Peritoneal dialysis-associated peritonitis caused by Neisseria.sicca: A case report and literature review.

Neisseria sicca, a Gram-negative diplococcus commonly found in the nasopharynx as part of normal bacterial flora, is typically non-pathogenic but has been associated with various diseases including endocarditis, conjunctivitis, pneumonia and meningitis (Jeurissen et al., 2006; Kozlova et al., 2020; Alcid, 1980; Carter et al., 2007). In this report, we present a case of peritonitis in a patient undergoing peritoneal dialysis caused by N. sicca and review the literature on Neisseria-associated peritonitis.

Infant Alstrom syndrome diagnosed by a new gene mutation: a case report.

Alstrom syndrome is a rare autosomal recessive disorder resulting from an ALMS1 gene mutation. Here, we present the clinical data of a case of an infant diagnosed with Alstrom syndrome through whole-exome sequencing. A 2-month-old male infant was admitted to Sichuan Provincial Maternity and Child Health Care Hospital on 30 May 2019 after "coughing for half a day and dyspnea for 2 hours". He was diagnosed with severe pneumonia, acute congestive heart failure, Grade III cardiac function, acute respiratory failure, and myocarditis. After treatment, he was discharged with a prescription for oral medication. After a 4-month follow-up, the patient's left ventricle exhibited spherical enlargement and a decrease in left ventricular function. The infant's whole-exome sequencing results revealed compound heterozygous mutations in the ALMS1 gene: c.2179dup (p. Y727Lfs*12), a frameshift mutation, that was heterozygous and originated from the mother, while c.11140C>T (p. Q3714*) was a heterozygous nonsense mutation that originated from the father. Both mutations are classified as "category 1-pathogenic mutations" according to the American College of Medical Genetics and Genomics (ACMG) assessment. A novel ALMS1 mutation was identified in this case report, highlighting the importance of genetic testing for the early diagnosis of Alstrom syndrome.

Over-expression of miR-3584-5p Represses Nav1.8 Channel Aggravating Neuropathic Pain caused by Chronic Constriction Injury.

Nav1.8, a tetrodotoxin-resistant voltage-gated sodium channels (VGSCs) subtype encoded by SCN10A, which plays an important role in the production and transmission of peripheral neuropathic pain signals. Studies have shown that VGSCs may be key targets of MicroRNAs (miRNAs) in the regulation of neuropathic pain. In our study, bioinformatics analysis showed that the targeting relationship between miR-3584-5p and Nav1.8 was the most closely. The purpose of this study was to investigate the roles of miR-3584-5p and Nav1.8 in neuropathic pain. The effects of miR-3584-5p on chronic constriction injury (CCI)-induced neuropathic pain in rats was investigated by intrathecal injection of miR-3584-5p agomir (an agonist, 20 µM, 15 µL) or antagomir (an antagonist, 20 µM, 15 µL). The results showed that over-expression of miR-3584-5p aggravated neuronal injury by hematoxylin-eosin (H&E) staining and mechanical/thermal hypersensitivity in CCI rats. MiR-3584-5p indirectly inhibited the expression of Nav1.8 by up-regulating the expression of key proteins in the ERK5/CREB signaling pathway, and also inhibited the current density of the Nav1.8 channel, changed its channel dynamics characteristic, thereby accelerating the transmission of pain signals, and further aggravating pain. Similarly, in PC12 and SH-SY5Y cell cultures, miR-3584-5p increased the level of reactive oxygen species (ROS) and inhibited mitochondrial membrane potential (Δψm) in the mitochondrial pathway, decreased the ratio of apoptosis-related factor Bcl-2/Bax, and thus promoted neuronal apoptosis. In brief, over-expression of miR-3584-5p aggravates neuropathic pain by directly inhibiting the current density of Nav1.8 channel and altering its channel dynamics, or indirectly inhibiting Nav1.8 expression through ERK5/CREB pathway, and promoting apoptosis through mitochondrial pathway.

[Advances of Claudin6-targeting drugs in cancer therapy].

CLDN6 is a member of the CLDNs family that is specifically and highly expressed in cancers such as ovarian, testicular, endocervical, liver and lung adenocarcinoma, but hardly expressed in adult normal tissues. CLDN6 is able to activate multiple signaling pathways, which take part in the development and progression of cancer, including promoting tumor growth, migration and invasion, and promoting chemoresistance in cancer. In recent years, CLDN6 has received much attention as a novel target for cancer therapeutics. Many types of anticancer drugs targeting CLDN6 have been developed, including antibody-conjugated drugs (ADC), monoclonal antibodies, bispecific antibodies, and chimeric antigen receptor T-cell immunotherapy (CAR-T). This paper briefly summarizes the structure, expression and function of CLDN6 in tumors, and reviews the current status and ideas of developing targeted CLDN6 anticancer drugs.

The Prognostic Value and the Oncogenic and Immunological Roles of Vacuolar Protein Sorting Associated Protein 26 A in Pancreatic Adenocarcinoma.

The identification of the prognostic markers and therapeutic targets might benefit the diagnosis and treatment of pancreatic adenocarcinoma (PAAD), one of the most aggressive malignancies. Vacuolar protein sorting associated protein 26 A (VPS26A) is a candidate prognosis gene for hepatocellular carcinoma, but its expression and function in PAAD remain unknown. The mRNA and protein expression of VPS26A in PAAD was explored and validated by bioinformatics and immunohistochemical analysis. The correlation between VPS26A expression and various clinical parameters, genetic status, diagnostic and prognostic value, survival and immune infiltration were evaluated, and the co-expressed gene-set enrichment analysis for VPS26A was performed. Cytologic and molecular experiments were further carried out to investigate the role and potential mechanism of VPS26A in PAAD. The mRNA and protein levels of VPS26A were elevated in PAAD tissues. High VPS26A expression was associated with the advanced histological type, tumor stage simplified, smoking status and tumor mutational burden score, and the poor prognosis of PAAD patients. VPS26A expression was significantly correlated with immune infiltration and immunotherapy response. VPS26A-co-expressed genes were mainly enriched in the regulation of cell adhesion and actin cytoskeleton and the immune-response-regulating signaling pathway. Our experiments further demonstrated that VPS26A promoted the proliferation, migration and invasion potentials of PAAD cell lines through activating the EGFR/ERK signaling. Our study suggested that VPS26A could be a potential biomarker and a therapeutic target for PAAD through comprehensive regulation of its growth, migration and immune microenvironment.

Analysis of the first measurement of CD4+T lymphocyte cell counts of newly reported HIV/AIDS cases in Taizhou City from 2012 to 2021 / 预防医学

Objective@#To investigate the level and timeliness of CD4+T lymphocyte cell (CD4 cell) counts at first measurement among newly reported HIV/AIDS cases in Taizhou City, Zhejiang Province from 2012 to 2021, so as to provide insights into improving the management of HIV/AIDS cases. @*Methods@#Demographic data and first measurement of CD4 cell counts of newly reported HIV/AIDS cases in Taizhou City from 2012 to 2021 were collected from the HIV/AIDS Comprehensive Control System of Chinese Disease Prevention and Control Information System. The level and time of CD4 cell counts at first measurement were descriptively analyzed, and factors affecting CD4 cell counts at first measurement were identified using a multivariable logistic regression model. @*Results@#A total of 4 834 newly reported HIV/AIDS cases were recorded in Taizhou City from 2012 to 2021, including 3 889 men (80.45%), 2 005 cases at ages of 20 to 39 years (41.48%), and 2 130 farmers (44.06%). There were 1 664 cases (34.42%) with CD4 cell counts of <200/mm3 at first detection, 2 576 (53.29%) with CD4 cell counts of 200/mm3 to 499/mm3, and 594 (12.29%) with CD4 cell counts of ≥500/mm3. The proportion of CD4 cell counts of <200/mm3 showed a tendency towards a rise from 2012 to 2021 (χ2trend =4.250, P<0.001). There were 3 465 cases (71.68%) that had an interval of ≤14 days between the first detection of CD4 cell counts and confirmatory HIV test, 740 (15.31%) that had an interval of >14 to 30 days, 315 (6.52%) that had an interval of >30 to 90 days, 135 (2.79%) that had an interval of >90 to 180 days, and 179 (3.70%) that had an interval of >180 days. The proportion of an interval of ≤14 days appeared a tendency towards a rise from 2012 to 2021 (χ2trend=6.874, P<0.001). Multivariable logistic regression analysis identified women (OR=0.630, 95%CI: 0.529-0.751), age of ≥20 years (OR: 1.958 to 3.218, 95%CI: 1.216-5.412), other or unknown routes of HIV infection (OR=1.785, 95%CI: 1.100-2.896), and identification by medical institutions (OR=1.779, 95%CI: 1.497-2.114) as factors affecting CD4 cell counts of <200/mm3 at first measurement. @*Conclusions@#The timely detection of CD4 cell counts at first measurement gradually increased with year among newly reported HIV/AIDS cases in Taizhou City from 2012 to 2021; however, there were still 34.42% of cases with CD4 cell counts of <200/mm3. Gender, age, route of HIV infection, and sample source were factors affecting CD4 cell counts of <200/mm3 at first measurement.

Simultaneous detection of 9 respiratory pathogens using a newly developed multiplex real-time PCR panel based on an automatic molecular detection and analysis system.

Timely identification of respiratory pathogens guides specific treatment, reduces hospital costs and minimizes the excessive use of antibiotics. A new multiplex real-time PCR panel was developed based on an automatic molecular detection and analysis system (AutoMolec system), consisting of three separate internally controlled assays. Mycoplasma pneumoniae, Chlamydia pneumoniae, adenovirus, human metapneumovirus, influenza B virus, respiratory syncytial virus and human parainfluenza virus 1-3 may be directly detected in original samples. The system's clinical performance was evaluated by comparison with an approved commercial kit, using 517 clinical samples. The limit of detection of the AutoMolec mRT-PCR panel ranged from 4 × 10-4 ∼3.3 TCID50/mL and no cross-reaction with common respiratory pathogens was observed. The AutoMolec mRT-PCR panel had 99.09% sensitivity and 100.0% specificity and overall detection consistency was 99.61%, making it comparable to that of the commercial kit. Therefore, the AutoMolec mRT-PCR panel has great potential for routine screening of respiratory infection in China.

Reference intervals of 14 biochemical markers for children and adolescence in China: the PRINCE study.

OBJECTIVES: The Pediatric Reference Intervals in China (PRINCE) was initiated to establish the reference intervals (RIs) of Chinese children, as well as to make it possible to compare the variability of biochemical markers among countries internationally. METHODS: Healthy participants, aged up to 20 years, from 11 provinces across China, were enrolled in PRINCE and according to a standard screening procedure, that included a questionnaire survey, physical examinations and laboratory tests. Fasting venous blood specimens were collected. All serum specimens were analyzed with Cobas C702 in the center laboratory, i.e. clinical laboratory of Beijing Children's Hospital, with certified qualification (ISO15189). The nonparametric method recommended by Clinical Laboratory Standards Institute guidelines, was used to calculate the age- and sex-specified RIs. RESULTS: Among the 15,150 participants enrolled, 12,352 children (6,093 males and 6,259 females) were included to calculate RIs. The RIs for total protein, albumin, globulin, calcium, phosphate, potassium, sodium, chlorine, alkaline phosphatase, γ-glutamyl transpeptadase, alanine aminotransferase, aspartate aminotransferase, creatinine and urea were established by age- or sex-partitions. Most biochemical markers displayed larger variability and higher dispersion during the periods between 28 days and 1 year old, and included 4-6 age partitions commonly during 1 to <20 years old. In addition, differences of RIs between sexes usually occurs around the initiation of puberty at 12-13 years old. CONCLUSIONS: The age- and sex-specified RIs of 14 biochemical markers in PRINCE study can provide a solid reference, which will be transferred into relevant RIs for other clinical laboratory's platforms according to the CLSI guidelines.

Recent advances on synthesis and biological activities of C-17 aza-heterocycle derived steroids.

Steroids modification for improving their biological activities is one of the most efficient and fruitful methods to develop novel medicines. Steroids with aza-heterocycles attaching to the C-17 owing various biological activities have received great attentions and some of the compounds are developed successfully as drugs. In this review, the research of the syntheses and biological activities of steroids bearing various aza-heterocycles published in the last 8 years is assembled, and some important structure-activity relationships (SARs) of active compounds are presented. According to the analysis of the literatures and our experiences in this field, the potential of aza-heterocyclic steroids as medicinal drugs is proposed.

Age and sex specific reference intervals of 13 hematological analytes in Chinese children and adolescents aged from 28 days up to 20 years: the PRINCE study.

OBJECTIVES: Pediatric Reference Intervals in China (PRINCE) is a nationwide initiative that aims to establish and validate harmonized reference intervals (RIs) for Chinese children and adolescents, in which 15,150 healthy volunteers aged up to 20 years were recruited from 11 centers to establish RIs and 7,557 children and adolescents were enrolled from 21 centers to validate RIs. METHODS: The complete blood cell counts (CBC) of venous whole blood were measured by hematology analyzers through Sysmex systems in different centers. Age- and sex-specific RIs were calculated according to the guidelines. RESULTS: Unlike adults with certain levels of analyte concentrations, hematological parameters of children changed through growth and development. Red blood cell counts, hemoglobin, and hematocrit increased with age, and revealed higher concentrations in boys than girls after puberty. White blood cell counts and platelet counts showed significant higher levels than adults before 2 years of age, and then gradually decreased without distinct sex differences. In addition, lymphocyte counts decreased with age while neutrophil counts showed an opposite trend. The lower and upper limits of pediatric RIs of CBC were different from those of adults. CONCLUSIONS: The validation of RIs indicated that the PRINCE study provided a version of RIs suitable for most of regions in China. This first harmonized pediatric RIs of CBC across China provided a robust database to understand the dynamic changes of hematologic parameters from birth to adolescence, and will contribute to clinical diagnosis and prognosis evaluation for pediatric patients as well.

Establishment and evaluation of a quadruple quantitative real-time PCR assay for simultaneous detection of human coronavirus subtypes.

BACKGROUND: The newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and four seasonal human coronaviruses (HCoVs) (HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1) still circulate worldwide. The early clinical symptoms of SARS-CoV-2 and seasonal HCoV infections are similar, so rapid and accurate identification of the subtypes of HCoVs is crucial for early diagnosis, early treatment, prevention and control of these infections. However, current multiplex molecular diagnostic techniques for HCoV subtypes including SARS-CoV-2 are limited. METHODS: We designed primers and probes specific for the S and N genes of SARS-CoV-2, the N gene of severe acute respiratory syndrome coronavirus (SARS-CoV), and the ORF1ab gene of four seasonal HCoVs, as well as the human B2M gene product. We developed and optimized a quadruple quantitative real-time PCR assay (qq-PCR) for simultaneous detection of SARS-CoV-2, SARS-CoV and four seasonal HCoVs. This assay was further tested for specificity and sensitivity, and validated using 184 clinical samples. RESULTS: The limit of detection of the qq-PCR assay was in the range 2.5 × 101 to 6.5 × 101 copies/µL for each gene and no cross-reactivity with other common respiratory viruses was observed. The intra-assay and inter-assay coefficients of variation were 0.5-2%. The qq-PCR assay had a 91.9% sensitivity and 100.0% specificity for SARS-CoV-2 and a 95.7% sensitivity and 100% specificity for seasonal HCoVs, using the approved commercial kits as the reference. Compared to the commercial kits, total detection consistency was 98.4% (181/184) for SARS-CoV-2 and 98.6% (142/144) for seasonal HCoVs. CONCLUSION: With the advantages of sensitivity, specificity, rapid detection, cost-effectiveness, and convenience, this qq-PCR assay has potential for clinical use for rapid discrimination between SARS-CoV-2, SARS-CoV and seasonal HCoVs.

Genome-wide DNA methylation profiles of autism spectrum disorder.

OBJECTIVES: We aimed to identify differentially methylated genes and related signaling pathways in autism spectrum disorder (ASD). METHODS: First, the DNA methylation profile in the brain samples (GSE131706 and GSE80017) and peripheral blood samples (GSE109905) was downloaded from the Gene Expression Omnibus database (GEO) dataset, followed by identification of differentially methylated genes and functional analysis. Second, the GSE109905 data set was used to further validate the methylation state and test the ability to diagnose disease of identified differentially methylated genes. Third, expression measurement of selected differentially methylated genes was performed in whole blood from an independent sample. Finally, protein-protein interaction (PPI) network of core differentially methylated genes was constructed. RESULTS: Totally, 74 differentially methylated genes were identified in ASD, including 38 hypermethylated genes and 36 hypomethylated genes. 15 differentially methylated genes were further identified after validation in the GSE109905 data set. Among these, major histocompatibility complex (HLA)-DQA1 was involved in the molecular function of myosin heavy chain class II receptor activity; HLA-DRB5 was involved in the signaling pathways of cell adhesion molecules, Epstein-Barr virus infection and antigen processing and presentation. In the PPI analysis, the interaction pairs of HLA-DQA1 and HLA-DRB5, FMN2 and ACTR3, and CALCOCO2 and BAZ2B were identified. Interestingly, FMN2, BAZ2B, HLA-DRB5, CALCOCO2 and DUSP22 had a potential diagnostic value for patients with ASD. The expression result of four differentially methylated genes (HLA-DRB5, NTM, IL16 and COL5A3) in the independent sample was consistent with the integrated analysis. CONCLUSIONS: Identified differentially methylated genes and enriched signaling pathway could be associated with ASD.

Identification of Differentially Expressed Genes Particularly Associated with Immunity in Uremia Patients by Bioinformatic Analysis.

Uremia is a common syndrome that happens to nearly all end-stage kidney diseases, which profound have changes in human gene expressions, but the related pathways are poorly understood. Gene Ontology categories and Kyoto Encyclopedia of Genes and Genomes pathways enriched in the differentially expressed genes (DEGs) were analyzed by using clusterProfiler, org.Hs.eg.db, and Pathview, and protein-protein interaction (PPI) network was built by Cytoscape. We identified 3432 DEGs (including 3368 down- and 64 up-regulated genes), of which there were 52 different molecular functions, and 178 genes were identified as immune genes controlled by the four transcription factors (POU domain class 6 transcription factor 1 (POU6F1), interferon regulator factor 7 [IRF7], forkhead box D3 (FOXD3), and interferon-stimulated response element [ISRE]). In the gender research, no significant difference was observed. The top 15 proteins of 178 immune-related genes were identified with the highest degree in PPI network. The DEG analysis of uremia patients was expected to provide fundamental information to relieve pain and add years to their life.

Genome-wide analysis and characterization of GRAS family in switchgrass.

Panicum virgatum, a model plant of cellulosic ethanol conversion, not only has high large biomass and strong adaptability to soil, but also grows well in marginal soil and has the advantage of improving saline-alkali soil. GRAS transcription factor gene family play important roles in individual environment adaption, and these vital functions has been proved in several plants, however, the research of GRAS in the development of switchgrass (Panicum virgatum) were limited. A comprehensive study was investigated to explore the relationship between GRAS gene family and resistance. According to the phylogenetic analysis, a total of 144 GRAS genes were identified and renamed which were classified into eight subfamilies. Chromosome distribution, tandem and segmental repeats analysis indicated that gene duplication events contributed a lot to the expansion of GRAS genes in the switchgrass genome. Sixty-six GRAS genes in switchgrass were identified as having orthologous genes with rice through gene duplication analysis. Most of these GRAS genes contained zero or one intron, and closely related genes in evolution shared similar motif composition. Interaction networks were analyzed including DELLA and ten interaction proteins that were primarily involved in gibberellin acid mediated signaling. Notably, online analysis indicated that the promoter regions of the identified PvGRAS genes contained many cis-elements including light responsive elements, suggesting that PvGRAS might involve in light signal cross-talking. This work provides key insights into resistance and bioavailability in switchgrass and would be helpful to further study the function of GRAS and GRAS-mediated signal transduction pathways.

Systematic Investigation of the Effect of Powerful Tianma Eucommia Capsule on Ischemic Stroke Using Network Pharmacology.

BACKGROUND: Ischemic stroke (IS) is a serious disease with a high rate of death and disability, and a growing number of people are becoming victims. Existing drugs not only have limited therapeutic effects but also have obvious side effects. Most importantly, drug resistance due to long-term or improper use of drugs is detrimental to patients. Therefore, it is urgent to find some alternative or supplementary medicines to alleviate the current embarrassment. Powerful Tianma Eucommia Capsule (PTEC) is mainly used to treat IS in China for thousands of years; however, the molecular mechanism is not clear. METHODS: Pharmacology ingredients and target genes were filtered and downloaded from websites. A pharmacology ingredient-target gene network was constructed to predict the molecular interactions between ingredients and target genes. Enrichment analysis was performed to explore the possible signal pathways. LeDock was used to simulate the interaction form between proteins and main active ingredients and to deduce key amino acid positions. RESULTS: Two hundred eighty-nine target genes and seventy-four pharmacological ingredients were obtained from public databases. Several key ingredients (quercetin, kaempferol, and stigmasterol) and primary core target genes (PTGS1, NCOA2, and PRSS1) were detected through ingredient-target gene network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis demonstrated that ingredients affect networks mainly in nuclear receptor activity and G protein-coupled amine receptor activity; besides, fluid shear stress and atherosclerosis, human cytomegalovirus infection, and hepatitis B signaling pathways might be the principal therapy ways. A series of presumed key amino acid sites (189ASP, 190SER, 192GLN, 57HIS, and 99TYE) were calculated in PRSS1. Six of the target genes were differentially expressed between male and female patients. CONCLUSIONS: Seven new putative target genes (ACHE, ADRA1A, AR, CHRM3, F7, GABRA1, and PRSS1) were observed in this work. Based on the result of GO and KEGG analysis, this work will be helpful to further demonstrate the molecular mechanism of PTEC treatment of IS.

Identification of a 14-Gene Prognostic Signature for Diffuse Large B Cell Lymphoma (DLBCL).

Although immunotherapy is a potential strategy to resist cancers, due to the inadequate acknowledge, this treatment is not always effective for diffuse large B cell lymphoma (DLBCL) patients. Based on the current situation, it is critical to systematically investigate the immune pattern. According to the result of univariate and multivariate cox proportional hazards, LASSO regression and Kaplan-Meier survival analysis on immune-related genes (IRGs), a prognostic signature, containing 14 IRGs (AQP9, LMBR1L, FGF20, TANK, CRP, ORM1, JAK1, BACH2, MTCP1, IFITM1, TNFSF10, FGF12, RFX5, and LAP3), was built. This model was validated by external data, and performed well. DLBCL patients were divided into low- and high-risk groups, according to risk scores from risk formula. The results of CIBERSORT showed that different immune status and infiltration pattern were observed in these two groups. Gene set enrichment analysis (GSEA) indicated 12 signaling pathways were significantly enriched in the high-risk group, such as natural killer cell-mediated cytotoxicity, toll-like receptor signaling pathway, and so on. In summary, 14 clinically significant IRGs were screened to build a risk score formula. This formula was an accurate tool to provide a certain basis for the treatment of DLBCL patients.

miR-874 directly targets AQP3 to inhibit cell proliferation, mobility and EMT in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a major type of lung cancer with high morbidity and high mortality. miR-874 has been determined to play a role in tumor suppression in several cancers. The purpose of our study was to detect the biological mechanisms of miR-874 and AQP3 in NSCLC. METHODS: CCK-8 and Transwell assays were utilized to perform cell invasion.Western blot was employed to evaluate the protein expression. RESULTS: The expression of miR-874 was lower in NSCLC tissues than that of corresponding adjacent nontumor tissues. Downregulation of miR-874 predicted a poor prognosis in NSCLC. The cell proliferation and mobility were suppressed by overexpression of miR-874, which were promoted by knockdown of miR-874 in A549 and H1299 cells. miR-874 mediated the expression of AQP3 by directly binding to the 3'-untranslated regions (UTR) of AQP3 mRNA in NSCLC cells. Moreover, miR-874 inhibited the proliferation and mobility by targeting AQP3 and inhibited the PI3K/AKT signaling pathway in A549 cells. miR-874 inhibited the growth of NSCLC in vivo. CONCLUSIONS: In conclusion, miR-874 inhibited proliferation and mobility by regulating AQP3 in NSCLC. The newly identified miR-874/AQP3 axis provides novel insight into the pathogenesis of NSCLC.

Zao Ren An Shen for insomnia: a systematic review with meta-analysis.

OBJECTIVE: To assess the effectiveness and safety of Zao Ren An Shen (ZRAS), a Chinese herbal medicine formula, for the treatment of insomnia. METHODS: Seven databases (ie, EMBASE, PubMed, the Cochrane library, and PsycINFO, Chinese National Knowledge Infrastructure, Wanfang and Chongqing VIP) were searched from their inception to 6 November 2018. Controlled trials comparing the effectiveness or safety of ZRAS to conventional treatments, a placebo or no-treatment in an insomnia population were selected. Primary outcomes were: sleep quality (assessed with the Pittsburgh Sleep Quality Index, PSQI), and the number of adverse events at post-treatment. The risk of bias was assessed with the Cochrane Collaboration's tool and meta-analyses were performed using RevMan 5.3. RESULTS: A total of 19 studies (1780 participants) were included. The effect of ZRAS on sleep quality (mean difference) was found to be superior compared to placebo in the sole placebo-controlled study located [-0.90 (-1.56, -0.24; 95% CI), p = 0.007] and similar to Benzodiazepine Receptor Agonists (BzRAs) [0.17 (-0.29, 0.64); 95% CI, p = 0.46]. The number of adverse events (relative risk) was lower for ZRAS than BzRAs [0.16 (0.12, 0.23; 95% CI), p < 0.001]. An overall high risk of bias was found in the selected studies. CONCLUSIONS: The results favor ZRAS against BzRAs and placebo for the treatment of insomnia. However, the poor methodology of the studies prevents strong recommendations for ZRAS. Clinical trials with higher quality designs are required.