Interactions among acute respiratory viruses in Beijing, Chongqing, Guangzhou, and Shanghai, China, 2009-2019.

Background: A viral infection can modify the risk to subsequent viral infections via cross-protective immunity, increased immunopathology, or disease-driven behavioral change. There is limited understanding of virus-virus interactions due to lack of long-term population-level data. Methods: Our study leverages passive surveillance data of 10 human acute respiratory viruses from Beijing, Chongqing, Guangzhou, and Shanghai collected during 2009 to 2019: influenza A and B viruses; respiratory syncytial virus A and B; human parainfluenza virus (HPIV), adenovirus, metapneumovirus (HMPV), coronavirus, bocavirus (HBoV), and rhinovirus (HRV). We used a multivariate Bayesian hierarchical model to evaluate correlations in monthly prevalence of test-positive samples between virus pairs, adjusting for potential confounders. Results: Of 101,643 lab-tested patients, 33,650 tested positive for any acute respiratory virus, and 4,113 were co-infected with multiple viruses. After adjusting for intrinsic seasonality, long-term trends and multiple comparisons, Bayesian multivariate modeling found positive correlations for HPIV/HRV in all cities and for HBoV/HRV and HBoV/HMPV in three cities. Models restricted to children further revealed statistically significant associations for another ten pairs in three of the four cities. In contrast, no consistent correlation across cities was found among adults. Most virus-virus interactions exhibited substantial spatial heterogeneity. Conclusions: There was strong evidence for interactions among common respiratory viruses in highly populated urban settings. Consistent positive interactions across multiple cities were observed in viruses known to typically infect children. Future intervention programs such as development of combination vaccines may consider spatially consistent virus-virus interactions for more effective control.

Clinical manifestations of respiratory syncytial virus infection and the risk of wheezing and recurrent wheezing illness: a systematic review and meta-analysis.

BACKGROUND: Respiratory syncytial virus (RSV) infection in infants is a global health priority. We aimed to investigate the common manifestations of RSV infection by age group and human development index (HDI) level and to assess its association with the development of wheezing and recurrent wheezing illness. METHODS: We searched the literature published between January 1, 2010 and June 2, 2022 in seven databases. Outcomes included common manifestations and long-term respiratory outcomes of RSV infection in children. Random- and fixed-effect models were used to estimate the effect size and their 95% confidence intervals. Subgroup analysis was conducted by age and HDI levels. This review was registered in PROSPERO (CRD42022379401). RESULTS: The meta-analysis included 47 studies. The top five manifestations were cough (92%), nasal congestion (58%), rhinorrhea (53%), shortness of breath (50%), and dyspnea (47%). The clinical symptoms were most severe in infants. In our analysis, compared to very high and high HDI countries, fewer studies in medium HDI countries reported related manifestations, and no study in low HDI countries reported that. The RSV-infected infants were more likely to develop wheezing than the non-infected infants [odds ratio (OR), 3.12; 95% CI, 2.59-3.76] and had a higher risk of developing wheezing illnesses after recovery (OR, 2.60; 95% CI, 2.51-2.70). CONCLUSIONS: Cough and shortness of breath are common manifestations of RSV infection. More attention should be given to infants and areas with low HDI levels. The current findings confirm an association between RSV infection and wheezing or recurrent wheezing illness.

Comparative study on epidemiological and etiological characteristics of patients with acute diarrhea with febrile or non-febrile symptoms in China.

BACKGROUND: Acute diarrhea with fever can potentially represent a more severe form of the disease compared to non-febrile diarrhea. This study was to investigate the epidemiological characteristics and enteric pathogen composition of febrile-diarrheal patients, and to explore factors including pathogens associated with fever by age group. METHODS: A nationwide surveillance study of acute diarrheal patients of all ages was conducted in 217 sentinel hospitals from 31 provinces (autonomous regions or municipalities) in China between 2011 and 2020. Seventeen diarrhea-related pathogens, including seven viruses and ten bacteria, were investigated and their association with occurrence of fever symptoms was assessed using multivariate logistic analysis. RESULTS: A total of 146,296 patients with acute diarrhea (18.6% with fever) were tested. Th diarrheal children below 5 years had the highest frequency of fever (24.2%), and related to significantly higher prevalence of viral enteropathogens (40.2%) as compared with other age groups (P < 0.001). Within each age group, the febrile-diarrheal patients were associated with a significantly higher prevalence of bacterial pathogens than afebrile-diarrheal patients (all P < 0.01). There was discrepancy when each pathogen was compared, i.e., nontyphoidal Salmonella (NTS) was overrepresented in febrile vs non-febrile patients of all age groups, while the febrile vs non-febrile difference for diarrheagenic Escherichia coli (DEC) was only significant for adult groups. The multivariate analysis revealed significant association between fever and infection with rotavirus A among children [odds ratio (OR) = 1.60], for DEC in adult groups (OR = 1.64), for NTS in both children (OR = 2.95) and adults (OR = 3.59). CONCLUSIONS: There are significant discrepancy of the infected enteric pathogens in patients with acute diarrhea with fever between age groups, and it is valuable for priority detection of NTS and rotavirus A in patients with children < 5 years old and NTS and DEC in adult patients. The results may be useful in identifying dominant pathogen candidates for the application of diagnostic assays and prevention control.

Comparing high-dose dual therapy with bismuth-containing quadruple therapy for the initial eradication of Helicobacter pylori infection on Hainan Island: A randomized, multicenter clinical trial.

BACKGROUND: Traditional bismuth-containing quadruple therapy, as a first-line eradication treatment for Helicobacter pylori (H. pylori), has several disadvantages, including drug side effects, low medication adherence, and high costs. Trials of high-dose dual treatment have demonstrated its advantages, which include good safety and adherence profiles. In this study, we investigated the efficacy, safety, and compliance of a high-dose dual therapy when compared with bismuth-based quadruple treatment for the initial eradication of H. pylori infection on Hainan Island, China. METHODS: We randomized 846 H. pylori-infected patients into two groups. A bismuth-containing quadruple therapy group was administered the following: esomeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg twice daily, and colloidal bismuth pectin in suspension 150 mg three times/day for 2 weeks. A high-dose dual therapy group was administered the following: esomeprazole 20 mg four times/day and amoxicillin 1000 mg three times/day for 2 weeks. Patients were given a 13C urea breath test at 4 weeks at treatment end. Adverse effects and compliance were evaluated at follow-up visits. RESULTS: Eradication rates in the high-dose dual therapy group were: 90.3% (381/422, 95% confidence interval [CI]: 87.1%-92.9%) in intention-to-treat (ITT) and 93.6% (381/407, 95% CI: 90.8%-95.8%) in per-protocol (PP) analyses. Eradication rates were 87.3% in ITT (370/424, 95% CI: 83.7%-90.3%) and 91.8% in PP analyses (370/403, 95% CI: 88.7%-94.3%) for quadruple therapy, with no statistical differences (P = 0.164 in ITT and P = 0.324 in PP analyses). Adverse effects were 13.5% (55/407) in the dual group and 17.4% (70/403) in the quadruple group (P = 0.129). Compliance was 92.4% (376/407) in the dual group and 86.6% (349/403) in the quadruple group (P = 0.007). CONCLUSIONS: High-dose dual therapy had high eradication rates comparable with bismuth-based quadruple treatment, with no differences in adverse effects, however higher adherence rates were recorded.

Infection and co-infection patterns of community-acquired pneumonia in patients of different ages in China from 2009 to 2020: a national surveillance study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) is associated with a substantial number of hospitalisations and deaths worldwide. Infection or co-infection patterns, along with their age dependence and clinical effects are poorly understood. We aimed to explore the causal and epidemiological characteristics by age, to better describe patterns of community-acquired pneumonia (CAP) and their association with severe disease. METHODS: National surveillance of CAP was conducted through a network of hospitals in 30 provinces in China from 2009-20 inclusive. Patients with CAP were included if they had evidence of acute respiratory tract, had evidence of pneumonia by chest radiography, diagnosis of pneumonia within 24 h of hospital admission, and resided in the study catchment area. For the enrolled patients with CAP, nasopharyngeal and oral swabs were taken and tested for eight viral pathogens; and blood, urine, or expectorated sputum was tested for six bacterial pathogens. Clinical outcomes, including SCAP, were investigated with respect to age and patterns of infections or co-infections by performing binary logistic regression and multivariate analysis. FINDINGS: Between January, 2009, and December, 2020, 18 807 patients with CAP (3771 [20·05%] with SCAP) were enrolled. For both children (aged ≤5 years) and older adults (aged >60 years), a higher overall rate of viral and bacterial infections, as well as viral-bacterial co-infections were seen in patients with SCAP than in patients with non-SCAP. For adults (aged 18-60 years), however, only a higher rate of bacterial-bacterial co-infection was observed. The most frequent pathogens associated with SCAP were respiratory syncytial virus (RSV; 21·30%) and Streptococcus pneumoniae (12·61%) among children, and influenza virus (10·94%) and Pseudomonas aeruginosa (15·37%) among older adults. Positive rates of detection of most of the tested pathogens decreased during 2020 compared with the 2009-19 period, except for RSV, P aeruginosa, and Klebsiella pneumoniae. Multivariate analyses showed SCAP was significantly associated with infection with human adenovirus, human rhinovirus, K pneumoniae, or co-infection of RSV and Haemophilus influenzae or RSV and Staphylococcus aureus in children and adolescents (aged <18 years), and significantly associated with infection with P aeruginosa, K pneumoniae, or S pneumoniae, or co-infection with P aeruginosa and K pneumoniae in adults (aged ≥18 years). INTERPRETATION: Both prevalence and infection pattern of respiratory pathogens differed between patients with SCAP and patients with non-SCAP in an age-dependent manner. These findings suggest potential advantages to age-related strategies for vaccine schedules, as well as clinical diagnosis, treatment, and therapy. FUNDING: China Mega-Project on Infectious Disease Prevention and The National Natural Science Funds of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Associate factors for endoscopic submucosal dissection operation time and postoperative delayed hemorrhage of early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a treatment for early gastric cancer with the advantages of small invasion, fewer complications, and a low local recurrence rate. However, there is a high risk of complications such as bleeding and perforation, and the operation time is also longer. ESD operation time is closely related to bleeding and perforation. AIM: To investigate the influencing factors associated with ESD operation time and postoperative delayed hemorrhage to provide a reference for early planning, early identification, and prevention of complications. METHODS: We conducted a retrospective study based on the clinical data of 520 patients with early gastric cancer in the Second Affiliated Hospital of Hainan Medical University from January 2019 to December 2021. The baseline data, clinical features, and endoscopic and pathological characteristics of patients were collected. The multivariate linear regression model was used to investigate the influencing factors of ESD operation time. Logistic regression analysis was carried out to evaluate the influencing factors of postoperative delayed hemorrhage. RESULTS: The multivariate analysis of ESD operation time showed that the maximum lesion diameter could affect 8.815% of ESD operation time when other influencing factors remained unchanged. The operation time increased by 3.766% or 10.247% if the lesion was mixed or concave. The operation time increased by 4.417% if combined with an ulcer or scar. The operation time increased by 3.692% if combined with perforation. If infiltrated into the submucosa, it increased by 2.536%. Multivariate analysis of delayed hemorrhage after ESD showed that the maximum diameter of the lesion, lesion morphology, and ESD operation time were independent influencing factors for delayed hemorrhage after ESD. Patients with lesion ≥ 3.0 cm (OR = 3.785, 95%CI: 1.165-4.277), lesion morphology-concave (OR = 10.985, 95%CI: 2.133-35.381), and ESD operation time ≥ 60 min (OR = 2.958, 95%CI: 1.117-3.526) were prone to delayed hemorrhage after ESD. CONCLUSION: If the maximum diameter of the lesion in patients with early gastric cancer is ≥ 3.0 cm, and the shape of the lesion is concave, or accompanied by an ulcer or scar, combined with perforation, and infiltrates into the submucosa, the ESD operation will take a longer time. When the maximum diameter of the lesion is ≥ 3.0 cm, the shape of the lesion is concave in patients and the operation time of ESD takes longer time, the risk of delayed hemorrhage after ESD is higher.

Tumor suppressive lncRNA MEG3 binds to EZH2 and enhances CXCL3 methylation in gallbladder cancer.

Gallbladder cancer is a malignant tumor with a high mortality rate. Accumulating evidence supports that lncRNA MEG3 may halt the progression of gallbladder cancer, while the downstream mechanism is rarely studied. Thus, we aim to investigate the molecular basis of the tumor-suppressing role of lncRNA MEG3 in gallbladder cancer. The expression of lncRNA MEG3 and CXCL3 was measured in patient serum and cell lines of gallbladder cancer. The viability, apoptosis, migration, and invasion of gallbladder cancer cells were assessed following ectopic MEG3 expression, as detected by CCK-8, flow cytometry, and Transwell assays. The interaction among lncRNA MEG3, EZH2, and CXCL3 was explored through ChIP, RNA pull-down, and RIP assays. The effects of lncRNA MEG3 and CXCL3 on tumor growth were evaluated by a mouse xenograft model. lncRNA MEG3 was expressed at a low level in gallbladder cancer patient serum and cell lines, while CXCL3 was highly expressed. MEG3 overexpression repressed the malignant behaviors of gallbladder cancer cells and promoted their apoptosis. MEG3 was mainly localized in the nucleus. MEG3 bound to EZH2, and EZH2 catalyzed the H3K27 trimethylation of the CXCL3 promoter region. MEG3 downregulated CXCL3 by activating EZH2-mediated H3K27 trimethylation of CXCL3; MEG3 overexpression attenuated cancer cell malignant behaviors in vitro and suppressed tumor growth in vivo in gallbladder cancer by inhibiting CXCL3 expression. Altogether, our results indicate that lncRNA MEG3 impedes gallbladder cancer development via the EZH2-CXCL3 axis, offering potential biomarkers for gallbladder cancer management.

Etiological and epidemiological features of acute meningitis or encephalitis in China: a nationwide active surveillance study.

BACKGROUND: Acute meningitis or encephalitis (AME) results from a neurological infection causing high case fatality and severe sequelae. AME lacked comprehensive surveillance in China. METHODS: Nation-wide surveillance of all-age patients with AME syndromes was conducted in 144 sentinel hospitals of 29 provinces in China. Eleven AME-causative viral and bacterial pathogens were tested with multiple diagnostic methods. FINDINGS: Between 2009 and 2018, 20,454 AME patients were recruited for tests. Based on 9,079 patients with all-four-virus tested, 28.43% (95% CI: 27.50%‒29.36%) of them had at least one virus-positive detection. Enterovirus was the most frequently determined virus in children <18 years, herpes simplex virus and Japanese encephalitis virus were the most frequently determined in 18-59 and ≥60 years age groups, respectively. Based on 6,802 patients with all-seven-bacteria tested, 4.43% (95% CI: 3.94%‒4.91%) had at least one bacteria-positive detection, Streptococcus pneumoniae and Neisseria meningitidis were the leading bacterium in children aged <5 years and 5-17 years, respectively. Staphylococcus aureus was the most frequently detected in adults aged 18-59 and ≥60 years. The pathogen spectrum also differed statistically significantly between northern and southern China. Joinpoint analysis revealed age-specific positive rates, with enterovirus, herpes simplex virus and mumps virus peaking at 3-6 years old, while Japanese encephalitis virus peaked in the ≥60 years old. As age increased, the positive rate for Streptococcus pneumoniae and Escherichia coli statistically significantly decreased, while for Staphylococcus aureus and Streptococcus suis it increased. INTERPRETATION: The current findings allow enhanced identification of the predominant AME-related pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures in China, and a possible reassessment of vaccination strategy. FUNDING: China Mega-Project on Infectious Disease Prevention and the National Natural Science Funds.

Broad Impacts of Coronavirus Disease 2019 (COVID-19) Pandemic on Acute Respiratory Infections in China: An Observational Study.

BACKGROUND: To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARIs). METHODS: Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for 8 viral pathogens (influenza virus [IFV], respiratory syncytial virus [RSV], human parainfluenza virus [HPIV], human adenovirus [HAdV], human metapneumovirus [HMPV], human coronavirus [HCoV], human bocavirus [HBoV], and human rhinovirus [HRV]) between 2012 and 2021, were analyzed to assess the changes in respiratory infections in China during the first COVID-19 pandemic year compared with pre-pandemic years. RESULTS: Test-positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012-2019, with changes ranging from -17.2% for RSV to -87.6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year-round, RSV, HPIV, HCoV, HRV, and HBoV resurged and went beyond historical levels during September 2020-January 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children <18 years and in northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus. CONCLUSIONS: Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children.

The changing pattern of enteric pathogen infections in China during the COVID-19 pandemic: a nation-wide observational study.

BACKGROUND: Non pharmaceutical interventions (NPI) including hand washing directives were implemented in China and worldwide to combat the COVID-19 pandemic, which are likely to have had impacted a broad spectrum of enteric pathogen infections. METHODS: Etiologically diagnostic data from 45 937 and 67 395 patients with acute diarrhea between 2012 and 2020, who were tested for seven viral pathogens and 13 bacteria respectively, were analyzed to assess the changes of enteric pathogen infections in China during the first COVID-19 pandemic year compared to pre-pandemic years. FINDINGS: Test positive rates of all enteric viruses decreased during 2020, compared to the average levels during 2012-2019, with a relative decrease of 71•75% for adenovirus, 58•76% for norovirus, 53•50% for rotavirus A, and 72•07% for the combination of other four uncommon viruses. In general, a larger reduction of positive rate in viruses was seen among adults than pediatric patients. A rebound of rotavirus A was seen after September 2020 in North China rather than South China. Test positive rates of bacteria decreased during 2020, compared to the average levels during 2012-2019, excepting for nontyphoidal Salmonella and Campylobacter coli with 66•53% and 90•48% increase respectively. This increase was larger for pediatric patients than for adult patients. INTERPRETATION: The activity of enteric pathogens changed profoundly alongside the NPIs implemented during the COVID-19 pandemic in China. Greater reductions of the test positive rates were found for almost all enteric viruses than for bacteria among acute diarrhea patients, with further large differences by age and geography. Lifting of NPIs will lead to resurgence of enteric pathogen infections, particularly in children whose immunity may not have been developed and/or waned. FUNDING: China Mega-Project on Infectious Disease Prevention; National Natural Science Funds.

Characteristics of diarrheagenic Escherichia coli among patients with acute diarrhea in China, 2009‒2018.

Objectives To investigate the epidemiological features of diarrheagenic Escherichia coli (DEC) in patients with acute diarrhea in China. Methods An active sentinel surveillance was performed in all-age patients with acute diarrhea in China, 2009‒2018. DEC was isolated and identified by serological assay and PCR from stool samples. Results DEC was determined in 6.68% (6,119/91,651) of the patients, with higher positive rates among females than among males (6.97% vs. 6.46%) and among 18‒59 years patients (7.88%) than among other age groups. Five pathotypes were identified, the most prevalent was enteroaggregative E. coli (EAEC), followed by enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC). Pediatric patients <5 years had higher positive rate of EAEC (2.07%), followed by EPEC (1.81%), and enterohemorrhagic E. coli (EHEC) (0.31%), while the 18‒59 years patients had higher infection of ETEC (2.36%). ETEC and EPEC were more frequently identified in urban than rural areas, with age and gender adjusted positive rate of 1.68% vs. 1.14% respectively, and 1.77% vs. 1.55%, while EIEC and EHEC were more frequently identified in rural areas. Conclusions These findings highlight the epidemiology features of DEC and underscores the need for conducting DEC surveillance.

Etiological and epidemiological features of acute respiratory infections in China.

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.

[From Passive Application to Active Design -Restructuring and Reshaping of Core Specialty Knowledge Systems of Biomedical Engineering (Biomedical Materials Track) Undergraduate Education].

Biomedical engineering (BME) (biomedical materials track) is a typical field of interdisciplinary integration. Its specialty education simultaneously undertakes the duo reformation responsibilities for the new engineering education and the new medical education due to its unique strengths in interdisciplinary nature, comprehensive scope of knowledge, and status of being on the cutting edge of technology. We made an analysis, in this paper, of the opportunities and challenges faced by BME (biomedical materials track) specialty education on the basis of the trends and frontiers of development in biomedical materials in the world. From the perspective of new requirements raised by major national strategies and industrial development for the qualifications and competence of professionals specializing in biomedical materials, thorough reflections were made on the specialized education of BME (biomedical materials track) under the background of the new engineering education and the new medical education. Furthermore, we proposed herein to reconstruct the specialized core knowledge system according to the main line of the reactions and the responses between the biomedical materials and human bodies at different levels and set up a series of courses of biomedical materials science centered on Materiobiology as the core. We also proposed to establish a diversified integrated reform model of the training system incorporating production, learning, research and application for highly competent BME (biomedical materials track) professionals. This paper attempts to contribute to the solution of the major issue of how to train the innovative talents and leaders who will pioneer a new round of diagnosis and treatment technology revolution and the development of the medical device industry.

Mindfulness-based online intervention on mental health and quality of life among COVID-19 patients in China: an intervention design.

BACKGROUND: COVID-19 can lead to increased psychological symptoms such as post-traumatic stress disorder (PTSD), depression, and anxiety among patients with COVID-19. Based on the previous mindfulness-based interventions proved to be effective, this protocol reports a design of a randomized controlled trial aiming to explore the efficacy and possible mechanism of a mindful living with challenge (MLWC) intervention developed for COVID-19 survivors in alleviating their psychological problems caused by both the disease and the pandemic. METHODS: In April 2021, more than 1600 eligible participants from Hubei Province of China will be assigned 1:1 to an online MLWC intervention group or a waitlist control group. All participants will be asked to complete online questionnaires at baseline, post-program, and 3-month follow-up. The differences of mental health status (e.g. PTSD) and physical symptoms including fatigue and sleeplessness between the COVID-19 survivors who receiving the online MLWC intervention and the control group will be assessed. In addition, the possible mediators and moderators of the link between the MLWC intervention and target outcomes will be evaluated by related verified scales, such as the Five Facets Mindfulness Questionnaire. Data will be analyzed based on an intention-to-treat approach, and SPSS software will be used to perform statistical analysis. DISCUSSION: The efficacy and potential mechanism of MLWC intervention in improving the quality of life and psychological status of COVID-19 survivors in China are expected to be reported. Findings from this study will shed light on a novel and feasible model in improving the psychological well-being of people during such public health emergencies. Trial registration Chinese Clinical Trial Registry (ChiCTR), ChiCTR2000037524; Registered on August 29, 2020, http://www.chictr.org.cn/showproj.aspx?proj=60034 .

Etiological, epidemiological, and clinical features of acute diarrhea in China.

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.

Collateral Circulation in Moyamoya Disease: A New Grading System.

Background and Purpose- Predicting the risk of stroke and determining intervention indications are highly important for patients with Moyamoya disease (MMD). Here, we evaluated a novel MMD grading system based on collateral circulation and Suzuki stage to evaluate symptoms and predict prognosis. Methods- In total, 301 idiopathic MMD patients were retrospectively analyzed between 2014 and 2016. A collateral circulation grading system with scores ranging from 1 to 12 was established: the anatomic extent of pial collateral blood flow from posterior cerebral artery to middle cerebral artery and anterior cerebral artery was scored from 1 to 6; perforator collateral and internal cerebral artery flow were scored as 6 to 1, which corresponded to Suzuki stages 1 to 6. Dynamic susceptibility contrast-magnetic resonance imaging was used to evaluate hemodynamic status. We assessed the association between the grading system and clinical characteristics. Results- We analyzed 364 symptomatic hemispheres of 301 patients (146 males, 28±16 years). Ischemic patients who presented with infarction were more likely to score <8 points (P<0.001), whereas those with ischemia symptoms (transient ischemic attack and headache) were more likely to score >8 points. Hemorrhagic patients who presented with intraparenchymal hemorrhage were more likely to score <8 points, whereas those who presented with intraventricular hemorrhage were more likely to score >8 points (P<0.001). According to dynamic susceptibility contrast-magnetic resonance imaging, lower scores were correlated with more severe time to peak delay (P<0.001) and worse relative cerebral blood volume ratio (P=0.016) and cerebral flow ratio (P=0.002). Encephaloduroarteriosynangiosis was performed in 348 symptomatic hemispheres. Patients who had collateral scores <4 points were more likely to have a postoperative stroke and a worse prognosis during the follow-up. Conclusions- This new MMD collateral grading system correlated well with clinical symptoms, hemodynamic status, and therapeutic prognosis and may facilitate risk stratification and prognosis predictions in patients with MMD.

Epidemiology of Moyamoya Disease in China: Single-Center, Population-Based Study.

BACKGROUND: To our knowledge, no previous study has described the nationwide epidemiologic features of moyamoya disease (MMD) in China. We describe the epidemiologic features including the relative prevalence, age distribution, gender distribution, and initial clinical manifestations of patients with MMD treated at a single institution in China. METHODS: Our cohort included 4128 patients with MMD. Their demographic and clinical characteristics were obtained by retrospective chart review. RESULTS: The median age for the onset of symptoms was 30.36 years. The age distribution of patients with MMD was bimodal, with the highest peak detection rate at 35-45 years of age and a smaller peak at 5-9 years of age. The ratio of female-to-male patients was 1:1. The disease occurred mainly in the Han people and was rarely seen in minority nationalities. In our cohort, transient ischemic attack was the most common initial clinical manifestation (48.13%). The other initial manifestations included infarction (22.62%), hemorrhage (16.45%), and headache 230/4128 (5.57%). In north and northeast China, the ischemic type was more predominate while the hemorrhagic type was relatively rare. However, the percentage of hemorrhagic type in East China was higher than anywhere else in China. CONCLUSIONS: This study confirmed some unique epidemiologic features as the studies previously reported in China, but it also revealed some new sight and tendency about moyamoya in China. As a lack of national epidemiologic studies, this study indicated the outline of moyamoya in China.

Encephaloduroarteriosynangiosis for pediatric moyamoya disease: long-term follow-up of 100 cases at a single center.

OBJECTIVE The object of this study was to summarize the long-term effect of encephaloduroarteriosynangiosis (EDAS) for the treatment of pediatric moyamoya disease (MMD) and to investigate factors influencing the clinical outcomes of EDAS. METHODS Clinical features, angiographic findings, and clinical outcomes were analyzed among MMD patients younger than 18 years who had been treated with EDAS between 2002 and 2007 at the authors' institution. The Kaplan-Meier method was used to estimate stroke risk after EDAS. Predictors of neurological outcome were assessed. RESULTS One hundred fifteen patients were identified. The mean age at symptom onset was 7.3 ± 4.0 years. The incidence of familial MMD was 11.3%. The female/male ratio was 1:1.16. A total of 232 EDAS procedures were performed, and the incidence of postoperative complications was 3%. Postoperative digital subtraction angiography was performed in 54% of the patients, and about 80% of the hemispheres showed good or excellent results. Neovascularization showed significant correlations with delay time (from symptom onset to first operation), Suzuki stage, and preoperative stroke (all p < 0.05). Clinical follow-up was available in 100 patients with a mean follow-up of 124.4 ± 10.5 months. Ten-year cumulative survival was 96.5% after surgery, and the risk of stroke was 0.33%/person-year. An independent life with no significant disability was reported by 92% of the patients. A good outcome correlated with a low Suzuki stage (p = 0.001). Older children and those without preoperative stroke had better clinical outcomes (p < 0.05). CONCLUSIONS On the basis of long-term follow-up data, the authors concluded that EDAS is a safe and effective treatment for pediatric MMD, can reduce the risk of subsequent neurological events, and can improve quality of life. The risk of ischemia-related complications was higher in younger patients, and older children showed better outcomes. Compensation was greater with more prominent cerebral ischemia. The long-term clinical outcome largely depended on the presence and extent of preoperative stroke.

Mitochondrial expression and activity of P-glycoprotein under oxidative stress in outer blood-retinal barrier.

AIM: To investigate the role of oxidative stress in regulating the functional expression of P-glycoprotein (P-gp) in mitochondria of D407 cells. METHODS: D407 cells were exposed to different ranges of concentrations of H2O2. The mitochondrial location of P-gp in the cells subjected to oxidative stress was detected by confocal analysis. Expression of P-gp in isolated mitochondria was assessed by Western blot. The pump activity of P-gp was evaluated by performing the efflux study on isolated mitochondria with Rhodamine 123 (Rho-123) alone and in the presence of P-gp inhibitor (Tariquidar) using flow cytometry analysis. The cells were pretreated with 10 mmol/L N-acetylcysteine (NAC) for 30min before exposing to H2O2, and analyzed the mitochondrial extracts by Western blot and flow cytometry. RESULTS: P-gp was co-localized in the mitochondria by confocal laser scanning microscopy, and it was also detected in the mitochondria of D407 cells using Western blot. Exposure to increasing concentrations of H2O2 led to gradually increased expression and location of P-gp in the mitochondria of cells. Rho-123 efflux assay showed higher uptake of Rho-123 on isolated mitochondria in the presence of Tariquidar both in normal and oxidative stress state. H2O2 up-regulated P-gp in D407 cells, which could be reversed by NAC treatment. CONCLUSION: H2O2 could up-regulate the functional expression of P-gp in mitochondria of D407 cells, while antioxidants might suppress oxidative-stress-induced over-expression of functional P-gp. It is indicative that limiting the mitochondrial P-gp transport in retinal pigment epithelium cells would be to improve the effect of mitochondria-targeted antioxidant therapy in age-related macular degeneration-like retinopathy.

Effect of baicalin on hippocampal damage in kainic acid-induced epileptic mice.

The aim of the present study was to determine the effect of baicalin on the expression of miR-497 and its target B-cell lymphoma-2 (Bcl-2) in the hippocampus of kainic acid (KA)-induced epileptic mice. To establish status epilepticus (SE), 0.1 µg/5 µl KA was injected into the lateral cerebral ventricle in mice, which then received an intraperitoneal injection of baicalin (100 mg/kg) after 1 and 8 h. Hematoxylin and eosin staining was used to observe the pathological changes in morphology and neuronal apoptosis was determined by terminal transferase-mediated dUTP nick end-labeling staining. Western blot analysis was used to detect the expression of Bcl-2 and cleaved caspase-3 proteins in the hippocampus, while reverse transcription-quantitative polymerase chain reaction was used to quantify hippocampal miR-497 expression. The results showed that baicalin significantly attenuated neuronal damage and apoptosis in the hippocampus 72 h after SE. In addition, baicalin decreased SE-induced expression of miR-497 and cleaved caspase-3 protein, while upregulating the expression of Bcl-2 protein. In conclusion, the present results suggest that baicalin possesses potent antiapoptotic properties and attenuates hippocampal injury in mice after SE, which may be associated with the downregulation of miR-497 and cleaved caspase-3 and the upregulation of Bcl-2.