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This paper studies the heterogeneous responses of firms to monetary policy shocks and the possible adverse effect of expansionary monetary policy on resource reallocation. Using Chinese firm‐level data, we find that when expansionary monetary shock hits the economy, less productive firms are more responsive than productive firms in terms of resource accumulation. We identify two mechanisms for this effect. First, less productive firms accumulate net worth more slowly. They have higher leverage ratio and are more sensitive to monetary policy changes (the intensive margin). Second, monetary expansion relaxes borrowing constraints, which enables unproductive firms to survive. The congestion effect prevents resources from allocating to more productive firms. Our finding is robust even if we use private firm subsamples or avoid the massive fiscal stimulus in China around 2009. We provide a simple model of firm dynamics to capture these effects. [ABSTRACT FROM AUTHOR]

Hand, foot, and mouth disease (HFMD) is a common infectious disease in children. Enterovirus A71 (EV-A71) is one of the main pathogens, and coxsackievirus A6 (CVA6) has gradually become the dominant pathogen of HFMD in recent years. This study was conducted mainly to assess the serological prevalence of EV-A71 and CVA6 antibodies in people of different ages, sexes, and regions through a systematic review and meta-analysis. A comprehensive study was performed based on the EV-A71 and CVA6 serological literature published before May 2022. Heterogeneity analysis (Cochrane's Q test and the I2 statistic) and random effect models were adopted. Subgroup and meta-regression analyses were used to identify potential sources of heterogeneity in the data, and all analysis was performed using STATA version 16.0. This study included 71 studies involving 55,176 people from 13 countries that met the inclusion criteria. The serological prevalence of EV-A71 antibody in different studies was 4.31-88.8%, and that of CVA6 antibody was 40.8-80.9%. Meta-analysis results showed that the serum positive rate for EV-A71 antibody was 45.9% (95% CI: 37.6-54.1%). The rate in the Chinese population was 47.8% (95% CI: 42.4-53.2%), and in the other countries, it was 38% (95% CI: 23-55%). The serum positive rate for CVA6 antibody was 58.3% (95% CI: 46.5-70.2%). The rate in the Chinese population was 49.1% (95% CI: 38.3-59.9%), and in the other countries, it was 68% (95% CI: 51-83%). Subgroup analysis was also conducted. The seroprevalence of EV-A71 and CVA6 antibodies is related to age rather than gender or region. The rates of EV-A71 and CVA6 seropositivity are considerably lower in children younger than five years of age. However, the rates gradually increase with age. The findings of this study suggest that children under five years of age may be susceptible to EV-A71 and CVA6. Thus, safety education and vaccination should be strengthened accordingly. This study provides a basis for understanding the risk factors for EV-A71 and CVA6 infection in China and for deciding how to formulate standard preventive measures to prevent the spread of the virus. [ABSTRACT FROM AUTHOR]

Recombination plays important roles in the genetic diversity and evolution of Enterovirus A71 (EV-A71). The phylogenetics of EV-A71 in mainland China found that one strain DL71 formed a new subgenotype C6 with unknown origin. This study investigated the detailed genetic characteristics of the new variant. DL71 formed a distinct cluster within genotype C based on the genome and individual genes (5′UTR, VP4, VP1, 2A, 2B, 2C, 3D, and 3′UTR). The average genetic distances of the genome and individual genes (VP3, 2A, 2B, 2C, 3A, 3C, and 3D) between DL71 and reference strains were greater than 0.1. Nine recombination events involving smaller fragments along DL71 genome were detected. The strains Fuyang-0805a (C4) and Tainan/5746/98 (C2) were identified as the parental strains of DL71. In the non-recombination regions, DL71 had higher identities with Fuyang-0805a than Tainan/5746/98, and located in the cluster with C4 strains. However, in the recombination regions, DL71 had higher identities with Tainan/5746/98 than Fuyang-0805a, and located in the cluster with C2 strains. Thus, DL71 was a novel multiple inter-subgenotype recombinant derived from the dominant subgenotype C4 and the sporadic subgenotype C2 strains. Monitoring the emergence of new variants by the whole-genome sequencing remains essential for preventing disease outbreaks and developing new vaccines. [ABSTRACT FROM AUTHOR]

This paper examines the impact of foreign entry deregulation in China on the export price and quality of manufacturing firms through input–output linkage. We create a unique dataset describing the extent of regulatory control over foreign entry across approximately 900 industries covering all primary, manufacturing and services sectors. Results suggest foreign entry deregulation encourages firms to improve product quality and increase export prices. Deregulation in the manufacturing sectors has more impact on downstream export price and quality, compared with services sectors. Moreover, firms having larger imported inputs benefit more from foreign entry deregulation. These effects are robust to alternative specifications. [ABSTRACT FROM AUTHOR]

Purpose: To determine the epidemiology characteristics of intestinal colonization of carbapenem-resistant Enterobacteriaceae (CRE) among inpatients in a pediatric hospital in China. Methods: A retrospective study was conducted from April to December 2019. Medical records were reviewed to extract the clinical information. Antimicrobial susceptibility was performed by broth microdilution method. Drug resistance determinants and plasmid types were analyzed using polymerase chain reaction (PCR) assays. Multilocus sequence typing (MLST) and Enterobacterial repetitive intergenic consensus sequences PCR (ERIC-PCR) were employed to determine the genetic relationships between strains. Results: A total of 90 CRE strains were isolated, with a fecal carriage rate of 8.6% (90/1052), and mainly distributed in E. aerogenes (n=30), K. pneumoniae (n=25) and E. coli (n=23). More than 50% of CRE colonizers had a history of invasive procedures and antibiotic exposures. As high as 91.1% (82/90) of CRE isolates carried carbapenemase genes, with blaNDM-5 (n=56) being the most common, and mainly found in E. aerogenes (51.8%, 29/56) and E. coli (32.1%, 18/56) isolates, which primarily belonged to ST4 (100%, 29/29) and ST692 (55.6%, 10/18), respectively. Followed by blaKPC-2 (n=12), and all found in K. pneumoniae ST11 isolates. Other carbapenemase genes including blaNDM-1, blaIMP-4 and blaIMP-26. Meanwhile, ESBL genes (blaCTX-M, blaTEM-1 and blaSHV) and AmpC genes (blaDHA-1 and blaEBC) were also detected. All CRE isolates showed high resistance to cephalosporins and carbapenemases (97.8%-100.0%) but remained susceptible to tigecycline (98.9%). IncX3 was a major plasmid type in NDM-containing strains (91.3%), and 91.7% of KPC-2-producing K. pneumoniae harboring IncFII and IncFIB plasmids. The ERIC-PCR revealed that several strains with identical STs were genetically similar. Conclusion: This study revealed a major intestinal colonization of ST4 NDM-5 E. aerogenes, ST11 KPC-2 K. pneumoniae and ST692 NDM-5 E. coli strains among inpatients in a pediatric hospital. Infection control measures should be implemented immediately to prevent the spread of these strains in clinical settings. [ABSTRACT FROM AUTHOR]

Background: The number of cancer patients with diabetes mellitus (DM) is steadily rising. Little is known about the nutritional status of this population. This study characterized the nutritional status and survival of cancer patients with diabetes compared with those without diabetes. Methods: A total of 8247 cancer patients were prospectively enrolled from 72 hospitals in China and followed until August 2019. A global estimation of the nutritional status was performed for each participant using standardized tools. The outcomes were cancer‐specific survival (CSS) and overall survival (OS). Results: The incidence of diabetes was 7.6% in the whole population. In comparison with the non‐DM group, the DM group had greater body weight, but a similar fat‐free mass, a lower handgrip strength and a decreased Karnofsky performance score. A higher proportion of patients with diabetes were overweight/obese as indicated by BMI. The percentage of patients who were at risk of malnutrition (evaluated by PG‐SGA) was higher in the DM group (score ≥ 4, 56.7% vs 52.9%). Patients with DM showed a worse CSS (4‐year CSS, 62% vs 73%) and OS (4‐year OS 39% vs 52%). Diabetes was associated with an increased risk of both cancer‐specific (hazard ratio (HR) = 1.282, 95% confidence interval (CI) 1.070‐1.536) and overall (HR = 1.206, 95% CI 1.040‐1.399) mortality. Conclusions: Cancer patients with diabetes had a larger body mass but lower muscle strength, poorer performance status and higher incidence of malnourishment. Diabetes was associated with compromised survival. Tailored nutritional intervention is necessary for this subpopulation of patients. [ABSTRACT FROM AUTHOR]

As the pillar of national economy, manufacturing industry is the largest primary energy consumer and emitter of carbon dioxide (CO2) in China. Therefore, capturing the determinants of CO2 emissions in manufacturing industry is extremely important for national efforts to mitigate carbon emissions. This paper explores the major driving forces behind CO2 emission changes in China's manufacturing industry during 2000–2015 from perspectives of the whole sector and 28 subsectors, by applying the temporal logarithmic mean Divisia index (LMDI) method. Moreover, an intersectoral LMDI model is built to uncover the intersectoral discrepancies of CO2 emissions among 28 subsectors. The temporal analysis indicates that industrial activity and energy intensity are crucial factors respectively contributing to the increase and mitigation of CO2 emissions. The intersectoral analysis reveals that energy intensity is the dominant factor responsible for the intersectoral discrepancies of CO2 emissions among 28 subsectors. The great mitigation towards CO2 emissions can be achieved if energy efficiency is largely improved in carbon-intensive subsectors. Priority should be given by governments to the industrial technology advancement, such as subsidies for energy-saving technological transformation and promotion of international advanced techniques and equipment, which can greatly improve production efficiency and mitigate emissions in manufacturing industry. [ABSTRACT FROM AUTHOR]

Enterovirus D68 (EV-D68), a member of Enterovirus genus of the Picornaviridae family, mainly causes respiratory system-related diseases as well as neurological complications in some patients. At present, there is no effective vaccine or treatment for the virus. The aim of this research was to systematically analyse the molecular epidemiology, recombination and changes in the epitope of EV-D68 in China from 2008 to 2022. Through phylogenetic analysis based on VP1 sequences, it was found that there was limited information about EV-D68 infection before 2011 and that EV-D68 infection was dominated by the A2 gene subtype from 2011 to 2013 and the B3 genotype from 2014 to 2018, during which A2 and B3 were coprevalent and alternately prevalent. We also constructed a phylogenetic tree using the EV-D68 full-length genome sequences, and the genotype of each sequence was consistent with that of the VP1 sequence evolutionary tree. Recombination analysis showed that MH341715 underwent intertypic recombination with the A2 genotype MH341729 at the 5′ untranslated region (5'UTR) and that P1-P3 underwent recombination with the B3 genotype MH341712. The capsid protein VP1 is one of the most important structural proteins. In VP1, the BC-loop (89–105 amino acids) and DE-loop (140–152 amino acids) are the most variable domains on the surface of the virus and are associated with epitopes. In this study, it was found that the dominant amino acid composition of the BC-loop and DE-loop continued to change with the epidemic of the virus; the amino acid composition also differed in different regions of the same genotypes. The ongoing genomic and molecular epidemiology of EV-D68 remains important for predicting emergence of new viruses and preventing major outbreaks of respiratory diseases. • EV-D68 infection was dominated by the A2 gene subtype from 2011 to 2013 and the B3 genotype from 2014 to 2018. • The full-length sequence phylogenetic tree genotype was consistent with the VP1 phylogenetic tree. • MH341715 was produced by recombination of MH341712 with MH341729. • The dominant amino acid composition of the BC-loop and DE-loop continued to change with the epidemic of the virus. [ABSTRACT FROM AUTHOR]

Methylmalonic acidemia (MMA) is a typical type of organic acidemia caused by defects in methylmalonyl-CoA mutase or adenosyl-cobalamin synthesis. Hydrocephalus (HC), results from an imbalance between production and absorption of cerebrospinal fluid (CSF), causeing enlarged cerebral ventricles and increased intracranial pressure, is a condition that requires urgent clinical decision-making. MMA without treatment could result in brain damage. However, HC in MMA was rarely reported. In this study, 147 MMA were identified from 9117 high risk children by gas chromatography mass spectrometry (GC/MS) for organic acidurias screening in urine samples and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for amino acids detection in blood samples. Totally 10 cases with MMA and HC were determined by brain MRI/CT, as well as gene mutation testing either by high throughput sequencing or Sanger sequencing. Besides, homocysteine was also analyzed for the 10 MMA with HC. Out of them, 9 cases carry out compound heterozygous mutations or homozygous mutation in MMACHC gene, and 1 case has MUTmutation. The mutation c.609G > A in MMACHC was the most common in the cbl type patients. Although MMA has a high incidence in Shandong province of China, especially cblC type. All of the 10 patients were not correctly diagnosed before developing HC. As a result, when a child develops progressive and refractory HC, the screening for inherited metabolic diseases should be immediately conducted. [ABSTRACT FROM AUTHOR]

Xuebijing (XBJ) injection is an ethnomedicinal formula that has been widely used in the therapy of sepsis in China. However, the underlying theraputic mechanisms remain uninvestigated. In this research, a metabolomic method based on UHPLC-Q-Orbitrap HRMS was applied tomake a holistic evaluation of XBJ on septic rats which were induced by the classical cecal ligation and puncture (CLP) operation. The plasma metabolic changes were profiled and evaluated by multivariate analytical (MVA) methods. In the results, a total of 41 differential metabolites were identified between CLP-operated group and sham-operated group, which were mainly involved in amino acid metabolism and lipid metabolism. After pathway analysis, it was finally discovered that the majority of the influenced metabolic pathways caused by sepsis mainly involved in energy metabolism, oxidative stress, and inflammation metabolism. When intervened by XBJ injection, 32 of the 41 disordered metabolites had been adjusted in reverse, which suggested that XBJ could mediate the abnormal metabolic pathways synergistically. In conclusion, the present study systematically investigated the efficacy and its underlying therapeutic mechanisms of XBJ on sepsis, while offering a new insight for the subsequent relevant exploration of other Chinese medicine at the same time. [ABSTRACT FROM AUTHOR]

Background: A marked increase in the incidence rate of scarlet fever imposed a considerable burden on the health of children aged 5 to 15 years. The main purpose of this study was to depict the spatiotemporal epidemiological characteristics of scarlet fever in Jiangsu Province, China in order to develop and implement effective scientific prevention and control strategies.Methods: Smoothed map was used to demonstrate the spatial distribution of scarlet fever in Jiangsu Province. In addition, a retrospective space-time analysis based on a discrete Poisson model was utilized to detect clusters of scarlet fever from 2005 to 2015.Results: During the years 2005-2015, a total of 15,873 scarlet fever cases occurred in Jiangsu Province, with an average annual incidence rate of 1.87 per 100,000. A majority of the cases (83.67%) occurred in children aged 3 to 9 years. Each year, two seasonal incidence peaks were observed, the higher occurring between March and July, the lower between November and the following January. The incidence in the southern regions of the province was generally higher than that in the northern regions. Seven clusters, all of which occurred during incidence peaks, were detected via space-time scan statistical analysis. The most likely cluster and one of the secondary clusters were detected in the southern and northern high endemic regions, respectively.Conclusion: The prevalence of scarlet fever in Jiangsu Province had a marked seasonality variation and was relatively endemic in some regions. Children aged 3 to 9 years were the major victims of this disease, and kindergartens and primary schools were the focus of surveillance and control. Targeted strategies and measures should be taken to reduce the incidence. [ABSTRACT FROM AUTHOR]

Introduction : Esophageal cancer is the fourth most common cause of cancer death in China. Patients with esophageal cancer are more likely to suffer from malnutrition. The purpose of this study is to assess nutritional status of patients with esophageal cancer from multiple perspectives and analyze the risk factors. Methods : A total of 1482 esophageal cancer patients were enrolled in the study. We investigated the Scored Patient Generated Subjective Global Assessment (PG-SGA) scores, NRS-2002 scores, Karnofsky performance status scores, anthropometric, and laboratory indicators of patients. Unconditional logistic regression analysis was applied to identify the risk factors of nutritional status. Results : PG-SGA (≥4) and NRS-2002 (≥3) showed the incidence of malnutrition were 76% and 50%, respectively. In the patients with PG-SGA score ≥4, the proportion of patients who did not receive any nutritional support was 60%. The incidence of malnutrition in females was significantly higher than that in males. Besides, abnormality rates of Red blood cell (P < 0.001), MAC (P = 0.037), and MAMC (P < 0.001) in males was significantly higher than that in females, while abnormality rates of TSF (P < 0.001) was lower than that in females. After adjusted with the other potential risk factors listed, unconditional logistic regression analysis indicated smoking (odds ratio: 2.868, 95% confidence interval: 1.660-4.954), drinking (OR: 1.726, 95% CI: 1.099-2.712), family history (OR: 1.840, 95% CI: 1.132-2.992), radiotherapy or chemotherapy (OR: 1.594, 95% CI: 1.065-2.387), and pathological stage (OR: 2.263, 95% CI: 1.084-4.726) might be the risk factors of nutritional status, while nutritional support can reduce the risk of malnutrition. Conclusion : Effective nutritional risk assessment methods and nutritional intervention measures can be adopted according to the research data to improve quality of life of esophageal cancer patients. [ABSTRACT FROM AUTHOR]

Background: Hand, foot and mouth disease (HFMD) is a rising public health problem and has attracted considerable attention worldwide. The purpose of this study was to develop an optimal model with meteorological factors to predict the epidemic of HFMD.Methods: Two types of methods, back propagation neural networks (BP) and auto-regressive integrated moving average (ARIMA), were employed to develop forecasting models, based on the monthly HFMD incidences and meteorological factors during 2009-2016 in Jiangsu province, China. Root mean square error (RMSE) and mean absolute percentage error (MAPE) were employed to select model and evaluate the performance of the models.Results: Four models were constructed. The multivariate BP model was constructed using the HFMD incidences lagged from 1 to 4 months, mean temperature, rainfall and their one order lagged terms as inputs. The other BP model was fitted just using the lagged HFMD incidences as inputs. The univariate ARIMA model was specified as ARIMA (1,0,1)(1,1,0)12 (AIC = 1132.12, BIC = 1440.43). And the multivariate ARIMAX with one order lagged temperature as external predictor was fitted based on this ARIMA model (AIC = 1132.37, BIC = 1142.76). The multivariate BP model performed the best in both model fitting stage and prospective forecasting stage, with a MAPE no more than 20%. The performance of the multivariate ARIMAX model was similar to that of the univariate ARIMA model. Both performed much worse than the two BP models, with a high MAPE near to 40%.Conclusion: The multivariate BP model effectively integrated the autocorrelation of the HFMD incidence series. Meanwhile, it also comprehensively combined the climatic variables and their hysteresis effects. The introduction of the climate terms significantly improved the prediction accuracy of the BP model. This model could be an ideal method to predict the epidemic level of HFMD, which is of great importance for the public health authorities. [ABSTRACT FROM AUTHOR]

Garcinia multiflora is a kind of evergreen tree which is widely distributed in the south of China. However, few researches focused on the constituents in different parts of G. multiflora as well as their potential targets and pathways in vivo. To clarify the chemical constituents of G. multiflora rapidly and predict the potential targets as well as pathways in vivo that this plant may have effects on, a feasible and accurate strategy was developed to identify the chemical constituents in fruits, leaves, and branches of G. multiflora by ultra‐high performance liquid chromatography with Q‐Exactive hybrid quadrupole‐orbitrap high‐resolution accurate mass spectrometry. Network pharmacology was then employed and a "compounds‐targets‐diseases" network was established. Sixty‐one compounds including polycyclic polyprenylated acylphloroglucinols, xanthones, and flavonoids were finally identified in different parts of G. multiflora, and the contents of seven constituents were quantified, respectively. On the basis of the network pharmacology analysis results, compounds in this plant were speculated to have potential pharmacodynamic effect on cancer, inflammatory, respiratory diseases, cardiovascular diseases, and metabolic diseases. This research will provide a new method for the advanced study on the pharmacodynamic materials basis of G. multiflora, and offer valuable evidences for medicinal purpose of this plant. [ABSTRACT FROM AUTHOR]

On the path to industrialization, the energy and environmental problems caused by the rapid growth of the manufacturing industry have attracted widespread attention. At the top scale of technological innovation, high-tech manufacturing is considered to have achieved a balance between the "Made in China 2025" strategy and energy conservation. Therefore, in this paper, we explore inter-factor substitution and the influence of different sources of technological progress on China's high-tech industries using an estimation model that incorporates a translog cost function and the 'panel seemingly unrelated regression' method. Changes in energy intensity are further decomposed into different causes including budget, output, factor substitution, and technological progress at various points throughout the period under study. The empirical findings show Morishima substitutions among three different input factors. The substitution elasticity between labor and energy is the highest, and further most sources of technological progress are biased toward saving energy. Technological progress and budget are the critical driving forces throughout the period. However, the effect of factor substitution has gradually increased in recent years. From a regional perspective, energy intensity in the Beijing-Tianjin-Hebei region shows the most apparent decline, while the smallest decline occurs in China's western region. [ABSTRACT FROM AUTHOR]

Background: Male breast cancer (MBC) is a rare disease. Although several large-scale studies have investigated MBC patients in other countries, the features of MBC patients in China have not been fully explored. This study aims to explore the features of Chinese MBC patients comprehensively., Methods: We retrospectively collected data of MBC patients from 36 centers in China. Overall survival (OS) was evaluated by the Kaplan-Meier method, log-rank test, and Cox regression analyses. Multivariate Cox analyses were used to identify independent prognostic factors of the patients., Results: In total, 1119 patients were included. The mean age at diagnosis was 60.9 years, and a significant extension over time was observed (P < 0.001). The majority of the patients (89.1 %) received mastectomy. Sentinel lymph node biopsy was performed in 7.8 % of the patients diagnosed in 2009 or earlier, and this percentage increased significantly to 38.8 % in 2020 or later (P < 0.001). The five-year OS rate for the population was 85.5 % [95 % confidence interval (CI), 82.8 %-88.4 %]. Multivariate Cox analysis identified taxane-based [T-based, hazard ratio (HR) = 0.32, 95 % CI, 0.13 to 0.78, P = 0.012] and anthracycline plus taxane-based (A + T-based, HR = 0.47, 95 % CI, 0.23 to 0.96, P = 0.037) regimens as independent protective factors for OS. However, the anthracycline-based regimen showed no significance in outcome (P = 0.175)., Conclusion: As the most extensive MBC study in China, we described the characteristics, treatment and prognosis of Chinese MBC population comprehensively. T-based and A + T-based regimens were protective factors for OS in these patients. More research is required for this population., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Affiliate stigma experienced by family caregivers of individuals with dementia may seriously affect home care and prognosis of these patients. This study aimed to explore the levels of perceived affiliate stigma and its influencing factors among family caregivers of patients with dementia in mainland China, which remains a relatively unexplored topic., Methods: In this cross-sectional study, purposive sampling was used to recruit dementia family caregivers from an online communication group between April and May 2022. A total of 727 eligible caregivers were included and asked to complete the demographic questionnaire, the affiliate stigma scale, and the caregiver burden inventory. Descriptive statistics, independent sample t-test, one-way analysis of variance, Pearson correlation analysis, and multiple linear regression were used to explore the factors that influence perceived affiliate stigma among dementia family caregivers., Results: The mean score for affiliate stigma of dementia family caregivers was 48.09 ± 16.38 (range: 22-86). Whether there were regular breaks during patient care, time-dependent burden, developmental burden, physical burden, and social burden were significant factors influencing the affiliate stigma of dementia family caregivers., Conclusion: Dementia family caregivers showed a moderate to high level of affiliate stigma. Those who had regular breaks during patient care, higher time-dependent burden, developmental burden, and physical burden and lower social burden exhibited higher levels of affiliate stigma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shi, Dong, Liang, Xie, Zhang, Li and Li.)

This study aims to investigate the status and influencing factors of two-way social support among old adults. A cross-sectional study of 408 convenient samples of old adults was conducted using socio-demographic questionnaire, Brief 2-Way Social Support Scale, Modified Barthel index, General Well-being Schedule, Family APGAR Index, and Lubben Social Network Scale 6. The two-way social support score for old adults in China was (43.74±7.86), with the receiving and giving social support scoring (22.80±4.06) and (20.94±4.52), respectively. The multiple linear regression analysis revealed that family care, residence place, socioeconomic status, and social network were associated with both receiving and giving social support. Chronic diseases and religious beliefs were related to receiving social support, while gender, general well-being, and residence form were related to giving social support. Tailored interventions based on the distinct influencing factors are needed to enhance old adults' social support both as recipients and providers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Over the past 70 years, China has advanced significantly in the prevention and treatment of infectious diseases while simultaneously undergoing a socioeconomic transformation, making it a useful source of data for analysing relationships between public health policy and the control of infectious diseases., Methods: We collected data on the incidence of notifiable infectious diseases and associated fatalities in Jiangsu province in southeast China from the Provincial Center for Disease Control and Prevention, Provincial Institute of Parasitic Diseases, and the Nationwide Notifiable Infectious Diseases Reporting Information System. We compared data from different historical periods using descriptive statistical methods, joinpoint regression, and correlation analysis., Results: During 1950-2022, 75 754 008 cases of 46 notifiable infectious diseases were reported in Jiangsu, with an average annual incidence was 1679.49 per 100 000 population and a fatality rate of 1.82 per 1000 persons. The incidence of classes A-B decreased (average annual percent change (AAPC) = -2.1) during the entire study period, while the incidence of class C increased (AAPC = 10.8) after 2004. The incidence of intestinal diseases (AAPC = -4.4) and vector-borne and zoonotic diseases (AAPC = -8.1) decreased rapidly, while the incidence of sexually transmitted and blood-borne diseases (AAPC = 1.8) increased. The number of medical and health institutions and the per capita gross domestic product correlated negatively with the annual incidence of diseases in classes A-B, but not with fatality rates., Conclusions: Although the annual incidence of many severe infectious diseases has decreased in Jiangsu since 1950, the incidence of sexually transmitted and blood-borne diseases increased. Socioeconomic growth and sustainable investment in health systems are associated with better control of infectious diseases., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)

Objectives: The aim of this study is to describe, visualize, and compare the trends and epidemiological features of the mortality rates of 10 notifiable respiratory infectious diseases in China from 2004 to 2020., Setting: Data were obtained from the database of the National Infectious Disease Surveillance System (NIDSS) and reports released by the National and local Health Commissions from 2004 to 2020. Spearman correlations and Joinpoint regression models were used to quantify the temporal trends of RIDs by calculating annual percentage changes (APCs) in the rates of mortality., Results: The overall mortality rate of RIDs was stable across China from 2004 to 2020 ( R = -0.38, P = 0.13), with an APC per year of -2.2% (95% CI: -4.6 to 0.3; P = 0.1000). However, the overall mortality rate of 10 RIDs in 2020 decreased by 31.80% ( P = 0.006) compared to the previous 5 years before the COVID-19 pandemic. The highest mortality occurred in northwestern, western, and northern China. Tuberculosis was the leading cause of RID mortality, and mortality from tuberculosis was relatively stable throughout the 17 years (R = -0.36, P = 0.16), with an APC of -1.9% (95% CI -4.1 to 0.4, P = 0.1000). Seasonal influenza was the only disease for which mortality significantly increased ( R = 0.73, P = 0.00089), with an APC of 29.70% (95% CI 16.60-44.40%; P = 0.0000). The highest yearly case fatality ratios (CFR) belong to avian influenza A H5N1 [687.5 per 1,000 (33/48)] and epidemic cerebrospinal meningitis [90.5748 per 1,000 (1,010/11,151)]. The age-specific CFR of 10 RIDs was highest among people over 85 years old [13.6551 per 1,000 (2,353/172,316)] and was lowest among children younger than 10 years, particularly in 5-year-old children [0.0552 per 1,000 (58/1,051,178)]., Conclusions: The mortality rates of 10 RIDs were relatively stable from 2004 to 2020 with significant differences among Chinese provinces and age groups. There was an increased mortality trend for seasonal influenza and concerted efforts are needed to reduce the mortality rate of seasonal influenza in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Wang, Wang, Shi, Jiang, Tseng, Liu, Chan and Zhang.)

Rapid and reliable diagnosis is important for the management of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid antigen detection test (RADT) is a rapid, inexpensive, and easy method. Several studies have reported that RADTs performed well in many countries; however, very few studies have been reported in China. In this study, we assessed the performance of the RADT (Ediagnosis COVID-19 antigen test kit). This study was conducted in a centralized isolation site in Shanghai and enrolled 716 patients with COVID-19 and 203 noninfected participants. Nasopharyngeal swabs from all participants were collected on the same day and tested using the RADT and real-time reverse transcription-PCR (RT-PCR). The performance of the RADT was evaluated in different scenarios, such as threshold cycle ( C T ) values, symptomatic phase, and symptoms on the day of testing. The results demonstrated that the sensitivity for patients with C T values lower than 20 was 96.55% (95% confidence interval [CI], 87.05 to 99.4). The sensitivities were 78.4% (95% CI, 69.96 to 85.05) for participants within 5 days after the first RT-PCR-positive result and 90.77% (95% CI, 80.34 to 96.19) within 5 days after symptom onset. Moreover, the sensitivity of the RADT was more than 80% for patients with symptoms on the day of testing, including fever (89.29%), cough (86.84%), stuffy nose (92.59%), runny nose (92%), sore throat (81.25%), and muscle pain (80.77%), especially for those with upper respiratory tract symptoms. The specificity of the RADT was good in all scenarios. During the SARS-CoV-2 epidemic, Ediagnosis performed excellently in individuals with a higher viral load (evidenced by lower C T values), individuals in the early symptomatic phase, and especially those with upper respiratory tract symptoms. IMPORTANCE RADTs have demonstrated excellent performance in many counties for screening SARS-CoV-2 infection, but very few studies have been conducted in China. The performance of RADTs is largely related to different real-life scenarios. In our study, the performance of the RADT was evaluated in different scenarios, such as C T values, symptomatic phase, and symptoms on the day of testing. The results demonstrated that Ediagnosis (an RADT made in China) performed excellently for individuals with a higher viral load (evidenced by lower C T values), individuals in the early symptomatic phase, and especially those with upper respiratory tract symptoms.

Background: Electro-acupuncture (EA) has promising effects on diastasis rectus abdominis (DRA), defined as a separation of the two muscle bellies of rectus abdominis. To study, there is scant knowledge or scarce high-quality evidence., Objective: We aimed to evaluate the long-term efficacy and safety of EA in treating DRA during postpartum. It was assumed that the improvement of DRA was more obvious in the EA group than in the control group., Design: Randomized, controlled, blinded trial (Clinical Trial Registration: ChiCTR2100041891)., Setting: Hangzhou Hospital of Traditional Chinese Medicine in China., Participants: Females aged 20-45 years without a past medical history of pathological rectus abdominal dissection were recruited from DRA inclusion criteria from 42 days to 1 year postpartum., Intervention: 110 participants were randomly assigned in a 1:1 ratio to a control group with no EA intervention ( n = 55), and EA group ( n = 55). The EA group received ten sessions of EA combined with physical exercise or only physical exercise for 2 weeks with a 26-week follow-up., Measurements: Outcomes were assessed at baseline, week 2, and week 26. The primary outcome was the change of the inter recti distance (IRD) and electromyographic evaluation of the pelvic floor. Secondary outcomes included elasticity of linea alba (LA), paraumbilical subcutaneous adipose tissue (SAT) measurement, body mass index (BMI), percentage body fat (F%), dyspepsia symptoms, menstrual symptoms, quality of life (QoL), pain performance of patients with lower back pain, postnatal depression symptoms (PDS), postpartum self-image, and DRA-related symptom assessment including urine leakage, frequency, and urgency, constipation, sexual dysfunction, and chronic pelvic pain., Results: A total of 110 maternal (55 in each group) were recruited. The mean difference in IRD from baseline to week 2 and week 26 in all states of the two groups were reduced compared with those before treatment, with statistical significance ( P < 0.05). The mean of IRD at the horizontal line of the umbilicus in the end-expiratory state was smaller in the EA group than in the control group, but the difference was not statistically significant ( P > 0.05) at week 2. The mean of IRD at the horizontal line of the umbilicus in head-up and flexed knee state was smaller in the EA group than in the control group, and the difference was statistically significant ( P < 0.05) at week 26. Five (9.1%) and thirteen (23.64%) adverse events were reported in EA and control groups, respectively. No serious adverse events were reported., Limitation: The frequency intensity of EA parameters was selected between 4 and 6 because of individual tolerance differences., Conclusion: EA is an effective approach to improve IRD, electromyographic evaluation of the pelvic floor, BMI, the elasticity of LA, paraumbilical SAT, and symptoms of DRA, with durable effects at 26 weeks., Primary Funding Source: The Construction Fund of Medical Key Disciplines of Hangzhou (Project Number: OO20200097), Hangzhou Medical and Health Science and Technology Project No. A20200483, and Zhejiang Traditional Chinese Medicine Science and Technology Plan Project (Project Number: 2021ZQ065)., Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier: ChiCTR2100041891., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Zhu, Jiang, Lu, Xiao, Wang, Chen, Sun, Deng, Gu, Zheng, Feng and Shi.)

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has caused wide dissemination among pediatric patients globally and thus has aroused public concern. Here, we investigated the clinical epidemiological characteristics of 140 nonreplicate clinical K. pneumoniae strains isolated from pediatric patients between January and December 2021. Of all isolates, 16.43% (23 of 140) were CRKP strains, which predominantly contained KPC carbapenemase. wzi sequencing demonstrated that KL47 (65.22%, 15 of 23) was the most frequent capsular type, followed by KL64 (17.39%, 4 of 23). A total of 23 CRKP strains were classified into three different O-genotypes, including OL101 (65.22%, 15 of 23), O1 (26.09%, 6 of 23), and O3 (8.7%, 2 of 23). Interestingly, KL47 strains were strongly associated with OL101, while KL64 strains were all linked with O1. Some capsule-deficient strains were identified by serological typing, phage-typing, depolymerase-typing, and uronic acid assay. In this study, compared with healthy children, higher titers of anti-capsular polysaccharides (CPS) IgG were first detected in the sera of K47 and K64 K. pneumoniae-infected children, which had the effective bactericidal activity against corresponding serotype K. pneumoniae strains. These findings will facilitate the development of novel therapeutic and vaccine strategies against K. pneumoniae infection in children. IMPORTANCE The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains resistant to numerous antibiotics and the limited therapeutic options available have become an urgent health threat to the immunocompromised pediatric population. Vaccines and antibodies, especially those targeting capsular polysaccharides, may be novel and effective prevention and treatment options. Thus, it is important to understand the spread of CRKP in pediatric populations. This research presents OL101:KL47 and O1:KL64 as the predominant combinations among CRKP strains in children in Shanghai, China. The primary carbapenemase gene is KPC in CRKP strains. Additionally, this study found elevated levels of anti-CPS IgG against K47 and K64 K. pneumoniae strains in pediatric patients for the first time. The significant bactericidal activity of these anti-CPS IgGs was confirmed.

Objectives: Although hypervirulent Klebsiella pneumoniae (hvKp) is an increasing public health problem, there remains limited epidemiological information regarding hvKp infections in children. Here, we conducted a clinical, molecular and phenotypic surveillance of hvKp strains in a pediatric population., Methods: Non-repetitive K. pneumoniae (Kp) strains consecutively collected during 2019-2020 were screened for hypervirulence genes ( prmpA , prmpA2 , iucA , iroB , and peg344 ) using PCR. Positive strains were further characterized by four phenotypic assays (string test, serum killing assay, siderophore production, Galleria mellonella lethality assay), followed by murine sepsis model to determine virulence in vitro and in vivo . Also, capsular types, sequence types, plasmid replicon types, antimicrobial resistance determinants and susceptibility were analyzed., Results: A total of 352 isolates were collected, wherein 83 (23.6%) were hypervirulence genes-positive Kp (hgKp). A significant increase in KPC-2-producing KL47-ST11 among hgKp strains was observed, from 5.3% (1/19) in 2019 to 67.6% (25/37) in 2020 ( P <.0001), suggesting the potential dissemination of the hybrid virulence and carbapenem-resistance encoding plasmid among children. Further, hgKp isolates were classified into hvKp (n = 27) and hgKp-low virulence (hgKp-Lv) (n = 56) based on virulence phenotypic assays. In hvKp, diverse genetic clones were observed and K1-ST23 or K2-ST25 strains with sensitivity to multiple antibiotics were prevalent (25.9%, 7/27). Compared with hgKp-Lv, hvKp infection had a higher propensity to involve severe pneumonia (22.2% vs. 12.5%) in elder children and significant higher mortality in mice ( P = 0.0086). Additionally, either hvKp or hgKp-Lv infections were mostly healthcare-associated and hospital-acquired (74.1% vs. 91.9%)., Conclusions: These data suggest that K1-ST23 and K2-ST25 are high-risk clones of hvKp, and the genetic convergence of virulence and carbapenem-resistance is increasing among children. Control measures are needed to prevent the dissemination in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Du, Pan, Wang, Yu, Shi, Liu, Li, He, Han and Zhang.)

We report here a hypermucoviscous, New Delhi metallo-β-lactamase 1 (NDM-1) and imipenemase 4 (IMP-4) carbapenemases-coproducing Klebsiella variicola isolate obtained from a pediatric patient. This strain was resistant to carbapenems and most other β-lactams. Although hypermucoviscous, this strain possessed attenuated virulence according to serum killing assay and Galleria mellonella infection model. Notably, two copies of bla NDM-1 were contained on two tandem IS CR1 elements and coexisted with bla IMP-4 in a novel hybrid multidrug resistance plasmid. This is the first description of the coexistence of bla NDM-1 isolated from a pediatric patient in China. This isolate exhibited hypermucoviscosity, a classic hypervirulence characteristic of K. pneumoniae, and contained multiple carbapenem-resistant genes, including bla IMP-4 in a single plasmid of hypermucoviscous K. variicola. IMPORTANCE As an important member of the Klebsiella pneumoniae complex, Klebsiella variicola is poorly studied as an emerging human pathogen. We, for the first time, report a unique K. variicola isolated from a pediatric patient in China. This isolate exhibited hypermucoviscosity, a classic hypervirulence characteristic of K. pneumoniae, and contained multiple carbapenem-resistant genes, including bla IMP-1 and bla NDM-1 . Interestingly, these antimicrobial resistance genes were located on a novel hybrid plasmid, and our results suggested that this plasmid might have been introduced from K. pneumoniae and undergone a series of integration and recombination evolutionary events. Overall, our study provides more insight into K . variicola and highlights its superior capability to acquire and maintain foreign resistance genes.

Enterovirus A71 (EV-A71) is an important pathogen of severe hand, foot, and mouth disease (HFMD) in young children. This study aimed to retrospectively analyze the molecular epidemiology and recombination of EV-A71 in mainland China during 1987-2017. Phylogenetic tree showed that besides the previously reported subgenotypes A, B5, C0, C2, C3, and C4, a new subgenotype C6 emerged in mainland China. Recombination analysis indicated that C4 EV-A71 was derived from a common ancestor as a "double-recombinant" virus by intertypic recombination between C EV-A71 and CVA4, CVA5, CVA14, and CVA16 strains in P3 region and intratypic recombination between C and B EV-A71 strains in P2 region. The B5 EV-A71 shared high similarity with C EV-A71 in P1 region while it contained an unidentified sequence in P2 and P3 regions with two possible recombination patterns: one occurred between C4 EV-A71 and CVA3, CVA5, CVA6, CVA10, and CVA12 stains with one breakpoint in 3C, and the other occurred between C1, C2, C3, and C5 EV-A71 and CVA4, CVA5, CVA14, and CVA16 strains with two breakpoints in the 2A/2B junction and 3C. The C2 EV-A71 was probably a recombinant virus between C4 EV-A71 and CVA8 strains with two breakpoints located in the 5'UTR and 2A/2B junction. Moreover, an incredible recombination of C6 EV-A71 occurred between C4 and C2 EV-A71 with multiple breakpoints. Thus, continuous studies on EV-A71 genome characteristics are still useful and essential for monitoring emergence of new viruses and preventing HFMD outbreaks., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.)

To understand the characteristics and influencing factors related to cluster infections in Jiangsu Province, China, we investigated case reports to explore transmission dynamics and influencing factors of scales of cluster infection. The effectiveness of interventions was assessed by changes in the time-dependent reproductive number (Rt). From 25th January to 29th February, Jiangsu Province reported a total of 134 clusters involving 617 cases. Household clusters accounted for 79.85% of the total. The time interval from onset to report of index cases was 8 days, which was longer than that of secondary cases (4 days) (χ2 = 22.763, P < 0.001) and had a relationship with the number of secondary cases (the correlation coefficient (r) = 0.193, P = 0.040). The average interval from onset to report was different between family cluster cases (4 days) and community cluster cases (7 days) (χ2 = 28.072, P < 0.001). The average time interval from onset to isolation of patients with secondary infection (5 days) was longer than that of patients without secondary infection (3 days) (F = 9.761, P = 0.002). Asymptomatic patients and non-familial clusters had impacts on the size of the clusters. The average reduction in the Rt value in family clusters (26.00%, 0.26 ± 0.22) was lower than that in other clusters (37.00%, 0.37 ± 0.26) (F = 4.400, P = 0.039). Early detection of asymptomatic patients and early reports of non-family clusters can effectively weaken cluster infections.

Objective: We investigated the epidemiological characteristics of drug resistance and virulence factors of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from paediatric patients in Shanghai., Methods: CRKP strains were consecutively collected between January and December in 2018. Antimicrobial susceptibility was determined by VITEK 2 compact. Polymerase chain reaction (PCR) was used to analyse drug resistance determinants, virulence genes and plasmid types. wzi sequencing and multilocus sequence typing was used to determine clonal relatedness., Results: Among 172 CRKP strains, bla KPC-2 and bla NDM-5 were the predominant carbapenemase genes. Compared with NDM-5, KPC-2 producers showed higher resistance rates to fluoroquinolones and aminoglycosides. The majority of KPC-2 producers belonged to KL64-ST11 background, while NDM-5 producers were mainly identified as KL62-ST48. Plasmid typing shown that IncF and IncFIB were the most prevalent plasmids in KPC-2 producers and IncX3 was widely spread in NDM-5-KP. Thirty-seven isolates carried various hypervirulence genes and the profiles of these genes showed high diversity., Conclusions: The predominant carbapenemase of CRKP strains from paediatric patients in Shanghai were KPC-2 and NDM-5. KL47-ST11 KPC-2-KP and KL62-ST48 NDM-5-KP were representative clonal lineages. Although not prevalent, hypervirulence associated genes have begun to spread. Active long-term surveillance should be performed in both drug resistance characteristics and virulence factors., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Infectious diarrhea can lead to a considerable global disease burden. Thus, the accurate prediction of an infectious diarrhea epidemic is crucial for public health authorities. This study was aimed at developing an optimal random forest (RF) model, considering meteorological factors used to predict an incidence of infectious diarrhea in Jiangsu Province, China., Methods: An RF model was developed and compared with classical autoregressive integrated moving average (ARIMA)/X models. Morbidity and meteorological data from 2012 to 2016 were used to construct the models and the data from 2017 were used for testing., Results: The RF model considered atmospheric pressure, precipitation, relative humidity, and their lagged terms, as well as 1-4 week lag morbidity and time variable as the predictors. Meanwhile, a univariate model ARIMA (1,0,1)(1,0,0) 52 (AIC = - 575.92, BIC = - 558.14) and a multivariable model ARIMAX (1,0,1)(1,0,0) 52 with 0-1 week lag precipitation (AIC = - 578.58, BIC = - 578.13) were developed as benchmarks. The RF model outperformed the ARIMA/X models with a mean absolute percentage error (MAPE) of approximately 20%. The performance of the ARIMAX model was comparable to that of the ARIMA model with a MAPE reaching approximately 30%., Conclusions: The RF model fitted the dynamic nature of an infectious diarrhea epidemic well and delivered an ideal prediction accuracy. It comprehensively combined the synchronous and lagged effects of meteorological factors; it also integrated the autocorrelation and seasonality of the morbidity. The RF model can be used to predict the epidemic level and has a high potential for practical implementation.

Influenza activity is subject to environmental factors. Accurate forecasting of influenza epidemics would permit timely and effective implementation of public health interventions, but it remains challenging. In this study, we aimed to develop random forest (RF) regression models including meterological factors to predict seasonal influenza activity in Jiangsu provine, China. Coefficient of determination (R2) and mean absolute percentage error (MAPE) were employed to evaluate the models' performance. Three RF models with optimum parameters were constructed to predict influenza like illness (ILI) activity, influenza A and B (Flu-A and Flu-B) positive rates in Jiangsu. The models for Flu-B and ILI presented excellent performance with MAPEs <10%. The predicted values of the Flu-A model also matched the real trend very well, although its MAPE reached to 19.49% in the test set. The lagged dependent variables were vital predictors in each model. Seasonality was more pronounced in the models for ILI and Flu-A. The modification effects of the meteorological factors and their lagged terms on the prediction accuracy differed across the three models, while temperature always played an important role. Notably, atmospheric pressure made a major contribution to ILI and Flu-B forecasting. In brief, RF models performed well in influenza activity prediction. Impacts of meteorological factors on the predictive models for influenza activity are type-specific.

We depicted the epidemiological characteristics of infectious diarrhoea in Jiangsu Province, China. Generalized additive models were employed to evaluate the age-specific effects of etiological and meteorological factors on prevalence. A long-term increasing prevalence with strong seasonality was observed. In those aged 0-5 years, disease risk increased rapidly with the positive rate of virus (rotavirus, norovirus, sapovirus, astrovirus) in the 20-50% range. In those aged > 20 years, disease risk increased with the positive rate of adenovirus and bacteria (Vibrio parahaemolyticus, Salmonella, Escherichia coli, Campylobacter jejuni) until reaching 5%, and thereafter stayed stable. The mean temperature, relative humidity, temperature range, and rainfall were all related to two-month lag morbidity in the group aged 0-5 years. Disease risk increased with relative humidity between 67-78%. Synchronous climate affected the incidence in those aged >20 years. Mean temperature and rainfall showed U-shape associations with disease risk (with threshold 15 °C and 100 mm per month, respectively). Meanwhile, disease risk increased gradually with sunshine duration over 150 hours per month. However, no associations were found in the group aged 6-19 years. In brief, etiological and meteorological factors had age-specific effects on the prevalence of infectious diarrhoea in Jiangsu. Surveillance efforts are needed to prevent its spread.

BACKGROUND This study aimed to identify NOTCH3 mutations and describe the genetic and clinical features and magnetic resonance imaging results in 11 unrelated patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) from Henan province in China. MATERIAL AND METHODS NOTCH3 was directly sequenced in 11 unrelated patients of Chinese descent. The clinical presentations and magnetic resonance imaging features were retrospectively analyzed in the 11 index patients with a definite diagnosis. RESULTS Seven different mutations were identified in 11 unrelated patients, including 4 novel mutations (p.P167S, p.P652S, p.C709R, and p.R1100H) in China and 3 reported mutations (p.C117R, p.R578C, and p.R607C). Four novel mutations (p.P167S, p.P652S, p.C709R, and p.R1100H) were predicted to be probably pathogenic using an online pathogenicity prediction program through comprehensive analysis. Clinical presentations in symptomatic patients included stroke, cognitive decline, psychiatric disturbances, and migraine. Multiple lacunars infarcts and leukoaraiosis were detected on MRI in most symptomatic patients, while white-matter lesions were identified in the temporal pole or the external capsule in all affected patients. CONCLUSIONS The mutation spectrum of CADASIL patients from Henan province in China displayed some differences from that of those reported previously. DNA sequencing was used to diagnose all 11 patients as having CADASIL, and we found 4 novel mutations. The present results further contribute to the enrichment of NOTCH3 mutation databases.

Background: is the most common pathogen causing death in children under 5 years old. This retrospective surveillance aimed to analyze serotype distribution, drug resistance, virulence factors, and molecular characteristics of pneumonia isolates from children in Shanghai, China. Streptococcus pneumoniae is the most common pathogen causing death in children under 5 years old. This retrospective surveillance aimed to analyze serotype distribution, drug resistance, virulence factors, and molecular characteristics of pneumonia isolates from children in Shanghai, China. Methods: A total of 287 clinical pneumococcal isolates were collected from January to December in 2018 and were divided into community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HAP) two groups according to where someone contracts the infection. All isolates were serotyped by multiplex sequential PCR and antimicrobial susceptibility testing was performed using E-test or disk diffusion method. The molecular epidemiology was analyzed using multilocus sequence typing and seven housekeeping genes were sequenced to identified the sequence types (STs). In addition, we investigated the presence of virulence genes via PCR. Results: The most common serotypes were 19F, 6A, 19A, 23F, 14, and 6B, and the coverage rates of the 7-, 10- and 13-valent pneumococcal conjugate vaccines were 58.9, 58.9, and 80.5%, respectively. More PCV13/non-PCV7 serotypes and higher rate of penicillin non-susceptible S. pneumoniae were seen in HAP. Molecular epidemiological typing showed a high level of diversity and five international antibiotic-resistant clones were found, including Taiwan 19F -14, Spain 23F -1, Spain 6B -2, Taiwan 23F -15 and Sweden 15A -25. No significant difference was observed in the presence of virulence genes among the isolates obtained from CAP and HAP. All of the S. pneumoniae isolates carried lytA, ply, psaA, pavA, spxB, htrA , and clpP , and the carriage rate of nanA and piaA were 96.2 and 99.0%. Conversely, cps2A, cbpA , and pspA were present in 33.8-44.3% of the isolates. Conclusions: Serotype changes and emerging multidrug-resistant international clones were found in current study. lytA, ply, psaA, pavA, spxB, htrA , and clpP may be good protein vaccine candidates. Long-term high-quality surveillance should be conducted to assess impact and effectiveness brought by vaccines, and provide a foundation for prevention strategies and vaccine policies.

Objective: Alzheimer's disease (AD) is the most common form of dementia characterized by memory loss at disease onset. The gene mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the frequent causes of AD. However, the clinical and genetic features of AD overlap with other neurodegenerative diseases. The present study aimed to identify the clinical and genetic characteristics in a Han Chinese AD cohort., Methods: Detailed clinical assessment was applied to all the patients. We screened amyloid precursor protein (APP), PSEN1, PSEN2, and microtubule-associated protein tau (MAPT) genes were assessed in 83 sporadic AD patients by Sanger sequencing. A total of 25 probands from families with AD were subjected to next-generation sequencing on 53 dementia-associated genes to capture the target region, and Sanger sequencing was used to detect the variants in the DNA sequence., Results: PSEN1 p.L226R was found in an early-onset AD (EOAD) family characterized by language impairment at disease onset, a novel probably pathogenetic variant (p.D534H) was identified in a frontal-temporal dementia gene, TANK-binding kinase 1 (TBK1) with a typical AD phenotype in a late-onset AD (LOAD) family, and a PSEN2p.H169N mutation and two benign MAPT (p.Q230R and p.V48L) mutations were detected in three EOAD patients., Conclusions: Thus, five variants were identified in a Han Chinese cohort. In the present study, a novel, probably damaging FTLD gene TBK1variant with a typical AD phenotype was detected. Also, the phenotypic characteristics of PSEN1 p.L226R, a PSEN2pathogenic mutation, and two likely benign MAPT variants were described. Hence, screening for mutations in other dementia genes could be further explored in clinically diagnosed AD patients., (© 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Objects: This study aimed to report a novel point mutation associated with juvenile amyotrophic lateral sclerosis (JALS) in a Chinese Han family., Methods: Detailed clinical assessment was applied to two patients, including proband (II-2) and his mother (I-2). Next-generation sequencing (NGS), also known as high-throughput sequencing in whole exon sequence, was performed in the proband to reach the target region. Sanger sequencing was also used to detect DNA sequence variants of the proband and other three members of his family., Results: The proband (II-2) and his mother (I-2) were successfully diagnosed according to the clinical manifestations and physical examination. A novel point mutation c.1157T > C in the exon 10 of the SETX gene was identified in II-2 and I-2, resulting in a substitution of methionine (ATG) to threonine (ACG). However, we ultimately did not find the same variant in the other two normal members of his family in addition to 100 unrelated normal subjects., Conclusion: We presented a novel probably pathogenic missense mutation in exon 10 of SETX gene in a Chinese Han family with JALS., (© 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Background: In the present study, a novel mutation in exon 46 at codon 2304 (G2304R) of the SYNE1 gene is described in a Chinese family (proband, mother, and sister) with Emery-Dreifuss muscular dystrophy-like, which clinically manifests as muscle weakness, muscle atrophy, joint contracture, and without significant cardiac abnormalities., Methods: Clinical examination and neuroimaging of the captured target region and high-throughput sequencing were performed in a family of four generations. Muscle changes were evaluated using magnetic resonance imaging and muscle biopsies., Results: Target region capture sequencing yielded a novel missense mutation in codon 2304 (G2304R), which is a heterozygous A to G point mutation at position 6910 (c.6910A > G) in exon 46 of SYNE1 leading to a glycine-to-arginine substitution (p.Gly2304Arg). The results were also identified by Sanger sequencing in three family members but not in the other three unaffected family members and 100 control subjects., Conclusions: This mutation is probably pathogenic and is the first of its kind reported in a familial Emery-Dreifuss muscular dystrophy-like.

The first Enterovirus 71 (EV71) strain isolated in 1969 was classified as genotype A. It is interesting that the genotype A disappeared nearly 40 years until its re-emergence in mainland China in 2008-2010. Few studies on genetic characterization of the re-emerged genotype A viruses have been reported. In this study, a series of analyses were performed on molecular epidemiology and genome recombination of genotype A viruses in China. Phylogenetic analysis indicated that except for 17 reported genotype A strains and 3 orphan strains (C0, C3 and B5), almost all EV71 strains in mainland China were belonging to subgenotype C4 during 1987-2011. The subgenotype C4 was further divided into 3 clades C4a1, C4a2, and C4b. The genotype A viruses co-circulated with the predominant clade C4a2 and the re-emerged clade C4b both in eastern and central China in 2008-2009. Moreover, comprehensive recombination analysis showed that the genotype A viruses were "triple-recombinant" by combination of intratypic and intertypic recombination. Intertypic recombination between the oldest C4b strain (SHZH98) and Coxsackievirus A5 (CVA5) and intratypic recombination between the SHZH98 and C1 strains both with one junction in 5'-UTR were observed for some specific C4a2 strains and the re-emerged C4b strain, respectively. And intratypic recombination between the re-emerged C4b strain and the specific C4a2 strains with one junction in 5'-UTR was observed for the Chinese genotype A viruses. Taken together, these results provided potential explanations for the genesis of Chinese genotype A viruses which were significant for preventing and controlling outbreaks.

Enterovirus 71 (EV71) is a neurotropic virus that causes various clinical manifestations in young children, ranging from asymptomatic to fatal. Different pathotypes of EV71 notably differ in virulence. Several virulence determinants of EV71 have been predicted. However, these reported virulence determinants could not be used to identify the EV71 strains of subgenotype C4, which mainly circulate in China. In this study, VP1 sequences of 37 EV71 strains from severe cases (SC-EV71) and 192 EV71 strains from mild cases (MC-EV71) in mainland China were analyzed to determine the potential virulence determinants in the capsid protein VP1 of EV71. Although most SC-EV71 strains belonged to subgenotype C4a, no specific genetic lineages in C4a were correlated with EV71 virulence. Interestingly, amino acid substitutions at nine positions (H22Q, P27S, N31S/D, E98K, E145G/Q, D164E, T240A/S, V249I, and A289T) were detected by aligning the VP1 sequences of the SC-EV71 and MC-EV71 strains. Moreover, both the constituent ratios of the conservative or mutated residues in the MC-EV71 and SC-EV71 strains and the changes in the VP1 3D structure resulting from these mutations confirmed that the conservative residues (22H, 249V, and 289A) and the mutated residues (27S, 31S/D, 98K, 145G/Q, 164E, and 240A/S) might be potential virulence determinants in VP1 of EV71. Furthermore, these results led to the hypothesis that VP1 acts as a sandwich switch for viral particle stabilization and cellular receptors attachment, and specific mutations in this protein can convert mild cases into severe cases. These findings highlight new opportunities for diagnostic and therapeutic interventions.

Background: Candida species is an important cause of nosocomial infection in neonatal intensive care units (NICUs). However, most reports in China have been limited to single institutions. The aim of this study is to investigate the epidemiology of invasive candidiasis in multiple NICUs across China., Methods: We retrospectively collected demographic data, clinical characteristics, microbiological results and outcome of preterm infants with invasive candidiasis discharged from 11 academic tertiary NICUs during January 2009 to December 2011., Results: There were 30,045 preterm infants discharged from 11 NICUs during the study period. We detected 223 infants with invasive candidiasis, resulting in an incidence of 0.74 cases per 100 preterm discharges from NICUs. In very low birth weight infants, the incidence was 3.42 cases per 100 very low birth weight discharges. Mean gestational age of infected infants was 31.4 weeks and median birth weight was 1410 gram. Among the cohort of infants with invasive candidiasis, 214 (96.0%) infants had positive blood culture for fungus, 5 infants had positive urine culture, 3 from cerebrospinal fluid and 1 from articular effusion in the shoulder joint. Among the cohort of infants with candidemia, 48 (22.4%) infants had fungal meningitis. Candida albicans accounted for 57.4% of total positive cultures. Overall mortality attributable to invasive candidiasis was 19.3%., Conclusions: Invasive candidiasis is a common problem among preterm neonates in China, especially among very low birth weight infants and it is associated with a high mortality. The preponderance of infections was due to Candida albicans.