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.

Objective:To investigate the possible mechanisms underlying the involvement of the gut microbiota metabolite trimethylamine oxide (TMAO) in the pathogenesis of chronic spontaneous urticaria (CSU) .Methods:From June 2023 to June 2024, 67 CSU patients were enrolled from the Dermatology and Cosmetic Center, the Third Affiliated Hospital of Chongqing Medical University, and 69 age-matched healthy controls were also collected at the same time. Serum TMAO levels in both groups were measured using enzyme-linked immunosorbent assay (ELISA) , and D-dimer levels were collected from the CSU patients. A degranulation model was established in rat basophilic leukemia RBL-2H3 cells using anti-DNP IgE/DNP-BSA (IgE/Ag group) ; these cells were additionally grouped to be treated with different concentrations of TMAO (IgE/Ag+10 μmol/L TMAO group, IgE/Ag + 50 μmol/L TMAO group, IgE/Ag + 100 μmol/L TMAO group) ; untreated RBL-2H3 cells served as a blank control group. To investigate the effect of the extracellular signal-regulated kinase (ERK) phosphorylation inhibitor U0126 on the action of TMAO, RBL-2H3 cells were divided into another 5 groups: blank group, IgE/Ag group, IgE/Ag + 1 μmol/L U0126 group, IgE/Ag + 100 μmol/L TMAO group, and IgE/Ag + 100 μmol/L TMAO + 1 μmol/L U0126 group. In vivo, a localized allergic reaction model was established in the ears of C57BL/6 mice using anti-DNP IgE/DNP-BSA (IgE/Ag group) , and additional groups included blank group, IgE group, IgE/Ag + solvent (DMSO) group, and IgE/Ag + 10 μg/μl TMAO group. ELISA was performed to detect levels of inflammatory mediators in cell culture supernatants and mouse serum. Toluidine blue staining was employed to observe mast cell degranulation in the cell experiment and mouse ear tissue samples, Evans blue staining to assess vascular permeability in mouse ear tissue samples, and Western blot analysis to detect the ERK phosphorylation levels. The t test was used for comparisons between two groups, and one-way analysis of variance for multiple comparisons. Results:Serum TMAO levels were significantly higher in the 67 CSU patients than in the 69 healthy controls ( t = 13.27, P < 0.001) . Among the 32 CSU patients with available data about D-dimer, serum TMAO levels were positively correlated with D-dimer levels ( r = 0.62, P < 0.001) . In RBL-2H3 cell experiments, degranulation rates were significantly higher in the IgE/Ag + 10, 50, and 100 μmol/L TMAO groups than in the IgE/Ag group; morphologically, RBL-2H3 cells treated with 10, 50, and 100 μmol/L TMAO became increasingly rounded; 50 and 100 μmol/L TMAO significantly promoted the production of β-hexosaminidase (β-Hex) , interleukin-6 (IL-6) , and tumor necrosis factor-α (TNF-α) (all P < 0.01) , and upregulated ERK phosphorylation levels ( P < 0.01) ; the levels of ERK phosphorylation, IL-6, TNF-α, and β-Hex were significantly lower in the IgE/Ag + U0126 group than in the IgE/Ag group, as well as lower in the IgE/Ag + TMAO + U0126 group than in the IgE/Ag + TMAO group (all P < 0.001) . In the mouse model of localized allergic reaction, the IgE/Ag + TMAO group showed increased vascular permeability, edema degree, and mast cell degranulation, as well as significantly elevated ERK phosphorylation levels and TNF-α expression in mouse ear tissues compared with the IgE/Ag + DMSO group (both P < 0.05) . Conclusion:Elevated serum TMAO may participate in the pathogenesis of CSU by upregulating ERK phosphorylation levels in mast cells and skin tissues, thereby promoting IgE/Ag-mediated degranulation of effector cells and production of inflammatory mediators.

Objective:To investigate the role of mechanosensor Yes-associated protein 1 (YAP1) in urothelial cells in inducing bladder dysfunction in a partial bladder outlet obstruction (pBOO) model.Methods:Ten female C57BL/6 mice were included in this study and randomly divided into pBOO and sham groups based on body weight using a stratified pairing method, with 5 mice in each group. The pBOO group underwent proximal urethral ligation surgery, while the sham group underwent a sham operation. Two weeks after surgery, the urinary pattern was analyzed using the urine spot test. The significant increase in urine spot numbers indicated the successful establishment of the pBOO model. The mice were then sacrificed, and bladder tissues were weighed and stained with hematoxylin and eosin (HE) to observe morphological changes. The bladder urothelial layer was further isolated, and total cell proteins were extracted to detect the expression levels of YAP1 protein using Western blotting. Mouse immortalized bladder urothelial cells were divided into three experimental groups: the negative control (NC) group, which was treated with YAP1-NC lentivirus; the overexpression (OE) group, which was treated with YAP1-OE lentivirus to induce YAP1 protein overexpression; and the verteporfin treatment (VP) group, which was treated with verteporfin on the basis of the OE group. Real-time quantitative PCR and Western blotting were used to verify the transcription and expression levels of YAP1 protein, the co-transcriptional activator TEAD4 protein, and the phosphorylated protein DRP1-616 (at serine 616) of dynamin-related protein 1 (DRP1). An ATP detection kit was used to measure the ATP release concentration in the NC, OE, and VP groups. The interaction between YAP1 and TEAD4 was investigated using co-immunoprecipitation, and the expression of the mitochondrial marker translocase of the outer mitochondrial membrane 20 (Tom20) was observed using immunofluorescence staining.Results:The results of the urine spot test showed that the number of urine spots on the filter paper in the pBOO group was higher than that in the sham group within 6 hours [(283.0±9.1) spots vs. (3.7±0.3) spots, P<0.01], and the urine spots were scattered. The bladder wet weight in the pBOO group was significantly higher than that in the sham group [(105.70±6.84) mg vs. (22.33±1.20) mg, P<0.01]. Histological observations revealed reduced bladder mucosal folds and increased detrusor muscle thickness in the pBOO group. The expression of YAP1 protein in the bladder urothelial cells of the pBOO group was significantly upregulated compared to the sham group [(1.26±0.08) vs. (0.50±0.04), P<0.01]. In vitro experiments showed that compared to the NC group, the OE group had significantly increased expression of DRP1-616 [(0.94±0.05) vs. (0.33±0.01), P<0.01] and higher ATP release concentration [(24.45±0.16) μmol/mg vs. (19.67±0.42) μmol/mg, P<0.01]. In contrast, the VP group had significantly decreased expression of DRP1-616 [(0.29±0.04) vs. (0.94±0.05), P<0.01] and lower ATP release concentration [(10.55±0.01) μmol/mg vs. (24.45±0.16) μmol/mg, P<0.01] compared to the OE group. Co-immunoprecipitation experiments using YAP1 and TEAD4 antibodies showed that YAP1 and TEAD4 proteins could interact and form a transcriptional complex to regulate ATP release. Immunofluorescence staining revealed increased expression of Tom20 in the OE group compared to the NC group [(104.20±3.28) vs. (74.51±3.87), P<0.01]. Conclusions:In the pBOO-induced bladder dysfunction model, YAP1 is highly expressed in urothelial cells. YAP1 forms a transcriptional complex with TEAD4 to regulate ATP release by promoting mitochondrial fission via DRP1-616 expression, which is a key mechanism underlying pBOO-induced bladder dysfunction.

Objective:To explore the effect of neck muscle group exercise on setup errors in postoperative radiotherapy for head and neck cancers.Methods:A total of 126 head and neck cancer patients scheduled for radiotherapy at the First Affiliated Hospital, Air Force Medical University from February 2021 to October 2022 were prospectively enrolled. Among these patients, four patients discontinued treatment due to personal reasons, and the remaining 126 patients were randomly divided into an experimental group and a control group, with 61 patients in each group. The experimental group received neck muscle group exercise, while the control group received routine treatment without intervention. Cone-beam CT (CBCT) scans were performed weekly to measure setup errors at the levels of the clivus and the 4 th and 7 th cervical vertebrae (C4 and C7, respectively). Three-dimensional displacement, systematic errors, and random errors were calculated for each level. The appropriate margins of planning target volumes (PTVs) were determined using the Van Herk formula. Results:Baseline characteristics were well-balanced between the two groups, with no statistically significant differences ( P > 0.05). Compared to the control group, the experimental group showed significantly smaller setup errors in the left-right ( x) and anterior-posterior ( z) directions at the clivus level, as well as in the z direction at the C4 and C7 vertebral levels ( t = 2.30, 5.29, 4.07, 2.40, P < 0.05). The required PTV margin in the z direction increased to 4.0 mm at C7 from 2.4 mm and 2.8 mm at the clivus in the experimental and control groups, respectively. Correlation analysis revealed a strong negative correlation between the x-direction at the clivus and C4 vertebral levels and the couch angle (RTN) among all patients ( r = -0.548, -0.452, P < 0.001). A moderate negative correlation was observed between the inferior-superior ( y) direction and the z-direction at the C4 and C7 vertebral levels ( r = -0.160, -0.222, P < 0.001). Conclusions:Neck muscle group exercise can reduce setup errors and PTV margins in the anterior-posterior direction in postoperative radiotherapy for head and neck cancer patients.

Under the background of breaking the " five only" evaluation criteria, continuously optimizing the scientific research performance evaluation system of hospitals to mobilize the enthusiasm and creativity of scientific researchers and guide the direction of scientific research development plays an important role in enhancing the overall scientific research capability of hospitals. Through literature analysis and expert consultation, a certain hospital has constructed a personal scientific research performance evaluation index system for medical staff in tertiary public hospitals, oriented towards innovation quality and member contributions, and began to implement it throughout the hospital in 2021. This index system included four categories of scientific research performance: vertical scientific research projects, academic influence, science and technology awards, and transformation of achievements, with a total of 20 indicators. The annual scientific research performance score of an individual would serve as the basis for the distribution of year-end scientific research performance and an important reference for applying for key and major projects within the hospital. After the application of this evaluation index system, the enthusiasm of medical staff for scientific research has been effectively stimulated. The average individual scientific research performance score increased from 0.974 in 2020 to 1.220 in 2023. All scientific research indicators involved in the evaluation system have shown growth, with a significant increase in high-quality results. This evaluation system can provide a reference for the scientific research performance evaluation of public hospitals under the background of breaking the " five only" evaluation criteria.

Objective:To improve the risk management process for clinical trial projects using healthcare failure mode and effect analysis(HFMEA), for references for enhancing the risk identification and preventing capabilities of drug clinical trial institutions.Methods:From June to December 2022, this study focused on the project management process of a clinical trial centre in a tertiary public hospital. Following HFMEA procedures, a research team was established. Core processes prone to failure modes in the drug clinical trial project management and their potential failure modes were identified through group discussions, literature analysis, the Delphi method, and decision tree analysis. High-risk failure modes were screened via risk assessment, corresponding improvement measures were formulated and performed, and their effectiveness was validated.Results:The study identified 6 main processes, 17 sub-processes, and 102 potential failure modes. Delphi analysis confirmed 88 failure modes, with 19 having a failure risk priority number(RPN)≥8.00. Decision tree analysis identified 16 high-risk failure modes, involving 5 main processes and 10 sub-processes. Targeted improvements, such as adopting standardized hospital contract templates and setting deadlines for final payment settlement, etc., were implemented. One year post-implementation(January 2024), the RPN for all 16 high-risk failure modes were<8.00.Conclusions:HFMEA could help hospital clinical trial institutions comprehensively and systematically identify high-risk failure modes in the project management process, develop targeted improvement measures, and improve the level of drug clinical trial project management.

OBJECTIVE To explore the APOA5 gene polymorphisms,serum lipase(LPS),soluble programmed death ligand 1(sPD-L1)and procalcitonin(PCT)in the severe acute pancreatitis(SAP)patients with secondary infectious pancreatic necrosis(IPN).METHODS A total of 122 patients with SAP who were treated in the First Affiliated Hospital of Hebei North University from Jan.2020 to Nov.2023 were recruited as the research subjects and were divided into the secondary group with 31 cases and the non-secondary group with 91 cases according to the status of secondary IPN.The APOA5 gene polymorphisms were detected for the two groups of patients by means of polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The levels of LPS,sPD-L1 and PCT as well as Ranson score were compared between he two groups.The association of the serum LPS,sPD-L1 and PCT with Ranson score was observed by Spearman analysis.The value of the joint detection of LPS,sPD-L1 and PCT in diagnosis of secondary IPN in the SAP patients was analyzed by means of receiver oper-ating characteristic(ROC)curves.RESULTS The frequencies of AA genotype and A allele at rs619054 locus of APOA5 gene were higher in the secondary group than in the non-secondary group(P＜0.05),and the frequency of G allele of the secondary group was lower than that of the non-secondary group(P＜0.05).There were significant differences in the levels of serum LPS,sPD-L1 and PCT as well as Ranson score between the secondary group and the non-secondary group(P＜0.05).Spearman analysis showed that the Ranson score was positively correlated with the levels of serum LPS,sPD-L1 and PCT(r=0.738,0.701,0.721,P＜0.05).ROC curve analysis indicated that the area under the curve(AUC)of the joint detection of the three indexes was higher than that of the single detection in diagnosis of secondary IPN in the SAP patients(P＜0.05),with the sensitivity 90.30％,the specifici-ty 84.60％.CONCLUSIONS The SAP patients with secondary IPN show the high expressions of LPS,sPD-L1 and PCT.The joint detection of the indexes may facilitate the diagnosis of the secondary IPN in the SAP patients.There is association between the levels of LPS,sPD-L1 and PCT and the Ranson score.The rs619054 locus of APOA5 gene may be involved in pathogenesis of secondary IPN in the SAP patients.

Objective:To report construction of Evidence-Based Guidelines for the Diagnosis and Treatment of Distal Radius Fractures in Adults (2024) using the Delphi method.Methods:Literature related to the study of adult distal radius fractures was fully searched for and evaluated. An expert group was established from representative experts from all over the nation. The related clinical issues were established by consulting the experts in the form of electronic questionnaires, strictly following the Delphi research method. After the first draft of Evidence-Based Guidelines for the Diagnosis and Treatment of Distal Radius Fractures in Adults (2024) was written, an expert consultation questionnaire was designed for the recommendation opinions to determine the recommendation strength.Results:The clinical issues were determined by 2 rounds of correspondence based on the Delphi method. For the both rounds of correspondence, the questionnaire recovery rates were respectively 88.68% (47/53) and 98.11% (52/53), and the expert authority coefficients >0.7. According to the screening criteria based on the importance of clinical issues (mean importance score <3.5 points or a coefficient of variation ≥0.25 points and a full score ratio <30%) and expert opinions, a total of 40 clinical issues were deleted in the first round of determination of clinical issues, and a total of 5 clinical issues deleted in the second round of determination of clinical issues. The reliability analysis of the results of the 2 rounds of questionnaires showed that the Cronbach α coefficient was >0.9. In the questionnaire to determine the recommendation strength, according to the screening criteria for the consistency of recommendation strength (consistency ≥ 70%) and expert opinions, a total of 26 recommendations were screened in the first round. In the second round when the remaining 4 recommendations were investigated, one recommendation reached the consistency of recommendation strength ≥ 70%. Eventually, 27 recommendations were formed.Conclusion:The Evidence-Based Guidelines for the Diagnosis and Treatment of Distal Radius Fractures in Adults (2024) constructed using the Delphi method shows good scientific validity, authority, and reliability, providing methodological references for guideline development and research.

BACKGROUND:Studies have shown that vascular factors have an important impact on the occurrence of diabetic foot.OBJECTIVE:To investigate the important role of angiopoietin-like protein 4 in the formation of diabetic foot.METHODS:(1)Bioinformatics analysis was performed on the gene expression profile data of diabetic foot patients to find the key genes.The skin samples of diabetic foot patients and healthy people were collected for hematoxylin-eosin staining,immunohistochemical staining,and qRT-PCR experiments to detect the expression of angiopoietin-like protein 4.(2)The immortalized human skin fibroblast cell line and primary human umbilical vein endothelial cells were cultured.The two kinds of cells were divided into control group and exogenous angiopoietin-like protein 4 supplemented group.The migration ability and proliferation ability of fibroblasts were detected by scratch assay and CCK-8 assay.The proliferation ability of endothelial cells was detected by Ki67 assay.RESULTS AND CONCLUSION:(1)Bioinformatics analysis results showed that the down-regulation of angiopoietin-like protein 4 gene might be the key gene leading to the formation of diabetic foot.(2)Hematoxylin-eosin staining exhibited that compared with normal skin,angiopoietin-like protein 4 was weakly expressed in diabetic foot skin,and the mRNA level was decreased(P＜0.01).(3)Scratch assay results demonstrated that compared with the control group,fibroblast migration ability was significantly enhanced in the angiopoietin-like protein 4 group.CCK-8 assay showed that the absorbance value of fibroblasts in the angiopoietin-like protein 4 group was higher than that of the control group at 24 and 48 hours(P＜0.01,P＜0.001).It is suggested that angiopoietin-like protein 4 can enhance the migration and proliferation of fibroblasts.(4)Ki67 assay results demonstrated that the number of Ki67 positive cells in the angiopoietin-like protein 4 group was significantly more than that in the control group.CCK-8 assay results showed that the absorbance value of endothelial cells in the angiopoietin-like protein 4 group was higher than that of the control group at 24 and 48 hours(P＜0.05,P＜0.001).(5)All findings suggest that angiopoietin-like protein 4 can enhance the proliferation of endothelial cells treated with high glucose.

Objective To research the correlation between triglyceride-glucose index(TyG)and the risk of colorectal polyps with different pathological types.Methods According to inclusion and exclusion criteria,453 patients who underwent fiberoptic colonoscopy at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 2022 to December 2023 were selected.Based on colonoscopy results,patients were divided into non-colorectal polyp group and a colorectal polyp group.The polyp group was further classified according to pathological results into non-adenomatous polyps,adenomatous polyps,and colorectal cancer groups.A retrospec-tive analysis was conducted on the general data of the study subjects,including relevant test indicators such as blood glucose and lipids.Logistic regression analysis was employed to identify risk factors associated with the occurrence of colorectal polyps.Receiver operating characteristic(ROC)curves were constructed to evaluate the predictive role of the TyG index in the development of colorectal polyps,and the TyG levels among different pathological types of colorectal polyps were compared.Results Patients in the polyp group exhibited high-er age,male proportion,body mass index(BMI),glycosylated hemoglobin(HbA1c),triglycerides(TG),lipoprotein(a),and TyG in-dex compared to the non-polyp group.After adjusting for confounding factors,Logistic regression analysis indicated a correlation between the TyG index and the occurrence of colorectal polyps(P＜0.05).The area under the curve(AUC)for the TyG index predicting the development of colorectal polyps was 0.756(95％CI:0.702-0.809,P＜0.001).The TyG index level in the non-colorectal polyp group was lower than that in the non-adenomatous polyp,adenomatous polyp,and colorectal cancer groups,with statistically significant differences(P＜0.05).Pairwise comparisons also showed statistically significant differences(P＜0.05).Conclusion The TyG in-dex may be correlated with the occurrence of colorectal polyps.There are significant differences in the TyG index levels among different pathological types of colorectal polyps.