OBJECTIVETo evaluate the inhibition effects of DNAzymes specific to Hepatitis B Virus(HBV) s gene and e gene on the expressions of Hepatitis B surface antigen(HBsAg) and Hepatitis B e antigen(HBeAg).

METHODSDNAzymes DrzBS and DrzBC specific to HBV s gene ORF A157UG and e gene ORF A1816UG, respectively, were designed and synthesized. The inhibition effects of DrzBS or DrzBC on the expressions of HBV s and e genes were observed in 2.2.15 cells.

RESULTSThe expression of HBV s or e genes was dramatically depressed after 2.2.15 cells treated by DrzBS or DrzBC. The concentration for effective inhibition was within 0.1-2.5 micromol/L and the inhibition showed a dose dependence within that concentration range. The maximum inhibition was 94.2% and 91.8% for DrzBS and DrzBC, respectively. The inhibition was maintained for 72 hours. The efficiency of inhibiting HbsAg, HbeAg in 2.2.15 cells by DrzBS, DrzBC was higher than that by antisense oligonucleotides for the same target genes. The concentrations for effective inhibition of the DNAzymes were at least 10-fold lower compared with antisense oligonucleotides. Neither inhibition on the replication of HBV DNA nor toxicity to 2.2.15 cells was observed.

CONCLUSIONDrzBS and DrzBC can highly block the expressions of HBV s gene and e gene in 2.2.15 HBV cell model and are proved a specific and effective anti-HBV gene therapeutic means.

DNA, Catalytic ; pharmacology ; therapeutic use ; DNA, Viral ; analysis ; Dose-Response Relationship, Drug ; Gene Expression ; drug effects ; Genetic Therapy ; Hepatitis B ; therapy ; Hepatitis B Surface Antigens ; genetics ; Hepatitis B e Antigens ; genetics

BACKGROUNDSleep disturbance is common in patients with emphysema. This study aimed to develop a novel model of sleep-related hypoxemia (SRH) in emphysema (SRHIE) with rats, and to explore the inflammatory status of SRHIE in lung, liver, pancreas, carotid artery and whole blood.

METHODSSeventy-five male Wistar rats were assigned to 5 groups with 15 per group according to the exposure conditions. The protocols varied with the degree of hypoxia exposure and severity of pre-existing emphysema caused by cigarette smoke exposure: (1) SRH control (SRHCtrl) group, sham smoke exposure (smoke exposure, exposed to smoke of 15 cigarettes twice everyday, 16 weeks) and SRH exposure (12.5% O2, 3 hours, SRH exposure, divide total hypoxia time (1.5 hours or 3 hours) into 4 periods evenly (22.5 minutes or 45 minutes) and distribute these hypoxia periods evenly into physiological sleep time of rats identified by electroencephalogram, week 9 to week 16); (2) Emphysema control (ECtrl) group, smoke exposure and sham SRH exposure (21% O2, 3 hours); (3) Short SRH in emphysema (SRHShort) group, smoke exposure and short SRH exposure (12.5% O2, 1.5 hours); (4) Mild SRH in emphysema (SRHMild) group, smoke exposure and mild SRH exposure (15% O2, 3 hours); (5) Standard SRH in emphysema (SRHStand) group, smoke exposure and SRH exposure (12.5% O2, 3 hours). ECtrl, SRHShort, SRHMild and SRHStand groups were groups with emphysematous rats. Two days before the end of exposure, 5 rats in each group were randomly selected for arterial blood gas analysis. In the rest 10 rats in each group, we obtained blood samples and bronchoalveolar lavage fluid (BALF) for routine tests. We also obtained tissue blocks of lung, liver, pancreas, and right carotid artery for pathologic scoring and measurements of liver oxidative stress (measuring hepatic oxidative stress enzymes, superoxide dismutase (SOD) activity, catalase (CAT) activity and malondialdehyde (MDA) concentration).

RESULTSEmphysematous groups had higher mean linear intercept (MLI) and mean alveolar number (MAN) values than SRHCtrl group. MLI values in SRHStand group were the highest (all P < 0.05). O2Sat in SRHStand rats when SRH exposure was (83.45 ± 1.76)%. Histological scores of lung, liver, pancreas and right carotid artery were higher in emphysematous groups than SRHCtrl group, and SRHStand group were the highest (all P < 0.05) (SOD and CAT values were lower and MDA values were higher in groups with emphysema than without and in SRHStand group than in ECtrl group (all P < 0.05)). MDA values were the highest in SRHStand group (all P < 0.05). Total cellular score in BALF and White blood cell (WBC) in whole blood were the highest in SRHStand group (all P < 0.05). Lymphocyte ratios were the highest in SRHStand group both in BALF and blood (all P < 0.05). Red blood cell (RBC) and hemoglobin in emphysematous groups were higher than that in SRHCtrl group, and SRHStand group were higher than ECtrl group (all P < 0.05).

CONCLUSIONSWith a proper novo model of SRHIE with Wistar rats, we have demonstrated SRH may aggravate the degree of emphysematous changes, polycythemia, oxidative stress and systematic inflammation. SRH and emphysema may have a synergistic action in causing systematic damages, and lymphocyte may be playing a central role in this process. Longer duration and more severe extent of SRHIE exposure also seem to result in more serious systematic damages. The mechanisms of all these concerned processes remain to be studied.

Animals ; Emphysema ; complications ; Hemoglobins ; analysis ; Hypoxia ; complications ; Inflammation ; etiology ; Male ; Oxidative Stress ; Rats ; Rats, Wistar ; Sleep ; physiology

Objective To explore the attitude towards 10 different populations with different characteristics on their social distance and acceptance among those people with or without suicidal attempts among college students in Chongqing.Methods 9808 college students were randomly selected from 11 universities in Chongqing and administered a self-constructed questionnaire"Suicide Attitude and Mental Health Status Questionnaire".A t-test was employed to analyze the social distance and degree of acceptance of college students with or without suicide attempts towards different groups as criminals,hypertensive,with suicide actions,homosexuals,depressive disorder,HIV infection,drug addiction,death of family members,hospitalization history in mental service and alcohol addiction.Results 169 college students had suicide attempts;the reporting rate of suicide attempts was 1.7%.Among college students.the scores higher than 50 on nine items related to social distance towards strangers with those 10 different characteristics and the top three were on those with HIV infection,drug addiction and hospitalization history in mental service.There were differences(P<0.05)in scores of social distance attitude towards strangers with drug addiction(with suicide attempts 83.38±21.82,without suicide attempts 78.55±21.55,t=2.88).hospitalization history in mental service(79.27±21.23,75.67±21.31,t=2.17),homosexuality(66.87±24.77,74.14±21.94,t=-4.25),alcohol addiction(66.72±21.80,61.00±22.80,t=3.23)and hypertension(56.65±20.40,53.36±21.05.t=2.01)between college students with or without suicide attempts.College students scored higher than 50 in 7 items of social rejective attitudes towards acquaintances,of those with hospitalization history in mental service,drug and alcohol addiction ranked the top three.It showed statistical significances in social rejection attitudes towards acquaintances with homosexuality(35.28±30.38,42.83±30.76,t=-3.14),severe depression(56.59±28.49,61.64±25.56,t=-2.53)and suicide behaviors(51.46±28.19,56.56±26.35,t=-2.48)between students with or without suicide attempts.Conclusion College students in Chongqing kept quite far social distance and restrictive behaviors in college students with or without suicide attempts.Targeted interventions on suicide attempters should be carried out accordingly.

Hereditary angioedema (HAE) is an autosomal dominant inherited disease characterized by recurrent and unpredictable episodes of subcutaneous or submucosal edema. These attacks could induce fatal risk when larynx is involved. The estimated prevalence of HAE is about 1 in 50 000. Due to its rarity and the diversity of clinical manifestations, HAE is known little by related physicians and misdiagnosis and mistreatment happens very often. Therefore, it is crucial to improve physicians′ understanding of HAE. To address this, a comprehensive management approach for the diagnosis and treatment of HAE have developed in our hospital. This approach includes intra-hospital multi-disciplinary treatment (MDT), collaboration with provincial network hospitals, patient education online and offline interacting with media propaganda. By implementing this approach, the diagnostic precision was significantly improved, the diagnostic time was significantly shortened, and the frequency of emergency interventions for severe laryngeal edema was significantly reduced. Additionally, the collection of data from HAE patients has provided valuable clinical insights for the diagnosis and treatment of HAE in China.

The 2021 edition of the international World Allergy Organization (WAO)/European Academy of Allergy and Clinical Immunology (EAACI) guideline for the management of hereditary angioedema (HAE) is mainly based on high-quality randomized controlled trials. It provides clinical classification for HAE and offers graded recommendations for on-demand therapy, short-term prophylactic therapy, and long-term prophylactic therapy. Additionally, it provides management strategies for people with different HAE types. This article focused on the interpretation of short-term, long-term prophylactic therapy and on-demand therapy for HAE, supplemented with the latest clinical evidence, aiming to provide references for the long-term management of HAE.

Hereditary angioedema (HAE) is an autosomal dominant inherited disease characterized by recurrent and unpredictable episodes of subcutaneous or submucosal edema. These attacks could induce fatal risk when larynx is involved. The estimated prevalence of HAE is about 1 in 50 000. Due to its rarity and the diversity of clinical manifestations, HAE is known little by related physicians and misdiagnosis and mistreatment happens very often. Therefore, it is crucial to improve physicians′ understanding of HAE. To address this, a comprehensive management approach for the diagnosis and treatment of HAE have developed in our hospital. This approach includes intra-hospital multi-disciplinary treatment (MDT), collaboration with provincial network hospitals, patient education online and offline interacting with media propaganda. By implementing this approach, the diagnostic precision was significantly improved, the diagnostic time was significantly shortened, and the frequency of emergency interventions for severe laryngeal edema was significantly reduced. Additionally, the collection of data from HAE patients has provided valuable clinical insights for the diagnosis and treatment of HAE in China.

The 2021 edition of the international World Allergy Organization (WAO)/European Academy of Allergy and Clinical Immunology (EAACI) guideline for the management of hereditary angioedema (HAE) is mainly based on high-quality randomized controlled trials. It provides clinical classification for HAE and offers graded recommendations for on-demand therapy, short-term prophylactic therapy, and long-term prophylactic therapy. Additionally, it provides management strategies for people with different HAE types. This article focused on the interpretation of short-term, long-term prophylactic therapy and on-demand therapy for HAE, supplemented with the latest clinical evidence, aiming to provide references for the long-term management of HAE.

OBJECTIVETo study the severe acute respiratory syndrome (SARS)-associated coronavirus genotype and its characteristics.

METHODSA SARS-associated coronavirus isolate named ZJ01 was obtained from throat swab samples taken from a patient in Hangzhou, Zhejing province. The complete genome sequence of ZJ01 consisted of 29,715 bp (GenBank accession: AY297028, version: gi: 30910859). Seventeen SARS-associated coronavirus genome sequences in GenBank were compared to analyze the common sequence variations and the probability of co-occurrence of multiple polymorphisms or mutations. Phylogenetic analysis of those sequences was done.

RESULTSBy bioinformatics processing and analysis, the 5 loci nucleotides at ZJ01 genome were found being T, T, G, T and T, respectively. Compared with other SARS-associated coronavirus genomes in the GenBank database, an A/G mutation was detected besides the other 4 mutation loci (C:G:C:C/T:T:T:T) involved in this genetic signature. Therefore a new definition was put forward according to the 5 mutation loci. SARS-associated coronavirus strains would be grouped into two genotypes (C:G:A:C:C/T:T:G:T:T), and abbreviated as SARS coronavirus C genotype and T genotype. On the basis of this new definition, the ZJ01 isolate belongs to SARS-associated coronavirus T genotype, first discovered and reported in mainland China. Phylogenetic analysis of the spike protein gene fragments of these SARS-associated coronavirus strains showed that the GZ01 isolate was phylogenetically distinct from other isolates, and compared with groups F1 and F2 of the T genotype, the isolates of BJ01 and CUHK-W1 were more closely related to the GZ01 isolate. It was interesting to find that two (A/G and C/T) of the five mutation loci occurred in the spike protein gene, which caused changes of Asp to Gly and Thr to Ile in the protein, respectively.

CONCLUSIONAttention should be paid to whether these genotype and mutation patterns are related to the virus's biological activities,epidemic characteristics and host clinical symptoms.

Genotype ; Humans ; Middle Aged ; Mutation ; SARS Virus ; genetics

Objective:To explore the risk factors of subsyndromal delirium (SSD) after cardiac surgery in adults and construct a risk model.Methods:The convenience sampling method was used to select 620 adult patients undergoing cardiac surgery admitted to the Surgical Intensive Care Unit (SICU) of Zhejiang Provincial People's Hospital from January 1, 2017 to December 31, 2018 as the research object. Patients with postoperative SSD were included in the SSD group, and patients without postoperative SSD were included in the non-SSD group. The preoperative, intraoperative and postoperative clinical data and various indicators of all patients were recorded in detail. Through univariate analysis and binary Logistic regression analysis, the risk factors of SSD after cardiac surgery in adults were explored, and the risk model function was constructed.Results:A total of 569 cases were included in the study. Among them, 399 cases of postoperative subdelirium did not occur (non-SSD group) , 170 cases of postoperative subdelirium occurred (SSD group) , and the incidence of SSD was 29.9%. Univariate analysis found that the influencing factors of adult SSD after cardiac surgery were age, emergency surgery, Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score, aortic occlusion time, deep hypothermia circulatory arrest time, intraoperative plasma transfusion, SICU stay time and the use of dexmedetomidine, and the differences between the two groups were statistically significant ( P<0.05) . The binary Logistic regression analysis found that age>76 years [odds ratio ( OR) =4.332, 95% confidence interval ( CI) : (2.103, 8.965) , P<0.001], emergency surgery [ OR=3.453, 95%CI: (1.143, 7.534) , P<0.05], APACHEⅡ score> 15 [ OR=5.453, 95% CI: (1.453, 9.536) , P<0.001], deep hypothermia circulatory arrest time > 34.2 min [ OR=2.132, 95% CI: (1.053, 5.532) , P<0.05] and SICU stay time > 50.0 h [ OR=1.675, 95% CI: (0.832, 5.233) , P<0.05] were independent risks of SSD after cardiac surgery in adults, and the use of dexmedetomidine [ OR=1.536, 95% CI: (0.763, 4.862) , P<0.05] was a protective factor. Conclusions:Age > 76 years, emergency surgery, APACHE Ⅱ score > 15, deep hypothermia circulatory arrest time > 34.2 min, and SICU stay time >50.0 h are independent risk factors for SSD after cardiac surgery in adults, and the use of dexmedetomidine can reduce the occurrence of SSD.

Objectives:To retrieve,evaluate and summarize the contemporary evidence of strategies for weaning from extracorporeal membrane oxygenation(ECMO)of adult patients,and to provide evidence-based reference for clinical practice. Methods:The Web of Science,Embase,Cochrane Library,PubMed,Wanfang Database,CNKI,VIP website,SinoMed,BMJ Best Practice,National Institute for Health and Care Excellence,Joanna Briggs Institute Library,UpToDate and the website of Agency for Healthcare Research and Quality,Society of Critical Care Medicine,American Association of Critical-Care Nurses,European Society of Intensive Care Medicine and Extracorporeal Life Support Organization were researched to collect the literature related to randomized controlled trials,systematic reviews,guidelines,evidence summaries,expert consensuses and clinical decisions in this field.The time limit for the retrieval is from the inception of databases until July 2023. Results:A total of 13 related literature were retrieved,including 4 guidelines,4 expert consensuses,3 clinical decisions and 2 system reviews.Totally 42 evidences were formulated based on retrieved literature,including adequately accessing the ability of gas exchange before weaning from veno-venous ECMO(V-V ECMO)and withdrawing from veno-arterial ECMO(V-A ECMO)as soon as possible when patients's heart function has recovered,involving six aspects such as team composition,anticoagulation measures,assessment before weaning,weaning implementation,cannula and wound management and quality measures. Conclusions:It is suggested to build a professional ECMO team based on the actual hospital situation,to follow the contemporary evidence to standardize the weaning process of patients from ECMO to ensure the patients'safety and improve the outcomes.