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Background: Little is known about the long-term risks of stroke and ischemic heart disease (IHD) in women who had a hysterectomy alone (HA) or with bilateral oophorectomy (HBO) for benign diseases, particularly in China where the burden of cardiovascular diseases (CVD) is high. We assessed mean levels of cardiovascular risk factors and relative risks of stroke and IHD in Chinese women who had a HA or HBO. Methods: A total of 302 510 women, aged 30 to 79 years were enrolled in the China Kadoorie Biobank from 2004 to 2008 and followed up for a mean of 9.8 years. The analysis involved premenopausal women without prior cardiovascular disease or cancer at enrollment. We calculated adjusted hazard ratios for incident cases of CVD and their pathological types (ischemic stroke, hemorrhagic stroke, and IHD) after HA and HBO. Analyses were stratified by age and region and adjusted for levels of education, household income, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diabetes, self-reported health, and number of pregnancies. Results: Among 282 722 eligible women, 8478 had HA, and 1360 had HBO. Women who had HA had 9% higher risk of CVD after HA (hazard ratio, 1.09 [95% CI, 1.06–1.12]) and 19% higher risk of CVD after HBO (1.19 [95% CI, 1.12–1.26]) compared with women who did not. Both HA and HBO were associated with higher risks of ischemic stroke and IHD but not with hemorrhagic stroke. The relative risks of CVD associated with HA and HBO were more extreme at younger age of surgery. Conclusions: Women who had either HA or HBO have higher risks of ischemic stroke and IHD, and these risks should be evaluated when discussing these interventions. Additional screening for risk factors for CVD should be considered in women following HA and HBO operations, especially if such operations are performed at younger age.

There is an urgent need for animal models of coronavirus disease 2019 to study immunopathogenesis and test therapeutic intervenes. In this study, we showed that NOD/SCID IL2rg

COVID-19 was officially declared a global pandemic disease on 11 March 2020, with severe implications for healthcare systems, economic activity, and human life worldwide. Fast and sensitive amplification of the severe acute respiratory syndrome virus 2 (SARS-CoV-2) nucleic acids is critical for controlling the spread of this disease. Here, a real-time reverse transcription recombinase-aided amplification (RT-RAA) assay, targeting conserved positions in the nucleocapsid protein gene (

The duration of SARS-CoV-2 genomic RNA shedding is much longer than that of infectious SARS-CoV-2 in most COVID-19 patients. It is very important to determine the relationship between test results and infectivity for efficient isolation, contact tracing, and post-isolation. We characterized the duration of viable SARS-CoV-2, viral genomic and subgenomic RNA (gRNA and sgRNA), and rapid antigen test positivity in nasal washes, oropharyngeal swabs, and feces of experimentally infected Syrian hamsters. The duration of viral genomic RNA shedding is longer than that of viral subgenomic RNA, and far longer than those of rapid antigen test (RAgT) and viral culture positivity. The rapid antigen test results were strongly correlated with the viral culture results. The trend of subgenomic RNA is similar to that of genomic RNA, and furthermore, the subgenomic RNA load is highly correlated with the genomic RNA load.

Influenza virus is a serious threat to global human health and public health security. There is an urgent need to develop new anti-influenza drugs. Lentinan (LNT) has attracted increasing attention in recent years. As potential protective agent, LNT has been shown to have anti-tumor, anti-inflammatory, and antiviral properties. However, there has been no further research into the anti-influenza action of lentinan in vivo, and the mechanism is still not fully understood. In this study, the anti-influenza effect and mechanism of Lentinan were studied in the Institute of Cancer Research (ICR) mouse model. The results showed that Lentinan had a high degree of protection in mice against infection with influenza A virus, delayed the emergence of clinical manifestations, improved the survival rate of mice, significantly prolonged the middle survival days, attenuated the weight loss, and reduced the lung coefficient of mice. It alleviated the pathological damage of mice infected with the influenza virus and improved blood indices. Lentinan treatment considerably inhibited inflammatory cytokine (TNF-α, IL-1β, IL-4, IL-5, IL-6) levels in the serum and lung and improved IFN-γ cytokine levels, which reduced cytokine storms caused by influenza virus infection. The underlying mechanisms of action involved Lentinan inhibiting the inflammatory response by regulating the TLR4/MyD88 signaling pathway. This study provides a foundation for the clinical application of Lentinan, and provides new insight into the development of novel immunomodulators.

Previous studies have shown that B.1.351 and other variants have extended the host range of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to mice. Sustained transmission is a prerequisite for viral maintenance in a population. However, no evidence of natural transmission of SARS-CoV-2 in wild mice has been documented to date. Here, we evaluated the replication and contact transmission of the B.1.351 variant in mice and rats. The B.1.351 variant could infect and replicate efficiently in the airways of mice and rats. Furthermore, the B.1.351 variant could not be transmitted in BALB/c or C57BL/6 mice but could be transmitted with moderate efficiency in rats by direct contact. Additionally, the B.1.351 variant did not transmit from inoculated Syrian hamsters to BALB/c mice. Moreover, the mouse-adapted SARS-CoV-2 strain C57MA14 did not transmit in mice. In summary, the risk of B.1.351 variant transmission in mice is extremely low, but the transmission risk in rats should not be neglected. We should pay more attention to the potential natural transmission of SARS-CoV-2 variants in rats and their possible spillback to humans.

Background Tobacco smoking is estimated to account for more than 1 million annual deaths in China, and the epidemic continues to increase in men. Large nationwide prospective studies linked to different health records can help to periodically assess disease burden attributed to smoking. We aimed to examine associations of smoking with incidence of and mortality from an extensive range of diseases in China. Methods We analysed data from the prospective China Kadoorie Biobank, which recruited 512 726 adults aged 30–79 years, of whom 210 201 were men and 302 525 were women. Participants who had no major disabilities were identified through local residential records in 100–150 administrative units, which were randomly selected by use of multistage cluster sampling, from each of the ten diverse study areas of China. They were invited and recruited between June 25, 2004, and July 15, 2008. Upon study entry, trained health workers administered a questionnaire assessing detailed smoking behaviours and other key characteristics (eg, sociodemographics, lifestyle, and medical history). Participants were followed up via electronic record linkages to death and disease registries and health insurance databases, from baseline to Jan 1, 2018. During a median 11-year follow-up (IQR 10–12), 285 542 (55·7%) participants were ever hospitalised, 48 869 (9·5%) died, and 5252 (1·0%) were lost to follow-up during the age-at-risk of 35–84 years. Cox regression yielded hazard ratios (HRs) associating smoking with disease incidence and mortality, adjusting for multiple testing. Findings At baseline, 74·3% of men and 3·2% of women (overall 32·4%) ever smoked regularly. During follow-up, 1 137 603 International Classification of Diseases, 10th revision (ICD-10)-coded incident events occurred, involving 476 distinct conditions and 85 causes of death, each with at least 100 cases. Compared with never-regular smokers, ever-regular smokers had significantly higher risks for nine of 18 ICD-10 chapters examined at age-at-risk of 35–84 years. For individual conditions, smokers had significantly higher risks of 56 diseases (50 for men and 24 for women) and 22 causes of death (17 for men and nine for women). Among men, ever-regular smokers had an HR of 1·09 (95% CI 1·08–1·11) for any disease incidence when compared with never-regular smokers, and significantly more episodes and longer duration of hospitalisation, particularly those due to cancer and respiratory diseases. For overall mortality, the HRs were greater in men from urban areas than in men from rural areas (1·50 [1·42–1·58] vs 1·25 [1·20–1·30]). Among men from urban areas who began smoking at younger than 18 years, the HRs were 2·06 (1·89–2·24) for overall mortality and 1·32 (1·27–1·37) for any disease incidence. In this population, 19·6% of male (24·3% of men residing in urban settings and 16·2% of men residing in rural settings) and 2·8% of female deaths were attributed to ever-regular smoking. Interpretation Among Chinese adults, smoking was associated with higher risks of morbidity and mortality from a wide range of diseases. Among men, the future smoking-attributed disease burden will increase further, highlighting a pressing need for reducing consumption through widespread cessation and uptake prevention. Funding British Heart Foundation, Cancer Research UK, Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, UK Medical Research Council, National Natural Science Foundation of China, Wellcome Trust.

Summary Background Stroke is a leading cause of death and disability worldwide. Despite considerable improvements in diagnosis and treatment, little is known about the short-term and long-term prognosis after a first stroke in low-income and middle-income countries, including China. We aimed to assess the short-term and long-term risk of recurrent stroke and mortality after a first stroke for each of the major pathological stroke types. Methods This population-based cohort study included adults aged 35–74 years without disability who were recruited to the China Kadoorie Biobank (CKB). A baseline survey was conducted in ten geographical areas (five urban, five rural) in China, and participants had clinical measurements recorded. Participants were followed up by monitoring death registries and by electronic linkage to health registries and health insurance claims databases, with follow-up until Jan 1, 2017. Participants were excluded from analyses if they had a previous history of stroke, transient ischaemic attack, or ischaemic heart disease at baseline. All incidences of fatal and non-fatal stroke during the study period were recorded by type (ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and unspecified type). Primary outcome measures were 28-day mortality, recurrent stroke, major vascular events (recurrent stroke, myocardial infarction, or vascular death), vascular mortality, and all-cause mortality. Findings Of 512 715 individuals in the CKB, 489 586 participants without previous ischaemic heart disease and stroke at recruitment were included, of whom 45 732 (42 073 [92%] confirmed by brain imaging) had a stroke during the study period. The mean age was 59·3 years (SD 9·8) for participants who had a stroke (54% women) and 50·8 years (10·3) for participants with no stroke (60% women). 36 588 (80%) of the incident cases of stroke were ischaemic stroke, 7440 (16%) were intracerebral haemorrhage, 702 (2%) were subarachnoid haemorrhage, and 1002 (2%) were an unspecified stroke type. 28-day mortality was 3% (95% CI 3–4) for ischaemic stroke, 47% (46–48)for intracerebral haemorrhage, 19% (17–22; 52% for rural areas and 32% for urban areas) subarachnoid haemorrhage, and 24% (22–27) for unspecified stroke. Among participants who survived stroke at 28 days, 41% (41–42) had recurrent stroke at 5 years (ischaemic stroke 41% [41–42], intracerebral haemorrhage 44% [42–46], subarachnoid haemorrhage 22% [18–27], unspecified stroke type 40% [35–44]) and mortality at 5 years was 17% ([17–18] ischaemic stroke 16% [15–16], intracerebral haemorrhage 28% [26–29], subarachnoid haemorrhage 16% [12–20], unspecified stroke type 15% [12–19]). After a first ischaemic stroke, 91% of recurrent strokes were also ischaemic stroke; after an intracerebral haemorrhage, 56% of recurrent strokes were intracerebral haemorrhage, and 41% of recurrent strokes were ischaemic stroke. Interpretation After a first stroke, the risk of recurrence or death within 5 years was high among this population of Chinese adults. Urgent improvements to secondary prevention of stroke in China are needed to reduce these risks. Funding Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, National Natural Science Foundation of China. Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Background: Cooking practice has transitioned from use of solid fuels to use of clean fuels, with addition of better ventilation facilities. However, the change in mortality risk associated with such a transition remains unclear. Methods: The China Kadoorie Biobank (CKB) Study enrolled participants (aged 30–79 years) from ten areas across China; we chose to study participants from five urban areas where transition from use of solid fuels to clean fuels for cooking was prevalent. Participants who reported regular cooking (weekly or more frequently) at baseline were categorised as persistent clean fuel users, previous solid fuel users, or persistent solid fuel users, according to self-reported fuel use histories. All-cause and cardiopulmonary mortality were identified through linkage to China's Disease Surveillance Point system and local mortality records. Findings: Between June 24, 2004, and July 15, 2008, 226 186 participants living in five urban areas of China were enrolled in the CKB Study. Among 171 677 participants who reported cooking regularly (weekly or more frequently), 75 785 (44%) were persistent clean fuel users, 80 511 (47%) were previous solid fuel users, and 15 381 (9%) were persistent solid fuel users. During a mean of 9·8 (SD 1·7) years of follow-up, 10 831 deaths were documented, including 3819 cardiovascular deaths and 761 respiratory deaths. Compared with persistent clean fuel users, persistent solid fuel users had significantly higher risks of all-cause mortality (hazard ratio [HR] 1·19, 95% CI 1·10–1·28), cardiovascular mortality (1·24, 1·10–1·39), and respiratory mortality (1·43, 1·10–1·85). The excess risk of all-cause and cardiopulmonary mortality fell by more than 60% in 5 years after cessation of solid fuel use and continued to decrease afterwards. Use of ventilation was associated with lower all-cause mortality risk, even among persistent clean fuel users (HR 0·78, 0·69–0·89). Interpretation: Solid fuel use for cooking is associated with a higher risk of mortality, and cessation of solid fuel use cuts excess mortality risks swiftly and substantially within 5 years. Ventilation use also lowers the risk of mortality, even among people who persistently use clean fuels. It is of prime importance for both policy makers and the public to accelerate the transition from solid fuels to clean fuels and promote efficient ventilation to minimise further adverse health effects.

We analyzed size of severe acute respiratory coronavirus 2 (SARS-CoV-2) aerosol particles shed by experimentally infected cynomolgus monkeys. Most exhaled particles were small, and virus was mainly released early during infection. By postinfection day 6, no virus was detected in breath, but air in the isolator contained large quantities of aerosolized virus.

Throughout the last decade, H5N6 avian influenza viruses (AIVs) circulating in poultry and infecting humans have caused increasing global concerns that they might become a pandemic threat to global health. Since AIVs could occasionally cause asymptomatic infections in geese, virus monitoring in such a host should be critical to the control of cross-species infection. In addition, previous studies showed that clade 2.3.4.4h H5N6 AIVs could infect mammals without adaptation. However, the pathogenicity and transmissibility of goose-origin clade 2.3.4.4h H5N6 AIVs in mammals remain unknown. In this study, two H5N6 AIVs were isolated from a domestic chicken (A/chicken/Hebei CK05/2019 (H5N6)) and a goose (A/goose/Hebei/GD07/2019(H5N6)). This study is the first to evaluate the pathogenicity and transmissibility of goose-origin clade 2.3.4.4h H5N6 AIVs in mammals by comparison with chicken-origin 2.3.4.4h H5N6 AIVs. The CK05 virus had an affinity for α-2,3-receptors, while the GD07 virus had an affinity for both α-2,3-and α-2,6-receptors. The GD07 virus had a higher replication capacity in vitro and more severe pathogenicity in mice than the CK05 virus. The CK05 virus could not be transmitted effectively among guinea pigs, whereas the GD07 virus could be transmitted through direct contact among guinea pigs. The results of this study indicated the potential health threat of clade 2.3.4.4h H5N6 AIVs to mammals and emphasized the importance of continuous monitoring of H5N6 AIVs, especially in waterfowl.

The traditional diagnosis model has great challenges for the etiological diagnosis of the central nervous system (CNS) diseases with similar clinical manifestations, especially for the diagnosis of rare pathogens. It is very important to make rapid and accurate identification of pathogens for guiding clinical choices in administering countermeasures.On August 22, 2020, a 49 years old Chinese male patient had a headache for two days, and then the computed tomography (CT) scan of the brain showed subarachnoid hemorrhage. Subsequently, he underwent twice craniotomy and about 3 weeks of hospitalization. Since September 20, the patient was in the local rehabilitation hospital for hyperbaric oxygen therapy for about three weeks. Then the patient developed acute purulent meningoencephalitis. In the absence of diagnosis of specific pathogenic bacteria, vancomycin (1 g every 12 hours), ceftazidime (2 g every 8 hours), mannitol dehydration (125 mL, every 8 hours), and sodium valproate (0.4 g tid) was used timely according to cerebrospinal fluid (CSF) examination and clinical manifestations. CSF smear and routine culture test were negative during hospitalization. We used the metagenomic next-generation sequencing (mNGS) analysis of CSF for quick and accurate diagnosis, which identified human herpesvirus type 4 (EBV), Corynebacterium corynebacterium, Achromobacter xylose oxidation, and Acinetobacter baumannii, But the mapping degree was not high. Then, we used the modified method-multiplex PCR-based targeted gene sequencing platform (ptNGS) to detect CSF samples and found that the sequences detected were Acinetobacter pittii (A. pittii) and Staphylococcus epidermidis. S. epidermidis might come from skin colonization during lumbar puncture, so it was excluded from the etiological diagnosis. Therefore, we highly suspected that A. pittii was the pathogen in this case. After about three weeks of hospitalization treatment, the patient's symptoms were relieved.In conclusion, empirical medication before the identification of pathogens is very important. The ptNGS may be an effective method for the diagnosis of pathogens.

BackgroundChanges in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs). The glycosylation patterns of IgG play a critical role in regulating the biological function and stability of IgG involved in the pathophysiology of many AIDs. However, the intracellular regulatory mechanisms underlying the effects of disturbances in various cytokines on IgG glycosylation are poorly understood. Thus, we investigated the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells.MethodsFirst, we established a controlled primary culture system in vitro to differentiate human CD19+ B cells into antibody-secreting cells (ASCs). Then, the IgG concentrations in the supernatants were measured by enzyme-linked immunoassay (ELISA) under IFN-γ, TNF-α, IL-21, IL-17A, BAFF, or APRIL stimulation. Next, the glycosylation levels of IgG under different stimuli were compared via a lectin microarray. The fine carbohydrate structures of IgG were confirmed by matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS). Finally, the expression of glycosyltransferases and glycosidases in B cells under stimulation with several cytokines was detected by real-time PCR and western blotting.ResultsWe found that cytokines significantly promoted IgG production in vitro and led to considerably different IgG glycan patterns. Specifically, the results of lectin microarray showed the galactose level of IgG was increased by IFN-γ stimulation (ppConclusionAbnormally elevated cytokines in the microenvironment regulates IgG glycan patterns by regulating intracellular glycosyltransferases in human B cells.

Environmental transmission of viruses to humans has become an early warning for potential epidemic outbreaks, such as SARS-CoV-2 and influenza virus outbreaks. Recently, an H7N9 virus, A/environment/Hebei/621/2019 (H7N9), was isolated by environmental swabs from a live poultry market in Hebei, China. We found that this isolate could be transmitted by direct contact and aerosol in mammals. More importantly, after 5 passages in mice, the virus acquired two adaptive mutations, PB1-H115Q and B2-E627K, exhibiting increased virulence and aerosol transmissibility. These results suggest that this H7N9 virus might potentially be transmitted between humans through environmental or airborne routes.

The detection of SARS-CoV-2 infection is the premise of quarantine. In many countries or areas, samples need to be shipped or inactivated before SARS-CoV-2 testing. In this study, we checked the influence of sample storage conditions on SARS-CoV-2 nucleic acid testing results, including sample inactivation time, storage temperature, and storage time. All of these conditions caused an increase in the cycle threshold values of the nucleic acid tests and led to the misclassification of at least 10.2% of positive cases as negative or suspected. The results highlight the importance of immediate testing of samples for SARS-CoV-2 nucleic acid detection.

Background and aims Observational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults. Methods and results The China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]). Conclusions This study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.

Objective Influenza season occurs every year in China, but its presentation was unusual in the period from December 2017 to early 2018. During this period, influenza activity was increasing across the country and was much greater than during the same period in previous years, with great harm to people’s health. Methods In this study, we isolated two human influenza virus strains—A/Hebei/F076/2018(H1N1) and B/Hebei/16275B/2018—from patients with severe influenza in Hebei, China, during the flu season in January 2018, and explored their genetic characteristics, pathogenicity, and transmissibility. Results A/Hebei/F076/2018(H1N1) belongs to the human-like H1N1 influenza virus lineage, whereas B/Hebei/16275B/2018 belongs to the Victoria lineage and is closely related to the World Health Organization reference strain B/Brisbane/60/2008. Pathogenicity tests revealed that A/Hebei/F076/2018(H1N1) replicated much more strongly in mice, with mice exhibiting 40% mortality, whereas B/Hebei/16275B/2018 was not lethal. Both viruses could be transmitted through direct contact and by the aerosol route between guinea pigs, but the H1N1 strain exhibited higher airborne transmissibility. Conclusions These results may contribute to the monitoring of influenza mutation and the prevention of an influenza outbreak.

Since December 2019, coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a great challenge to the world's public health system. Nosocomial infections have occurred frequently in medical institutions worldwide during this pandemic. Thus, there is an urgent need to construct an effective surveillance and early warning system for pathogen exposure and infection to prevent nosocomial infections in negative-pressure wards. In this study, visualization and construction of an infection risk assessment of SARS-CoV-2 through aerosol and surface transmission in a negative-pressure ward were performed to describe the distribution regularity and infection risk of SARS-CoV-2, the critical factors of infection, the air changes per hour (ACHs) and the viral variation that affect infection risk. The SARS-CoV-2 distribution data from this model were verified by field test data from the Wuhan Huoshenshan Hospital ICU ward. ACHs have a great impact on the infection risk from airborne exposure, while they have little effect on the infection risk from surface exposure. The variant strains demonstrated significantly increased viral loads and risks of infection. The level of protection for nurses and surgeons should be increased when treating patients infected with variant strains, and new disinfection methods, electrostatic adsorption and other air purification methods should be used in all human environments. The results of this study may provide a theoretical reference and technical support for reducing the occurrence of nosocomial infections.

The coronavirus disease 2019 (COVID-19), caused by a novel virus of the β-coronavirus genus (SARS-CoV-2), has been spreading globally. As of July 2020, there have been more than 17 million cases worldwide. Determining multiple transmission routes of SARS-CoV-2 is critical to improving safety practices for the public and stemming the spread of SARS-CoV-2 effectively. This article mainly focuses on published studies on the transmission routes of SARS-CoV-2 including contact transmission, droplet transmission, aerosol transmission and fecal-oral transmission, as well as related research approaches, such as epidemiological investigations, environmental sampling in hospitals and laboratories and animal models. We also provide four specific recommendations for the prevention and control of SARS-CoV-2 that may help reduce the risk of SARS-CoV-2 infection under different environmental conditions. First, social distancing, rational use of face masks and respirators, eye protection, and hand disinfection for medical staff and the general public deserve further attention and promotion. Second, aerodynamic characteristics, such as size distribution, release regularity, aerosol diffusion, survival and decline, infectious dose and spread distance, still require further investigation in order to identify the transmissibility of COVID-19. Third, background monitoring of the distribution of pathogenic microorganisms and environmental disinfection in crowded public places, such as railway stations, schools, hospitals and other densely populated areas, can give early warning of outbreaks and curb the transmission routes of SARS-CoV-2 in those high-risk areas. Forth, establishing novel predictive models can help us to not only assess transmission and impacts in communities, but also better implement corresponding emergency response measures.

Background Influenza A virus (IAV) continues to pose serious threats to public health. The current prophylaxis and therapeutic interventions for IAV requires frequent changes due to the continuous antigenic drift and antigenic shift of IAV. Emerging evidence indicates that the host microRNAs (miRNAs) play critical roles in intricate host-pathogen interaction networks. Cellular miRNAs may directly target virus to inhibit its infection and be developed as potential anti-virus drugs. Methods In this study, we established a broad-spectrum anti-IAV miRNA screening method using miRanda software. The screened miRNAs were further verified by luciferase assay, viral protein expression assay and virus replication assay. Results Five cellular miRNAs (miR-188-3p, miR-345-5p, miR-3183, miR-15-3p and miR-769-3p), targeting 99.96, 95.31, 92.9, 94.58 and 97.24% of human IAV strains recorded in NCBI, respectively, were chosen for further experimental verification. Finally, we found that miR-188-3p downregulated PB2 expression at both mRNA and protein levels by directly targeted the predicted sites on PB2 and effectively inhibited the replication of IAV (H1N1, H5N6 and H7N9) in A549 cells. Conclusions This is the first report screening cellular miRNAs that broad-spectrum inhibiting IAV infection. These findings suggested that cellular miR-188-3p could be used for RNAi-mediated anti-IAV therapeutic strategies.

Background Lean body mass has been identified as a key determinant of left ventricular mass and wall thickness. However, the importance of lean body mass or other body‐size measures as normative determinants of carotid intima‐media thickness ( cIMT ), a widely used early indicator of atherosclerosis, has not been well established. Methods and Results Carotid artery ultrasound measurements of cIMT and carotid artery plaque burden (derived from plaque number and maximum size) and measurements of body size, including height, body mass index, weight, body fat proportion, and lean body mass ([1−body fat proportion]×weight), were recorded in 25 020 participants from 10 regions of China. Analyses were restricted to a healthy younger subset (n=6617) defined as never or long‐term ex‐regular smokers aged cIMT , but was not associated with plaque burden: overall, each 10 kg higher lean body mass was associated with a 0.03 (95% CI , 0.03–0.04) mm higher cIMT ( P =5×10 −33 ). Fat mass, height, and other body‐size measures were more weakly associated with cIMT . Conclusions The strong association of lean body mass with cIMT, but not with plaque burden, in healthy adults suggests a normative relationship rather than reflecting atherosclerotic pathology. Common mechanisms may underlie the associations of lean body mass with cIMT and with nonatherosclerotic vascular traits.

Background In China, alcohol consumption has increased significantly in recent decades. Little evidence exists, however, about temporal trends in levels and patterns of alcohol consumption and associated factors in adult populations. Methods In 2004–08, the China Kadoorie Biobank recruited ~ 512,000 adults (41% men, mean age 52 years [SD 10.7]) from 10 (5 urban, 5 rural) geographically diverse regions across China, with ~ 25,000 randomly selected participants resurveyed in 2013–14. The self-reported prevalence and patterns (e.g., amount, beverage type, heavy drinking episodes) of alcohol drinking at baseline and resurvey were compared and related to socio-demographic, health and other factors. Results At baseline, 33% of men drank alcohol at least weekly (i.e., current regular), compared to only 2% of women. In men, current regular drinking was more common in urban (38%) than in rural (29%) areas at baseline. Among men, the proportion of current regular drinkers slightly decreased at resurvey (33% baseline vs. 29% resurvey), while the proportion of ex-regular drinkers slightly increased (4% vs. 6%), particularly among older men, with more than half of ex-regular drinkers stopping for health reasons. Among current regular drinkers, the proportion engaging in heavy episodic drinking (i.e., > 60 g/session) increased (30% baseline vs. 35% resurvey) in both rural (29% vs. 33%) and urban (31% vs. 36%) areas, particularly among younger men born in the 1970s (41% vs. 47%). Alcohol intake involved primarily spirits, at both baseline and resurvey. Those engaging in heavy drinking episodes tended to have multiple other health-related risk factors (e.g., regular smoking, low fruit intake, low physical activity and hypertension). Conclusions Among Chinese men, the proportion of drinkers engaging in harmful drinking behaviours increased in the past decade, particularly among younger men. Harmful drinking patterns tended to cluster with other unhealthy lifestyles and health-related risk factors. Electronic supplementary material The online version of this article (10.1186/s12889-019-6502-1) contains supplementary material, which is available to authorized users.

Rationale Little evidence from large-scale cohort studies exists about the relationship of solid fuel use with hospitalization and mortality from major respiratory diseases. Objectives To examine the associations of solid fuel use and risks of acute and chronic respiratory diseases. Methods A cohort study of 277,838 Chinese never-smokers with no prior major chronic diseases at baseline. During 9 years of follow-up, 19,823 first hospitalization episodes or deaths from major respiratory diseases, including 10,553 chronic lower respiratory disease (CLRD), 4,398 chronic obstructive pulmonary disease (COPD), and 7,324 acute lower respiratory infection (ALRI), were recorded. Cox regression yielded adjusted hazard ratios (HRs) for disease risks associated with self-reported primary cooking fuel use. Measurements and Main Results Overall, 91% of participants reported regular cooking, with 52% using solid fuels. Compared with clean fuel users, solid fuel users had an adjusted HR of 1.36 (95% confidence interval, 1.32–1.40) for major respiratory diseases, whereas those who switched from solid to clean fuels had a weaker HR (1.14, 1.10–1.17). The HRs were higher in wood (1.37, 1.33–1.41) than coal users (1.22, 1.15–1.29) and in those with prolonged use (≥40 yr, 1.54, 1.48–1.60; Conclusions Among Chinese adults, solid fuel use for cooking was associated with higher risks of major respiratory disease admissions and death, and switching to clean fuels or use of ventilated cookstoves had lower risk than not switching.

MicroRNAs (miRNAs) may become efficient antiviral agents against the Ebola virus (EBOV) targeting viral genomic RNAs or transcripts. We previously conducted a genome-wide search for differentially expressed miRNAs during viral replication and transcription. In this study, we established a rapid screen for miRNAs with inhibitory effects against EBOV using a tetracistronic transcription- and replication-competent virus-like particle (trVLP) system. This system uses a minigenome comprising an EBOV leader region, luciferase reporter, VP40, GP, VP24, EBOV trailer region, and three noncoding regions from the EBOV genome and can be used to model the life cycle of EBOV under biosafety level (BSL) 2 conditions. Informatic analysis was performed to select up-regulated miRNAs targeting the coding regions of the minigenome with the highest binding energy to perform inhibitory effect screening. Among these miRNAs, miR-150-3p had the most significant inhibitory effect. Reverse transcription polymerase chain reaction (RT-PCR), Western blot, and double fluorescence reporter experiments demonstrated that miR-150-3p inhibited the reproduction of trVLPs via the regulation of GP and VP40 expression by directly targeting the coding regions of GP and VP40. This novel, rapid, and convenient screening method will efficiently facilitate the exploration of miRNAs against EBOV under BSL-2 conditions.

Since 2013, highly pathogenic avian influenza H5N6 viruses have emerged in poultry and caused sporadic infections in humans, increasing global concerns regarding their potential as human pandemic threats. Here, we characterized the receptor-binding specificities, pathogenicities and transmissibilities of three H5N6 viruses isolated from poultry in China. The surface genes hemagglutinin (HA) and neuraminidase (NA) were closely related to the human-originating strain A/Changsha/1/2014 (H5N6). Phylogenetic analyses showed that the HA genes were clustered in the 2.3.4.4 clade, and the NA genes were derived from H6N6 viruses. These H5N6 viruses bound both α-2,3-linked and α-2,6-linked sialic acid receptors, but they exhibited different pathogenicities in mice. In addition, one virus was fully infective and transmissible by direct contact in guinea pigs. These results highlight the importance of monitoring the continual adaptation of H5N6 viruses in poultry due to their potential threat to human health.

Understanding how infected cells respond to Ebola virus (EBOV) and how this response changes during the process of viral replication and transcription are very important for establishing effective antiviral strategies. In this study, we conducted a genome-wide screen to identify long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), micro RNAs (miRNAs), and mRNAs differentially expressed during replication and transcription using a tetracistronic transcription and replication-competent virus-like particle (trVLP) system that models the life cycle of EBOV in 293T cells. To characterize the expression patterns of these differentially expressed RNAs, we performed a series cluster analysis, and up- or down-regulated genes were selected to establish a gene co-expression network. Competing endogenous RNA (ceRNA) networks based on the RNAs responsible for the effects induced by EBOV replication and transcription in human cells, including circRNAs, lncRNAs, miRNAs, and mRNAs, were constructed for the first time. Based on these networks, the interaction details of circRNA-chr19 were explored. Our results demonstrated that circRNA-chr19 targeting miR-30b-3p regulated CLDN18 expression by functioning as a ceRNA. These findings may have important implications for further studies of the mechanisms of EBOV replication and transcription. These RNAs potentially have important functions and may be promising targets for EBOV therapy.

Background Self‐rated health ( SRH ) is a strong predictor of mortality in different populations. However, the associations between SRH measures and risk of ischemic heart disease ( IHD ) have not been extensively explored, especially in a Chinese population. Methods and Results More than 500 000 adults from 10 cities in China were followed from baseline (2004–2008) through December 31, 2013. Global and age‐comparative SRH were reported from baseline questionnaires. Incident IHD cases were identified through links to well‐established disease registry systems and the national health insurance system. During 3 423 542 person‐years of follow‐up, we identified 24 705 incident cases of IHD . In multivariable‐adjusted models, both global and age‐comparative SRH was significantly associated with incident IHD . Compared with excellent SRH , the hazard ratios for good, fair, and poor SRH were 1.02 (95% confidence interval [CI], 0.98–1.07), 1.32 (95% CI, 1.27–1.37), and 1.76 (95% CI, 1.68–1.85), respectively. Compared with better age‐comparative SRH , the hazard ratios for same and worse age‐comparative SRH were 1.23 (95% CI, 1.19–1.27) and 1.78 (95% CI, 1.70–1.86), respectively. The associations persisted in all subgroup analyses, although they were slightly modified by study location, education, and income levels. Conclusions A simple questionnaire for self‐assessment of health status was significantly associated with incident IHD in Chinese adults. Individuals and healthcare providers can use SRH measures as a convenient tool for assessing future IHD risk.

Background Ebola virus emerged in West Africa in December 2013. The high population mobility and poor public health infrastructure in this region led to the development of the largest Ebola virus disease (EVD) outbreak to date. Methodology/Principal findings On September 26, 2014, China dispatched a Mobile Biosafety Level-3 Laboratory (MBSL-3 Lab) and a well-trained diagnostic team to Sierra Leone to assist in EVD diagnosis using quantitative real-time PCR, which allowed the diagnosis of suspected EVD cases in less than 4 hours from the time of sample receiving. This laboratory was composed of three container vehicles equipped with advanced ventilation system, communication system, electricity and gas supply system. We strictly applied multiple safety precautions to reduce exposure risks. Personnel, materials, water and air flow management were the key elements of the biosafety measures in the MBSL-3 Lab. Air samples were regularly collected from the MBSL-3 Lab, but no evidence of Ebola virus infectious aerosols was detected. Potentially contaminated objects were also tested by collecting swabs. On one occasion, a pipette tested positive for EVD. A total of 1,635 suspected EVD cases (824 positive [50.4%]) were tested from September 28 to November 11, 2014, and no member of the diagnostic team was infected with Ebola virus or other pathogens, including Lassa fever. The specimens tested included blood (69.2%) and oral swabs (30.8%) with positivity rates of 54.2% and 41.9%, respectively. The China mobile laboratory was thus instrumental in the EVD outbreak response by providing timely and reliable diagnostics. Conclusions/Significance The MBSL-3 Lab significantly contributed to establishing a suitable laboratory response capacity during the emergence of EVD in Sierra Leone., Author summary A Mobile Biosafety Level-3 Laboratory (MBSL-3 Lab) and a well-trained diagnostic team were dispatched to Sierra Leone to assist in Ebola virus disease (EVD) diagnosis when the largest outbreak of EVD to date emerged in West Africa in 2014. This setup allowed for the diagnosis of suspected EVD cases in less than 4 hours from the time of sample receiving. The laboratory was composed of three container vehicles and was equipped with advanced ventilation system, communication system, electricity and gas supply system. Multiple safety precautions were strictly applied to reduce exposure risks. A total of 1,635 suspected EVD cases were evaluated from September 28 to November 11, 2014, and none of the staff members was infected with Ebola virus or other pathogens. The China mobile laboratory was thus instrumental in the EVD outbreak response by providing timely and accurate diagnostics. Therefore, the MBSL-3 Lab played a significant role in establishing a suitable laboratory response capacity during the emergence of EVD in Sierra Leone.

Rho GTPase activating protein 26 (ARHGAP26) is a negative regulator of the Rho family that converts the small G proteins RhoA and Cdc42 to their inactive GDP-bound forms. It is essential for the CLIC/GEEC endocytic pathway, cell spreading, and muscle development. The present study shows that ARHGAP26 mRNA undergoes extensive A-to-I RNA editing in the 3′ UTR that is specifically catalyzed by ADAR1. Furthermore, the mRNA and protein levels of ARHGAP26 were decreased in cells in which ADAR1 was knocked down. Conversely, ADAR1 overexpression increased the abundance of ARHGAP26 mRNA and protein. In addition, we found that both miR-30b-3p and miR-573 target the ARHGAP26 gene and that RNA editing of ARHGAP26 mediated by ADAR1 abolished the repression of its expression by miR-30b-3p or miR-573. When ADAR1 was overexpressed, the reduced abundance of ARHGAP26 protein mediated by miR-30b-3p or miR-573 was rescued. Importantly, we also found that knocking down ADAR1 elevated RhoA activity, which was consistent with the reduced level of ARHGAP26. Conversely, when ADAR1 was overexpressed, the amount of RhoA-GTP decreased. The similar expression patterns of ARHGAP26 and ADAR1 in human tissue samples further confirmed our findings. Taken together, our results suggest that ADAR1 regulates the expression of ARHGAP26 through A-to-I RNA editing by disrupting the binding of miR-30b-3p and miR-573 within the 3′ UTR of ARHGAP26. This study provides a novel insight into the mechanism by which ADAR1 and its RNA editing function regulate microRNA-mediated modulation of target genes.