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.

In order to explore the effects of lipopolysaccharide(LPS)on the repair of bovine endo-metrial stromal cells(BESCs)during inflammatory response,BESCs were treated by LPS in this study.Cell apoptosis rate was detected using flow cytometry,cell viability was measured using the CCK-8 assay,cell migration ability was observed using a scratch assay,and the expression of con-nective tissue growth factor(CTGF),transforming growth factor-beta 3(TGF-β3)and vascular endothelial growth factor(VEGF)mRNA was measured using qRT-PCR.Additionally,the expression of key proteins in the PI3K/AKT and Wnt/β-catenin signaling pathways was assessed using Western blot analysis.The results showed that cell viability of BESCs significantly decreased(P＜0.01),cell migration ability decreased(P＜0.05),apoptosis rate of BESCs increased(P＜0.01),CTGF and TGF-β3 mRNA expression levels decreased(P＜0.01),while VEGF mRNA ex-pression increased after treatment with LPS(P＜0.01).The phosphorylation levels of PI3K,AKT and GSK-3β proteins decreased(P＜0.05),as well as the expression levels of c-Myc and Cyclin-D1 proteins also decreased(P＜0.01).These results indicated that LPS can inhibit the proliferation of BESCs and promote cell apoptosis possibly through the inhibition of the PI3K/AKT and Wnt/β-catenin signaling pathways.

This study investigated the disease characteristics and clinical traits of Nocardia infection,and analyzed the antibiotic resistance phenotypes,antibiotic resistance genes,and evolutionary characteristics of the strains,to provide a basis for Nocardia diag-nosis and treatment.A total of 31 Nocardia strains from a hospital in Hebei Province were collected from 2020 to 2023.The strains were identified through mass spectrometry and whole genome sequencing.Antibiotic susceptibility testing was conducted with the broth macrodilution method,and whole genome sequencing data were used to predict antibiotic resistance genes and comprehensively ana-lyze antibiotic resistance phenotypes.The 31 strains of Nocardia comprised 21 strains of Nocardia farcinica,3 strains of Nocardia ter-penica,three strains of Nocardia brasiliensis,two strains of Nocardia cyriacigeorgica,and two strains of Nocardia nova.The ceftriaxone susceptibility of 21 Nocardia farcinica strains was 85.7%,and all 31 strains were susceptible to imipenem,except for three strains of Nocardia brasiliensis.Rifampicin,aminoglycoside,and β-lactam resistance genes were found in Nocardia farcinica.Pathogenic tests should be carried out in a timely manner for suspected Nocardia infections.In clinical treatment of Nocardia infection,infected strains should be confirmed,and antibiotics should be used rationally according to the antibiotic susceptibility test results.

In order to explore the effects of lipopolysaccharide(LPS)on the repair of bovine endo-metrial stromal cells(BESCs)during inflammatory response,BESCs were treated by LPS in this study.Cell apoptosis rate was detected using flow cytometry,cell viability was measured using the CCK-8 assay,cell migration ability was observed using a scratch assay,and the expression of con-nective tissue growth factor(CTGF),transforming growth factor-beta 3(TGF-β3)and vascular endothelial growth factor(VEGF)mRNA was measured using qRT-PCR.Additionally,the expression of key proteins in the PI3K/AKT and Wnt/β-catenin signaling pathways was assessed using Western blot analysis.The results showed that cell viability of BESCs significantly decreased(P＜0.01),cell migration ability decreased(P＜0.05),apoptosis rate of BESCs increased(P＜0.01),CTGF and TGF-β3 mRNA expression levels decreased(P＜0.01),while VEGF mRNA ex-pression increased after treatment with LPS(P＜0.01).The phosphorylation levels of PI3K,AKT and GSK-3β proteins decreased(P＜0.05),as well as the expression levels of c-Myc and Cyclin-D1 proteins also decreased(P＜0.01).These results indicated that LPS can inhibit the proliferation of BESCs and promote cell apoptosis possibly through the inhibition of the PI3K/AKT and Wnt/β-catenin signaling pathways.

This study investigated the disease characteristics and clinical traits of Nocardia infection,and analyzed the antibiotic resistance phenotypes,antibiotic resistance genes,and evolutionary characteristics of the strains,to provide a basis for Nocardia diag-nosis and treatment.A total of 31 Nocardia strains from a hospital in Hebei Province were collected from 2020 to 2023.The strains were identified through mass spectrometry and whole genome sequencing.Antibiotic susceptibility testing was conducted with the broth macrodilution method,and whole genome sequencing data were used to predict antibiotic resistance genes and comprehensively ana-lyze antibiotic resistance phenotypes.The 31 strains of Nocardia comprised 21 strains of Nocardia farcinica,3 strains of Nocardia ter-penica,three strains of Nocardia brasiliensis,two strains of Nocardia cyriacigeorgica,and two strains of Nocardia nova.The ceftriaxone susceptibility of 21 Nocardia farcinica strains was 85.7%,and all 31 strains were susceptible to imipenem,except for three strains of Nocardia brasiliensis.Rifampicin,aminoglycoside,and β-lactam resistance genes were found in Nocardia farcinica.Pathogenic tests should be carried out in a timely manner for suspected Nocardia infections.In clinical treatment of Nocardia infection,infected strains should be confirmed,and antibiotics should be used rationally according to the antibiotic susceptibility test results.

Medical device related infections caused by bacteria are common complications in clinical practice,and preventing bacterial colonization on the surface of medical materials is one of the important challenges in the medical field.Therefore,there is an urgent need to construct medical coatings that combine antibacterial properties and biocompatibility.In this study,a γ-polyglutamic acid(γ-PGA)complex with long-chain alkyl quaternary ammonium salts formed by electrostatic and hydrophobic interactions was prepared,which was insoluble in water but soluble in organic solvents(e.g.,ethanol),and was capable of constructing antimicrobial coatings on the surfaces of medical materials in a simple and efficient manner.The bactericidal effect of the coating was verified using viable bacteria counting experiments,and the results showed that the bactericidal rate of the coated thermoplastic polyurethane(TPU)membrane against Staphylococcus aureus was greater than 99.9%compared with that of the uncoated TPU membrane.In addition,a cytotoxicity assay was performed using the L929 fibroblast and cell proliferation detection kit(CCK-8),which showed that the survival rate of L929 fibroblasts on coated TPU was greater than 90%.Meanwhile,the hemolysis rate of coated erythrocytes was tested using fresh rabbit red blood cells(RBCs),and the hemolysis rate on the coated TPU surface was 1.5%.The above results indicated that the coating had good biocompatibility.The preparation method of medical antibacterial coating reported in this study provided a new idea for preventing bacterial infections related to implantable/interventional medical devices.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective:To explore the therapeutic efficacy and prognostic factors of combined rituximab and intensive chemotherapy for sporadic adult Burkitt lymphoma (BL) .Methods:This retrospective study examined the clinical and survival data of 30 patients newly diagnosed with BL between July 2011 and February 2023 at the Blood Diseases Hospital. Kaplan-Meier method was used for survival analysis, and the log-rank test was used for univariate analysis of prognostic factors.Results:The median age of the 30 patients was 43 years (24 - 66 years), and the male to female ratio was 3: 2. Extranodal invasion was present in 80% of the patients, with involvement of the bone marrow in 53.3% and central nervous system in 10.0%. The Ann Arbor stage was Ⅲ and Ⅳ in 86.7%. According to the number of Burkitt Lymphoma International Prognostic Index (BL-IPI) risk factors, patients were classified as low risk (0) in 20.0%, intermediate risk (1) in 43.3%, and high risk (≥2) in 36.7%. All patients were treated with an induction regimen of rituximab combined with intensive chemotherapy, with objective and complete response rates of 80.0% and 76.7%, respectively. The median follow-up was 49 months (6-153 months), and the 5-year progression-free survival (PFS) and overall survival (OS) rates were both (76.7±7.7) %. All patients with limited stage ( n=4) achieved continuous complete remission (CCR). Patients who had high risk, advanced stage sensitive to induction therapy ( n=10) sequentially received first-line autologous hematopoietic stem cell transplantation (auto-HSCT) as consolidation therapy; 9 patients achieved CCR, whereas 1 patient with central nervous system invasion developed early disease progression and died. The BL-IPI low, intermediate, and high risk groups had respective 5-year PFS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % ( P=0.0069) and OS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % ( P=0.0075). The main adverse effects of induction therapy were myelosuppression and secondary infections, which were effectively managed by appropriate symptomatic treatment. Univariate analysis demonstrated that worse PFS was associated with BL-IPI score ≥2 ( HR=4.90, 95% CI 1.02-23.45, P=0.0329) ; extranodal invasion at ≥2 sites ( HR=12.62, 95% CI 2.59-61.62, P=0.0021) ; and failure to achieve first complete response (CR1) after induction therapy ( HR=31.86, 95% CI 4.19-242.20, P<0.0001) . Conclusions:Intensive immunochemotherapy regimens were effective and well-tolerated by adult patients with highly aggressive BL. Treatment efficacy was ideal in patients with limited-stage disease, whereas prognosis was unsatisfactory in patients with high-risk BL-IPI. Sequential first-line auto-HSCT consolidation therapy may further improve outcomes in patients with high-risk advanced-stage disease who are sensitive to induction therapy. BL-IPI score ≥2, extranodal invasion at ≥2 sites, and failure to achieve CR1 after induction therapy were adverse prognostic factors in adult patients with BL.

This study aims to integrate data mining techniques of single cell transcriptomics and spatial transcriptomics, along with animal experiment validation, so as to systematically characterize the protective effects of Jianpi Tongluo Formula(JTF) on the cartilage in knee osteoarthritis(KOA) and elucidate the underlying molecular mechanisms. Single cell transcriptomics and spatial transcriptomics datasets(GSE254844 and GSE255460) of the cartilage tissue obtained from KOA patients were analyzed to map the single cell-spatial heterogeneity and identify key pathogenic factors. After that, a KOA rat model was established via knee joint injection of papain. The intervention effects of JTF on the expression features of these key factors were assessed through real-time quantitative polymerase chain reaction(PCR), Western blot, and immunohistochemical staining. As a result, the integrated single cell and spatial transcriptomics data identified distinct cell subsets with different pathological changes in different regions of the inflamed cartilage tissue in KOA, and their differentiation trajectories were closely related to the inflammatory fibrosis-like pathological changes of chondrocytes. Accordingly, the expression levels of the two key effect targets, namely nuclear receptor coactivator 4(NCOA4) and high mobility group box 1(HMGB1) were significantly reduced in the articular surface and superficial zone of the inflamed joints when JTF effectively alleviated various pathological changes in KOA rats, thus reversing the abnormal chondrocyte autophagy level, relieving the inflammatory responses and fibrosis-like pathological changes, and promoting the repair of chondrocyte function. Collectively, this study revealed the heterogeneous characteristics and dynamic changes of inflamed cartilage tissue in different regions and different cell subsets in KOA patients. It is worth noting that NCOA4 and HMGB1 were crucial in regulating chondrocyte autophagy and inflammatory reaction, while JTF could reverse the regulation of NCOA4 and HMGB1 and correct the abnormal molecular signal axis in the target cells of the inflamed joints. The research can provide a new research idea and scientific basis for developing a personalized therapeutic schedule targeting the spatiotemporal heterogeneity characteristics of KOA.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Osteoarthritis, Knee/pathology* ; Humans ; Male ; Cartilage, Articular/metabolism* ; Chondrocytes/metabolism* ; Rats, Sprague-Dawley ; Female ; Protective Agents/administration & dosage* ; Single-Cell Analysis ; Middle Aged ; HMGB1 Protein/metabolism*