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 explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

AIM: To explore the variance in efficacy between botulinum toxin A(BTA)injection and extraocular muscle surgery in managing large-angle(≥+60 PD)acute acquired concomitant esotropia(AACE).METHODS: A retrospective analysis was conducted on clinical data of 60 patients with AACE treated at our hospital from June 2020 to December 2022. Patients were divided into three groups based on different treatments: 2.5 IU BTA injection group(14 cases), 5.0 IU BTA injection group(29 cases), and surgical group(17 cases). Follow-up was conducted for 6 mo after treatment to observe the degree of strabismus after the correction of refractive error, visual function, treatment effectiveness, and occurrence of complications after BTA injection.RESULTS: At 6 mo post-treatment, the degree of strabismus in the surgical group and the 5.0 IU BTA injection group was lower than that in the 2.5 IU BTA injection group(P<0.017). However, there was no significant difference in the degree of strabismus between the surgical group and the 5.0 IU BTA injection group(P>0.017). The effective rate of the 5.0 IU BTA injection group was higher than that of the 2.5 IU BTA injection group(86% vs 43%, P<0.017). There was no difference in visual function among the three groups(P>0.05). The incidence of complications after treatment was not significantly different between the 2.5 IU BTA injection group and the 5.0 IU BTA injection group(43% vs 52%, P>0.05).CONCLUSION: For AACE patients with esotropia degree ≥+60 PD, bilateral medial rectus injection of 5.0 IU BTA can yield outcomes comparable to traditional extraocular muscle surgery, with the advantages of minimal trauma and simple and convenient operation.

Objective:To compare the clinical outcomes of arthroscopic external tension band fixation versus open reduction and internal fixation in the treatment of greater tubercle fracture of the humerus.Methods:A retrospective cohort study was conducted on 55 patients with greater tubercle fracture of the humerus admitted to Taizhou Hospital of Zhejiang Province from September 2019 to June 2022, including 24 males and 31 females, aged 26-80 years [(61.7±10.5)years]. Out of them, 35 patients treated with open reduction and internal fixation (open reduction group), and 20 patients were treated with external anchor tension band under arthroscopy (arthroscopy group). The operation time, and the Visual Analogue Scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score, Constant-Murley score and shoulder active range of motion (anterior flexion, abduction and posterior extension) before operation, at 1 month after operation and at the last follow-up were compared between the two groups. Bone healing was observed in both groups at the last follow-up. Postoperative complications were compared between the two groups.Results:All the patients were followed up for 12-29 months [(16.9±4.0)months]. There was no significant difference in operation time between the two groups ( P>0.05). There were no significant differences in the VAS score, ASES score, Constant-Murley score and shoulder active range of motion between the two groups before operation ( P>0.05). The VAS score of the arthroscopy group was 3(2, 3)points at 1 month after operation, which was significantly lower than that of the open reduction group [4(3, 4) points] ( P<0.01). No significant difference was found in the VAS score at the last follow-up between the two groups ( P>0.05).The ASES scores of the arthroscopy group were (70.6±4.2)points and (90.2±3.7)points at 1 month after operation and at the last follow-up respectively, which were significantly higher than those of the open reduction group [(64.7±6.4)points and (87.5±4.9)points respectively] ( P<0.05 or 0.01). There was no significant difference in the Constant-Murley score between the arthroscopy group [(71.8±4.3)points] and the open reduction group [(70.9±5.3)points] at 1 month after operation ( P>0.05), while the Constant-Murley score of the arthroscopy group was (94.1±3.1)points at the last follow-up, which was significantly higher than that of the open reduction group [(89.2±4.7)points] ( P<0.01). At 1 month after operation and at the last follow-up, ranges of motion of the anterior flexion, abduction and posterior extension were (52.7±12.3)° and (140.0±16.9)°, (57.4±8.6)° and (125.0±14.3)°, and 16(15, 19)° and 25(20, 30)° in the arthroscopy group respectively, which were significantly higher than those in the open reduction group [(42.2±5.2)° and (110.9±14.0)°, (52.8±6.0)° and (103.7±11.7)°, and 10(10, 20)° and 16(15, 25)° respectively] ( P<0.05 or 0.01). At the last follow-up, it was found that bony union was achieved in both groups. There were no obvious complications such as incision infection or joint stiffnessin both groups. In the open reduction group, 2 patients had internal fixation failure within 1-3 months after operation but was treated with revision operation; 6 patients developed shoulder stiffness at 3-6 months after operation but had outpatient rehabilitation. The incidence rate of postoperative complications in the arthroscopy group [0%(0/20)] was significantly lower than that in the open reduction group [23%(8/35)] ( P<0.05). Conclusion:Compared with open reduction and internal fixation with plates and screws, arthroscopic external anchor tension band fixation in the treatment of greater tuberosity fracture of the humerus has the advantages of earlier pain relief, better shoulder functional improvement, better recovery of shoulder mobility, and fewer complications.

Background::Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.Methods::This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results::The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.Conclusions::The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Objective To investigate the serum tumor necrosis factor like weak inducer of apoptosis(TWE AK),sterol regulatory element-binding protein 1(SREBP-1)levels in patients with prostate cancer(PC)and their relationship with clinical pathological characteristics and progression free survival prognosis.Method A total of 94 PC patients who underwent PC radical surgery in Wuhan Dongxihu District People's Hospital from January 2018 to January 2020 were selected as the PC group.Meanwhile,50 patients with benign prostatic hyperplasia(BPH)during the same period were selected as the BPH group,and 50 healthy individuals who underwent physical examination during the same period were selected as the control group.Enzyme linked immunosorbent assay(ELISA)was used to detect the expression levels of serum TWEAK and SREBP-1.Kaplan-Meier survival analysis was used to analyze the effects of serum TWEAK and SREBP-1 on the progression free survival in prostate cancer patients.Multivariate COX regression analysis was used to analyze factors affecting the prognosis of progression free survival in prostate cancer patients.Results The serum TWEAK(77.14±15.46 ng/L)and SREBP-1(334.14±33.81 ng/L)levels in the PC group were higher than those in the BPH group(38.69±10.58 ng/L,201.69±28.74 ng/L)and control group(36.26±10.27 ng/L,189.51±27.65 ng/L),with significant differences(t=23.752,25.249;34.636,37.821,all P＜0.05).There was a positive correlation between serum TWEAK and SREBP-1 expression in PC patients(r=0.668,P=0.001).The serum TWEAK and SREBP-1 levels in PC patients with Gleason score＞7,TNM stage Ⅲ,and preoperative prostate specific antigen(PSA)level ≥ 20 ng/ml were higher than those with Gleason score≤7,TNM stage Ⅰ～Ⅱ,and preoperative PSA level＜20ng/ml,with significance differences(t=8.465～16.597,all P＜0.05).The 3-year overall progression free survival rates of the TWEAK high expression and low expression groups were 60.42％(29/48)and 86.96％(40/46),respectively.The 3-year overall progression free survival rates of the SREBP-1 high expression and low expression groups were 57.78％(26/45)and 87.76％(43/49),respectively.The 3-year cumulative progression free survival rates of the TWEAK high expression group and the SREBP-1 high expression group were lower than those of the TWEAK low expression group and the SREBP-1 low expression group,and the differences were significant(Log rankx2=8.125,9.547,P=0.004,0.002).TNM stage Ⅲ(OR=1.448,P＜0.001),Gleason score＞7(OR=1.401,P＜0.001),preoperative PSA ≥ 20 ng/ml(OR=1.353,P＜0.001),serum TWEAK(OR=1.338,P＜0.001),and SREBP-1(OR=1.293,P＜0.001)were independent risk factors affecting the progression free survival prognosis of PC patients.Conclusion Serum TWEAK and SREBP-1 in prostate cancer patients were increased,and they were correlated with the clinical pathological characteristics of PC.They could be serum biomarkers for evaluating the prognosis of progression free survival.

Objective:To investigate the predictive value of a clinical imaging model based on multi-slice helical computer tomography (MSCT) examination in predicting prognosis of advanced gastric adenocarcinoma.Methods:The retrospective cohort study was conducted. The clinicopatho-logical data of 88 patients with advanced gastric adenocarcinoma who were admitted to the Ningbo Yinzhou No.2 Hospital from January 2019 to January 2021 were collected. There were 62 males and 26 females, aged (60±15)years. All patients underwent preoperative MSCT examination. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers. Univariate and multivariate analyses were conducted using the Logistic regression model. The receiver opera-ting characteristic curve was used to analyze the predictive efficacy of prognosis, and the area under the curve (AUC), sensitivity, and specificity were calculated. Results:(1) Surgical situations and follow-up. All 88 patients underwent radical gastrectomy for gastric cancer and were diagnosed with advanced gastric adenocarcinoma through postoperative pathological examination. All 88 patients were followed up after surgery for 41(range, 36?48)months, with a 3-year overall survival rate of 69.32%. (2) Analysis of factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery. Results of multivariate analysis showed that preoperative carcinoembryonic antigen (CEA) and extramural venous invasion (EMVI) were independent factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery ( odds ratio=1.10, 7.72, 95% confidence interval as 1.01?3.82, 1.42?15.42, P<0.05). (3) Construction and evaluation of predictive model. The AUC of predictive efficacy of prognosis for advanced gastric adenocarcinoma of preoperative CEA and EMVI were 0.90 (95% confidence interval as 0.82?0.97) and 0.80 (95% confidence intervalas 0.71?0.89), respectively, with sensitivity of 85.25% and 78.69% and specificity of 100.00% and 81.48%, respec-tively. A predictive model was constructed by combining preoperative CEA and EMVI based on the results of multivariate analysis, and the AUC of the predictive model was 0.93 (95% confidence interval as 0.87?0.98), with sensitivity and specificity of 86.89% and 96.30%. Conclusions:CEA and EMVI are independent factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery. The predictive model constructed by combining preoperative CEA and EMVI has good predictive efficacy for patient prognosis.

Objective:To investigate effect of vitexin on macrophage polarization and its impact on tumor growth in a mouse model of prostate cancer.Methods:C57BL/6J male mice were used to establish RM-1 prostate cancer xenograft model.Mice were ran-domly divided into model group,vitexin-low,medium and high doses groups(40,80,160 mg/kg),and cisplatin group as positive control.After continuous administration for 16 days,mice were euthanized and tumor mass was measured.HE staining was performed to observe tumor morphology.Immunohistochemistry was used to detect Ki67 positive rate.Flow cytometry was conducted to measure expressions of CD86+CD11b and CD206+CD11b in tumor-associated macrophages.CCK8 assay was performed to assess cytotoxic effect of vitexin on RAW264.7 macrophages to determine suitable concentrations.RT-qPCR was used to measure mRNA expressions of M2 macrophage markers,including arginase-1(ARG-1),Fizz1 and Ym1.Results:Vitexin inhibited tumor volume and weight,induced tumor tissue necrosis,suppressed Ki67 protein expression,increased expression of CD86+CD11b+M1 macrophages,and inhibited CD206+CD11b+M2 macrophage expression in mouse tumor tissues in vivo.Vitexin at concentrations of 10～20 μmol/L showed no cyto-toxicity on RAW264.7 macrophages in vitro,and promoted expression of iNOS in IL-4-induced M2 macrophages while inhibiting CD206 expression,as well as suppressed mRNA expressions of ARG-1,Fizz1 and Ym1.Conclusion:Vitexin effectively inhibits tumor growth in a mouse model of prostate cancer,possibly by regulating M2 macrophages towards an M1 phenotype and exerting immunomodulatory effects.

In order to explore the role of BspE protein in Brucella infection,yeast two-hybrid tech-nique was used to screen host cell proteins that interact with BspE protein.The constructed BspE recombinant plasmid pGBKT7-BspE was used as bait plasmid to hybridize with the RAW264.7-cD-NA library of mouse mononuclear macrophages by yeast two-hybridization technique.The positive clones were extracted by plasmid,sequenced and co-immunoprecipitation to determine the host cell proteins that could interact with BspE.The subcellular localization of BspE proteins was analyzed by confocal laser microscopy.The physical and chemical properties,protein structure and function of BspE interacting proteins were analyzed by bioinformatics.The siRNA for one of the BspE inter-acting proteins was synthesized,the expression of its gene was silenced in HEK293T cells,and the silenced cells was infected with Brucella M5-90 and the number of intracellular bacteria was coun-ted.The results showed that the decoy plasmid pGBKT7-BspE was successfully constructed,and the plasmid could express BspE protein in yeast.Eight positive clones were obtained from the host cell genome library by yeast two-hybridization.The positive clones were identified as RBM27 and PCBP1 by sequencing,backcross and co-immunoprecipitation.Bioinformatics was used to predict the cell location,protein structure and amino acid composition of RBM27 and PCBP1.After siRNA interference,the expression level of PCBP1 was significantly decreased and the amount of M5-90 in the cell was increased.Brucellosis secreted protein BspE interacts with host proteins RBM27 and PCBPl,and PCBP1 negatively regulates the proliferation of Brucellosis.

Objective To investigate the infection of Helicobacter pylori (Hp) and its relationships with hypertension, glucose and lipid metabolism in the physical examination population. Methods A total of 287 individuals undergoing physical examinations were selected as study subjects. Based on the results of ¹⁴C-urea breath test screening for Hp infection, participants were divided into Hp-positive group (n=125) and Hp-negative group (n=162). Baseline characteristics and glycolipid metabolism levels were compared between the two groups. Multivariate Logistic regression analysis was used to identify factors influencing Hp infection in the study population. Results The Hp infection rate among the 287 individuals was 43.55%. The frequency of eating out in the Hp-positive group was 34.40%, which was significantly higher than 13.58% in the Hp-negative group (P < 0.05). Fasting blood glucose (FBG), insulin resistance index (HOMA-IR), total cholesterol (TC) and triacylglycerol (TG) in the HP-positive group were significantly higher, and high-density lipoprotein cholesterol (HDL-C) was significantly lower than that in the Hp-negative group (P < 0.05). Multivariate Logistic regression analysis revealed that eating out (OR=1.401, 95%CI, 1.142 to 1.717), FBG (OR=3.865, 95%CI, 1.810 to 8.253), TC (OR=4.141, 95%CI, 2.025 to 8.469), TG (OR= 4.259, 95%CI, 2.128 to 8.524) and HDL-C (OR=4.125, 95%CI, 1.989 to 8.552) were factors influencing Hp infection in the study population (P < 0.05). HOMA-IR was not associated with Hp infection in the study population (P>0.05). Conclusion The prevalence of Hp infection is high among individuals undergoing physical examinations, and Hp infection has significant association with abnormalities in glycolipid metabolism, but no association with hypertension.