The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

Dengue fever，caused by the dengue virus，is an acute viral infectious disease，which frequently outbreaks in tropical and subtropical regions worldwide，and has become a significant global health burden and threat. The development of dengue vaccines and antiviral drugs has made rapid and significant progress recently. The existing CYD-TDV vaccine is primarily suitable for individuals prior infection，while vaccines such as TAK-003 and Butantan-DV have demonstrated good safety and efficacy in uninfected individuals of different age groups；several other types of dengue vaccines have also entered clinical research stages. For antiviral drugs，an oral antiviral drug JNJ-1802 has shown significant antiviral activity against the dengue virus and good tolerability in clinical trials. It has now entered community field research to validate its effectiveness in real-world settings. Several other drugs are also under continuous development. This article reviews the research progress in the development of vaccines and antiviral drugs for dengue fever to provide reference for further study and clinical application.

Objective To report two cases of meningitis caused by Corynebacterium and review relevant literature to enhance clinical awareness of the pathogenicity of Corynebacterium species.Methods The clinical details were reported for 2 cases of meningitis caused by Corynebacterium.Similar case reports were retrieved from PubMed,CNKI,Wanfang,VIP,and CBM databases using search terms"Corynebacterium meningitis"and"cerebrospinal fluid shunt infection".Clinical data of the identified patients were reviewed and analyzed.Results Both patients with meningitis caused by Corynebacterium developed symptoms of fever,abdominal pain,and unconsciousness following lumboperitoneal shunt procedures.The culture of cerebrospinal fluid was positive for Corynebacterium.Both patients improved significantly after vancomycin treatment.Literature search yielded 29 similar cases.Overall,the 31 cases(including the two cases in this report)included 20 males and 11 females,aged between 4 weeks to 87 years.The identified Corynebacterium species included C.jeikeium in 12 cases,C.striatum in 9 cases,C.xerosis in 2 cases,C.bovis in 2 cases,C.aquaticum,C.equine,and C.minutissimum one case each,and unspecified Corynebacterium species in 3 cases.Underlying diseases were reporetd in most patients,including immune disorder in 2 cases,malignant tumor in 8 cases,genetic disease in 2 cases,premature with hydrocephalus in 4 cases,brain trauma in 2 cases,intracranial vascular malformation in 2 cases,and cerebral aneurysm in 2 cases.Risk factors for Corynebacterium meningitis included chemotherapy for malignancy in 5 cases,long term use of steroids and immunosuppressants in 2 cases,invasive procedures in 24 cases,and prior antibiotic use in 11 cases.Vancomycin was the most commonly prescribed treatment.The drainage tube and/or venous catheter were also removed or replaced in 19 cases.Twenty-five patients recovered after treatment and 6 patients died.Conclusions Corynebacterium species are emerging as opportunistic pathogens.Clinicians should be aware of the infections caused by Corynebacterium if patients have undergone invasive procedures or are immunocompromised,especially when associated with fever,altered consciousness,and clinical signs of encephalitis/meningitis.If cerebrospinal fluid test is positive for Corynebacterium,specific treatment should be prescribed promptly for Corynebacterium infection.

Objective:To investigate the predictive values of 18F-FDG PET/CT image feature and metabolic parameters for the malignant potential of gastrointestinal stromal tumor (GIST). Methods:From March 2014 to June 2020, the 18F-FDG PET/CT imaging and surgical pathological data of 35 patients with GIST (27 males, 8 females; age 44-84 years) from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology and Zhongnan Hospital of Wuhan University were analyzed retrospectively. Patients were divided into ring-shaped uptake group and other uptake patterns group according to 18F-FDG PET/CT image feature. Fisher′s exact test was used to analyze the differences of tumor necrosis and National Institutes of Health (NIH) risk classification (short for NIH classification) between different image feature groups. Mann-Whitney U test was used to analyze the differences of SUV max , metabolic parameters at different thresholds (2.5, 40%, 50%) of SUV max (metabolic tumor volume (MTV; MTV 2.5, MTV 40%, MTV 50%) and total lesion glycolysis (TLG; TLG 2.5, TLG 40%, TLG 50%)) between different clinicopathological features (lesion location, tumor diameter, mitotic count, Ki-67, necrosis, image feature, NIH classification) groups. Spearman rank correlation analysis was used to explore the correlation between clinicopathological features and metabolic parameters. ROC curve analysis was used to distinguish NIH classification of different metabolic parameters. Delong test was used to compared differences between different AUCs. Results:Of 35 GIST patients, 11(31.4%) were ring-shaped uptake and 24(68.6%) were other uptake patterns, and the differences of necrosis (7/11 vs 12.5%(3/24); P=0.004) and NIH classification (11/11 vs 25.0%(6/24); P<0.001) between the two groups were significant. There were significant differences of metabolic parameters between different groups of tumor diameter, mitotic count, necrosis, image feature, NIH classification ( z values: from -4.70 to -2.09, all P<0.05), while there were no significant differences of Ki-67 ( z values: from -0.83 to -0.71, all P>0.05). Metabolic parameters were correlated with mitotic count, tumor diameter, necrosis, image feature and NIH classification ( rs values: 0.36-0.81, all P<0.05), while was not correlated with Ki-67 ( rs values: 0.12-0.14, all P>0.05). The differences of AUCs between SUV max and MTV 2.5, TLG 2.5, TLG 40%, TLG 50%were significant (0.752, 0.856, 0.856, 0.882, 0.886; z values: 1.96-2.12, all P<0.05). Conclusions:The NIH classification of GIST with ring-shaped uptake on 18F-FDG PET/CT is higher and more prone to necrosis. The 18F-FDG PET/CT metabolic parameters based on different thresholds of SUV max have certain significance for the prediction of NIH classification of GIST, and may be superior to SUV max.

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*

OBJECTIVE: To explore the genetic basis of a patient with clinically suspected Loeys-Dietz syndrome (LDS). METHODS: A child who had presented at Beijing Anzhen Hospital in September 2018 was selected as the study subject. Clinical data and family history of the patient were collected, along with peripheral blood samples of the proband and his parents. Whole exome sequencing (WES) was carried out through next-generation sequencing. RESULTS: Candidate variants were searched through bioinformatic analysis focusing on genes associated with hereditary aortic aneurysms. Candidate variant was verified by Sanger sequencing. The patient was found to have cardiovascular abnormalities including early-onset aortic dilatation and coarctation, and LDS syndrome was suspected. WES revealed that he has harbored a heterozygous c.1526G>T missense variant of the TGFBR2 gene. The same variant was not found in either parent and was predicted as likely pathogenic (PM1+PM2_Supporting+ PM6+PP3+PP4) based on the guidelines from the American College for Medical Genetics and Genomics (ACMG). CONCLUSION The TGFBR2 c.1526G>T variant probably underlay the LDS in this patient and was unreported previously in China. Above finding has enriched the mutational spectrum of the TGFBR2 gene associated with the LDS and provided a basis for the genetic counseling for the patient.
Child ; Humans ; Male ; China ; Computational Biology ; Family ; Loeys-Dietz Syndrome/genetics* ; Mutation ; Receptor, Transforming Growth Factor-beta Type II/genetics*

OBJECTIVE: To explore the genetic basis for a patient with Dilated cardiomyopathy. METHODS: A patient admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University in April 2022 was selected as the study subject. Clinical data and family history of the patient was collected. Targeted exome sequencing was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of the American College of Medical Genetics and Genomics (ACMG). RESULTS: DNA sequencing revealed that the patient has harbored a heterozygous c.5044dupG frameshift variant of the FLNC gene. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION The heterozygous c.5044dupG variant of the FLNC gene probably underlay the pathogenesis in this patient, which has provided a basis for the genetic counseling for his family.
Humans ; Cardiomyopathy, Dilated/genetics* ; Genetic Testing ; Genetic Counseling ; Computational Biology ; Frameshift Mutation ; Mutation ; Filamins

Objective To observe the effect of high-frequency repetitive transcranial magnetic stimulation on hemiplegic shoulder pain during convalescence of stroke.Methods A total of 40 patients with hemiplegic shoulder pain during convalescing stroke who were hospitalized in Rehabilitation Medicine Department of Jiaxing Second Hospital from January 2021 to June 2022 were selected and randomly divided into treatment group(rTMS group)and control group(sham rTMS group),with 20 cases in each group.Both groups were given anti-inflammatory and analgesic drugs and conventional rehabilitation treatment.On this basis,the treatment group was combined with rTMS treatment(stimulation frequency was 10.0Hz,stimulation intensity was 80%resting motor threshold,stimulation time was 10s,interval was 50s,total treatment time was 20 minutes,once a day from Monday to Friday,continued treatment 2 days apart,20 times as a course of treatment,a total of 4 weeks),while the control group received sham rTMS.Before treatment,2 and 4 weeks after treatment,numerical pain rating scale(NPRS)was used to assess the degree of shoulder pain,passive shoulder range of motion was measured by protractor,upper limb motor function of hemiplegic side was assessed by Fugl Meyer assessment upper extremity(FMA-UE),and the ability of daily living activities was assessed by modified Barthel index(MBI).Results After treatment,NPRS score of shoulder pain in 2 groups was significantly decreased compared with before treatment(P<0.001),passive shoulder motion and Fugl-Meyer upper limb motor function were significantly improved compared with before treatment(P<0.001),and the treatment group was significantly better than the control group,the difference between groups was statistically significant(P<0.05).The modified Barthel index in 2 groups was significantly improved compared with before treatment(P<0.001),but there was no statistical significance between 2 groups(P>0.05).Conclusion 10.0Hz high-frequency repetitive transcranial magnetic stimulation can significantly relieve hemiplegic shoulder pain during the convalession of stroke,improve the passive range of motion of the affected shoulder,and improve the upper limb motor function of the affected side,but the effect is not significant in improving the ability of daily living activities.

Objective:To analyze the policy tools designed for function orientation and development of China′s infectious disease hospitals, in order to provide references for formulating and optimizing the functional implementation and sustainable development policies of these hospitals.Methods:Consulting the website of Peking University Law and official websites on health, and using such keywords as " medical institutions, infectious diseases, hospitals for infectious diseases, public health emergencies, specialized hospitals", and searching the national policy texts on the functions and development of infectious disease hospitals issued from December 1991 to January 2023. By means of Rothwell and Zegveld′s policy tool classification method, Nvivo 11 Pro software was used to analyze the text content from the dimensions of demand-type, supply-type, and environmental-type policy tools.Results:A total of 41 policy texts were included and 204 codes were obtained through text analysis. Of all the tools, environmental and supply-oriented policy tools were used the most, being 104 (50.99%) and 95 (46.56%) respectively, while demand-oriented policy tools were used the least, only 5 (2.45%). Of all the environmental-oriented policy tools, " goal planning" was the most used, being 34 (16.67%), while " publicity and guidance" was less used, only 4 (1.96%). Among the supply-oriented policy tools, " clarifying the reporting and handling service functions of public health emergencies" was the most widely used, being 34 (16.67%), while " Informationization" and " infrastructure construction" was less used, being 8 (3.92%) and 6 (2.94%) respectively. Few of the demand-oriented policy tools were in use, as " government purchase" and " medical insurance support" were both 2 (0.98% each), and " social medical care" was only 1 (0.49%).Conclusions:The distribution of three types of policy tools for function and development of infectious disease hospitals is unbalanced, the use of environmental and supply-oriented policy tools is excessive and internal structure is unbalanced. The proportion of environmental-oriented policy tools needs to be adjusted, and the frequency of use of supporting tools such as relevant standards, norms, incentives, supervision and publicity should be increased. Supply-oriented policies need to be further optimized, especially in terms of personnel training, funding, information technology and infrastructure construction. Demand-oriented policy tools are seriously underused and need to be further developed.

Objective　To study the efficacy and safety of hard channel puncture drainage in the treatment of multiple septated chronic subdural hematoma (CSDH) in the elderly by comparison with drilling drainage. Methods Twenty-one over-80-year-old patients with unilateral multiple septated CSDH were treated with drilling drainage in 9 cases (drilling group) and hard channel puncture drainage in 12 cases (hard channel group). The operation time, hematoma clearance rate in 1 week after operation, postoperative complications and hematoma recurrence in 3 months after operation were compared between the two groups. Results　The two groups of patients successfully completed the operation. The operation time ranged from 50 to 95 min with a mean of (78±14) min in the drilling group and 22 to 40 min with a mean of (29±5) min in the hard channel group. The difference was significant (P<0.05); One week after operation, the hematoma clearance rate ranged from 92% to100% with a mean of 96%±3% in the drilling group and 90% to 100% with a mean of 94%±3% in the hard channel group. The difference was not significant (P>0.05). Postoperative complications: there was no epilepsy in the drilling group, and 1 epilepsy in the hard channel group (8.3%). The difference was not significant (P>0.05). There were no other complications such as intracranial space occupying gas, brain parenchyma injury, intracranial infection in both groups. Hematoma recurrence 3 months after operation: there was no recurrence in the drilling group and 3 cases (25%) in the hard channel group. The difference was not significant (P>0.05). Conclusions　Hard channel puncture drainage is safe and effective in the treatment of elderly multiple septated CSDH. Compared with drilling drainage, it has shorter operation time, less trauma and is more suitable for patients with important organ diseases.