ObjectiveTo evaluate pharmacological effects of Shengmai injection（SMI）on cerebral ischemia and study its neuroprotective mechanism. MethodsMale specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a sham group， a model group， a low-dose SMI group（3 mL·kg^-1）， a middle-dose SMI group（6 mL·kg^-1）， a high-dose SMI group（12 mL·kg^-1）， and a Ginaton group（4 mL·kg^-1）according to the random number table method， with 12 rats in each group. The rat model of cerebral ischemia-reperfusion（MCAO/R）was prepared via the suture method. The administration groups were intraperitoneally injected with corresponding concentrations of SMI or Ginaton injection after reperfusion， which was conducted for 3 consecutive days. The sham group and model group were administered the equivalent volume of physiological saline. The pharmacological effects of SMI on brain injury in MCAO/R rats were evaluated by neurological function scores， cerebral infarction area， hematoxylin-eosin （HE） staining， Nissl staining， terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining， and Western blot. The dominant link and key protein of SMI treating cerebral injury were explored using proteomic analysis. The related mechanisms of SMI were further validated using enzyme-linked immunosorbent assay （ELISA）， Western blot， and chloride ion fluorescence probe with oxygen-glucose deprivation/reoxygenation（OGD/R）-treated PC12 cells and MCAO/R rats. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly decreased density of Nissl bodies and neurons（P<0.01）. Compared with the model group， the SMI groups exhibited significantly decreased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly increased density of Nissl bodies and neurons （P<0.05）. The proteomic analysis results showed that oxidative stress and inflammatory response were important processes of SMI intervening in MCAO/R injury， and the chloride intracellular channel protein 1 （CLIC1） was one of key proteins in its action network. The levels of representative indicators of oxidative stress and inflammatory response in the MCAO/R rats of the SMI groups were significantly reduced， compared with those in the model group（P<0.05， P<0.01）， and the expression levels of CLIC1 and downstream NOD-like receptor protein 3 （NLRP3） decreased （P<0.01）. In addition， the experimental results based on the OGD/R PC12 cells showed that SMI significantly increased the cell survival rate（P<0.01） and significantly decreased the intracellular chloride ion concentration（P<0.05）. ConclusionSMI has neuroprotective effects. Oxidative stress and inflammatory response are key processes of SMI intervening in MCAO/R injury. The potential mechanism is closely related to the regulation of CLIC1.

Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

Objective To examine the quinolone resistance and mechanisms of resistance,including prevalence of transferable mechanisms of quinolone resistance(TMQR)genes in carbapenem-resistant Klebsiella pneumoniae(CRKP).Methods Antimicrobial susceptibility was tested for CRKP isolated from 7 hospitals in China during 2019 by broth microdilution method.Genome sequencing analysis was performed on Illumina HiseqX sequencing platform.The virulence genes,multilocus sequence typing(MLST),chromosome quinolone resistance-determining region(QRDR)variation,and prevalence of TMQR genes in CRKP were analyzed.Results Overall,98.4％and 99.2％of the 481 CRKP strains were non-susceptible to levofloxacin and ciprofloxacin,respectively.ST11(77.8％)and ST15(15.8％)were the dominant clones.Among the 303 CRKP strains carrying virulence gene(CV-CRKP),ST11 type and ST15 type strains accounted for 92.1％and 5.0％,respectively,while ST11 and ST15 type strains accounted for 53.4％and 34.3％in the 178 CRKP strains without the virulence gene(non-CV-CRKP).All of the ST11 and ST 15 type strains were resistant to quinolones associated with gyrA and parC mutation.All of the quinolone-sensitive strains were not ST11 type or not ST15 type.TMQR analysis showed that qnrS1(61.1％,294 strains),qnrB4(10.0％,48 strains)and aac(6)-Ib-cr(18.7％,90 strains)were most prevalent in CRKPs,while qnrB1(4 strains),qnrB2(2 strains),qnrD1(2 strains)and qnrB6(1 strain)were infrequently identified in CRKPs.Specifically,qnrB4 was mainly identified in high-level levofloxacin-resistant strains(MIC≥8 mg/L),while aac(6)-Ib-cr was found mainly in ciprofloxacin-resistant strains(MIC＞8 mg/L).Conclusions Clinical CRKPs were highly resistant to quinolone.The rate of QRDR variation were high in quinolone resistant CRKP strains,with high TMQR gene carriage.

Objective:To provide evidence-based recommendations for the prevention and management of lower limb ischemia in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients during treatment according to search, evaluate, and summarize the best evidence on the prevention and management of lower limb ischemia in patients with VA-ECMO.Methods:Based on the PIPOST framework (population, intervention, professional, outcome, setting, and type of evidence), an evidence-based question was formulated. A systematic search was conducted according to the "6S" evidence pyramid model in both domestic and international databases, as well as professional association websites, for all evidence related to the prevention and management of lower limb ischemia in VA-ECMO patients (aged ≥18 years). The types of evidence included clinical decisions, guidelines, expert consensus, systematic reviews, evidence summaries, and original studies. The search was conducted from the construction of the databases to February 2024. Two researchers independently conducted a literature quality evaluation, extracted and summarized evidence from the studies that met the quality criteria.Results:A total of 13 articles were included, consisting of 3 clinical decisions, 3 guidelines, 3 expert consensus, 3 systematic reviews, and 1 randomized controlled trial. A total of 18 pieces of evidence in 7 dimensions were summarized, including risk factors of VA-ECMO lower limb ischemia, evaluation before catheterization, evaluation and monitoring during treatment, prevention of lower limb ischemia, treatment of lower limb ischemia, management of distal perfusion catheter (DPC), and monitoring after VA-ECMO weaning.Conclusion:This evidence summary provides evidence-based recommendations for the prevention and management of lower limb ischemia in VA-ECMO patients, aiming to assist clinical healthcare professionals in developing tailored strategies for the prevention and management of lower limb ischemia based on during VA-ECMO support.

Objective:To evaluate the role of microRNA-149-5p (miR-149-5p) in resveratrol-induced reduction of lipopolysaccharide (LPS)-induced cardiomyocyte injury in rats.Methods:Rat cardiomyocyte cell line H9C2 was cultured and then divided into 5 groups ( n=27 each) using a random number method: control group (C group), LPS group, resveratrol group (RSV group), miR149-5p inhibitor negative control group (LRN group), and miR149-5p inhibitor group (LRI group). A cardiomyocyte injury model was prepared by incubating cells with culture medium containing 10 μg/ml LPS for 24 h. RSV group was incubated with resveratrol (final concentration of 10 μmol/L) for 24 h, followed by incubation with culture medium containing 10 μg/ml LPS for another 24 h. LRN group and LRI group were transfected with miR149-5p inhibitor negative control and miR149-5p inhibitor, respectively, and then the other treatments were similar to those previously described in RSV group. The cell viability was measured by CCK-8 assay, the apoptosis rate by flow cytometry, the concentration of lactate dehydrogenase (LDH) and content of glutathione (GSH) in the supernatant by microplate method, the content of malondialdehyde (MDA) by TBA reaction method, the activity of superoxide dismutase (SOD) by WST-1 method, the level of reactive oxygen species (ROS) by DCFH-DA fluorescent probe, the concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the supernatant by enzyme-linked immunosorbent assay, and the expression of miR-149-5p by quantitative real-time polymerase chain reaction. Results:Compared with C group, the expression of miR-149-5p was significantly down-regulated, the cell viability was decreased, the concentrations of LDH, TNF-α and IL-6 in supernatant, apoptosis rate, ROS level and MDA content were increased, and the GSH content and SOD activity were decreased in LPS group ( P<0.05). Compared with LPS group, the expression of miR-149-5p was significantly up-regulated, the cell viability was increased, the concentrations of LDH, TNF-α and IL-6 in supernatant, apoptosis rate, ROS level and MDA content were decreased, and the GSH content and SOD activity were increased in RSV group ( P<0.05). Compared with RSV group or LRN group, the expression of miR-149-5p was significantly down-regulated, the cell viability was decreased, the concentrations of LDH, TNF-α and IL-6 in supernatant, apoptosis rate, ROS level and MDA content were increased, and the GSH content and SOD activity were decreased in LRI group ( P<0.05). Conclusions:The mechanism by which resveratrol alleviates LPS-induced cardiomyocyte injury is associated with the up-regulation of miR-149-5p expression and inhibition of cell apoptosis, oxidative stress and inflammatory responses in rats.

Herb-induced liver injury (HILI) is a type of drug-induced liver injury (DILI) caused by Chinese herb medicines, natural medicines or their related preparations. With the increasing number of reports on HILI events in recent years, traditional Chinese medicine is facing great challenges and controversies. Compared to other types of DILI, HILI is more complicated in terms of diagnosis and risk factors.This article reviews the current research status on the herb-induced liver injury.

Objective:To investigate the driver gene mutation status and prognostic influencing factors in patients with operable lung adenosquamous carcinoma (LASC).Methods:A retrospective case series study was conducted. Clinical and pathologic data were retrospectively collected from patients with LASC who underwent surgical treatment at the Second Affiliated Hospital of Air Force Military Medical University from January 2008 to December 2018, and the patients' surgically resected specimens were sequenced for epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) genes. The distribution of driver gene EGFR and KRAS mutations in patients was analyzed, and the differences in the distribution of mutations among patients stratified by clinical factors were compared; disease-free survival (DFS) of patients stratified by clinical factors was analyzed by the Kaplan-Meier method, and the comparison between groups was performed by the log-rank test.Results:A total of 106 patients were included, including 64 (60.4%) males and 42 (39.6%) females, aged (58±10) years old. Patients with EGFR and KRAS gene mutations accounted for 38.7% (41/106), of which 33.0% (35/106) were patients with EGFR mutations and 5.7% (6/106) were patients with KRAS mutations. The EGFR mutation loci included 19del, L858R, L861Q and 20in, and the KRAS mutation loci included G12A, G12D, G12C and G12V. Patients aged ≤65 years old, female, with lesions in the lower lobe of the left lung, non-squamous cell carcinoma as the main pathological component, and with a smoking index of <400 were more likely to have EGFR and KRAS gene mutations, but the differences were not statistically significant (all P>0.05), and there was no statistically significant difference in the proportions of patients with EGFR and KRAS gene mutations among patients with different TNM stages, T stages and N stages (all P > 0.05). The median follow-up time was 51 months (range: 14-96 months). The difference in DFS among patients with different N stages was statistically significant ( P= 0.002), and the DFS of N 0 stage was better than that of N 1, N 2 and N 3 stages, and the differences were statistically significant (all P < 0.05). The median DFS time of N 0, N 1 and N 2 stages was 44.4, 17.5 and 23.9 months, respectively, and the median DFS time of N 3 stage (1 case) was 8.7 months. Patients with different TNM stages had a tendency to have differences in DFS, but the difference was not statistically significant ( P = 0.060); the difference in DFS between patients with different pathological components was not statistically significant ( P = 0.177); patients without pleural invasion had a tendency to have better DFS than patients with pleural invasion, but the difference was not statistically significant ( P = 0.252). The difference in DFS between patients with and without driver gene EGFR and KRAS mutations was not statistically significant ( P = 0.809), and further subgroup analysis showed that the difference in DFS among mutated patients with different TNM stages was not statistically significant ( P = 0.684). Conclusions:The driver gene EGFR and KRAS mutations are more common in patients with early LASC; DFS may be related to TNM stage and N stage, but may not be related to the mutation status of EGFR and KRAS genes, the type of pathology, or whether or not the pleura is invaded.Objective To investigate the driver gene mutation status and prognostic influencing factors in patients with operable lung adenosquamous carcinoma (LASC). Methods A retrospective case series study was conducted. Clinical and pathologic data were retrospectively collected from patients with LASC who underwent surgical treatment at the Second Affiliated Hospital of Air Force Military Medical University from January 2008 to December 2018, and the patients' surgically resected specimens were sequenced for epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) genes. The distribution of driver gene EGFR and KRAS mutations in patients was analyzed, and the differences in the distribution of mutations among patients stratified by clinical factors were compared; disease-free survival (DFS) of patients stratified by clinical factors was analyzed by the Kaplan-Meier method, and the comparison between groups was performed by the log-rank test. Results A total of 106 patients were included, including 64 (60.4%) males and 42 (39.6%) females, aged (58±10) years old. Patients with EGFR and KRAS gene mutations accounted for 38.7% (41/106), of which 33.0% (35/106) were patients with EGFR mutations and 5.7% (6/106) were patients with KRAS mutations. The EGFR mutation loci included 19del, L858R, L861Q and 20in, and the KRAS mutation loci included G12A, G12D, G12C and G12V. Patients aged ≤65 years old, female, with lesions in the lower lobe of the left lung, non-squamous cell carcinoma as the main pathological component, and with a smoking index of <400 were more likely to have EGFR and KRAS gene mutations, but the differences were not statistically significant (all P>0.05), and there was no statistically significant difference in the proportions of patients with EGFR and KRAS gene mutations among patients with different TNM stages, T stages and N stages (all P > 0.05). The median follow-up time was 51 months (range: 14-96 months). The difference in DFS among patients with different N stages was statistically significant ( P= 0.002), and the DFS of N 0 stage was better than that of N 1, N 2 and N 3 stages, and the differences were statistically significant (all P < 0.05). The median DFS time of N 0, N 1 and N 2 stages was 44.4, 17.5 and 23.9 months, respectively, and the median DFS time of N 3 stage (1 case) was 8.7 months. Patients with different TNM stages had a tendency to have differences in DFS, but the difference was not statistically significant ( P = 0.060); the difference in DFS between patients with different pathological components was not statistically significant ( P = 0.177); patients without pleural invasion had a tendency to have better DFS than patients with pleural invasion, but the difference was not statistically significant ( P = 0.252). The difference in DFS between patients with and without driver gene EGFR and KRAS mutations was not statistically significant ( P = 0.809), and further subgroup analysis showed that the difference in DFS among mutated patients with different TNM stages was not statistically significant ( P = 0.684). Conclusions The driver gene EGFR and KRAS mutations are more common in patients with early LASC; DFS may be related to TNM stage and N stage, but may not be related to the mutation status of EGFR and KRAS genes, the type of pathology, or whether or not the pleura is invaded.

Objective:To explore the influencing factors of esophageal and gastric varices (EGV) in patients with liver cirrhosis, and to construct a column chart prediction model for EGV occurrence.Methods:A cross-sectional study was conducted to select patients ( n=127) who underwent gastroscopy at Minhang Hospital, Fudan University from January 2022 to April 2023 due to liver cirrhosis. Patients were divided into EGV group ( n=74) and non EGV group ( n=53) based on the presence of EGV. Clinical and auxiliary examination data of the two groups were compared. Univariate and multivariate logistic regression analysis were used to explore the independent influencing factors of EGV occurrence, and a column chart prediction model was further constructed to evaluate its predictive efficacy. Results:Multivariate logistic regression analysis showed that splenomegaly ( OR=28.38, 95% CI: 6.30-127.89, P<0.001), schistosomiasis infection ( OR=0.05, 95% CI: 0.01-0.28, P=0.001), and fatty liver ( OR=0.09, 95% CI: 0.02-0.33, P<0.001) were independent influencing factors for the occurrence of EGV in patients with liver cirrhosis. Based on this model, a column chart was constructed to predict the probability of EGV occurrence in patients with liver cirrhosis. The column chart model showed good consistency and discrimination (area under the curve was 0.927, 95% CI: 0.883-0.972), and was internally validated using the Bootstrap method, showing an average absolute error of 0.029. Conclusions:Spleen enlargement, schistosomiasis infection, and fatty liver are independent influencing factors for the occurrence of EGV in patients with liver cirrhosis. The Nomogram column chart prediction model for the occurrence of EGV in patients with liver cirrhosis has good predictive performance and can provide scientific basis for non-invasive risk screening and prevention strategies for EGV in liver cirrhosis.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective:To research the efficacy and safety of robotic thyroidectomy and bilateral modified radical neck dissection through bilateral axillo-breast approach (BABA) .Methods:We retrospectively analyzed the clinical data of 37 patients with thyroid cancer who received bilateral modified radical neck dissection through the BABA at the Department of Thyroid and Breast Surgery of the 960th Hospital of the People’s Liberation Army from Jan. 2014 to Jan. 2023. There were 24 females and 13 males, and the average age of the patients was (33,22±10.53) years old. The tumor diameter, number of lymph node dissection and metastasis in the central and lateral regions, average operation time, average hospital stay, complications, and aesthetic score were recorded. SPSS 25.0 software was used for statistical analysis, and the measurement data was calculated using mean ± standard deviation ( ± s), and the counting data was expressed in percentages and numbers. Results:A total of 37 thyroid cancer patients underwent robotic bilateral regional lymph node dissection. The 37 patients received total thyroidectomy, bilateral central compartment and cervical lateral regional lymph node dissection. All the pathological types were papillary carcinoma, with a maximal tumor diameter of (1.47±0.85) cm. The average number of central lymph nodes dissected was 19.46±8.84, and there were (10.24±5.95) metastases; The average number of lymph nodes removed from the bilateral cervical region was 38.92±14.21, and there were (7.92±5.84) metastases. The average operation time was (288.05±77.09) min, the average length of stay in the hospital was (10.76±3.92) days, and the average length of stay in the hospital following surgery was (8.03±2.08) days. These patients had no permanent hypoparathyroidism, permanent recurrent laryngeal nerve palsy, infection, accessory nerve injury and phrenic nerve injury after operation. Transient hypoparathyroidism occurred in 15 patients, transient recurrent laryngeal nerve palsy occurred in 1 patient, and chyle leak occurred in 2 patients. One month after surgery, the aesthetic score was 9.51±0.69.Two patients were found lymph node metastases during the (27.81±15.10) months of follow-up, and received robotic cervical lymph node dissection with BABA.Conclusion:For carefully chosen thyroid cancer patients with bilateral lateral cervical region lymph node metastases, robotic bilateral cervical lymph node regional dissection via BABA is safe and feasible, and good cosmetic results can be obtained.