Objective To explore the protective effect of exercise-induced metabolite-3 (EIM-3) on myocardial ischemia-reperfusion (I/R) injury and explore its underlying molecular mechanisms. Methods The physicochemical properties and half-life of EIM-3 were analyzed using the Human Metabolome Database (HMDB, https://hmdb.ca/). A primary rat cardiomyocyte hypoxia/reoxygenation (H/R) injury model was established. Cell apoptosis and viability were assessed using TUNEL assay and cell counting kit-8, respectively. Lactate dehydrogenase (LDH) levels in the cell culture supernatant were measured. Intracellular reactive oxygen species (ROS) levels were detected. Transcriptomic analysis was performed to identify potential signaling pathways and targets of EIM-3. Results Plasma levels of EIM-3 were elevated post-exercise. EIM-3 was characterized as a phospholipid small-molecule compound with a partition coefficient (logP) of 5.58 and a solubility (logS) of −7.6, indicating favorable lipophilicity and cell membrane permeability. In cardiomyocytes H/R injury modles, EIM-3 significantly inhibited apoptosis, increased cell viability, reduced intracellular ROS levels, and decreased LDH release (P＜0.01). Transcriptomic analysis suggested that EIM-3 exerts its protective function potentially by regulating glucose metabolim. Quantitative real-time polymerase chain reaction results confirmed that EIM-3 significantly upregulated the transcriptional level of pyruvate kinase M2 (PKM2) in a dose-dependent manner (P＜0.001). Conclusions EIM-3 protects cardiomyocytes against I/R injury by modulating glucose metabolim. This study provides foundational insights into the mechanisms underlying exercise-induced cardioprotection.

BACKGROUND: The achievement of an optimal return to sport (RTS) has remained a key goal after sports-related injuries, with the ongoing debate on the effectiveness of different surgical approaches for anterior cruciate ligament (ACL) rupture. This study aims to assess clinical outcomes and RTS across various surgical methods, such as anatomical single-bundle reconstruction (ASBR), central-axial single-bundle reconstruction (CASBR), and double-bundle reconstruction (DBR). METHODS: A randomized clinical trial was conducted, comprising 191 patients who underwent ACL rupture. These patients were divided into three groups based on the ACL reconstruction techniques they received (ASBR, CASBR, DBR). Over the 2-year follow-up period, the study assessed RTS through four single-hop tests, isokinetic extension tests, and limb asymmetry indices. Postoperative graft status was determined using the signal-to-noise quotient (SNQ), while knee function was evaluated using the International Knee Documentation Committee 2000 (IKDC-2000) score, Lysholm score, Tegner score, and degree of knee laxity. A binary logistic regression model was developed to forecast the factors influencing ideal RTS. RESULTS: DBR (67.63%) and CASBR (58.00%) exhibited higher RTS passing rates compared to ASBR (30.39%; χ2 = 19.57, P <0.05). Quadriceps strength symmetry in the lower limbs was identified as the key determinant of RTS ( χ2 = 17.08, P <0.05). The RTS rate was influenced by SNQs of the graft's tibial site (odds ratio: 0.544) and quadriceps strength of the reconstructed knee joint at 60°/s (odds ratio: 6.346). Notably, the DBR group showed enhanced knee stability, evidenced by superior results in the Lachman test ( χ2 = 13.49, P <0.01), objective IKDC-2000 ( χ2 = 27.02, P = 0.002), and anterior instability test ( χ2 = 9.46, P <0.01). Furthermore, DBR demonstrated superior clinical outcomes based on the Lysholm score (DBR: 89.57 ± 7.72, CASBR: 83.00 ± 12.71, ASBR: 83.21 ± 11.95; F = 10.452, P <0.01) and IKDC-2000 score (DBR: 90.95 ± 7.00, CASBR: 84.64 ± 12.68, ASBR: 83.63 ± 11.41; F = 11.78, P <0.01). CONCLUSION: For patients with ACL rupture, more ideal RTS rate and clinical outcomes were shown in the DBR group than in the ASBR and CASBR groups. Autograft status and quadriceps strength are postively related to RTS. TRIAL REGISTRATION ClinicalTrials.gov (NCT05400460).
Humans ; Anterior Cruciate Ligament Reconstruction/methods* ; Male ; Female ; Adult ; Anterior Cruciate Ligament Injuries/surgery* ; Young Adult ; Return to Sport ; Adolescent ; Anterior Cruciate Ligament/surgery* ; Treatment Outcome

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective:To evaluate the healthcare accessibility and quality of diagnosis and treatment services of Internet hospitals in China.Methods:One hundred and eighty Internet hospitals in 60 cities were seleted based on the sampling of development levels in the eastern, central and western regions of China. From April to May 2023, standardized patients methodology was applied to evaluate the accessibility(including the number of Internet hospitals, functional settings, online doctor status, the doctor′s attending rate and consultation fees) and diagnosis and treatment service quality(including the diagnosis and treatment services quality, response speed and patient′s evaluation) of Internet hospitals.Results:The average opening rate of Internet hospitals in China was 52.9% (560/1 058), the average online rate of doctors was 64.2% (1 099/1 713), the average doctor′s attending rate was 33.6% (112/333), the average consultation fee was 4.85 yuan, the average score of consultation was 1.92 out of 9, the average score of diagnosis and treatment was 1.12 out of 4, the average score of the response speed was 1.70 out of 3, and patient satisfaction was 2.73 out of 3.Conclusions:The Internet hospital accessibility in China is unevenly developed, and the overall quality of diagnosis and treatment is low. It is recommended to accurately position and optimize the function of Internet hospital, establish the incentive mechanism for online consultation doctors, construct and improve the regulatory system of Internet hospital diagnosis and treatment, so as to improve the accessibility and quality of diagnosis and treatment of Internet hospitals.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood. Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival. Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group.Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity. Conclusions The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood. Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival. Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group.Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity. Conclusions The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood. Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival. Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group.Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity. Conclusions The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.

Objective:To investigate the risk factors for early complications after laparoscopy-assisted gastrectomy in patients with gastric cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 196 patients who underwent laparos-copy-assisted radical gastrectomy at Peking Union Medical College Hospital from March 2016 to March 2019 were collected. There were 144 males and 52 females, aged (61±10)years. Observation indicators: (1) early complications after laparoscopy-assisted radical gastrectomy and treatment; (2) analysis of risk factors for early complications after laparoscopy-assisted radical gastrectomy.Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( P25,P75). Count data were represented as absolute numbers. Univariate analysis was conducted using the t test, Mann-Whitney U test or chi-square test. Multivariate analysis was conducted using the Logistic regressional model. Results:(1) Early complications after laparoscopy-assisted radical gastrectomy and treatment: 51 of 196 patients had early postoperative complications, including 7 cases of grade Ⅰ according to Clavien-Dindo classi-fication system, 32 cases of grade Ⅱ, 9 cases of grade Ⅲa, 3 cases of grade Ⅲb. There was no grade Ⅳ or Ⅴ complication. There were 25 cases with abdominal complications, 7 cases with thoracic complications, 3 cases with internal/catheter related complications and 16 cases with other unclassified complications. All patients with complications were improved after symptomatic and supportive treatments. (2) Analysis of risk factors for early complications after laparoscopy-assisted radical gastrectomy: results of univariate analysis showed that the lymphocyte count, neutrophil-to-lymphocyte ratio, radiotherapy, operation time, volume of intraoperative blood loss, T stage, lymph node metastasis were related factors for early complications after laparoscopy-assisted radical gastrectomy in patients with gastric cancer ( Z=?2.048, χ2=6.385, 4.168, 8.068, 6.336, 12.497, 7.522, P<0.05). Results of multivariate analysis showed that the neutrophil/lymphocyte ratio ≥1.96, operation time ≥222 minutes, and lymph node metastasis were independent risk factors for early complica-tions after laparoscopy-assisted radical gastrectomy in patients with gastric cancer ( odds ratio=2.279, 2.245, 2.226, 95% confidence interval as 1.149-4.519, 1.116-4.517, 1.125-4.402, P<0.05). Conclusions:The abdominal complications are the most common early complications after laparoscopy-assisted radical gastrectomy. The neutrophil-to-lymphocyte ratio ≥1.96, operation time ≥222 minutes, and lymph node metastasis are independent risk factors for early complications after laparoscopy-assisted radical gastrectomy in patients with gastric cancer.

Objective To study the effect of deep brain stimulation of subthalamic nucleus (STN-DBS) on non-motor symptoms (NMSs) in patients with Parkinson's disease (PD).Methods Seventeen PD patients,admitted to and accepted bilateral STN-DBS in our hospital from 2012 to 2018,were chosen in our study.Unified Parkinson's Rating Scale (UPDRS) Ⅲ and Non-motor Symptoms Scale (NMSS) were used to evaluate the motor symptoms and non-motor symptoms one week before and 12 months after surgery.The correlations of motor symptoms and non-motor symptoms with age and gender were analyzed.Results The UPDRS Ⅲ total scores of 17 patients were 33.48+10.00 one week before DBS and 10.59±6.70 one year after DBS,with statistically significant difference (P＜0.05).The NMSS total scores were 144.47±51.31 one week before DBS and 86.35±40.23 one year after DBS,with statistically significant difference (P＜0.05).There were statistically significant differences in scores of sleep and fatigue,mental and behavioral abnormalities,sensory abnormality,cognitive impairment and constipation between one week before and one year after surgery (P＜0.05).NMSS scores showed no significant correlation with gender,but showed significant correlations with age,course of disease and Hoehn-Yahr grading (P＜0.05).Conclusion Bilateral STN-DBS can significantly improve some non-motor symptoms to a certain degree.

OBJECTIVE Toinvestigatethedifferenceofcytotoxiceffectsofhydroxycamptothecin(HCPT)onhuman lungcancercelsA549andhumanembryolungfibroblastcelsMRC-5.METHODS A549celsandMRC-5celswere treated with HCPT 20-200 μmol·L-1 for 24,48 and 72 h,or pulse treated with HCPT 50-400 μmol·L-1 for 24 h along with 5 d release.cellsurvival was detected by MTT assay.Morphological changes for both types of cells were observed under an inverted phase-contrast microscope.cellcycle and apoptosis in both cells treated with HCPT 50 μmol·L-1 for 48 h weredeterminedbyflowcytometry.RESULTS HCPT20-200μmol·L-1inhibitedthesurvivalofbothcelsinaconcen-tration-dependent manner and more cytotoxicity was observed in A549 cells for 48 h.The concentration-effect correlation coefficient(r)of HCPT in A549 and MRC-5 cells for 48 h was 0.898 (P=0.015)and 0.996 (P=2.56E-5)respectively. The inhibition rates were significantly different between A549 and MRC-5 cells with treatment of HCPT 20,50,80,1 00, 1 60 and 200 μmol·L-1 for 48 h (P<0.05).The IC50 of HCPT on A549 and MRC-5 cells was (24.00 ±0.69)μmol·L-1 and (1 23.63 ±3.89)μmol·L-1 respectively,indicating that A549 cells were 5-fold more sensitive to HCPT than MRC-5 cells at 48 h.After exposure to HCPT 50 μmol·L-1 for 48 h,some A549 cells were rounded up and shrank dramatical y, and some cells underwent membrane blebbing or lysing while MRC-5 cells had no obvious changes.cellcycle and apop-tosis analysis showed that A549 cells were arrested at both S and G2/M phases and apoptosis occurred but MRC-5 cells were just arrested at S phase.In the recovery growth curve,the growth of A549 cells was inhibited to a larger extent than MRC-5 cells and the growth retardation stil existed for 24 h in both cells.The survival of MRC-5 cells was faster than that ofA549cels,althoughtherewasnocompleterecoveryineithercel.CONCLUSION A549celsaremoresensitiveto HCPT than MRC-5 cells due to the fact that HCPT induces cellcycle arrest at both S and G2/M phases and apoptosis in A549 cells,but only triggers S phase arrest in the MRC-5 cells.