Mutations within the Shank3 gene, which encodes a key postsynaptic density (PSD) protein at glutamatergic synapses, contribute to the genetic etiology of defined autism spectrum disorders (ASDs), including Phelan-McDermid syndrome (PMS) and intellectual disabilities (ID). Although there are a series of genetic mouse models to study Shank3 gene in ASDs, there are few rat models with species-specific advantages. In this study, we established and characterized a novel rat model with a deletion spanning exons 11–21 of Shank3 , leading to a complete loss of the major SHANK3 isoforms. Synaptic function and plasticity of Shank3 -deficient rats were impaired detected by biochemical and electrophysiological analyses. Shank3 -depleted rats showed impaired social memory but not impaired social interaction behaviors. In addition, impaired learning and memory, increased anxiety-like behavior, increased mechanical pain threshold and decreased thermal sensation were observed in Shank3 -deficient rats. It is worth to note that Shank3 -deficient rats had nearly normal levels of the endogenous social neurohormones oxytocin (OXT) and arginine-vasopressin (AVP). This new rat model will help to further investigate the etiology and assess potential therapeutic target and strategy for Shank3 -related neurodevelopmental disorders.

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Background Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide and is characterized by a partially reversible airflow limitation. Currently, many studies put forward that COPD is associated with both genetic and environmental factors. It has been reported that germline mutations in telomerase are risk factors for COPD susceptibility. In this study, we validated the association between TERT polymorphisms and COPD risk with a case–control study in the Chinese Li population. Methods A total of 279 COPD patients and 290 control individuals were recruited. We identified five single nucleotide polymorphisms (SNPs) in TERT that were associated with COPD. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in logistic regression models after adjusting for age and gender to assess the association. Results In the genetic model analysis, we found the “C/T‐T/T” genotype of rs10069690 in TERT was associated with an increased COPD risk in the dominant model (p = 0.046); the rs2853677 in TERT was significantly associated with increased COPD risk based on the codominant model (“A/G” genotype, p = 0.033), dominant model (A/G‐G/G genotype, p = 0.0091), and log‐additive model (p = 0.023). The rs2853676 in TERT could increase the risk of COPD in the dominant model (“C/T‐T/T” genotype, p = 0.026) and in the Log‐additive model (p = 0.022). Conclusion Our data shed new light on the association between TERT SNPs and COPD susceptibility in the Chinese Li population.

Objectives: To investigate the association between dectin-1 gene single nucleotide polymorphisms (SNPs) and susceptibility to fungal infection (FI). Methods: Databases were searched electronically and manually to identify case–control studies concerning dectin-1 SNPs and FI, which were published up to 12 November 2018. The Newcastle–Ottawa Quality Assessment Scale was used to determine the study quality and bias. The SNP frequencies of the B (the variant or minor allele) and A (the wild or major allele) alleles of the dectin-1 gene in both cases and controls were analyzed with regard to FI susceptibility. Results: Eight high-quality studies were included in the review. Systemic review of the included studies demonstrated that dectin-1 SNPs rs3901533 and rs7309123 might be associated with susceptibility to invasive pulmonary aspergillosis infection; moreover, rs16910527 SNP can possibly increase the susceptibility to oropharyngeal candidiasis in HIV-positive patients. The meta-analysis identified significant associations between dectin-1 SNPs and overall FI risk in the homozygote model (pooled odds ratio (OR) 1.77, P=0.04). When classified by subtypes, significant associations were also found for deep FI in the homozygote model (pooled OR 2.46, P=0.01) and the recessive model (pooled OR 2.85, P=0.002). There appeared to be no significant association between dectin-1 SNPs and superficial FI. Conclusion: Systemic review of the included studies suggested that dectin-1 SNPs rs3901533, rs7309123, and rs16910527 might play a role in FI susceptibility. The meta-analysis provided convincing evidence that dectin-1 SNPs might have an important role in FI susceptibility, especially for deep FI.

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Background: Radiotherapy and chemotherapy-induced oral mucositis can affect cancer patients’ quality of life, even necessitate cancer therapy and influence prognosis. Chinese patent medicines (CPMs) have been widely used as complementary alternative medicines for the prevention and treatment of oral mucositis, and their efficacy and safety require further evaluation. Therefore, this study was conducted to provide references for clinical practice.Methods: Ten databases were searched electronically and manually to identify randomized controlled trials (RCTs) from their inception to August 2021, concerning the prevention and treatment of radiotherapy and chemotherapy-induced oral mucositis with CPMs. The prevalence, pain level, and the severity of radiotherapy and chemotherapy-induced oral mucositis, as well as the effectiveness rate and adverse effects of CPMs, were set as the outcome criteria. The assessment criteria of the Cochrane Handbook were used to determine study quality and bias, and meta-analysis was conducted using Review Manager 5.4.1 software.Results: A total of 2,312 cases from 27 RCTs were included. Most studies were considered to have a low or unclear risk of bias. More research is available on the use of CPMs in the prevention of radiotherapy and chemotherapy-induced oral mucositis than in its treatment. As for the prevention, it was proved that CPMs could significantly reduce the prevalence of radiotherapy and chemotherapy-induced oral mucositis, especially for the severe types, and decrease pain levels (p < 0.05). For treatment, CPMs could alleviate the symptoms, promote the healing of ulceration in radiotherapy and chemotherapy-induced oral mucositis, and thus improve the efficiency of clinical treatment (p < 0.05). The results of subgroup analyses were mainly consistent with the above results. The adverse effects of CPMs mainly included gastrointestinal reactions and bitter taste, and no serious adverse events were reported.Conclusions: This systematic review and meta-analysis indicated CPMs might be effective for the prevention and treatment of radiotherapy and chemotherapy-induced oral mucositis through reducing the prevalence, decreasing the occurrence of severe types, alleviating the symptoms, and promoting the healing of ulceration. However, due to the limited number of eligible studies and the publication bias, more high-quality, double-blinded, placebo-controlled RCTs are still needed in future research.Systematic Review Registration: [https://inplasy.com/], identifier [INPLASY2021100100].

Objective Chronic obstructive pulmonary disease (COPD) is a complicated multi-factor, multi-gene disease. Here, we aimed to assess the association of genetic polymorphisms in LINC01414/ LINC00824 and interactions with COPD susceptibility. Methods Three single nucleotide polymorphisms (SNPs) in LINC01414/LINC00824 was genotyped by Agena MassARRAY platform among 315 COPD patients and 314 controls. Logistic analysis adjusted by age and gender were applied to estimate the genetic contribution of selected SNPs to COPD susceptibility. Results LINC01414 rs699467 (OR = 0.73, 95% CI 0.56–0.94, p = 0.015) and LINC00824 rs7815944 (OR = 0.56, 95% CI 0.31–0.99, p = 0.046) might be protective factors for COPD occurrence, while LINC01414 rs298207 (OR = 2.88, 95% CI 1.31–6.31, p = 0.008) risk-allele was related to the increased risk of COPD in the whole population. Rs7815944 was associated with the reduced risk of COPD in the subjects aged > 70 years (OR = 0.29, p = 0.005). Rs6994670 (OR = 0.57, p = 0.007) contribute to a reduced COPD risk, while rs298207 (OR = 7.94, p = 0.009) was related to a higher susceptibility to COPD at age ≤ 70 years. Rs298207 (OR = 2.54, p = 0.043) and rs7815944 (OR = 0.43, p = 0.028) variants was associated COPD risk among males. Rs7815944 (OR = 0.16, p = 0.031) was related to the reduced susceptibility of COPD in former smokers. Moreover, the association between rs298207 genotype and COPD patients with dyspnea was found (OR = 0.50, p = 0.016), and rs7815944 was related to COPD patients with wheezing (OR = 0.22, p = 0.008). Conclusion Our finding provided further insights into LINC01414/LINC00824 polymorphisms at risk of COPD occurrence and accumulated evidence for the genetic susceptibility of COPD.

Background Serum indicators AFP, CA50, CA125, CA153, CA19-9, CEA, f-PSA, SCC-Ag have been confirmed as tumor markers (TMs). We conducted a genome-wide association study on 8 tumor markers of our 427 Han population in southern China, in order to identify genetic loci that are significantly associated with the level of 8 tumor markers. Methods We use Gene Titan multi-channel instrument and Axiom Analysis Suite 6.0 software for genotyping. We used IMPUTE2 software for imputation, and 1000 Genomes Project (Phase 3) was used as haplotype reference. After necessary quality control and statistical analysis, genetic loci genome-wide associated with TMs (p < 5E-8) will be identified. Finally, we selected Top SNPs (p < 5E-7) from the GWAS results for replication test. We used SPSS software to draw the distribution box plots of serum TMs under different genotypes of significant loci. Results The results showed that there were only MUC1 (mucin 1)-rs4072037 significantly genome-wide associated with CA153 (p = 1.28E-18). However, we found that a total of 30 genetic loci have a suggestively significant genome-wide association with the level of 8 serum tumor markers (p < 5E-6). Then 3 Top SNPs (p < 5E-7) were selected for replication verification. The results showed that MUC1-rs4072037 was still significantly associated with CA153 in another population (p = 3.73E-08). Comparing with the TT genotype of rs4072037, the CA153 level was higher under CC or CT genotype of rs4072037. Conclusion MUC1-rs4072037 is significantly genome-wide associated with CA153 level. There are 30 genetic loci suggestively genome-wide associated with level of tumor markers among the Han population from Southern China.