenty key differentially expressed genes were validated by qRT-PCR,which confirmed the reliability of RNA-Seq results.Conclusion Impairment of reproductive function induced by HFD in zebrafish may be associated with three regulatory mechanisms including ciliary system,metabolic dysregulation,and aberrant cell adhesion molecule signaling.This study provides mechanistic insights and identifies potential therapeutic targets for clinical management of diet-associated infertility.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective:To explore the composition of gut microbiome, the characteristics of virulence factor genes and their relationship with liver metabolic inflammation in overweight or obese children.Methods:A case-control design was conducted. From the children who visited the West China Second University Hospital of Sichuan University for medical or physical examinations between August 2021 and April 2022, a total of 23 obese children (obesity group), 8 overweight children (overweight group), and 22 healthy children (control group) were recruited. The body mass index of children was calculated after anthropometric measurements; metabolic inflammation indexes such as the levels of fasting blood glucose and hepatic function and renal function etc. were detected. The composition and abundance of gut microbiota in the feces of the children were detected by metagenomic sequencing technology and the Shannon index and Simpson index were calculated to assess the α diversity of virulence factor genes. The Wilcoxon rank-sum test was used for pairwise comparison between groups. The Spearman′s rank correlation test was used for correlation analysis, and the Benjamini-Hochberg method was used to correct the P-value of multiple tests. Results:The obese group included 23 children aged 8.5 (6.3, 11.8) years, of whom 9 (39%) were male. The overweight group consisted of 8 children aged 9.2 (5.5, 12.3) years, of whom 4 were male. The control group comprised 22 children aged 5.3 (5.1, 5.4) years, of whom 10 (45%) were male. The obese group exhibited higher levels of alanine aminotransferase (ALT), gamma-glutamyl transferase (γ-GT), globulin, and uric acid compared to those of the control group (all P<0.05), with ALT also higher than that of the overweight group ( P<0.05). The levels of fasting blood glucose, γ-GT, globulin, and uric acid in the overweight group were all higher than those in the control group (all P<0.05). The abundance of Coprococcus A (0.76 (0.00, 3.11) vs. 0.00 (0.00, 0.00), false discovery rate ( FDR)<0.05) and Parasutterella (0.89 (0.08, 1.79) vs. 0.00 (0.00, 0.08), FDR<0.05) in the gut of children in the obese group were both higher than those of the control group. The number of virulence factor genes in the obese group was higher than those of the control group (941 (886, 977) vs. 890 (807, 920), P<0.05). The Simpson index and Shannon index of gut microbial virulence factor genes in the obese group were both higher than those of the control group (0.993 (0.992, 0.993) vs. 0.991(0.990, 0.991), (5.50 (5.46, 5.56) vs. 5.37 (5.30, 5.43), both P<0.01). The abundance of gut microbiota virulence factors genes all showed positive correlations with fasting blood glucose, ALT, γ-GT, and uric acid levels in children (all r>0.3, all FDR<0.05). The abundance of 17 gut microbial virulence factor genes were all positively associated with γ-GT levels (all r>0.3, all FDR<0.05). The virulence factor genes (LpxH, LpxB, LpxK) of lipopolysaccharide were all positively correlated with plasma γ-GT and globulin levels (all r>0.3, all FDR<0.05). Conclusions:Overweight or obese children exhibited elevated liver metabolic-inflammatory markers compared to their normal-weight counterparts. Notably, obese children demonstrated gut microbiota dysbiosis accompanied by enrichment of virulence factor genes, which may promote liver metabolic inflammation through pathways such as lipopolysaccharide biosynthesis.

Objective To compare the effects of different exercise acclimatization(EA)durations on liver injury and inflammatory response in mice with exertional heatstroke(EHS).Methods A total of 168 male C57BL/6 mice were randomly assigned to four groups using a random number table:no exercise acclimation group(EA0W,n=54),1-week exercise acclimation group(EA1W,n=54),2-week exercise acclimation group(EA2W,n=54),and blank control group(n=6).The blank control group did not undergo acclimatization training or EHS modeling.The EA1W and EA2W groups underwent daily 2-hour exercise training at a speed of 10 m/min in an environment maintained at(26.0±0.5)℃for 1 and 2 weeks,respectively,followed by a 2-day rest after training completion.EHS modeling was performed in mice of EA0W,EA1W,and EA2W groups through running at 10 m/min under controlled environmental conditions(39.5℃ambient temperature,65%relative humidity).The modeling endpoint was defined as loss of consciousness accompanied by a core body temperature≥42.7℃.All modeling procedures were systematically documented.Following modeling,18 mice from EA0W,EA1W,and EA2W groups underwent 24-hour survival analysis.Blood samples from the abdominal aorta and liver tissues were collected at 6,12 and 24 hours post-modeling(6 mice per time point for each group).Plasma levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatine kinase(CK)were quantified.Interleukin(IL)-1β and IL-6 concentrations were determined using enzyme-linked immunosorbent assay(ELISA).Liver tissue specimens underwent hematoxylin-eosin(HE)staining and pathological scoring.Results The EHS model was successfully established in all EA groups.When all mice in EA0W group developed EHS(65 min after the modeling initiation),the incidence rates in EA1W and EA2W groups were 50.0%and 22.2%,respectively,with a statistically significant difference between EA0W group and the latter two groups(P<0.05).When all mice in the three groups developed EHS,the time to EHS onset was significantly longer in both EA1W and EA2W groups compared to EA0W group,with EA2W group showing a longer onset time than EA1W group(P<0.05).Survival analysis revealed a significantly higher 24-hour survival rate in EA2W group(61.1%)compared to EA0W group(33.3%)(P<0.05),while no significant difference was observed between EA1W group and the other two groups(P>0.05).The levels of IL-1β,IL-6,and CK were highest at 6 h post-modeling in all EA groups(P<0.05),and liver injury was most severe at 12 h post-modeling(P<0.05).Compared to EA0W group,the levels of ALT,AST,and IL-1β,as well as liver pathology scores,were significantly lower at 12 h post-modeling in both EA1W and EA2W groups(P<0.05),with EA2W group showing significantly lower ALT and AST levels,as well as liver pathology scores than EA1W group(P<0.05).At 6 h post-modeling,CK levels were significantly higher in EA1W and EA2W groups compared to EA0W group(P<0.05),with EA2W group exhibiting higher CK levels than in EA1W group(P<0.05).Conclusions Exercise acclimation helps reduce the incidence of EHS.Following EHS onset,the survival rate of exercise-acclimated mice is higher than that non-acclimated mice,with a significantly higher survival rate in mice acclimated for 2 weeks compared to non-acclimated mice.However,no significant difference in survival rate is observed between mice acclimated for 1 week and non-acclimated mice.Additionally,exercise acclimation for 2 weeks is more effective in reducing liver injury and inflammatory responses compared to 1-week acclimation.

Objective To develop nanobodies with broad-spectrum reactivity,specificity,and high sensitivity that can be used for detecting multiple subtypes of influenza A virus,and to establish a nanobody-based enzyme-linked immunosorbent assay(ELISA)method.Methods Gene sequences of twelve nanobodies against influenza A virus were retrieved from the National Center for Biotechnology Information(NCBI)and nanobody databases.The nanoantibodies were prepared using molecular biological techniques including gene synthesis and recombinant expression.The binding activity,specificity,sensitivity,and affinity of these nanobodies were determined by ELISA screening and Gator affinity analysis.A double-antibody sandwich ELISA assay was established by combining the selected nanobody with a traditional mouse monoclonal antibody.Results Twelve nanobodies were expressed and purified.Two nanobodies capable of binding to multiple subtypes of influenza virus including H1,H3,H5,H7,and H9 were obtained and designated as VHH54 and KV108.Both nanobodies showed no cross-reactivity with other respiratory virus antigens.Furthermore,the KV108 nanobody exhibited the highest binding affinity,with a dissociation constant of 5.94×10-9mol/L for the influenza virus nucleoprotein(NP),and the lowest detection concentration for the NP antigen reached 0.00064 μg/mL.The double-antibody sandwich ELISA,using a combination of KV108 and a mouse monoclonal antibody,could sensitively detect the five common subtypes of influenza A virus(H1N1,H3N2,H5N1,H7N9,and H9N2).The lowest detection limit reached 110-403 PFU/mL,which was higher than that of the commercial colloidal gold kitfor influenza virus detection.Conclusion This study has identified a nanobody KV108,which is capable of binding to multiple subtypes of influenza virus,and established a nanobody-based ELISA method that can detect multiple subtypes of influenza A virus.This study can facilitate the development of nanobody-based influenza detection technologies.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Objective To preliminarily explore the safety of collecting colostrum in the third trimester,and to evaluate postpartum breastfeeding in pregnant women with hyperglycemia during pregnancy.Methods Pregnant women with hyperglycemia during pregnancy who had prenatal examinations in Obstetrics and Gynecology Hospital,Fudan University from Jul to Nov 2022 were prospectively divided into the colostrum collection group(n=52)in the third trimester and the control group(n=55)by randomized controlled grouping method.The t-test,χ2 test,Fisher's exact probability method and rank sum test were used for statistical analysis of the data to compare the delivery outcomes,neonatal outcomes and postpartum breastfeeding status between the two groups.Results There were no significant differences in the gestational weeks at delivery,delivery methods,breastfeeding rates at 42 days postpartum and 4 months postpartum between the two groups of pregnant women with hyperglycemia during pregnancy.There were also no significant differences in the Apgar scores at 1 minute and 5 minutes after birth and the neonatal hospitalization rate.The proportion of formula milk as the first supplementary feeding after delivery and the delayed lactation rate at 3 days postpartum in the colostrum collection group were significantly lower than those in the control group(P<0.05).The exclusive breastfeeding rates at 24 hours postpartum and 3 days postpartum in the colostrum collection group were significantly higher than those in the control group(P<0.05).Conclusion Collecting colostrum in the third trimester among pregnant women with hyperglycemia during pregnancy is safe,and it can reduce the rate of supplementary feeding with formula milk after delivery,and increase the exclusive breastfeeding rates at 24 hours postpartum and 3 days postpartum.

Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P＜0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P＜0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P＜0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.