Objective To explore the predictive performance of machine learning models integrating clinico-pathological features and inflammatory markers for lymphovascular invasion (LVI) before gastric cancer surgery. Methods A retrospective cohort of 193 gastric cancer patients from The First Hospital of Lanzhou University (training set) and 185 patients from Zhongshan Hospital, Fudan University (validation set) was included. Preoperative clinical pathological characteristics, tumor markers, and inflammatory markers were collected to identify independent risk factors for LVI. Six machine learning models were established in the training set. Model performance was evaluated using area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, decision curve analysis (DCA), and Brier scores. Shapley additive explanations (SHAP) was applied for model interpretability. Results The multivariate logistic regression showed increased tumor invasion depth (T-stage), lymph node metastases (N-stage), and the systemic immune-inflammation index (SII) were independent risk factors for gastric cancer LVI (P＜0.05). Using these three indicators, 6 machine learning models were developed, all of which demonstrated favorable predictive performance, with 0.79 and 0.76 of minimum AUC values in the training set and the validation set, respectively. Among them, the light gradient boosting machine (LightGBM) model exhibited the best overall performance, achieving AUCs of 0.83 and 0.82 in the training set and the validation set, along with Brier scores of 0.163 and 0.187, respectively. Calibration and DCA curves further confirmed that the model possesses strong predictive accuracy and application value. SHAP analysis showed the feature importance in LightGBM model, identifying the N-stage as the top contributor, followed by the T-stage and the SII. Conclusion The machine learning models incorporating clinical pathological features and inflammatory indicators can effectively predict LVI status in gastric cancer, with the LightGBM model demonstrating optimal performance.

Clinical death refers to the permanent cessation of life functions. This article reviews the definition of clinical death and the various scenarios in which it occurs, classifies the process of clinical death, and discusses the criteria for determining uncontrollable cardiac death, controllable cardiac death and the criteria and workflow for determining brain death. It elaborates on the relationship between brain death and death, and proposes the areas to note when standardizing the medical documentation of death cases. Based on this, it introduces the content of the management system and workflow construction for death determination in medical institutions, including management structure, personnel qualifications, document norms, quality control system and training mechanism. Paying attention to the construction of the management system and workflow for death determination in medical institutions is of great significance for ensuring medical quality and safety, promoting the healthy development of organ donation, and maintaining the seriousness of legal and ethical practices.

In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

Objective:To analyze the clinical characteristics and treatment outcomes of children with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibody-mediated necrotizing myopathy, and to explore early identification and management strategies to provide reference for clinical diagnosis and treatment.Methods:A retrospective analysis was conducted on the clinical data and treatment outcomes of 10 pediatric patients with anti-HMGCR antibody-mediated necrotizing myopathy admitted to the Department of Rheumatology, Children′s Hospital of Fudan University from December 2020 to December 2024. Statistical description was performed using SPSS 22.0.Results:Among the 10 patients, the male-to-female ratio was 1:4, the age of onset was (7.2±4.0) years, and the disease duration at diagnosis was (22.2±19.6) months. None had a history of statin exposure. Six patients presented with muscle weakness, and4 were diagnosed due to asymptomatic elevation of creatine kinase (CK); 4 had dermatomyositis-like rashes. All patients showed significantly elevated CK levels [median 3 291(1 969, 8 776)U/L] and underwent muscle biopsy. Histopathological findings revealed myofiber degeneration, necrosis, and regeneration in all cases, with inflammatory infiltration in 9 cases, MHC-Ⅰ positivity in all, and C5b-9 positivity in 9 cases. The median follow-up duration was (15.7±6.3) months. At the last follow-up, muscle strength was normal or nearly normal, and the CK median value had decreased to 977.5 (211.0, 3 536.0) U/L.Conclusion:For patients with suspected idiopathic inflammatory myopathy and significantly elevated CK, muscle-specific antibody testing-including anti-HMGCR-and muscle biopsy should be performed promptly regardless of the presence of skin rash, to ensure accurate diagnosis and guide treatment, thereby avoiding misdiagnosis or missed diagnosis.

To investigate the potential protective effect of thalidomide (THD) on diabetic nephropathy (DN) and its underlying mechanisms. Twenty-four C57BL/6J mice were randomly divided into control, DN and DN+THD200 groups by random number table method. The DN mouse model was established via intraperitoneal injection of streptozotocin. The DN+THD200 group received THD treatment (200 mg·kg -1·d -1) for 8 weeks. Blood and urine biochemical parameters, as well as renal histopathological changes, were compared among the three groups. For in vitro experiments, a high glucose (HG)-induced injury model was established in mouse glomerular podocytes (MPC5). Cells were divided into control (NG), HG, HG+DMSO, HG+THD100 (100 μg/ml), and HG+THD200 (200 μg/ml) groups. THD-treated cells were exposed to THD for 24 h. Western blotting and real-time quantitative PCR were performed to respectively detect protein and mRNA expression levels of ferroptosis-related molecules, including nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO-1), and glutathione peroxidase 4 (GPX4). Immunofluorescence was used to evaluate the expression of solute carrier family 7 member 11 (SLC7A11) and 4-hydroxynonenal (4-HNE). The results showed that, compared with control group, DN group exhibited significantly lower blood urea nitrogen, serum creatinine and 24 h urinary albumin levels (all P<0.05). Compared with DN group, DN+THD200 group exhibited significantly lower blood urea nitrogen, serum creatinine and 24 h urinary albumin levels (all P<0.05). Histopathological examination revealed glomerular expansion, mesangial widening, and basement membrane thickening in DN group compared to control group, which were markedly ameliorated by THD treatment. In vitro, HG group showed significantly decreased protein and mRNA expression levels of GPX4, NRF2 and HO-1 compared to NG group. Both HG+THD100 and HG+THD200 groups exhibited upregulated expression levels of these proteins and corresponding mRNA compared to HG group (all P<0.05). Immunofluorescence demonstrated HG group had enhanced 4-HNE fluorescence intensity and reduced SLC7A11 fluorescence intensity, which were reversed by THD treatment. THD alleviates renal injury in DN mice and mitigates HG-induced ferroptosis in MPC5 cells, potentially via activation of NRF2-HO-1-GPX4 signaling pathway.

Objective:To evaluate the expression of tertiary lymphoid structures (TLS) in renal tissues, and the relationship between TLS and clinicopathological changes and prognosis in idiopathic membranous nephropathy (IMN) patients.Methods:It was a single center retrospective study. The patients with IMN diagnosed by renal biopsy at Shengjing Hospital Affiliated to China Medical University from January 2018 to December 2020 were enrolled, and their clinicopathological data were collected. Immunohistochemistry was used to evaluate the expression of TLS in renal tissues. According to whether TLS expression in renal tissues was positive or not, the patients were divided into TLS-positive group and TLS-negative group, and the baseline differences in clinicopathological data between the two groups were compared. The clinical remission included complete remission and partial remission. Logistic regression analysis was used to analyze the correlation between serum phospholipase A2 receptor (PLA2R) antibody titer and positive TLS expression in renal tissues. Kaplan-Meier survival curve and log-rank test were performed to analyze the differences of proteinuria remission rates between TLS-positive and TLS-negative groups. Cox regression analysis was employed to identify the related factors of proteinuria remission. The receiver operating characteristic (ROC) curve was used to evaluate the value of TLS in predicting proteinuria remission.Results:A total of 120 IMN patients were included in this study, with age of 50.00 (40.00, 57.75) years and 78 (65.00%) males. The 24-hour urinary protein was (7.54±4.14) g, 89 (74.17%) patients were positive for serum PLA2R antibody, and the serum PLA2R antibody titer was 90.49 (48.88, 155.33) RU/ml. Immunohistochemical results showed that TLS was mainly distributed in the renal cortex glomeruli or around renal blood vessels in renal tissues. There were 43 patients in the TLS-positive group and 77 patients in the TLS-negative group. The positive rate of serum PLA2R antibody in the TLS-positive group was 83.72% (36/43). Compared with the TLS-negative group, the TLS-positive group had lower serum albumin ( t=-3.474, P<0.001) and estimated glomerular filtration rate ( Z=-2.076, P=0.045), while serum creatinine ( t=2.006, P=0.028), 24-hour urinary protein ( t=4.140, P<0.001), serum PLA2R antibody titer ( Z=4.628, P=0.001), glomerulosclerosis degree ( Z=2.403, P=0.019), and proportions of hypertension ( χ2=6.511, P=0.011), renal interstitial fibrosis ( χ2=4.088, P=0.043), renal interstitial inflammatory cell infiltration ( χ2=9.261, P=0.002), tubular atrophy ( χ2=4.936, P=0.026) and extremely high-risk of kidney disease progression ( χ2=9.352, P=0.002) were higher. Multivariate logistic regression analysis showed that serum PLA2R antibody titer was an independent factor correlated with positive TLS expression in renal tissues ( OR=1.014, 95% CI 1.007-1.021). The median follow-up time was 18.00 (95% CI 16.07-19.93) months. Kaplan-Meier survival curve showed that the proteinuria remission rate in the TLS-positive group was lower than that in the TLS-negative group (Log-rank χ2=9.339, P=0.002). Cox regression analysis showed that positive TLS expression was an independent factor correlated with proteinuria remission ( HR=0.228, 95% CI 0.177-0.297). ROC curve showed that TLS had a certain clinical predictive value for proteinuria remission ( AUC=0.703, 95% CI 0.608-0.798). Conclusions:IMN patients with positive TLS expression in renal tissues have a lower proteinuria remission rate, more severe pathological damage, and a higher risk of disease progression. TLS is expected to become a pathological marker for predicting the severity and prognosis of IMN.

Mandibular reconstruction refers to the restoration of the continuity of the mandible through techniques such as autologous bone grafting,thereby restoring the patient's basic appearance,reconstructing the occlusal relationship,and restoring functions such as opening the mouth,chewing,and swallowing,in order to achieve a unity of oral and maxillofacial forms and functions.Due to the fact that mastication necessitates the coordinated efforts of the masticatory muscles,mandible,dental arch,and tongue,the recovery of masticatory function not only serves as a robust indicator for the success of surgery but also enhances the patients'quality of life,facilitating an early return to normal life.Currently,for the rehabilitation of oral function in patients after mandibular reconstruction surgery,standardized tools have been established in the fields of swallowing,occlusion,and speech assessment,and targeted training has been implemented,yielding significant therapeutic outcomes.However,research related to masticatory function faces two major challenges.First,existing assessment tools primarily focus on a single dimension,such as masticatory efficiency or subjective perception,and an integrated assessment system that encompasses multiple dimensions,including bite force distribution and oral sensory perception,has not yet been established.Second,although individual studies have explored factors affecting postoperative masticatory function,a systematic consensus has not been veached,leading to a lack of precision and individualization in clinical interventions,which significantly prolongs the patients'rehabilitation period.This paper reviews the scope and limitations of existing assessment tools for masticatory function in patients after mandibular reconstruction and systematically analyzes the key factors affecting postoperative masticatory function,aiming to promote a shift in clinical practice from"structural reconstruction"to a"function-perception collaborative rehabilitation"approach,and to provide a theoretical framework for constructing evidence-based,personalized masticatory rehabilitation programs.

Objectives:This study aims to evaluate the causal relationship between plasma proteins and myocardial infarction(MI)using two-sample bidirectional Mendelian randomization(MR)analysis,identify key biomarkers,and validate their expression.Methods:The study utilized publicly available genome-wide association study(GWAS)data of 4 907 plasma proteins as the exposure factor,with single nucleotide polymorphisms(SNPs)as instrumental variables,and four MI datasets as outcomes.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,complemented by simple model,weighted model,weighted median estimator(WME),and MR-Egger regression methods to assess the causal relationship between exposure factors and outcomes.Venn diagrams and word clouds were used to screen proteins associated with MI as candidate biomarkers.Reverse MR analysis was conducted to evaluate reverse causality.Sensitivity analysis was performed to assess the robustness of the results.Immunohistochemistry(IHC)was used to validate the expression of proteasome activator subunit 1(PSME1)and vacuolar protein sorting 29(VPS29)in the aorta of mice,and enzyme-linked immunosorbent assay(ELISA)was used to verify the expression of PSME1 and VPS29 in plasma from patients with acute myocardial infarction(AMI).Results:The two-sample MR analysis indicated that PSME1 was significantly negatively associated with myocardial infarction in all four datasets,with OR(95%CI)of 0.684(0.557-0.839),0.990(0.987-0.993),0.579(0.448-0.748),and 0.993(0.990-0.996),respectively,with all P<0.001.Similarly,VPS29 also showed a significant negative association with MI in all four datasets,with OR(95%CI)of 0.902(0.862-0.945),0.998(0.997-0.999),0.866(0.808-0.929),and 0.998(0.997-0.999),respectively,with all P<0.001.Reverse MR analysis did not detect reverse causality,and sensitivity analysis confirmed the robustness of the results.IHC results showed significantly reduced expression of PSME1 and VPS29 in the aortas of AMI mice with an atherosclerotic background compared to control mice(both P<0.05).ELISA results indicated significantly lower plasma levels of PSME1 and VPS29 in AMI patients compared to healthy controls(both P<0.05).Conclusions:Higher levels of PSME1 and VPS29 are negatively associated with the risk of MI,suggesting that PSME1 and VPS29 may serve as protective biomarkers for cardiovascular diseases.

AIM:To study the effect of nicotinamide mononucleotide(NMN)on renal fibrosis in mice with Al-port syndrome(AS)through TGFβ/Smad3 pathway.METHODS:SPF grade female X-linked AS(COL4A5 KI)mice were divided into model group(AS group)and model drug administration group(AS+NMN group).while female C57BL/6 mice served as the wild-type(WT)group,with 7 to 8 mice in each group.The mice in the administration group were given oral administration at 8 weeks of age for 8 weeks to 16 weeks of age.The remaining mice were given saline intragastric ad-ministration.The ratio of urinary microalbumin to urinary creatinine(UACR)was measured by biochemical method.After sampling,the renal fibrosis was analyzed by Masson staining.The expression levels of desmin and α-smooth muscle actin(α-SMA)were detected by immunohistochemistry.The expressions of fibrosis-related proteins desmin,α-SMA,trans-forming growth factor β(TGFβ),Smad3,p-Smad3,and fibronectin were detected by Western blot.RESULTS:Com-pared with the model group,UACR(13 weeks,P＜0.01;15 weeks,P＜0.01)and fibrosis-related protein expression(P＜0.05)in AS mice were significantly decreased after NMN treatment.CONCLUSION:Treatment with NMN attenuates renal fibrosis in AS mice through TGFβ/Smad3 signaling pathway.

Objective:To investigate the role of the structural gene vgrG of the type Ⅵ secretion system (T6SS) of Klebsiella pneumoniae ( Kpn), and evaluate the growth ability in vitro and pathogenicity of the bacteria after vgrG was deleted. Methods:Using sequences published by the National Center for Biotechnology Information (NCBI), primers were designed to amplify the upstream and downstream homology arms of vgrG via PCR. These fragments were cloned into the vector pKO3-Km after overlapping, the recombinant vector pKO3-Km- vgrG was transferred into Kpn competent cells, and the vgrG deletion strain Δ vgrG was obtained through homologous recombination. The vgrG promoter with the complete gene fragment was amplify by PCR and cloned into the pBAD33 vector. The pBAD33- vgrG was then transferred into Δ vgrG competent cells to obtain the complemented strain CΔ vgrG. The wild-type strain (WT), Δ vgrG strain and CΔ vgrG strain were cultured in LB (Luria-Bertani) liquid medium to compare growth rates. Adhesion to human lung epithelial A549 cells and intracellular survival in macrophages Raw264.7 cells were assessed. In vivo experiments included mouse survival analysis ( n=10) and lung bacterial load quantification ( n=6). Statistical comparisons were performed using the Student t-test. Results:The Δ vgrG strain was obtained through homologous recombination. It was identified by specific primers that compared with the WT strain, the complete vgrG fragment (2 487 bp) was deleted. On this basis, the CΔ vgrG strain was obtained. Deletion of vgrG did not significantly affect Kpn growth in vitro growth ability of bacteria before on after Kpn deleted vgrG [(1.40±0.10) vs (1.20±0.30), t=0.63, P>0.05]. The viscosity of WT strain was significantly higher than that of the Δ vgrG strain [(0.96±0.04) vs (0.38±0.05), t=9.72, P<0.05], the viscosity of the CΔ vgrG strain was also significantly higher than that of the Δ vgrG strain ( P<0.05). At the cellular level, the amount of adherent bacteria of the WT strain to A549 cells was significantly greater than that of the Δ vgrG strain [(5 367.00±318.00) CFU vs (4 067.00±88.19) CFU, t=3.94, P<0.05], the amount of adherent bacteria of CΔ vgrG strain was also significantly higher than that of Δ vgrG strain ( P<0.05). After 12 h infection, the WT strain survival rate in macrophages was significantly higher than that of the Δ vgrG strain[(69.00±1.00)% vs (47.50±2.50)%, t=7.99, P<0.05]. At the animal level, the survival rate of WT strain group after lethal dose infection of mice was significantly lower than that of Δ vgrG strain group [(16.67±8.82)% vs (53.33±6.67)%, t=3.32, P<0.05]; mice infected with semi-lethal dose and the number of bacteria load in the lungs of WT strain group was significantly higher than that of the Δ vgrG strain group[ (4.97±0.06) lg CFU/g vs (4.05 ±0.04) lg CFU/g, t=12.27, P<0.01], the amount of bacteria in the lungs of mice in CΔ vgrG strain group was also significantly higher than that in Δ vgrG strain group ( P<0.01). Conclusions:The vgrG gene does not affect the growth of Kpn in vitro, but it is involved in the adhesion of Kpn to epithelial cells, resistance to macrophage killing and pathogenicity to mice.