BACKGROUND:Allogeneic hematopoietic stem cell transplantation is currently the most effective method for the radical treatment of thalassemia major,but only half of patients can find compatible bone marrow or peripheral blood stem cells.Sib-derived umbilical cord blood stem cells have different characteristics from bone marrow and peripheral blood stem cells,and are a potential alternative source of hematopoietic stem cells for transplantation in patients with thalassemia major.OBJECTIVE:To investigate the therapeutic effect of human leukocyte antigen matched sibling fresh umbilical cord blood transplantation in the treatment of β-thalassemia major in children.METHODS:Forty-eight children with β-thalassemia major,including 28 males and 20 females,with a median age of 4 years old,were selected from Nanfang Hospital of Southern Medical University from June 2010 to June 2020.All of them received fresh cord blood transplantation from human leukocyte antigen matched sibling.Transplantation conditioning adopted a myeloablative regiment without anti-thymocyte globulin.A combination of cyclosporine A and mycophenolate mofetil with or without short-range methotrexate was administered for graft-versus-host disease.RESULTS AND CONCLUSION:(1)The median infused doses of total nucleated cells and CD34+cells were 8.17×107/kg and 2.40×105/kg,respectively in 48 children.The median follow-up time after cord blood transplantation was 98 months,and 44 cases were successfully engrafted.The median time to neutrophil and platelet engraftment was 28 and 31 days,respectively.Among them,37 cases were found to be donor-type complete chimerism detected as evidence of implantation after transplantation,7 cases were found to be stable mixed chimerism.(2)Among the 44 children with successful implantation,four patients developed acute graft-versus-host disease,and were scored as grade Ⅰ(n=2)and grade Ⅱ(n=2).All the affected organs were skin,and no chronic graft-versus-host disease occurred.(3)After umbilical cord blood transplantation,cytomegalovirus infection and activation occurred in 5 of the 48 cases,sepsis in 12 cases,invasive fungal disease in 3 cases,stomatitis in 21 cases,hemorrhagic cystitis in 8 cases,and hepatic vein occlusion in 1 case.(4)Among 48 children,47 patients survived;1 died of severe pneumonia combined with acute heart failure 28 days after transplantation;43 survived without disease;3 had primary implantation failure,and 1 had pancytopenia after transplantation.The 5-year probabilities of overall survival and disease-free survival were 98％and 89％,respectively.The cumulative incidence of transplant-related deaths at 1 year was 2.1％.(5)The above results indicate that human leukocyte antigen matched sibling fresh umbilical cord blood transplantation is effective in the treatment of β-thalassemia major in children with a low incidence of graft-versus-host disease.

Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC50=5.41 nM)than that of tubastatin A(TubA)(IC50=15.11 nM),along with a favorable subtype selectivity profile(selectivity index ≈ 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC50=2.59 μM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

Objective To investigate the effect of tirofiban combined with oxiracetam on acute anterior circulation progressive cerebral infarction.Methods A total of 171 patients with acute anteri-or circulation progressive cerebral infarction from October 2022 to January 2024 were enrolled and ran-domly divided into three groups using a random number table.The control group of 57 patients re-ceived conventional treatment,the observation group A received tirofiban in addition to conventional treatment,and the observation group B received oxiracetam on the basis of observation group A's treat-ment.The effectiveness indicators[including the rates of neurological improvement and neurological deterioration at 14 days after treatment,the rate of good prognosis and modified Rankin Scale(MRS)scores at 90 days after treatment,as well as the National Institutes of Health Stroke Scale(NIHSS)scores at 7 and 14 days after treatment and their differences from baseline],cognitive function[as-sessed using the Montreal Cognitive Assessment(MOCA)],and safety indicators(incidence rates of symptomatic intracranial hemorrhage,fatal intracranial hemorrhage,and mortality at 90 days after treat-ment)were compared among the three groups.Results There were no statistically significant differ-ences in the rates of neurological improvement and neurological deterioration at 14 days after treatment,the rate of good prognosis,and MRS scores at 90 days after treatment among the three groups(P＞0.05).There were statistically significant differences in NIHSS scores between baseline and 7 and 14 days after treatment in all three groups(P＜0.05),and the differences in NIHSS scores from baseline at the above time points were higher in observation group B than in observation group A and the control group(P＜0.05).There were no statistically significant differences in MOCA scores among the three groups before treatment(P＞0.05);however,the MOCA scores in the observation group B were higher than those in observation group A and the control group at 14,30,and 90 days after treatment(P＜0.05).There were no statistically significant differences in the incidence rates of symptomatic intracranial hemorrhage,fatal intracranial hemorrhage,and mortality at 90 days after treatment among the three groups(P＞0.05).Conclusion Tirofiban combined with oxiracetam can improve cognitive function in patients with acute anterior circulation progressive cerebral infarc-tion without increasing the risk of hemorrhage,and has better prognosis.

Mitochondria, ubiquitous energy-producing organelles in eukaryotic cells, can have their normal functions disrupted by bacterial infections, leading to mitochondrial dysfunction. This dysfunction is closely associated with inflammatory diseases. Periodontitis, a chronic inflammatory disorder of periodontal tissues caused by pathogenic microorganisms, has been increasingly linked to mitochondrial dysfunction in its pathogenesis and progression. Compared to healthy periodontal tissues, inflammatory lesions exhibit more pronounced mitochondrial dysfunction—a pathological process that is strongly correlated with periodontal pathogen infection. Studies reveal that these pathogens disrupt mitochondrial homeostasis in host cells (e.g., gingival epithelial cells and fibroblasts) through multiple mechanisms, including disrupting mitochondrial biogenesis, altering mitochondrial dynamics (promoting excessive fission), inhibiting mitophagy, impairing mitochondrial dysfunction-associated apoptosis, and inducing endogenous oxidative stress, which upregulates pro-inflammatory cytokines. Collectively, these processes drive the establishment and persistence of an inflammatory microenvironment. This review explores how periodontal pathogens affect mitochondrial function and their mechanistic contributions to periodontitis progression, with the goal of providing novel insights for developing mitochondria-targeted therapeutic strategies.

The Screening Tool of Older Persons' Prescriptions(STOPP)and the Screening Tool to Alert to Right Treatment(START)play a crucial role in identifying potentially inappropriate prescriptions among the elderly.As the aging population continues to grow, there is an urgent need for effective tools to address the challenges of multimorbidity and polypharmacy in elderly patients in China.However, the development of rational medication screening tools has significantly lagged, and there is currently a lack of sensitive and effective instruments in China.This article analyzes the newly added entries in the third edition of STOPP/START, aiming to provide a reference for managing multiple medication regimens and for the development of relevant tools for elderly patients in China.

General practice standardized residency training is a crucial part of postgraduate education for cultivating general practitioner. The factors influencing the quality of general practice residency training cover various aspects such as the residents themselves, teaching staff, management and decision-making levels, as well as teaching resources. Guided by the goal of "fostering virtue through education", and integrated the spirit of Norman Bethune and modern innovation theories and the educational philosophy, the China-Japan Union Hospital of Jilin University has carried out comprehensive reforms in this field. It has constructed a PDCA cycle management system based on the concept of total quality management to improve the quality of education from multiple links such as quality planning and process monitoring. In terms of faculty development, based on the dissipative structure theory, a mechanism of "selection, evaluation, incentive, and elimination" has been established. Teacher communities have been formed and a training college has been established to strengthen the teaching team. In terms of platform construction, the linkage between "teaching base-community" and "on campus-off campus" has been strengthened and resources have been integrated. The reform has achieved remarkable results, and our practice may provide a reference for general practice medical education.

Over the past 40 years,prenatal ultrasound in China has undergone a transformative evolution,from basic grayscale imaging to the integration of artificial intelligence(AI).Initial efforts focused on identifying major fetal anomalies and establishing standardized screening systems.In subsequent decades,advances such as 3D/4D imaging,quantitative diagnostic models and multimodal approaches enhanced the accuracy and scope of assessments.Recently,the emergence of AI-driven diagnostics,early trimester screening and multi-omics integration have ushered Chinese prenatal ultrasound into an era of precision and intelligence.Chinese scholars have not only adopted global innovations,but also contributed original,locally adapted solutions and multidisciplinary frameworks.Looking ahead,future development will emphasize intelligent assistance,equitable access,evidence-based systems,and cross-disciplinary integration-driving continued improvement in birth defect prevention and maternal-fetal health.

Objective: To analyze the status and trends of physical fitness test data among college freshmen with different body mass index (BMI) groups from 2014 to 2024, providing the scientific evidence for monitoring and intervening in college students physical health. Methods: A census was conducted on all 67 949 freshmen at Civil Aviation University of China from 2014 to 2024. Physical tests included vital capacity, sit and reach, sit ups, 50 m sprint, standing long jump, pull ups, and 800 m/1 000 m run. Freshmen were divided into underweight, normal weight, overweight and obese groups according to WHO BMI standards. The Kruskal-Wallis H test was used to compare differences in physical fitness indicators across gender and BMI groups, while the Mann-Kendall trend test was employed to detect upward or downward trends in physical indicators over time. Results: From 2014 to 2024, statistically significant differences were observed in vital capacity, 50 m sprint, standing long jump, and sit and reach among different BMI groups for both genders (boy: Z =2 396.40, 4 160.33, 4 662.23, 531.85; girl: Z =593.37, 308.86, 499.37, 128.70). Significant differences were also found in 1 000 m run and pull ups for boys, and 800 m run and sit ups for girls across BMI groups (boy: Z =6 574.80, 6 880.48; girl: Z =528.56, 146.18) ( P <0.01). Overall physical test scores showed a declining trend during 2014-2024, particularly pronounced in overweight and obese groups. Male vital capacity in 2014 exceeded national survey data( d =320 mL), with the gap widening to 734 mL by 2019, while the female vital capacity difference increased from 271 mL in 2014 to 576 mL in 2019. Male 1 000 m run times were 23.0 s and 17.5 s faster than national data in 2014 and 2019 respectively, while female 800 m run times were 22.3 s and 21.5 s faster than corresponding national data. Conclusions Physical health status among freshmen at this university varies across BMI groups and changes over time. Although overall test scores remain higher than national levels, the declining trend in physical fitness performance requires attention.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome