Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

OBJECTIVE: To observe the efficacy of the combined treatment with acupuncture and governor vessel moxibustion on ankylosing spondylitis (AS) at early-middle stage and investigate the effect on bone marrow edema of sacroiliac joint. METHODS: Seventy patients of AS at early-middle stage were randomized into an observation group (35 cases) and a control group (35 cases, 1 case dropped off ). In the control group, the recombinant human tumor necrosis factor receptor-antibody of type Ⅱ fusion protein for injection was injected subcutaneously, 25 mg each time, once on every Monday and Friday, consecutively for 3 weeks. In the observation group, on the base of the intervention as the control group, acupuncture combined with governor vessel moxibustion were provided. Acupuncture was applied to Dazhui (GV 14), Changqiang (GV 1), Zhibian (BL 54), Baihui (GV 20), etc.; the thermal needling technique was adopted at Dazhui (GV 4) and Changqiang (GV 1) for promoting the circulation of the governor vessel, and the ginger-isolated moxibustion on the governor vessel was combined. Such intervention measure was provided once daily. One treatment session contained 7 treatments and 3 sessions were required. Before and after treatment, the scores of Spondyloarthritis Research Consortium of Canada (SPARCC), Bath ankylosing spondylitis disease activity index (BASDAI) and Bath ankylosing spondylitis functional index (BASFI) and Bath ankylosing spondylitis patient global score (BAS-G) were observed in the two groups separately. The efficacy and adverse effects were assessed in the two groups after treatment. RESULTS: The scores of SPARCC, BASDAI, BASFI and BAS-G were all reduced after treatment compared with those before treatment in the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). The total effective rate was 97.1% (34/35) in the observation group, higher than 82.4% (28/34) in the control group (P<0.05). There were 4 cases of gastrointestinal reactions and 1 case of skin rashes in the control group; and 3 cases of local skin redness and pruritus after governor vessel moxibustion, no any drug adverse effect was found in the observation group. CONCLUSION Based on the western medicine treatment, the combined therapy of acupuncture and governor vessel moxibustion may relieve bone marrow edema of sacroiliac joint in patients with AS at early-middle stage, control the progression of disease and improve the daily life activity. This therapy is relatively safe and effective.
Acupuncture Points ; Acupuncture Therapy/methods* ; Bone Marrow ; Edema/therapy* ; Humans ; Moxibustion/methods* ; Sacroiliac Joint ; Spondylitis, Ankylosing/therapy*

Gut microbiome sequencing studies have great potential to translate microbial analysis outcomes into human health research. Sequencing strategies of 16S amplicon and whole-metagenome shotgun (WMS) are two main methods in microbiome research with respective advantages. However, how sample heterogeneity, sequencers and library preparation protocols affect the sequencing reproducibility of gut microbiome needs further investigation. This study aims to provide a reference for the selection of sequencing technologies by comparing differences in microbial composition from different sampling sites. The results of three widely adopted sequencers showed that the technical repetition correlation (r= 0. 94) was high in WMS method, while the biological repetition correlation (r = 0. 69) was low. Bray-Curtis distance identified that dissimilarity from biological replicates was larger than that of technical replicates (P<0. 001). In addition, dissimilarity and specific taxonomic profiles were observed between 16S and WMS datasets. Our results imply that homogenization is a necessary step before sample DNA extraction. The sequencers contributed less to taxonomic variation than the library preparation protocols. We developed an empirical Bayes approach that " borrowed information" in calculations and analyzed batch effect parameters using standardized data and prior distributions of (non-) parameters, which may improve population comparability between 16S and WMS and provide a basis for further application to fusion analysis of published 16S and microbial datasets.

OBJECTIVE: To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes. METHODS: The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables. RESULTS: The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120－0.407), 0.404 (95%CI: 0.135－0.673), and 0.799 (95%CI: 0.590－1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120－1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181－0.788, P<0.05). CONCLUSION Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.
Blood Pressure ; Chronic Disease ; Female ; Heart Rate ; Humans ; Hypertension ; Male ; Middle Aged ; Pedigree

Objective: To observe the effect of poloxamer 188 (P188) on megakaryocyte cultivation and induction from cord blood mononuclear cells in order to obtain more megakaryocyte progenitor cells (MPC). Methods: The cord blood mononuclear cells were isolated and inoculated in cell culture bag or cell culture flask respectively. The WIGGENS shaker and cell culture bags were used to mimick WAVE Bioreactor for three-dimensional (3D) cell culture, and the P188 was added to induction medium, The cells were detected for morphology, surface marker, viability, and number on day 14. Results: In the two-dimensional (2D) culture, CD41(+), CD41(+)/CD61(+), CD61(+) megakaryocytic numbers increased significantly after adding P188 (all P<0.01). And in the 3D culture of adding P188, the cell volume became larger and the nuclear shape was irregular, the cytoplasm appeared magenta granules, and the megakaryocyte cells became more mature. By 3D culture, the expression of CD41/CD61 was (36.30±1.27)% vs (23.95±1.34)%, hence the differentiation for MPC was significantly higher than that in the 2D group (P<0.01). Furthermore, adding P188 in 3D culture resulted in highest differentiation efficiency for MPC [(59.45±1.20)%]. There were no significantly differences in terms of cell viability and cell number among 3D culture containing P188, 2D and 3D culture groups (all P>0.05). Conclusion: 3D culture was beneficial for the differentiation of MPC, but the cell viability was lower than 2D group; However, the satisfied cell growth and better induction efficiency were obtained by adding of P188, which might provide a new method of megakaryocytes production for clinical application.
Bioreactors ; Cell Differentiation ; Cells, Cultured ; Fetal Blood ; Megakaryocytes ; Poloxamer

Clinical breakpoints are used in phaseⅡorⅢclinical trials to categorize microorganisms if susceptibility to new tested antibacterial agents that means the patient infected by the pathogen will be enrolled the study or not.The role of this consensus is to define procedure and required data to setting breakpoints and how to revaluate it in clinical trials.

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.

OBJECTIVETo investigate the effect of Shenshao Decoction on the inflammatory status: in the aorta in a rat model of atherosclerosis.

METHODSForty Sprague-Dawley rats were randomly divided into: five groups, 8 rats in each group: control untreated group, atherosclerosis group, atherosclerosis with Shenshao Decoction (low dose) group, atherosclerosis with Shenshao Decoction (high dose) group, atherosclerosis with simvastatin group. To stimulate atherosclerosis, the rats were fed vitamin D3 and a high-cholesterol diet. Four weeks later, treatments were maintained for eight weeks. Morphology changes were investigated by hematoxylin and eosin staining. Serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were obtained by enzymatic assays with use of an automated biochemical analyzer. The expression of malondialdehyde (MDA), glutathione peroxidase (GSH-PX) were detected by enzyme-enzymelinked immunosorbent assay. The expression levels of interleukin (IL)-1β, IL-17A, and IL-23 were detected by linked immunoblotting.

RESULTSShenshao Decoction treatment decreased TC, TG, LDL-C and MDA and increased: GSH-PX levels (P<0.01). Compared with the control group, IL-1β, IL-17A, and IL-23 were lower in the high and

CONCLUSIONShenshao Decoction: could attenuate the progression of aortal atherosclerotic plaques by inhibiting the inflammatory response in a rat atherosclerotic model.

Animals ; Aorta, Thoracic ; drug effects ; pathology ; Atherosclerosis ; blood ; drug therapy ; pathology ; Cholesterol ; blood ; Cholesterol, LDL ; blood ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Glutathione Peroxidase ; blood ; Immunohistochemistry ; Inflammation ; drug therapy ; pathology ; Interleukin-17 ; metabolism ; Interleukin-1beta ; metabolism ; Interleukin-23 ; metabolism ; Male ; Malondialdehyde ; blood ; Rats ; Rats, Sprague-Dawley ; Triglycerides ; blood

Objective To explore the suicide intention and its influential factors among primary and junior high school students in rural areas of Anhui province,in order to provide evidence for early intervention related to mental health problems.Methods All students from 3 junior high and 5 primary schools in Changfeng county of Anhui were recruited as the study subjects using the cluster sampling method.Data were collected by using Children' s Depression Inventory,the Family APGAR Index,the Trait Coping Style Questionnaire,the Children' s Self-Esteem Scale,Social Anxiety Scale for Children,and the Quality of Life Scale.Chi-square test and Logistic regression were used to analyze the suicidal ideation and its influential factors respectively.Results 8.64％ (252/2917) of the studied children had suicidal ideation.Out of them,9.80％ (166/1694) and 7.03％ (86/1223) were left-behind or non-left-behind children.There was statistically significant difference on suicide ideation between the left-behind children and non-left-behind children (P=0.015).Data from the multivariate logistic regression analysis showed that social anxiety and negative coping style were the risk factors for suicidal ideation (P ＜0.05) while better family function and quality of life were the protective factors of suicidal ideation (P＜0.05).Conclusion Suicide ideation was relatively prevalent among rural children in Anhui province.Family,school and society should carry out different kinds of preventive measures to prevent suicide related behaviors in children from this area.

OBJECTIVETo evaluate the efficacy and safety of endoscopic mucous resection with transparent cap (EMR-Cap) and endoscopic multi-band mucosectomy (MBM) in the treatment of early esophageal cancer and precancerous lesion.

METHODSA retrospective study was performed to review 30 EMR-Cap cases from December 2008 to December 2009 and 32 MBM cases from January 2010 to January 2011 of early esophageal cancer and precancerous lesions. The differences between these two techniques in efficacy, safety, and cost were compared.

RESULTSIn EMR-Cap group, the median resection time was 26(10-56) min and median procedure time was 43(22-81) min, significantly longer than those in MBM group [10(7-18) min and 32(28-45) min, P=0.036 and 0.038, respectively]. There were no significant differences between the two groups in total thickness and depth of resected lesions (P>0.05). In EMR-Cap group, the median cost was significantly higher than that of MBM group [(5466±354) vs. (4014±368) RMB, P=0.008)].

CONCLUSIONSEMR-Cap and MBM are minimally invasive, safe and effective methods in the treatment of early esophageal cancer and precancerous lesions. Compared to the EMR-Cap, MBM is simple with shorter treatment time and lower cost.

Aged ; Endoscopy ; methods ; Esophageal Neoplasms ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Mucous Membrane ; surgery ; Precancerous Conditions ; surgery ; Retrospective Studies ; Treatment Outcome