Objective To evaluate a rapid biochip system for the determination of muhidrugresistant tuberculosis (MDR-TB) in Mycobacterium tuberculosis isolates. MethodsA total of 1 186 clinical strains, including 800 rifampin (RFP) resistant isolates, 797 isoniozid (INH)resistant isolates, 791 MDR-TB and 380 susceptible strains, were selected from Beijing Chest Hospital, Shanghai Pulmonary Hospital and Guangzhou Chest Hospital respectively using stratified sampling method. Biochips were used to detect loci of rpoB 511 (T→C), 513 (A→C, C→A), 516 (G→T, A→T, A→G) , 526 (C→T, C→G, A→T, A→G), 531 (C→T, C→G), 533 (T→C), katG 315 ( G→C, G→A) and inhA -15 (C→T). Absolute concentration drug susceptibility test of RFP and INH were performed to serve as the gold standard to calculate susceptibility, specificity and overall concordance of biochip test. All polymerase chain reaction (PCR) products were sequenced to confirm the mutations. ResultsThe concordances between the biochip system and absolute concentration drug susceptibility test were 93.7％ ( 1 108/1 183 ) for RFP, 83. 8％(994/1 186) for INH and 82.4％ (975/1 183) for MDR-TB. Compared with absolute concentration drug susceptibility test, the biochip method displayed a sensitivity of 92. 0％ (733/797) and 77. 4％ (617/797)and a specificity of 97. 2％ (375/386) and 96. 9％ (377/389) for RIF and INH, respectively. For MDR-TB, the biochip system reached a sensitivity of 74. 6％ ( 588/788 ) and a specificity of 98.0％ ( 387/395 ).Among rpoB mutants, mutations were mostly detected at codon 531[64. 5％ (480/744)]. In stains with mutations in katG or inhA, 77.4％ ( 487/629 ) had mutation at codon 315 ( TCG ) of katG only. The sequencing results had a high concordance with that of the biochip method. There were slight differences in 5 strains, among which one strain was detected by biochip as katG 315(G→C) mutant, but was identified by sequencing as wild type, and mutation types other than those detected by the biochip were confirmed in the other 4 strains by sequencing. Conclusion This biochip system is adapted for extensive application in clinical diagnosis, as it allows fast and reliable detection of resistance to isoniazid and rifampin in tuberculosis clinical isolates.

Objective To study the genotypes of representative Mycobacterium tuberculosis (M.tuberculosis) strains from China with spacer oligonucleotide typing (spoligotyping),and to investigate the prevalence of different genotypes TB in China,and analyse the relationship between genotype and drug resistance.Methods 4017 clinical isolates were collected by Chinese Center for Disease Control and Prevention from 2007 to 2008 in 31 provinces in China according to sampling principle of epidemiology.Drug susceptibility testing was performed using proportion method,and spoligotyping was chosen to carry out genotyping of these M.tuberculosis.In addition,chi-square test was used to compare the differences among the detection rate of different genotypes.Results Among the 4017 M.tuberculosis isolates,2500 ( 62.2％ ) isolates belonged to Beijing genotype.The percentage of Beijing genotypes in the northern of China was higher than that in the southern of China ( 76.5％ vs.53.2％,x2 =219.69,P ＜ 0.05 ),while T1 genotypes were more common in the southern China,compared with that in northern China ( 13.3％ vs.4.3％,x2 =219.69,P ＜ 0.05 ).The differences were statistically significant.The proportions of Rifampinresistant (21.7％ vs.21.7％ ),Ofloxacin-resistant (4.9％ vs.2.4％ ) and Multidrug-resistant ( 11.3％vs.7.4％ ) isolates among Beijing genotype strains were significantly higher than those among non-Beijing strains (x2 =22.10,14.42 and 14.83,respectively,P ＜ 0.05 ).Conclusions Beijing genotype was still predominant epidemic genotypes.The percentage of Beijing genotype showed difference between distinct areas,and the percentage of Beijing genotypes in northern China was higher than that in southern China.Beijing genotype strains reveal correlation with Rifampin-resistance,Ofloxacin-resistance and Multidrug-resistance.

Objective To investigate the effect of cinacalcet combined with low －dose calcitriol in the treatment of patients with secondary hyperparathyroidism of end －stage renal disease.Methods A prospective analysis was conducted in 129 patients with end－stage renal disease and secondary hyperparathyroidism from April 2015 to August 2017 in the Department of Nephrology of Integrative Medicine Hospital of Wenzhou City,Zhejiang Province.The patients were randomly divided into 3 groups:group A received cinacalcet,group B received calcitriol, group C received cinacalcet and low－dose calcitriol for 3 months,respectively.Before and after treatment,the levels of serum phosphorus and serum calcium in the three groups were measured.The levels of parathyroid hormone and the parathyroid hormone clearance rate were measured to find out the therapeutic effect.Results The levels of serum calcium,phosphorus and total parathyroid hormone in group A were significantly lower than those before treatment(t＝3.269,2.263,4.233,all P＜0.05).PTH was significantly decreased,blood calcium and phosphorus significantly in-creased compared with those before treatment,the differences were statistically significant(t＝2.827,2.386,3.342, all P＜0.05).The phosphorus,total parathyroid hormone levels of group C were significantly decreased(t＝3.085, 5.142,all P＜0.05),and no significant change in serum calcium level(t＝0.258,P＞0.05).The total parathyroid hormone level:group B＞group A ＞group C,the whole parathyroid hormone clearance rate:group C ＞group A ＞group B,the differences were statistically significant(t ＝3.642,3.263,all P＜0.05).After treatment,the serum calcium level among the three groups had statistically significant difference,group B＞group C＞group A,the serum phosphorus level among the three groups after treatment had statistically significant difference,group B＞group A ＞group C (t＝3.265,3.332,all P＜0.05).Conclusion The combined use of cinacalcet and low－dose calcitriol in the treatment of secondary hyperparathyroidism in patients with end－stage renal disease can significantly reduce the level of parathyroid hormone and serum phosphorus,and without affecting serum calcium concentration.

Objective To explore the effects of Atractylenolide-Ⅲ(AT-Ⅲ)on the intestinal immune barrier and kidney of rats with immunoglobulin A nephropathy(IgAN),and develop AT-Ⅲ nanoparticles to optimize its protective efficacy.Methods In this study,the zeolitic imidazolate framework(ZIF-8)loaded with AT-Ⅲ was used to prepare ZIF-8@AT-Ⅲnanoparticles.Morphological and structural characterization of the prepared samples was conducted using transmission electron microscopy and X-ray powder diffraction.48 rats were randomly divided into the normal control group,IgAN group,IgAN+AT-Ⅲ group,and IgAN+ZIF-8@AT-Ⅲ group.IgAN rats were treated with AT-Ⅲ and ZIF-8@AT-Ⅲ,and the detections of hepatic and renal function,glomerular IgA deposition,and intestinal immune barrier function were performed.Results The synthesis of ZIF-8@AT-Ⅲ nanoparticles with elevated drug loading,stability,and pH responsiveness had been successfully accomplished.The average particle size of ZIF-8@AT-Ⅲ nanoparticles was(70.62±1.07)nm,the Zeta potential was(-26.46±1.22)mV,the drug loading capacity was(19.2±1.3％),and the encapsulation efficiency was(64.0％±0.6％).Furthermore,rapid release was observed in a pH 5.5 environment,which was significantly higher than that in the pH 7.4 environment.Both AT-Ⅲ and ZIF-8@AT-Ⅲcould alleviate the destruction of intestinal wall structure and the infiltration of inflammatory cells,significantly downregulate the levels of(DAO)and(D-LA)in the serum.Moreover,there is a noteworthy upregulation in the expression of(ZO-1)and Claudin-5 in intestinal mucosal tissue,thereby substantially improving the immune barrier function and intestinal permeability in IgAN rats.This intervention also inhibited the deposition of IgA in renal glomeruli and alleviated kidney damage,and ZIF-8@AT-Ⅲ was more effective than AT-Ⅲ.Conclusion AT-Ⅲ alleviates IgAN in rats by improving intestinal immune barrier function and permeability.ZIF-8-loaded AT-Ⅲ serves as an excellent drug delivery system,enhancing the therapeutic efficacy of AT-Ⅲ in IgAN treatment.