[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.

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.

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.

[Study on sensitivity of climatic factors on influenza A (H1N1) based on classification and regression tree and wavelet analysis].

OBJECTIVE: To analyze the periodicity of pandemic influenza A (H1N1) in Changsha in year 2009 and its correlation with sensitive climatic factors. METHODS: The information of 5439 cases of influenza A (H1N1) and synchronous meteorological data during the period between May 22th and December 31st in year 2009 (223 days in total) in Changsha city were collected. The classification and regression tree (CART) was employed to screen the sensitive climatic factors on influenza A (H1N1); meanwhile, cross wavelet transform and wavelet coherence analysis were applied to assess and compare the periodicity of the pandemic disease and its association with the time-lag phase features of the sensitive climatic factors. RESULTS: The results of CART indicated that the daily minimum temperature and daily absolute humidity were the sensitive climatic factors for the popularity of influenza A (H1N1) in Changsha. The peak of the incidence of influenza A (H1N1) was in the period between October and December (Median (M) = 44.00 cases per day), simultaneously the daily minimum temperature (M = 13°C) and daily absolute humidity (M = 6.69 g/m(3)) were relatively low. The results of wavelet analysis demonstrated that a period of 16 days was found in the epidemic threshold in Changsha, while the daily minimum temperature and daily absolute humidity were the relatively sensitive climatic factors. The number of daily reported patients was statistically relevant to the daily minimum temperature and daily absolute humidity. The frequency domain was mostly in the period of (16 ± 2) days. In the initial stage of the disease (from August 9th and September 8th), a 6-day lag was found between the incidence and the daily minimum temperature. In the peak period of the disease, the daily minimum temperature and daily absolute humidity were negatively relevant to the incidence of the disease. CONCLUSION: In the pandemic period, the incidence of influenza A (H1N1) showed periodic features; and the sensitive climatic factors did have a "driving effect" on the incidence of influenza A (H1N1).

[Study on the influence of landscape elements regarding on the transmission of hemorrhagic fever with renal syndrome in Changsha].

OBJECTIVE: To explore the influence of landscape elements on the transmission of hemorrhagic fever with renal syndrome (HFRS) in Changsha. METHODS: A total of 327 cases of HFRS diagnosed between year 2005 - 2009 were recruited in the study. Based on the demographic data, meteorological data and the data of second national land survey during the same period, a GIS landscape elements database of HFRS at the township scale of Changsha was established. Spatial-temporal cluster analysis methods were adopted to explore the influence of landscape elements on the spatial-temporal distribution of HFRS in Changsha during the year of 2005 - 2009. RESULTS: The annual incidences of HFRS in Changsha between year 2005 - 2009 were 1.16/100 000 (70 cases), 0.95/100 000 (58 cases), 1.40/100 000(87 cases), 0.75/100 000(47 cases) and 1.02/100 000(65 cases) respectively. The results of poisson regression model analysis of principal component showed that the incidence of HFRS was positively correlated with farmland area (M = 29.00 km2) and urban and rural area (M = 6.12 km2; incidence rate ratios (IRR) = 1.34, 95% CI: 1.27 - 1.41); but negatively correlated with forestland area (M = 39.00 km2; IRR = 0.67, 95% CI: 0.55 - 0.81) and garden plot area (M = 0.99 km2; IRR = 0.74, 95% CI: 0.63 - 0.86). A significant cluster of the spatial-temporal distribution of HFRS cases was found in the study. The primary cluster (28.9 N, 113.37 E, radius at 22.22 km, RR = 5.23, log likelihood ratio (LLR) = 51.61, P <0.01, 67 cases of HFRS and incidence at 4.4/100 000) was found between year 2006 and 2007; and the secondary cluster (28.2 N, 113.6 E, RR = 10.77, LLR = 16.01, P < 0.01, 11 cases of HFRS and the incidence at 10.6/100 000) was found between year 2008 and 2009. CONCLUSION: The landscape elements were found to be closely related to the prevalence and transmission of HFRS.

[Analysis of genetic features of influenza B virus in Hunan province from 2007 to 2010].

OBJECTIVE: To investigate the gene variations of influenza B virus isolated in Hunan province from 2007 to 2010. METHODS: A total of 42 strains of influenza B virus,which were isolated in the Influenza Surveillance Network Laboratories in Hunan province between year 2007 and 2010, were selected for the study. The hemagglutinin 1 (HA1) and neuraminidase (NA) genes of the selected strains were amplified by RT-PCR, and the sequence of the purified product were detected and homologically compared with the sequence of influenza vaccine strains isolated from Northern Hemisphere by WHO during the same period. In addition, the phylogenetic trees were constructed to characterize the molecular features. RESULTS: In the Victoria branch of the HA1 gene phylogenetic tree, the strains isolated from year 2007 to 2009 were included in the V1 sub-branch, as well as the vaccine strain Malaysia/2506/2004; the strains isolated in year 2010 were involved in the V2 sub-branch, similar to the vaccine strains Brisbane/60/2008. In the Yamagata branch,the strains isolated in year 2007 were in the Y1 sub-branch,different from the strains isolated between year 2008 and 2010, which were in the Y2 sub-branch, instead. All virus in NA gene phylogenetic tree were included in the Yamagata branch, indicated their Yamagata origin. The genetic sequence analysis of the 7 strains isolated in year 2010 revealed that the viruses were classified as genotype 2 and genotype 15. The results of homological comparison between HA1 molecule and the influenza vaccine strains recommended by WHO were as below: Victoria lineage, 98.6% - 99.1% in 2007, 98.6% - 99.1% in 2008, 98.1% - 99.1% in 2009, and 97.6% - 99.1% in 2010; and Yamagata lineage, 97.9% - 98.5% in 2007, 97.9% - 98.5% in 2009 and 97.9% - 98.2% in 2010. The major mutations of the strains isolated in year 2007 were found in sites R48K, K88R, P108A, D197N and S230G. While the major mutations of the strains isolated between year 2009 and 2010 were sited in K88R, S150I, N166Y, D197N and S230G. CONCLUSION: The prevalent influenza B virus isolated in Hunan province from 2007 to 2010 has mutated and evolved continuously.

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.

[Risk factors of death cases of hand-foot-and-mouth disease in Hunan province].

OBJECTIVE: To study risk factors of death cases of hand foot and mouth diseases (HFMD) in Hunan province, so as to provide scientific evidence for further prevention and control. METHODS: The 105 death cases of HFMD between January and October, 2010 in Hunan Province were selected as case group; and the 210 survival cases of serious HFMD, which were matched by gender and resident places with a ratio at 2:1 in the same period in Hunan were selected as control group. The basic information, hospitalized experience and previous medical history had been surveyed and the relevant risk factors were analyzed by single factor and multi-factor logistic regression. RESULTS: In case group, 79.05% (83/105) of the cases lived in rural area and 9.52% (10/105) of the cases lived in urban-rural midst area. In control group, 87.62% (184/210) of the cases lived in rural area and 11.43% (24/210) of the cases lived in urban-rural midst area. In case group, 59.05% (62/105) of the patients first visited rural (private) clinics and 20.00% (21/105) first visited community hospitals in villages and towns; while in control group, 43.81% (92/210) and 13.33% (28/210) chose rural (private) clinics and community hospitals in villages and towns as the first choice respectively.22.86% (24/105) of the case group and 39.05% (82/210) of the control group were diagnosed as HFMD in their first visit to hospital.27.62% (29/105) of the case group and 7.14% (15/210) in control group were provided pyrazolone in the treatment. For glucocorticoid, 80.95% (85/105) and 5.71% (6/105) of the case group were given as treatment by rural (private) clinics and community hospitals in villages and towns separately; while the proportions in the control group were 41.43% (87/210) and 0.48% (1/210) respectively. For antibiotics, 35.24% (37/105) and 23.81% (25/105) of the case group were prescribed by rural (private) clinics and community hospitals in villages and towns separately; while the percentages in the control group were 15.71% (33/210) and 7.14% (15/210). 3.81% (4/105) of the case group and 11.90% (25/210) of the control group were vaccinated in one month before the onset. The results of single-factor logistic regression indicated that living in rural areas (OR = 0.075, 95%CI: 0.016 - 0.343) and in rural-urban midst areas (OR = 0.069, 95%CI: 0.013 - 0.368), diagnosis of HFMD in the first visit to hospital (OR = 0.463, 95%CI: 0.271 - 0.788) and vaccination one month before the onset (OR = 0.293, 95%CI: 0.099 - 0.866) were four protective factors; while rural (private) clinics as the first choice (OR = 4.717, 95%CI: 1.891 - 11.767), community hospital in villages and towns as the first choice (OR = 5.250, 95%CI: 1.883 - 14.641), medication of pyrazolone (OR = 4.961, 95%CI: 2.520 - 9.766), medication of glucocorticoid in rural (private) clinics (OR = 6.009, 95%CI: 3.435 - 10.510) and in community hospital in villages and towns (OR = 12.667, 95%CI: 1.505 - 106.638), medication of antibiotics in rural (private) clinics (OR = 2.918, 95%CI: 1.690 - 5.040) and in community hospital in villages and towns (OR = 4.062, 95%CI: 2.036 - 8.108) were seven risk factors. The results of multi-factors logistic regression showed that medication of pyrazolone (OR = 2.311, 95%CI: 1.062 - 5.030), medication of glucocorticoid in rural (private) clinics (OR = 5.480, 95%CI: 3.039 - 9.880), medication of antibiotics in rural (private) clinics (OR = 2.430, 95%CI: 1.301 - 4.538) and medication of antibiotics in community hospitals in villages and towns (OR = 3.344, 95%CI: 1.477 - 7.569) were the risk factors of death of HFMD. CONCLUSION: The risk factors of HFMD deaths include the medication of pyrazolone, glucocorticoid and antibiotics by rural (private) clinics and medical institutions in villages and towns. The department concerned should revise the technical manual to standardize the medication of the above drugs.

Multicomponent amorphous nanofibers electrospun from hot aqueous solutions of a poorly soluble drug.

PURPOSE: To design and fabricate multicomponent amorphous electrospun nanofibers for synergistically improving the dissolution rate and permeation profiles of poorly water-soluble drugs. METHODS: Nanofibers were designed to be composed of a poorly water soluble drug, helicid, a hydrophilic polymer polyvinylpyrrolidone as filament-forming matrix, sodium dodecyl sulfate as transmembrane enhancer and mannitol as taste masking agent, and were prepared from hot aqueous co-dissolving solutions of them. An elevated temperature electrospinning process was developed to fabricate the composite nanofibers, which were characterized using FESEM, DSC, XRD, ATR-FTIR, in vitro dissolution and permeation tests. RESULTS: The composite nanofibers were homogeneous with smooth surfaces and uniform structure, and the components were combined together in an amorphous state because of the favorable interactions such as hydrogen bonding, electrostatic interaction and hydrophobic interactions among them. In vitro dissolution and permeation tests demonstrated that the composite nanofibers had a dissolution rate over 26-fold faster than that of crude helicid particles and a 10-fold higher permeation rate across sublingual mucosa. CONCLUSIONS: A new type of amorphous material in the form of nanofibers was prepared from hot aqueous solutions of multiple ingredients using an electrospinning process. The amorphous nanofibers were able to improve the dissolution rate and permeation rate of helicid.

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.

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.

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.

[An investigation on nosocomial infection with severe acute respiratory syndrome in health-care workers at 13 key hospitals in Guangdong Province].

OBJECTIVE: To analysis the risk factors influencing nosocomial infection of severe acute respiratory syndrome (SARS) in health-care workers and to evaluate effectiveness of its control and preventive measures in 13 key hospitals caring for SARS patients. METHODS: Number of SARS patients, clinical conditions of them, its attack rate in health-care workers, and characteristics of hospitals, including their environment, isolating measures, etc. were investigated at the 13 hospital in Guangzhou to analyze the risk factors influencing nosocomial infection of SARS and its attack rates in health-care workers before and after implementation of preventive measures and to evaluate their effectiveness. RESULTS: Totally, 841 patients with SARS were treated at the 13 hospitals in Guangzhou and 285 health-care workers caring for them infected nosocomially. Attack rate in health-care workers was higher at general hospitals, hospital accepting more cases in critical conditions and hospitals with poor precautious measures, and lower in hospitals with isolated wards or areas, or department of infection, specially caring for SARS patients, and those with effective intervention measures to prevent secondary infection. CONCLUSION: Nosocomial infection of SARS in health-care workers was affected by clinical condition of SARS patients, characteristics and environment of hospitals and their personal protective measures adopted.

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.