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 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.

Objective:To construct a prediction model for peripherally inserted central catheter-related upper extremity deep vein thrombosis (PICC-UEDVT) in patients with traumatic brain injury (TBI) and validate its effectiveness.Methods:A case-control study was conducted on the clinical data of 222 TBI patients admitted to Xiangya Hospital of Central South University from January 2019 to December 2021, including 171 males and 51 females, aged 18-86 years [54.5(46.0, 65.0)years]. Glasgow coma scale (GCS) motor score was 4.0(3.0, 5.0)points on the day of catheterization. A total of 82 patients (36.9%) had PICC-UEDVT. The patients were randomly divided with a ratio of 7∶3 into training set ( n=156, including 58 with PICC-UEDVT) and validation set ( n=66, including 24 with PICC-UEDVT) using R programming language. The baseline data of general information, intravenous medication, catheterization, and laboratory indices were compared between the training set and the validation set. Lasso regression analysis was employed to identify those variables, with the diagnosis of PICC-UEDVT as the outcome variable. Variables with non-zero regression coefficients were included in a multifactorial Logistic regression model and independent variables were selected based on the Akaike Information Criterion (AIC) of R programming language. The regression equation was constructed, based on which, the predictive nomogram model was constructed for PICC-UEDVT in TBI patients. Receiver operating characteristic (ROC) curves for the training set and validation set were plotted and the discriminability of the model was assessed. The calibration of the model was evaluated using the Hosmer-Lemeshow (H-L) goodness-of-fit test and calibration curves and the clinical practicality of the model was assessed with decision curve analysis (DCA). Results:The baseline analysis of both the training set and the validation set demonstrated a well-balanced sample distribution. Through Lasso regression analysis, 5 prediction variables were identified: GCS motor score on the day of catheterization, Caprini score on the day of catheterization, use of glucocorticoids, tip position of the catheter, and D-dimer (D-D) level before catheterization. The multivariate Logistic regression analysis revealed that the Caprini score on the day of catheterization ( OR=1.20, 95% CI 1.08, 1.33), use of glucocorticoids ( OR=3.13, 95% CI 0.99, 10.46), and D-D level before catheterization ( OR=1.16, 95% CI 1.07, 1.33) were independent risk factors for PICC-UEDVT in TBI patients. The regression equation was developed as: Logit [ P/(1- P)]=-2.56+0.18×"Caprini score on the day of catheterization"+1.14×"use of glucocorticoids"+0.15×"D-D level before catheterization". In the prediction model which was constructed based on the equation, the AUC values for the training set and validation set were 0.73 (95% CI 0.65, 0.81) and 0.77 (95% CI 0.65, 0.87) respectively. The H-L goodness-of-fit test indicated χ2=3.28, P=0.950 for the training set and χ2=13.05, P=0.160 for the validation set. Calibration curves for both sets demonstrated alignment between the actual and predicted probabilities of PICC-UEDVT in TBI patients. DCA results showed that the net benefit rate of patients was optimal when the threshold probability ranged from 15% to 72% for the training set and from 10% to 81% for the validation set. Conclusion:The prediction model based on the Caprini score on the day of catheterization, use of glucocorticoids, and D-D level before catheterization demonstrates good predictive accuracy, calibration and clinical practicality in predicting PICC-UEDVT in TBI patients.

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 compare the efficacy of MRI-transrectal ultrasound(TRUS)software fusion-guided biopsy and cognitive fusion-guided biopsy for detecting prostate cancer(PC).Methods Data of 120 patients with suspected PC(127 lesions)who underwent transperineal prostate biopsy with 2-3 times of target biopsy(TB)and 10 times of system biopsy were retrospectively analyzed.According to TB guidance methods,73 cases(78 lesions)received MRI-TRUS software fusion-guided biopsy were classified into group A,and 47 cases(49 lesions)received cognitive fusion-guided biopsy were classified into group B.The positive rate of PC,clinic significant PC(csPC)and PC in different sized lesions by TB were compared between groups,and the positive rate of PC between 2 or 3 times TB was also compared within each group.Results The positive rate of PC and csPC detected by TB was 55.13%(43/78)and 39.74%(31/78)in group A,53.06%(26/49)and 34.69%(17/49)in group B,respectively,no significant difference was found(all P＞0.05).The positive rate of PC in lesions with the maximum diameter≤10 mm detected by TB in group A was higher than that in group B(P＜0.05),but no significant difference of lesions with the maximum diameter＞10 mm and＜15 mm nor≥15 mm was found between groups(all P＞0.05).No significant difference of positive rate of PC was found between 2 and 3 times TB in group A(P＞0.05),while positive rate of PC of 3 times TB was significantly higher than that of 2 times TB in group B(P＜0.05).Conclusion MRI-TRUS software fusion-guided biopsy had positive rate of PC and csPC similar to that of cognitive fusion-guided biopsy,but was helpful for reducing times of TB and increasing detecting rate for lesions with the maximum diameter≤10 mm.