Epidemiological investigation of a case with SARS-CoV-2 infection associated with overseas countries at an international harbor / 预防医学

Objective@#To investigate the origin of infection and risk factors of a case with SARS-CoV-2 infection associated with overseas countries in the Ningbo-Zhoushan Port, Zhejiang Province, so as to provide the evidence for improving the COVID-19 control measures at ports.@*Methods@#Ningbo Center for Disease Control and Prevention ( CDC ) and Beilun CDC conducted case finding and epidemiological surveys immediately after being informed. The general information, history of vaccination and the travel during the latest 14 days were collected from the positive case, and all close contacts were tracked. Saliva samples were collected for SARS-CoV-2 nucleic acid testing and whole-genome sequencing, and the sequencing results were aligned with the GISAID's EpiCoV database. The origin of infection and transmission route of the positive case was investigated.@*Results@#A case was identified positive for SARS-CoV-2 nucleic acid during company M's routine screening in the Ningbo-Zhoushan Port on August 10, 2021, and was confirmed positive for SARS-CoV-2 nucleic acid by Beilun CDC and Ningbo CDC on August 11. Whole-genome sequencing showed SARS-CoV-2 B.1.617.2 ( Delta ) variant, which shared the highest homology with the virus sequence uploaded by Russia on June, 2021 ( Russia/MOW-RII-MH27356S/2021 ). The case was a bundling worker for overseas container ships, and reported communicated with foreign boatmen and contacted materials without protected interventions on the SINOKOR AKITA Container Ship between August 4 and 5, 2021. This ship anchored at Vladivostok, Russia from July 27 to 29, anchored at Ningbo Harbor on August 4, and departed on August 5. Then, 11 boatmen from this ship were tested positive for SARS-CoV-2 nucleic acid on August 8. One asymptomatic case was reported in this epidemic; 254 close contacts and 617 secondary close contacts were identified, and all were tested negative for SARS-CoV-2 nucleic acid. No new cases with SARS-CoV-2 infections were detected until August 25, 2021, and the emergency response was therefore terminated.@*Conclusions@#The infection was a sporadic COVID-19 epidemic associated with overseas countries, which was caused by Delta variant infection through contacts with foreign boatmen or materials by a bundling worker in Ningbo-Zhoushan Port; fortunately, no epidemic spread occurred. Intensified closed-loop management and increased frequency of SARS-CoV-2 nucleic acid test among high-risk populations, and improving the precision and rapid emergency treatment of COVID-19 epidemics are required for the containment of COVID-19 at ports.

Epidemiological feature, viral shedding, and antibody seroconversion among asymptomatic carriers and symptomatic/ presymptomatic COVID-19 patients

Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. However, data concerning the epidemiological features, viral shedding, and antibody dynamics between asymptomatic SARS-CoV-2 carriers and COVID-19 patients remain controversial. We enrolled 193 subjects infected with SARS-CoV-2 in Ningbo and Zhoushan, Zhejiang, China from January 21 to March 6, 2020. All subjects were followed up to monitor the dynamics of immunoglobulin M (IgM) and IgG against SARS-CoV-2. Of those, 31 were asymptomatic carriers, 149 were symptomatic patients, and 14 were presymptomatic patients. Compared to symptomatic patients, asymptomatic carriers were younger and had higher levels of white blood cell and lymphocyte, lower levels of C-reactive protein and viral load, and shorter viral shedding duration. Conversion of IgM from positive to negative was shorter in asymptomatic carriers than in COVID-19 patients (P=0.030). The proportion of those persistently seropositive for IgG was higher in COVID-19 patients than in asymptomatic carriers (P=0.037). Viral load was higher in symptomatic than presymptomatic patients. Viral shedding was longer in presymptomatic patients than in asymptomatic carriers. Conclusively, asymptomatic carriers have a higher antiviral immunity to clear SARS-CoV-2 than do symptomatic patients and this antiviral immunity is not contributable to humoral immunity.

Relations between high risk sexual behavior and HIV infection among men who have sex with men in ways of meeting male partners / 中华流行病学杂志

Objective@#To understand the relations between high risk sexual behavior and HIV infection among MSM in ways of finding male partners in Ningbo.@*Methods@#A cross-sectional study was conducted in Ningbo between April and November in 2018. Data related to socio-demographics, ways of finding male partners, adoption of gay apps and sexual behaviors were collected by snowball method. Blood samples were drawn for HIV antibody testing. Classified data was evaluated by chi-square test. Related factors on HIV infection were analyzed by multivariate logistic regression.@*Results@#A total of 735 participants were included in this study. Ways of finding male partners would through gay apps (60.8%, 447/735), QQ/Wechat (32.3%, 237/735) and gay-places (6.9%, 51/735). Related information on high risk sexual behavior and HIV infection among gay apps users were found as: 16.8%(75) had sexual behavior once per week in the past 6 months, 41.8% (187/447) had multiple sexual partners, 12.1% (54/447) had unprotected anal intercourse in the last time, 52.3% (234/447) having had unprotected anal intercourse in the past 6 months. The overall HIV prevalence rate was 12.1%(54/447). Among the HIV cases who got infected within the two years, 68.6%(24/35) of them had used gay apps for less than two years. Results from the, multivariate logistic regression analysis showed that gay apps users were more susceptible to infected HIV than those who used the QQ/Wechat (OR=3.03, 95%CI: 1.30-7.07).@*Conclusions@#Gay apps was popularly known among the Ningbo MSM, and was associated with the high risk sexual behaviors and HIV infection. HIV control and prevention programs should be strengthened in the MSM population who used the gay apps. Related surveillance and intervention programs for MSM, who use the gay apps, need to be further reinforced.

Survival analysis of HIV/AIDS patients with access to highly antiretroviral therapy in Ningbo during 2004-2015 / 中华流行病学杂志

Objective To understand the epidemiology characteristics and survival status of HIV/AIDS patients with access to highly antiretroviral therapy (HAART) in Ningbo during 2004-2015.Methods A retrospective cohort study was conducted among HIV/AIDS patients diagnosed between 2004 and 2015.Life Tables were used to estimate survival rates,and Kaplan-Meier curve with Log rank test were used to describe the survival curves and the Cox proportional hazard model was used to determine predictors of mortality.Results Of the subjects,the median age when starting HAART was 35 years (IQR:27-45 years).Most of them were males,local residents,married,infected through heterosexual sexual transmission,and their baseline CD4 T cells counts were mainly ≤ 200 cells/μ 1,and most of them were at clinical stage Ⅰ (WHO).The cumulative survival rate was 96.75％ for the first year,92.36％ for the fifth year,91.87％ for the seventh year and 90.02％ for the tenth year.The risk of the mortality was 17.34 times higher for those aged ＞60 years compared with those aged ≤20 years (95％ CI:2.11-142.71),2.83 times higher for those at clinical stage ⅣV (WHO) compared with those at clinical stage Ⅰ (WHO) (95％CI:1.67-4.80) and 3.26 times higher for those with drug resistance compared with those without drug resistance (95％ CI:1.77-6.01).Blood transmission,lower CD4 + T cell level,BMI ＜ 18.5,unmarried were the risk factors for the mortality.Conclusions The effect of HAART was obvious in the HIV/AIDS patients in Ningbo,their survival rate was high.The finding indicated that it is necessary to strengthen the health care for old population and health education about AIDS prevention and control,and conduct large scale screening.Early discovery,early diagnosis,early treatment and improving treatment compliancy are still the effective ways to reduce the mortality.

Survival analysis of HIV/AIDS patients with access to highly antiretroviral therapy in Ningbo during 2004-2015 / 中华流行病学杂志

Objective To understand the epidemiology characteristics and survival status of HIV/AIDS patients with access to highly antiretroviral therapy (HAART) in Ningbo during 2004-2015.Methods A retrospective cohort study was conducted among HIV/AIDS patients diagnosed between 2004 and 2015.Life Tables were used to estimate survival rates,and Kaplan-Meier curve with Log rank test were used to describe the survival curves and the Cox proportional hazard model was used to determine predictors of mortality.Results Of the subjects,the median age when starting HAART was 35 years (IQR:27-45 years).Most of them were males,local residents,married,infected through heterosexual sexual transmission,and their baseline CD4 T cells counts were mainly ≤ 200 cells/μ 1,and most of them were at clinical stage Ⅰ (WHO).The cumulative survival rate was 96.75％ for the first year,92.36％ for the fifth year,91.87％ for the seventh year and 90.02％ for the tenth year.The risk of the mortality was 17.34 times higher for those aged ＞60 years compared with those aged ≤20 years (95％ CI:2.11-142.71),2.83 times higher for those at clinical stage ⅣV (WHO) compared with those at clinical stage Ⅰ (WHO) (95％CI:1.67-4.80) and 3.26 times higher for those with drug resistance compared with those without drug resistance (95％ CI:1.77-6.01).Blood transmission,lower CD4 + T cell level,BMI ＜ 18.5,unmarried were the risk factors for the mortality.Conclusions The effect of HAART was obvious in the HIV/AIDS patients in Ningbo,their survival rate was high.The finding indicated that it is necessary to strengthen the health care for old population and health education about AIDS prevention and control,and conduct large scale screening.Early discovery,early diagnosis,early treatment and improving treatment compliancy are still the effective ways to reduce the mortality.

Improvement of butanol production by Escherichia coli via Tn5 transposon mediated mutagenesis / 生物工程学报

For engineering an efficient butanol-producing Escherichia coli strain, many efforts have been paid on the known genes or pathways based on current knowledge. However, many genes in the genome could also contribute to butanol production in an unexpected way. In this work, we used Tn5 transposon to construct a mutant library including 1 196 strains in a previously engineered butanol-producing E. coli strain. To screen the strains with improved titer of butanol production, we developed a high-throughput method for pyruvate detection based on dinitrophenylhydrazine reaction using 96-well microplate reader, because pyruvate is the precursor of butanol and its concentration is inversely correlated with butanol in the fermentation broth. Using this method, we successfully screened three mutants with increased butanol titer. The insertion sites of Tn5 transposon was in the ORFs of pykA, tdk, and cadC by inverse PCR and sequencing. These found genes would be efficient targets for further strain improvement. And the genome scanning strategy described here will be helpful for other microbial cell factory construction.

Iodine nutritional status and prevalence of thyroid nodules among residents using non-iodized salt in Ningbo City, Zhejiang Province / 中华地方病学杂志

Objective To investigate the iodine nutritional status,thyroid function and the prevalence of thyroid nodules of residents using non-iodized salt in Ningbo City,Zhejiang Province.Methods In 2011,using typical sampling method,6 villages/communities consumption of non-iodized salt were selected as study fields and residents aged 6-70 were selected as study subjects in Ningbo.Urinary iodine detection,thyroid ultrasound examination and tests of thyroid function [free triiodothyronine (FT3),free thyroxine (FT4),thyroid stimulating hormone (TSH),thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb)] were performed in all participants.Urinary iodine concentration (UIC) was determined by arsenic cerium catalytic spectrophotometry,and thyroid function was monitored by chemiluminescence method.Results A total of 1 177 residents agreed to participate in the study,482 were male,and 695 were female (including 2 pregnant women).The participants' mean age was (48.54 ± 13.98) years.The median UIC in all participants was 90.36 μg/L,and the proportions with a UIC ＜ 100μg/L was 56.07％ (660/1 177).Furthermore,the median UIC in male was 97.05 μg/L and in female was 83.84 μg/L,there was a significant difference in UICs between male and female (Z =-2.99,P ＜ 0.05).Similarly,significant difference in UICs was observed among age groups (x2 =99.34,P ＜ 0.01).Among the participants,19.88％ had thyroid nodules,with standardized prevalence rate of 13.95％.Furthermore,in male,11.83％ had thyroid nodules,with standardized prevalence rate of 8.11％,and in female was 25.47％,with standardized prevalence rate of 19.83％,there was a significant difference in the detection rate of thyroid nodules between male and female (x2 =33.25,P ＜ 0.01).Likewise,significant difference in the detection rate of thyroid nodules was observed among age groups (x2=49.65,P＜ 0.01),and there was a positive and significant correlation between the detection rate of thyroid nodules and increasing age (x2trend =44.22,P ＜ 0.01).Conclusions The residents who using non-iodized salt in Ningbo City are in the status of iodine deficiency.The detection rate of thyroid nodules is higher in female than in male and it has increased with age.

Risk factors for thyroid nodules among residents of Ningbo City in Zhejiang Province / 中华地方病学杂志

Objective To investigate the prevalence of thyroid nodules among residents of Ningbo City and to explore the risk factors for thyroid nodules.Methods Totally 3 596 residents aged 6-70 were selected by multistage stratified cluster random sampling in Ningbo City,2011.Thyroid ultrasound examination was performed in all participants,while salt iodine and urinary iodine were measured.Possible risk factors for thyroid nodules were analyzed by single factor and multi-factor logistic regression.Results The prevalence rate of thyroid nodules in residents of Ningbo City was 22.66％ (815/3 596),with standardized prevalence rate of 17.69％.Female [(odds ratio (OR) =2.06,95％ confidence interval (CI) =1.74-2.43],groups of aged 18-(OR =3.42,95％ CI =1.22-9.61),aged 40-(OR =13.06,95％ CI =4.80-35.51),aged 65-(OR =16.67,95％ CI =5.97-46.54) and occasional consumption of seafood habits (less than twice per week,OR =1.23,95％ CI =1.02-1.49) were significant associated with thyroid nodules.Conclusions There is no link Letween iodine nutrition and thyroid nodules.It is demonstrated that female and aged ≥ 18 groups have higher risk of thyroid nodules; frequent consumption of seafood seems to be a protective factor.

Discovery of a novel gene involved in autolysis of Clostridium cells

Cell autolysis plays important physiological roles in the life cycle of clostridial cells. Understanding the genetic basis of the autolysis phenomenon of pathogenic Clostridium or solvent producing Clostridium cells might provide new insights into this important species. Genes that might be involved in autolysis of Clostridium acetobutylicum, a model clostridial species, were investigated in this study. Twelve putative autolysin genes were predicted in C. acetobutylicum DSM 1731 genome through bioinformatics analysis. Of these 12 genes, gene SMB_G3117 was selected for testing the in tracellular autolysin activity, growth profile, viable cell numbers, and cellular morphology. We found that overexpression of SMB_G3117 gene led to earlier ceased growth, significantly increased number of dead cells, and clear electrolucent cavities, while disruption of SMB_G3117 gene exhibited remarkably reduced intracellular autolysin activity. These results indicate that SMB_G3117 is a novel gene involved in cellular autolysis of C. acetobutylicum.

Developing controllable hypermutable Clostridium cells through manipulating its methyl-directed mismatch repair system

Development of controllable hypermutable cells can greatly benefit understanding and harnessing microbial evolution. However, there have not been any similar systems developed for Clostridium, an important bacterial genus. Here we report a novel two-step strategy for developing controllable hypermutable cells of Clostridium acetobutylicum, an important and representative industrial strain. Firstly, the mutS/L operon essential for methyldirected mismatch repair (MMR) activity was inactivated from the genome of C. acetobutylicum to generate hypermutable cells with over 250-fold increased mutation rates. Secondly, a proofreading control system carrying an inducibly expressed mutS/L operon was constructed. The hypermutable cells and the proofreading control system were integrated to form a controllable hypermutable system SMBMutC, of which the mutation rates can be regulated by the concentration of anhydrotetracycline (aTc). Duplication of the miniPthl-tetR module of the proofreading control system further significantly expanded the regulatory space of the mutation rates, demonstrating hypermutable Clostridium cells with controllable mutation rates are generated. The developed C. acetobutylicum strain SMBMutC2 showed higher survival capacities than the control strain facing butanol-stress, indicating greatly increased evolvability and adaptability of the controllable hypermutable cells under environmental challenges.

Genetic modification systems for Clostridium acetobutylicum / 生物工程学报

Clostridium acetobutylicum, a biofuel-butanol producer, has attracted worldwide interests. Strain improvement is important for the process of biobutanol industrialization where efficient genetic modification systems are essential. In this review, the history of genetic modification systems of C. acetobutylicum was introduced, and the types and principles of these systems and their disadvantages are summarized and analysed. The development of updated genetic modification systems for C. acetobutylicum is also proposed.