BACKGROUND: Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China. METHODS: Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate. RESULTS: Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P  <0.05). CONCLUSIONS: This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics. REGISTRATION ClinicalTrials.gov , NCT03484806.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Heart Valve Diseases/therapy* ; Kaplan-Meier Estimate ; Tertiary Care Centers ; Treatment Outcome

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Objective To systematically evaluate the risk factors for new-onset atrial fibrillation (NOAF) after off-pump coronary bypass grafting (OPCABG). Methods PubMed, EMbase, Web of Science, The Cochrane Library, Wanfang data, CBM, VIP, and CNKI databases were systematically searched by computer to collect studies related to the risk factors for NOAF after OPCABG from the establishment of the database to July 2023. Literature screening and quality evaluation were conducted independently by two researchers. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the literature. RevMan 5.3 and Stata15.0 were used for meta-analysis. Results Finally, 19 case-control studies related to the risk factors for NOAF after OPCABG were included, all of which were high-quality literature with NOS score≥6 points, with a total of 7019 subjects. The results of meta-analysis showed that the following factors were associated with NOAF after OPCABG: (1) the patient’s own factors: age (MD=3.51, 95%CI 2.39 to 4.63, P<0.01); (2) preoperative factors: history of hypertension (OR=1.17, 95%CI 1.04 to 1.32, P=0.01), history of myocardial infarction (OR=1.21, 95%CI 1.06 to 1.38, P<0.01), history of percutaneous coronary intervention (OR=2.22, 95%CI 1.03 to 4.77, P=0.04), EuroSCOREⅡ score (MD=0.59, 95%CI 0.25 to 0.94, P<0.01), low-density lipoprotein (MD=0.11, 95%CI 0.02 to 0.20, P=0.02), left atrial diameter (MD=1.64, 95%CI 0.24 to 3.04, P=0.02); (3) postoperative and treatment factors: left ventricular end-diastolic diameter (MD=1.16, 95%CI 0.33 to 1.99, P<0.01), left ventricular ejection fraction (MD=0.90, 95%CI 0.07 to 1.73, P=0.03), mechanical ventilation time (MD=2.78, 95%CI 1.65 to 3.90, P<0.01), B-type natriuretic peptide (MD=219.67, 95%CI 27.46 to 411.88, P=0.03), ICU retention time (MD=7.07, 95%CI 5.64 to 8.50, P<0.01). Conclusion The existing evidence shows that age, history of hypertension, history of myocardial infarction, history of percutaneous coronary intervention, preoperative EuroSCOREⅡscore, preoperative low-density lipoprotein, preoperative left atrial diameter, postoperative left ventricular end-diastolic diameter, postoperative left ventricular ejection fraction, postoperative mechanical ventilation time, postoperative B-type natriuretic peptide, and postoperative ICU retention time are risk factors for NOAF after OPCABG. Clinical attention should be paid to the above factors to achieve early identification, thereby reducing the incidence of NOAF after OPCABG and improving the clinical prognosis of patients.

Objective To investigate the effects of electroacupuncture for the restoration of muscle regeneration and the secretion of exosomes around acupoints in a model of erector spinae muscle injury.Methods Forty SPF-grade male SD rats were randomly divided into blank group,model group,electroacupuncture group,and electroacupuncture+exosome inhibitor group,with 10 rats per group.Except for the blank group,the erector spinae muscle injury models were established in other groups by intramuscular injection of 0.5%bupivacaine.The blank control group received no treatment,whereas the rats in the electroacupuncture and electroacupuncture+exosome inhibitor groups were treated with electroacupuncture at"Weizhong"(BL40)and"Shenshu"(BL23)acupoints,respectively,stimulation was applied daily for 7 consecutive days,with each session lasting 20 minutes.The parameters used were a sparse-dense wave waveform,a frequency of 2/10 Hz,and a current intensity of 1 mA.The exosome inhibitor GW4869(3 g/L,50 μL per acupoint)was injected 1 h before each electroacupuncture in the electroacupuncture+exosome inhibitor group.After intervention,the erector spinae muscles were collected and observed by HE and Masson staining for morphological changes.The expression of paired box gene 7(Pax7)and recombinant myogenic differentiation(MyoD)was detected by immunohistochemistry,while the expression of myogenin(MyoG)and myosin heavy chain(MyHC)proteins was detected by western blotting.The serum exosomes of rats in each group were extracted and identified by transmission electron microscopy and nanoparticle tracking analysis,and the expression of Alix,differentiation cluster 63(CD63),and tumor susceptibility gene 101(TSG101)proteins were detected by Western blotting.Results Compared with the blank group,the model group,the electroacupuncture group,and the electroacupuncture+exosome inhibitor group exhibited spinae muscle fiber fragmentation,degeneration,necrosis,and inflammatory cell infiltration in HE staining.The result of Masson staining showed that collagen fiber hyperplasia was increased.The model group showed increased expression of MyoD,Pax7,MyoG,MyHC,and CD63,while TSG101 expression was downregulated(P<0.05).In the electroacupuncture group,the expression of MyoD,Pax7,Alix,and TSG101 was elevated(P<0.05),and the expression of MyHC and CD63 was decreased(P<0.05).The electroacupuncture+exosome inhibitor group displayed increased expression of MyHC,Alix,and TSG101(P<0.05),and the expression of CD63 was decreased(P<0.05).Compared with the model group,the electroacupuncture group and the electroacupuncture+exosome inhibitor group showed reduced muscle fiber degeneration,necrotic areas,and inflammatory cell infiltration as observed in HE staining,along with decreased collagen fiber hyperplasia in Masson staining.Specifically,the electroacupuncture group demonstrated increased expression of MyoD,Pax7,MyoG,Alix,and TSG101(P<0.05),and the expression of CD63 was decreased(P<0.05).The electroacupuncture+exosome inhibitor group displayed downregulated expression of Pax7,MyoG,MyHC,and CD63(P<0.05),and the expression of Alix and TSG101 was regulated(P<0.05).Compared with the electroacupuncture+exosome inhibitor group,the electroacupuncture group exhibited less muscle fiber degeneration and necrosis,reduced inflammatory cell infiltration in HE staining,and decreased stained collagen fibers in Masson staining.The electroacupuncture group showed increased expression of MyoD,Pax7,MyoG,MyHC,Alix,and CD63(P<0.05).Conclusion Electroacupuncture can up-regulate the expression of Pax7 and MyoD,and promote the regeneration of erector spinae muscles,which may be related to stimulating the secretion of exosomes around the acupoint.Exosomes may be an important mediator for the efficacy of acupuncture.

Objective To investigate the effects of electroacupuncture for the restoration of muscle regeneration and the secretion of exosomes around acupoints in a model of erector spinae muscle injury.Methods Forty SPF-grade male SD rats were randomly divided into blank group,model group,electroacupuncture group,and electroacupuncture+exosome inhibitor group,with 10 rats per group.Except for the blank group,the erector spinae muscle injury models were established in other groups by intramuscular injection of 0.5%bupivacaine.The blank control group received no treatment,whereas the rats in the electroacupuncture and electroacupuncture+exosome inhibitor groups were treated with electroacupuncture at"Weizhong"(BL40)and"Shenshu"(BL23)acupoints,respectively,stimulation was applied daily for 7 consecutive days,with each session lasting 20 minutes.The parameters used were a sparse-dense wave waveform,a frequency of 2/10 Hz,and a current intensity of 1 mA.The exosome inhibitor GW4869(3 g/L,50 μL per acupoint)was injected 1 h before each electroacupuncture in the electroacupuncture+exosome inhibitor group.After intervention,the erector spinae muscles were collected and observed by HE and Masson staining for morphological changes.The expression of paired box gene 7(Pax7)and recombinant myogenic differentiation(MyoD)was detected by immunohistochemistry,while the expression of myogenin(MyoG)and myosin heavy chain(MyHC)proteins was detected by western blotting.The serum exosomes of rats in each group were extracted and identified by transmission electron microscopy and nanoparticle tracking analysis,and the expression of Alix,differentiation cluster 63(CD63),and tumor susceptibility gene 101(TSG101)proteins were detected by Western blotting.Results Compared with the blank group,the model group,the electroacupuncture group,and the electroacupuncture+exosome inhibitor group exhibited spinae muscle fiber fragmentation,degeneration,necrosis,and inflammatory cell infiltration in HE staining.The result of Masson staining showed that collagen fiber hyperplasia was increased.The model group showed increased expression of MyoD,Pax7,MyoG,MyHC,and CD63,while TSG101 expression was downregulated(P<0.05).In the electroacupuncture group,the expression of MyoD,Pax7,Alix,and TSG101 was elevated(P<0.05),and the expression of MyHC and CD63 was decreased(P<0.05).The electroacupuncture+exosome inhibitor group displayed increased expression of MyHC,Alix,and TSG101(P<0.05),and the expression of CD63 was decreased(P<0.05).Compared with the model group,the electroacupuncture group and the electroacupuncture+exosome inhibitor group showed reduced muscle fiber degeneration,necrotic areas,and inflammatory cell infiltration as observed in HE staining,along with decreased collagen fiber hyperplasia in Masson staining.Specifically,the electroacupuncture group demonstrated increased expression of MyoD,Pax7,MyoG,Alix,and TSG101(P<0.05),and the expression of CD63 was decreased(P<0.05).The electroacupuncture+exosome inhibitor group displayed downregulated expression of Pax7,MyoG,MyHC,and CD63(P<0.05),and the expression of Alix and TSG101 was regulated(P<0.05).Compared with the electroacupuncture+exosome inhibitor group,the electroacupuncture group exhibited less muscle fiber degeneration and necrosis,reduced inflammatory cell infiltration in HE staining,and decreased stained collagen fibers in Masson staining.The electroacupuncture group showed increased expression of MyoD,Pax7,MyoG,MyHC,Alix,and CD63(P<0.05).Conclusion Electroacupuncture can up-regulate the expression of Pax7 and MyoD,and promote the regeneration of erector spinae muscles,which may be related to stimulating the secretion of exosomes around the acupoint.Exosomes may be an important mediator for the efficacy of acupuncture.

Objective:To analyze the clinical features and immunotherapy responsiveness of patients with myelin oligodendrocyte glycoprotein immunoglobulin G-antibody associated disease (MOGAD) with epilepsy, and display the risk factors of epilepsy in MOGAD.Methods:Eighty-nine patients with MOGAD diagnosed at the First Affiliated Hospital of Zhengzhou University between October 2019 and May 2023 were enrolled and classified into 2 groups upon MOGAD with ( n=29) or without epilepsy ( n=60). The Expanded Disability Status Scale (EDSS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) were used for evaluation of severity, and EDSS or CASE scores on the 30th day after first-line immunotherapy initiation lower than that on admission were defined as well treatment responsiveness. The differences of general data, clinical manifestations, cerebrospinal fluid (CSF) and peripheral blood biochemical examination results, and immunotherapy reactivity between the 2 groups were thoroughly explicated. In addition, the risk factors of epilepsy in MOGAD were analyzed by univariate and multivariate Logistic regression analysis. Results:Compared with patients with MOGAD without epilepsy, patients with MOGAD with epilepsy were characterized by lower age of onset [24.5(10.3, 34.0) years vs 11.0(6.5, 20.0) years, Z=-2.348, P=0.019], higher percentage of male patients [43.3%(26/60) vs 75.9%(22/29), χ 2=8.326, P=0.004], higher virus infection rate [28.3%(17/60) vs 51.7%(15/29), χ 2=4.645, P=0.031], higher incidence of prodromal symptoms [11.7%(7/60) vs 34.5%(10/29), χ 2=6.586, P=0.010], higher blood-brain barrier breakdown rate [35.0%(21/60) vs 58.6%(17/29), χ 2=4.458, P=0.035], higher percentage of CSF albumin level>450 mg/L [48.3%(29/60) vs 75.9%(22/29), χ 2=6.056, P=0.014] and higher creatine kinase level [45.50(28.50, 69.75) U/L vs 57.50(41.75, 97.25) U/L, Z=-2.349, P=0.019]; more epilepsy [0(0) vs 29/29 (100.0%), χ 2=89.000, P<0.001] and disturbance of consciousness [0(0) vs 6/29(20.7%), χ 2=10.224, P=0.001] as clinical manifestations, and more cerebral cortex lesions [30/60(50.0%) vs 25/29(86.2%), χ 2=10.856, P=0.001] on magnetic resonance imaging. Nevertheless, the patients with MOGAD without epilepsy were featured with more visual impairment [23/60(38.3%) vs 3/29(10.3%), χ 2=7.406, P=0.007], limb weakness [18/60(30.0%) vs 1/29(3.4%), χ 2=8.209, P=0.004], sensory disturbance [15/60(25.0%) vs 0(0), Fisher exact probability test, P=0.002] and more cervical cord lesions [22/60(36.7%) vs 4/29(13.8%), χ 2=4.946, P=0.026] on magnetic resonance imaging. Immunotherapy responsiveness was relatively poor in the MOGAD with epilepsy group [EDSS score lower than that on admission: 15/29(51.7%) vs 46/60(76.7%), χ 2=5.641, P=0.018; CASE score lower than that on admission: 16/29(55.2%) vs 47/60(78.3%), χ 2=5.072, P=0.024] compared with the MOGAD without epilepsy group. Male was the independent risk factor of epilepsy in MOGAD ( OR=7.078, 95% CI 1.709-29.326, P=0.007). Conclusions:Compared with patients with MOGAD without epilepsy, patients with MOGAD with epilepsy reported more male patients, lower age of onset and higher incidence of prodromal symptoms, blood-brain barrier dysfunction rate, virus infection rate, CSF albumin level and creatine kinase level; clinical phenotypes were mainly meningoencephalitis and more cerebral cortex lesions were shown on magnetic resonance imaging. MOGAD with epilepsy was closely related to poor immunotherapy responsiveness, and gender was found to be the independent risk factor for epilepsy in MOGAD.

Construction of smart hospitals is of great significance to the substantial development of medical institutions and the reform of medical and health systems and meanwhile it serves as a crucial support for the high-quality development of pub-lic hospitals.Guangdong Second Provincial General Hospital actively responds to national policies,constantly exploring standard-ized application of new smart medical technology.It has successfully built itself into a first full-scene smart hospital.Through gradually deepening the intelligent construction of hospitals,the hospital has achieved obvious achievements in hospital manage-ment such as medical services,medical resources,medical data,hospital operation logistics,and medical environment improve-ment.Their practical experience can provide references for the intelligent construction of hospitals domestically.

Objective:To evaluate the effect of inhaled medication compliance intervention in elderly patients with chronic obstructive pulmonary disease (COPD) based on integrated theory of health behavior change.Methods:A total of 117 elderly COPD patients who visited Respiratory Department of Beijing Chaoyang Hospital Affiliated to Capital Medical University from July to December 2021 were selected by the convenient sampling method. According to the random number table method, they were divided into the experimental group and the control group. 7 cases fell off during follow-up, and a total of 110 cases were finally included in the study, of which 55 cases were in the experimental group and 55 cases in the control group. The control group adopted the conventional health education method, while the experimental group adopted the intervention plan of inhalation medication compliance of elderly COPD patients based on the integrated theory of health behavior change. The accuracy of inhalation device use, inhalant medication compliance, forced expiratory volume in the first second (FEV 1) and Chronic Obstructive Pulmonary Diseases Assessment Test (CAT) scores were compared between the two groups before intervention and 3 months after intervention. Results:After 3 months of intervention, the inhalation device use accuracy, inhalation medication compliance in experimental group were higher than those in the control group, the score of CAT in experimental group was lower than that in the control group, the differences were statistically significant ( P<0.05). There was no statistically significant difference in FEV 1 between two groups ( P>0.05) . Conclusions:The intervention plan for inhalation medication compliance in elderly patients with chronic obstructive pulmonary disease based on the integrated theory of health behavior changes can improve their inhalation medication compliance and improve their quality of life.

The optimal protocol for neuromodulation by transcranial direct current stimulation (tDCS) remains unclear. Using the rotarod paradigm, we found that mouse motor learning was enhanced by anodal tDCS (3.2 mA/cm²) during but not before or after the performance of a task. Dual-task experiments showed that motor learning enhancement was specific to the task accompanied by anodal tDCS. Studies using a mouse model of stroke induced by middle cerebral artery occlusion showed that concurrent anodal tDCS restored motor learning capability in a task-specific manner. Transcranial in vivo Ca²⁺ imaging further showed that anodal tDCS elevated and cathodal tDCS suppressed neuronal activity in the primary motor cortex (M1). Anodal tDCS specifically promoted the activity of task-related M1 neurons during task performance, suggesting that elevated Hebbian synaptic potentiation in task-activated circuits accounts for the motor learning enhancement. Thus, application of tDCS concurrent with the targeted behavioral dysfunction could be an effective approach to treating brain disorders.
Transcranial Direct Current Stimulation/methods* ; Motor Cortex/physiology* ; Neurons ; Transcranial Magnetic Stimulation

Xanthoria elegans is a lichen symbiosis, that inhabits extreme environments and can absorb UV-B. We reported the de novo sequencing and assembly of X. elegans genome. The whole genome was approximately 44.63 Mb, with a GC content of 40.69%. Genome assembly generated 207 scaffolds with an N50 length of 563,100 bp, N90 length of 122,672 bp. The genome comprised 9,581 genes, some encoded enzymes involved in the secondary metabolism such as terpene, polyketides. To further understand the UV-B absorbing and adaptability to extreme environments mechanisms of X. elegans, we searched the secondary metabolites genes and gene-cluster from the genome using genome-mining and bioinformatics analysis.The results revealed that 7 NR-PKSs, 12 HR-PKSs and 2 hybrid PKS-PKSs from X. elegans were isolated, they belong to Type I PKS (T1PKS) according to the domain architecture; phylogenetic analysis and BGCs comparison linked the putative products to two NR-PKSs and three HR-PKSs, the putative products of two NR-PKSs were emodin xanthrone (most likely parietin) and mycophelonic acid, the putative products of three HR-PKSs were soppilines, (þ)-asperlin and macrolactone brefeldin A, respectively. 5 PKSs from X. elegans build a correlation between the SMs carbon skeleton and PKS genes based on the domain architecture, phylogenetic and BGC comparison. Although the function of 16 PKSs remains unclear, the findings emphasize that the genes from X. elegans represent an unexploited source of novel polyketide and utilization of lichen gene resources.