Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

ObjectiveTo understand the cooperative work and mechanism in the corona virus disease 2019 containment action by the support-to-Hebei epidemiological investigation group formed by five provinces， summarize the existing challenges， and discuss the relevant mechanism， so as to provide evidence for future support actions. MethodsA questionnaire survey was used to investigate the members from five provinces of the support-to-Hebei epidemiological investigation team. The content included basic information， work situation， problems in cooperative work， and suggestions in support mechanisms. ResultsA total of 104 questionnaires were issued， of which 101 valid questionnaires were collected with an effective response rate of 97.12%. The proportions of respondents who participated in the epidemic-related data preparation， case investigation， technical training， supervision of key venues， and specimen collection was 93.07%， 85.15%， 81.19%， 65.35%， and 44.55%， respectively. The respondents believed that information sharing channel of local epidemic situation was blocked （95.05%）， coordination mechanism among local departments was insufficient （84.16%）， communication and coordination mechanism among the dispatch institutions， support team， and local departments was unperfect （84.16%）， management of the dispatch institutions to the support team was relatively loose （79.21%）， dispatch institutions failed to make full use of professional advantages of the support team （72.28%）， and majority of the support team members engaged in a single profession （59.41%）. The respondents suggested that local departments should improve the information sharing mechanism （95.05%）， strengthen communication and coordination among the dispatch institutions， support team， and local departments （92.08%）， and dispatch institutions should clarify the tasks and responsibilities of the support team （91.09%）， formulate cross-regional emergency support plans （87.13%） and evaluation plans of support action （72.28%）. ConclusionIn order to ensure the efficiency and accuracy of future support actions， it is necessary to improve the mechanism of emergency coordination， communication and matching， response procedures， team management， and support evaluation.

Objective: To assess clinical effect and safety of botulinum toxin A injection in external urethral sphincter for male patient with neurogenic detrusor underactivity(DU). Methods: A prospective and self-controlled trail was conducted from August 2012 to October 2017. Male patients with nerve injury, dysuria more than 6 months, DU(bladder contractility index less than 100) were enrolled in this study. Exclusion criteria included patients with acute urinary tract infection, bladder stone, benign prostate hyperplasia, urethral stricture and urethral diverticulum.100 IU BTX-A was dissolved in 4ml normal saline, and the solution of BTX- A was injected into 4 different points(3-o’clock, 6-o’clock, 9-o’clock, and 12-o’clock) in external urinary sphincter with each point of 1ml solution. Patients were evaluated at baseline and 12 weeks after injection. The outcomes included post void residual (PVR), maximum flow rate (Q_max), maximum detrusor pressure during voiding phases (P_det.max), maximum urethral closure pressure (MUCP), the case number of intermittent catheterization (IC)and the score of quality of life (QOL score). Adverse events were also recorded. Results: A total of 58 male patients (all from Guangdong provincial work injury rehabilitation hospital)with mean age 28.6 years suffered from cerebral palsy (n=2), cerebrovascular accident(n=19)and spinal cord injury(n=37) were included into the study. Compared to baseline data, significant difference were observed at week 12 in PVR (56.68 ml vs. 280.11 ml, P<0.001), P_det.max(23.95 cmH₂O vs. 30.01 cmH₂O, P=0.019), Q_max(6.74 ml/s vs. 3.28 ml/s, P=0.042), MUCP(48.25 cmH₂O vs. 79.34 cmH₂O, P<0.001), the case number of IC(40 vs. 58, P<0.001) and QOL score(3.63 vs.5.22, P<0.001) respectively. 5 cases developed perineal pain and 16 cases developed mild transient haematuria. These adverse events were disappeared by medical symptomatic treatment during 3-5 days. Conclusions BTX-A externalurethral sphincter injections help reduce urethra resistance and also improve the quality of life for patients with neurogenic detrusor underactivity.

Objective To investigate the serum and placental expressions of asymmetric dimethylarginine (ADMA) and nitric oxide(NO) in fetal growth restriction (FGR),and explore the biological role and mechanisms of ADMA in FGR.Methods Fifty patients with FGR (FGR group)and 50 normal term pregnant women (control group) were detected for the levels of ADMA in maternal sera and placentas with enzyme linked immunosorbent assay (ELISA).The level of NO in maternal sera was analyzed with nitrate reductase method,and the placental tissue sections were analyzed with pathological morphologly.Results For FGR group,the main pathological changes were growth retardation of villi,increased syncytiotrophoblast nodules,and the lack terminal villi;and the incidence rate of pathological change of placental tissue was significantly higher than that in control group [64.0％ (32/50) vs 12.0％ (6/50),x2 =7.90,P ＜ 0.01].For the placental pathological change group,the concentrations of ADMA in the placentas and sera were significantly higher than the normal group [placenta ADMA:(2.21 ± 0.72) μmol/L vs (1.69 ± 0.77) μmol/L,t =3.33,P ＜ 0.01;serum ADMA:(2.01 ± 0.70) μmoL/L vs (1.18 ± 0.54) μmol/L,t =6.66,P ＜0.01].The expression of ADMA was up-regulated in maternal sera and placentas from FGR group compared to normal pregnancy [placenta ADMA (2.24 ± 0.81) μmol/L vs (1.53 ± 0.59) μmol/L,t =5.00,P ＜0.01;serum ADMA (1.89 ±0.75) μmol/L vs (1.10 ±0.43) μ mol/L,t =6.45,P ＜ 0.O1].The NO was extremely lower expressed in maternal sera with FGR than normal pregnancy [(39.59 ± 9.15) μmol/L vs (58.02 ± 15.45) μmol/L t =-7.26,P ＜ 0.01)].For FGR group,a significant negative correlation was observed between ADMA and NO expressions in sera (r =-0.693,P ＜ 0.01).Conelusions ADMA was associated with the occurrence and development of the FGR,and its mechanism maybe inhibits NO synthesis to result in placental malperfusion.

Objective To determine the clinical significance of pulmonary function test(PFT)in evaluating the features and severity of lung impairments associated with connective tissue diseases(CTD)by comparing the differences of pulmonary function test parameters among groups of CTD associated pulmonary disorders.Methods Cases of CTD associated pulmonary disorders were prospectively enrolled and assigned into 3 groups according to their lung impairments:CTD associated pulmonary arterial hypertension group (CTD-PAH,n=29),CTD associated interstitial lung disease group(CTD-ILD,n=35),CTD associated PAH plus ILD group(CTD-PAH+ILD,n=16)and CTD control group(n=34).Pulmonary function test parameters,including total lung capacity(TLC % predicted),forced vital capacity(FVC % predicted),forced expiratory volume in the first second(FEV_(1.0)% predicted),FE_(1.0)%/FVC and diffusing capacity of the lung for carbon monoxide(DLco,% predicted)were measured and compared among the four groups.Results One hundred and forteen eases were included and predominantly female with average onset age of 35～39 years old.CTDs that were predisposed to lung diseases were mixed connective disease(MCTD),systemic sclerosis(SSc),systemic lupus erythematosus(SLE)and primary Sj(o)ren syndrome(pSS),in order.There were 10,29 and 46 percent of patients presented with decreased TLC% in CTD-PAH,CTD-ILD and CTD-PAH+ILD group respectively,50,36 and 71 percent of patients with decreased FVC% respectively,54,47 and 71 percent of patients with decreased FEV_(1.0)% respectively,and 100,82 and 100 percent with decreased DLco% respectively.ANOVA analysis demonstrated that TLC%,FVC%,FEV_(1.0)%,DLco% had significant differences between CTD control group and each of the CTD associated lung disease group(P＜0.05),although none of them was lack of difference between the PAH and ILD groups.TLC% was significantly higher in CTD-PAH group than CTD-PAH+ILD group[(89±15)% vs(79±12)%,P＜0.05],while FVC% was significantly lower in CTDPAH+ILD group either than CTD-PAH group or than CTD-ILD group[(81±13)%,(80±16)% vs(65±22)%,P＜0.05].ConclusionPulmonary function test may be valuable in early screening for CTD associated lung disorders than distinguishing CTD-PAH from ILD,which usually reveal restrictive ventilation dysfunction and/or diffusing capacity dysfunction.

OBJECTIVETo understand the mutational patterns and mechanism of short tandem repeats(STRs).

METHODSThe DNA samples of 19 parent-child pairs with mutations in three loci (FGA, D12S391, and D11S554) were genotyped by silver staining on STR. Alleles to be sequenced were excised from gels, reamplified by PCR, and purified. Sequencing was performed by use of cycle sequencing.

RESULTSThere were 18 out of 19 pedigrees in which the 'new' alleles gained or lost a single repeat (8 gains, 7 losses, and 3 being indistinguishable). Only one pedigree lost two repeats. In the 19 pedigrees, there were 13 pedigrees whose 'new' alleles came from fathers, 3 from mothers, 3 from either father or mother. The ratio was 4 1 between fathers and mothers. The mutation of three STR loci occurred in the long, uninterrupted tetranucleotide repeat regions ('CTTT' in FGA, 'AGAT' in D12S391, and 'AAAG' in D11S554).

CONCLUSIONSingle- step mutations accounted for 95% of STR mutation events in these three loci: FGA, D12S391, and D11S554. The rest were double step mutations. There was no insertion or deletion of an incomplete repeat in any of the pedigrees. The mutation was mainly caused by fathers. The long, uninterrupted tetranucleotide repeats in these three loci might be susceptible to mutation.

Alleles ; Base Sequence ; DNA ; chemistry ; genetics ; DNA Mutational Analysis ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Microsatellite Repeats ; genetics ; Mutation ; Nuclear Family ; Tandem Repeat Sequences ; genetics