Objective To systematically review the incidence of antibiotic-associated diarrhea(AAD)in critically ill patients in China,and to provide evidence-based basis for the rational use of antibiotics.Methods PubMed,Embase,Web of Science,Cochrane Library,CNKI,WanFang Data,VIP and SionMed databases were electronically searched to collect studies on the incidence of AAD in acute and critically ill patients in China from inception to April 23,2024.Two reviewers independently screened literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was then performed using Stata 17.0 software.Results A total of 50 studies involving 26,512 subjects were included.Meta-analysis results showed that the incidence of AAD in critically ill patients in China was 26.5%[95%CI(22.9%,30.1%)].Subgroup analysis showed that the incidence of AAD in critically ill children in China was 40.6%[95%CI(30.7%,50.4%)],and in critically ill adults in China was 18.7%[95%CI(16.1%,21.4%)],among which the incidence of AAD in children in East China and adults in Southwest China was the lowest.The incidence of AAD in children and adults in Northeast China was the highest.Conclusion The incidence of AAD in critically ill patients in China is relatively high,and it is necessary to carry out effective intervention measures,such as rational selection and standardized use of antibiotics,early prevention and detection of AAD occurrence,to reduce the medical burden caused by AAD in critically ill patients and improve the quality of prognosis.

Objective To systematically review the incidence of antibiotic-associated diarrhea(AAD)in critically ill patients in China,and to provide evidence-based basis for the rational use of antibiotics.Methods PubMed,Embase,Web of Science,Cochrane Library,CNKI,WanFang Data,VIP and SionMed databases were electronically searched to collect studies on the incidence of AAD in acute and critically ill patients in China from inception to April 23,2024.Two reviewers independently screened literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was then performed using Stata 17.0 software.Results A total of 50 studies involving 26,512 subjects were included.Meta-analysis results showed that the incidence of AAD in critically ill patients in China was 26.5%[95%CI(22.9%,30.1%)].Subgroup analysis showed that the incidence of AAD in critically ill children in China was 40.6%[95%CI(30.7%,50.4%)],and in critically ill adults in China was 18.7%[95%CI(16.1%,21.4%)],among which the incidence of AAD in children in East China and adults in Southwest China was the lowest.The incidence of AAD in children and adults in Northeast China was the highest.Conclusion The incidence of AAD in critically ill patients in China is relatively high,and it is necessary to carry out effective intervention measures,such as rational selection and standardized use of antibiotics,early prevention and detection of AAD occurrence,to reduce the medical burden caused by AAD in critically ill patients and improve the quality of prognosis.

Objective:To explore the role of long non-coding RNA (LncRNA) AC000061.1 involved in the pathogenesis of nonobstructive azoospermia (NOA) by regulating the CFTR gene expression. Methods:Bioinformatics analysis was conducted with the use of gene microarray to screen the differentially expressed LncRNAs and corresponding mRNAs in the testicular tissue of patients in three groups including obstructive azoospermia (OA) group ( n=50), NOA group ( n=50), and control group ( n=50). The expression of apoptosis-related gene Bcl-2 in the testicular tissue of patients in these three groups was detected by qRT-PCR and Western blotting. Additionally, qRT-PCR was performed to determine the expression of LncRNA AC000061.1 and CFTR mRNA in the testicular tissue, serum, and seminal plasma of patients in the three groups, and enzyme-linked immunosorbent assay (ELISA) was conducted to detect the CFTR protein level in the serum and seminal plasma. LncRNA AC000061.1 overexpression (H-LncRNA group) and silencing vectors (Si-LncRNA group) and empty vectors were constructed and transfected into the testicular cancer cell line NTERA-2. Subsequently, the expression of LncRNA AC000061.1 and CFTR mRNA was determined by qRT-PCR, and CFTR protein expression was measured by Western blotting assay. Cell proliferation was assessed using CCK-8 and cell apoptosis was evaluated by flow cytometry and TUNEL. Results:Microarray analysis and qRT-PCR showed that the expression of LncRNA AC006100.1 and CFTR decreased in NOA group compared with control group ( P=0.033 and P=0.042). But there was no difference in the expression of LncRNA AC000061.1 between OA group and control group, while CFTR in OA group was lowly expressed compared with that in control group ( P=0.039). Bcl-2 expression was sequentially upregulated in OA and NOA groups relative to normal control group ( P=0.031 and P=0.008). No significant difference was noted in the serum levels of LncRNA AC000061.1 and CFTR mRNA and protein among the three groups ( P>0.05). The results also showed sequentially decreased levels of LncRNA AC000061.1 and CFTR mRNA and protein in seminal plasma in NOA and OA groups when compared with control group ( P=0.002, P=0.038 and P=0.006, P=0.026) and a positive correlation of LncRNA AC000061.1 expression with CFTR mRNA expression ( r=0.169, P=0.039). LncRNA AC000061.1 and CFTR mRNA and protein expression decreased in Si-LncRNA group ( P=0.005, P=0.003), but significantly increased in H-LncRNA group ( P=0.002, P=0.009). Furthermore, cell proliferation was significantly repressed while apoptosis rate was elevated in Si-LncRNA group ( P=0.003 and P=0.001). On the contrary, enhanced cell proliferation and inhibited apoptosis were observed in H-LncRNA group ( P=0.017 and P=0.017). Conclusion:LncRNA AC00006.1 in the testicular tissue of NOA patients induced abnormal cell proliferation and apoptosis via mediating CFTR gene expression, thereby participating in the pathogenesis of NOA.

Objective:To explore the role of long non-coding RNA (LncRNA) AC000061.1 involved in the pathogenesis of nonobstructive azoospermia (NOA) by regulating the CFTR gene expression. Methods:Bioinformatics analysis was conducted with the use of gene microarray to screen the differentially expressed LncRNAs and corresponding mRNAs in the testicular tissue of patients in three groups including obstructive azoospermia (OA) group ( n=50), NOA group ( n=50), and control group ( n=50). The expression of apoptosis-related gene Bcl-2 in the testicular tissue of patients in these three groups was detected by qRT-PCR and Western blotting. Additionally, qRT-PCR was performed to determine the expression of LncRNA AC000061.1 and CFTR mRNA in the testicular tissue, serum, and seminal plasma of patients in the three groups, and enzyme-linked immunosorbent assay (ELISA) was conducted to detect the CFTR protein level in the serum and seminal plasma. LncRNA AC000061.1 overexpression (H-LncRNA group) and silencing vectors (Si-LncRNA group) and empty vectors were constructed and transfected into the testicular cancer cell line NTERA-2. Subsequently, the expression of LncRNA AC000061.1 and CFTR mRNA was determined by qRT-PCR, and CFTR protein expression was measured by Western blotting assay. Cell proliferation was assessed using CCK-8 and cell apoptosis was evaluated by flow cytometry and TUNEL. Results:Microarray analysis and qRT-PCR showed that the expression of LncRNA AC006100.1 and CFTR decreased in NOA group compared with control group ( P=0.033 and P=0.042). But there was no difference in the expression of LncRNA AC000061.1 between OA group and control group, while CFTR in OA group was lowly expressed compared with that in control group ( P=0.039). Bcl-2 expression was sequentially upregulated in OA and NOA groups relative to normal control group ( P=0.031 and P=0.008). No significant difference was noted in the serum levels of LncRNA AC000061.1 and CFTR mRNA and protein among the three groups ( P>0.05). The results also showed sequentially decreased levels of LncRNA AC000061.1 and CFTR mRNA and protein in seminal plasma in NOA and OA groups when compared with control group ( P=0.002, P=0.038 and P=0.006, P=0.026) and a positive correlation of LncRNA AC000061.1 expression with CFTR mRNA expression ( r=0.169, P=0.039). LncRNA AC000061.1 and CFTR mRNA and protein expression decreased in Si-LncRNA group ( P=0.005, P=0.003), but significantly increased in H-LncRNA group ( P=0.002, P=0.009). Furthermore, cell proliferation was significantly repressed while apoptosis rate was elevated in Si-LncRNA group ( P=0.003 and P=0.001). On the contrary, enhanced cell proliferation and inhibited apoptosis were observed in H-LncRNA group ( P=0.017 and P=0.017). Conclusion:LncRNA AC00006.1 in the testicular tissue of NOA patients induced abnormal cell proliferation and apoptosis via mediating CFTR gene expression, thereby participating in the pathogenesis of NOA.

Objective: To explore the genetic basis for a pedigree affected with Marfan syndrome (MFS). Methods: Clinical data of the patients was collected.With genomic DNA extracted from peripheral blood samples, potential mutation was detected by targeted exome sequencing.Candidate variants were validated by Sanger sequencing and bioinformatic analysis. Results: Targeted exome sequencing and Sanger sequencing revealed a missense c. 649T>C(p.Trp217Arg) variant in the exon 7 of FBN1 gene, which was unreported previously.Bioinformatics analysis suggested that the variant can cause amino acid replacement and affect the structure and function of fibrillin-1. Conclusion A novel missense variant of the FBN1 gene was identified, which probably underlies the autosomal dominant MFS in this pedigree.

Objective: To investigate the expression and clinical significance of circDLGAP4 from peripheral blood in coronary heart disease (CAD). Methods: The relative expression level of circDLGAP4 in peripheral blood leukocytes (PBLs) from 142 CAD patients and 169 healthy controls were detected by real-time PCR. Logistic regression, Spearman correlation and multivariate regression analysis were used to investigate the correlation of circDLGAP4 with CAD. THP-1 macrophages were treated with oxidized low density lipoprotein (ox-LDL) to construct an atherosclerotic foam cell model. The levels of circDLGAP4 mRNA were detected at different time points. Results: The mRNA expression of circDLGAP4 in PBLs of CAD patients was significantly decreased compared with controls (P=0.019). With increased unit (2 -ΔCt ) of circDLGAP4 expression, the risk of CAD occurrence reduced by 41.6% (adjusted OR=0.584, 95% CI: 0.394-0.866, P=0.007). The expression of circDLGAP4 was negatively correlated with T2DM history (β=-0.182，P=0.030). The level of circDLGAP4 in ox-LDL-treated THP-1 macrophages was decreased in a time-dependent manner. Conclusion The expression of circDLGAP4 was significantly decreased in PBLs of CAD patients and THP-1 macrophages-derived foam cells, and might be a protective factor in the pathophysiology of CAD.

Objective: To explore the relationship between HCM pathogenic gene mutations and clinical phenotypes by analyzing the prenatal diagnosis and genetic characteristics of a pregnant woman from a family with hypertrophic cardiomyopathy (HCM). Methods: The clinical data of the proband and her family members was collected. The DNA was extracted from the peripheral blood, amniotic fluid cells and cultured amniotic fluid cells of proband. Next generation sequencing (NGS) was utilized for screening pathogenetic loci of the proband. The suspected mutation sequences of HCM pathogenic candidate genes MYH7 and MYBPC3 were directly sequenced after PCR. Pathogenicity prediction of amniotic fluid cells was performed by using genetic data and bioinformatics software, such as Mutation taster, PolyPhen-2 and ANTHEPROT. Results: The sequencing results showed that heterozygous mutations of MYH7 c.1988G＞A (p.Arg663His) and MYBPC3 c.151G＞A (p.Ala51Thr) were found in the proband. The phenotype of her father was normal, and no abnormal mutations were detectable. Her mother also showed normal phenotype but carried MYBPC3 c.151G＞A heterozygous mutation. Only MYH7 c.1988G＞A heterozygous mutation was found in the fetus and no abnormal variation of MYBPC3 was showed. The prediction of mutation effect and analysis of protein structure and function revealed that the two missense mutations could affect the hydrophobicity and antigenicity of the protein. The genetic data demonstrated MYH7 c.1988G＞A was defined as a pathogenic mutation. Conclusion MYH7 c.1988G＞A should be a newly generated pathogenic mutation in the proband, or caused by reproductive chimerism of her parents. MYBPC3 c.151G＞A mutation may promote the occurrence of HCM. Although the fetus only carries MYH7 c.1988G＞A, her phenotype may still display as HCM.