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.

Objective: To investigate the awareness of core tuberculosis (TB) knowledge and the willingness to TB preventive intervention among secondary school students in Lanzhou City, so as to provide a reference basis for the prevention and control of TB in schools. Methods: From April to June 2024, a total of 1 127 secondary school students from 8 schools in 4 districts (counties) of Lanzhou City were recruited by stratified cluster sampling method to conduct a questionnaire survey on the awareness of core TB knowledge and the willingness for preventive intervention against latent tuberculosis infection. Data were analysed using χ 2 test and binary Logistic regression model. Results: The overall awareness rate of core TB knowledge among secondary school students in Lanzhou City was 74.48%, while only 25.91% demonstrated awareness of all core knowledge items. The lowest awareness was observed for the item "tuberculosis is a chronic infectious disease" (61.84%). About 94.85% of the students reported willingness to receive preventive interventions after a diagnosis of latent tuberculosis infection. Multifactorial Logistic regression analysis showed that students whose father s education was junior high school ( OR=3.14, 95%CI =1.22-8.08), senior high school or secondary vocational school ( OR=3.55，95%CI =1.16-10.86) had a higher willingness to receive preventive interventions than those whose father s education was primary school or below (both P <0.05). In addition, students who recognized "suspected tuberculosis" were also more likely to express willingness to receive preventive interventions ( OR=1.96, 95%CI =1.01-3.80, P <0.05). Conclusions The total awareness rate of core TB knowledge among secondary school students in Lanzhou City is low; willingness to receive preventive interventions for latent tuberculosis infection is high and it is related to father s literacy and core TB knowledge level.

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

Hepatitis B virus (HBV)-specific CD8⁺ T cells play a central role in controlling HBV infection; however, their function is impaired during chronic HBV infection, manifesting as a state of dysfunction. Recent studies have revealed that CD8⁺ T cell dysfunction in chronic HBV infection differs from the classical exhaustion observed in other viral infections or tumors. In 2024, several pivotal studies further elucidated novel mechanisms underlying CD8⁺ T cell dysfunction in chronic HBV infection and identified new therapeutic targets, including 4-1BB and transforming growth factor-beta (TGF-β). This review, while elucidating the dysfunction of CD8⁺ T cells in chronic HBV infection and its underlying mechanisms, focuses on summarizing the key findings from these latest studies and explores their translational value and clinical significance.
Humans ; Hepatitis B, Chronic/virology* ; CD8-Positive T-Lymphocytes/immunology* ; Hepatitis B virus/physiology* ; Animals ; Transforming Growth Factor beta/immunology*

OBJECTIVES: To investigate the mechanism mediating the regulatory effect of miR-155-5p on proliferation of human submandibular gland epithelial cells (HSGECs) in primary Sjogren's syndrome (pSS). METHODS: Dual luciferase reporter assay was used to verify the targeting relationship between miR-155-5p and the PI3K/AKT pathway. In a HSGEC model of pSS induced by simulation with TRAIL and INF-γ, the effects of miR-155-inhibitor-NC or miR-155 inhibitor on cell viability, cell cycle, apoptosis and proliferation were evaluated using CKK8 assay, flow cytometry and colony formation assay. ELISA and RT-PCR were used to detect the expressions of inflammatory cytokines and miR-155-5p mRNA in the cells; Western blotting was performed to detect the expressions of proteins in the PI3K/AKT signaling pathway. RESULTS: Dual luciferase assay showed that miR-155-5p targets the PI3K/AKT pathway via PIK3R1 mRNA. The HSGEC model of pSS showed significantly decreased cell viability, cell clone formation ability and expressions IL-10 and IL-4 and increased cell apoptosis, cell percentage in G2 phase, expressions of TNF‑α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-Akt/AKT ratio, and PIK3R1 protein expression. Treatment of the cell models with miR-155 inhibitor significantly increased the cell viability, G1 phase cell percentage, colony formation ability, and expressions of IL-10 and IL-4 levels, and obviously reduced cell apoptosis rate, G2 phase cell percentage, expressions of TNF-α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-AKT/AKT ratio, and PIK3R1 protein expression. CONCLUSIONS In HSGEC model of pSS, inhibition of miR-155-5p can promote cell proliferation and reduced cell apoptosis by targeting PI3K1 mRNA to negatively regulate the overexpression of PI3K/AKT signaling pathway.
Humans ; MicroRNAs/genetics* ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Sjogren's Syndrome/pathology* ; Epithelial Cells/cytology* ; Submandibular Gland/cytology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Apoptosis ; Class Ia Phosphatidylinositol 3-Kinase ; Cells, Cultured

OBJECTIVES: To explore the therapeutic mechanism of puerarin for alleviating synovitis in rats with collagen-induced arthritis (CIA). METHODS: In a SD rat model of CIA, we tested the effects of daily gavage of puerarin at low, moderate and high doses (10, 30, and 100 mg/kg, respectively) for 3 weeks, with tripterygium glycosides (GTW, 10 mg/kg) as the positive control, on swelling in the hind limb joints regions evaluated by arthritis index scoring. Mass fraction of the liver of the rats was calculated, and pathologies in joint synovial membrane were observed with HE staining. The expressions of transforming growth factor β‑activated kinase-1 (TAK1), Toll-like receptor 4 (TLR4), and nuclear factor kappa-Bp65 (NF‑κB p65) at the mRNA and protein levels in the synovial tissues were detected using Real-time PCR and Western blotting. RESULTS: Compared with those in the model group, the rats in GTW group and high-dose puerarin group showed significantly reduced mass fraction of the liver. Treatment with GTW and puerarin at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, and improved synovitis in CIA rats (P<0.05), and the effects of puerarin showed an obvious dose dependence. Both GTW and puerarin treatments significantly lowered TAK1, TLR4, and NF‑κB p65 mRNA and protein expressions in the synovium of CIA rats. CONCLUSIONS Puerarin alleviates synovium damages in CIA rats possibly by suppressing the TLR4/NF‑κB signaling pathway via downregulating TAK1 expression.
Animals ; Toll-Like Receptor 4/metabolism* ; Rats, Sprague-Dawley ; Rats ; MAP Kinase Kinase Kinases/metabolism* ; Signal Transduction/drug effects* ; Arthritis, Rheumatoid/drug therapy* ; NF-kappa B/metabolism* ; Isoflavones/therapeutic use* ; Male ; Arthritis, Experimental/drug therapy* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/metabolism*

Objective Investigating the impact of miR-15a-5p on autophagy in trophoblast cells of pre-eclamptic placenta.Methods Collect 20 cases of normal placental tissue and 20 cases of preeclamptic placental tissue from December 2020 to December 2022.Use fluorescence quantitative PCR to detect the expression of miR-15a-5p in placental tissue and trophoblast cells,and study its correlation with patient blood pressure.The HTR8-S/Vneo cells are divided into normal group(control)and hypoxia group,and the effect of hypoxia on the expression of miR-15a-5p is observed.Additionally,mimic-NC group,mimic-NC+hypoxia group,miR-15a-5p mimic group,miR-15a-5p mimic+hypoxia group,inhibitor-NC group,inhibitor-NC+hypoxia group,miR-15a-5p inhibitor group,and miR-15a-5p inhibitor+hypoxia groups are set up to observe the effect of miR-15a-5p on hypoxia-induced autophagy-related proteins LC3B and p62 protein in trophoblast cells.Western blot is used to detect the expression levels of autophagy-related proteins LC3B and p62 protein in each group;TargetScan website predicts the target genes of miR-15a-5p,and detects their expression levels in placental tissue and trophoblast cells.Results Compared with the control group,the expression levels of miR-15a-5p were significantly increased in the placentas and hypoxic trophoblasts of preeclampsia,and they were positively correlated with the blood pressure of the patients.Under hypoxic conditions,the overexpressed miR-15a-5p promoted the protein expression of LC3BII/I,while the relative expression of P62 was decreased.But after interference with miR-15a-5p,LC3BII/I expression was down-regulated and P62 expression was up-regulated.The results of quantitative PCR and Western blot showed that the expression levels of YAP1 in the preeclampsia placental tissues and hypoxic trophoblasts were significantly reduced.Conclusion The upregulation of miR-15a-5p in trophoblast cells of the placenta in individuals with preeclampsia could enhance autophagy in preeclampsia by forming a complex with YAP1.

Objective: To investigate the characteristics and trend of stroke incidence in Jining City, Shangdong Province from 2015 to 2022, so as to provide the reference for formulating prevention and control strategies of stroke. Methods: Data of stroke incidence in Jining City from 2015 to 2022 were collected from Shandong Provincial Chronic Disease Surveillance Information Management System. The crude incidence was estimated, standardized using the data of the sixth national population census in 2010, and analyzed by age, gender and subtype. The trend in incidence of stroke was analyzed using annual percent change (APC). Results: A total of 316 267 cases of stroke were reported in Jining City from 2015 to 2022, with a crude incidence of 474.17/105 and a standardized incidence of 371.43/105. The incidence of stroke peaked from March to May (90 409 cases, 28.59%). There were 278 901 cases of ischemic stroke (88.19%) and 37 366 cases of hemorrhagic stroke (11.81%). The crude incidence of stroke was higher in males than in females (525.45/105 vs. 420.16/105, P<0.05). The crude incidence of stroke increased with age (P<0.05), reaching a peak in the age group of 80 years and above (2 764.92/105). From 2015 to 2022, the crude incidence of stroke in the overall population, males, females, the age groups of 0-<30 years and 40-<50 years showed increasing trends (APC=6.142%, 6.992%, 5.054%, 3.693% and 6.587%, all P<0.05); the crude incidence of ischemic stroke in the overall population, males and females showed increasing trends (APC=7.489%, 6.593% and 5.456%, all P<0.05), while the crude incidence rates of hemorrhagic stroke did not show significant trends (APC=3.455%, 2.804% and 1.919%, all P>0.05). Conclusions The crude incidence of stroke increased in Jining City from 2015 to 2022, with ischemic stroke as the predominant subtype. March to May was the peak period for disease onset, and young and middle-aged men should be focused on.

Objective:To explore the barrier factors in the implementation of advance care planning for critically ill and end-life patients in China. Provide reference for the implementation of advance care planning in critically ill and end-life patients in China.Methods:The literature from CNKI, Chinese Biomedical Literature Database, Wanfang database, VIP, PubMed and Web of Science database on the implementation of advance care planning for critically ill and end-life patients in China were searched. The search deadline was from database establishment to January 15, 2023. To analyze the literature meeting the inclusion and exclusion criteria.Results:A total of 18 literatures were included, and the barrier factors to the implementation of advance care planning for critically ill and end-life patients in China included six categories (27 types): social and cultural factors (4 types), patient factors (4 types), family factors (5 types), medical staff factors (8 types), interpersonal interaction factors (4 types), policy and legal factors (2 types).Conclusions:The implementation of advance care planning for critically ill and end-life patients in China is affected by a variety of barrier factors. The improvement measures should be formulated according to the modifiable barrier factors to promote the implementation of advance medical care plan for critically ill and end-life patients in China.

OBJECTIVE:There is no consensus on which sit-up strategy to adopt in knee osteoarthritis patients of different ages.Therefore,this study evaluated the biomechanical characteristics of sit-ups in knee osteoarthritis patients of different ages compared with healthy individuals by meta-analysis system and analyzed the sit-up movement patterns of patients of different ages to provide a reference for improving the sit-up function of patients. METHODS:By March 2023,observational studies of biomechanical characteristics of sitting up in patients with knee osteoarthritis and healthy population were retrieved on PubMed,Web of Science and CNKI.Subjects were required to be patients over 50 years of age with knee osteoarthritis who had Kellgren-Lawrence severity grading≥Ⅰ on knee imaging and who had regular knee pain.Subjects were analyzed by age(50-60 years vs.over 60 years)and severity(mild to moderate patients vs.severe patients)subgroups according to inclusion and exclusion criteria.Quality assessment was performed using the modified Down and black scale.Stata 16.0 software was used to perform subgroup analysis to determine the biomechanical characteristics of sitting up in patients with knee osteoarthritis of different ages and severities. RESULTS:A total of 14 randomized controlled trials(824 subjects)were included in the meta-analysis.The mean quality score of all included literature was 76.2,with a range of 66.7 to 86.7,all of which were of medium to high quality and representative.The included studies were of moderate to high quality and representative.Meta-analysis results found that(1)compared to healthy individuals,patients with knee osteoarthritis had longer total sitting up time(SMD=0.92,95%CI:0.76-1.09),P<0.001)and longer extension phase time(SMD=0.46,95%CI:0.18-0.74,P=0.001).Compared to mild to moderate patients,the total duration increased more significantly in severe patients(P<0.001)and the duration of the extension phase increased more significantly in patients over 60 years of age than in patients 50-60 years of age(P=0.001).(2)Compared to healthy individuals,patients with knee osteoarthritis had greater sitting-up trunk flexion motion range(SMD=0.64,95%CI:0.37-0.91,P<0.001);knee flexion motion range(SMD=-0.47,95%CI:-0.70 to-0.24,P<0.001)and ankle dorsiflexion motion range(SMD=-0.32,95%CI:-0.56 to-0.08,P=0.01)were smaller.And knee flexion motion range decreased more significantly in patients over 60 years of age than in patients 50-60 years of age(P<0.001).(3)The peak hip flexion moment(SMD=-0.57,95%CI:-0.83 to-0.31,P<0.001)and peak knee extension moment(SMD=-0.83,95%CI:-1.08 to-0.59,P<0.001)were smaller in patients with knee osteoarthritis. CONCLUSION:(1)Patients with knee osteoarthritis over the age of 60 years have a longer sit-up cushion and extension phase than patients aged 50 to 60 years.The increase in total sit-up duration was also more pronounced in patients with higher severity grades.The increased length of sitting up in patients with advanced age and knee osteoarthritis severity may increase the duration of cartilage loading,exacerbate knee pain symptoms,and increase the difficulty of sitting up in this population.(2)Patients with knee osteoarthritis exhibit limited knee and ankle flexion motion range.Knee mobility is more limited in patients over 60 years of age.(3)Patients with knee osteoarthritis have reduced peak hip flexion and knee extension moments,which may be a compensatory strategy for pain relief.