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 explore the effect of the knockdown of transmembrane 9 superfamily protein member 2 (TM9SF2) on the replication of vesicular stomatitis virus (VSV), and investigate its role in the mechanism of antiviral innate immunity. Methods Small interfering RNA (siRNA) was used to knock down the TM9SF2 gene in human non-small cell lung cancer A549 cells. The CCK-8 method was used to assess cell proliferation. A VSV-green fluorescent protein (VSV-GFP) infected cell model was established. The plaque assay was used to measure the viral titer in the supernatant. RT-qPCR and Western blotting were employed to quantify the mRNA and protein levels of VSV genome replication in A549 cells following VSV infection, as well as the expression of interferon β (IFN-β) mRNA and interferon regulatory factor 3 (IRF3) protein phosphorylation following polyinosinic-polycytidylic acid (poly(I:C)) stimulation. Results Compared to the negative control, the knockdown of TM9SF2 exhibited a significant effect, with no observed impact on A549 cell proliferation. The VSV-GFP infected A549 cell model was successfully established. After viral stimulation, fluorescence intensity was reduced following TM9SF2 knockdown, and the mRNA and protein levels of VSV were significantly downregulated. The viral titer of VSV was decreased. After poly(I:C) stimulation, TM9SF2 knockdown significantly upregulated the mRNA level of IFN-β and the phosphorylation level of IRF3 protein. Conclusion The knockdown of TM9SF2 inhibits the replication of vesicular stomatitis virus, and positively regulates the type I interferon signaling pathway, thus enhancing the host's antiviral innate immune response.
Humans ; Virus Replication/genetics* ; Signal Transduction ; Membrane Proteins/metabolism* ; A549 Cells ; Vesiculovirus/physiology* ; Interferon-beta/metabolism* ; Interferon Regulatory Factor-3/genetics* ; Interferon Type I/metabolism* ; Vesicular Stomatitis/immunology* ; Gene Knockdown Techniques ; Vesicular stomatitis Indiana virus/physiology* ; RNA, Small Interfering/genetics*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective:To observe the effects of moxibustion on the levels of glucose-6-phosphate dehydrogenase(G6PD)and reduced nicotinamide adenine dinucleotide phosphate(NADPH)in the plasma and spleen and the CD4+T-cell number in the spleen of rats with adjuvant arthritis,thus to explore the mechanism in rheumatoid arthritis(RA)treatment with moxibustion by regulating the CD4+T-cell proliferation through G6PD-mediated pentose phosphate pathway. Methods:Twenty-seven male Sprague-Dawley rats were randomly divided into a blank group,a model group,and a moxibustion group,with 9 rats in each group.Incomplete Freund's adjuvant was used to induce inflammation in the model group and the moxibustion group.The blank group and the model group were not intervened.In the moxibustion group,suspended moxibustion was performed at bilateral Zusanli(ST36),Guanyuan(CV4),and Ashi points for 30 min,once a day for 24 times in total.Hematoxylin-eosin staining was used to evaluate the histopathological changes of rat synovial tissue;the swelling degree of the rat toes was observed by measuring the toe volume;G6PD and NADPH in the spleen and plasma were detected by Western blotting and enzyme-linked immunosorbent assay.Flow cytometry was used to detect the CD4+T-cell number in the spleen. Results:Compared with the blank group,the levels of G6PD and NADPH in the plasma and spleen and the CD4+T-cell number in the spleen were significantly increased in the model group(P<0.01 or P<0.05).Compared with the model group,the NADPH level in the spleen and plasma and the CD4+T-cell number in the spleen in the moxibustion group decreased significantly(P<0.05 or P<0.01),and the G6PD level in the plasma decreased significantly(P<0.05),but there was no significant difference in the G6PD level in the spleen(P>0.05). Conclusion:Moxibustion can regulate immunity and improve joint synovial inflammation in RA.The mechanism may be that the G6PD-mediated pentose phosphate pathway reduces the production of metabolite NAPDH in CD4+T cells,thereby inhibiting the proliferation of naive CD4+T cells.

Objective:To explore the current situation of the intrinsic capacity of elderly people in the community and analyze its influencing factors.Methods:From September 2022 to March 2023, convenience sampling was used to select 360 elderly community residents from Xicheng District, Beijing, and Xingtai City, Hebei Province, as the research subjects. The subjects were surveyed using the Intrinsic Capacity Assessment Questionnaire, Intrinsic Capacity Influencing Factors Questionnaire, Barthel Index, and Lawton Instrumental Activities of Daily Living Scale.Results:A total of 360 questionnaires were distributed, and 360 valid questionnaires were collected, with an effective response rate of 100.0% (360/360). The overall impairment rate of intrinsic capacity among 360 elderly people in the community was 90.3% (325/360), and the impairment rates in various fields from high to low were sensation, psychology, vitality, cognition, and exercise. Multiple linear regression analysis showed that age, gender, residential pattern, education level, work status, grip strength, number of geriatric syndrome, self-rated health status, adverse life events, number of social activities, transportation conditions, and social security were the influencing factors of the intrinsic capacity of elderly people in the community, and the difference was statistically significant ( P<0.05) . Conclusions:The impairment rate of intrinsic capacity among elderly people in the community is relatively high. Grassroots medical and nursing staff should assess the intrinsic capacity of elderly people in the community in health promotion work, identify elderly people with decreased intrinsic capacity early and carry out effective interventions to prevent elderly people from becoming disabled and dependent on care.

Objective:To explore the influencing factors for hypoglycemia in elderly patients during peri-colonoscopy, construct and validate a risk prediction model.Methods:The factors influencing hypoglycemia in elderly patients during the peri-colonoscopy period were identified through a literature review and semi-structured interviews. After two rounds of Delphi expert consultation, the survey questionnaire was determined. From January to September 2023, convenience sampling was used to select elderly patients who underwent colonoscopy in the Department of Gastroenterology at the Affiliated Hospital of Qingdao University as participants for a questionnaire survey. Univariate and multivariate Logistic regression was used to explore the influencing factors of hypoglycemia in elderly patients during the peri-colonoscopy period, and a nomogram model of hypoglycemia risk in elderly patients during the peri-colonoscopy period was drawn. The area under the receiver operating characteristic curve ( AUC) of the subjects and the Hosmer-Lemeshow goodness of fit test were used to evaluate the model's predictive performance. The clinical decision curve of DCA was implemented to evaluate the model's clinical benefit ability. Results:A total of 558 questionnaires were distributed (392 for the modeling group and 166 for the validation group) and 558 valid questionnaires were collected, with a valid response rate of 100.00%. Among 558 elderly patients, a total of 130 cases (89 in the modeling group and 41 in the validation group) experienced hypoglycemia during the peri-colonoscopy period, with an incidence of 23.30%. Multivariate Logistic regression analysis showed that serum albumin, age, previous hypoglycemia frequency, insulin use, fasting time, and nutritional risk were independent influencing factors (all P<0.05). The AUCs of the modeling and validation groups were 0.933 and 0.899, respectively. Hosmer Lemeshow test showed that the model had good calibration accuracy, and the DCA curve indicated that the model had good clinical effectiveness. Conclusions:The nomogram model has good predictive performance and can intuitively and concisely predict the risk of hypoglycemia in elderly patients during the peri-colonoscopy period, providing reference for medical and nursing staff.

Objective:To investigate and distinguish the useful index of recognizing blood culture contamination and bloodstream infection when the blood cultures were positive in clinical practice, and to help clinicians to recognize blood culture contamination.Methods:A retrospective study was conducted to analyze the clinical data and distribution of bacteria of blood culture from 303 patients with positive blood culture from January to December 2021 in Huashan Hospital, Fudan University. Age, distribution of departments, positive time of blood culture, neutrophil ratio, procalcitonin and C-reactive protein (CRP) were compared between bloodstream infection group and blood culture contamination group. Mann-Whitney U test and chi-square test were used for statistical comparisons. The factors for recognizing blood culture contamination were analyzed by multivariate logistic regression. Results:A total of 303 patients with positive blood culture were enrolled and divided into two groups, including 237 cases in bloodstream infection group and 66 cases in blood culture contamination group, with the contamination rate of 21.78%. There was statistically significant difference in the distribution of departments between the two groups ( χ2=11.28, P=0.024). The proportion of age≥60 years old (52.7%(125/237) vs 36.4%(24/66)), the neutrophil ratio(0.86(0.79, 0.91) vs 0.82(0.75, 0.88)), the levels of procalcitonin (1.05(0.23, 6.64) μg/L vs 0.17(0.11, 0.72) μg/L) and CRP (60.55(24.83, 132.83) mg/L vs 40.64(8.98, 95.83) mg/L) in the bloodstream infection group were higher than those in blood culture contamination group, and the differences were statistically significant ( χ2=5.54, U=9 523.00, 10 906.00 and 9 278.50, respectively, all P<0.05). Among the 303 patients with positive blood culture, 253 patients had a single positive blood culture, 41 patients had twice positive blood cultures and nine patients had three times positive blood cultures. The highest contamination rate of detected pathogen was coagulase-negative staphylococcus (54.72%(29/53)) in the patients with single positive blood culture. The positive time of blood culture in the bloodstream infection group was 3(3, 4) d, which was shorter than 4(3, 4) d in the blood culture contamination group, and the difference was statistically significant ( U=6 521.00, P=0.026). Multivariate logistic regression analysis showed that when the time to positivity ≤3 days and procalcitonin level ≥2.00 μg/L, the positive blood culture results were more likely to be bloodstream infection (odds ratio ( OR)=2.16, 1.96, respectively, both P<0.05). Conclusions:Bacteria associated with blood culture, time to positivity and clinical index all play important roles in recognizing blood culture contamination. When the time to positivity ≤3 days and procalcitonin level ≥2.00 μg/L, the positive blood culture results are more likely to be bloodstream infection.

Objective To investigate the relationship between cognitive impairment and sleep parameters in acute ischemic stroke patients with obstructive sleep apnea(OSA).Methods A total of 343 patients with acute ischemic stroke and OSA were selected.The cognitive function was assessed using the simple mental state examination scale(MMSE).Patients were divided into the stroke with OSA and cognitive impairment group(MMSE＜27 points,n=119)and the stroke with OSA without cognitive impairment group(MMSE≥27 points,n=224).General data,TOAST etiological classification and distribution of cerebral infarction lesions were collected.The intelligent sleep monitoring system was used to calculate apnea hypopnea index(AHI)and evaluate OSA.Objective sleep monitoring parameters were collected at night.Sleep monitoring was conducted within 24 h of admission and continuous monitoring for≥3 nights.Continuous monitoring duration≥7 h every night to obtain night sleep structure parameters.Multifactor Logistics regression was used to analyze the relationship between cognitive impairment and sleep parameters in stroke patients with OSA.Results Compared with the stroke with OSA without cognitive impairment group,the proportion of age,diabetes history and HHcy history,the proportion of patients with infarct lesions located in frontal,temporal,parietal,occipital,thalamus,basal ganglia,brainstem and hemioval center increased in the stroke with OSA and cognitive impairment group,and the number of years of education decreased,the number of waking times,the proportion of light sleep and AHI increased,the nighttime sleep efficiency and deep sleep period decreased(P＜0.05).Logistics regression analysis showed that after controlling for years of education,age and other interference factors,nighttime sleep efficiency and AHI were strongly associated with cognitive impairment in acute ischemic stroke patients with OSA(P＜0.05).The increased nighttime sleep efficiency was protective factor for cognitive impairment,and increased AHI was risk factor for cognitive impairment.Conclusion Cognitive impairment in acute ischemic stroke patients with OSA is closely related to sleep parameters,in which the increased sleep efficiency at night is a protective factor for cognitive impairment,and the increased AHI is a risk factor.