OBJECTIVES: Metastasis is the primary cause of death in osteosarcoma, and current clinical treatments remain limited. BRD4, a key epigenetic regulator, has shown therapeutic promise in various cancers through its inhibition. However, the mechanistic role of BRD4 in osteosarcoma remains poorly understood. This study aims to elucidate the molecular mechanisms by which BRD4 regulate osteosarcoma progression and to explore novel therapeutic strategies. METHODS: Immunofluorescence was used to assess BRD4 expression levels in a tissue microarray containing 80 osteosarcoma samples from different patients. The Gene Expression Omnibus (GEO) dataset (GSE42352, containing survival data from 88 osteosarcoma patients) was downloaded to perform Kaplan-Meier survival analysis based on BRD4 gene expression levels. In vivo, an orthotopic intramedullary osteosarcoma model was established using HOS cells in C57 mice, followed by treatment with varying doses of the BRD4 inhibitor (+)-JQ1. Micro-CT, 3D reconstruction of bone tissue, and HE staining were employed to evaluate pathological changes in bone and intestinal lymph nodes. In vitro, cell viability was measured using the methyl thiazolyl tetrazolium (MTT) assay, while colony formation and Transwell assays assessed proliferative and invasive capacities. Chromatin-bound BRD4 was analyzed via co-immunoprecipitation combined with mass spectrometry (Co-IP/MS), and O-GlcNAc glycosylation sites and glycan chains of BRD4 were identified using Co-IP with Nano-LC MS/MS. Real-time PCR and Western blotting were used to analyze the relative mRNA and protein expression levels of target genes, respectively. RESULTS: BRD4 was positively expressed in 61.25% (49/80) of osteosarcoma tissues. Patients with high BRD4 expression exhibited significantly shorter survival times (P<0.05). In the orthotopic mouse model, intervention with (+)-JQ1, a potent and commonly used BETi, significantly inhibited tumor growth in vivo and reduced bone destruction (P<0.05). (+)-JQ1 treatment significantly suppressed the proliferation (P<0.001), invasion (P<0.001), and migration (P<0.05) of HOS cells. In osteosarcoma cells, BRD4 exhibited O-GlcNAc modifications at both N- and C- C-termini, particularly at Thr73, which is essential for protein stability. This modification also contributed to the activation of the EGFR tyrosine kinase inhibitor resistance pathway (KEGG Pathway: hsa01521). (+)-JQ1 treatment displaced BRD4 from enhancers and downregulated the transcription of pathway-related genes, such as EGFR and PDGFC, thereby suppressing the malignant behavior of osteosarcoma cells. CONCLUSIONS BRD4 promotes osteosarcoma progression via O-GlcNAc modification at Thr73 and plays a crucial role in tumor growth and metastasis.
Osteosarcoma/drug therapy* ; Humans ; Transcription Factors/metabolism* ; Animals ; Cell Cycle Proteins ; Mice ; Bone Neoplasms/drug therapy* ; Azepines/pharmacology* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Triazoles/pharmacology* ; Mice, Inbred C57BL ; Nuclear Proteins/metabolism* ; Gene Expression Regulation, Neoplastic ; Male ; Bromodomain Containing Proteins

Objective To analyze the allocation efficiency of medical and health resources in 26 tertiary hospitals in Suzhou from 2017 to 2022 and perform quantitative analysis in order to provide suggestions for relevant departments to rationally coordinate the health resources allocation,regional health planning and hospital management.Methods The number of health technicians,the number of beds in health institutions and the total health expenditure were selected as input indicators,while the number of diagnostic and treatment visits and the number of discharged patients were selected as output indicators.The efficiency was measured by the SBM(Slack-Based Measure)model and the SBM window model respectively.Results Influenced by public health emergencies,the allocation efficiency of medical resources in tertiary hospitals in Suzhou city decreased first and then started to increase Under the two models,the average efficiency scores of 26 hospitals were 0.687 and 0.707,respectively.Notably,under the SBM window model,19 hospitals(73％)achieved efficiency scores near or above the average.Conclusion The two models present a conclusion that the overall efficiency of the tertiary hospitals in Suzhou is generally effective.To further enhance the allo-cation and utilization of medical resources,it is suggested that a comprehensive consideration of health needs guide the planning of medical resource distribution.Leveraging information technology to innovate medical service models,and strengthening internal de-velopment and management practices are essential strategies for promoting high-quality development in tertiary hospitals.

Objective:To investigate the urodynamic characteristics in Parkinson's disease(PD)versus multiple system atrophy(MSA)patients with lower urinary tract symptoms(LUTS).Methods:We performed a retrospective study in PD and MSA patients admitted to the First Affiliated Hospital of Zhengzhou University and undergone urodynamic examinations from January 2016 to June 2019.A total of 178 patients, mean age(59.2±9.7)years were enrolled, with 64 PD patients, 74 MSA patients and 40 normal controls.Urodynamic parameters included maximum flow rate(Qmax), post-voided residual urine volume(PVR), bladder compliance(BC), overactive bladder(OAB), maximum cystometric capacity(MCC)and detrusor pressure at maximum flow rate(PdetQmax). Bladder function was assessed.Results:Frequent urination(68.8%)was the most common LUTS in PD patients, as opposed to urinary retention(91.9%)in MSA patients.The Qmax, PdetQmax and incidence of OAB were higher and the PVR were lower in PD patients than in MSA patients [free-flow(FF)-Qmax: (13.5±7.1)ml/s vs.(10.1±5.2)ml/s, U=26.98, P<0.01]; pressure-flow study(PFS)-Qmax: [(13.6±5.7)ml/s vs.(10.5±3.3)ml/s, U=34.90, P<0.01]; PFS-PdetQmax: [(23.9±11.3)cm H 2O vs.(16.3±8.6)cmH 2O, U=35.04, P<0.01]; OAB: (46.9% vs.27.0%, χ2=5.85, P<0.01); FF-PVR: [(30.4±20.0)ml vs.(161.7±79.8)ml, U=-71.81, P<0.01]; PFS-PVR: [(65.9±30.7)ml vs.(212.6±83.0)ml, U=-65.29, P<0.01]. Compared with the control group, the incidences of OAB and PFS-PVR were increased and the MCC and PdetQmax were decreased in the PD group(OAB: 46.9% vs.7.5%, χ2=6.15, P<0.018); PFS-PVR: [(65.9±30.7)ml vs.(22.2±10.4)ml, U=47.25, P<0.01]; MCC: [(305.1±79.7)ml vs.(389.6±65.2)ml, U=-52.13, P<0.01]; PdetQmax: [(23.9±11.3)cmH 2O vs.(37.3±10.3)cmH 2O, U=-49.88, P<0.01]. Compared also with the control group, the MSA group had a lower Qmax, PdetQmax and MCC, FF-Qmax: [(10.1±5.2)ml/s vs.(16.3±4.7)ml/s, U=-50.11, P<0.01]; PFS-Qmax: [(10.5±3.3)ml/s vs.(13.1±5.0)ml/s, U=-27.54, P<0.05]; PdetQmax: [(16.3±8.6)cmH 2O vs.(37.3±10.3)cmH 2O, U=-84.92, P<0.01]; MCC: [(284.3±71.8)ml vs.(389.6±65.2)ml, U=-39.31, P<0.01], a higher PVR, lower bladder compliance(BC)and a higher incidence of OAB(FF-PVR: [(161.7±79.8)ml vs.(22.0±13.0)ml, U=84.82, P<0.01]; PFS-PVR: [(212.6±83.0)ml vs.(22.2±10.4)ml, U=112.54, P<0.01]; BC: (28.4% vs.7.5%, χ2=6.81, P<0.01); OAB: (27.0% vs.7.5%, χ2=17.62, P<0.01). Conclusions:PD and MSA patients with LUTS have bladder dysfunction.MSA patients have more serious bladder dysfunction than PD patients.

Objective: To investigate the sex- and age-specific association between resting heart rate and hypertension in rural adult residents of Henan province. Methods: At baseline, a total of 20 194 participants were randomly selected from Xin'an County of Henan province between July 2007 and August 2008. After excluding participants with hypertension or without resting heart rate data at baseline, and participants died or without hypertension outcome or diagnosed as gestational hypertension during follow-up between July 2013 and October 2014, 10 212 participants were finally included in this study. Multiple linear regression model was used to examine the association between resting heart rate and change of blood pressure. Logistic regression model was used to estimate the association between resting heart rate and risk of hypertension. Results: There were 2 059 new hypertensive cases (839 male) during the 6 years follow-up. After controlling for potential confounders, per 5 beats/minutes increases in resting heart rate was associated with 0.18 mmHg (1 mmHg=0.133 kPa) (95%CI 0.01-0.36 mmHg, P=0.046) absolute increase in systolic blood pressure and 7% higher risk of developing hypertension in women (95%CI 1.03-1.11, P<0.05). Compared with resting heart rate<70 beats/minutes, the adjusted RRs for 76-82 and>82 beats/minutes groups were 1.39 (95%CI 1.18-1.63, P<0.05) and 1.22 (95%CI 1.02-1.45, P<0.05), respectively. For both age groups, increased resting heart rate was positively associated with risk of hypertension in women(RR=1.05(95% CI 1.01-1.10), P<0.05 (the women those <60 years); RR=1.14(95% CI 1.04-1.25), P<0.05 (the women those≥60 years). However, no significant association was found between resting heart rate and hypertension in male residents. Conclusions: Increased resting heart rate is associated with high risk of hypertension in women who live in rural area, especially in elder women of this cohort.
Adult ; Blood Pressure ; Cohort Studies ; Female ; Heart Rate ; Humans ; Hypertension ; Male ; Risk Factors ; Rural Population

With the advancement and development of life science and technology,many problems in liver surgery have been solved,and the surgical procedures of liver surgery have been continuously developed and the indications for surgery have been continuously expanded.Benign and malignant lesions and even donor liver can be performed under laparoscopy.The indications for laparoscopic liver resection are expanding,from superficial liver resection to a wider range of anatomical resection.At the same time of technological advancement,along with the development of the humanistic spirit,liver resection is not only the removal of lesions,but the pursuit of rehabilitation,which is "the best rehabilitation with minimal trauma".Laparoscopic liver resection has been greatly developed due to the spread of the concept of "precise medicine".

Objective To investigate the effect of active immunization on prevention of post-transplantation de novo hepatitis B virus (HBV) infection in patients receiving liver grafts from hepatitis B core antibody (HBcAb) positive donors.Methods A retrospective analysis was conducted. Eighty-seven children undergoing liver transplantation from HBcAb positive donors admitted to Tianjin First Center Hospital from October 2012 to December 2016 were enrolled, and the data of donors and recipients were collected. The hepatitis B vaccine was given before operation for hepatitis B surface antibody (HBsAb) >1000 U/L; hepatitis B immunoglobulin (HBIG) 100 U/kg was given during the operation, in order to prevent children from HBV infected by obtaining passive immunity quickly, children with HBsAb< 200 U/L after operation were injected with hepatitis B vaccine for booster immunization. HBV markers and liver function of recipients were determined before liver transplantation and during the follow-up, which up to April 2017. According to the children got de novo HBV infection after operation or not, the preventive effect of active immunization before and after transplantation operation on HBV infection was analyzed and compared.Results In 87 children who received HBcAb positive donor livers, 9 (10.3％) developed de novo HBV infection, which occurred in 16 (10, 25) months after liver transplantation. Among the 9 children with HBV infection, 7 children had HBsAb < 1000 U/L before the operation, the ratio was statistically increased as compared with the children without HBV infection [77.8％ (7/9) vs. 37.2％ (29/78),P < 0.05]. After the transplantation, 62 children of 78 without HBV infection showed a good response to hepatitis B vaccination, 1 child after inoculation of hepatitis B vaccine, the titer of HBsAb was still less than 200 U/L, 15 children without administration of hepatitis B vaccine, only with HBIG injection for prevention. The HBsAb of children with de nove HBV infection were less than 200 U/L after operation, the ratio was significantly increased as compared with children without HBV infection [100.0％ (9/9) vs. 20.5％ (16/78),P < 0.01].Conclusions The establishment of active immunization method can effectively prevent children with de novo HBV infection occurred inpediatric recipients from HBcAb positive donors with preventive treatment.

[Objective]To explore the intermediate result of the use of allograft grafting for bone defects in revision total hip arthroplasty.[Methods]A retrospective study was carried out on 22 patients(22 hips) with the use of allograft grafting for bone defects in revision of total hip arthroplasty from April 2000 to April 2005.There were 13 male and 9 female with mean age of 65.5 years.According to the AAOS system,the bone defects in acetabulum were classified into type I in 5 hips,type II 14 hips and type III 3 hips,and on the femoral side,they were classified into type I in 3 hips,type II 12 hips and type III 2 hips.The reconstruction of bone defects in acetabulum contained structural bone graft in 5 hips,impaction bone graft in 12 hips,and metal wire mesh with bone graft in 5 hips.On the femoral side,3 hips were dealed with structural bone graft,12 hips were done with impaction bone graft,and 2 hips were repaired by metal wire mesh with bone graft.Harris Hip Score System and radiography were used to evaluate the clinical efficiency.[Results]The mean follow-up time was 61 months(37～97 months).Harris score improved from 45 points(30～65) pre-revision to 86 points(62～96) at the final follow-up.Insion drainage occurred in one hip.One patient remain slight pain in hip.No prothesis loosening,radiolucent lines were observed during the follow-up.None need to second revision.[Conclusion]During the THA revision surgery,adopting suitable allografts to repair the different types of bone defects is feasible and the mid-term result is good.