OBJECTIVE:Neuromuscular exercise is a new comprehensive rehabilitation therapy in recent years,but its effect on knee osteoarthritis is still controversial.The purpose of this paper is to systematically evaluate the efficacy of neuromuscular exercise on knee osteoarthritis pain and function. METHODS:The randomized controlled trials addressing neuromuscular exercise in the treatment of knee osteoarthritis pain and function were retrieved from PubMed,Cochrane Library,Embase,EBSCO,CNKI,Web of Science,China Biomedical Database(CBM),VIP,and WanFang Database.The retrieval time ranged from database inception to October 2023.The neuromuscular training group(experimental group)was given neuromuscular training or neuromuscular training as the main intervention;the control group was a blank group or given conventional rehabilitation.Outcome indicators included the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,walking time,knee stability,and the maximum number of knee flexion in 30 seconds.The risk of bias was evaluated by the Cochrane Collaboration tool and the Physiotherapy Evidence Database.Meta-analysis was performed using RevMan 5.4 software. RESULTS:A total of 11 randomized controlled trials were included,and 628 samples were extracted.The results of Meta-analysis showed that the experimental group was superior to the control group in terms of WOMAC pain score[standardized mean difference(SMD)=0.38,95%confidence interval(CI):0.08-0.69,P=0.01],knee stability(SMD=0.57,95%CI:0.23-0.92,P=0.001),the maximum number of knee joint flexion in 30 seconds(SMD=0.35,95%CI:0.05-0.65,P=0.02),and WOMAC physical function score(SMD=-0.79,95%CI:-1.30 to-0.28,P=0.002).In both groups,walking speed was increased and walking ability was improved in patients with knee osteoarthritis,but there was no significant difference(walking time:SMD=-0.22,95%CI:-0.48-0.03,P=0.09). CONCLUSION:Neuromuscular exercise can effectively improve knee joint pain,enhance the stability of the knee joint,and promote functional recovery in patients with knee osteoarthritis.However,more high-quality randomized controlled trials are still needed to further confirm the research.

In the context of the development of transplant oncology, it is of great clinical significance to find a drug with both antitumor and immunosuppressive effects for liver transplantation patients with hepatocellular carcinoma (HCC). The antitumor effect of ginkgolic acid (GA) has been confirmed, and some studies suggest that GA may also have an immunosuppressive effect. The immunosuppressive effect of GA was evaluated by histopathology, T-cell subpopulation, and cytokine detection in rat liver transplantation and mouse cardiac transplantation models, and transcriptomic and metabolomic analysis was used to explore the underlying mechanism of the GA immunosuppressive effect. Metabolites, activation, and ferroptosis markers of CD8⁺ T cells were detected in vivo and in vitro. Based on rat liver transplantation and mouse cardiac transplantation models, the immunosuppressive effect of GA was first confirmed by histopathology, T-cell subpopulation, and cytokine detection. In the mouse cardiac transplantation model, transcriptomics combined with metabolomics demonstrated for the first time that GA inhibited lactate dehydrogenase A (LDHA) expression and pyruvate metabolism in CD8⁺ T cells. It was confirmed in vivo and in vitro that GA inhibited pyruvate metabolism of CD8⁺ T cells through LDHA, inhibiting their activation and inducing ferroptosis. Overexpression of LDHA partially reversed the effect of GA on the metabolism, activation, and ferroptosis of CD8⁺ T cells in vitro. GA mediates metabolic reprogramming through LDHA to inhibit the activation and induce ferroptosis of CD8⁺ T cells to exert an immunosuppressive effect, which lays an experimental foundation for the future clinical application of its immunosuppressive effect.

Myocardial infarction (MI) is the leading cause of cardiovascular disease-related death worldwide. Nonetheless, existing therapeutic approaches for MI are hampered by issues such as reliance on pharmacological agents and suboptimal patient adherence. Caffeic acid (CA) is a bioactive polyphenolic compound with important anti-inflammatory, anti-bacterial and anti-oxidant functions. Still, its specific role and mechanism in treating cardiovascular disease remain to be further studied. In recent years, a large number of studies have shown that the kelch-like ECH-associated protein 1/nuclear factor erythroid 2 related factor 2 (Keap1/Nrf2) pathway is a key factor in the occurrence and development of cardiovascular diseases. In this study, H₂O₂-induced oxidative stress model of H9c2 cells and left anterior descending branch (LAD) conjunctival induced acute myocardial infarction reperfusion (AMI/R) model were used to evaluate the protective effect of CA on the heart. The interaction between CA and Keap1 was analyzed by CA-labeled fluorescence probe, target fishing, isothermal titration calorimetry (ITC), protein crystallography and surface plasmon resonance (SPR). Our results suggested that CA binds Keap1 and degrades Keap1 in a p62-dependent manner, further promoting nuclear transcription of Nrf2 and thus effectively reducing oxidative stress. In addition, based on the three-dimensional eutectic structure, it was confirmed that CA directly targets Keap1 protein by interacting with residues M550 and N532, inducing conformation changes in Keap1 protein. We also found that the CA analog chlorogenic acid (GCA) can bind Keap1. In conclusion, this study elucidates a novel molecular mechanism and structural basis for the protective effects of CA against oxidative damage via the Keap1-Nrf2 pathway.

Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Objective : To analyze the influencing factors associated with the coexistence of multidrug-resistantEscherichia coli(MDR-ECO) infection and active tuberculosis(ATB) in patients with lung infections. Methods: A total of 204 hospitalized patients with lung infections caused by MDR-ECO were enrolled. Among them, patients with coexisting ATB were identified and assigned to the observation group. Univariate and multivariate Logistic regression analysis were performed to identify the risk factors for the coexistence of MDR-ECO lung infection and ATB. Results : Factors such as patient age, neutrophil count, hemoglobin level, malignancy, rheumatoid arthritis, history of antibiotic exposure, and history of surgery within the past year were found to be influencing factors for the coexistence of MDR-ECO lung infection and ATB(allP<0.05). Specifically, advanced age(95%CI: 0.949-0.992,P=0.008), decreased neutrophils(95%CI: 0.750-0.922,P<0.001), and a history of antibiotic exposure(95%CI: 1.202-2.596,P=0.004) were identified as risk factors. Conclusion Some patients with MDR-ECO lung infections are prone to coexisting with ATB. Therefore, it is recommended to strengthen ATB screening among high-risk patients, including those at peak ages for susceptibility, with low neutrophil counts, and with a history of antibiotic exposure.

Objective To investigate the effect of rehabilitation instruction based on resourceful theory on the execution intention of exercise behaviour in patient with the first-episode stroke.Methods From September 2022 to February 2023,a total of 80 inpatients with first-episode stroke from a general hospital in Anhui Province participated in the study.Patients in Wards Ⅰ and Ⅱ were assigned to an intervention group,while those in Wards Ⅲ and Ⅳ were assigned to a control group,with 40 patients per group.The patients in control group received standard interventions,while those in the intervention group were offered with a rehabilitation instruction based on resourceful theory in addition to the standard interventions.Stroke patient rehabilitation exercise behaviour execution intention questionnaire,resourcefulness scale and modified Barthel were employed for assessments before and after the intervention.Results After the intervention,the intervention group showed significantly higher scores inexecutive intention of exercise behaviour,resourcefulness level and daily living activities compared to those in the control group(all P＜0.01).Conclusion Rehabilitation instruction based on the theory of resourcefulness can effectively increase the executive intention of exercise behaviour in the patients with first-episode stroke,improve the resourcefulness thinking levels and enhance the daily living activity of the patients.

Objective To explore the value of pelvic CT angiography(CTA)digital three-dimensional reconstruction model(abbreviated as"three-dimensional model")in the diagnosis of female pelvic mass.Methods A total of 98 patients with pelvic mass who were hospitalized and operated in Xi'an People's Hos-pital(Xi'an Fourth Hospital)from January 2021 to April 2023 were selected.All patients underwent B-ultra-sound and CTA examination before operation,and the original data of CTA were collected.The digital three-dimensional model of pelvic mass was established by three-dimensional reconstruction software,and the source of pelvic mass was judged according to the blood supply of pelvic mass.Taking postoperative pathological di-agnosis as the gold standard,the coincidence rate between different preoperative diagnosis methods(B-ultra-sound,CTA examination and three-dimensional model)was compared.The receiver operating characteristic(ROC)curve was plotted to evaluate the efficacy of different preoperative diagnostic methods in judging the ovarian origin of pelvic tumors.Results A total of 130 pelvic masses were included in 98 patients,and the average maximum diameter of the mass was(71.61±3.03)mm,including 83 ovarian masses and 47 non-ovarian masses.Taking postoperative pathological diagnosis as the gold standard,the diagnostic coincidence rate of the preoperative three-dimensional model was 72.31％,which was higher than that of B-ultrasound(58.46％)and CTA(52.31％),and the differences were statistically significant(P＜0.001).The sensitivity,specificity,positive predictive value,negative predictive value,accuracy,Kappa value,and area under the ROC curve were 79.51％,91.49％,94.29％,71.67％,83.85％,0.67 and 0.855,respectively,when the three-dimensional model showed that the blood supply of the mass originated from ovarian artery or uterine artery-ovarian branch.Conclusion The three-dimensional model of pelvic CTA can directly display the blood supply source,characteristics of mass,and the relationship between mass and adjacent organs,which can guide the clinical treatment.It has certain clinical value to judge the ovarian origin of pelvic mass by using ovarian artery and uterine artery-ovarian branch.

OBJECTIVE:At present,there are a variety of treatment methods for scoliosis using specific exercise therapy,but there is a lack of comparison of efficacy between different specific exercise therapy.This article compared the effectiveness of different specific exercise therapies to treat adolescent idiopathic scoliosis through a network meta-analysis. METHODS:Domestic and foreign electronic databases of relevant studies were searched for randomized controlled trials of specific exercise therapy for adolescent idiopathic scoliosis.Search time was from January 2000 to July 2023.The literature was screened by two reviewers using RevMan 5.4 and Stata 16.0 software to extract data and assess the bias risk of of inclusion studies. RESULTS:(1)This article includes 20 randomized controlled trials with 1 377 patients.Of them,12 studies involved Schroth therapy;2 studies involved BSPTS therapy,and 6 studies involved SEAS therapy.(2)The network meta-analysis indicated that in terms of improving Cobb angle and reducing trunk rotation angle in scoliosis patients,the BSPTS therapy group and Schroth therapy group were better than the conventional control group[WMD=-4.60,95%CI(-8.37,-0.82),P<0.05;WMD=-3.37,95%CI(-4.98,-1.75),P<0.05;WMD=-3.20,95%CI(-5.50,-0.90),P<0.05;WMD=-2.13,95%CI(-3.16,-1.09),P<0.05].The Schroth therapy group performed better than the conventional control group effective in improving the International Society for Scoliosis Research-22 Questionnaire quality of life score[WMD=1.41,95%CI(0.07,2.75),P<0.05]. CONCLUSION:Given the current evidence,BSPTS therapy group and Schroth therapy group were better than the conventional control group in improving Cobb angle and reducing trunk rotation angle.In the comparison of different specific exercise therapies,BSPTS therapy can be preferred to improve Cobb angle and reduce trunk rotation angle in adolescent idiopathic scoliosis patients.In addition,Schroth therapy may be the best treatment to improve the quality of life of adolescent idiopathic scoliosis patients.Limited by the quantity and quality of the included studies,the above conclusions should be interpreted with caution and need more high-quality studies to further validation.

Objective To investigate the effect of the protein kinase RNA-like endoplasmic reticulum kinase(PERK)/eukaryotic initiation factor 2α(eIF2α)pathway in endoplasmic reticulum stress on the activation of hepatic stellate cells(HSC).Methods Pathological sections of normal liver tissue after surgery were collected from 11 patients with hepatic fibrosis(S1-S4)and 9 patients with hepatic hemangioma and hepatic adenoma confirmed by liver biopsy,and immunohistochemistry was used to measure the protein expression levels of PERK,eIF2α,and C/EBP homologous protein(CHOP).Human HSC-LX2 cells were treated with different concentrations of the endoplasmic reticulum stress inducer thapsigargin(0,125,250,500,and 1 000 nmol/L),and qRT-PCR was used to measure the mRNA expression level of PERK,while Western blot was used to measure the protein expression levels of PERK,inositol requiring protein 1(IRE1),activating transcription factor 6(ATF6),CHOP,and α-smooth muscle actin(α-SMA).The method of lentivirus transfection was used to construct a PERK stable overexpression LX-2 group and a control group;qRT-PCR was used to measure the mRNA expression levels of PERK,eIF2α,and α-SMA,Western blot was used to measure the protein expression levels of PERK,phosphorylated eIF2α(p-eIF2α),and α-SMA,and immunofluorescence assay was used to measure the expression of collagen type Ⅰ alpha 1(COL1A1).The independent samples t-test was used for comparison of normally distributed continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.Results Compared with normal liver tissue,the liver tissue of patients with hepatic fibrosis had significantly higher expression levels of PERK,eIF2α,and CHOP(Z=-3.56,t=-5.75,Z=-3.52,all P<0.001).Compared with the solvent group,the groups treated with different concentrations of thapsigargin had significant increases in the expression levels of the endoplasmic reticulum-associated proteins PERK,CHOP,IRE1,ATF6,and α-SMA(all P<0.05).Compared with the control group,the PERK stable overexpression group had significant increases in the mRNA expression levels of PERK,eIF2α,and α-SMA and the protein expression levels of PERK,p-eIF2α,and α-SMA(all P<0.05),and immunofluorescence assay showed a significant increase in the expression level of COL1A1 in the PERK stable overexpression group(P<0.05).Conclusion PERK overexpression can induce the expression of α-SMA and COL1A1 in LX-2 cells,suggesting that the PERK signaling pathway might be one of the important mechanisms of HSC activation.

Objective:To analyze the image characteristics of gastrointestinal stromal tumor(GIST) and leiomyoma under white-light endoscopy and ultrasound endoscopy, so as to establish a nomogram model and to validate its performance.Methods:From August 1, 2019, to December 1, 2022, the clinical data of 224 patients with GIST or leiomyoma who underwent endoscopic ultrasound examination at the First Affiliated Hospital of Soochow University were retrospectively analyzed. The 224 patients were divided into the modeling group of 145 cases (78 cases of GIST and 67 cases of leiomyoma), and the validation group of 79 cases (41 cases of GIST and 38 cases of leiomyoma). The basic data of patients, parameters of white-light endoscopy and ultrasound endoscopy were screened to establish a binary logistic regression model and draw a nomogram. The receiver operating characteristic curve (ROC) was drawn, and the area under the curve (AUC) was used to evaluate the diagnostic efficiency of the model, and calibration curve was used to evaluate the consistency of predicted and observed probabilities. The model′s performance was compared with the diagnostic results of junior physicians (attending physicians) and senior physicians (associated chief physician). Decision curve analysis (DCA) was performed to evaluate the net benefit of the model. Independent sample t-test and chi-square test were used for statistical analysis. Results:Under white-light endoscopy, there were statistically significant differences in the lesion locations (esophagus: 0 vs. 56.7% (38/67); cardia: 11.5% (9/78) vs. 13.4% (9/67); gastric: 88.5% (69/78) vs. 29.9% (20/67)) and tumor morphyology (spherical or spheroid: 80.8% (63/78) vs. 28.4% (19/67); shuttle: 19.2% (15/78) vs. 71.6% (48/67)) between GIST and leiomyoma in the modeling group ( χ2=64.51 and 46.37, both P<0.001). Under ultrasound endoscopy, the proportion of patients with GIST whose lesions originated from the muscularis propria layer, with indistinct borders and with internal hyperechoic area were all higher than those of patients with leiomyoma (96.2% (75/78) vs. 62.7% (42/67); 53.8% (42/78) vs. 13.4% (9/67); 35.9% (28/78) vs. 10.4% (7/67)), and the differences were statistically significant ( χ2=25.91, 25.82 and 12.75, all P<0.001). Based on the logistic regression model, a nomogram model was established with age, tumor morphology, lesion origin, boundary clarity, and hyperechoic foci as predictive indicators. In the modeling group, the accuracy of nomogram model in the diagnosis of GIST and leiomyoma was 89.7% and 83.6%, respectively. In the validation group, the sensitivity, specificity, and accuracy in GIST and leiomyoma diagnosis of the nomogram model and senior physicians were all higher than those of junior physicians in differentiating GIST from leiomyoma (90.2%, 87.8% vs. 82.9%; 81.6%, 84.2% vs. 78.9%; 86.1%, 86.1% vs. 81.0%, respectively), and the sensitivity, specificity, and accuracy of the nomogram model were equal to those of senior physicians in differentiating GIST from leiomyoma. The AUCs of the nomogram model in the modeling group and validation group were 0.932 (95% confidence interval 0.891 to 0.974) and 0.916 (95% confidence interval 0.854 to 0.978), respectively. The calibration curves of the model indicated that the consistency between the predicted probabilities and observed probabilities was good, and DCA suggested good clinical net benefits of the model. Conclusion:The model exhibits good test efficiency, discrimination, prediction consistency and clinical net benefit when age, tumor morphology, lesion origin, boundary clarity, and hyperechoic foci are selected as indicators.