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 investigate the efficacy of precise ultrasound-guided stellate ganglion block(UG-SGB)combined with ozonated autohemotherapy in the treatment of sudden hearing loss.Methods Fifty-seven patients with sudden hearing loss,27 males and 30 females,aged 19-82 years,BMI 20-29 kg/m2,ASA physical status Ⅰ or Ⅱ,were randomly divided into drugs combined with UG-SGB and ozonated autohemotherapy treatment group(group U,n=29)and drugs group(group D,n=28)accord-ing to the random number table.All patients were given drug therapy.In addition to the treatment above,pa-tients in group U also received precise ultrasound-guided stellate ganglion block once on affected side com-bined with ozonated autohemotherapy once daily for 10 consecutive days.Patients in group D received drug therapy only.The average hearing threshold of the two groups was compared before treatment(T0),at dis-charge(T1),1 month(T2),3 months(T3),and 6 months after discharge(T4).The hearing improve-ment of the two groups was also compared at T1-T4 on the basis of T0.Moreover,tinnitus rate of the two groups was recorded T0-T4.In addition,adverse reactions such as toxicosis of local anaesthetics,pneumo-thorax were recorded.Results Compared with T0,the average hearing threshold was reduced significantly in both groups at T1-T4(P＜0.05),the incidence of tinnitus was reduced significantly at T1-T4 in both groups(P＜0.05).Compared with T,,the average hearing threshold was reduced significantly in group U at T2-T4(P＜0.05).The average hearing threshold of group U was lower than that in group D at T1-T4(P＜0.05).The hearing improvement in group U was better than that in group D at T2-T4(P＜0.05).The proportion of complete hearing recovery in group U was increased significantly than that in group D at T2-T4(P＜0.05)The proportion of effective hearing improvement in group U was decreased than that in group D at T3-T4(P＜0.05).No obvious adverse reaction was recorded,such as toxicosis of local anaesthetics,pneumothorax.Conclusion Precise ultrasound-guided stellate ganglion block combined with ozonated auto-hemotherapy based on drug treatment significantly improves the average hearing threshold of patients with sudden hearing loss in acute stage and improve their hearing.

Objective:To establish a green fluorescent protein(GFP)and firefly luciferase(Luc)double-labeled Epstein-Barr virus(EBV)infec-ted B lymphoblastoid cell lines(B-LCL)and apply them to mouse models,then compare the advantages and disadvantages of models inocu-lated by intravenous(IV)or subcutaneous(SC).Methods:B lymphoblastoid cell lines double-tagged with GFP/Luc(B-LCL-GL)were con-structed through lentivirus transduction,puromycin intervention.Subcutaneous xenograft and hematogenous metastasis models were re-spectively established by subcutaneous or intravenous injection of B-LCL-GL cells at three concentrations in(NOD)/Prkdcscid/IL-2Rγnull(NPG)mice for in vivo bioluminescence imaging.Results:In the B-LCL-GL group,the ratio of the GFP-positive cell population was 92.5%,and the average luminescence intensity was as high as 4.80E+08 Photons/s,which was considerably higher than that of untreated B-LCLs.In the hematogenous metastasis models,tumor bioluminescence was initially located in the peritoneal area and then spread throughout the en-tire body between 7 and 28 days.In the subcutaneous xenograft models,strong central and weak peripheral tumor-related biolumines-cence signal was detected on day 7 in the three groups,which then spread throughout the body on day 28 in the high-dose group.Taken to-gether,there was no significant difference in tumor progression between the two routes of administration when using the same dose of B-LCL-GL cells.However,the survival analysis indicated that the IV injection group,in which all the mice ultimately died,had a shorter time frame for testing than that of the SC injection group,in which the mice survived until day 100 in the low-dose and medium-dose groups,thus allowing for long-term testing.Conclusions:GFP and Luc dual-positive B-LCLs were successfully established to generate hematogenous metastasis and subcutaneous xenograft models,which allow the monitoring of the location and size of lymphomas in vivo.It provide plat-form for the study of tumor characteristics and selecting anti-tumor drugs.

【Objective】 To investigate the serological and molecular genetic characteristics of B(A) and cisAB blood groups discovered in our laboratory. 【Methods】 ABO blood group serology and genetic tests were used to identify blood groups of 6 blood samples, submitted by blood center and hospitals in Shandong, and pedigree investigation was carried on 2 of them. 【Results】 Among the 6 samples, serological results were B(A) in 5 cases and cisAB in 1 case. The results of genetic tests were consistent with the serological results, as the alleles included B(A)04, B(A)02 and cisAB01, and all genotypes were heterozygous with O. Serological pedigree study was conducted on 2 samples: One cisAB patient with his 4 relatives(cisAB type father and three O type relatives) and one B(A)02/O1 donor with his 3 relatives[ B(A) type father/brother and O type mother). For B(A)02/O1 donor, the results of genetic testing were consistent with the serological results, as the paternal genotype was the same as that of the proband, the younger brother was B(A)02/O2, and the maternal genotype was O1/O2. 【Conclusion】 The cisAB and B(A) blood groups are often indistinguishable by serological phenotypes and require genetic confirmation. CisAB pedigree investigation revealed 2 cases of cisAB blood type and B(A) pedigree investigation revealed 3 cases of B(A). The genotyping of cisAB and B(A) in this region were cisAB01/O2, B(A)02/O1, B(A)02/O2, B(A)04/O1 and B(A)04/O2. B(A)and cisAB subtypes can be accurately identified through genetic testing and pedigree investigation, which can provide a reliable basis for blood transfusion selection and ensure the safety of clinical blood transfusion.

Background::The study aimed to describe the aortic valve morphology in Chinese patients underwent transcatheter aortic valve replacement (TAVR) for symptomatic severe aortic stenosis (AS), and the impact of sizing strategies and related procedural outcomes.Methods::Patients with severe AS who underwent TAVR were consecutively enrolled from 2012 to 2019. The anatomy and morphology of the aortic root were assessed. "Downsize" strategy was preformed when patients had complex morphology. The clinical outcomes of patients who performed downsize strategy were compared with those received annular sizing strategy. The primary outcome was device success rate, and secondary outcomes included Valve Academic Research Consortium-3 clinical outcomes variables based on 1-year follow-up.Results::A total of 293 patients were enrolled. Among them, 95 patients (32.4%) had bicuspid aortic valve. The calcium volume (Hounsfield Unit-850) of aortic root was 449.90 (243.15-782.15) mm 3. Calcium is distributed mostly on the leaflet level. Downsize strategy was performed in 204 patients (69.6%). Compared with the patients who performed annular sizing strategy, those received downsize strategy achieved a similar device success rate (82.0% [73] vs. 83.3% [170], P= 0.79). Aortic valve gradients (downsize strategy group vs. annular sizing group, 11.28 mmHg vs. 11.88 mmHg, P = 0.64) and percentages of patients with moderate or severe paravalvular regurgitation 2.0% (4/204) vs. 4.5% (4/89), P = 0.21) were similar in the two groups at 30 days after TAVR. These echocardiographic results were sustainable for one year. Conclusions::Chinese TAVR patients have more prevalent bicuspid morphology and large calcium volume of aortic root. Calcium is distributed mostly on the leaflet level. Compare with annular sizing strategy, downsize strategy provided a non-inferior device success rate and transcatheter heart valve hemodynamic performance in self-expanding TAVR procedure.

Objective:To analyze the clinical features of the recurrence of febrile seizures(FS), and observe the efficacy of levetiracetam(LEV)in preventing FS recurrence.Methods:We retrospectively analyzed the clinical data of 101 cases of FS recurrence who were admitted to the Department of Neurology of our hospital from May 2017 to May 2020, and collected the information of the recurrence after discharge and adverse effects of LEV application.Cox proportional hazards model regression was applied to explore the relationship between FS recurrence and LEV prophylaxis.Results:Among 101 cases of recurrent FS, the section of 18-60 months(63/101)composed the dominant proportion, of which the episode of 18-36 months(40/101)took the biggest recurrence rate.All 101 recurrent FS cases occurred within 24 hours of fever-beginning time, and 74.3%(75/101)occurred within 3 hours of fever onset.39.6% cases(40/101)were non-high febrile seizures, of which 30.0%(12/40)even had a temperature ≤38°C at the onset.Ninty-five cases of FS were included in the retrospective cohort study.Thirty-eight cases(4 lost to follow-up)were treated with LEV, while 57 cases(7 lost to follow-up)were not treated with any anticonvulsant drugs.The recurrence rate in the prophylactic group was 17.6%(6/34), compared with 44.0%(22/50)in the control group.The recurrence rate of the prophylactic group was statistically lower than that of the control group( χ2=6.325, P=0.012). Cox regression analysis was used to explore the relationship between FS recurrence and various factors, suggesting LEV prophylaxis( OR=0.325, 95% CI 0.129-0.821)and family history of FS( OR=3.060, 95% CI 1.427-6.560)affect the recurrence of FS.Then FS family history was stratified, LEV prophylaxis still statistically reduced the recurrence of FS( OR=0.316, 95% CI 0.124-0.802). Conclusion:The risk of recurrence increases significantly after 18 months of the age.Besides, FS recurrence is relatively common in the initial episode of fever and in the stage of low fever.For children at months of high probability of recurrence, prophylactic drugs should be used in the initial episode of fever and in the stage of low fever.LEV prophylaxis therapy is effective, with mild adverse reactions.

The current epidemic situation of corona virus disease-19 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 inZhejiang Province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance"strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinarypersonalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in10% patients'blood samples at acute periodand 50% of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifyingcytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance"strategyeffectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviraleffects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favoredthe balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short periods of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis should be prescribed rationally and was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbialdysbiosis with decreasedprobiotics such as and . Nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the SARS-CoV-2 infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience above and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.

Clinical trial management system is independently developed by our hospital, which basically realized the whole process management and data collection of clinical trials. Based on the platform, the functional architecture of data remote monitoring and auditing was established. By desensitizing and encrypting of data, the project and subject hologram were visualized to facilitate to review of data. The data remote monitoring and auditing cloud platform adopts the B/S architecture pattern. Users register to apply for an account through the cloud platform, and access to the account via HTTPS security protocol. The authorized users were able to view the relevant items online to ensure the secure data transmission and easy operating. The electronic management of data is the direction of future efforts. By compliance with laws and regulations, the remote monitoring/auditing can be realized, and the data security and personal privacy can be ensured with the application of information technology. In this paper, the feasibility of remote monitoring/auditing mode is explored, specific technical schemes and system functions are suggested, and the realization scenarios are conceived in case of major public health emergencies.

Severe and critically ill patients with coronavirus disease 2019 (COVID-19) were usually with underlying diseases, which led to the problems of complicated drug use, potential drug-drug interactions and medication errors in special patients. Based on ( 6), and -19: , we summarized the experience in the use of antiviral drugs, corticosteroids, vascular active drugs, antibacterial, probiotics, nutrition support schemes in severe and critically ill COVID-19 patients. It is also suggested to focus on medication management for evaluation of drug efficacy and duration of treatment, prevention and treatment of adverse drug reactions, identification of potential drug-drug interactions, individualized medication monitoring based on biosafety protection, and medication administration for special patients.
Adrenal Cortex Hormones ; adverse effects ; therapeutic use ; Anti-Bacterial Agents ; therapeutic use ; Antiviral Agents ; adverse effects ; therapeutic use ; Betacoronavirus ; isolation & purification ; Coronavirus Infections ; drug therapy ; Critical Illness ; Drug Therapy ; Humans ; Nutritional Support ; Pandemics ; Pneumonia, Viral ; drug therapy ; Probiotics ; administration & dosage