EV71 5'UTR interacts with 3D protein affecting replication through the AKT-mTOR pathway.

BACKGROUND: EV71 is one of the important pathogens of Hand-foot-and-mouth disease (HFMD), which causes serious neurological symptoms. Several studies have speculated that there will be interaction between 5'UTR and 3D protein. However, whether 5'UTR interacts with the 3D protein in regulating virus replication has not been clarified. METHODS: Four 5'UTR mutation sites (nt88C/T, nt90-102-3C, nt157G/A and nt574T/A) and two 3D protein mutation sites (S37N and R142K) were mutated or co-mutated using virulent strains as templates. The replication of these mutant viruses and their effect on autophagy were determined. RESULTS: 5'UTR single-point mutant strains, except for EGFP-EV71(nt90-102-3C), triggered replication attenuation. The replication ability of them was weaker than that of the parent strain the virulent strain SDLY107 which is the fatal strain that can cause severe neurological complications. While the replication level of the co-mutant strains showed different characteristics. 5 co-mutant strains with interaction were screened: EGFP-EV71(S37N-nt88C/T), EGFP-EV71(S37N-nt574T/A), EGFP-EV71(R142K-nt574T/A), EGFP-EV71(R142K-nt88C/T), and EGFP-EV71(R142K-nt157G/A). The results showed that the high replicative strains significantly promoted the accumulation of autophagosomes in host cells and hindered the degradation of autolysosomes. The low replicative strains had a low ability to regulate the autophagy of host cells. In addition, the high replicative strains also significantly inhibited the phosphorylation of AKT and mTOR. CONCLUSIONS: EV71 5'UTR interacted with the 3D protein during virus replication. The co-mutation of S37N and nt88C/T, S37N and nt574T/ A, R142K and nt574T/A induced incomplete autophagy of host cells and promoted virus replication by inhibiting the autophagy pathway AKT-mTOR. The co-mutation of R142K and nt88C/T, and R142K and nt157G/A significantly reduced the inhibitory effect of EV71 on the AKT-mTOR pathway and reduced the replication ability of the virus.

Epidemiology of human papillomavirus on condyloma acuminatum in Shandong Province，China.

Condyloma acuminatum (CA) is a sexually transmitted disease (STD) caused by human papillomavirus (HPV) infection. It is important to study the prevalence and distribution of HPV genotypes before implementing the HPV vaccination program. Therefore, the aim of this study was to evaluate the epidemiological characteristics of CA cases and the distribution of HPV genotypes in Shandong Province, China. One-to-one questionnaire surveys were conducted on all patients diagnosed with CA in sentinel hospitals from Shandong Province, China. HPV genotypes were determined using the polymerase chain reaction (PCR)-reverse dot blot hybridization method. The study enrolled 1185 patients (870 males and 315 females) and found that CA patients are mainly males and sexually active people between the ages of 20 and 40. Recurrence occurred in 34.7% patients. Among the 880 CA patients who underwent HPV typing, the HPV test positivity rate was 91.4%. In these cases, low-risk (LR) HPV infection was predominant, with an infection rate of 91.3%, while high-risk (HR) HPV genotypes were found in 53.5% patients. The most frequent HPV genotypes encountered were HPV6 (57.8%), HPV11 (37.2%), HPV16 (13.7%), and HPV42 (10.3%). HPV6 and/or HPV11 are the main infections in all patients, and more than half of the patients are coinfected with HR-HPV. However, unlike other regions, HPV42 has a higher prevalence rate among CA patients in Shandong Province and is a nonvaccine HPV genotype. Therefore, regular HPV typing helps to understand the characteristics of specific genotypes and the choice of the best type for vaccine coverage.

Health Services Utilization in China during the COVID-19 Pandemic: Results from a Large-Scale Online Survey.

Timely access to essential health services is a concern as COVID-19 continues. This study aimed to investigate health services utilization during the first wave of the pandemic in China. A cross-sectional online survey was conducted using a self-administrated questionnaire in March 2020. Descriptive statistics and logistic regression were used for data analysis. A total of 4744 respondents were included, with 52.00% reporting affected services utilization. Clinical testing (68.14%) and drug purchase (49.61%) were the most affected types. Higher education level, being married, chronic disease, frequently visiting a provincial medical institution, spending more time on pandemic-related information, perception of high-risk of infection, perception of large health impact of the pandemic, and anxiety/depression were significant predictors for reporting affected services utilization. For the 431 chronic disease respondents, 62.18% reported interruption, especially for drug purchase (58.58%). Affected health services utilization was reported during the first wave of the pandemic in China, especially for those with higher education level, chronic diseases, and COVID-19 related concerns. Enhancing primary healthcare, use of telehealth, extended prescription, and public communication were countermeasures undertaken by China during the rapid rise period. As COVID-19 progresses, the changing disease characteristics, adapted health system, along with enhanced public awareness/knowledge should be considered for the evolution of health services utilization, and further investigation is needed.

Association between changes in depressive symptoms and hip fracture among middle-aged and older Chinese individuals: a prospective cohort study.

BACKGROUND: Although studies have shown that depressive symptoms are associated with an increased risk of hip fracture (HF). Depressive symptoms are dynamic, and it is unclear whether HF risk persists if depressive symptoms remit. This study aims to examine the associations between changes in depressive symptoms and HF risk. METHODS: Data were from the China Health and Retirement Longitudinal Study from 2011 to 2018. Depressive symptoms were measured using the 10-item version of the Center for Epidemiological Studied Depression scale (cutoff ≥ 10). Changes in depressive symptoms were classified into four groups by two successive surveys (stable low/no, recent-onset, recently remitted, and stable high depressive symptoms). Multivariable logistic regressions were performed to assess whether changes in depressive symptoms were associated with HF incidents reported through 2018, adjusting for age, sex, educational level, marital status and other potential confounding factors. RESULTS: In total, 8574 participants were included, 265 (3.1%) of whom had reported HF incidents in the subsequent 5-year period. Participants with recent-onset (OR = 1.97, 95% CI = 1.40-2.77) or stable high (OR = 2.15, 95% CI = 1.53-3.02) symptoms had a higher risk of HF than those with stable low/no depressive symptoms, whereas those with improved depressive symptoms (OR = 1.27, 95% CI = 0.89-1.82) had no elevation in HF risk. CONCLUSION: Stable high and recent-onset depressive symptoms were associated with increased HF risk, and no elevated HF risk was observed if symptoms remitted, suggesting that strategies to reduce depressive symptoms may be beneficial for HF prevention.

Clinical laboratory parameters and fatality of Severe fever with thrombocytopenia syndrome patients: A systematic review and meta-analysis.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high case fatality rate. Unfortunately, no vaccine or antiviral specifically targeting SFTS virus (SFTSV) are available for the time being. Our objective was to investigate the association between clinical laboratory parameters and fatality of SFTS patients. METHODS: The systematic review was conducted in accordance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. We searched (from inception to 24th February 2022) Web of Science, PubMed, National Knowledge Infrastructure databases and Wan Fang Data for relevant researchers on SFTS. Studies were eligible if they reported on laboratory parameters of SFTS patients and were stratified by clinical outcomes. A modified version of Newcastle-Ottawa scale was used to evaluate the quality of included studies. Standardized mean difference (SMD) was used to evaluate the association between laboratory parameters and outcomes. The between-study heterogeneity was evaluated quantitatively by standard Chi-square and the index of heterogeneity (I2). Heterogeneity was explored by subgroup and sensitivity analyses, and univariable meta-regression. Publication bias was determined using funnel plots and Egger's test. RESULTS: We identified 34 relevant studies, with over 3300 participants across three countries. The following factors were strongly (SMD>1 or SMD<-0.5) and significantly (P<0.05) associated mortality: thrombin time (TT) (SMD = 1.53), viral load (SMD = 1.47), activated partial-thromboplastin time (APTT) (SMD = 1.37), aspartate aminotransferase (AST) (SMD = 1.19), lactate dehydrogenase (LDH) (SMD = 1.13), platelet count (PLT) (SMD = -0.47), monocyte percentage (MON%) (SMD = -0.47), lymphocyte percentage (LYM%) (SMD = -0.46) and albumin (ALB) (SMD = -0.43). Alanine aminotransferase, AST, creatin phosphokinase, LDH, PLT, partial-thromboplastin time and viral load contributed to the risk of dying of SFTS patients in each subgroup analyses. Sensitivity analysis demonstrated that the results above were robust. CONCLUSIONS/SIGNIFICANCE: The abnormal levels of viral load, PLT, coagulation function and liver function, significantly increase the risk of SFTS mortality, suggesting that SFTS patients with above symptoms call for special concern.

Clinical symptoms associated with fatality of severe fever with thrombocytopenia syndrome: A systematic review and meta-analysis.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection disease that is deadly if left untreated. Identification of potential risk factors with prognosis value may help to focus clinical management and reduce case fatality. However, information about these factors is conflicting and scattered. In this study, documents on SFTS were collected by searching PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI) and Chinese Wan Fang Database through 12 January 2021. Meta-analysis was performed by using Stata and Review Manage software. 29 studies were included, involving 3011 participants with 38 clinical symptoms. The following factors were strongly (OR>5) and significantly (P-value<0.05) associated with mortality: hematemesis (OR=13.73), slurred speech (OR=5.05), disturbance of consciousness (OR=9.20), coma (OR=47.84), disseminated intravascular coagulation (OR=11.79), multiple organ dysfunction (OR=21.30), shock (OR=8.20) and acute kidney injury (OR=6.22). Non-specific symptoms, underlying diseases, respiratory symptoms and gastrointestinal symptoms were not associated with mortality of SFTS patients. Neurological symptoms and severe complications significantly increasing the death risk of SFTS cases can be identified by medical staff in resource-constrained settings and should be considered as core factors in future researchers that aim at improving the prognosis of SFTS patients.

Combined impact of lifestyle-related factors on total mortality among the elder Chinese: a prospective cohort study.

BACKGROUND: The combined impact of healthy lifestyle factors on total mortality among elder Chinese is unclear. This study aimed to investigate the overall impact of lifestyle factors on total mortality in a senior Chinese population, and determine whether these associations were consistent in the presence of different characteristics, including physical comorbidities. METHODS: The Chinese Longitudinal Healthy Longevity Survey (CLHLS) is a large population-based prospective cohort study in 22 of 31 provinces from mainland China. We included 15,163 adults aged ≥65 years recruited from 1998- to 2002 and followed-up until 2014. A healthy lifestyle score was calculated considering five lifestyle factors (exercise, smoking, dietary diversity, body mass index and drinking). The scores ranged from zero to five points and were classified into the following three categories: unhealthy (0-1 point), intermediate (2-3 points) and healthy (4-5 points). Cox proportional hazards regression analyses were used to assess the associations between the combined healthy lifestyle score and total mortality, adjusting for demographic characteristics and physical comorbidities, as appropriate. Stratification analyses and interaction analyses were further performed. RESULTS: Among the 15,163 participants, the mean age (SD) was 86.2 (11.6) years. During an average follow-up period of 12.5 (SD = 3.9) years, 9655 deaths occurred. The adjusted hazard ratios (HRs) of total mortality decreased as the number of healthy lifestyle factors increased. Compared to the unhealthy lifestyle group, the healthy lifestyle group had a HR and 95% CI of 0.78 and 0.72-0.83. The population attributable risk of total death among those without a healthy lifestyle was 25.2%. A healthier lifestyle pattern was associated with a lower total mortality risk among individuals with different severities of physical comorbidities, although the associations were stronger among those with fatal physical comorbidities (p-interaction < .001). CONCLUSIONS: In this large-scale study, a healthier lifestyle measured by regular exercise participation, never smoking, never drinking, good dietary diversity and normal weight, was inversely associated with total mortality, regardless of physical comorbidity status. These findings support the necessity of multiple lifestyle modifications to prevent premature death in both general elderly populations and those with physical comorbidities.

Scoring Model for Predicting the Occurrence of Severe Illness in Hospitalized Patients with Severe Fever with Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever with high mortality. Severe cases progressed rapidly, with deaths occurring within 2 weeks. Therefore, constructing a model to predict disease progression among hospitalized patients plays an important role in clinical practice. The development cohort included 121 patients with SFTS, 25 with severe SFTS, and 96 with mild SFTS. Two of the 64 variables were independent risk factors, including neurological symptoms (odds ratio [OR], 12.915; 95% confidence interval [CI], 3.342-49.916; P < 0.001) and aspartate aminotransferase/alanine aminotransferase levels (OR, 1.891; 95% CI, 1.272-2.813; P = 0.002). The model's area under the curve (AUC) was 0.882 (95% CI: 0.808-0.956). The mean AUC value obtained from the internal validation was 0.883 (95% CI: 0.809-0.957). The AUC in the external validation cohort was 0.873 (95% CI: 0.775-0.972). This model can be used to identify severely ill patients as early as possible with high predictive value, stability, and repeatability. This model can help clinicians with their treatment plans.

State of the Art of Non-Invasive Electrode Materials for Brain-Computer Interface.

The brain-computer interface (BCI) has emerged in recent years and has attracted great attention. As an indispensable part of the BCI signal acquisition system, brain electrodes have a great influence on the quality of the signal, which determines the final effect. Due to the special usage scenario of brain electrodes, some specific properties are required for them. In this study, we review the development of three major types of EEG electrodes from the perspective of material selection and structural design, including dry electrodes, wet electrodes, and semi-dry electrodes. Additionally, we provide a reference for the current chaotic performance evaluation of EEG electrodes in some aspects such as electrochemical performance, stability, and so on. Moreover, the challenges and future expectations for EEG electrodes are analyzed.

Research progress on coronavirus S proteins and their receptors.

Coronaviruses are a large family of important pathogens that cause human and animal diseases. At the end of 2019, a pneumonia epidemic caused by a novel coronavirus brought attention to coronaviruses. Exploring the interaction between the virus and its receptor will be helpful in developing preventive vaccines and therapeutic drugs. The coronavirus spike protein (S) plays an important role in both binding to receptors on host cells and fusion of the viral membrane with the host cell membrane. This review introduces the structure and function of the S protein and its receptor, focusing on the binding mode and binding region of both.