ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective:To investigate the risk factors of non-valvular paroxysmal atrial fibrillation (NVPAF) with cerebral ischemic stroke(CIS) and analyze NVPAF by using left atrial automatic imaging (AFILA). Logistic regression model was established for left atrial(LA) function parameters.Methods:A total of 205 patients with NVPAF were included in the study and divided into the NVPAF group without ischemic stroke (154 patients) and the CIS group (51 patients). The clinical baseline data, blood biochemical results and AFILA ultrasound data of all patients were collected. Univariate analysis was performed to compare the above data between the two groups of patients. The independent risk factors were obtained by multivariate logistic regression analysis. Logistic regression model was compared with CHA2DS2-VASc scoring system in terms of area under ROC curve, sensitivity and specificity.Results:There were significant differences in age, CHA2DS2-VASc score, taking anticoagulant drugs, history of hypertension, diabetes and coronary heart disease, LAEF, S_R, S_CT, WBC, NEUT, HCY, UREA, NDD, NT-proBNP, Fibrinogen(Fib), Cardiac troponin I(cTnI) and NLR between the two groups (all P<0.05). The results of multifactor analysis showed that: age, hypertension, S_ CT, UREA, NLR, Fib and cTnI were independent risk factors associated with CIS in patients with paroxysmal atrial fibrillation[ OR value: 1.608 ( P=0.003), 3.821 ( P=0.019), 1.259 ( P=0.001), 1.326( P=0.001), 1.352 ( P=0.011), 1.502 ( P=0.042), 7.651( P=0.001)]. After adjusting for the age, sex and history of hypertension included in CHA2DS2-VASc score, S_CT significantly led to NVPAF complicated with stroke[ OR value 1.259 (1.095-1.447), P=0.001]. The diagnostic efficacy of Logistic regression model is better than that of CHA2DS2-VASc scoring (AUC of 0.931 vs 0.717, 95% CI: 0.896-0.967 vs 0.634-0.799, sensitivity of 0.883 vs 0.755, specificity of 0.849 vs 0.713, all P<0.001). Conclusions:Age, hypertension, S_CT, UREA, NLR, fibrinogen, cTnI are independently associated risk factors for patients with combined CIS; The diagnostic efficacy of Logistic regression model is better than that of CHA2DS2-VASc scoring model.And the sensitivity and specificity are high.

Objective To evaluate the in vitro synergistic antifungal activity of HDAC inhibitors in combination with azole drugs against azoles-resistant Candida strains. Methods The checkerboard microdilution method was used to evaluate the antifungal activity of the HDAC inhibitors in combination with azole drugs against clinically drug-resistant strains. The fungistatic activity and toxicity of Rocilinostat was determined through time-growth curve assay and cytotoxicity assay. Results The compound Rocilinostat combined with azole drugs showed excellent synergistic antifungal activity against a variety of azoles-resistant Candida albicans and Candida glabrata. The combination of high concentration Rocilinostat with FLC exhibited fungistatic effects. Very low toxicity was detected with Rocilinostat towards normal cells. Rocilinostat showed better HDAC inhibitory activity than SAHA. Conclusion As a fungi HDAC inhibitor, Rocilinostat has excellent in vitro synergistic antifungal activity and no severe toxicity to normal human cells.

OBJECTIVE: To carry out genetic testing for two families affected with cobalamin C (cblC) and establish a rapid method for the detection of a hotspot pathogenic variant c.609G>A of the MMACHC gene by using a PCR-high-resolution melting curve (PCR-HRM) method. METHODS: Genomic DNA was extracted from peripheral blood samples of the probands and their parents. Potential variants of the MMACHC gene was analyzed by Sanger sequencing. The c.609G>A variant of the MMACHC gene was screened among 100 healthy children with the PCR-HRM method. RESULTS: Sanger sequencing revealed that proband 1 carried compound heterozygous variants c.394C>T and c.609G>A of the MMACHC gene, while proband 2 carried compound heterozygous variants c.482G>A and c.609G>A of the same gene. PCR-HRM analysis of the two probands and the 100 healthy children were consistent with the Sanger sequencing. CONCLUSION c.609G>A is a hotspot pathogenic variant of the MMACHC gene. The diagnosis of cblC may be rapidly attained through detection by PCR-HRM.

Objective: To investigate the in vitro antibacterial activity of triclosan combined with different antibacterial agents against triclosan-resistant multidrug-resistant Acinetobacter baumannii (A.baumannii). Methods: A total of 626 A. baumannii strains were collected from the First Affiliated Hospital of Wenzhou Medical University from 2016 to 2017. The sensitivity of these A. baumannii strains to common antibiotics was detected by VITEK 2-compact automatical microbiological analyzer and the minimum inhibitory concentrations (MIC) of triclosan were detected by agar dilution method. Checkerboard method was used to detect the changes in MIC values of triclosan against 16 triclosan-resistant multidrug-resistant A. baumannii strains after it was used in combination with four external ointments, including gentamicin, erythromycin, chloramphenicol and kanamycin, and three common antibiotics of imipenem, meropenem and ciprofloxacin, respectively. Fractional inhibitory concentration index (FICI) was used to evaluate the joint bacteriostatic effects. Results: Among the 626 A. baumannii strains, 17 were resistant to triclosan with a drug resistance rate of 2.7% (17/626). These triclosan-resistant strains had high MIC values for ciprofloxacin, imipenem, ceftazidime and other commonly used clinical antibiotic and most of them were multidrug-resistant. After triclosan was used in combination with seven different antibacterial drugs, the MIC values of all drugs decreased to various degrees compared with those when they were used alone. Triclosan in combination with gentamicin, chloramphenicol and ciprofloxacin showed synergistic effects on 62.5%, 56.25% and 62.5% of the 16 strains and additive effects on 37.5%, 43.75% and 37.5%, respectively. When it was used in combination with erythromycin, kanamycin, imipenem and meropenem, synergistic effects on 37.5%, 25%, 12.5% and 12.5%, additive effects on 37.5%, 56.25%, 62.5% and 62.5%, and indifferent effects on 25%, 18.75%, 25% and 25% of the strains were detected, respectively. No antagonistic effect was found between triclosan and any of the above antibiotics. Conclusions Triclosan combined with gentamicin, chloramphenicol and ciprofloxacin had better in vitro antibacterial effects against the triclosan-resistant multidrug-resistant A. baumannii strains in this study with synergistic and additive effects. Some indifferent effects were found between triclosan and kanamycin, erythromycin, imipenem and meropenem, but no antagonistic effects were detected.

Objective To investigate the spectrum of CYP21A2 gene mutation and the correlation between genotype and phenotype in patients with 21-hydroxylase deficiency in Tianjin and surrounding areas.Methods Genomic DNA was extracted from the peripheral blood samples of the proband.Locus-specific PCR,direct sequencing of PCR amplification products,and multiplex ligation-dependent probe amplification were applied to detect pathogenic gene CYP21A2 and the relationship between genotypes and phenotypes was analyzed.Results (1) Of 35 patients with 21-hydroxylase deficiency,25 were classified as salt-wasting phenotype and 10 were simple virilizing phenotype.(2) 69 mutant alleles were detected in a total of 70 alleles in 35 patients.Only one mutant allele was detected in one patient.Two mutant alleles were detected in all other patients,with the mutation detection rate 98.6％.(3) A total of 6 types of mutations were detected,of which c.293-13C/A＞G (I2G) was the most common,accounting for 57.1％ (40/70),followed by 18.6％ (13/70) for large gene deletion or conversion,and 14.3％ (10/70) for p.I173N.In addition,a novel mutation,c.949C＞T (p.R317X),which has not been reported previously,was detected as a pathogenic mutation.(4) Correlation analysis of genotype and phenotype in 35 children showed that the phenotype predicted by genotype was consistent with the actual salt-wasting phenotype in 31 children,and those in three children were inconsistent with the actual clinical phenotype.Conclusion The mutation characteristics of CYP21A2 gene in patients with 21-hydroxylase deficiency in Tianjin and surrounding areas are slightly different from those reported in other regions in China.A mutation c.949C＞T has not been reported,which enriches the mutation spectrum of CYP21A2 gene and provide the foundation for genetic counseling and prenatal diagnosis.

OBJECTIVE: To detect pathogenic variation in a pedigree affected with hereditary spastic paraplegia type 31 and explore its molecular pathogenesis. METHODS: Customized Roche NimbleGen capture probes were used to capture all exons of the target genes in relation with hereditary spastic paraplegia. The DNA samples were also assayed with fluorescent quantitative PCR as well as chromosomal microarray analysis using CytoScan HD chip. RESULTS: The proband and her father and grandfather were found to carry a deletion for position 85 992 693-86 842 693 on chromosome 2, which spanned approximately 900 kb and encompassed the REEP1 gene. The latter has been specifically associated with hereditary spastic paraplegia type 31. The same deletion was not found in her mother who is phenotypically normal. CONCLUSION The deletional variation of the REEP1 gene probably underlies the disease in this pedigree.
Female ; Humans ; Membrane Transport Proteins ; supply & distribution ; Paraplegia ; Pedigree ; Sequence Deletion ; Spastic Paraplegia, Hereditary ; genetics

Objective: To evaluate the in vitro antibiotic effects of colistin combined with meropenem, levofloxacin or fosfomycin against colistin-heteroresistant Acinetobacter baumannii (A.baumannii). Methods: A total of 576 A. baumannii clinical isolates were collected from the First Affiliated Hospital of Wenzhou Medical University from 2014 to 2015. Minimal inhibitory concentrations (MICs) of colistin against A. baumannii were detected by broth dilution method. Colistin-heteroresistant A. baumannii isolates were screened using population analysis profiles (PAPs). MICs of colistin combined with meropenem, levofloxacin or fosfomycin, and the four drugs used alone against colistin-heteroresistant A. baumannii were detected by checkerboard method and broth dilution method. Fractional inhibitory concentration index (FICI) was calculated to evaluate antibiotic effects. Results: None of the 576 A. baumannii isolates was resistant to colistin as indicated by the broth dilution method. Nine colistin-heteroresistant A. baumannii isolates were identified using PAPs. Compared with the MICs of colistin used alone, the MICs of colistin used in combination with meropenem, levofloxacin or fosfomycin against colistin-heteroresistant isolates were all decreased. Colistin-meropenem combination showed synergistic (55.6%), additive (33.3%) and indifferent effects (11.1%), but no antagonistic effect. Colistin-levofloxacin combination showed synergistic (55.6%), additive (22.2%) and indifferent effects (22.2%), but no antagonistic effect. Colistin-fosfomycin combination showed synergistic (77.8%) and additive (22.2%) effects, but no indifferent or antagonistic effect. Conclusion In vitro use of colistin in combination with meropenem, levofloxacin or fosfomycin has synergistic and additive antibacterial effects against colistin-heteroresistant A. baumannii. Combinations of colistin-meropenem and colistin-levofloxacin have fewer indifferent effects and no antagonistic effect.

Objective To evaluate the difference in coronary microcirculation and short term prognosis in patients with different collateral circulation and underwent elective percutaneous coronary intervention ( PCI) with complete occlusion of coronary artery. Methods The study included 42 patients who had been admitted in our hospital for NSTEMI or STEMI between 01/2012 to 12/2015 without receiving revascularization treatment and whose symptoms persisted for over 6 months. According to the results of coronary angiography and the Rentrop grade, the patients were divided into 2 groups: poor collateral circulation formation group (group A, Rentrop=0 -1, n=17) and well established collateral circulation group (group B, Rentrop=2-3, n=25). The basic clinical data and the result of coronary angiography were compared. A pressure-temperature sensor wire was used to measure index of mierocirculatory resistance ( IMR) immediately after PCI. An echocardiograph was used to measure left ventricular end systolic diameter ( LVEDd) and left ventricular ejection fraction ( LVEF) postoperatively and again at 3 months after operation to evaluate the changes in cardiac function. Results The IMR value of group A was significantly higher than group B (P﹤0. 05), the grade of collateral circulation had negative correlation with IMR value (r=-0. 671, P﹤0. 05). The mean changes in LVEDd in 3 months in group B was -0. 28 mm, while in group A was 5. 76 mm (P﹤0. 05). The mean changes in LVEF in 3 mouths in group B was 5. 36% and in group A was -3. 82% (P﹤0. 05). The grading of coronary collateral circulation had negative correlation with the changes of LVEDd in 3 months (r= -0. 669, P﹤0. 05), but had positive correlation with the changes of LVEF (r=0. 657, P ﹤0. 05). The IMR value had positive correlation with the changes of LVEDd in 3 months (r=0. 686, P﹤0. 05), but had negative correlation with the changes of the LVEF (r= -0. 664, P﹤ 0. 05 ) . Conclusions Patients with poor collateral circulation was more prone to coronary microcirculatory injury than patients with good collateral circulation. Patients with good collateral circulation and microcirculation had better prognosis after the revascularization of the infarction-related vessel.

Objective To explore if any rules in electrocardiogram changes after transcatheter closure of perimembranous ventricular septal defects ( PMVSD ) . Methods We included all the 358 patients who have accepted transcatheter closure of PMVSD in our hospital between July 2006 to October 2014 and the electrocardiogram (ECG) done in hospital and during follow up in 1,3, 6 and 12 months after operation were all reviewed. Results No changes were found in heart rates and electrical axis during follow-up as compared to preclosure ECG. PR interval was shorter, the QRS duration and QT interval were longer than preclosure. Incidence rate of arrhythmia was 38. 0% ( 136/358 ) and incidence rate of serious arrhythmias ( including Ⅱ° or Ⅲ° atrioventricular block and complete left bundle branch block) was 5. 0%(18/358). Among the 180 patients who had ECG done in all follow up between the first 12 months post closure, the rates of new developed arrhythmias was 12. 8% ( 23/180 ) and severe arrhythmia was 0. 6%(1/180) during follow-up. Conclusions Incidence rate of serious arrhythmias after transcatheter closure of PMVSD is low and most patients have good clinical outcome.