CBPH assay for the highest sensitive detection of SARS-COV-2 in the semen.

BACKGROUND: Great concerns have been raised on SARS-CoV-2 impact on men's andrological well-being, and many studies have attempted to determine whether SARS-CoV-2 is present in the semen and till now the data are unclear and somehow ambiguous. However, these studies used quantitative real-time (qRT) PCR, which is not sufficiently sensitive to detect nucleic acids in clinical samples with a low viral load. METHODS: The clinical performance of various nucleic acid detection methods (qRT-PCR, OSN-qRT-PCR, cd-PCR, and CBPH) was assessed for SARS-CoV-2 using 236 clinical samples from laboratory-confirmed COVID-19 cases. Then, the presence of SARS-CoV-2 in the semen of 12 recovering patients was investigated using qRT-PCR, OSN-qRT-PCR, cd-PCR, and CBPH in parallel using 24 paired semen, blood, throat swab, and urine samples. RESULTS: The sensitivity and specificity along with AUC of CBPH was markedly higher than the other 3methods. Although qRT-PCR, OSN-qRT-PCR and cdPCR detected no SARS-CoV-2 RNA in throat swab, blood, urine, and semen samples of the 12 patients, CBPH detected the presence of SARS-CoV-2 genome fragments in semen samples, but not in paired urine samples, of 3 of 12 patients. The existing SARS-CoV-2 genome fragments were metabolized over time. CONCLUSIONS: Both OSN-qRT-PCR and cdPCR had better performance than qRT-PCR, and CBPH had the highest diagnostic performance in detecting SARS-CoV-2, which contributed the most improvement to the determination of the critical value in gray area samples with low vrial load, which then provides a rational screening strategy for studying the clearance of coronavirus in the semen over time in patients recovering from COVID-19. Although the presence of SARS-CoV-2 fragments in the semen was demonstrated by CBPH, COVID-19 is unlikely to be sexually transmitted from male partners for at least 3 months after hospital discharge.

Safety and immunogenicity of heterologous boosting with orally aerosolised or intramuscular Ad5-nCoV vaccine and homologous boosting with inactivated vaccines (BBIBP-CorV or CoronaVac) in children and adolescents: a randomised, open-label, parallel-controlled, non-inferiority, single-centre study.

BACKGROUND: Heterologous booster immunisation with orally administered aerosolised Ad5-nCoV vaccine (AAd5) has been shown to be safe and highly immunogenic in adults. Here, we aimed to assess the safety and immunogenicity of heterologous booster immunisation with orally administered AAd5 in children and adolescents aged 6-17 years who had received two doses of inactivated vaccine (BBIBP-CorV or CoronaVac). METHODS: We did a randomised, open-label, parallel-controlled, non-inferiority study to assess the safety and immunogenicity of heterologous booster immunisation with AAd5 (0·1 mL) or intramuscular Ad5-nCoV vaccine (IMAd5; 0·3 mL) and homologous booster immunisation with inactivated vaccine (BBIBP-CorV or CoronaVac; 0·5 mL) in children (aged 6-12 years) and adolescents (aged 13-17 years) who had received two doses of inactivated vaccine at least 3 months earlier in Hunan, China. Children and adolescents who were previously immunised with two-dose BBIBP-CorV or CoronaVac were recruited for eligibility screening at least 3 months after the second dose. A stratified block method was used for randomisation, and participants were stratified by age and randomly assigned (3:1:1) to receive AAd5, IMAd5, or inactivated vaccine. The study staff and participants were not masked to treatment allocation. Laboratory and statistical staff were masked during the study. In this interim analysis, adverse events within 14 days and geometric mean titre (GMT) of serum neutralising antibodies on day 28 after the booster vaccination, based on the per-protocol population, were used as the primary outcomes. The analysis of non-inferiority was based on comparison using a one-sided 97·5% CI with a non-inferiority margin of 0·67. This study was registered at ClinicalTrials.gov, NCT05330871, and is ongoing. FINDINGS: Between April 17 and May 28, 2022, 436 participants were screened and 360 were enrolled: 220 received AAd5, 70 received IMAd5, and 70 received inactivated vaccine. Within 14 days after booster vaccination, vaccine-related adverse reactions were reported: 35 adverse events (in 13 [12%] of 110 children and 22 [20%] of 110 adolescents) in 220 individuals in the AAd5 group, 35 (in 18 [51%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 13 (in five [14%] of 35 children and eight [23%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. Solicited adverse reactions were also reported: 34 (13 [12%] of 110 children and 21 [10%] of 110 adolescents) in 220 individuals in the AAd5 group, 34 (17 [49%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 12 (five [14%] of 35 children and seven [20%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. The GMTs of neutralising antibodies against ancestral SARS-CoV-2 Wuhan-Hu-1 (Pango lineage B) in the AAd5 group were significantly higher than the GMTs in the inactivated vaccine group (adjusted GMT ratio 10·2 [95% CI 8·0-13·1]; p<0·0001). INTERPRETATION: Our study shows that a heterologous booster with AAd5 is safe and highly immunogenic against ancestral SARS-CoV-2 Wuhan-Hu-1 in children and adolescents. FUNDING: National Key R&D Program of China.

[Mechanism of Zicui Decoction in treatment of diabetic kidney disease based on network pharmacology and molecular docking].

This study aimed to explore the potential mechanism of Zicui Decoction in the treatment of diabetic kidney disease(DKD) based on network pharmacology and molecular docking. The DKD-related targets were searched from DrugBank, Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man Database(OMIM), GeneCards, DisGeNET, Comparative Toxico-genomics Database(CTD), and PharmGKB. The targets of the serum active ingredients of Zicui Decoction were predicted from the SwissTargetPrediction. The obtained results were then mapped to harvest the potential targets of Zicui Decoction against DKD. Cytoscape 3.8.2 was employed to construct the "serum active ingredient of Zicui Decoction-potential target-DKD" network. The protein-protein interaction(PPI) network was constructed using the STRING. The key targets were then subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis using the DAVID V6.8 for uncovering its action mechanims. The serum active ingredients of Zicui Decoction were then docked to the core terget proteins with PyMOL and AutoDock Vina. The results of network analysis showed that there were 173 targets associated with 12 serum active ingredients and 6 756 targets related to DKD. The mapping revealed 124 potential targets, of which 26 were the key targets of Zicui Decoction against DKD and 3 were the core teargets. GO analysis yielded 34 entries(P≤0.01 and benjamini≤0.01), and in the treatment of DKD with Zicui Decoction, such biological processes as ERK cascade, regulation of apoptosis, proliferation and migration, and regulation of fibroblast proliferation and ligand receptor binding were involved. According to the KEGG analysis, 19 signaling pathways(P≤0.01 and benjamini≤0.01) were screened out, among which the PI3 K-Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway, and VEGF signaling pathway were closely associated with DKD. Molecular docking verified a good binding ability of the three serum active ingredients to the core targets. In conclusion, Zicui Decoction alleviates DKD possibly by inhibiting inflammation, regulating autophagy, and anti-fibrosis.

Efficacy and safety of Zicuiyin decoction on diabetic kidney disease: A multicenter, randomized controlled trial.

BACKGROUD: Zicuiyin (ZCY) decoction created by Xichun Zhang in the Qing dynasty has been used on diabetes mellitus and complications for more than two centuries in China. Huangkui capsule (HKC) is a listed Chinese patent medicine to treat diabetic kidney disease (DKD). To determine whether ZCY is non-inferior to HKC in the treatment of DKD, a multicenter, parallel-control, open-label, randomized clinical trial was conducted. METHODS: In this clinical trial, 88 DKD patients were recruited at three centers in Tianjin from January 2018 to December 2019. They were randomized to receive HKC (2.5 g, TID) or ZCY (crude drug amount 75 g, 150 ml, BID) for eight weeks based on routine treatment. The primary outcome was the change of estimated glomerular filtration rate (eGFR). The secondary outcomes included change of serum creatinine (SCr), urinary albumin excretion rate, 24 h urinary protein, urinary albumin-creatinine ratio, glycosylated hemoglobin A1c, symptom scores, and microbiota compositions profiles. RESULTS: The change of eGFR in HKC and ZCY groups were -7.08 ± 24.65 and 2.57 ± 18.49 ml/min/1.73 m2, respectively (p < 0.05). The 95% lower confidence limit for the difference between the estimated means was 1.93 ml/min/1.73 m2, establishing the superiority of ZCY. Compared to HKC, ZCY could significantly decrease SCr and symptom scores (p < 0.05). There were no significant differences in other outcomes between the two groups (p > 0.05). ZCY ameliorated gut microbiota dysbiosis, including increased Prevotellaceae and Lactobacillaceae and decreased Enterobacteriales, Clostridiaceae and Micrococcaceae. No severe adverse events were reported in any group. CONCLUSIONS: ZCY had better efficacy in improving and protecting kidney function. It would be an alternative option to treat DKD, especially those who decline eGFR and gut microbiota dysbiosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-OON-17012076. Registered July 21, 2017.

Risks associated with cryopreserved semen in a human sperm bank during and after the COVID-19 pandemic.

RESEARCH QUESTION: What are the risks associated with cryopreserved semen collected during and after the coronavirus disease 2019 (COVID-19) pandemic wave in Wuhan, China? DESIGN: Retrospective cohort study involving young adult men who were qualified sperm donors at the Hunan Province Human Sperm Bank (China) during the pandemic wave (1 January 2020 to 30 January 2020) and after the wave and return to work (7 April 2020 to 30 May 30 2020). One hundred paired semen and blood specimens from 100 donors were included. One-step single-tube nested quantitative real-time polymerase chain reaction (OSN-qRT-PCR) was used to detect SARS-CoV-2. Moreover, to control the unacceptable risk of false-negative results, a second round of screening was performed with pooled RNA from negative semen samples using crystal digital PCR (cd-PCR). RESULTS: For individual blood and semen samples, the target genes, namely the nucleocapsid protein (N) and open reading frame (ORF-1ab) genes, tested negative in all of the 100 paired samples. Further, as per cd-PCR results, there were >20,000 droplets per well in the RNA for each combined sample and no positive droplets were present for either of the aforementioned target genes. A total of 100 paired semen and blood samples from these two groups tested negative for SARS-CoV-2. CONCLUSIONS: Cryopreserved semen at the Hunan Province Human Sperm Bank during and after the COVID-19 pandemic wave was free of SARS-CoV-2 and was judged safe for external use in the future.

A five-compartment model of age-specific transmissibility of SARS-CoV-2.

BACKGROUND: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also called 2019-nCoV) causes different morbidity risks to individuals in different age groups. This study attempts to quantify the age-specific transmissibility using a mathematical model. METHODS: An epidemiological model with five compartments (susceptible-exposed-symptomatic-asymptomatic-recovered/removed [SEIAR]) was developed based on observed transmission features. Coronavirus disease 2019 (COVID-19) cases were divided into four age groups: group 1, those ≤ 14 years old; group 2, those 15 to 44 years old; group 3, those 45 to 64 years old; and group 4, those ≥ 65 years old. The model was initially based on cases (including imported cases and secondary cases) collected in Hunan Province from January 5 to February 19, 2020. Another dataset, from Jilin Province, was used to test the model. RESULTS: The age-specific SEIAR model fitted the data well in each age group (P < 0.001). In Hunan Province, the highest transmissibility was from age group 4 to 3 (median: ß43 = 7.71 × 10- 9; SAR43 = 3.86 × 10- 8), followed by group 3 to 4 (median: ß34 = 3.07 × 10- 9; SAR34 = 1.53 × 10- 8), group 2 to 2 (median: ß22 = 1.24 × 10- 9; SAR22 = 6.21 × 10- 9), and group 3 to 1 (median: ß31 = 4.10 × 10- 10; SAR31 = 2.08 × 10- 9). The lowest transmissibility was from age group 3 to 3 (median: ß33 = 1.64 × 10- 19; SAR33 = 8.19 × 10- 19), followed by group 4 to 4 (median: ß44 = 3.66 × 10- 17; SAR44 = 1.83 × 10- 16), group 3 to 2 (median: ß32 = 1.21 × 10- 16; SAR32 = 6.06 × 10- 16), and group 1 to 4 (median: ß14 = 7.20 × 10- 14; SAR14 = 3.60 × 10- 13). In Jilin Province, the highest transmissibility occurred from age group 4 to 4 (median: ß43 = 4.27 × 10- 8; SAR43 = 2.13 × 10- 7), followed by group 3 to 4 (median: ß34 = 1.81 × 10- 8; SAR34 = 9.03 × 10- 8). CONCLUSIONS: SARS-CoV-2 exhibits high transmissibility between middle-aged (45 to 64 years old) and elderly (≥ 65 years old) people. Children (≤ 14 years old) have very low susceptibility to COVID-19. This study will improve our understanding of the transmission feature of SARS-CoV-2 in different age groups and suggest the most prevention measures should be applied to middle-aged and elderly people.

Emergency Response for a Laboratory Biosafety Incident.

On December 14, 2017, a faculty member of a university in Hunan Province reported that an anthrax vaccine strain might have recovered virulence during an undergraduate experiment and potential exposure could not be ruled out for the students involved. Upon receiving the case report, the CDC, health bureaus, and local governments at the county, prefectural, and provincial levels promptly organized experts in different fields (including epidemiologists, biosafety experts, and laboratory testing experts) for case investigation, evaluation, and response. As the investigation results showed, no virulence recovery was identified in the involved anthrax vaccine strain; and no contamination of Bacillus anthracis was detected at the involved areas. Thus, the university returned to normal functioning.

Identification of the first case of SFTSV infection in the Hunan Province of China and epidemiological surveillance in the locality.

This study reports the etiological identification, clinical diagnosis, and the results of the local epidemiological surveillance of the first case of severe fever with thrombocytopenia syndrome virus (SFTSV) infection in 2014 in Hunan Province, China. The infected patient was isolated and closely monitored. The virus is a member of the Bunyaviridae sandfly family and is characterized by real-time PCR, electron microscopy, immunofluorescence, and whole-genome sequencing. We also detected IgG and IgM antibodies against SFTSV among the local human population and domestic animals in a serological surveillance. Prevalence of SFTSV-specific antibodies was monitored in the local population for two years after the identification of the first SFTS case. Approximately 5% (4/77) of the people who had direct contact with the patient were seropositive, which is significantly higher than the seropositivity of the general local population [1.57% (44/2800), P < 0.05]. Furthermore, the percentage of the general population who were seropositive was higher in 2015 than in 2014 (χ2 = 7.481, P = 0.006). The epidemiological investigation found that the SFTSV is epidemic in goats, cattle, and chickens in Hunan Province. The risk of infection of domestic animals can be minimized by feeding in pens rather than allowing foraging.

Hand, Foot, and Mouth Disease in Hunan Province, China, 2009-2014: Epidemiology and Death Risk Factors.

Hand, foot, and mouth disease (HFMD) is an arising public health problem in Asia, including China. Epidemiological data is necessary to enable judicious public health responses and interventions. We analyzed the epidemiological and laboratory data of 759,301 HFMD cases reported to the Hunan Provincial Center for Disease Control and Prevention from 1 January 2009 to 31 December 2014. Univariate and multivariable conditional logistic regression analyses were used to identify risk factors of fatality in HFMD. The incidence of HFMD was highest among children aged 1-3 years, compared with other age groups. Of the total HFMD cases, 7,222 (0.95%) were considered severe and 338 (0.04%) were fatal. Enterovirus-A71 was the major cause of severe and fatal cases (65.75% and 88.78%, respectively). For severe cases, the median time from symptom onset to diagnosis was 0.5 days (interquartile range [IQR] 0-1.5 days); the median time from diagnosis to severe illness was 2 days (IQR 1-3 days). For fatal cases, the median time from symptom onset to diagnosis was 0.5 days (IQR 0-1.5 days); the median time from diagnosis to death was 1.5 days (IQR 0.5-2.5 days). In multivariable analysis, the abuse of antibiotic, glucocorticoid and pyrazolone in village clinics at basic medical institutions were identified as independent risk factors for HFMD fatal cases. In conclusion, our results suggest that the future direction to control and respond to HFMD is intensive surveillance of enterovirus-A71 and improving the ability to diagnose disease and treat patients, especially in basic medical institutions.

Risk factors for death in children with severe hand, foot, and mouth disease in Hunan, China.

BACKGROUND: In recent years, outbreaks of hand, foot, and mouth disease (HFMD) have increased throughout East and Southeast Asia, especially in mainland China. The disease now presents as an increasingly serious public health threat in China. METHODS: A case-control study was designed to examine risk factors associated with death from severe HFMD. A total of 553 severe HFMD cases were collected from the National Surveillance System. RESULTS: Multifactorial logistic regression was used to analyse independent associations between potential influence factors and death from severe HFMD. We found that the migrants were more likely to die from severe HFMD than the resident population (OR = 3.07, 95%CI: 1.39-8.32). Additionally, the children whose first visit was to a village-level clinic had a high risk of death from severe HFMD. Patients with EV71 infection or symptoms of convulsion, dyspnoea, cyanosis, coolness of extremities, and vomiting had an increased risk of death from severe HFMD. While breastfeeding children, having a confirmed diagnosis at the first visit to the hospital and with symptom of hyperarousal were identified as protective factors for death from severe HFMD. CONCLUSIONS: To reduce the mortality from severe HFMD, doctors and health care providers need to pay attention to the patients with EV71 infection or with symptoms of convulsion, dyspnoea, cyanosis, coolness of extremities, and vomiting. Health administration departments should pay more attention to the rational allocation of health resources. Furthermore, they should increase financial support and manpower in village-level health institutions.

Effects of Humidity Variation on the Hantavirus Infection and Hemorrhagic Fever with Renal Syndrome Occurrence in Subtropical China.

Infection rates of rodents have a significant influence on the transmission of hemorrhagic fever with renal syndrome (HFRS). In this study, four cities and two counties with high HFRS incidence in eastern Hunan Province in China were studied, and surveillance data of rodents, as well as HFRS cases and related environmental variables from 2007 to 2010, were collected. Results indicate that the distribution and infection rates of rodents are closely associated with environmental conditions. Hantavirus infections in rodents were positively correlated with temperature vegetation dryness index and negatively correlated with elevation. The predictive risk maps based on multivariate regression model revealed that the annual variation of infection risks is small, whereas monthly variation is large and corresponded well to the seasonal variation of human HFRS incidence. The identification of risk factors and risk prediction provides decision support for rodent surveillance and the prevention and control of HFRS.

Time-specific ecologic niche models forecast the risk of hemorrhagic fever with renal syndrome in Dongting Lake district, China, 2005-2010.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS), a rodent-borne infectious disease, is one of the most serious public health threats in China. Increasing our understanding of the spatial and temporal patterns of HFRS infections could guide local prevention and control strategies. METHODOLOGY/PRINCIPAL FINDINGS: We employed statistical models to analyze HFRS case data together with environmental data from the Dongting Lake district during 2005-2010. Specifically, time-specific ecologic niche models (ENMs) were used to quantify and identify risk factors associated with HFRS transmission as well as forecast seasonal variation in risk across geographic areas. Results showed that the Maximum Entropy model provided the best predictive ability (AUC = 0.755). Time-specific Maximum Entropy models showed that the potential risk areas of HFRS significantly varied across seasons. High-risk areas were mainly found in the southeastern and southwestern areas of the Dongting Lake district. Our findings based on models focused on the spring and winter seasons showed particularly good performance. The potential risk areas were smaller in March, May and August compared with those identified for June, July and October to December. Both normalized difference vegetation index (NDVI) and land use types were found to be the dominant risk factors. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that time-specific ENMs provide a useful tool to forecast the spatial and temporal risk of HFRS.

Correlation analysis of EV71 detection and case severity in hand, foot, and mouth disease in the Hunan Province of China.

An increase in the incidence of hand, foot and mouth disease (HFMD) cases has been observed in the Hunan province of mainland China since 2009 with a particularly higher level of severe cases in 2010-2012. Intestinal viruses of the picornaviridae family are responsible for the human syndrome associated with HFMD with enterovirus 71 (EV71) and Coxsackievirus A16 (Cox A16) being the most common causative strains. HFMD cases associated with EV71 are generally more severe with an increased association of morbidity and mortality. In this study, the etiology surveillance data of HFMD cases in Hunan province from March 2010 to October 2012 were analyzed to determine if there is a statistically relevant linear correlation exists between the detection rate of EV71 in mild cases and the proportion of severe cases among all HFMD patients. As the cases progressed from mild to severe to fatal, the likelihood of EV71 detection increased (25.78%, 52.20% and 84.18%, respectively). For all cases in the timeframe evaluated in this study, the presence of virus was detected in 63.21% of cases; among cases showing positivity for virus, EV71 infection accounted for 50.14%. These results provide evidence to support the observed higher morbidity and mortality associated with this outbreak and emphasizes the importance of early detection in order to implement necessary prevention measures to mitigate disease progression.

Animal reservoir, natural and socioeconomic variations and the transmission of hemorrhagic fever with renal syndrome in Chenzhou, China, 2006-2010.

BACKGROUND: China has the highest incidence of hemorrhagic fever with renal syndrome (HFRS) worldwide. Reported cases account for 90% of the total number of global cases. By 2010, approximately 1.4 million HFRS cases had been reported in China. This study aimed to explore the effect of the rodent reservoir, and natural and socioeconomic variables, on the transmission pattern of HFRS. METHODOLOGY/PRINCIPAL FINDINGS: Data on monthly HFRS cases were collected from 2006 to 2010. Dynamic rodent monitoring data, normalized difference vegetation index (NDVI) data, climate data, and socioeconomic data were also obtained. Principal component analysis was performed, and the time-lag relationships between the extracted principal components and HFRS cases were analyzed. Polynomial distributed lag (PDL) models were used to fit and forecast HFRS transmission. Four principal components were extracted. Component 1 (F1) represented rodent density, the NDVI, and monthly average temperature. Component 2 (F2) represented monthly average rainfall and monthly average relative humidity. Component 3 (F3) represented rodent density and monthly average relative humidity. The last component (F4) represented gross domestic product and the urbanization rate. F2, F3, and F4 were significantly correlated, with the monthly HFRS incidence with lags of 4 months (r = -0.289, P<0.05), 5 months (r = -0.523, P<0.001), and 0 months (r = -0.376, P<0.01), respectively. F1 was correlated with the monthly HFRS incidence, with a lag of 4 months (r = 0.179, P = 0.192). Multivariate PDL modeling revealed that the four principal components were significantly associated with the transmission of HFRS. CONCLUSIONS: The monthly trend in HFRS cases was significantly associated with the local rodent reservoir, climatic factors, the NDVI, and socioeconomic conditions present during the previous months. The findings of this study may facilitate the development of early warning systems for the control and prevention of HFRS and similar diseases.

[The influence of familial factors on post rabies exposure vaccination in rural habitats].

OBJECTIVE: To understand the current situation of potential exposure to rabies among the rural habitats in Hunan province, and to study the impact related to familial factors on post rabies exposure vaccination. METHODS: In total, 40 villages from 20 townships of 4 counties were selected by multistage sampling method. Study samples were selected from these villagers and familial basic information and vaccination post rabies exposures were recorded through questionnaires. Data were statistically analyzed by SPSS 17.0. RESULTS: Among 3042 villagers from 864 households being surveyed, 124 person-time exposures were found from January, 2009 to October, 2010, with a total exposure rate as 4.08%, and the annual average exposure rate as 2.33%. Data from univariate analysis showed that the rates on post rabies exposure vaccination were statistically correlated with the following four factors:knowledge on the score of rabies prevention (χ(2) = 8.260, P = 0.042), whether being involved in the new type of rural cooperative medical care(P = 0.035), family disposable cash income in the year of 2009(χ(2) = 10.831, P = 0.031), distance between the households and the health facilities in towns and townships(χ(2) = 9.071, P = 0.033). Results from logistic regression analysis indicated that the score of knowledge on rabies prevention(O∧R = 1.420, 95% CI:1.055-1.905)and the annual disposable cash income of the family in 2009(O∧R = 1.480, 95% CI:1.044-2.098)were independent factors that influencing the rabies vaccination. CONCLUSION: Strengthening the education programs on rabies prevention in rural habitats and increasing family income were feasible way to increase the rate of rabies vaccination in rural areas of Hunan province.

Atmospheric moisture variability and transmission of hemorrhagic fever with renal syndrome in Changsha City, Mainland China, 1991-2010.

BACKGROUND: The transmission of hemorrhagic fever with renal syndrome (HFRS) is influenced by environmental determinants. This study aimed to explore the association between atmospheric moisture variability and the transmission of hemorrhagic fever with renal syndrome (HFRS) for the period of 1991-2010 in Changsha, China. METHODS AND FINDINGS: Wavelet analyses were performed by using monthly reported time series data of HFRS cases to detect and quantify the periodicity of HFRS. A generalized linear model with a Poisson distribution and a log link model were used to quantify the relationship between climate and HFRS cases, highlighting the importance of moisture conditions. There was a continuous annual oscillation mode and multi-annual cycle around 3-4 years from 1994 to 1999. There was a significant association of HFRS incidence with moisture conditions and the Multivariate El Niño-Southern Oscillation Index (MEI). Particularly, atmospheric moisture has a significant effect on the propagation of HFRS; annual incidence of HFRS was positively correlated with annual precipitation and annual mean absolute humidity. CONCLUSIONS: The final model had good accuracy in forecasting the occurrence of HFRS and moisture condition can be used in disease surveillance and risk management to provide early warning of potential epidemics of this disease.

[Virological surveillance of pandemic (H1N1) 2009 virus and its genetic characteristics in Hunan Province, 2009-2011].

To understand and master the dynamic variation of the pandemic influenza A (H1N1) 2009 in Hunan province from 2009 to 2011, and to know the genetic characteristics and drug resistance of the pandemic (H1N1) 2009 viruses. Throat swab specimens of influenza-like illness patients were collected from sentinel hospitals and tested for influenza by fluorescent PCR or virus isolation methods. Partial isolates were selected for sequencing. The sequences were used for phylogenetic analysis by MEGA 5. 05 software. From the 20th week of 2009 to the 52nd week of 2011, 17 773 specimens were tested. 3 831 specimens were influenza-positive with a positive rate of 21. 6%, of which 1 794 were positive specimens of pandemic (H1N1) 2009, accounting for 46. 8%00 of the influenza-positives. There were 2 epidemic peaks of pandemic (H1N1) 2009, which were in the 41st-53rd week of 2009 and the 1st-12nd week of 2011, respectively. The HA genes of 23 strains that were selected for sequencing had close relationship; the distribution of strains in the phylogenetic tree was basically in chronological order. The complete genome sequence analysis showed that all of 8 gene segments of 7 strains were homologous to the vaccine strain, and there was no gene reassortment. The HA amino acid sites of the 23 strains were highly similar to the vaccine strain (98. 2% - 100. 0% in homology), but all 23 strains had P83S, S203T and 1321V mutations. The 222 site mutation that may lead to enhanced virulence was found in the A/Hunan/YQ30/2009 strain. The mutation was D222E. There was no oseltamivir resistance mutation found in all strains. The pandemic (H1N1) 2009 in Hunan province from 2009 to 2011 had a bimodal distribution. There was no large-scale variation of virus genes. The clinical use of oseltamivir was still effective. Key words: Pandemic (H1N1) 2009; Surveillance; Genetic characteristics

Investigating the effects of food available and climatic variables on the animal host density of hemorrhagic Fever with renal syndrome in changsha, china.

BACKGROUND: The transmission of hemorrhagic fever with renal syndrome (HFRS) is influenced by population dynamics of its main host, rodents. It is therefore important to better understand rodents' characteristic in epidemic areas. METHODOLOGY/PRINCIPAL FINDINGS: We examined the potential impact of food available and climatic variability on HFRS rodent host and developed forecasting models. Monthly rodent density of HFRS host and climate data in Changsha from January 2004 to December 2011 were obtained. Monthly normalized difference vegetation index (NDVI) and temperature vegetation dryness index (TVDI) for rice paddies were extracted from MODIS data. Cross-correlation analysis were carried out to explore correlation between climatic variables and food available with monthly rodent data. We used auto-regressive integrated moving average model with explanatory variables to examine the independent contribution of climatic variables and food supply to rodent density. The results indicated that relative rodent density of HFRS host was significantly correlated with monthly mean temperatures, monthly accumulative precipitation, TVDI and NDVI with lags of 1-6 months. CONCLUSIONS/SIGNIFICANCE: Food available plays a significant role in population fluctuations of HFRS host in Changsha. The model developed in this study has implications for HFRS control and prevention.

hMSH2 and nm23 expression in sporadic colorectal cancer and its clinical significance.

OBJECTIVE: To study the expression of the mismatch repair proteins hMSH2 and nm23 in sporadic colorectal cancer, determine any inter-relationship, and further investigate any clinical significance. METHODS: Expression of hMSH2 and nm23 proteins was assessed in 87 colorectal cancer tissues by SP immunohistochemistry, with analysis of survival using follow-up data. RESULTS: In the sporadic colorectal cancer tissues, nm23 protein expression appeared independent of the histological type (P > 0.05), but correlated with the invasion depth and lymphatic metastasis (P < 0.05). In contrast, hMSH2 protein expression was not significantly correlated with these clinicopathologic features (P > 0.05), although it positively correlated with that of nm23 protein in the sporadic colorectal cancers (rs=0.635, P < 0.05). Combined expression of the two was found to be related with invasion depth, lymphatic metastasis and prognosis of sporadic colorectal cancer (P < 0.05). CONCLUSION: nm23 protein level was related with the degree of malignancy, and could be used as an index to predict the invasion and metastasis potential. The expression of hMSH2 protein is positively correlated that of nm23 protein, and the combined expression of the two has certain guiding significance for the prognosis of sporadic colorectal cancer.