Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and is characterized by primary left ventricular hypertrophy usually caused by mutations in sarcomere genes. The mechanism underlying cardiac remodeling in HCM remains incompletely understood. An investigation of HCM through integrative analysis at multi-omics levels will be helpful for treating HCM. DNA methylation and chromatin accessibility, as well as gene expression, were assessed by nucleosome occupancy and methylome sequencing (NOMe-seq) and RNA-seq, respectively, using the cardiac tissues of HCM patients. Compared with those of the controls, the transcriptome, DNA methylome, and chromatin accessibility of the HCM myocardium showed multifaceted differences. At the transcriptome level, HCM hearts returned to the fetal gene program through decreased sarcomeric and metabolic gene expression and increased extracellular matrix gene expression. In the DNA methylome, hypermethylated and hypomethylated differentially methylated regions were identified in HCM. At the chromatin accessibility level, HCM hearts showed changes in different genome elements. Several transcription factors, including SP1 and EGR1, exhibited a fetal-like pattern of binding motifs in nucleosome-depleted regions in HCM. In particular, the inhibition of SP1 or EGR1 in an HCM mouse model harboring sarcomere mutations markedly alleviated the HCM phenotype of the mutant mice and reversed fetal gene reprogramming. Overall, this study not only provides a high-precision multi-omics map of HCM heart tissue but also sheds light on the therapeutic strategy by intervening in the fetal gene reprogramming in HCM.
Cardiomyopathy, Hypertrophic/metabolism* ; Humans ; Animals ; DNA Methylation ; Mice ; Transcriptome ; Chromatin/genetics* ; Early Growth Response Protein 1/metabolism* ; Male ; Epigenome ; Nucleosomes/genetics* ; Female ; Middle Aged ; Disease Models, Animal ; Adult

OBJECTIVE: We aimed to understand the willingness and barriers to the acceptance of tuberculosis (TB) preventive treatment (TPT) among people with latent TB infection (LTBI) in China. METHODS: A multicenter cross-sectional study was conducted from May 18, 2023 to December 31, 2023 across 10 counties in China. According to a national technical guide, we included healthcare workers, students, teachers, and others occupations aged 15-65 years as our research participants. RESULTS: Overall, 17.0% (183/1,077) of participants accepted TPT. There were statistically significant differences in the acceptance rate of TPT among different sexes, ages, educational levels, and occupations ( P < 0.05). The main barriers to TPT acceptance were misconceptions that it had uncertain effects on prevention (57.8%, 517/894), and concerns about side effects (32.7%, 292/894). CONCLUSION An enhanced and comprehensive understanding of LTBI and TPT among people with LTBI is vital to further expand TPT in China. Moreover, targeted policies need to be developed to address barriers faced by different groups of people.
Humans ; China/epidemiology* ; Adult ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Young Adult ; Adolescent ; Aged ; Latent Tuberculosis/prevention & control* ; Patient Acceptance of Health Care ; Tuberculosis/prevention & control* ; Antitubercular Agents/therapeutic use* ; Health Knowledge, Attitudes, Practice

Humans ; Artificial Intelligence ; Lung Neoplasms/pathology* ; Mediastinum/pathology* ; Lymph Nodes/pathology* ; Neoplasm Staging ; Lymph Node Excision

OBJECTIVE: To compare the effectiveness of posterolateral approach lumbar interbody fusion assisted by one-hole split endoscope (OSE) and traditional posterior lumbar interbody fusion (PLIF) in the treatment of L_{4, 5} degenerative lumbar spondylolisthesis (DLS). METHODS: The clinical data of 58 patients with DLS who met the selection criteria admitted between February 2020 and March 2022 were retrospectively analyzed, of which 26 were treated with OSE-assisted posterolateral approach lumbar interbody fusion (OSE group) and 32 were treated with PLIF (PLIF group). There was no significant difference between the two groups in terms of gender, age, body mass index, Meyerding grade, lower limb symptom side, decompression side, stenosis type, and preoperative low back pain visual analogue scale (VAS) score, leg pain VAS score, Oswestry disability index (ODI), and the height of the anterior and posterior margins of the intervertebral space (P>0.05). The operation time, intraoperative blood loss, postoperative hospital stay, and complications were compared between the two groups. The low back pain and leg pain VAS scores and ODI before operation, at 1 month, 6 months after operation, and last follow-up, the height of anterior and posterior margins of the intervertebral space before operation, at 6 months after operation, and last follow-up, the modified MacNab criteria at last follow-up after operation were used to evaluate the effectiveness; and the Bridwell method at last follow-up was used to evaluate the interbody fusion. RESULTS: Both groups successfully completed the operation. Compared with the PLIF group, the OSE group showed a decrease in intraoperative blood loss and postoperative hospital stay, but an increase in operation time, with significant differences (P<0.05). In the OSE group, no complication such as nerve root injury and thecal sac tear occurred; in the PLIF group, there were 1 case of thecal sac tear and 1 case of epidural hematoma, which were cured after conservative management. Both groups of patients were followed up 13-20 months with an average of 15.5 months. There was no complication such as loosening, sinking, or displacement of the fusion cage. The low back pain and leg pain VAS scores, ODI, and the height of anterior and posterior margins of the intervertebral space at each time point after operation in both groups were significantly improved when compared with those before operation (P<0.05). Except for the VAS score of lower back pain in the OSE group being significantly better than that in the PLIF group at 1 month after operation (P<0.05), there was no significant difference in all indicators between the two groups at all other time points (P>0.05). At last follow-up, both groups achieved bone fusion, and there was no significant difference in Bridwell interbody fusion and modified MacNab standard evaluation between the two groups (P>0.05). CONCLUSION OSE-assisted posterolateral approach lumbar interbody fusion for L_{4, 5} DLS, although the operation time is relatively long, but the postoperative hospitalization stay is short, the complications are few, the operation is safe and effective, and the early effectiveness is satisfactory.
Humans ; Spondylolisthesis/surgery* ; Low Back Pain/surgery* ; Retrospective Studies ; Lumbosacral Region ; Blood Loss, Surgical ; Endoscopes

BACKGROUND: Preoperative diagnosis and differential diagnosis of small solid pulmonary nodules are very difficult. Computed tomography (CT), as a common method for lung cancer screening, is widely used in clinical practice. The aim of this study was to analyze the clinical data of patients with malignant pulmonary nodules and intrapulmonary lymph nodes in the clinical diagnosis and treatment of <1 cm solid pulmonary nodules, so as to provide reference for the differentiation of the two. METHODS: Patients with solid pulmonary nodules who underwent surgery from June 2017 to June 2020 were analyzed retrospectively. The clinical data of 145 nodules (lung adenocarcinoma 60, lung carcinoid 2, malignant mesothelioma 1, sarcomatoid carcinoma 1, lymph node 81) were collected and finally divided into two groups: lung adenocarcinoma and intrapulmonary lymph nodes, and their clinical data were statistically analyzed. According to the results of univariate analysis (χ² test, t test), the variables with statistical differences were selected and included in Logistic regression multivariate analysis. The predictive variables were determined and the receiver operating characteristic (ROC) curve was drawn to get the area under the curve (AUC) value of the area under the curve. RESULTS: Logistic regression analysis showed that the longest diameter, Max CT value, lobulation sign and spiculation sign were important indicators for distinguishing lung adenocarcinoma from intrapulmonary lymph nodes, and the risk ratios were 106.645 (95%CI: 3.828-2,971.220, P<0.01), 0.980 (95%CI: 0.969-0.991, P<0.01), 3.550 (95%CI: 1.299-9.701, P=0.01), 3.618 (95%CI: 1.288-10.163, P=0.02). According to the results of Logistic regression analysis, the prediction model is determined, the ROC curve is drawn, and the AUC value under the curve is calculated to be 0.877 (95%CI: 0.821-0.933, P<0.01). CONCLUSIONS For <1 cm solid pulmonary nodules, among many factors, the longest diameter, Max CT value, lobulation sign and spiculation sign are more important in distinguishing malignant pulmonary nodules from intrapulmonary lymph nodes.

Objective UPLC-MS/MS bio-analysis method was developed for the simultaneous determination ofberberine,naringin,hesperidin,and neohesperidin in plasma of rats.Methods UPLC Acquity BEH C18 (50 rmm × 2.1 mm,1.7 μm) column was used,mobile phases were containing 0.05％ formic acid and 2 mmol/L ammonium formate in water (A)-containing 0.05％ formic acid in acetonitrile (B) as the mobile phase gradient elution;SD rats were randomly divided into oral administration berberine group,Citrus aurantium extract group,and berberine and C.aurantium extract compatibility group.Results UPLC-MS/MS method could be applied to determination of berberine,naringin,hesperidin,and neohesperidin,method validation meets the requirements of biological sample analysis.When rats were administered with berberine and C.aurantium extract compatibility,the plasma concentration of berberine was much more than single dose of berberine group and the bioavailability of berberine was increased.Meanwhile,naringin and neohesperidin can be detected in rat's plasma.Conclusion The bioavailability of flavonoids is significantly improved as well compared to the single dose of C.aurantium extract.This suggests that berberine and C.aurantium extract compatibility has significant drug-drug interaction.

Objective Few studies are reported on the construction of a finite element model of human complex knee joint using multimodality CT and MRI images.In this study, we developed a finite element model of the knee joint for total knee arthroplasty (TKA) using matched and fused CT and MRI data, hoping to provide a useful tool for the simulation study of knee joint biomechanics of TKA.Methods The CT and MRI image data about an intact knee of a 26-year-old male volunteer were imported into the Mimics software for the establishment of 3D models of bony and soft-tissue structures.A complete knee model was developed following the registration and fusion of the constructed 3D models based on the external landmarks.After the simulated implantation of TKA components, a finite element model of the TKA knee was constructed with the Hypermesh software.Then the finite element model was analyzed following the definition of its material behavior, boundary conditions and loading.Results The finite element model of the TKA knee, which was composed of bones, ligaments, components, polyethylene insert and bone cement, was developed from CT-MRI image registration and fusion and maintained its important spatial relationship among different structures in the TKA knee.The results obtained from the finite element analysis showed the characteristics of stress distribution in the TKA knee.Conclusion The finite element model of the knee joint for TKA can be established by matching and fusing CT and MRI image data, which can be employed as a useful tool for the study of knee joint biomechanics of TKA.

Objective To investigate the expression of Polo-like kinase 1 in renal clear cell carcinoma and tissue adjacent to carcinoma;impact of BI2536 on the cell proliferation of renal clear cell carcinoma A498 cell line.Methods We select 12 cases of renal cancer Specimens of randical surgery between January 2013 and December 2014.The study included 7 male patients and 5 female patients,whose age ranged from 41 to 68 years(mean 49 years).Tumors were single and the location of tumor included 5 in left kidney,7 in right kidney.The size of renal tumor ranged from 2.1 to 6.3 cm.All patients did not have radiotherapy and chemotherapy preoperative who have no local and distant matastasis.The pathological results demonstrated renal clear cell carcinoma in 12 cases.At the same time,we collect the tissue 2 centimeters away as control,which pathological results demonstrated normal tissue.The expression of PLK1 was detected by western bloting in tissues from 12 cases of renal clear cell carcinoma and tissue adjacent to carcinoma and quantitative analysis was made.Cell proliferation of A498 cell line at the different concentrations of BI2536 were assayed by flow cytometry (0,20,40,60μg/L).Results The expression of PLK1 in renal clear cell carcinoma tissue are 0.74 ±0.2 and 0.21 ±0.13.The carcinoma tissue is higher than tissue adjacent to carcinoma (P =0.02).BI2536 act on A498 after 48 hours,the A498 cell number were arrested at G2/M phase at 0μg/L,20μg/L,40μg/L and 60μg/L were (10.28 ± 0.47) ％,(14.35 ± 0.85) ％,(20.49 ± 0.78) ％ and (23.90 ± 0.54) ％,respectively.The A498 cell number were arrested at G2/M phase increase when we incearse the concentrations of BI2536 at 48 hours (P ＜ 0.05).Conclusions The higher expression of PLK1 in renal clear cell carcinoma and the proliferation of the renal clear carcinoma cell can be repressed by BI2536 both reveal PLK1 may be used as the molecular maker and therapeutics target of renal clear cell carcinoma.

Objective To evaluate the effect of AIDS health education in university students to provide the theoretical basis for AIDS prevention in the young college students .Methods In order to know about the situation of awareness HIV/AIDS ,a general survey of HIV/AIDS related knowledge was conducted in freshmen of Dali college by self‐made questionnaire In December 2010 , then various forms of health education was took for college students ,such as theoretical study ,lecture and so on .Investigation a‐mong students once again ,and compared with the baseline survey results in December 2012 .Results The accuracy of HIV/AIDS health knowledge in the young college students after had health education was higher significantly than that before(P<0 .05);The score of AIDS elated problem have been weighted ,and awareness was defined as≥60 ;Before health education ,2 619 students knew about AIDS related knowledge ,872 students did not ,the average score was (64 .50 ± 10 .22) ,the total awareness rate was 75 .67% ;after the health education ,3 323 students know about AIDS related knowledge ,138 students did not ,the average score was (84 .94 ± 12 .68) ,the total awareness rate was 96 .01% .After continuing health education ,the total score was significantly increased (P<0 .01) .Conclusion The awareness rate of AIDS could be improved by health education in various forms and that was impor‐tant for the prevention of AIDS among college students .