As a new generation of molecular diagnostic tools emerged in recent years,the clustered regularly interspaced short palindromic repeats/CRISPR-associated(CRISPR-Cas)systems have been widely used in gene editing,nucleic acid detection,and other fields.Due to its high specificity,high sensitivity,without expensive equipment,simple operation,and inexpensive characteristics in nucleic acid detection,the Cas13a subtype has shown great potential in the field of pathogen detection.This article reviews the mechanism of action of CRISPR-Cas13a,its application in pathogen detection,and related detection methods,and looks forward to the application prospects of Cas13a.To facilitate future investigations on the CRISPR-Cas13a systems and their potential in pathogen detection,this study aims to offer inspiration and serve as a valuable reference.

Objective To observe the effects of Wuhu Decoction on autophagy and the expressions of IL-8,IL-23 and muc5ac in lung tissue of asthmatic mice induced by exosomes of bone marrow mesenchymal stem cells infected by RSV(BMSCs-Exo-RSV);To explore its mechanism in the treatment of asthma.Methods Totally 40 male SPF C57 mice were randomly divided into blank group,model group,Wuhu Decoction group and ribavirin group,with 10 mice in each group.The blank group was given PBS nasal drops,and the other groups were given BMSCs-Exo-RSV nasal drops once every other day for 7 times.24 hours after the end of modeling,Wuhu Decoction group was given Wuhu Decoction,and ribavirin group was given ribavirin solution,the blank group and model group were given distilled water,once a day,for consecutive 7 d.The general behavior of mice was observed,the peak expiratory flow(PEF)and forced vital capacity(FVC)were detected,HE and Masson staining were used to observe the inflammatory infiltration and collagen deposition in the lung tissue,RT-qPCR was used to detect the expressions of LC3A/B,beclin-1,p62,IL-8,IL-23 and muc5ac mRNA in lung tissue,Western blot was used to detect the expressions of LC3B,beclin-1 and p62 proteins in lung tissue,immunohistochemstry was used to detect the expression of IL-8,IL-23,muc5ac proteins in lung tissue.Results Compared with the blank group,the body mass of mice in the model group decreased,and showed behavioral changes such as shortness of breath,nodding wheezing,lifting of upper limbs,shrugging,vertical hair,scratching nose,etc.,the PEF and FVC were decreased(P<0.01),inflammatory infiltration and collagen deposition in lung tissue increased,the expressions of LC3A/B,beclin-1,IL-8,IL-23 and muc5ac mRNA in lung tissue increased,the expression of p62 mRNA decreased(P<0.01),while the expression of LC3BⅡ,beclin-1,IL-8,IL-23 and muc5ac proteins and the ratio of LC3BⅡ/Ⅰ increased(P<0.01),while the expression of LC3BⅠand p62 protein decreased(P<0.01).Compared with the model group,the symptoms of Wuhu Decoction group and ribavirin group were improved,the PEF and FVC were increased(P<0.01,P<0.05),the inflammatory infiltration and collagen deposition in lung tissue were reduced,the expression of LC3A/B,beclin-1,IL-8,IL-23 and muc5ac mRNA in lung tissue decreased(P<0.01),the expression of p62 mRNA increased(P<0.01),the expressions of LC3BⅡ,beclin-1,IL-8,IL-23 and muc5ac protein and the ratio of LC3BⅡ/Ⅰ decreased(P<0.05,P<0.01),while the expressions of LC3BⅠ and p62 protein increased(P<0.01).Conclusion BMSCs-Exo-RSV can promote autophagy and the expressions of IL-8,IL-23 and muc5ac in lung tissue of mice to induce asthma changes.Wuhu Decoction has therapeutic effect on asthmatic mice by inhibiting autophagy and reducing the expressions of IL-8,IL-23 and muc5ac.

Asthma is characterized by chronic airway inflammation and airway hyper-responsiveness. However, the differences in pathophysiology and phenotypic symptomology make a diagnosis of "asthma" too broad hindering individualized treatment. Four asthmatic inflammatory phenotypes have been identified based on inflammatory cell profiles in sputum: eosinophilic, neutrophilic, paucigranulocytic, and mixed-granulocytic. Paucigranulocytic asthma may be one of the most common phenotypes in stable asthmatic patients, yet it remains much less studied than the other inflammatory phenotypes. Understanding of paucigranulocytic asthma in terms of phenotypic discrimination, distribution, stability, surrogate biomarkers, underlying pathophysiology, clinical characteristics, and current therapies is fragmented, which impedes clinical management of patients. This review brings together existing knowledge and ongoing research about asthma phenotypes, with a focus on paucigranulocytic asthma, in order to present a comprehensive picture that may clarify specific inflammatory phenotypes and thus improve clinical diagnoses and disease management.
Humans ; Asthma/drug therapy* ; Inflammation/diagnosis* ; Respiratory System ; Phenotype ; Biomarkers ; Sputum ; Eosinophils ; Neutrophils

Objective To use the DNA-pool technology to sequence patients with essential hypertension(EH) for exploring the single nucleotide polymorphism(SNP) mutation situation in Chinese patients with EH.Methods One hundred EH outpatients in the Shenzhen Sun Yat-sen Cardiovascular Hospital from March to June 2014 were continuously collected.The genomic DNA was performed the fragmentation process to 400-800 bp for conducting the database creation and sequencing.The sequencing results were compared with hg19 in the human gene bank(National Center of Biotechnology Information).Results A total of 120.8 Gb original sequence data were generated.The sequencing depth was 36.13 times,the coverage rate reached 99.88%.A total of 4 305 668 SNP loci were detected by the bioinformatic analysis,in which the C:G→T:A motation types were miximal,reaching 12 314 variation sites.Conclusion This study verifies that the data obtained by using the DNA-pool whole genome resequencing method replenishes the Chinese gene database of EH and provides some help for EH gene reasearch in the future.

Objective To explore the association between cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene polymorphism and susceptibility to ankylosing spondylitis (AS). Methods The case-control studies from Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Wanfang, Weipu, PubMed, Cochrane Library, OvidSP, Wiley Online Library, Elsevier Science Direct, Springer Link databases for the association of CTLA-4 gene polymorphism with AS. The association strength was assessed with chi-squared test by Stata 12.0 software. Results Seven references of CTLA-4 gene +49A/G (rs231775) polymorphism were enrolled which included 1119 AS patients and 995 controls (healthy subjects or non-AS patients), which showed that there were no statistical difference between AS and control groups under recessive, dominant, co-dominant, additive and allele gene models. Five references of CTLA-4 gene-318C/T (rs5742909) polymorphism were enrolled which included 635 AS patients and 512 controls, which showed that there were no statistical difference between AS and control groups under recessive and additive gene models; however, there were statistical difference between AS and control groups under dominant model [ OR=1.651, 95%CI (1.052, 2.590), P=0.029], co-dominant model [OR=0.621, 95%CI (0.403, 0.957), P=0.031] and allele model [OR=1.587, 95%CI (1.068, 2.357), P=0.022]. Conclusion The meta analysis reveal that CTLA-4 gene rs231775 single nucleotide polymorphism is not associated with the susceptibility to AS; rs5742909 SNP is associated with the susceptibility to AS, which suggests that C→T mutation increases the risk of AS.

Objective To explore the association between C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and susceptibility to hyperuricemia and gout.Methods The case-control studies from Chinese Biomedical Database,Chinese National Knowledge Infrastructure,Wanfang,Weipu,PubMed,Cochrane Library,OvidSP,Wiley Online Library,EBSCO,Elsevier Science Direct,Springer Link and Google scholar databases for the association of C677T polymorphism of MTHFR gene with hyperuricemia and gout.The pooled odds ratios (OR) with 95％ confidence intervals (CI) were appropriately derived from randomeffects or fixed-effects models to assess the association strength by RevMan 5.3 and Stata 12.0 software.Results Ten references enrolled 1 899 hyperuricemia patients and 5 403 controls,and 3 references enrolled 209 gout patients and 194 controls in total.The meta analysis showed that carriers of genotype CC [OR=0.42,95％CI (0.29,0.63),P＜0.01] and allele C [OR=0.54,95％CI (0.42,0.71),P＜0.01] had lower risk of hyperuricemia;genotype TT [OR=1.55,95％CI (1.32,1.83),P＜0.01] and allele T [OR=1.84,95％CI (1.38,2.45),P＜0.01] had higher risk of hyperuricemia,carriers of genotype CC [OR=0.32,95％CI (0.15,0.68),P=0.003] and allele C [OR=0.35,95％CI (0.17,0.70),P=0.003] hadlower risk of gout;genotype TT [OR=2.92,95％CI (1.74,4.92),P＜0.01] allele T [OR=2.69,95％CI(1.50,4.84),P=0.0009] had higher risk of gout.Conclusion The meta analysis reveals that C677T polymorphism of MTHFR gene is associated with the susceptibility to hyperuricemia and gout.

BACKGROUND:Parathyroid hormone related peptides are accompanied by the syndrome of humoral hypercalcemia of malignancy. As a potential therapeutic drug of promoting the healing of bone fracture, parathyroid hormone related peptides have significant clinical application value.
OBJECTIVE:To explore the regulating effects of parathyroid hormone related peptides in diabetic osteoporotic fracture
METHODS:A computer-based online research of CNKI and PubMed databases was performed to col ect articles published between 1990 and 2013, with the key words“parathyroid hormone related peptides, diabetes, osteoporotic fracture”in Chinese and English. There were 1 279 articles after the initial survey. A total of 43 articles were included according inclusion and exclusion criteria.
RESULTS AND CONCLUSION:Animal and clinical experiments demonstrated that parathyroid hormone related peptides notably accelerate bone fracture healing, and improve the repair process of islet cellfunction defects that are related with diabetes. Meanwhile, as an analogue, parathyroid hormone has been identified as clinical medication in the treatment of fracture. But the appropriate dose, and method of application at the different stages of bone fracture healing and the problem of drug combination need further investigation.

Objective To explore the association between the polymorphism in-308 site of tumor necrosis factor (TNF)-α promoter region and ankylosing spondylitis (AS).Methods The case-control studies from PubMed,Cochrane Library,Ovid,Chinese Biomedical Database,Chinese National Knowledge Infrastructure,Wanfang and Weipu databases for the association polymorphism in-308 site of TNF-α promoter region with AS.The pooled odds ratios (OR) with 95％ confidence intervals (CI) were appropriately derived from random-effects models or fixed-effects models to assess the association strength by RevMan 5.2 and Stata 12.0 software.Results Nineteen references enrolled 2 155 AS patients and 2 367 controls in total.The meta analysis showed that the frequencies of GG vs (AA +GA) genotypes was not statistically different between AS group and the control group in total populations [OR=1.20,95％CI (0.85,1.70),P=0.30],in the populations of Asian origin [OR=1.29,,95％CI (0.66,2.52),P=0.45] and in the populations of non-Asian origin [OR=1.16,95％CI (0.78,1.72),P=0.46].The analysis also showed that the frequencies of AA vs (GG +GA) genotypes was not statisticalLY differenT between AS group and the control group in total populations[OR=0.78,95％CI (0.53,1.15),P=0.21],in the populations of Asian origin [OR=1.15,95％CI (0.33,4.00),P=0.82] and in the populations of non-Asian origin[OR=0.69,95％CI (0.42,1.13),P=0.14].The analysis also showed that the frequencies of allele G vs A was not statistically different between AS group and the control group in total populations [OR=1.09,95％CI (0.79,1.50),P=0.61],in the populations of Asian origin [OR=1.17,95％CI (0.65,2.09),P=0.60] and in the populations of non-Asian origin [OR=1.05,95％CI (0.71,1.54),P=0.81].Conclusion The Meta-analysis reveales that all genotypes and alleles of-308 site of TNF-α promoter region may not be associated with AS.

Objectives: To explore the association between the polymorphism in -857 site of tumor necrosis factor (TNF)-α promoter region and the susceptibility to ankylosing spondylitis (AS). Methods: Case-control studies Pubmed, Cochrane Library, Ovid, Chinese Biomedical Database(CBM), Chinese National Knowledge In-frastructure(CNKI), Wanfang and Weipu data bases from inception to October 2013 for the association between TNF-α-857 C/T polymorphism and the susceptibility to AS were collected. Meta-analysis was performed by Revman 5.2 and Stata 12.0 software. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were de-rived from random-effects or fixed-effects models to assess the strength of the association. Results: Nine case-control studies were included in the final meta-analysis, including a total of 933 AS patients and 1094 controls. Statistically significant differences between AS and control groups were observed in the susceptibility to AS and TNF-α-857 genotype CC [OR=0.46, 95%CI (0.26, 0.81), P=0.007], allele C [OR=0.61, 95%CI (0.41, 0.91), P=0.02] and T [OR=1.64, 95%CI (1.10, 2.43), P=0.02]. But, no statistical difference in the fre-quency of genotype TT [OR=1.49, 95%CI (0.95, 2.34), P=0.08] was observed between AS and control groups. There were obvious heterogeneities among the studies of genotype CC(P<0.00001, I2=87%), allele C(P<0.00001, I2=84%) and allele T(P<0.00001, I2 =84%), except genotype TT(P=0.09, I2=42%). Sensitivity analysis was per-formed by leaving out one study at a time, but the heterogeneity remained obvious. It was symmetric of the funnel plots of genotype CC, allele C and T with AS, but genotype TT. There was no statistical significance in genotype CC[Begg′s test(z=0.52, P=0.602), Egger′s test(t=0.23, P=0.825)], genotype TT[Begg′s test(z=0.94, P=0.348), Egger′s test(t=1.26, P=0.248)], allele C[Begg′s test(z=0.31, P=0.754), Egger′s test(t=0.72, P=0.494)] or allele T[Begg′s test(z=0.31, P=0.754), Egger′s test(t=-0.72, P=0.494)]. Conclusions: Genotype CC, allele C and T of TNF-α-857 are associated with the susceptibility to AS, and T-allele carriers have higher risk of AS.

Objective of the study is to explore how to apply ARIMA model in prediction of outpatients headcount,describe the modeling process,build the prediction model,and verify its applicability to serve decision making for hospital management.Methods Data originates from the outpatient statements of the HIS integrated statistics and management decision making support system.The data collection ranges from the monthly outpatients headcount from 1999 to 2005,in which the monthly data from 1999 to 2004 were used to build the time sequence model,and those of 2005 to verify the model so built.The statistic software was programmed with SPSS13.0.Results The ARIMA(1,0.1)(0,1,1)12 model was built by megns of model identification,parameter estimate.inspection/diagnosis,and model appraisal.This model features high fitting precision,as the relative error or outpatients headcount for the year is 6.85%,and that for the months ranges from-3.15%to-9.80%,with the actual values falling within the 95%upper and lower thresholds of the prediction results.Conclusion This study proves that ARIMA model fits the purpose of outpatients headcount prediction.In the meantime,prediction of such headcount should also take into account such factors as the data volume,hospital environment and patient satisfaction.