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.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Objective To investigate the improvement effect of Necrostatin-1 (Nec-1) on mouse models with immune checkpoint inhibitor (ICI) -associated myocarditis (ICIAM) and potential mechanism. Methods Ten male BALB/c mice aged 6-8 weeks were selected to construct the ICIAM models. The echocardiography and serum myocardial injury markers were used to assess cardiac function of mice. The levels of inflammatory markers including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Hematoxylin-eosin (HE) staining was used to evaluate myocardial inflammation, and Masson staining was used to evaluate myocardial fibrosis. The expressions of myocardial necroptosis proteins including receptor-interacting protein kinase 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL) and their phosphorylated forms were detected by Western blotting. The spleen lymphocytes were extracted and co-cultured with HL-1 cell line. Cell viability was measured by cell counting kit-8 (CCK-8). The release of reactive oxygen species (ROS) and changes of mitochondrial membrane potential were observed. RIP1, RIP3, MLKL and their phosphorylated forms were determined. The levels of markers of oxidative stress, including malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were measured. Results Nec-1 significantly improved the cardiac function injury of mice induced by ICI, and inhibited the release of TNF-α and IL-1β in plasma of ICIAM mice (P＜0.001); inhibited expressions of phosphorylated RIP1, RIP3 and MLKL (P＜0.05); decreased MDA activity, and increased SOD and GSH-Px activity (P＜0.001). In HL-1 cells, Nec-1 intervention inhibited the RIP1-RIP3-MLKL pathway (P＜0.05), improved decrease of the cell viability induced by lymphocytes (P＜0.001), decreased ROS release, increased mitochondrial membrane potential, inhibited MDA activity, and increased SOD and GSH-Px activities (P＜0.001). Conclusions Necroptosis plays an important role in the occurrence and development of ICIAM，but Nec-1 could alleviate the progression of ICIAM by inhibiting necroptosis induced by oxidative stress in cardiomyocytes; RIP1 maybe a new target in treatment of ICIAM.

Objective : To explore the mechanism of proliferation of gastric cancer cells induced byHelicobacter pylori(Hp) from the perspective of the mitochondrial unfolded protein response(UPRMT). Methods : C57BL6/J mice, human gastric cancer cells AGS and SGC-7901 cells were infected with Hp, mitochondrial proteins were extracted, and the expressions of UPRMT, including activation of transcription factor 5(ATF5), heat shock protein 60(mtHSP60), heat shock protein 70(mtHSP70) and mitochondrial protease(ClpP), were detected by Western blot. Immunohistochemistry was used to locate the expression sites of 4 proteins in mouse gastric tissue. AGS and SGC-7901 cells were infected with Hp, and cell proliferation was detected by RTCA and CCK-8. Finally, the expression of four indexes in gastric cancer tissues was analyzed by TCGA samples in the UALCAN database. Results : Hp infection could significantly promote the expression of ATF5, mtHSP60, mtHSP70 and ClpP in the mitochondria of gastric epithelial cells of C57BL6/J mice, AGS and SGC-7901 cells, and promote the proliferation of gastric cancer cells. When compared to normal gastric tissues in TCGA samples, ATF5, mtHSP60, mtHSP70, and ClpP were highly expressed in gastric cancer tissues, with statistically significant difference(allP<0.01). Conclusion Hp infection can induce UPRMTin gastric epithelial cells and gastric cancer cells, which in turn promotes cell proliferation.

Objective To evaluate the effects of combining immune checkpoint inhibitors,trastuzumab,and chemotherapy on the left and right ventricular function in patients with advanced gastric adenocarcinoma expressing human epidermal growth factor receptor 2(HER2).Methods 25 patients with advanced HER2-positive gastric adenocarcinoma who received HER2-ASTRUM therapy(sruili monoclonal antibody combined with trastuzumab and DOS regimen)underwent echocardiographic examinations at baseline(T1),after completion of 4 cycles(T2),and 6 cycles(T3)of chemotherapy.Left ventricular strain,left ventricular myocardial work,right ventricular strain,and ejection fraction were further analyzed.Results Compared with T1,both T2 and T3 showed a decrease in left ventricular ejection fraction(LVEF),(T1,T2,and T3 were[67.3±2.7]％,[63.0±2.9]％and[61.3±3.2]％,P＜0.05).T3 showed a decrease in right ventricular ejection fraction(RVEF),([59.3±7.8]％vs[43.7±6.6]％,P＜0.05),while T2 showed no significant change in RVEF.Both right ventricular global longitudinal strain(RVGLS),(T1,T2,and T3 were[-25.7±5.7]％,[-22.4±5.3]％and[-19.1±3.6]％,respectively;P＜0.05)and right ventricular free-wall longitudinal strain(RVFWLS),(T1,T2,and T3 were[-20.9±4.7]％,[-18.9±4.1]％and[-16.1±3.9]％,P＜0.05)decreased in all three time points.The global work index(GWI)was lower in T2 and T3 than in T1(P＜0.05),while the global constructive work(GCW),global wasted work(GWW),and global work efficiency(GWE)did not show significant changes.Conclusions Combination of trastuzumab,immune checkpoint inhibitors,and chemotherapy has an impact on left ventricular strain,LVEF,and right ventricular strain,as well as GWI,in HER2-positive patients with gastric adenocarcinoma.Left ventricular global longitudinal strain(LVGLS),RVFWLS,and RVGLS can more sensitively monitor cardiac function and detect cardiac dysfunction related to cancer treatment in a timely manner.

Objective To analyze the changes in left ventricular deformation function in patients with diffuse large B-cell lymphoma(DLBCL)treated with different doses of anthracycline chemotherapy using 3D speckle-tracking imaging(3D-STI).Methods 66 DLBCL patients receiving anthracycline chemotherapy were enrolled.Based on the cumulative dose of anthracycline received,the patients were divided into a high-dose group(＞360 mg/m2,n=39)and a low-dose group(≤360 mg/m2,n=27).Patients underwent transthoracic echocardiography before chemotherapy and within one week after completion of the entire chemotherapy cycle.Left ventricular global longitudinal strain(LVGLS),left ventricular global circumferential strain(LVGCS),and other indices were analyzed using 3D-STI to assess changes in left ventricular deformation indices after chemotherapy and between two groups.Results Compared to baseline,DLBCL patients showed significant reductions in LVGLS,LVGCS and left atrial global longitudinal strain(LAGLS)after treatment completion(P＜0.001).When comparing the high-dose group with the low-dose group,there was a significant increase in relative LVGCS change rate at the end of chemotherapy(21.12[6.52,35.37]vs 5.49[-14.73,27.01];P=0.03).However,there were no statistically significant differences in relative left ventricular ejection fraction(LVEF),LVGLS,LVGCS,LVEF change rate,or LVGLS change rate between the two groups.Conclusions 3D-STI can be a potential method to identify the sub-clinical deterioration of left ventricular systolic function in patients received anthracycline chemotherapy,the difference of change rate of LVGCS may predict the variation of sub-clinical deterioration of left ventricular function between patients received high and low doses of anthracycline chemotherapy.

As an important advance in the treatment of anti-tumor therapy,immune checkpoint inhibitors significantly prolong the survival of patients with malignant tumors.At the same time,immune-related adverse reactions are also increasing,among which ICIs have increased the risk of acute coronary events,but clinical reports are rare.This paper analyzes the history of a patient with pulmonary small cell neuroendocrine carcinoma who developed acute myocardial infarction after ICIs treatment,suggesting that clinicians should be alert to the occurrence of ICIs-related acute myocardial infarction,and improve the prognosis of patients through early identification and intervention.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Background and purpose:Outcomes for cancer patients with steroid-resistant immune checkpoint inhibitor-associated myocarditis(srICIAM)are poor.Intensified immunosuppressive therapies,including tofacitinib,a novel Janus kinase(JAK)inhibitor,may have some therapeutic benefits.However,due to the lack of sufficient clinical data,the effectiveness of such treatments and their impact on cardiovascular outcomes remain unclear.This study aimed to investigate the therapeutic effect of tofacitinib on srICIAM.Methods:This retrospective case-control study included 36 malignant tumor patients who received immune checkpoint inhibitor treatment at Zhongshan Hospital affiliated to Fudan University from July 2019 to May 2022 and developed srICIAM.Patients receiving corticosteroids in combination with tofacitinib were assigned to the tofacitinib group(n=19),while those not treated with tofacitinib were allocated to the control group(n=17).The study compared clinical characteristics,laboratory findings,and imaging results between the two groups.Additionally,follow-up was conducted to monitor the incidence of cardiovascular endpoints in these patients.The research plan was approved by the Ethics Committee of Zhongshan Hospital Affiliated to Fudan University(Approval Number:B2021-275R).This study was conducted in accordance with the ethical guidelines of the Helsinki Declaration.Results:Compared to the control group,and with no significant difference in the cumulative dose and duration of corticosteroids(P＜0.05),the tofacitinib group showed a shorter myocarditis recovery time(median recovery time:86.5 days vs 126.5 days,P=0.021).The myocarditis-related mortality rate was significantly lower in the tofacitinib group than in the control group(5%vs 35%,P=0.025).Conclusion:Tofacitinib may reduce mortality and promote cardiac recovery in srICIAM patients without impeding the anti-tumor effect.It may become one of the potential treatment strategies in the future.

Objective To evaluate the efficacy and safety of high intensity focused ultrasound(HFIU)combined with endometrial ablation in the treatment of adenomyosis(AM)patients with heavy menstrual bleeding(HMB).Method A total of 199 patients with AM combined with HMB who underwent HIFU treatment at the Obstetrics and Gynecology Center of Affiliated Hospital of Chengdu University of TCM from July 2020 to September 2022 were selected and divided into two groups according to the ablation range.The combined ablation group included 80 cases with lesion and endometrial ablation(endometrial ablation rate≥30%),while the lesion ablation group 119 cases with simple lesion ablation.A 1∶1 propensity score matching was performed on the two groups,resulting in 59 patients in each group.A 6-month follow-up was conducted.The clinical manifestations(menstrual volume,degree of dysmenorrhea,uterine and lesion volume),quality of life(MS-QOL,UFS-QOL),and postoperative adverse reactions between the two groups before and 6 months after surgery was compared.Results Menstrual volume,degree of dysmenorrhea,uterine and lesion volume,MS-QOL score,and UFS-QOL score of the both groups were improved 6 months after surgery,when compared to those before surgery(P<0.05).Significantly reduced menstrual volume,degree of dysmenorrhea,and lower MS-QOL score were observed in the combined ablation group when compared with the lesion ablation group(P<0.05),but there was no statistical significance in uterine and lesion volume and UFS-QOL score(P>0.05).There was no difference in the incidence of adverse reactions between the two groups(P>0.05),but the combined ablation group had longer vaginal bleeding and fluid flow time(P<0.05).Conclusion The combined HIFU and endometrial ablation can effectively reduce menstrual flow,alleviate dysmenorrhea,and improve quality of life in patients with AM combined with HMB.Although it increases vaginal bleeding and fluid flow time,reasonable symptomatic management can effectively prevent the occurrence of adverse consequences such as infection.