Objective To demonstrate the efficacy and safety of Hangzhou tacrolimus capsule(Saishi Tac capsule, Hangzhou Zhongmei Huadong Pharmaceutical Co. Ltd, China) in Chinese kidney transplant recipients. Methods Multicenter, randomized open-labeled, prospective controlled clinical trial was performed in de novo Chinese kidney transplant recipients. According to including and excluding criterions, 65 kidney recipients from 9 transplant centers were enrolled. The mean age of recipients was (36.53 ± 5.71 ) years, and 8 received living donor transplantion. The time of cold ischemia and warm ischemia was (4.08 ± 5.43) h and (3.90 ± 2.15) min respectively. The number of mismatched HLA was (2.1 ± 0.8). The recipients accepted Saishi Tac capsule + mycophenolate steroid 60 days, followed by 5-10 μg/L until the terminal observation time point (12 weeks after transplantation). The efficacy and safety were estimated during the period. The primary efficacy endpoint of the study was the incidence of biopsy-confirmed acute rejection. Graft survival and renal function (evaluated by serum creatinine) were the secondary endpoints. Safety was assessed by monitoring laboratory parameters and adverse events reported over the course of the study, such as infection, hepatic damage, hypertension, hyperlipema, diabetes mellitus and other adverse affairs.Results The dose of Tac at 1 st, 2nd, 4th and 8th week postoperation was (6.54 ± 1.69), (6.39 ±1.45),(6.73± 1.25), (6.25 ± 1.02) and (6.03 ± 1.16) mg, corresponding values to the C0 were (8.24±2.09),(9.39± 1.35),(9.93± 1.87),(7.23± 1.16) and (6.43± 1.26) μg/L. During 12weeks of follow-up, the incidence of biopsy-confirmed acute rejection was 12.3% (8/65), among which 6 cases were reversed by implosive therapy. The survival rate of graft kidney was 96.9% (63/65). The incidence of hypertension and hepatic damage was both 7.7% and morbidity of lung infection was 7.6%. There were 3 patients (4.6%) complicated with hyperlipema and diabetes mellitus respectively. Conclusion During the first 3 months of treatment Saishi Tac capsule was safe and effective to Chinese kidney transplant recipients.

Objective To investigate the risk factors of single and multiple bronchoscopic lavage therapy in children with refractory Mycoplasma pneumoniae pneumonia(RMPP).Methods Retrospective analysis was conducted of the clinical data of 332 RMPP children at Department of Respiratory Disease,Children's Hospital of Soochow University from January 2011 to December 2016.The patients were divided into the single group and the multiple group (≥2 times),and the correlative index were compared between the 2 groups.Logistic regression analysis was performed to analyze the risk factors of multiple bronchoscopic lavage therapy in RMPP patients.Results Among 332 children,223 cases were in the single group and 109 cases in the multiple group.Children undergoing multiple bronchoscopy had the fever duration ≥ 10 days before the bronchoscopy and course of disease ≥ 10 days before the bronchoscopy,more than those in the single group [118 cases (52.9％) vs.71 cases (65.1％),69 cases (29.6％) vs.45 cases(41.3％)],and the differences were statistically significant(all P ＜ 0.05).At the same time,the use of glucocorticoid,macrolide,glucocorticoid combined with macrolide antibiotics in the first week of illness were significantly lower in the multiple groups than those in the single group,and the differences were statistically significant (all P ＜ 0.05).In the multiple group,the percentage of neutrophils (N),C-reactive protein (CRP),CRP ＞ 44 mg/L,lactate dehydrogenase (LDH) and LDH ＞ 480 U/L were higher than those in the single group,and the differences were significant (all P ＜ 0.05).In addition,the mixed infection and pleural effusion of multiple group were higher than those of the single group.The proportion of bronchoscopy in the multiple group was higher than that of the single group.In bronchoscopy,the mucus plug blocking and mucosal erosion were more than those of the single group,and the differences were statistically significant (x2 =5.397,13.31,all P ＜ 0.05).After adjusted by multiple regression analysis,6 factors were independent risk factors for multiple bronchoscopic procedures.They were the fever duration before the bronchoscopy ≥ 10 days[odds ratio (OR) =19.504,95 ％ confidence interval (CI):7.350-51.754,P =0.000],the unuse of macrolide antibiotics in the first week of illness (OR =5.072,95％ CI:2.230-11.537,P =0.000),the unuse of glucocorticoid in the first week of illness (OR =14.051,95 ％ CI:4.755-41.522,P =0.000),CRP ＞ 44 mg/L (OR =2.638,95 ％ CI:1.356-5.133,P =0.004),LDH ＞ 480 U/L(OR =2.326,95％ CI:1.302-4.157,P =0.004) and mucosal erosion (OR =11.15,95％ CI:2.503-49.715,P =0.002).Conclusion Severe inflammatory reaction and whether or not to actively resist infection and inflammation in the early stage,were important risk factors for multiple bronchoscopic procedures.

Objective To analyze the changes in lung function and inflammatory indicators such as eosino-phils(EOS),Creola bodies and exhaled nitric oxide(FeNO),and to explore their value in early diagnosing asthma. Methods One hundred and thirty-five infants with high-risk asthma were selected as an observation group who were admitted to Department of Respiratory,Childrenˊs Hospital of Soochow University from April 2016 to August 2017 due to asthmatic bronchitis and asthmatic bronchopneumonia,and a total of 200 non -asthmatic and non -allergic healthy children who were screened and followed up at the Department of Cardiology in the same period were selected as a healthy control group for the measurement of moist respiratory lung function and FeNO. In the observation group,the bronchial dilation test(BDT),EOS and Creola bodies were performed simultaneously. Classification of lung function:23%≤time to peak ratio(TPTEF/Te)<28% had mild obstruction,15%≤TPTEF/Te<23% had moderate obstruc-tion,and TPTEF/Te<15% showed severe obstruction. Results The TPTEF/Te[17. 20%(8. 10%)],volume to peak ratio(VPEF/Ve)[21. 20%(6. 20%)],tidal volume per kilogram of body weight(VT/kg)[7. 80(3. 70)]and ratio of tidal expiratory flow 25% to peak tidal expiratory flow(25/PF)[0. 54(0. 20)]in the observation group were signifi-cantly lower than those in the healthy control group[22. 30%(9. 22%),27. 15%(7. 10%),8. 90(3. 17),0. 60 (0. 18)],and the differences were statistically significant(Z＝ -6. 81,-9. 35,-3. 16,-3. 52,all P<0. 05). BDT positive rate in the mild obstruction group was 20. 00%(3/15 cases),BDT positive rate in the moderate obstruction group was 26. 56%(17/64 cases),and BDT positive rate in the severe obstruction group was 48. 72%(19/39 cases). The higher the degree of obstruction,the higher the value of BDT positive diagnosis(F＝6. 353,P<0. 05). BDT of VPEF/Ve,25/PF and TPTEF/Te were consistent and statistically significant(Kappa＝0. 78,0. 49,all P<0. 001). Ti-dal expiratory flow 50% -remaining(TEF50% -r)[(117. 86 ± 42. 16)mL/s],tidal expiratory flow 25% -remai- ning(TEF25% -r)[(82. 82 ± 35. 44)mL/s]in the second wheezing group were higher than those in the first whee-zing group[(92. 81 ± 28. 40)mL/s,(65. 22 ± 24. 93)mL/s],and the differences were statistically significant( t＝3. 34,2. 77,all P <0. 05). There was no statistically significant difference in sputum EOS,FeNO and Creola body scores among wheezing children between the first and second groups(all P>0. 05). FeNO in the observation group [3. 80(5. 43)μg/L]was significantly lower than that in the healthy control group[9. 60(11. 3)μg/L],and the diffe-rence was statistically significant(Z＝14. 56,P<0. 05). Sputum EOS had a positive correlation with blood EOS and Creola bodies(r＝0. 20,0. 21,all P<0. 05);there was no correlation between lung function parameters and inflamma-tory indices(all P>0. 05). Conclusions In the acute phase of infant asthma attack,the pulmonary function presents different degrees of obstructive ventilation dysfunction,the higher the degree of obstruction,the higher the diagnostic value of BDT. The value of single FeNO measurement is limited,and continuous dynamic monitoring may be more mea-ningful in predicting the occurrence of asthma. Detection of Creola bodies may be helpful in predicting asthma.

Objective:To investigate the clinical characteristics and risk factors of bronchiolitis obliterans (BO) after adenovirus pneumonia.Methods:Clinical data of 266 children with adenovirus pneumonia hospitalized in Children′s Hospital of Soochow University from January 2011 to December 2017 were retrospectively analyzed.Accor-ding to whether they developed BO, children with adenovirus pneumonia were divided into the BO group and the non-BO group.Clinical features of the BO group and the non-BO group were compared by t test, rank sum test or chi square test.Risk factors were analyzed by Logistic regression approach. Results:Among 266 children with adenovirus pneumonia included, 37 patients were developed into BO group, and their age was significantly younger than that of the non-BO group [12.0(8.0, 17.5) months vs.32.0(13.0, 48.0) months, P<0.001]. Compared with the non-BO group, there were more proportion of preterm infants[10.8%(4/37 cases) vs.3.1%(7/229 cases), P=0.028], more instances of comorbidities [21.6%(8/37 cases) vs.4.4%(10/229), P<0.001] and more children with allergic diseas[35.1%(13/37 cases) vs.20.1%(46/229 cases), P=0.041] in the BO group, and the difference was statistically significant.The duration of fever in the BO group was significantly longer than that of the non-BO group [10(4.0, 13.5) d vs.6(4.0, 9.0) d, P=0.011] children with symptoms of wheezing, shortness of breath, and hypoxemia in the BO group were significantly more than the non-BO group[81.1%(30/37 cases) vs.27.9%(64/229 cases), P<0.001; 64.9%(24/37 cases) vs.5.7%(13/229 cases), P<0.001; 59.5%(22/37 cases) vs.6.6%(15/229 cases), P<0.001]. The platelet count, IgG level, and CD3 -CD 19+ lymphocyte percentage were significantly higher in the BO group than the non-BO group [(364±104)×10 9/L vs.(297±105)×10 9/L, P=0.001; 6.74(4.92, 10.16) g/L vs.5.93(1.00, 8.04) g/L, P=0.016; (33.5±15.3)% vs.(26.1±10.2)%, P=0.008]. In contrast, the percentage of CD3 + CD4 + lymphocytes in the BO group was lower than the non-BO group[(29.1±8.0)% vs.(32.5±9.4)%, P=0.044], the difference was statistically significant.The BO group had a higher rate of mixed bacterial infection than the non-BO groups[37.8%(14/37 cases) vs.16.6%(38/229 cases), P=0.003]. An age<26 months, comorbidities, premature birth history, wheezing, shortness of breath, and hypoxemia were independent risk factors for BO after adenovirus pneumonia( OR=4.808, 30.667, 7.558, 3.909, 8.842, 8.607, all P<0.05). Conclusions:An age of less than 26 months, a history of premature delivery comorbidities, wheezing, shortness of breath and hypoxemia, are independent risk factors for BO after adenovirus pneumonia.Children with above manifestations should receive high resolution CT as soon as possible to determine whether it is BO.

Objective:To evaluate clinical effect of tampon tamponade combined with wedge resection of the nail folds in the treatment of ingrown toenail-induced paronychia.Methods:A total of 96 patients with ingrown toenail-induced paronychia were collected from Department of Emergency Medicine, General Hospital of Ningxia Medical University between August 2017 and April 2019, and randomly and equally divided into 2 groups by using a random number table: control group treated surgically with the Winograd method, and treatment group treated with tampon tamponade combined with wedge resection of the nail folds. All the patients were followed up for 6 - 23 months after surgery.Results:Six months after operation, 47 (97.92%) and 41 (85.42%) cases were cured in the treatment group and control group respectively, and the cure rate significantly differed between the 2 groups ( χ2 = 4.909, P < 0.05) . The visual analogue scale scores for pain were significantly lower in the treatment group than in the control group on day 3 and 1 month after operation (both P < 0.05) . The postoperative recurrence rate and infection rate were 0 and 2.08% in the treatment group respectively, which were significantly lower than those in the control group (6.25%, 12.5%, respectively, both P < 0.05) . Conclusion:Tampon tamponade combined with wedge resection of the nail folds is effective for the treatment of ingrown toenail-induced paronychia with a simple operative procedure and a low postoperative recurrence rate, and is worthy of clinical promotion.

Objective:To analyze the positive detection rate, main genotypes of β-thalassemia in western region of Guangxi Zhuang Autonomous Region (referred to as Guangxi).Methods:Retrospective analysis of 26 189 individuals who underwent gene testing for thalassemia at the Affiliated Hospital of Youjiang Medical University for Nationalities from January 2013 to December 2019. Using the crossing breakpoint PCR (Gap-PCR) and reverse dot blot (RDB) techniques to detect Chinese common type of 7 kinds of α-thalassemia and 17 kinds of β-thalassemia genotypes, high-throughput sequencing(Sanger) was performed for suspected rare β-thalassemia. Gap-PCR was used for suspected deletion β-thalassemia types.Results:β-thalassemia was diagnosed in 4 495 (17.16%) of 26 189 samples. A total of 6 177 alleles of 20 types of β-thalassemia were detected, mainly CD17 (2 712 cases, 43.90%) and CD41-42 (2 240 cases, 36.26%), including 7 rare alleles: Gγ +( Aγδβ) 0, SEA-HPFH, Hb New York, Hb G-Taipei, Hb Hezhou, Hb G-Coushatta and IVS-Ⅱ-81. There were 3 903 case (86.83%) heterozygous, 273 case (6.07%) double heterozygous, and 319 case (7.10%) homozygous among 4 495 β-thalassaemia subjects. A total of 48 genotypes were detected. The two most common genotypes were CD17/β N (1 890 cases, 42.05%) and CD41-42/β N (1 212 cases, 26.96%), accounted for 69.01% (3 102/4 495). Seven rare genotypes were detected: Gγ +( Aγδβ) 0/β N in 3 cases, Hb New York/β N in 3 cases, Hb G-Taipei/β N in 2 cases, SEA-HPFH/β N, Hb Hezhou/β N, Hb G-Coushatta/β N and IVS-Ⅱ-81/β N in 1 case each. A total of 1 041 cases (3.97%, 1 041/26 189) of 116 types of αβ-thalassemia were detected, mainly -- SEA/αα composite CD17/β N (144 cases, 13.83%), followed by -α 3.7/αα composite CD17/β N (112 cases, 10.76%). Conclusions:Western region of Guangxi is a high prevalence area of β-thalassemia, CD17/β N and CD41-42/β N are the main genotypes. The variation spectrum of β-thalassemia is complex and diverse, with rich genotype.

γ-aminobutyric acid can be produced by a one-step enzymatic reaction catalyzed by glutamic acid decarboxylase. The reaction system is simple and environmentally friendly. However, the majority of GAD enzymes catalyze the reaction under acidic pH at a relatively narrow range. Thus, inorganic salts are usually needed to maintain the optimal catalytic environment, which adds additional components to the reaction system. In addition, the pH of solution will gradually rise along with the production of γ-aminobutyric acid, which is not conducive for GAD to function continuously. In this study, we cloned the glutamate decarboxylase LpGAD from a Lactobacillus plantarum capable of efficiently producing γ-aminobutyric acid, and rationally engineered the catalytic pH range of LpGAD based on surface charge. A triple point mutant LpGAD^{S24R/D88R/Y309K} was obtained from different combinations of 9 point mutations. The enzyme activity at pH 6.0 was 1.68 times of that of the wild type, suggesting the catalytic pH range of the mutant was widened, and the possible mechanism underpinning this increase was discussed through kinetic simulation. Furthermore, we overexpressed the Lpgad and Lpgad^{S24R/D88R/Y309K} genes in Corynebacterium glutamicum E01 and optimized the transformation conditions. An optimized whole cell transformation process was conducted under 40 ℃, cell mass (OD₆₀₀) 20, 100 g/L l-glutamic acid substrate and 100 μmol/L pyridoxal 5-phosphate. The γ-aminobutyric acid titer of the recombinant strain reached 402.8 g/L in a fed-batch reaction carried out in a 5 L fermenter without adjusting pH, which was 1.63 times higher than that of the control. This study expanded the catalytic pH range of and increased the enzyme activity of LpGAD. The improved production efficiency of γ-aminobutyric acid may facilitate its large-scale production.
Glutamate Decarboxylase/genetics* ; Lactobacillus plantarum/genetics* ; Catalysis ; gamma-Aminobutyric Acid ; Hydrogen-Ion Concentration ; Glutamic Acid

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.