Objective:To understand the current situation and problems of research design in adverse drug reaction (ADR) signal detection study in China.Methods:The literature on ADR signal detection study in SinoMed, CNKI, WanFang Data and VIP databases were retrieved (up to May 30, 2022). The research purpose, research direction (target drug, target ADR), source database of signals, target drug role, reference drug, signal detection algorithm, and bias control of the literature were analyzed descriptively one by one.Results:A total of 165 articles were included, of which 146 (88.5%) were published in core journals. From 2013 to 2022 (January to May, 2022), there were 4, 3, 2, 7, 8, 11, 20, 29, 55, and 26 relevant articles, respectively. Problems in these studies were as follows: research purposes were not clear in 6.7% (11/165) of the literature; target ADRs were selected as non targeted in 80.6% (133/165) of the literature; the domestic database was less utilized [only 9.7% (16/165)]; did the selection range of the target drug role were not mentioned in 33.9% (56/165) of the literature; only a single algorithm for signal detection was used in 36.4% (60/165) of the literature; bias analysis was not conducted in 85.5% (141/165) of the literature.Conclusions:The domestic literature on ADR signal detection has problems of poor standardization in research design, such as unclear research purpose and direction, incomplete research items, etc. Chinese scholars should further improve the quality of research design while strengthening the research on ADR signal detection.

Objective:To understand the problems of data mining in adverse drug reaction (ADR)/adverse event (AE) signal detection study in China.Methods:The literature on ADR/AE signal detection study in SinoMed, CNKI, WanFang Data and VIP databases were retrieved (up to May 30, 2022). The relevant content of the data mining in the literature was investiagted and evaluated from the following 4 dimensions and 9 items: (1) background data, including 1 item; (2) data preprocessing, including 4 items such as drug mapping, AE mapping, missing value processing, and data deduplication; (3) data mining algorithm (DMA), including 3 items such as DMA selection, DMA formula interpretation, and signal threshold; (4) interpretation of the results, including 1 item. According to the relevant specifications and technical requirements of data mining, the reporting/reporting error-free rate of the 4 dimensions and 9 items in the literature was taken as the overall quality evaluation index. Reporting/reporting error-free rate ≥60% was considered to be an excellent level of overall quality.Results:A total of 165 articles were included. On the background data dimension, the reporting/reporting error-free rate of using all the other drug data of the entire database in the literature was 35.2% (58/165), which did not reach an excellent level. On the data preprocessing dimension, the reporting/reporting error-free rates of drug mapping, AE mapping, missing value processing, and data deduplication in the literature were 22.4% (37/165), 73.9% (122/165), 10.3% (17/165), and 55.2% (91/165), respectively. The reporting/reporting error-free rate on this dimension was 40.5% (267/660), which did not reach the excellent level, only the rate of AE mapping reached the excellent level. On the DMA dimension, the reporting/reporting error-free rates of ≥2 DMA, DMA formula interpretation, and signal threshold in the literature were 63.6% (105/165), 78.2% (129/165), and 87.9% (145/165), respectively. The reporting/reporting error-free rate on this dimension was 76.6% (379/495), which reached an excellent level. The reporting/reporting error-free rate was 87.4% (144/165), reaching an excellent level. The signals were interpreted as "positive" or "negative" signals in 7 articles, and the meaning of signals were interpreted as causality in 14 articles. The overall reporting/reporting error-free rate in the 165 literature, analyzed from 9 items on 4 dimensions, was 57.1% (848/1 485), which did not reach the excellent level.Conclusion:The main problems in the domestic literature of ADR/AE signal detection study are the incomplete selection of background data and the lack of data preprocessing, suggesting that the further relevant studies in China should be improved on above 2 dimensions for better quality of ADR/AE signal detection research.

Objective:To understand the current situation and problems of research design in adverse drug reaction (ADR) signal detection study in China.Methods:The literature on ADR signal detection study in SinoMed, CNKI, WanFang Data and VIP databases were retrieved (up to May 30, 2022). The research purpose, research direction (target drug, target ADR), source database of signals, target drug role, reference drug, signal detection algorithm, and bias control of the literature were analyzed descriptively one by one.Results:A total of 165 articles were included, of which 146 (88.5%) were published in core journals. From 2013 to 2022 (January to May, 2022), there were 4, 3, 2, 7, 8, 11, 20, 29, 55, and 26 relevant articles, respectively. Problems in these studies were as follows: research purposes were not clear in 6.7% (11/165) of the literature; target ADRs were selected as non targeted in 80.6% (133/165) of the literature; the domestic database was less utilized [only 9.7% (16/165)]; did the selection range of the target drug role were not mentioned in 33.9% (56/165) of the literature; only a single algorithm for signal detection was used in 36.4% (60/165) of the literature; bias analysis was not conducted in 85.5% (141/165) of the literature.Conclusions:The domestic literature on ADR signal detection has problems of poor standardization in research design, such as unclear research purpose and direction, incomplete research items, etc. Chinese scholars should further improve the quality of research design while strengthening the research on ADR signal detection.

Objective:To understand the problems of data mining in adverse drug reaction (ADR)/adverse event (AE) signal detection study in China.Methods:The literature on ADR/AE signal detection study in SinoMed, CNKI, WanFang Data and VIP databases were retrieved (up to May 30, 2022). The relevant content of the data mining in the literature was investiagted and evaluated from the following 4 dimensions and 9 items: (1) background data, including 1 item; (2) data preprocessing, including 4 items such as drug mapping, AE mapping, missing value processing, and data deduplication; (3) data mining algorithm (DMA), including 3 items such as DMA selection, DMA formula interpretation, and signal threshold; (4) interpretation of the results, including 1 item. According to the relevant specifications and technical requirements of data mining, the reporting/reporting error-free rate of the 4 dimensions and 9 items in the literature was taken as the overall quality evaluation index. Reporting/reporting error-free rate ≥60% was considered to be an excellent level of overall quality.Results:A total of 165 articles were included. On the background data dimension, the reporting/reporting error-free rate of using all the other drug data of the entire database in the literature was 35.2% (58/165), which did not reach an excellent level. On the data preprocessing dimension, the reporting/reporting error-free rates of drug mapping, AE mapping, missing value processing, and data deduplication in the literature were 22.4% (37/165), 73.9% (122/165), 10.3% (17/165), and 55.2% (91/165), respectively. The reporting/reporting error-free rate on this dimension was 40.5% (267/660), which did not reach the excellent level, only the rate of AE mapping reached the excellent level. On the DMA dimension, the reporting/reporting error-free rates of ≥2 DMA, DMA formula interpretation, and signal threshold in the literature were 63.6% (105/165), 78.2% (129/165), and 87.9% (145/165), respectively. The reporting/reporting error-free rate on this dimension was 76.6% (379/495), which reached an excellent level. The reporting/reporting error-free rate was 87.4% (144/165), reaching an excellent level. The signals were interpreted as "positive" or "negative" signals in 7 articles, and the meaning of signals were interpreted as causality in 14 articles. The overall reporting/reporting error-free rate in the 165 literature, analyzed from 9 items on 4 dimensions, was 57.1% (848/1 485), which did not reach the excellent level.Conclusion:The main problems in the domestic literature of ADR/AE signal detection study are the incomplete selection of background data and the lack of data preprocessing, suggesting that the further relevant studies in China should be improved on above 2 dimensions for better quality of ADR/AE signal detection research.

Objective: To investigate the current status of knowledge and practice pertaining to nosocomial infection control among medical professionals in grassroots healthcare institutions, so as to provide the evidence of improving the level of infection control in grassroots healthcare institutions. Methods: All medical professionals working in grassroots healthcare institutions in Pukou District, Nanjing City, were enrolled. The participants' demographic features and knowledge and practice of nosocomial infection control were collected using self-designed questionnaires and descriptively analyzed. Results: A total of 402 participants were enrolled, included 116 men ( 28.86% ) and 286 women ( 71.14% ). The respondents were predominantly at ages of 41 years and older ( 187 subjects, 46.52% ), with bachelor and above as the predominant educational level ( 200 subjects, 49.75% ) and intermediate title and above as the predominant professional title ( 168 subjects, 41.79%) , and there were 236 participants ( 58.71% ) with the length of service for more than 10 years. The awareness rate of nosocomial infection control knowledge was 56.22% among medical professionals working in grassroots healthcare institutions, with the highest awareness for COVID-19 prevention and control ( 89.55% ) and the lowest awareness for the key aspects in nosocomial infection control ( 39.55% ). The formation rate of implementing nosocomial infection control practices was 84.08%, with a low rate for “Implement satisfactorily the isolation interventions for patients with multidrug resistant bacteria” ( 71.14% ) and “Implement satisfactorily the control measures for nosocomial infections in key departments and key aspects”( 64.68% ). Conclusions Low levels are seen in the awareness of nosocomial infection control, behaviors of multidrug resistance management and key aspects in nosocomial infection control among medical professionals in grassroots healthcare institutions in Pukou District.

OBJECTIVES: Varicella-zoster virus (VZV) is one of the most common etiologies of viral meningitis/encephalitis. The early clinical manifestations and cerebrospinal fluid (CSF) changes of VZV meningitis/encephalitis lack specificity, and it is easy to be misdiagnosed as other viral encephalitides or tuberculous meningitis. This study aims to investigate whether the clinical characteristics, CSF analysis findings, and CSF cytokine levels could distinguish VZV meningitis/encephalitis from central nervous system (CNS) herpes simplex virus (HSV) and Mycobacterium tuberculosis (MTB) infections. METHODS: The medical records from 157 CNS infections, including 49 HSV (45 HSV-1, 4 HSV-2), 55 VZV, and 53 MTB infections between January 2018 and June 2021 in the Cytology Laboratory, Department of Neurology, Third Xiangya Hospital of Central South University were retrospectively reviewed. The data of 3 groups included demographic characteristics, laboratory results, radiographic findings, and outcomes. The levels of 12 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, IFN-γ, IFN-α, and TNF-α) in the CSF of 68 patients (13 HSV, 22 VZV, and 33 MTB infection cases) were quantified. Clinical and laboratory data were compared among the 3 groups. RESULTS: The most common clinical manifestations in the 3 groups were fever, headache, vomiting, and neck stiffness. The clinical manifestations of HSV and VZV CNS disease were similar, although fever and altered consciousness were less common in the VZV group than those in the HSV and MTB groups (63.6% vs 87.8% vs 96.2%, P<0.001, and 14.5% vs 26.5% vs 47.2%, P=0.004, respectively). Seven patients (7/55, 12.7%) presented cutaneous zoster in the VZV group. CSF leukocyte count was significantly higher in the VZV group (230×10⁶ cells/mL) and MTB groups (276×10⁶ cells/mL) than that in the HSV group (87×10⁶ cells/mL, P=0.002). CSF protein level was significantly higher in the VZV than that in the HSV group (1 034 mg/L vs 694 mg/L, P=0.011) but lower than that in the MTB group (1 744 mg/L, P<0.001). IL-6 (VZV vs HSV vs MTB: 2 855.93 pg/mL vs 2 128.26 pg/mL vs 354.77 pg/mL, P=0.029) and IL-8 (VZV vs HSV vs MTB: 4 001.46 pg/mL vs 1 578.11 pg/mL vs 1 023.25 pg/mL, P=0.046) levels were significantly different among the 3 groups and were elevated in the VZV group.Post hoc analysis revealed that IL-6 and IL-8 were significantly higher in the VZV group than those in the MTB group (P=0.002 and P=0.035, respectively), but not in the HSV group (P>0.05). CONCLUSIONS VZV meningitis/encephalitis presents with CSF hypercellularity and proteinemia, challenging the classical view of CSF profiles in viral encephalitis. CSF IL-6 and IL-8 levels are elevated in patients with VZV meningitis/encephalitis, indicating a more intense inflammatory response in these patients.
Humans ; Central Nervous System Infections ; Encephalitis ; Encephalitis, Varicella Zoster/diagnosis* ; Encephalitis, Viral/diagnosis* ; Herpesvirus 3, Human ; Interleukin-6 ; Interleukin-8 ; Meningitis ; Retrospective Studies

Objective:To investigate the application value of noninvasive prenatal DNA screening combined with nuchal translucency thickness measurement in the diagnosis of fetal chromosome aneuploidy.Methods:A total of 5 730 pregnant women who were screened for fetal chromosomal diseases in the Quzhou Maternal and Child Health Hospital from January 2017 to March 2019 were included in this study. All of them underwent noninvasive prenatal DNA screening and nuchal translucency thickness measurement. The results of amniocentesis were used as the gold standard to evaluate the diagnostic efficacy of noninvasive prenatal DNA screening, nuchal translucency thickness measurement and their combination.Results:Noninvasive prenatal DNA screening revealed that 64 (1.12%) women out of 5 730 pregnant women had high risk of developing chromosomal abnormalities. Ultrasound examination results showed that nuchal translucency was thickened in 140 (2.44%) women. The outcome of adverse pregnancy increased with the increase of nuchal translucency thickness. Among the 68 pregnant women who underwent amniocentesis, 51 women developed chromosomal abnormalities, with trisomy 21 syndrome being the majority (23/51,45.10%). The diagnostic efficacy of noninvasive prenatal DNA screening combined with nuchal translucency thickness measurement in the diagnosis of fetal chromosomal aneuploidy reached the ideal level.Conclusion:Noninvasive prenatal DNA screening combined with nuchal translucency thickness measurement has a high clinical application value. The combined method can be used as the main prenatal DNA screening method for pregnant women and it can effectively avoid the birth of children with chromosomal abnormalities.

Objective:To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients.Methods:A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m 2) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results:Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%).Conclusions:The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m 2) plus S-1 regimen for 2 weeks. However, it′s still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.

Autism spectrum disorder (ASD), a representative disease of children's neurodevelopmental disorders, brings huge pressure and financial burden to families and society. It is of great significance to explore its etiology and pathogenesis. Therefore, we established an ASD Cohort based on the existing China National Birth Cohort (CNBC), which applied parallel design to recruit and follow up families who achieved pregnancy after receiving assisted reproductive technologies (ART) and families with spontaneous conception. The main aims of this study are to compare the incidence of ASD among children born after ART with those born under spontaneous pregnancy, and to evaluate the impact of ART on the neurobehavioral development of offspring. Additionally, with a variety of clinical and behavioral related information collected during pregnancy and at early life of offspring, we are able to investigate the risk factors associated with ASD comprehensively. This article briefly introduces the objectives, contents, preliminary progress, strength and limitations, as well as further prospects of the ASD cohort study, mainly focusing on the overall design and current progress.

The importance of gut microbes to human health has gradually attracted attention. With the use of animal models, it has been revealed that maternal microbes during pregnancy could influence their children's health outcomes through shaping their microbial composition and regulating the development of their metabolic and immune system. However, the physiological mechanism of the human body is more complex and is affected by the interaction of multiple factors. The research results obtained from animal models are often inconsistent with human studies. At present, the influence of maternal intestinal microbes during pregnancy on the microbial colonization in their offspring and on a series of children's health outcomes is still unclear. Establishing a sub-cohort to detect the microbiome of the women across pregnancy and of their offspring, and further to integrate with variety of environmental and behavioral exposures can better provide reliable support for the research on the mechanism of children's health and diseases. This paper briefly introduces the research objectives, content, progress, strength and limitations of the sub-cohort study.