OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To investigate the influence of Ku80 inhibition on the chemotherapeutic sensitivity of the T-acute lymphoblastic leukemia (T-ALL) cell line Jurkat,and to explore the potential mechanism.Methods:The transcription and expression level of Ku80 in 6 hematological malignant cell lines were detected by RT-qPCR and Western blot,respectively.The expression of Ku80 in Jurkat cells was detected by Western blot after transfection with the recombinant shKu80 lentiviral vector.The proliferation capacity of Jurkat cells was explored by CCK-8 after Ku80 inhibition.The colony formation ability,apoptosis,and γH2AX(a protein marker of DNA damage)expression in Jurkat cells were investigated after Ku80 silencing and co-treated with etoposide(VP16)for 4 hours through soft agar assay,flow cytometry and Western blot,respectively.Results:The Mrna level and protein expression of Ku80 were both highest in Jurkat among 6 hematological malignant cell lines.Ku80 expression was successfully down regulated in Jurkat cells after relative plasmid transfected.The proliferative ability of cells was significantly decreased after Ku80 inhibition (P<0.05).The colony formation capacity of Jurkat cells was obviously reduced and the cells apoptosis and Γh2ax expression were increased after Ku80 inhibition,with or without VP16 incubation.Conclusion:Targeted silencing of Ku80 could enhance the sensitivity of VP16 in Jurkat cells,which might be associated with the elevated level of DNA damage accumulation.

Objective:To investigate the effect of exosomes loaded with Lycium barbarum miRNA(Lb-miR2911)on spermato-genic function recovery in non-obstructive azoospermia(NOA)rats through cross-regulation of the Wnt/β-catenin signaling pathways.Methods:We established an NOA model in 30 four-week-old male SD rats by intraperitoneal injection of busulfan.At 5 weeks after modeling,we equally randomized the rats into a model control group(MC,untreated),an Lb-miR2911EXO group(Lb-miR2911EXO,treated by intratesticular injection of Lb-miR2911-loaded exosomes),and a sham group(Shame,treated by intratesticular injection of exosomes-empty drug),with another 10 male SD rats taken as normal controls(NC).We observed the uptake and metabolic changes of Lb-miR2911 in the testis tissue of the rats by RNA FISH at 2 and 6 weeks after treatment,detected cell proliferation,spermatogenesis and gene expressions of the Wnt/β-catenin signaling pathways in the testis tissue by Transcriptome sequencing analysis combined with Western blot and RT-PCR at 12 weeks,evaluated the recovery of the spermatogenic function based on the testis tissue morphology and sperm quality,and assessed the organ toxicity of Lb-miR2911 in the tissue and organs of the rats based on histomorphological analysis and the levels of serum TNF-α,IL-1β,Aspartate aminotransferase(AST),Alanine aminotransferase(ALT)and other relevant indi-cators.Results:After 12 weeks of treatment,histomorphological analysis showed regular arrangement of spermatogenic cells at all levels in the testis tissue,with a large number of mature sperm in the tubular lumen,and with significantly higher Johnsen scores,tes-tis weight,testicular index,sperm concentration and sperm motility in the Lb-miR2911EXO than in the sham group(all P<0.05).Compared with the model controls,the Lb-miR2911EXO group exhibited remarkably down-regulated gene expression of DACT3(P<0.05),up-regulated expressions of DVL2 and β-catenin(P<0.05),elevated levels of p-DVL2 and β-catenin(nucleus)proteins(P<0.05),increased expressions of cell proliferation-related genes CCND1,CCNE1 and CCNE2(P<0.05)and spermatogenesis-related genes DMC1,CCR6,JAM2 and KLC3(P<0.05).No pathological changes were observed in the lung,liver and kidney tis-sues of the rats,or in the levels of serum TNF-α,IL-1β,AST,ALT,creatinine and urea nitrogen in the rats treated with Lb-miR2911EXO compared with the normal controls(P>0.05).Conclusion:Lb-miR2911-loaded exosomes promote spermatogenic function recovery in NOA rats through cross-regulation of the DACT3,Wnt and β-catenin signaling pathways.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

OBJECTIVE: To investigate the influence of Ku80 inhibition on the chemotherapeutic sensitivity of the T-acute lymphoblastic leukemia(T-ALL) cell line Jurkat, and to explore the potential mechanism. METHODS: The transcription and expression level of Ku80 in 6 hematological malignant cell lines were detected by RT-qPCR and Western blot, respectively. The expression of Ku80 in Jurkat cells was detected by Western blot after transfection with the recombinant shKu80 lentiviral vector. The proliferation capacity of Jurkat cells was explored by CCK-8 after Ku80 inhibition. The colony formation ability, apoptosis, and γH2AX(a protein marker of DNA damage) expression in Jurkat cells were investigated after Ku80 silencing and co-treated with etoposide(VP16) for 4 hours through soft agar assay, flow cytometry and Western blot, respectively. RESULTS: The mRNA level and protein expression of Ku80 were both highest in Jurkat among 6 hematological malignant cell lines. Ku80 expression was successfully down regulated in Jurkat cells after relative plasmid transfected. The proliferative ability of cells was significantly decreased after Ku80 inhibition(P < 0.05). The colony formation capacity of Jurkat cells was obviously reduced and the cells apoptosis and γH2AX expression were increased after Ku80 inhibition, with or without VP16 incubation. CONCLUSION Targeted silencing of Ku80 could enhance the sensitivity of VP16 in Jurkat cells, which might be associated with the elevated level of DNA damage accumulation.
Humans ; Ku Autoantigen/metabolism* ; Jurkat Cells ; Apoptosis/drug effects* ; Cell Proliferation ; Etoposide/pharmacology* ; DNA Damage ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Objective: To further elucidate the clinical efficacy and safety of a combination regimen based on the BTK inhibitor zebutanil bridging CD19 Chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) . Methods: Twenty-one patients with high-risk r/r DLBCL were treated with a zanubrutinib-based regimen bridging CAR-T between June 2020 and June 2023 at the Department of Hematology, Tongji Hospital, Tongji University and the Second Affiliated Hospital of Zhejiang University, and the efficacy and safety were retrospectively analyzed. Results: All 21 patients were enrolled, and the median age was 57 years (range: 38-76). Fourteen patients (66.7%) had an eastern cooperative oncology group performance status score (ECOG score) of ≥2. Eighteen patients (85.7%) had an international prognostic index (IPI) score of ≥3. Three patients (14.3%) had an IPI score of 2 but had extranodal infiltration. Fourteen patients (66.7%) had double-expression of DLBCL and seven (33.3%) had TP53 mutations. With a median follow-up of 24.8 (95% CI 17.0-31.6) months, the objective response rate was 81.0%, and 11 patients (52.4%) achieved complete remission. The median progression-free survival (PFS) was 12.8 months, and the median overall survival (OS) was not reached. The 1-year PFS rate was 52.4% (95% CI 29.8% -74.3%), and the 1-year OS rate was 80.1% (95% CI 58.1% -94.6%). Moreover, 18 patients (85.7%) had grade 1-2 cytokine-release syndrome, and two patients (9.5%) had grade 1 immune effector cell-associated neurotoxicity syndrome. Conclusion: Zanubrutinib-based combination bridging regimen of CAR-T therapy for r/r DLBCL has high efficacy and demonstrated a good safety profile.
Humans ; Middle Aged ; Receptors, Chimeric Antigen/therapeutic use* ; Retrospective Studies ; Immunotherapy, Adoptive/adverse effects* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Cell- and Tissue-Based Therapy ; Antigens, CD19/adverse effects*

Humans ; Receptors, Chimeric Antigen ; Immunotherapy, Adoptive ; Hematologic Neoplasms/therapy* ; Cell- and Tissue-Based Therapy

OBJECTIVE: To explore the effect of carvacrol on the biological behavior of leukemia cells and its regulation to circ-0008717/miR-217 molecular axis. METHODS: Human acute lymphoblastic leukemia cells Molt-4 were cultured in vitro, and different concentrations of carvacrol were added to the cells. si-NC and si-circ-0008717 were transfected into Molt-4 cells (si-NC group, si-circ-0008717 group). pcDNA, pcDNA-circ-0008717, anti-miR-NC, anti-miR-217 were transfected into Molt-4 cells and then added to carvacrol-treated cells (carvacrol+pcDNA group, carvacrol+pcDNA-circ-0008717 group, carvacrol+anti-miR-NC group, carvacrol+anti-miR-217 group). MTT, plate clone formation experiment, and flow cytometry were used to detect the viability of the cell, colony formation number, and apoptosis rate of cells, respectively. The RT-qPCR method was used to detect the expression levels of circ-0008717 and miR-217. The dual luciferase reporter gene experiment was used to detect the targeting relationship between circ-0008717 and miR-217. RESULTS: After carvacrol treatment, the cell viability decreased significantly (r=-0.9405), expression level of circ-0008717 decreased (r=-0.9117), colonies formed number decreased (r=-0.9256), while the cell apoptosis rate increased (r= 0.8464), and the expression level of miR-217 increased (r=0.9468). Compared with the si-NC group, the expression level of miR-217 in si-circ-0008717 group increased (P＜0.001), the cell apoptosis rate increased (P＜0.001), while cell viability decreased (P＜0001), the number of colonies formed decreased (P＜0.001). Compared with the carvacrol+pcDNA group, the cell viability of the carvacrol+pcDNA-circ-0008717 group increased (P＜0.001), the number of colonies formed increased (P＜0.001), while the cell apoptosis rate decreased (P＜0.001). circ-0008717 could target miR-217. The cell viability of the carvacrol+anti-miR-217 group increased (P＜0.001), and the number of colonies formed increased (P＜0.001), while the cell apoptosis rate decreased (P＜0001) as compared with the carvacrol+anti-miR-NC group. CONCLUSION Carvacrol can promote the expression of miR-217 by down-regulating the expression of circ-0008717, thereby reducing the proliferation and cloning ability of leukemia cells and promoting cell apoptosis.
Antagomirs ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cymenes ; Humans ; Leukemia ; MicroRNAs/genetics*

OBJECTIVE: To detect the expression of multiple myeloma-associated antigen (MMSA)-8 and MMSA-1 in bone marrow mononuclear cells of patients with acute myeloid leukemia, and explore their roles in acute myeloid leukemia. METHODS: A total of 83 patients with M2 acute myeloid leukemia in our hospital from January 2019 to January 2020 were selected as research group, during the same period, 15 patients diagnosed iron deficiency anemia were selected as control group. Real-time fluorescence quantitative PCR was used to detect the levels of MMSA-8 and MMSA-1 in bone marrow mononuclear cells. Patients in the research group were divided into remission and non remission according to the clinical curative effect, and were divided into good prognosis, medium prognosis, and poor prognosis according to the prognosis. The relationship between MMSA-8, MMSA-1 and clinical efficacy, prognosis was analyzed. In addition, the general data of patients in the research group were collected, including white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), and percentage of bone marrow progenitor cells at admission. Pearson method was used to analyze the correlation between MMSA-8, MMSA-1 and clinical data, and MMSA-8 and MMSA-1. RESULTS: The analysis results about mRNA levels of MMSA-8 and MMSA-1 in bone marrow mononuclear cells of patients showed that patients in the research group were significantly higher than those in the control group (P<0.05); In the research group, patients without remission were also significantly higher than those with remission, as well as those with medium and poor prognosis than with good prognosis, while only mRNA level of MMSA-1 in patients with poor prognosis was significantly higher than those with medium prognosis (P<0.05). Pearson analysis showed that MMSA-8, MMSA-1 were positively correlated with WBC (r=0.468, r=0.516), and MMSA-8 was positively correlated with MMSA-1 (r=0.318). CONCLUSION The levels of MMSA-8 and MMSA-1 in bone marrow mononuclear cells of patients with M2 acute myeloid leukemia are increased, which are closely related to the occurrence and development of the disease, and have certain value for the prognosis.
Bone Marrow ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Multiple Myeloma/genetics* ; Prognosis ; RNA, Messenger

Benign prostatic hyperplasia （BPH） model， as a carrier of BPH， is vital for exploring the pathogenesis of the disease and evaluating the efficacy of corresponding drugs. This paper reviewed the in vivo and in vitro models of BPH， the modeling principles and methods， and evaluation indicators， and analyzed the advantages and disadvantages of different types of models. At present， the BPH model is getting closer to the clinical characteristics of human BPH， providing powerful support for the evaluation of drug efficacy. Furthermore， the model has been developed towards cytology to allow further research on the pathogenesis of BPH. The relevant testing indicators reflect the core pathological changes of BPH from different levels， providing a guarantee for further exploring the pathogenesis of BPH and the development of prevention and control drugs. However， no model can fully simulate the natural development process of human BPH， and each model and evaluation criterion has its unique advantages and limitations. In terms of model evaluation， most BPH models are assessed based on benign prostate enlargement （BPE）， and there is still a lack of reliable models to simulate BPH progression and combine with bladder dysfunction. In terms of indicator evaluation， symptom-reflected behavioral indicators are absent in the replication of BPH models in animals. The study of the BPH model in traditional Chinese medicine （TCM） only focuses on the replication and investigation of the "disease" model， rather than the "syndromes" and "signs"， which cannot simulate the syndrome differentiation and treatment under the guidance of the TCM theory. In view of the above deficiencies， we should further improve the modeling method based on clinical characteristics， explore the multifactor composite models， especially those of disease-syndrome combination suitable for basic research of TCM， replicate the model closing to disease development， and optimize the evaluation indicators， which is of great theoretical and practical significance to develop drugs for effective prevention and control of BPH.