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Inflammation is a complex physiological phenomenon, which is the body's defensive response, but abnormal inflammation can have adverse effects, and many diseases are related to the inflammatory response. AMPK, as a key sensor of cellular energy status, plays a crucial role in regulating cellular energy homeostasis and glycolipid metabolism. In recent years, the anti-inflammation effect of AMPK and related signalling cascade has begun to enter everyone's field of vision – not least the impact on metabolic diseases. A great number of studies have shown that anti-inflammatory drugs work through AMPK and related pathways.Herein, this article summarises recent advances in compounds that show anti-inflammatory effects by activating AMPK and attempts to comment on them.

Background: Influenza vaccination is an important prevention strategy for flu illness. However, the vaccination rate is still low in Guangzhou, China. This study aimed to understand the status of knowledge, the attitude towards the vaccines’ reliability and safety, and other aspects associated with the willingness and practice of influenza vaccines in the pediatric and adult populations of Guangzhou city. Methods: This study was performed in eleven districts in Guangzhou between November 2020 and December 2020, including the Yuexiu, Liwan, Haizhu, Tianhe, Baiyun, Panyu, Huadu, Nansha, Huangpu, Zengcheng, and Conghua districts. The parents of children and teenagers under the age of eighteen in Guangzhou were surveyed using self-administered questionnaires in four domains: demographic information, the knowledge status and perception of influenza vaccination, the willingness and attitude towards influenza vaccination, and previous vaccine uptake. A multivariable logistic regression was employed to assess the possible determinants of willingness and practice to receive influenza vaccination, calculating the odds ratios (ORs) and 95% confidence interval (CI). A two-sided p-value < 0.05 was deemed statistically significant. Results: A total of 13,213 valid questionnaires were collected (validity rate 98.8%). Out of these participants, 42.62% (5631 participants) expressed a willingness to receive the influenza vaccine, while 55.40% (7320 participants) reported that their children and teenagers had been vaccinated against the flu. Furthermore, 40.44% of the respondents (5343 participants) or other family members had received the influenza vaccine. Logistic regression indicated that factors such as being female (OR = 1.395, 95% CI: 1.278–1.522), being involved in the work of COVID-19 prevention and control (1.551, 1.396–1.724), affirming the preventive effects of vaccination (2.474, 2.106–2.906), knowing about annual influenza vaccination (2.756, 2.540–2.992), and understanding prioritized influenza vaccination populations (1.464, 1.343–1.596) were all positively associated with vaccination willingness. Conversely, middle-aged persons (aged 40–49 years old) (0.726, 0.617–0.853), higher educational levels (undergraduate versus middle school) (0.858, 0.768–0.959), heightened concerns about vaccine safety (considering side effects are obvious versus considering it is safe and basically no side effects) (0.284, 0.188–0.429) and lower knowledge scores (0.813, 0.701–0.942) were adversely linked with vaccination willingness. Conclusion: These findings provide essential insights for altering the perception of influence and influenza vaccination, as well as enhancing health communication strategies to improve influenza vaccine uptake among Guangzhou residents.

ObjectiveTo evaluate the effect of an intervention with a required non-mandatory vaccination rate on improving influenza vaccination among healthcare workers in 2021 – 2022 influenza season. MethodsWe conducted a non-randomized community intervention trial on influenza vaccination among healthcare workers in 7 hospitals in Nanshan district of Shenzhen city during an influenza season from October 2021 to April 2022. Free on-site influenza vaccination and prompt publicity for the vaccination were carried out among all the participants; compared to the 2 139 control participants in 3 hospitals, an additional dissemination about the expected non-mandatory vaccination rate of 80% and 60% for the staff working in departments assessed as at high- and low-risk of influenza infection was implemented among 4 599 participants in 4 hospitals of the intervention group. Pearson′s chi-square test for adjusted ratio estimators was used to test the baseline and post-intervention vaccination rates for the intervention and control group. ResultsOver the influenza season for the participants working in high-risk departments, the influenza vaccination rate was 62.67% and 23.71% in the intervention and the control group, with a significant absolute rate difference (ARD) of 38.96% (95% confidence interval: 14.17% – 63.75%) between the two groups (P < 0.05); for the participants of low-risk departments, the influenza vaccination rate was 34.57% and 22.96% in the intervention and the control group (P > 0.05); for all the participants, the influenza vaccination rate was 43.90% and 23.19% in the intervention and in the control group (P > 0.05). The intervention of dissemination about the expected vaccination rate showed a significant impact upon the influenza vaccination rate for the participants working in high-risk departments but not for those in low-risk departments. ConclusionUnder the premise of without both reward and punishment for having influenza vaccination, the dissemination of a high expected non-mandatory vaccination rate may increase the influenza vaccination rate among healthcare workers intervened.

Abstract Background The combined effect of serum uric acid (SUA) and blood glucose on cognition has not been explored. This study aimed to examine the separate and combined association of SUA and fasting plasma glucose (FPG) or diabetes mellitus (DM) with cognition in a sample of Chinese middle-aged and elderly population. Methods A total of 6,509 participants aged 45 years or older who participated in the China Health and Retirement Longitudinal Study (CHARLS, 2011) were included. The three cognitive domains assessed were episodic memory, mental status, and global cognition (the sum of the first two terms). Higher scores indicated better cognition. SUA and FPG were measured. The participants were grouped based on SUA and FPG quartiles to evaluate their combined associations of cognition with SUA Q1–Q3 only (Low SUA), with FPG Q4 only (High FPG), without low SUA and high FPG levels (Non), and with low SUA and high FPG levels (Both), multivariate linear regression models were used to analyze their association. Results Lower SUA quartiles were associated with poorer performance in global cognition and episodic memory compared with the highest quartile. Although no association was found between FPG or DM and cognition, high FPG or DM combined with low SUA levels in women (βFPG = -0.983, 95% CI: -1.563–-0.402; βDM = -0.800, 95% CI: -1.369–-0.232) had poorer cognition than those with low SUA level only (βFPG = -0.469, 95% CI: -0.926–-0.013; βDM = -0.667, 95% CI: -1.060–-0.275). Conclusion Maintaining an appropriate level of SUA may be important to prevent cognitive impairment in women with high FPG.

BackgroundAir pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages.ObjectiveTo construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution.MethodsData on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO2, NO2, CO, PM2.5, PM10, and maximum 8 h O3 concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model.ResultsPM2.5, NO2, SO2, and O3 were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM2.5, NO2, SO2 and O3 were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI .ConclusionThe J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.

Abstract Background Non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19) may have suppressed the transmission of other infectious diseases. This study aimed to evaluate the impact of different degrees of NPIs during the COVID-19 pandemic on hand, foot and mouth disease (HFMD) in Guangzhou, China. Methods Weekly reported HFMD cases and pathogens information during 2015–2021 in Guangzhou were collected from the China National Notifiable Disease Reporting System. The observed number of HFMD cases in 2020 and 2021 was compared to the average level in the same period during 2015–2019. Then, an interrupted time-series segmented regression analysis was applied to estimate the impact of NPIs on HFMD, such as social distancing, suspension of schools, community management and mask wearing. The effects across different subgroups stratified by gender, children groups and enterovirus subtype of HFMD were also examined. Results A total of 13,224 and 36,353 HFMD cases were reported in 2020 and 2021, which decreased by 80.80% and 15.06% respectively compared with the average number of cases in the same period during 2015–2019. A significant drop in the number of HFMD cases during time when strict NPIs were applied (relative change: 69.07% [95% confidence interval (CI): 68.84%–69.30%]). The HFMD incidence rebounded to historical levels in 2021 as the lockdown eased. The slightest reduction of HFMD cases was found among children at kindergartens or childcare centres among the three children groups (children at kindergartens or childcare centres: 55.50% [95% CI: 54.96%–56.03%]; children living at home: 72.64% [95% CI: 72.38%–72.89%]; others: 74.06% [95% CI: 73.19%–74.91%]). Conclusions The strong NPIs during the COVID-19 epidemic may have a significant beneficial effect on mitigating HFMD. However, the incidence of HFMD rebounded as the NPIs became less stringent. Authorities should consider applying these NPIs during HFMD outbreaks and strengthening personal hygiene in routine prevention.

ObstructiveTo develop and validate radiomics and machine learning models for identifying encrusted stents and compare their recognition performance with multiple metrics.MethodsA total of 354 patients with ureteral stent placement were enrolled from two medical institutions and divided into the training cohort (n = 189), internal validation cohort (n = 81) and external validation cohort (n = 84). Based on features selected by Wilcoxon test, Spearman Correlation Analysis and least absolute shrinkage and selection operator (LASSO) regression algorithm, six machine learning models based on radiomics features were established with six classifiers (LR, DT, SVM, RF, XGBoost, KNN). After comparison with those models, the most robust model was selected. Considering its feature importance as radscore, the combined model and a nomogram were constructed by incorporating indwelling time. Accuracy, sensitivity, specificity, area under the curve (AUC), decision curve analysis (DCA) and calibration curve were used to evaluate the recognition performance of models.Results1,409 radiomics features were extracted from 641 volumes of interest (VOIs) and 20 significant radiomics features were selected. Considering the superior performance (AUC 0.810, 95%CI, 0.722–0.888) in the external validation cohort, feature importance of XGBoost was used as a radscore, constructing a combined model and a nomogram with indwelling time. The accuracy, sensitivity, specificity and AUC of the combined model were 98, 100, 97.3% and 0.999 for the training cohort, 83.3, 80, 84.5% and 0.867 for the internal cohort and 78.2, 76.3, 78.8% and 0.820 for the external cohort, respectively. DCA indicates the favorable clinical utility of models.ConclusionMachine learning model based on radiomics features enables to identify ureteral stent encrustation with high accuracy.

BackgroundPrevious studies involving uric acid (UA) in some specialized disease populations have found that high UA is associated with enhanced patient function. The mechanism to explain this association may be that UA, an important antioxidant, exerts neuroprotective effects. Patients with schizophrenia (SCZ) have severe oxidative stress abnormalities, and cognitive impairment is a major obstacle to their rehabilitation. Only few studies have been conducted on UA and cognitive impairment in SCZ. This study aims to clarify the relationship between UA and cognitive impairment and explore whether UA could be used as a potential biological marker of cognition in SCZ during maintenance period.MethodsA total of 752 cases of SCZ during maintenance period from Baiyun Jingkang Hospital were included. Cognition was measured using the Mini-Mental State Examination scale. UA was measured using the Plus method. The participants were grouped on the basis of UA to evaluate the association of cognition with low-normal (3.50–5.07 mg/dL for men, 2.50–4.19 mg/dL for women), middle-normal (5.07–6.39 mg/dL for men, 4.19–5.18 mg/dL for women), high-normal (6.39–7.00 mg/dL for men, 5.18–6.00 mg/dL for women), and high (>7.00 mg/dL for men, >6.00 mg/dL for women) levels of UA. Multiple logistic regression and linear regression models and restricted cubic spline (RCS) were utilized to evaluate the relationship.ResultsUric acid was positively associated with cognitive function. Subgroup analyses showed that high UA was associated with enhanced cognition in participants with low anticholinergic cognitive burden (ACB).ConclusionUric acid may be used as a simple objective biological indicator to assess cognition in SCZ during maintenance period.

Objectives: An outbreak of the SARS-CoV-2 Delta variant occurred in Guangzhou in 2021. This study aimed to identify the transmission dynamics and epidemiological characteristics of the Delta variant outbreak to formulate an effective prevention strategy. Methods: A total of 13102 close contacts and 69 index cases were collected. The incubation period, serial interval, and time interval from the exposure of close contacts to the symptom onset of cases were estimated. Transmission risks based on the exposure time and various characteristics were also assessed. Results: The mean time from exposure to symptom onset among non-household presymptomatic transmission was 3.83 ± 2.29 days, the incubation period was 5 days, and the serial interval was 3 days. The secondary attack rate was high within 4 days before onset and 4–10 days after symptom onset. Compared with other contact types, household contact had a higher transmission risk. The transmission risk increased with the number and frequency of contact with index cases. Cycle threshold (Ct) values were associated with lower transmission risk (adjusted odds ratio [OR] 0.93 [95% CI 0.88–0.99] for ORF 1ab gene; adjusted OR 0.91 [95% CI 0.86–0.97] for N gene). Conclusion: The contact tracing period may need to be extended to 4 days before symptom onset. The low Ct value of index cases, the high number and frequency of contact with index cases, and household contacts were associated with a higher transmission risk of SARS-CoV-2 Delta.

Background: Chronic pruritus (CP) is a common and aggravating symptom associated with skin and systemic diseases. Although clinical reports suggest that Chinese herbal medicine (CHM) is safe and effective in Chronic pruritus treatment, evidence to prove it is lacking. Therefore, in this review, we evaluated the therapeutic effects and safety of Chinese herbal medicine for the treatment of Chronic pruritus.Methods: Nine databases were searched for relevant randomized controlled trials (RCTs) from the inception of the database to 20 April 2022. The randomized controlled trials that compared the treatment of Chinese herbal medicine or a combination of Chinese herbal medicine and conventional western medicine treatment (WM) with western medicine treatment intervention for patients with Chronic pruritus were selected. We evaluated the effects of treatment with Chinese herbal medicine on the degree of pruritus, the Dermatology Life Quality Index (DLQI) score, response rate, recurrence rate, and incidence of adverse events in patients with Chronic pruritus. The risk of bias in each trial was evaluated using the Cochrane Collaboration tool. The RevMan software (version 5.3) was used for performing meta-analyses to determine the comparative effects.Results: Twenty-four randomized controlled trials were included, compared with placebo, moderate-quality evidence from one study showed that Chinese herbal medicine was associated with reduced visual analogue scale (VAS) (MD: −2.08; 95% CI = −2.34 to −1.82). Compared with western medicine treatment, low-to moderate-quality evidence from 8 studies indicated that Chinese herbal medicine was associated with reduced visual analogue scale, 4 studies indicated that Chinese herbal medicine was associated with reduced Dermatology Life Quality Index (MD = −1.80, 95% CI = −2.98 to −.62), and 7 studies indicated that Chinese herbal medicine was associated with improved Effective rate (RR: 1.26; 95% CI = 1.19–1.34). Compared with combination of Chinese herbal medicine and western medicine treatment, 16 studies indicated that Chinese herbal medicine was associated with reduced visual analogue scale, 4 studies indicated that Chinese herbal medicine was associated with reduced Dermatology Life Quality Index (MD = −2.37, 95% CI = −2.61 to −2.13), and 13 studies indicated that Chinese herbal medicine was associated with improved Effective rate (RR: 1.28; 95% CI = 1.21–1.36). No significant difference in the occurrence of adverse events in using Chinese herbal medicine or western medicine treatment was reported.Conclusion: The efficacy of Chinese herbal medicine used with or without western medicine treatment was better than western medicine treatment in treating chronic pruritus. However, only a few good studies are available regarding Chronic pruritus, and thus, high-quality studies are necessary to validate the conclusions of this study.

BackgroundThe association between blood lipids and cognitive function in schizophrenia is still controversial. Thus, the present study aimed to verify the association between various lipid parameters and cognitive impairment in schizophrenic patients and potential lipid pathways.MethodsA total of 447 adult inpatients with schizophrenia were divided into cognitive normal and cognitive impairment groups based on the Mini-Mental State Examination with a cut-off of 26. The blood lipid parameters were defined as abnormal levels based on the guideline. The liquid chromatography-mass spectrometry method was used to preliminarily explore the potential lipid metabolism pathway associated with cognitive impairment.ResultsThere were 368 (82.3%) patients who had cognitive impairment. Herein, apolipoprotein B was positively associated with cognitive function in overall patients and age (≥45 and

Focal adhesion kinase (FAK, also known as PTK2) is a tyrosine kinase that regulates integrin and growth factor signaling pathways and is involved in the migration, proliferation and survival of cancer cells. FAK is a promising target for cancer treatment. Many small molecule FAK inhibitors have been identified and proven in both preclinical and clinical studies to be effective inhibitors of tumor growth and metastasis. There are many signaling pathways, such as those involving FAK, Src, AKT, MAPK, PI3K, and EGFR/HER-2, that provide survival signals in cancer cells. Dual inhibitors that simultaneously block FAK and another factor can significantly improve efficacy and overcome some of the shortcomings of single-target inhibitors, including drug resistance. In this review, the antitumor mechanisms and research status of dual inhibitors of FAK and other targets, such as Pyk2, IGF-IR, ALK, VEGFR-3, JAK2, EGFR, S6K1, and HDAC2, are summarized, providing new ideas for the development of effective FAK dual-target preparations.

Abstract Background We investigated college students’ attitude and compliance towards a prevention strategy involving use of non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19). Methods We conducted a cross-sectional online survey in four universities in Guangdong Province (China) based on purposive sampling. A self-administered questionnaire was given to College students (CSs) to measure the supportive attitude towards an outbreak control strategy and adoption of NPIs in respondents. Results A total of 44,446 CSs participated between 31 January and 10 February 2020; 92.7% of respondents supported the outbreak control strategy. The proportion of respondents who avoided public places, wore a facemask, avoid gatherings, and washed hands more frequently than usual was 94.8, 92.8, 91.2 and 86.9%. respectively. A total of 76.5% respondents adopted all four measures. A supportive attitude was associated with NPI adoption. Students who were female, postgraduate, anxious, and not depressed tended to have a higher supportive attitude and higher chance of NPI adoption. Conclusions Higher supportiveness towards the disease control strategy for the Chinese public may lead to higher adoption rate of NPIs. Psychosocial factors were related to a supportive attitude and adoption of the NPI. We believe that our findings could aid policymakers to create NPIs to prevent and control emerging infectious diseases such as COVID-19.

The PI3K-Akt-mTOR pathway is a viable target for cancer treatment and can be used to treat various malignant tumours, including follicular lymphoma and breast cancer. Both enzymes, PI3K and mTOR, are critical in this pathway. Hence, in recent years, an array of inhibitors targeting these two targets have been studied, showing dual PI3K/mTOR inhibition compared with single targeting small molecule inhibitors. Inhibitors not only inhibit cell proliferation but also promote cell apoptosis. These inhibitors show high potency and little drug resistance even at low doses, suggesting that PI3K/mTOR inhibitors are promising cancer drugs. Herein, we summarised the recent research of PI3K/mTOR dual inhibitors—for example, structure-activity relationship, pharmacokinetics, and clinical practice, and briefly commented on them.Clinical Trial Registration:https://clinicaltrials.gov.

The relationship between body mass index (BMI) and cognitive impairment remains controversial, especially in older people. This study aims to confirm the association of phenotypic and genetic obesity with cognitive impairment and the benefits of adhering to a healthy lifestyle. This prospective study included 10,798 participants (aged ≥ 50 years) with normal cognitive function from the Health and Retirement Study in the United States. Participants were divided into low (lowest quintile), intermediate (quintiles 2–4), and high (highest quintile) groups according to their polygenic risk score (PRS) for BMI. The risk of cognitive impairment was estimated using Cox proportional hazard models. Higher PRS for BMI was associated with an increased risk, whereas phenotypic obesity was related to a decreased risk of cognitive impairment. Never smoking, moderate drinking, and active physical activity were considered favourable and associated with a lower risk of cognitive impairment compared with current smoking, never drinking, and inactive, respectively. A favourable lifestyle was associated with a low risk of cognitive impairment, even in subjects with low BMI and high PRS for BMI. This study suggest that regardless of obesity status, including phenotypic and genetic, adhering to a favourable lifestyle is beneficial to cognitive function.

Background: Diabetes mellitus (DM) is a recognised risk factor for cognitive dysfunction. The purpose of this study was to explore the relationship between active treatment for DM and cognitive function in middle-aged (< 60 years) and older adults (≥60 years), respectively.Methods: A total of 13,691 participants (58.55 ± 9.64 years, 47.40% of men) from the Chinese Health and Retirement Longitudinal Study (CHARLS) were included. The participants were classified into three groups according to whether or not they have diabetes and to their diabetes treatment status: diabetes-free, treated-diabetes and untreated-diabetes, in which the diabetes-free group was regarded as reference specially. Cognitive function was assessed by two interview-based measurements for mental intactness and episodic memory.Results: Compared with the participants in the diabetes-free group, the older participants in the treated-diabetes group had better performance in terms of mental intactness (β = 0.37, 95% CI = 0.04–0.70). No significant association was observed in the middle-aged participants. In the subgroup analyses, the lower cognitive score was only observed in people without depression, who had never smoked and drunk, and with a normal weight (body mass index: 18.5–23.9 kg/m2).Conclusion: The cognitive function of actively treated diabetic patients was better than that of patients without diabetes, but the improvement was significant only in elderly people. Depression, smoking, drinking, and an abnormal weight may attenuate this effect.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mimics the influenza A (H1N1) virus in terms of clinical presentation, transmission mechanism, and seasonal coincidence. Comprehensive data for the clinical severity of adult patients co-infected by both H1N1 and SARS-CoV-2, and, particularly, the relationship with PCR cycle threshold (Ct) values are not yet available. All participants in this study were tested for H1N1 and SARS-CoV-2 simultaneously at admission. Demographic, clinical, treatment, and laboratory data were extracted from electronic medical records and compared among adults hospitalized for H1N1 infection, SARS-CoV-2 infection and co-infection with both viruses. Ct values for viral RNA detection were further compared within SARS-CoV-2 and co-infection groups. Score on seven-category ordinal scale of clinical status at day 7 and day 14 were assessed. Among patients with monoinfection, H1N1 infection had higher frequency of onset symptoms but lower incidence of adverse events during hospitalization than SAR-CoV-2 infection (P < 0.05). Co-infection had an increased odds of acute kidney injury, acute heart failure, secondary bacterial infections, multilobar infiltrates and admittance to ICU than monoinfection. Score on seven-category scale at day 7 and day 14 was higher in patients with coinfection than patients with SAR-CoV-2 monoinfection (P

Pulmonary fibrosis is a fatal chronic progressive respiratory disease, characterized by continuous scarring of the lung parenchyma, leading to respiratory failure and death. The incidence of PF has increased over time. There are drugs, yet, there are some limitations. Hence, it is of importance to find new therapies and new drugs to replace the treatment of pulmonary fibrosis. In recent years, there have been a great number of research reports on the treatment of traditional Chinese medicine polysaccharides in various system fields. Among them, the treatment of PF has also gained extensive attention. This review summarized the source of polysaccharides, the drug activity of traditional Chinese medicine, and the protective effects on targets of Pulmonary fibrosis. We hope it can inspire researchers to design and develop polysaccharides, serving as a reference for potential clinical therapeutic drugs.

Background: Higher visit-to-visit cholesterol has been associated with cognitive decline. However, the association between long-term increase or decrease in cholesterol and cognitive decline remains unclear.Methods: A total of 4,915 participants aged ≥45 years with normal cognition in baseline were included. The participants were divided into four groups, namely low–low, low–high, high–low, and high–high, according to the diagnostic thresholds of total cholesterol (TC), non-high-density lipoprotein cholesterol (NHDL-C), low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) after 4 years of follow-up. Cognitive function was assessed by episodic memory and mental intactness. Binary logistic regression was used to analyse the association of cholesterol variation with cognitive decline.Results: Among the participants, 979 (19.9%) experienced global cognitive decline. The odds ratio (OR) of global cognitive and memory function decline were remarkably lower in participants in the low–high NHDL-C group than those in the low–low group [OR and 95% confidence interval (CI): 0.50 [0.26–0.95] for global cognitive decline, 0.45 [0.25–0.82] for memory function decline]. The lower OR was also significant in females (OR [95% CI]: 0.38 [0.17–0.87] for global cognitive decline; 0.44 [0.19–0.97] for memory function decline) and participants without cardiovascular disease (OR [95% CI]: 0.31 [0.11–0.87] for global cognitive decline; 0.34 [0.14–0.83] for memory function decline). The increases in other cholesterol were also negatively associated with the risk of cognitive decline although not significantly.Conclusions: A longitudinal increase in NHDL-C may be protective for cognition in females or individuals without cardiovascular disease.

Background: Respiratory viruses are known to contribute to asthma exacerbations. A meta-analysis of three studies reported no association between coronavirus disease 2019 (COVID-19) mortality and preexisting asthma. This study aimed to investigate the mortality of patients with COVID-19 in relation to preexisting asthma and other allergic diseases associated with changes in respiratory function.Methods: PubMed, Embase, and the Cochrane Library were queried for papers published up to April 9, 2021: (1) population: patients who tested positive for SARS-CoV-2 according to the WHO guidelines; (2) exposure: preexisting asthma or allergic rhinitis; (3) outcomes: mortality, ICU admission, and/or hospitalization; and (4) language: English. For studies that reported adjusted models, the most adjusted model was used for this meta-analysis; otherwise, unadjusted results were used.Results: Twenty-four studies (1,169,441 patients) were included in this meta-analysis. Patients who died of COVID-19 were not more likely to have preexisting asthma (OR = 0.95, 95%CI: 0.78–1.15, P = 0.602; I2 = 63.5%, Pheterogeneity < 0.001). Patients with COVID-19 and admitted to the ICU (OR = 1.17, 95%CI: 0.81–1.68, P = 0.407; I2 = 91.1%, Pheterogeneity = 0.407), or hospitalized (OR = 0.91, 95%CI: 0.76–1.10, P = 0.338; I2 = 79.1%, Pheterogeneity < 0.001) were not more likely to have preexisting asthma. The results for mortality and hospitalization remained non-significant when considering the adjusted and unadjusted models separately. The results from the sensitivity analyses were consistent with the primary analyses, suggesting the robustness of our results.Conclusion: This meta-analysis suggests that the patients who died from COVID-19, were admitted to the ICU, or hospitalized were not more likely to have asthma.

Data are limited on the viral load, viral shedding patterns, and potential infectivity of asymptomatic patients (APs) with coronavirus disease 2019 (COVID-19). This study included 31 adult patients who were virologically confirmed to have COVID-19 but were asymptomatic on admission. Among these 31 patients, 22 presented symptoms after admission and were defined as asymptomatic patients in the incubation period (APIs); the other nine patients remained asymptomatic during hospitalization and were defined as asymptomatic patients (APs). The median cycle threshold (Ct) value of APs (39.0, interquartile range (IQR) 37.5–39.5) was significantly higher than that of APIs (34.5, IQR 32.2–37.0), indicating a lower viral load in APs. However, the duration of viral shedding remained similar in the two groups (7 days, IQR 5–14 days vs. 8 days, IQR 5–16 days). The study findings demonstrated that although APs with COVID-19 have a lower viral load, they still have certain period of viral shedding, which suggests the possibility of transmission during their asymptomatic period. Further longitudinal surveillance of these asymptomatic cases via virus nucleic acid testing are warranted.

In this paper, the method of mutual information is used to study the economic dependence among the provinces in Chinaʼs Eastern Coastal Economic Belt from 2015 to 2020, and the core structure of the dependence is depicted. The results show that, first of all, there is a wide range of economic dependence among the provinces in the Eastern Coastal Economic Belt, and the dependence changes with the different states of economic development. Secondly, the phenomenon of geographical clustering is not obvious. Most provinces maintain a strong economic dependence relationship with the economically developed provinces, and this dependence relationship is relatively stable, while the economically underdeveloped provinces are often on the edge of the dependence structure. Finally, the economically developed provinces maintain strong economic dependence with each other, such as Jiangsu (No. 7), Shandong (No. 9), and Zhejiang (No. 12), and Beijing (No. 1), Guangdong (No. 3), and Shanghai (No. 10). However, the former three provinces are more in the core position of this structure, that is, the other provinces maintain the stronger dependence relationship with these three provinces.

By calculating the mutual information of stock indexes of 10 primary industry sectors in China, this paper analyzes the dependence relationship among Chinese stock sectors during the COVID-19 and the dynamic evolution of the relationship by using the sliding window method. According to the actual situation of the development of COVID-19 in China, the samples were divided into three stages, namely, calm period, pandemic period, and post-pandemic period. The results show that the dependence relationship among Chinese stock sectors is significantly enhanced in the pandemic period, but it decreases in the post-pandemic period and the dependence structure is similar to that in the calm period. The industrials sector is most closely connected with other sectors in the pandemic period. The information technology sector and telecommunication services sector maintain strong dependence in the three periods and share little contact with other sectors. In the pandemic period, the dependence between the consumer staples sector and other sectors is significantly enhanced, and consumer staples sector and health care sector maintain a strong dependence. From the results of the sliding window, the Chinese stock market is sensitive to the impact of COVID-19, but the duration of the impact on the dependence among the stock sectors is not long.

The phenomenon of COVID-19 patients tested positive for SARS-CoV-2 after discharge (redetectable as positive, RP) emerged globally. The data of incidence rate and risk factors for RP event and the clinical features of RP patients may provide recommendations for virus containment and cases management for COVID-19. We prospectively collected and analyzed the epidemiological, clinical and virological data from 285 adult patients with COVID-19 and acquired their definite clinical outcome (getting PCR positive or not during post-discharge surveillance). By March 10, 27 (9.5%) discharged patients had tested positive for SARS-CoV-2 in their nasopharyngeal swab after a median duration of 7·0 days (IQR 5·0-8·0). Compared to first admission, RP patients generally had milder clinical symptoms, lower viral load, shorter length of stay and improved pulmonary conditions at readmission (p0.05). A prolonged duration of viral shedding (>10 days) during the first hospitalization [adjusted odds ratio [aOR]: 5.82, 95% confidence interval [CI]: 2.50-13.57 for N gene; aOR: 9.64, 95% CI: 3.91-23.73 for ORF gene] and higher Ct value (ORF) in the third week of the first hospitalization (aOR: 0.69; 95% CI: 0.50-0.95) were associated with RP events. In conclusion, RP events occurred in nearly 10% of COVID-19 patients shortly after the negative tests, were not associated with worsening symptoms and unlikely reflect reinfection. Patients' lack of efficiency in virus clearance was a risk factor for RP result. It is noteworthy that elder RP patients (≥ 60 years old) were more susceptible to clinical symptoms at readmission.

This study mainly uses the method of effective transfer entropy (ETE) to study the risk transmission in each year among the 11 provinces and municipalities in the Yangtze River Economic Belt during the last five years. From the results of the risk transmission network, centralities of the regions, and maximum spanning trees, it can be seen that, in the years of 2015 and 2016, the risk transmission in the Yangtze River Economic Belt is relatively large, and in 2015, Shanghai is the main risk exporter. This may be mainly due to the violent turbulence in the Chinese stock market, and in 2016, although Chinese stock market is in a stable position, the whole risk transmission is still high, but the difference from 2015 is that the input and output risk of each province and municipality are more uniform and are no longer like Shanghai as the main exporter of risk in 2015. From the perspective of risk spillover, the overall trend is from the western region of China to the central region, and finally to the eastern region. Specifically, from the results of the maximum spanning tree, except the stock market crash period in 2015, Chongqing, Guizhou, and Yunnan (the western region) are the main exporters of risk, while Jiangsu, Zhejiang, and Shanghai (the eastern region) are often at the edge at this time, and from the results of the centrality of the region indexes, Hubei, Jiangxi, and Anhui (the central region) are in the hub position of risk transmission.

ABSTRACT Cronobacter sakazakii is an important pathogen associated with the development of necrotizing enterocolitis (NEC), infant sepsis, and meningitis. Several randomized prospective clinical trials demonstrated that oral probiotics could decrease the incidence of NEC. Previously, we isolated and characterized a novel probiotic, Bacteroides fragilis strain ZY-312. However, it remains unclear how ZY-312 protects the host from the effects of C. sakazakii infection. To understand the underlying mechanisms triggering the probiotic effects, we tested the hypothesis that there was cross talk between probiotics/probiotics-modulated microbiota and the local immune system, governed by the permeability of the intestinal mucosa, using in vitro and in vivo models for the intestinal permeability. The probiotic effects of ZY-312 on intestinal epithelial cells were first examined, and the results revealed that ZY-312 inhibited C. sakazakii invasion, C. sakazakii-induced dual cell death (pyroptosis and apoptosis), and epithelial barrier dysfunction in vitro and in vivo. The presence of ZY-312 also resulted in decreased expression of an inflammasome (NOD-like receptor family member pyrin domain-containing protein 3 [NLRP3]), caspase-3, and serine protease caspase-1 in a neonatal rat model. Furthermore, ZY-312 significantly modulated the compositions of the intestinal bacterial communities and decreased the relative abundances of Proteobacteria and Gammaproteobacteria but increased the relative abundances of Bacteroides and Bacillus in neonatal rats. In conclusion, our findings have shown for the first time that the probiotic B. fragilis ZY-312 suppresses C. sakazakii-induced NEC by modulating the proinflammatory response and dual cell death (apoptosis and pyroptosis). IMPORTANCE Cronobacter sakazakii is an opportunistic pathogenic bacterium that can cause necrotizing enterocolitis (NEC). However, the mechanism of pathogenicity of C. sakazakii is largely unknown. Here we have now demonstrated that apoptotic and pyroptotic stimuli are effectors of C. sakazakii-induced NEC. Previously, we isolated a novel probiotic strain candidate from fecal samples from healthy infants and characterized it as Bacteroides fragilis strain ZY-312. Functional characterization reveals that ZY-312 inhibited C. sakazakii invasion, restoring epithelial barrier dysfunction, decreasing the expression of inflammatory cytokines, and reducing dual cell death (pyroptosis and apoptosis). Furthermore, the presence of ZY-132 was sufficient to hinder the adverse reaction seen with C. sakazakii in a C. sakazakii-induced NEC model. Taking the results together, our study demonstrated the utility of ZY-312 as a promising probiotic agent for the prevention of NEC.

Enterovirus A71 (EV-A71) is a major pathogen that causes severe and fatal cases of hand-foot-and-mouth disease (HFMD). HFMD caused by EV-A71 seriously endangers children’s health. Although autophagy is an important antiviral defense mechanism, some viruses have evolved strategies to utilize autophagy to promote self-replication. EV-A71 can utilize autophagy vesicles as replication scaffolds, indicating that EV-A71 infection is closely related to its autophagy induction mechanism. VP1, a structural protein of EV-A71, has been reported to induce autophagy, but the underlying mechanism is still unclear. In this study, we found that the C-terminus (aa 251–297) of VP1 induces autophagy. Mass spectrometry analysis suggested that prohibitin 2 (PHB2) interacts with the C-terminus of the EV-A71 VP1 protein, and this was further verified by coimmunoprecipitation assays. After PHB2 knockdown, EV-A71 replication, viral particle release, and viral protein synthesis were reduced, and autophagy was inhibited. The results suggest that PHB2 interaction with VP1 is essential for induction of autophagy and the infectivity of EV-A71. Furthermore, we confirmed that EV-A71 induced complete autophagy that required autolysosomal acidification, thus affecting EV-A71 infection. In summary, this study revealed that the host protein PHB2 is involved in an autophagy mechanism during EV-A71 infection.

Human adenovirus type 55 (HAdV-B55) is a recently identified acute respiratory disease (ARD) pathogen in HAdV species B with a recombinant genome between renal HAdV-B11 and respiratory HAdV-B14. Since HAdV-B55 first appeared in China school in 2006, no more ARD cases associated with it had been reported until 2011, when there was an outbreak of adult severe community-acquired pneumonia (CAP) in Beijing, China. Reported here is the bioinformatics analysis of the re-emergent HAdV-B55 responsible for this outbreak. Recombination and protein sequence analysis re-confirmed that this isolate (BJ01) was a recombinant virus with the capsid hexon gene from HAdV-B11. The selection pressures for the three capsid proteins, i.e., hexon, penton base, and fiber genes, were all negative, along with very low non-synonymous (dN) and synonymous (dS) substitutions/site (

Vimentin (VIM) is a surface receptor for enterovirus-A71, mediating the initial binding and subsequent increase in EV-A71 infectivity. The caspid protein VP1 variation, A289T, is reportedly closely associated with less severe central nervous system (CNS) infections in humans. However, it is unclear whether VIM is associated with a reduction in CNS infections of EV-A71 in the presence of A289T. We investigated whether VIM served as a receptor for EV-A71 in the presence of an A298T substitution in VP1. EV-A71-289A and EV-A71-289T were used to infect human rhabdomyosarcoma cells, control human brain microvascular endothelial cells (HBMECs), and VIM-knockout (KO) HBMECs and inoculated BALB/c mice, SV129 mice, and VIM-KO SV129 mice. Furthermore, we cloned VP1-289A-Flag and VP1-289T-Flag proteins for co-immunoprecipitation analysis. Analysis of viral function revealed that the capacity of viral attachment, replication, and protein synthesis and secretion decreased in HBMECs during an EV-A71-289A infection, the infectivity being higher than that of EV-A71-289T upon VIM-KO. Histopathological and immunohistochemical analyses of brain tissue revealed that cerebral cortical damage was more extensive in EV-A71-289A than in EV-A71-289T infections in control SV129 mice; however, no significant difference was observed upon VIM-KO. Co-immunoprecipitation analysis revealed an interaction between VP1 and VIM, which was attenuated in VP1 harboring A289T; however, this attenuation was reversed by VIM (1-58) peptide. The A289T variation of VP1 specifically decreased the virulence of EV-A71 in HBMECs, and the attenuated interaction between VP1 harboring the A289T variation and VIM essentially decreased the CNS infectivity of EV-A71 in vitro and vivo.

Circulating microRNA-21 (miR-21) is known to be aberrantly expressed in hepatocellular carcinoma (HCC) patients, and this implies that microRNA-21 is a promising and novel indicator of HCC. However, a systematic evaluation of the performance of microRNA-21 as a diagnostic marker for HCC has yet to be conducted. Therefore, the test performance of circulating miR-21 for HCC was assessed in this study.Three common international databases and a Chinese electronic database were used to search for literature on the diagnostic accuracy of microRNA-21 for HCC. The pooled results included the sensitivity and specificity of microRNA-21 for HCC detection and were analyzed with a random effect model. The area under summary receiver operating characteristic curve (AUC) was used to estimate overall test performance.A total of 339 HCC patients and 338 controls without HCC from four published studies were eligible for the meta-analysis and included in our study. The test performance of circulating miR-21 in HCC detection was assessed with the summary estimates of sensitivity and specificity, which were 81.2% (95% CI: 70.8% to 88.4%) and 84.8% (95% CI: 75.1% to 91.2%), respectively. The value of AUC was 0.90 (95% CI: 0.87 to 0.92). Significant inter-study heterogeneity was detected by our analysis, and sub-group analyses suggested that the type of control group was probably a source of heterogeneity.Our current findings suggested that circulating miR-21 can serve as a potential co-biomarker for early-stage HCC diagnosis. Thorough large-scale studies are needed to confirm the generalizability of our findings.

Findings on the association between long-term intake of fish or long-chain n-3 polyunsaturated fatty acids (PUFAs) and risk of atrial fibrillation (AF) are inconsistent in observational studies. We conducted a meta-analysis of prospective studies to separately examine the associations between fish consumption and dietary intake of n-3 PUFAs with the risk of AF. A systematic search was conducted in PubMed and Embase to identify relevant studies. Risk estimates were combined using a random-effect model. Seven prospective cohort studies covering 206,811 participants and 12,913 AF cases were eligible. The summary relative risk of AF for the highest vs. lowest category of fish consumption and dietary intake of n-3 PUFAs was 1.01(95% confidence interval: 0.94–1.09) and 1.03 (95% confidence interval: 0.97–1.09), respectively. These null associations persisted in subgroup and dose-response analyses. There was little evidence of publication bias. This meta-analysis suggests that neither long-term intake of fish, nor of n-3 PUFAs were significantly associated with lower risk of AF.