To study the kinetics in vivo of a Hantaan virus DNA vaccine, we constructed a fusion DNA vaccine,pEGFP/S, by cloning the S segment of Hantavirus into the vector, pEGFP-C1, which encodes Green fluorescent protein EGFP. In this report, we provide evidence that pEGFP/S was distributed and persistently expressed for more than 60 days in several organs after inoculation. Our findings suggest that the persistent immune responses induced by a Hantaan virus DNA vaccine are likely due to the plasmid pEGFP/S deposited in vivo, which acts as a booster immunization.

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

China ; epidemiology ; Humans ; Neoplasms ; epidemiology ; Registries

To study the mechanism of Shenkangling (SKL), a compound traditional Chinese herbal medicine, combined with prednisone in treating adriamycin-induced nephropathy in rats.

Objective To understand the situation of iodized salt consumption at the household level and non-iodized salt distribution in those areas with low iodized salt coverage.Methods In 2010,iodized salt was monitored in 31 provinces and Xinjiang Production and Construction Corps in accordance with the Monitoring Program of the National Iodine Deficiency Disorders (Trial) (hereinafter referred to as the Program) requirements.Under the jurisdiction of counties (cities,districts,banners) with more than 9 townships (towns,street offices),based on the location of east,west,south,north and center,9 townships (town,district offices) were selected using simple random sampling method; 4 administrative villages (neighborhoods) were selected in each township (town,district office); and 8 residents in each administrative village (neighborhood) were selected.Under the jurisdiction of counties (cities,districts,banners) with less than 9 townships (towns,street offices),based on the location of east,west,south,north and center,1 township(town,district office) was selected using simple random sampling method; 4 administrative villages(neighborhoods) were selected in each township(town,district office);and 15 residents in each administrative village(neighborhood) were selected.Iodized salt coverage rate,qualification rate of iodized salt and consumption rate of qualified iodized salt were calculated in various provinces.The salt samples were tested by semi-quantitative method on the spot and then tested with quantitative method in laboratories.The standard of qualified iodized salt was set as 20-50 mg/kg and that of non-iodized salt was set as ＜ 5 mg/kg (GB/T 13025.7-1999).Results In 2010,a total of 2862 counties(districts,cities and banners) and 14 divisions of Xinjiang Production and Construction Corps,reported the monitoring results,and the monitoring coverage rate was 99.79％(2876/2882).A total of 826 696 copies of edible salt samples were tested,the coverage rate of iodized salt was 98.63％,the consumption rate of qualified iodized salt was 97.95％,and the coverage rate of qualified iodized salt was 96.63％.At province level,only in Tibet iodized salt coverage rate was ＜ 90％.At county level,2755 counties qualified iodized salt coverage rate was ≥90％,and 33 counties iodized salt coverage rate was ＜ 80％.The counties with qualified iodized salt coverage rate of 90％ or more accounted for 96.63％(2785/2882) of the total counties.Conclusions The counties where non-iodized salt coverage is higher than 20％ mainly distributed in the western or coastal areas and adjacent areas with higher iodine.These areas need policy and funding support from governments at all levels to reducc the gap between these areas and other areas.

Aorta, Thoracic ; pathology ; Child ; Child, Preschool ; Female ; Heart Defects, Congenital ; diagnosis ; mortality ; Humans ; Infant ; Infant, Newborn ; Male ; Vascular Malformations ; diagnosis ; mortality

OBJECTIVETo evaluate the effects of left atrial plication (LAP) in patients with giant left atrium (GLA) associated with mitral valve disease.

METHODSTwenty-three patients with left atrial diameter (LAD) over 8.0 cm were enrolled. All cases underwent valve replacement and LAP between November 1993 and November 2004 were studied retrospectively. According to New York Heart Association (NYHA) classification, 15 belonged to class III, 8 to class IV. Mitral valve replacements were performed in 18 patients (mechanical valve in 17 and biological valve in 1), double value replacement in 5, tricuspid valve plasty (TVP) in 15, atrial fibrillation radiofrequency ablation in 2.

RESULTSLow output syndrome happened in 3, respiratory failure in 2. The early death was in 3 cases (operative mortality 13%). The causes of death were: heart failure in 2 cases and stroke in 1. LAD was decreased significantly in patients after operation.

CONCLUSIONSLAP has considerably beneficial effects on improvement of postoperative respiratory and cardiac function, reducing operative mortality. Atrial fibrillation radiofrequency ablation is effective in patients with GLA associated with valve disease. It may be recommended for patients with GLA during mitral valve surgery, especially for patients with LAD > 8.0 cm.

Adult ; Atrial Fibrillation ; complications ; surgery ; Bioprosthesis ; Cardiomegaly ; complications ; surgery ; Catheter Ablation ; Female ; Heart Atria ; surgery ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Male ; Middle Aged ; Mitral Valve Insufficiency ; complications ; surgery ; Mitral Valve Stenosis ; complications ; surgery ; Retrospective Studies ; Treatment Outcome

BACKGROUNDRepair of anterior mitral leaflet (AML) prolapse is still a technical challenge for cardiac surgeons. It is an important issue to find a way to repair the AML prolapse with a reliable and reproducible technique.

METHODSBetween January 2002 and June 2009, the operation of chordal transfer based on the "edge-to-edge" technique was performed in 21 patients with serious mitral valve regurgitation because of prolapse of the anterior leaflet. After the operation, echocardiography was performed in each patient before discharge and at the time of follow-up.

RESULTSAll patients survived the operation. One patient required mitral valve replacement because of anterior leaflet perforation 3 days after the operation. The other patients were free from reoperation. At the time of follow-up, all these patients were in New York Heart Association (NYHA) functional class I. In all these patients, pre-discharge and follow-up echocardiography showed neither stenosis nor significant regurgitation of the mitral valve: the cross-sectional area of the mitral valve was 3.3 - 4.8 cm(2) (mean (3.78 ± 0.52) cm(2)), the mean regurgitation area was (0.45 ± 0.22) cm(2). At the same time, both dimension of left atrium and left ventricle reduced significantly (left atrium diameter: pre-operation (48.26 ± 11.12) mm, post-operation (37.57 ± 9.56) mm, P < 0.05; the end-diastolic diameter of the left ventricle: pre-operation (61.43 ± 8.24) mm, post-operation (42.35 ± 10.79) mm, P < 0.01).

CONCLUSION"Edge-to-edge" chordal transfer technique is a simple, reliable, and reproducible technique that can provide good results for repair of anterior leaflet prolapse of mitral valve.

Adolescent ; Adult ; Aged ; Chordae Tendineae ; surgery ; Echocardiography ; Female ; Humans ; Male ; Middle Aged ; Mitral Valve ; surgery ; Mitral Valve Prolapse ; diagnostic imaging ; surgery ; Suture Techniques

Liver cancer is a common cancer and a leading cause of cancer deaths in China. To aid the government in establishing a control plan for this disease, we provided real-time surveillance information by analyzing liver cancer incidence and mortality in China in 2009 reported by the National Central Cancer Registry. Liver cancer incidence and cases of death were retrieved from the national database using the ICD-10 topography code "C22". Crude incidence and mortality were calculated and stratified by sex, age, and location (urban/rural). China's population in 1982 and Segi (world) population structures were used for age-standardized rates. In cancer registration areas in 2009, the crude incidence of liver cancer was 28.71/100,000, making it the fourth most common cancer in China, third most common in males, and fifth most common in females. The crude mortality of liver cancer was 26.04/100,000, making it the second leading cause of cancer death in China and urban areas and the third leading cause in rural areas. Incidence and mortality were higher in males than in females and were higher in rural areas than in urban areas. The age-specific incidence and mortality were relatively low among age groups under 30 years but dramatically increased and peaked in the 80-84 years old group. These findings confirm that liver cancer is a common and fatal cancer in China. Primary and secondary prevention such as health education, hepatitis B virus vaccination, and early detection should be carried out both in males and females, in urban and rural areas.
Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Incidence ; Infant ; Liver Neoplasms ; epidemiology ; mortality ; Male ; Middle Aged ; Registries ; Rural Population ; Sex Factors ; Urban Population ; Young Adult

AIMTo determine whether repetitive exposure to high sustained +Gz acceleration induces persisting changes in the myocardial free radical metabolism and observe the protective effects of low-G training and antioxidant tea polyphenols (TP).

METHODSThirty-two male Wistar rats were randomly divided into four groups (n=8 each): group A, restrained, was only submitted to +1 Gz for 5 min. Group B, centrifuged, was exposed to five plateaus of 30 s at +10 Gz for intermittent times, three times a week, for three weeks. Group C, low-G trained, was exposed to +2 Gz for 5 min about 1 h prior to +10 Gz stress, and group D was orally given TP at dose of 200 mg/kg about 1 h prior to +10 Gz stress. On the next day morning after last centrifuge run, the rats were decapitated and the hearts were quickly removed. Malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity were measured. Additionally, CuZn-SOD and inducible NO synthase (iNOS) enzymatic contents were examined by immunohistochemical staining and their mRNA were analyzed by semi-quantitative reverse transcription polymerase chain reaction(RT-PCR).

RESULTSCompared with group A, MDA concentration and iNOS enzymatic content in myocardial mitochondria were increased significantly (P < 0.05) in group B. Compared with group B, mitochondrial SOD activity was significantly increased in group C (P < 0.05). iNOS enzymatic content was significantly decreased in group C and D. There were no significant differences of CuZn-SOD content, CuZn-SOD and iNOS mRNA levels among the four groups.

CONCLUSIONRepeated high +Gz exposure can induce myocardial free radical metabolic disorder and mainly result in mitochondrial peroxidative injury. But low-G training and natural antioxidant TP have protective effects, and the former is better.

Acceleration ; Adaptation, Physiological ; physiology ; Animals ; Free Radicals ; metabolism ; Male ; Myocardium ; metabolism ; Polyphenols ; pharmacology ; Rats ; Rats, Wistar ; Tea ; chemistry