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 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 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.

Objective:This study aims to obtain the prevalence and features associated with Violence Against Children (VAC) in China and, thus, formulate a prevention strategy.Methods:The mortality-related data of VAC was sourced from the National Disease Surveillance Points System (DSP) during 2013-2021. We analyzed the DSP data regarding children aged 0-17 years old who died from violence. The hospital cases of VAC was sourced from the National Injury Surveillance System (NISS), 2013-2021. We analyzed the data from NISS with the parameter of "intentional injury" caused by VAC in children aged between 0-17 years. Using robust linear regression, we analyze the time trend in the proportion of violence incidence. To understand the variations in the incidence of different types of violence across genders, we apply the chi-square test and adjusted Pearson residuals.Results:The overall trend of death caused by VAC has declined; it was reduced to 0.14/100 000 in 2021 from 0.33/100 000 in 2013. In 2021, male VAC mortality (0.15/100 000) was higher than females (0.13/100 000). The proportion of VAC cases to all injury cases has declined from 3.34% in 2013 to 2.29% in 2021. Among 9 344 VAC cases supervised by hospitals in 2021, the number of males (7 503 cases) was around 4 times that of females (1 841 cases), and the top three modes of violence were blunt tools (64.77%), falls (7.46%) and sharp instruments (6.18%), and 45 cases of sexual violence included 38 girls and 7 boys.Conclusions:The declining death rate due to VAC may be related to the benign development of Chinese society. Prevention strategies targeting training in parenting skills and problem-solving should be prioritized.

BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo. Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.

Objective:To compare the cost-effectiveness of hospitalized Chinese patients undergoing nucleic acid screening strategies for hepatitis B and hepatitis C, immunological screening strategy, and no screening strategy under different willingness to pay (WTP). The results might aid to decision-making for the optimal strategy.Methods:In this study, nucleic acid screening, immunological screening and no screening were used as screening strategies, and China′s GDP in 2021 (80 976 yuan) was used as the threshold of WTP to construct a Markov model. After introducing parameters related to the diagnosis and treatment of hepatitis B and C in inpatients, a cohort population of 100 000 inpatients was simulated by TreeAge Pro 2021 software, the total cost, total health effects, incremental cost-effectiveness ratio and average cost-effectiveness ratio of different screening strategies were calculated, and cost-effectiveness analysis was conducted. Univariate and probabilistic sensitivity analysis were used to assess the impact of parameter uncertainty on the final results.Results:Compared with the non-screening strategy, the incremental total cost of the hepatitis B immunological screening strategy for cohort patients was 11 049 536 yuan, and the incremental cost-effectiveness ratio was 24 762 yuan/quality-adjusted life years (QALY), while the total incremental cost of nucleic acid screening was 19 208 059 yuan, and the incremental cost-effectiveness ratio was 29 873 yuan/QALY; the incremental cost-effectiveness ratio of nucleic acid screening and immunological screening was 45 834 yuan/QALY. Compared with the non-screening strategy, the incremental cost-effectiveness ratio of hepatitis C immunological screening strategy was 5 731 yuan/QALY, the incremental cost-effectiveness ratio of nucleic acid screening strategy was 8 722 yuan/QALY, the incremental cost-effectiveness ratio of nucleic acid screening and immunological screening was 45 591 yuan/QALY. The results of probabilistic sensitivity analysis showed that when the cost of nucleic acid testing exceeded 214.53 yuan, it was not cost-effective to perform hepatitis B nucleic acid screening under the WTP as 1 fold GDP. When the cost of nucleic acid testing exceeded 132.18 yuan, it was not cost-effective to conduct hepatitis C screening under the WTP as 1 fold GDP.Conclusions:Nucleic acid screening strategy can achieve more cost-effectiveness and is worthy of vigorous promotion. Compared with no screening, both the nucleic acid and immunological screening strategies are cost-effective, and hepatitis nucleic acid screening is the optimal strategy for hospitalized patients.

Periodontitis is an infectious disease caused by an imbalance between the local microbiota and host immune response. Epidemiologically, periodontitis is closely related to the occurrence, development, and poor prognosis of T2D and is recognized as a potential risk factor for T2D. In recent years, increasing attention has been given to the role of the virulence factors produced by disorders of the subgingival microbiota in the pathological mechanism of T2D, including islet β-cell dysfunction and insulin resistance (IR). However, the related mechanisms have not been well summarized. This review highlights periodontitis-derived virulence factors, reviews how these stimuli directly or indirectly regulate islet β-cell dysfunction. The mechanisms by which IR is induced in insulin-targeting tissues (the liver, visceral adipose tissue, and skeletal muscle) are explained, clarifying the influence of periodontitis on the occurrence and development of T2D. In addition, the positive effects of periodontal therapy on T2D are overviewed. Finally, the limitations and prospects of the current research are discussed. In summary, periodontitis is worthy of attention as a promoting factor of T2D. Understanding on the effect of disseminated periodontitis-derived virulence factors on the T2D-related tissues and cells may provide new treatment options for reducing the risk of T2D associated with periodontitis.
Humans ; Diabetes Mellitus, Type 2/complications* ; Periodontitis

Objective:To analyze the risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery, and to provide a reasonable basis for preoperative evaluation and postoperative follow-up. Methods:This study retrospective analyzed the relationship between clinicopathological factors and clinical outcome（recurrence, canceration, recurrence-free survival, and canceration-free survival） in 148 patients undergoing surgical treatment in Chongqing General Hospital from 2014 to 2017. Results:The five-year overall recurrence rate was 14.86% and the overall recurrence rate was 8.78%. Univariate analysis showed that smoking index, laryngopharyngeal reflux and lesion range were significantly associated with recurrence（P<0.05）, and smoking index and lesion range were significantly associated with canceration（P<0.05）. Multivariate logistic regression analysis showed that smoking index ≥600 and laryngopharyngeal reflux were independent risk factors for recurrence（P<0.05）, and smoking index ≥600 and lesion range ≥1/2 vocal cord were independent risk factors for canceration（P<0.05）. The mean carcinogenesis interval for the postoperative smoking cessation group was significantly longer（P<0.05）. Conclusion:Excessive smoking, laryngopharyngeal reflux and a wide range of lesions may be related to postoperative recurrence or malignant progression of precancerous lesions in the vocal cord, and further large-scale multi-center prospective randomized controlled studies are needed to clarify the effects of the above factors on recurrence and malignant changes in the future.
Humans ; Vocal Cords/pathology* ; Retrospective Studies ; Laryngopharyngeal Reflux/complications* ; Prospective Studies ; Precancerous Conditions/pathology* ; Risk Factors

Objective:To investigate the etiological diagnostic value of metagenomic sequencing in central nervous system (CNS) infectious diseases.Methods:A total of 170 patients with central nervous system infection admitted to the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2020 were selected as the study subjects according to inclusion and exclusion criteria. General clinical data and pathogen test results were collected. All included patients underwent routine examination and mNGS test, and were divided into the conventional method test group and mNGS test group according to the test results. The measurement data conforming to normal distribution were represented by ± s; The measurement data that did not conform to normal distribution were represented by median and interquartile range. The classification data were expressed by the number of cases and percentage( n,%), and were compared by χ2 test or Fisher's exact test. Consistency test was represented by Kappa value. The detection of pathogenic microorganisms by the two methods and the rule of pathogen spectrum were compared and analyzed. Results:The overall positive rate of mNGS in CNS infectious diseases was higher than that of conventional methods (58.23% vs. 18.82%), and the difference was statistically significant ( P<0.01). Among the 20 samples which were both positive by the two methods, 10 cases were completely pathogenic, 5 cases were partially consistent and 5 cases were completely inconsistent. In the detection of tuberculous nervous system infection, the positive rates were 66.7%, 53.8%, 44.0%, 40.0%, 4.0% in blood T-SPOT, cerebrospinal fluid mNGS, ADA, Mycobacterium tuberculosis DNA and tuberculous specific antibody, respectively. The positive rate of acid-fast staining was 0. The positive rate of mNGS combined with conventional method was 80.8%. Conclusions:The detection rate of mNGS in CNS infection is better than that of conventional methods. However, it does not show obvious superiority in the detection rate of Mycobacterium tuberculosis associated nervous system infection. In general, mNGS detection of pathogenic bacteria is more extensive, which is conducive to a thorough and comprehensive understanding of the bacterial characteristics of central nervous system infection. The combination of the two methods can make up for the deficiency of clinical routine detection to a certain extent, and can maximize the detection rate.

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.