1. Bioinformatics analysis on structure and function and expression vector construction of SARS-CoV-2 related protein TMPRSS2
Ben-Jin XU ; Hong-Rong YAN ; Miao DU ; Yan XUAN ; Yan-Xiang HOU ; Ya-Nan YANG ; Ling LIU ; Zhuo-Xi LI ; Lei FAN ; Jing LI ; Xiao-Cong CHEN ; Wen-Ting TANG ; Jun-Xiao YU ; Jie MEN ; Bin-Yu SONG ; Xiao-Liang LIU
Chinese Pharmacological Bulletin 2022;38(8):1218-1226
Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.
2.Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China.
Yan MA ; Dong Shan ZHU ; Ren Bo CHEN ; Nan Nan SHI ; Si Hong LIU ; Yi Pin FAN ; Gui Hui WU ; Pu Ye YANG ; Jiang Feng BAI ; Hong CHEN ; Li Ying CHEN ; Qiao FENG ; Tuan Mao GUO ; Yong HOU ; Gui Fen HU ; Xiao Mei HU ; Yun Hong HU ; Jin HUANG ; Qiu Hua HUANG ; Shao Zhen HUANG ; Liang JI ; Hai Hao JIN ; Xiao LEI ; Chun Yan LI ; Min Qing LI ; Qun Tang LI ; Xian Yong LI ; Hong De LIU ; Jin Ping LIU ; Zhang LIU ; Yu Ting MA ; Ya MAO ; Liu Fen MO ; Hui NA ; Jing Wei WANG ; Fang Li SONG ; Sheng SUN ; Dong Ting WANG ; Ming Xuan WANG ; Xiao Yan WANG ; Yin Zhen WANG ; Yu Dong WANG ; Wei WU ; Lan Ping WU ; Yan Hua XIAO ; Hai Jun XIE ; Hong Ming XU ; Shou Fang XU ; Rui Xia XUE ; Chun YANG ; Kai Jun YANG ; Sheng Li YUAN ; Gong Qi ZHANG ; Jin Bo ZHANG ; Lin Song ZHANG ; Shu Sen ZHAO ; Wan Ying ZHAO ; Kai ZHENG ; Ying Chun ZHOU ; Jun Teng ZHU ; Tian Qing ZHU ; Hua Min ZHANG ; Yan Ping WANG ; Yong Yan WANG
Biomedical and Environmental Sciences 2020;33(12):893-905
Objective:
Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.
Methods:
A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio (
Results:
Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks.
Conclusion
Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult
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Aged
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COVID-19/virology*
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China/epidemiology*
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Comorbidity
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Female
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Humans
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Male
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Middle Aged
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Retrospective Studies
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Severity of Illness Index
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Treatment Outcome
3. Immunogenicity and safety of co-immunization with 23-valent pneumococcal polysaccharide vaccine and influenza virus split vaccine for children aged 3-7 years
Zhiguo WANG ; Xiang SUN ; Min ZHANG ; Fenyang TANG ; Fubao MA ; Yan XU ; Ran HU ; Yanli MA ; Yanhui XIAO ; Haiping CHEN ; Linyun LUO
Chinese Journal of Microbiology and Immunology 2019;39(10):758-762
Objective:
To evaluate the immunogenicity and safety of concomitant administration of 23-valent pneumococcal polysaccharide vaccine (PPV23) and trivalent influenza vaccine (TIV) in preschoolers.
Methods:
A total of 1 035 children aged 3-7 years were enrolled in this study and randomly divided into three groups, inoculated PPV23, TIV and both, respectively. A one-year follow-up study was conducted for immunogenicity and safety analysis.
Results:
A total of 1 035 serological specimens were collected, including 327 in PPV23 group, 348 in TIV group and 360 in concomitant vaccination group. No significant differences in geometric mean concentrations (GMC) of seven pneumococcal serotypes were observed between the PPV23 group and the concomitant vaccination group. Compared with the TIV group, the concomitant vaccination group showed higher serological conversion rate of H3 type (88.75% vs 84.20%,
4. Study of mumps immunity after administrating measles-mumps-rubella vaccine among children aged 2-7 years old in Jiangsu Province in 2015
Yuanbao LIU ; Ying HU ; Xiuying DENG ; Zhiguo WANG ; Xiang SUN ; Peishan LU ; Hongxiong GUO ; Fenyang TANG ; Minghao ZHOU
Chinese Journal of Preventive Medicine 2017;51(7):593-597
Objective:
To investigate the immunity to mumps after administrating measles-mumps-rubella vaccine (MMR) among children aged 2-7 years old in Jiangsu province in 2015.
Methods:
A total of 4 190 healthy children aged 2-7 years old, living in local places for at least 3 months, and having been vaccinated at least 1 dose MMR were recruited to the study from Wujin district of Changzhou city, Gaogang district of Taizhou city and Ganyu district of Lianyungang city by using stratified cluster random sampling method between September and November, 2015. Those who did not accept MMR vaccination, who refused venous blood collection, who had affected mumps according to the memory of parents or teachers and who were diagnosed serious disease by clinical doctors were excluded from study. The self-designed questionnaire was used to collect the general information of the subjects and their MMR immunization history; and 0.5-2.0 ml of venous blood was collected from each subject. ELISA was used to detect the mumps antibody level in the serum of patients. Positive was defined as the antibody level ≥108 mU/ml, and negative as <108 mU/ml. χ2 test was used to compare the difference in positive rates among subjects; and analysis of variance was used to compare the GMC changes in different time points after MMR vaccination.
Results:
Among 4 190 children, 2 280 were males (54.42%) and 1 910 were females(45.58%), and the positive rate of IgG antibody was 81.38% (3 344). There were 3 156 (95.18%) children vaccinated with one dose MMR, 187 (4.80%) children with two dose MMR, and 1 (0.02%) child with three dose MMR. The difference in positive rate of IgG antibody among different aged subjects showed statistical significance (χ2=58.61,
5.Antibiotic resistance and molecular characterization of Vibrio cholera strains isolated from an outbreak of cholera epidemic in Jiangsu province.
Chen DONG ; Xuefeng ZHANG ; Changjun BAO ; Yefei ZHU ; Ling ZHUANG ; Zhongming TAN ; Huimin QIAN ; Fenyang TANG
Chinese Journal of Preventive Medicine 2015;49(2):128-131
OBJECTIVETo assess the antibiotic resistance and molecular characterization of cholera strains and to provide basis for clinical treatment and prevention of cholera.
METHODS4 stains isolated from an outbreak of cholera epidemic in Huai'an City in Jiangsu province in September 2010 were characterized using antibiotic susceptibility, biotype analysis, virluence genes detection, ctxB gene sequencing, and PFGE analysis.
RESULTSThe 4 strains were all resistant to sulphamethoxazole/trimethoprim, erythromycin, streptomycin. High drug susceptibility of the samples was found to 6 kinds of antibiotics such as amikacin, norfloxacin, ciprofloxacin, gentamicin, chloramphenicol, ampicillin. The isolates expressed phenotypic traits of both serogroup O1 ogawa and El Tor and carried 9 kinds of virulence genes, ctxA, ace, zot, toxR, tcpI, ompU, rtxC, tcpA, and hlyA gene. They were also identified as harboring the classical ctxB genotype based on amino acid residue substitutions. The PFGE profiles of NotI showed a single banding pattern, while SfiI's was 2 banding patterns.
CONCLUSIONThe bacterium type of Vibrio cholerae causing the epidemic outbreak of cholera belonged to the atypical EL Tor variant which was also identified as toxicogenic strain. The mapping of the strains prompted that there should be the common contamination source. Drug sensitivity test can guide the clinical drug use, in order to reduce the emergence of resistant strains.
Anti-Bacterial Agents ; Cholera ; Cholera Toxin ; Disease Outbreaks ; Drug Resistance, Bacterial ; Drug Resistance, Microbial ; Epidemics ; Genotype ; Humans ; Vibrio cholerae ; Vibrio cholerae O1 ; Virulence
7.Emergence of truncated PB1-F2 protein of H3N2 influenza virus during its epidemic period in Jiangsu Province, China.
Pingmin WEI ; Pengfei LUO ; Wei LI ; Hairong ZI ; Xian QI ; Fei DENG ; Yuanfang QIN ; Bin WU ; Fenyang TANG
Chinese Medical Journal 2014;127(8):1487-1492
BACKGROUNDPB1-F2 protein has been proven to increase the pathogenicity of influenza A virus (IAV) strains in primary infection and in secondary bacterial infection. It can also regulate the activity of viral polymerase. However, it was shown in another retrospective study that a portion of IAVs do not express full-length PB1-F2 protein during virus development; different kinds of stop codons cause exits in the open reading frames and form PB1-F2 gene products with the corresponding genotypes. Truncated PB1-F2 in human H3N2 IAVs has long been detected in North America but its evolution in China is still unclear.
METHODSInfluenza-like illnesses (ILIs) from the whole of Jiangsu Province were collected and inspected to determine the type and subtype of the viruses. A portion of isolates collected in the epidemic period were selected as samples for later whole-genome sequencing, and the exact sequences were determined and analyzed.
RESULTSH3N2 influenza virus was one of the epidemical strains which had been prevalent during 2009-2010, in Jiangsu. Five H3N2 isolates with truncated PB1-F2 protein (25aa) were detected in influenza samples from Nanjing and Xuzhou, while seven similar H3N2 isolates were also reported in Niigata, Japan.
CONCLUSIONThis emergence indicates the possibility that there has been transmission of the H3N2 virus between the two countries.
China ; epidemiology ; Humans ; Influenza A Virus, H3N2 Subtype ; genetics ; metabolism ; Influenza, Human ; virology ; Viral Proteins ; chemistry ; genetics ; metabolism
8.An outbreak of brucellosis in a village in Jiangsu province.
Lunhui XIANG ; Weizhong ZHOU ; Fenyang TANG ; Yefei ZHU ; Zhongming TAN ; Xiaoyong LIU ; Meng BAO ; Man DIAO ; Guoqing SHI
Chinese Journal of Epidemiology 2014;35(10):1135-1137
OBJECTIVETo investigate the cause and related risk factors of an outbreak caused by Brucellosis.
METHODSEpidemiological investigation and laboratory test were carried out among occupationally invloved population including sheep slaughters and sellers in the village.
RESULTS18 people were serology positive among the 129 occupationally involved persons under survey. Seven of them were confirmed cases, 11 were latent infection, to make the overall attack rate as 14%. 90% of the sheep were from high-risk areas of Brucella. Among the occupationally involved persons, 89% of them never wore face masks, 84% never wear overalls and 70% never wear gloves. Factors as:work but wearing no gloves (RR = 7.4, 95%CI:1.1-53.0), with hand wound (RR = 3.4, 95%CI:1.1-11.0) could increase the risk of Brucella infection.
CONCLUSIONThe cause of this outbreak was due to the plentiful influx of unchecked sheep from the northern part of China and the employees in the process of sheep slaughtering or trading were lack of effective prevention programs.
Abattoirs ; Animals ; Brucella ; isolation & purification ; Brucellosis ; epidemiology ; China ; epidemiology ; Commerce ; Disease Outbreaks ; Humans ; Incidence ; Occupational Diseases ; epidemiology ; Risk Factors ; Sheep ; microbiology
9.An outbreak of brucellosis in a village in Jiangsu province
Lunhui XIANG ; Weizhong ZHOU ; Fenyang TANG ; Yefei ZHU ; Zhongming TAN ; Xiaoyong LIU ; Meng BAO ; Man DIAO ; Guoqing SHI
Chinese Journal of Epidemiology 2014;(10):1135-1137
Objective To investigate the cause and related risk factors of an outbreak caused by Brucellosis. Methods Epidemiological investigation and laboratory test were carried out among occupationally invloved population including sheep slaughters and sellers in the village. Results 18 people were serology positive among the 129 occupationally involved persons under survey. Seven of them were confirmed cases,11 were latent infection,to make the overall attack rate as 14%. 90%of the sheep were from high-risk areas of Brucella. Among the occupationally involved persons,89%of them never wore face masks,84%never wear overalls and 70%never wear gloves. Factors as:work but wearing no gloves(RR=7.4,95%CI:1.1-53.0),with hand wound(RR=3.4,95%CI:1.1-11.0) could increase the risk of Brucella infection. Conclusion The cause of this outbreak was due to the plentiful influx of unchecked sheep from the northern part of China and the employees in the process of sheep slaughtering or trading were lack of effective prevention programs.
10.Epidemiological investigation on an outbreak of autumn tsutsugamushi disease in Taizhou region of Jiangsu Province
Kai CHU ; Zhongming TAN ; Dong WEN ; Qianhua YI ; Fanyue MENG ; Fenyang TANG
Chinese Journal of Infectious Diseases 2013;(6):358-361
Objective To analyze the epidemiological and clinical characteristics of an outbreak of tsutsugamushi disease in Taizhou region of Jiangsu Province,and to clarify new changes of endemic focus of tsutsugamushi disease in Jiangsu Province.Methods The definition of tsutsugamushi infected cases was determined,field epidemiological investigation with analysis of clinical features and polymerase chain reaction (PCR) results to diagnose tsutsugamushi disease were combined.Some of the positive samples were conducted genotyping by amplification and sequencing.Results The outbreak occurred from October to November,2011.The endemic focus located on the plain with humid climate and abundant rainfall.Fifteen cases of tsutsugamushi disease were found,including 6 PCR confirmed cases,5 clinically diagnosed cases,and 4 suspected cases.The main clinical symptoms were fever in 15 cases,skin rash in 14 cases,lymphadenectasis in 3 cases,skin eschar or ulcer in 12 cases,and liver dysfunction in 3 cases.None of the patients developed severe complications,and all recovered rapidly after the treatment.Comparing the sequencing results of positive samples with standard strains,the homology of base sequences was 99.00% with that of Kawasaki.Conclusions The outbreak of tsutsugamushi disease in Jiangsu Province in 2011 is of autumn type in transitional endemic focus,and the pathogen is Kawasaki Orientia tsutsugamushi.

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