Objective To compare the efficacy of uniform multi-drug therapy (UMDT) versus routine multi-drug therapy (RMDT) for the treatment of multi-bacillary (MB) leprosy patients based on bacterial index changes and frequencies of leprosy reaction.Methods This study recruited newly diagnosed leprosy patients after taking informed consent in three districts of Guizhou province as well as in one district of Yunnan province from November 2003 to June 2005.The patients received 6-month UMDT or 2-year RMDT.Clinical follow up and bacterial reexamination were carried out once a year.Changes of bacterial index (BI) and frequencies of leprosy reaction were compared between the patients receiving RMDT and UMDT.Results A total of 166 patients received UMDT and 170 received RMDT in this study.Among the UMDT-treated patients,114 were skin smear positive,and 83 had been followed up for 42 months; of the RMDT-treated patients,149 underwent all the bacterial examinations during a 48-month follow up.The mean bacterial index decreased from 2.84 before treatment to 0.33 at the end of the 42-month follow up in the 83 patients,and from 2.55 to 0.26 at the end of the 48-month follow up in the 149 patients,with no significant difference in the changes of bacterial index between the two groups (t =0.77,P ＞ 0.05).Bacterial index became negative in 73.5％ (61/83) of the UMDT-treated patients and in 77.2％ (115/149) of the RMDT-treated patients (x2 =0.40,P＞ 0.05)at the end of follow up.During the follow up peroid,the incidence of type Ⅰ leprosy reaction was 14.6％ (13/89) in the UMDT group,significantly higher than that in the RMDT group (3.4％ (5/149),x2 =10.08,P＜ 0.01 ).Conclusions There is no significant difference in mean bacterial index changes and bacterial clearance rate during the follow up peroid between UMDT- and RMDT-treated patients.The incidence of type Ⅰ leprosy reaction is higher in the UMDT group than in the RMDT group,and further investigation is needed to clarify the mechanisms underlying the phenomenon.

Objective To assess the efficacy of 6-month uniform multidrug therapy in various types of leprosy. Methods A field trial was conducted among 166 patients with different types of leprosy. All patients were treated with uniform multidrug therapy for 6 months, then followed up for 2 years. Clinical and bacterio-logical improvements were evaluated. Results Among the 166 patients, 31 dropped out due to various reasons,and 135 completed the 6-month treatment and 2-year follow-up. Among the 135 patients, 45 (33.3%) were skin smear negative, and the other smear-positive 90 had an average bacterial index (BI) of 2.91±1.45 (range: 0.1-6.0) before treatment. At the end of the 2-year follow-up, the 45 skin smear-negative patients showed 93.3% improvement in skin lesions and 80.0% improvement in nerve impairments, and the smear-posi-tive 90 patients showed 95.6% improvements in skin lesions and 77.8% improvement in nerve impairments.Skin smear turned negative in 49 (54.4%) out of the smear-positive 90 patients with the average BI declining to 0.66±0.99. The annual decrease in BI reached 0.9 during the first 2.5 years after the beginning of treat-ment. Twenty-five patients developed leprosy reaction during the follow-up, including 13 cases of type Ⅰ leprosy reaction and 12 cases of type Ⅱ leprosy reaction. Relapse was noted in 1 patient with muhibacillary leprosy 13 months after the termination of treatment. Conclusions The short-term efficacy of uniform multidrug therapy is similar to that of 2-year treatment with routine multidrug therapy. However, further studies are required to survey the incidence of leprosy reaction and relapse in patients treated with uniform multidrug therapy.

Objective To detect the pre- and post-treatment levels of serum interleukin (IL-20) in asthmatic patients during the acute exacerbation period and to investigate the role of IL-20 in the pathogenesis of bronchial asthma and relative clinical significance. Methods Forty-five cases of mild to moderate asthma outpatients in the First Affiliated Hospital of Guangxi Medical University from May 2013 to October 2013 were chosen as the asthma group and 32 healthy people who underwent routine physical examination as the control group. All the patients were treated with inhalation salmeterol and fluticasone 50/250 μg/μg (sucking twice a day) together with ventolin if necessary , and even with theophylline sustained-release tablets as the additional treatment in moderate asthma group for 1 week. The serum levels of IL-20 as well as immunoglobulin E (IgE) were detected by ELISA in the asthma group before and after treatment as well as in the control group. Other data including ECP , the number of eosinophil ceils (EOS) and the pulmonary function (FEV1%) were detected as well. The differences of IL-20 levels between the asthma group before and after treatment and the control group were analyzed and the correlation between IL-20 and Ig E, EOS, ECP and FEV1% were analyzed. Results Compared with the healthy control group [(13.58 ± 6.17)pg/L], the levels of IL-20 in the mild and moderate asthma pretreatment group were significantly increased [(23.43 ± 13.60)pg/L and (33.78 ± 22.69)pg/L]. Compared with the mild asthma group, the levels of IL-20 in the moderate asthma pretreatment group were significantly higher. After treatment , the levels of IL-20 [(15.73 ± 8.27)pg/L and (19.64 ± 11.69)pg/L] were decreased respectively in the asthmatic patients. The Pearson correlative analysis showed that there were positive correlations between the levels of 1L-20 and IgE , EOS and ECP respectively and there were negative correlations between IL-20 levels and FEV1%. Conclusion IL-20 may be involved in the pathogenesis of asthma.

Objective To investigate the effect of IL‐1βon the expression and release of high mobility group box 1 (HMGB1) from normal human bronchiolar epithelial cell (HBE) .Methods HBE135‐E6E7 was developed and methyltetrazolium (MTT) as‐say was used to assess the viability of HBE cell line under different concentration of IL‐1β.The mRNA expression of HMGB1 in HBE after stimulating with IL‐1βwere determined by Real‐time PCR;the level and location of HMGB1 in the cytoplasm ,nucleus and culture medium of HBE after stimulating with IL‐1β were detected by Western blot and ELISA assay .The expression and translocation of HMGB1 of HBE after stimulating with IL‐1β were detected by Immunofluorescence .Results 0 .1 ,1 .0 ,10 .0 ng/mL IL‐1βdid not influence the cell viability of HBE ;IL‐1β increased the mRNA expression of HMGB1 in HBE in does‐and time‐dependent manner and increased the protein expression of HMGB1 in HBE .In comparison with control group ,the levels of HMGB1 in the culture medium significantly increased after stimulation with IL‐1βat 1 .0 ,10 .0 ng/mL for 24 h(P<0 .05)in the dose dependent experiments;and in time dependent experiments ,10 .0 ng/mL IL‐1βsignificantly increased HMGB1 level in the cul‐ture medium after stimulation for both 12 h and 24 h (P< 0 .05) .After stimulation with IL‐1β (10 .0 ng/mL ) for 24 h ,the HMGB1 expression in cytoplasm significantly increased in plasmosin and decreased in nucleus .HMGB1 translocated from nuclei to cytoplasm after stimulation with IL‐1β(10 .0 ng/mL ) for 24 h .Conclusion IL‐1βcould induce HMGB1 expression and release in human bronchial epithelial cells ,which indicates that HMGB1 may involve in IL‐1β‐mediated chronic airway inflammation .

OBJECTIVE: To carry out genetic and metabolite analysis for an infant with cerebral creatine deficiency syndrome type 2 (CCDS2). METHODS: Clinical data of the child was collected. Whole-exome sequencing was carried out to identify potential variants by next generation sequencing. Candidate variants were confirmed by Sanger sequencing. Metabolites were determined by tandem mass spectrometry and magnetic resonance spectroscopy. Treatment was carried out following the diagnosis and genetic counseling for the affected family. RESULTS: Two novel heterozygous variants (c.289delC and c.392-1G>C) of the GAMT gene were identified in the proband, which were respectively inherited from her father and mother. In silico analysis suggested both variants to be pathogenic. Creatine (Cr) level of the child was very low, and cerebral guanidinoacetate (GAA) level was slightly increased. But both had recovered to normal in two weeks, and cerebral Cr level was significantly improved after two months. Intellectual and motor development of the child were significantly improved. CONCLUSION The child was diagnosed with CCDS type 2, for which pathogenic variants of the GAMT gene may be accountable. Treatment has attained a satisfactory effect for the patient.

BACKGROUND:It is known that N6-methyladenosine(m6A)plays a role in the pathogenesis of various diseases and studies have suggested its involvement in the pathologic changes of steroid-induced femoral head necrosis(SNFH).However,research on m6A methylation modifications in steroid-induced femoral head necrosis is limited. OBJECTIVE:Using bioinformatics methods to identify the differential expression of m6A-related genes in steroid-induced femoral head necrosis and to predict miRNAs associated with these genes to further elucidate the role and mechanism of m6A methylation in steroid-induced femoral head necrosis. METHODS:Differential gene expression between steroid-induced femoral head necrosis and control groups was analyzed using GSE123568 gene expression data and identified using the"limma"package in R.Functional enrichment analysis was performed on the differentially expressed genes.Differential analysis of the related genes was carried out using the"ggstatsplot"package in R.The differential genes were cross-validated using the GSE74089 dataset.An mRNA-miRNA regulatory network was constructed,and co-expression analysis was performed on the module genes followed by enrichment analysis.Differences in immune cell infiltration between steroid-induced femoral head necrosis and control groups were quantified using the ssGSEA method. RESULTS AND CONCLUSION:Correlation analysis revealed 13 m6A-related genes,and further analysis through the protein-protein interaction network identification and receiver operating characteristic curve analysis showed that YTHDF2 was expected to be a core differential gene as a potential early biomarker.Enrichment analysis indicated that differentially expressed genes were mainly involved in inflammation and immune response and were closely related to osteoclasts.Cross-validation analysis showed that differential gene expression results between the two datasets were consistent.mRNA-miRNA regulatory network analysis revealed that YTHDF2 was negatively correlated with miRNA-27a.Immune infiltration analysis revealed an increase in immune cell infiltration in steroid-induced femoral head necrosis,and YTHDF2 was positively correlated with the infiltration of CD4+T cells.To conclude,m6A-related gene YTHDF2 can serve as a potential biomarker of steroid-induced femoral head necrosis and is valuable for the early clinical diagnosis and treatment of steroid-induced femoral head necrosis.The negative correlation between YTHDF2 and mir-27a and the positive correlation between YTHDF2 and CD4+T cell infiltration provide new insights into the early diagnosis and treatment of steroid-induced femoral head necrosis and shed light on the mechanism of m6A in steroid-induced femoral head necrosis.

Objective To investigate the application prospect of the most extensive genome engineering pig internationally in preclinical xenotransplantation. Methods Porcine endogenous retrovirus (PERV) knockout combined with 3 major heterologous antigen gene knockouts and 9 humanized genes for inhibition of complement activation, regulation of coagulation disorders, anti-inflammatory and anti-phagocytosis were transferred into a pig (PERV-KO/3-KO/9-TG) as a donor, and the heart, liver and kidney were obtained and transplanted to 3 Rhesus macaque recipients respectively to establish a preclinical research model of pig-to-Rhesus macaque xenotransplantation. The functional status of xenografts after blood flow reconstruction was observed and the survival of recipients was summarized. The hemodynamics of xenografts were monitored. The change of hematological indexes of each recipient was compared. The histopathological manifestation of xenografts was observed. Results After the blood flow was reconstructed, all xenografts showed ruddy color, soft texture and good perfusion. The transplant heart, liver and kidney showed full arterial and venous blood flow and good perfusion at 1 d after operation. The postoperative survival time of heart, liver, and kidney transplant recipients was 7, 26, and 1 d, respectively. The levels of creatine kinase, creatine kinase isoenzyme, and lactate dehydrogenase increased in heart transplant recipient at 1 d after operation, and gradually recovered to near normal levels at 6 d after operation. All indexes increased sharply at 7 d after operation. The level of aspartate aminotransferase increased in liver transplant recipients at 2 d after operation, and the alanine aminotransferase basically returned to normal at 10 d after operation, but the total bilirubin continued to increase. Both aspartate aminotransferase and alanine aminotransferase increased at 12 d after operation, and reached a peak at 15 d after operation. The kidney transplant recipient developed mild proteinuria at 1 d after operation, and died of sudden severe arrhythmia. Histopathology showed that the tissue structure of cardiac and renal xenografts was close to normal, and liver xenografts presented with patchy necrosis, the liver tissue structure was disordered, accompanied by inflammatory damage, interstitial hemorrhage and thrombotic microangiopathy. Conclusions PERV-KO/3-KO/9-TG pig shows advantages in overcoming hyperacute rejection, mitigating humoral rejection and coagulation dysregulation. However, whether it can be used as potential donor for clinical xenotransplantation needs further evaluation.

Objective:To investigate the efficacy and safety of plasma exchange(PE) in the treatment of autoimmune hemolytic anemia in children.Methods:The data from 8 hospitals in China during November 2014 to April 2017 were collected, and the clinical characteristics of PE in children with AHA were analyzed retrospectively.Results:A total of 21 children with AHA were included in the study, including 17 cases from PICU and 4 cases from pediatric kidney ward, with 11 boys and 10 girls, and the median age was 3.64(0.25, 11.10)years old, and median hospital stay was 12(4, 45)days.There were 15 cases(71.4%) with infection, 2 cases(9.5%)with autoimmune diseases, 4 cases(19.0%) with unknown.Consciousness disturbance occurred in 4 patients before replacement and recovered to normal after PE.The volume of blood decreased in two cases(9.5%) and completely relieved.There were 20 cases of anemia (95.2%), 15 cases were normal after PE, and 5 cases were improved.Jaundice occurred in 18 cases (85.7%), 12 cases were normal after PE, 6 cases were improved.Hepatosplenomegaly was found in 11 cases, 10 cases were normal after PE, 1 case was improved.After PE, the hemoglobin and red blood cell count increased, while the total bilirubin, indirect bilirubin, urea nitrogen and lactate dehydrogenase decreased, there were significant differences between pre-and post-replacement ( P<0.05). Only 1 case had allergic reaction, which was improved after symptomatic treatment, and PE was continued.After PE, 2 cases (9.5%) had complete remission, 16 cases (76.2%) had partial remission and 3 cases (14.3%) had been discharged. Conclusion:PE therapy can obviously improve the clinical symptoms and laboratory indexes of children with AHA who have failed to respond to conservative treatment.It can be used as a treatment measure for children with severe AHA and has a good safety.