Objective To analyze the clinical and laboratory phenotypes of Duchenne muscular dystrophy(DMD)in a retrospective study of 96 cases and to evaluate therapeutic efficacy of glucocorticosteroid.Methods The clinical phenotype,laboratory examinations resuhs and the records in the follow-up in 96 patients with DMD were collected.The level of serum creatine kinase(CK)and motor ability before and after glucocorticosteroid therapy were analyzed by statistical analysis.Their myocardium impairments and intelligence conditions were also assessed.Results(1)The level of serum CK (mmol/L)had three peaks at the age of ≤ 3 years old(16 547.9 ±770.9),5 years old(14 371.9 ± 696.7)and 8 years old(13 089.8 ± 877.6).The CK level significantly decreased after dexamethasone (5-10 mg,iv)treatment for 10-15 days,but increased again after prednisone acetate(0.50-0.75 mg · kg-1 · d-1,oral)administration for one month(F =6.758,P =0.003).(2)The motor ability improved in 51 DMD cases with long-term oral admission of prednisone,including 24 cases receiving repeated dexamethasone,iv.(3)The myocardial perfusion imaging in 37 DMD cases showed remarkable uneven “spotted like” radionuclide distribution in ventricle.(4)The intelligence quotients in 24 DMD were lower than normal population.Conclusions There are high CK hyperlipidemia and myocardial damage in the sub-clinical stage of DMD and myocardium impairment is positively correlated with age.Glucocorticosteroid therapy has an important effect on the protection of motor and cardiac functions,with recommendation of using in early stage of disease.

Objective To investigate the clinical and molecular pathological features of dysferlinopathy in China.Methods Four patients with limb-girdle muscular dystrophy2B(LGMD2B)and 4 patients with Miyoshi-type distal muscular dystrophy(MMD)were clinically analyzed, their skeletal muscle were biopsied and immunohistochemical stained.Four cases of each Duchenne-Aran muscular atrophy and myotis were served as controls.Results The clinical situation of dysferlinopathy was characterized by progressive muscle weakness and atrophy, consistent with progressive muscular dystrophy.Histochemical staining revealed muscle fibers degenerating, regenerating and necrosis in a varying degree.Connective tissue was seen proliferated and inflammatory cells infiltrated in the majority of cases.Immunohistochemical staining with anti-dysferlin monoclonal antibody identified the deficiency of dysferlin on the sarcolemma and in the sarcoplasm of 8 cases with dysferlinopathy.Conclusions(1)The clinical and pathological characters of dysferlinopathy are consistent with progressive muscular dystrophy;(2)Anti-dysferlin monoclonal antibody immunohistochemical staining is a reliable method to diagnose dysferlinopathy, which is worth of wide application in clinic.

Objective To achieve detailed genomic characterization and investigate the antibiotic-resistant mechanisms of plasmid pA1137 carrying the aminoglycoside resistance gene aacC2.Methods Antibiotic-resistant genes were deter-mined by PCR.Conjugation experiments were performed to verify the transferability of plasmid pA 1137.The minimum in-hibitory concentration(MIC)values of bacterial strains were tested with microdilution method.The genetic background, mobile elements and antibiotic resistance mechanisms of pA 1137 were determined using a whole genome sequencing meth-od.Results Both carbapenem-resistant gene blaIMP-8and aminoglycoside-resistant genes aacC2 and aacA4 were carried by A1137 isolated from Enterobacter cloacae(ECL).aacC2 was located in plasmid pA1137 while the other two resistant genes were observed in chromosomes.Plasmid pA1137 was an IncFⅡplasmid,whose total length was 68.97 kb,and GenBank accession number was MF190369.Plasmid pA1137 contained multiple replicons and intact conjugative transfer regions,so it could be transferred into ECL through conjugation experiments and confer corresponding antibiotic resistance to the transconjugant A1137-EC600.Conclusion IncFⅡ plasmid pA1137 has a single accessory region, the first reported Tn5403-based aacC2-tmrB-related region,which can cause stable inheritance and mediate the resistance to aminoglycoside antibiotics in ECL A1137.

OBJECTIVEThe inactivating mutation of thyrotropin receptor (TSHR) gene results in partial or complete insensitivity of thyrotropin (TSH) and dysfunction of the TSH-TSHR-cAMP cascade. Therefore, it may cause congenital hypothyroidism (CH). Depending on the degree of impairment of TSHR function, patients can present with subclinical hypothyroidism at one extreme of the spectrum, or severe hypothyroidism at the other. This study aimed to understand the relation between inactivating mutations of TSHR gene and Chinese children with CH.

METHODS(1) Seventy-nine Chinese children with CH, including 14 subclinical hypothyroidism patients (8 boys and 6 girls, age 1 - 5.5 years) and 65 hypothyroidism patients (27 boys and 38 girls, age 1.5 - 6 years) were enrolled in this study. Meanwhile, 100 normal children were enrolled as control, 40 were male and 60 were female. The age of the normal children were at a range of 1 - 8 years. (2) Total genomic DNA was extracted from peripheral blood leukocytes of the 79 patients and 100 normal subjects. Exons 1 - 10 of TSHR gene were individually amplified by polymerase chain reaction (PCR) and mutations were detected by direct sequencing.

RESULTS(1) A compound heterozygous missense mutations (Pro52Thr/Val689Gly) and a heterozygous missense mutation (Gly245Ser) were detected in 79 patients. The mutations of Pro52Thr and Gly245Ser were located within the extracellular domain of TSHR, while Val689Gly was located within the intracellular domain of TSHR. In 30 patients the normal cytosine at position 2181 in exon 10 was replaced by a guanine (GAC-->GAG), resulting in the replacement of Glu(727) by Asp. In 47 patients, the normal thymidine at position 561 in exon 7 was replaced by a cytosine (AAT-->AAC). This substitution did not change the amino acid (Asn) at position 187. (2) In 33 normal children the normal cytosine at position 2181 in exon 10 was also replaced by a guanine (GAC-->GAG) and in 50 normal children the normal thymidine at position 561 in exon 7 was replaced by a cytosine (AAT-->AAC).

CONCLUSIONSThree heterozygous missense mutations (Pro52Thr, Gly245Ser, Val689Gly) of TSHR gene were firstly detected in Chinese children with CH. There was a polymorphism in exon 10 at nucleotide 2181 (GAC-->GAG) and in exon 7 at nucleotide 561 (AAT-->AAC) in TSHR gene. The inactivating mutation of TSHR gene is an infrequent pathogeny for CH.

Amino Acid Substitution ; genetics ; Asian Continental Ancestry Group ; Child ; Congenital Hypothyroidism ; genetics ; DNA ; analysis ; Exons ; genetics ; Female ; Gene Silencing ; Genes, gag ; genetics ; Humans ; Hypothyroidism ; genetics ; Male ; Mutation ; Mutation, Missense ; genetics ; Polymorphism, Genetic ; genetics ; Receptors, Thyrotropin ; metabolism ; Thyrotropin ; genetics

OBJECTIVETo investigate the clinical, pathological and genetic characteristics in a family with autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD).

METHODSClinical data and skeletal muscle specimens were collected from two patients (the proband and her daughter) for pathological analysis. DNA samples of the proband and her family members (7 persons from 3 generations) were obtained for PCR amplification and direct DNA sequencing of the lamin A/C (LMNA) gene. Haplotype analysis was performed after the identification of mutation.

RESULTSThe proband had typical clinical manifestation of EDMD: joint contracture, progressive muscle weakness and atrophy and cardiac conduction dysfunction. Muscular pathology revealed myopathic changes combined with slight neuropathic changes. A heterozygous missense mutation 1583 (C to G)(T528R) was identified in exon 9 of the LMNA gene in the two patients, but not in other family members. Haplotype analysis indicated that the proband and her daughter shared the same causative haplotype.

CONCLUSIONThis is the first report of the phenotype and genotype of AD-EDMD in Chinese.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; DNA Mutational Analysis ; Female ; Haplotypes ; genetics ; Heterozygote ; Humans ; Immunohistochemistry ; Male ; Muscular Dystrophy, Emery-Dreifuss ; genetics ; metabolism ; pathology ; physiopathology ; Mutation ; Pedigree ; Phenotype

Objective: To observe the effect of moxibustion on the colonic mucosal barrier of rats with ulcerative colitis (UC) induced by dextran sulfate sodium (DSS). Methods: Forty male Sprague-Dawley rats were randomly divided into a normal group and a modeling group, with 20 rats in each group. Rats in the modeling group were subjected to preparing experimental UC models by drinking 4％ DSS for seven consecutive days. Two modeled rats and two normal rats were randomly selected for model identification. After the success of UC model was confirmed, the remaining 18 modeled rats were randomly divided into three groups, a model group, a model + herbal cake-partitioned moxibustion group, and a model + mild moxibustion group, with six rats in each group; the remaining normal rats were randomly divided into three groups, a normal group, a normal + herbal cake-partitioned moxibustion group, and a normal + mild moxibustion group, with six rats in each group. After 7 d of intervention with the herbal cake-partitioned moxibustion or the mild moxibustion, hematoxylin-eosin (HE) staining technique was used to observe the pathological changes of colon tissue under a light microscope; Western blotting and/or immunohistochemical techniques were used to detect the protein expression levels of Occludin, Claudin, junction adhesion molecular 1 (JAM1), mucin 2 (MUC2), and transforming growth factor beta1 (TGF-β1) in rat colon tissue. Results: Compared with the normal group, the colon tissue was severely damaged, the pathological score was significantly increased, and the protein expression levels of Occludin, Claudin, JAM1, MUC2, and TGF-β1 were significantly decreased in the model group (P<0.01); while there were no significant differences in the colonic histopathological score, protein expression levels of Occludin, Claudin, JAM1, MUC2, and TGF-β1 in the normal + herbal cake-partitioned moxibustion group and the normal + mild moxibustion group (P>0.05). Compared with the model group, the model + herbal cake-partitioned moxibustion group and the model + mild moxibustion group showed repaired colon tissue, ulcer healing, significantly reduced pathological score, and significantly increased protein expression levels of JAM1, MUC2, and TGF-β1 (P<0.05); the Occludin protein expression level in the colon tissue of the model + mild moxibustion group was increased (P<0.01). Conclusion: Neither herbal cake-partitioned moxibustion nor mild moxibustion influences the colonic histopathology and intestinal mucosal barrier-related protein expression in the normal rats; both herbal cake-partitioned moxibustion and mild moxibustion can up-regulate the protein expression levels of JAM1, MUC2, and TGF-β1 in the colon tissue of UC rats. Mild moxibustion can up-regulate Occludin protein expression. This may be a mechanism of moxibustion in reducing colonic mucosa inflammation in UC.

Objective To analyze the resistance of clinically cefoxitin -non -susceptible Klebsiella pneumoniae isolates and the prevalence ofβ-lactamase.Methods WHONET 5.6 was used to analyze the resist-ance of 62 strains with non -susceptibility to cefoxitin recovered.Chi -square test was adopted to compare the resistance rates of 62 isolates with the 239 Klebsiella pneumoniae isolates susceptible to cefoxitin collected during the same period.Meanwhile, the 62 clinical isolates were further taken for preliminary screening for ESBLs and carbapenmase by disk -diffusion tests and modified Hodge tests, respectively.Further analysis for detecting the resistant genes encoding AmpC and carbapenemase was carried out by PCR and DNA sequencing.Results On the whole, cefoxin -non - susceptible Klebsiella pneumoniae isolates displayed higher resistances towards all the antimicrobial agents tested ( P <0.05), except for ampicilin.Preliminary screening test showed that 55 strains (88.7%) were ESBLs producers and 39 strains (62.9%) were carbapenemase producers.PCR and DNA sequencing showed that 8 (12.9%) produced AmpC and 39 (62.9%) strains produced KPC carbapenemase, respectively.Conclusion Most of the Klebsiella pneu-moniae isolates non - susceptibilitible to cefoxitin produce KPC carbapenemase and ESBLs, with AmpC being prevalent, posing a great challenge to clinical therapy and infection control.

This study was aimed to investigate the changes of muscle protein synthesis and degradation under different movement conditions, so as to provide theoretical basis for muscle atrophy mechanism. Sprague Dawley (SD) rats were randomly divided into control, endurance training (treadmill training), hind limb overhanging and eccentric training (treadmill training, angle -16º) groups. The gastrocnemius muscles of rats were taken and weighed. The muscle was sectioned, and HE staining was employed to determine the cell's cross-sectional area. Protein expression of p-Akt was measured by immunohistochemistry; and the expressions of MuRF1 and FoxO1 were determined by Western blot. The results showed that, compared with control group, hind limb overhanging and eccentric training groups exhibited decreased muscle weight and cross-sectional area, but endurance training group did not show any changes. The expressions of p-Akt in endurance and eccentric training groups, not in hind limb overhanging group, were significantly higher than that in control group. Compared with that of control, MuRF1 protein remained unchanged in endurance training groups, but was increased in eccentric training and hind limb overhanging groups; FoxO1 protein was decreased in endurance training group, but was increased in eccentric training and hind limb overhanging groups. These results indicate that movement (endurance and eccentric training) can activate Akt expression, but does not increase muscle weight, whereas eccentric training and hind limb overhanging can increase the expressions of MuRF1 and FoxO1, and induce amyotrophy, suggesting MuRF1 and FoxO1 are major determinant factors in muscle atrophy.
Animals ; Forkhead Transcription Factors ; physiology ; Hindlimb Suspension ; Muscle Proteins ; physiology ; Muscle, Skeletal ; physiology ; Muscular Atrophy ; physiopathology ; Nerve Tissue Proteins ; physiology ; Physical Conditioning, Animal ; Proto-Oncogene Proteins c-akt ; physiology ; Rats ; Rats, Sprague-Dawley ; Tripartite Motif Proteins ; Ubiquitin-Protein Ligases ; physiology

This review summarised and compared the contents and methods of America,s Health Rankings (AHR)and the County Health Rankings(CHR)in the United States by using literature review.AHR and CHR are the currently widely used population health assessment index ranking systems in the United States,respectively,which provided an analysis of population health on a state-by-state basis and a county-by-county basis by evaluating a histori-cal and comprehensive set of health outcomes and health determinants data to determine the health benchmarks and state/county rankings.The selection criteria of each indicator take into account of reliability, availability, stability, and intervention.The determination of weights of each indicator took into considerations the literature review,a histori-cal perspective,weights used by other rankings,internal analyses of the variation in outcomes explained by each factor, and pragmatic issues involving communications and stakeholder engagement.By comparison, it was found that AHR and CHR have a higher level of accuracy in the classification as they are well -defined by population demographics and geography respectively.The evaluation of health cities and health villages and towns in China is more complicated. There are few studies on village and town health rankings systems.This article reviewed the evaluation methods of AHR and CHR with a view to providing a reference for research on the evaluation system of City Health Rankings and the Village and Town Health Rankings in China.

Objective To investigate the current status of sleep and its influencing factors among diabetic patients in communities. Methods Using the method of cluster sampling,a total of 449 diabetic patients were selected from 20 communities in Beilun District,Ningbo City. A well -structured questionnaire and physical examination were applied to obtain information,and pittsburgh Sleep Quality Index( pSQI)was also used to compare the sleeping quality of diabetic patients with norm population. Results Out of 449 patients,177(39. 42%)had poor sleeping quality. Compared with norm (3. 88 ± 2. 52),sleeping quality of diabetic patients(5. 50 ± 3. 82)was poorer(p<0. 01). Multivariable logistic regression showed that BMI,family income and cardiovascular diseases( CVD)were the influencing factors of sleeping quality,the value of OR and 95% confidence interval(95%CI)were 0. 93(0. 87-0. 99),0. 35(0. 15-0. 80)and 1. 58(1. 01-2. 47) respectively. Besides,multivariable linear regression showed that family income and retirement were associated with sleeping quality(p<0. 05). Conclusion Sleep disorder remains a common problem among diabetic patients Low BMI,low family income,non-retiree and CVD contribute to poor status of sleep.