BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Objective:To systematically review qualitative studies on the experiences of musculoskeletal symptoms in breast cancer patients undergoing endocrine therapy, and to gain insights into the initiation, development, and effects of these symptoms, along with their implications for patients, to guide the creation of targeted strategies for symptom management.Methods:The qualitative studies on the experiences of musculoskeletal symptoms in breast cancer patients undergoing endocrine therapy were performed across several databases, which included the Cochrane Library, Joanna Briggs Institute Evidence based Healthcare Center Database, PubMed, Embase, CINAHL, Web of Science, Scopus, CNKI, Wanfang Data, and Chinese Biomedical Literature Database. The retrieval period was from the establishment of the database to April 30, 2024. The studies' quality was evaluated utilizing the iteration of the Joanna Briggs Institute Qualitative Assessment and Review Instrument designed for qualitative research. Data synthesis was carried out using Meta-aggregation techniques.Results:A total of 15 articles were included and 41 results were extracted, which were grouped into 11 new categories and integrated into 3 primary themes: the manifestation of bone and joint symptoms was highly unique and varied, prominently featuring experiences such as migratory joint pain, morning stiffness, and cramps affecting both large and small joints, frequently associated with functional limitations; these symptoms significantly influence patients' everyday activities and mental health, contributing to feelings of anxiety, avoidance behaviors, fear, and a reduction in overall quality of life; to manage the intricate nature of their symptoms, patients employ a variety of coping mechanisms, such as engaging in physical activity, taking dietary supplements, consulting about medications, and seeking support from external sources.Conclusions:During endocrine therapy for breast cancer, patients exhibit diverse characteristics of musculoskeletal symptoms, and the resulting fear of recurrence, avoidance behaviors, and anxiety have a negative impact on their psychological well-being and overall health. Healthcare professionals should take into account individual differences, such as age, menopausal status, type of endocrine therapy, medication adherence, and factors that may exacerbate or alleviate symptoms, in order to effectively predict, assess, and manage bone and joint symptoms during endocrine therapy.

Objective:To systematically review qualitative studies on the experiences of musculoskeletal symptoms in breast cancer patients undergoing endocrine therapy, and to gain insights into the initiation, development, and effects of these symptoms, along with their implications for patients, to guide the creation of targeted strategies for symptom management.Methods:The qualitative studies on the experiences of musculoskeletal symptoms in breast cancer patients undergoing endocrine therapy were performed across several databases, which included the Cochrane Library, Joanna Briggs Institute Evidence based Healthcare Center Database, PubMed, Embase, CINAHL, Web of Science, Scopus, CNKI, Wanfang Data, and Chinese Biomedical Literature Database. The retrieval period was from the establishment of the database to April 30, 2024. The studies' quality was evaluated utilizing the iteration of the Joanna Briggs Institute Qualitative Assessment and Review Instrument designed for qualitative research. Data synthesis was carried out using Meta-aggregation techniques.Results:A total of 15 articles were included and 41 results were extracted, which were grouped into 11 new categories and integrated into 3 primary themes: the manifestation of bone and joint symptoms was highly unique and varied, prominently featuring experiences such as migratory joint pain, morning stiffness, and cramps affecting both large and small joints, frequently associated with functional limitations; these symptoms significantly influence patients' everyday activities and mental health, contributing to feelings of anxiety, avoidance behaviors, fear, and a reduction in overall quality of life; to manage the intricate nature of their symptoms, patients employ a variety of coping mechanisms, such as engaging in physical activity, taking dietary supplements, consulting about medications, and seeking support from external sources.Conclusions:During endocrine therapy for breast cancer, patients exhibit diverse characteristics of musculoskeletal symptoms, and the resulting fear of recurrence, avoidance behaviors, and anxiety have a negative impact on their psychological well-being and overall health. Healthcare professionals should take into account individual differences, such as age, menopausal status, type of endocrine therapy, medication adherence, and factors that may exacerbate or alleviate symptoms, in order to effectively predict, assess, and manage bone and joint symptoms during endocrine therapy.

Objective:To explore the differences of gene expression profiles of precursors of exhausted T cells (Tpex) and terminal exhausted T cells (Tex) in the peripheral blood of patients with active pulmonary tuberculosis (ATB).Methods:Twenty-five cases of ATB, 13 cases of latent tuberculosis infection (LTBI) and 10 health controls were enrolled from January 2021 to October 2022 in the Fifth People′s Hospital of Wuxi. The proportions of Tpex and Tex in the peripheral blood mononuclear cells (PBMCs) of the three groups were detected by flowcytometry. PBMCs of ATB were separated into Tpex and Tex by fluorescence-activated cell sorting. RNA-sequencing was performed and up-regulated and down-regulated genes were screended. Differently expressed genes were analyzed by gene set enrichment analysis of gene ontology (GO) to find regulatory pathways affecting cell metabolism and function. Wilcoxon matched-pairs signed rank test, Kruskal-Wallis test and Dunn multiple comparsion test were used for statistical analysis.Results:The proportion of Tpex in ATB group was 2.86%(1.74%), which was lower than 7.93%(6.16%) of Tex, and the difference was statistically significant ( Z=-3.91, P<0.001). The proportions of Tpex and Tex in LTBI group were 9.47%(6.26%) and 7.43%(5.48%), respectively, and the difference was not statistically significant ( Z=-0.93, P=0.345). The proportions of Tpex and Tex in healthy control group were 8.42%(2.69%) and 6.49%(5.14%), respectively, with no statistical significance ( Z=-1.36, P=0.170). There was statistical difference of the proportion of Tpex among the three groups ( H=21.93, P<0.001), and the proportion of Tpex in ATB group was lower than those in LTBI and heathy control groups, and the differences were both statistically significant ( Z=4.16, P<0.001 and Z=3.34, P=0.003, respectively), while the proportions of Tex in these three groups were not statistically different ( H=2.17, P=0.338). Compared with Tex, the gene expressions of memory markers, such as B-cell lymphoma 2 of Tpex were up-regulated, and the gene expressions of exhausted markers, such as lymphocyte activation gene 3 were down-regulated. In terms of cellular metabolism, the gene expressions of mitochondrial protein complex, mitochondrial matrix and oxidative phosphorylation of Tpex were up-regulated, and the gene expressions of glycolysis were down-regulated. The gene expressions of pyruvate metabolism in Tex were up-regulated, and the gene expressions of CD4 + T lymphocyte activation and differentiation and glycolytic process in Tpex were down-regulated. Conclusions:Tpex in ATB express more characteristics of memory cells and less features of exhausted markers compared with Tex, and the function of mitochondria of Tpex preserves well.

Objective To analyze the core genes of lung ischemia-reperfusion injury and construct a competitive endogenous RNA (ceRNA) network. Methods Original data of GSE145989 were downloaded from the Gene Expression Omnibus (GEO) database as the training set, and the GSE172222 and GSE9634 datasets were used as the validation sets, and the differentially-expressed genes (DEG) were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Protein-protein interaction (PPI) network was constructed, and the core genes were screened, and the diagnostic values of these core genes and the immune infiltration levels of immune cells were evaluated. The ceRNA network was constructed and validated. The targeted drugs based on ceRNA network were assessed. Results A total of 179 DEG were identified, including 61 down-regulated and 118 up-regulated genes. GO analysis showed that DEGs were associated with multiple biological processes, such as cell migration, differentiation and regulation, etc. They were correlated with cell components, such as vesicle membrane, serosa and membrane raft, etc. They were also associated with multiple molecular functions, such as chemokine receptor, G protein-coupled receptor, immune receptor activity and antigen binding, etc. KEGG pathway enrichment analysis revealed that DEG were involved in tumor necrosis factor (TNF), Wnt, interleukin (IL)-17 and nuclear factor (NF)-κB signaling pathways, etc. PPI network suggested that CD8A, IL2RG, STAT1, CD3G and SYK were the core genes of lung ischemia-reperfusion injury. The ceRNA network prompted that miR-146a-3p, miR-28-5p and miR-593-3p were related to the expression level of CD3G. The miR-149-3p, miR-342-5p, miR-873-5p and miR-491-5p were correlated with the expression level of IL-2RG. The miR-194-3p, miR-512-3p, miR-377-3p and miR-590-3p were associated with the expression level of SYK. The miR-590-3p and miR-875-3p were related to the expression level of CD8A. The miR-143-5p, miR-1231, miR-590-3p and miR-875-3p were associated with the expression level of STAT1. There were 13 targeted drugs for CD3G, 4 targeted drugs for IL-2RG, 28 targeted drugs for SYK and 3 targeted drugs for lncRNA MUC2. No targeted drugs were identified for CD8A, STAT1 and other ceRNA network genes. Conclusions CD8A, IL2RG, STAT1, CD3G and SYK are the core genes of lung ischemia-reperfusion injury. The research and analysis of these core genes probably contribute to the diagnosis of lung ischemia-reperfusion injury and providing novel research ideas and therapeutic targets.

Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.

Objective To explore the expression of prohibitin(PHB)in tumor tissues and analyze its effect on the prognosis of patients with digestive system malignant tumor(DT)and its mechanism.Methods ①The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)database were used to compare the expression of PHB in tumor tissues and normal tissues.②Five pairs of gastric cancer and adjacent tissues and 5 pairs of colon cancer and adjacent tissues were collected,and RT-qPCR was used to verify the mRNA expression levels.③ RT-qPCR and Western blotting were used to verify the differential expression of PHB in normal gastric mucosa cells(GES-1),gastric cancer cells(AGS,MKN45 and HGC27),normal colon cells NCM-460 and human colon cancer cell line SW480.④R language was used to analyze the effect of PHB on the prognosis,tumor microenvironment,tumor mutation burden and microsatellite instability of DT patients.⑤CIBERSORT algorithm was used to study the correlation between PHB expression in tumor tissues and tumor immune cell infiltration.Gene Set Enrichment Analysis(GSEA)was used to explore the biological function of PHB.⑥R language was used to analyze the relationship between PHB and drug sensitivity.Results ①PHB was highly expressed in colon cancer,cholangiocarcinoma,esophageal cancer,liver cancer,rectal cancer and gastric cancer(P＜0.01).②RT-qPCR and Western blotting showed that PHB was highly expressed in the tissues and cell lines of gastric cancer(P＜0.01)and colon cancer(P＜0.01).③The differential expression of PHB was associated with poor prognosis of hepatocellular carcinoma(P=0.002).In cholangiocarcinoma,gastric cancer,pancreatic cancer,liver cancer and esophageal cancer,PHB was positively correlated with tumor mutation burden and microsatellite instability(P＜0.05).④PHB was positively correlated with M2 macrophages in colon cancer(P=0.03).In cholangiocarcinoma,it was positively correlated with activated CD4+memory T cells(P＜0.05).In esophageal carcinoma,it was positively correlated with activated hypertrophy(P=0.03).It was positively correlated with M0 and M2 macrophages and monocytes in hepatocellular carcinoma(P＜0.05).It was positively correlated with resting dendritic cells,eosinophils and activated CD4+memory T cells in rectal cancer(P＜0.05).It was positively correlated with M0 macrophages,activated mast cells,neutrophils,resting natural killer cells,activated CD4+memory T cells and follicular helper T cells in gastric cancer(P＜0.05).⑤PHB was mainly enriched in class I receptors,PPAR and calcium signaling pathways(P＜0.05).⑥ The expression of PHB was positively correlated with the sensitivity of 13 drugs,including ammonafide,prasinolide and abiraterone(P＜0.05).Conclusion The expression of PHB is significantly related to the infiltration of various immune cells in DT and poor prognosis in DT patients,which may become a new biomarker and potential immunomodulatory target of DT.

Objective:To explore the predictive effect of intraocular fluid testing in the assessment of retinal detachment (RD) occurring in acute retinal necrosis syndrome (ARN).Methods:A retrospective study. From January 2019 to October 2023, 40 patients with 40 eyes diagnosed as ARN in Nanjing Medical University Eye Hospital were collected for this study. According to whether RD occurred during the follow-up period, the patients were divided into RD group (group A) and no RD group (group B), with 18 patients 18 eyes and 22 patients 22 eyes, respectively. All patients were given intravitreal 20 mg/ml ganciclovir 0.1 ml (ganciclovir 2 mg), 2 to 3 times per week after diagnosis. The concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (BFGF), vascular cell adhesion factor (VCAM), interleukin (IL)-6, IL-8, and IL-10 in the preaqueous solution were measured before the first injection of ganciclovir. The loads of herpes simplex virus (HSV) and varicella-herpes zoster virus (VZV) were detected by fluorescence quantitative polymerase chain reaction. Receiver operating characteristic curve (ROC curve) calculated and analyzed the area under ROC curve (AUC) of inflammatory cytokines in aqueous humor and HSV-DNA and VZV-DNA loads in predicting RD in ARN patients to evaluate their predictive value.Results:In 18 eyes in group A and 22 eyes in group B, VZV and HSV was infected in 16 and 2 eyes and 21 and 1 eyes, respectively. The VZV-DNA and HSV-DNA load were compared between the two groups, the difference was statistically significant ( Z=-3.762, P<0.001); compared with group B, the concentrations of VEGF in humor ( Z=-3.996), BFGF ( Z=-2.430), IL-6 ( Z=-3.303), IL-8 ( Z=-3.480), and IL-10 ( Z=-3.409) increased significantly in group A, the difference was statistically significant ( P<0.05); there was no statistically significant difference in VCAM between the two groups ( Z=-0.054, P=0.957). The ROC curve analysis showed that the AUC of VEGF, nucleic acid copies, IL-10, IL-8, IL-6, and bFGF for predicting RD in ARN was 0.871, 0.848, 0.828, 0.823, 0.806, 0.737, respectively. The AUC of combination of VEGF, IL-10, IL-8, IL-6, and BFGF predicted the RD in ARN was 0.924. The optimal cut-off value of nucleic acid copies was 0.40×10 6, and IL-10, IL-8 and IL-6 were 50.65, 1 695.50 and 6 634.0 pg/ml, respectively. Conclusion:Aqueous humor viral load as well as cytokines alone or in combination have a reference value for predicting RD secondary to ARN.

Objective:To conduct a thorough analysis of the clinical characteristics in patients with trisomy 8 syndrome and autoimmune diseases, and to provide a new perspective on the diagnosis and management of the fever of unknown origin (FUO).Methods:Patients who were admitted to Huashan Hospital, Fudan University between July 1st, 2021 and May 1st, 2024 for FUO and subsequently diagnosed with trisomy 8 syndrome with autoimmune diseases were included. In this retrospective cohort study, patients were divided into infection and non-infection group according to the etiological evidence, and the clinical characteristics and treatments were collected and compared between the two groups. Statistical analysis was performed using the Mann-Whitney U test. Results:Among the nine enrolled patients, one case was associated with Behet syndrome (BD) without myelodysplastic syndrome (MDS) and without co-occurring infection, eight cases were associated with MDS, among which six cases had both BD and MDS, one case had allergic pneumonia, and one case had rheumatoid arthritis. Six MDS cases had infections. The C-reactive protein (CRP) level in the infection group was significantly higher than that in the non-infection group(72.39(14.62, 132.70) mg/L vs 3.68(2.30, 10.09) mg/L; Z=1.00, P=0.048). There were no statistically significant differences in other inflammatory markers (such as white blood cell count, platelet count, erythrocyte sedimentation rate, ferritin, and neutrophil CD64 index) between the infection and non-infection groups (all P>0.05). In the infection group, one had bacterial infection, five had fungal infections, including two cases of disseminated aspergillosis, one case of mixed bacterial, fungal, and viral infections, one case of mucormycosis combined with Enterococcus faecalis infection, and one case of pulmonary aspergillosis combined with disseminated Mycobacterium abscessus infection. Among the nine patients, eight patients received immunosuppressive treatment centered on the glucocorticoids and (or) thalidomide, and all six infected patients received the above immunosuppressive treatment based on the anti-infection therapy. Eight of the nine cases were stable and followed up regularly, while one case died due to worsening of illness. Conclusions:Autoimmune diseases associated with trisomy 8 syndrome is rare. In addition to anti-infection treatment, glucocorticoids, thalidomide or other immunosuppressive drugs should be administrated to suppress the inflammatory response in patients with co-infection, and the disease could be well controlled.