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 analyze the influenza vaccination trend of hospitalized elderly people (≥ 60 years old) in Beijing from 2013 to 2019. METHODS: The influenza vaccination status and hospitalization information of elderly people were extracted from the Beijing Elderly Influenza Vaccination database (2013-2019) and the Beijing Urban Employee Basic Medical Insurance database (2013-2019), se-parately. The influenza vaccine coverage rates and annual percentage change were calculated to compare the vaccination trends of elderly people hospitalized due to different diseases. The subjects in 2018-2019 influenza season were divided into different groups according to demographic status, health conditions and hospitalization outcomes to describe and compare the distribution of influenza vaccination rates. RESULTS: The influenza vaccine coverage rates among the elderly people hospitalized due to cardiovascular diseases, cerebrovascular diseases, respiratory diseases or diabetes mellitus were 14.6%, 13.4%, 13.4% and 11.8%, respectively. The influenza vaccination rate among those hospitalized for cardiovascular diseases remained the highest across six influenza seasons and those hospitalized for diabetes mellitus remained the lowest. The largest annual decline of influenza vaccine coverage rate was observed among the hospitalized elderly due to diabetes mellitus (-7.85%). The distribution of vaccinated population was significantly associated with age, gender, hospitalization outcome and comorbidities among the hospitalized elderly people with specific diseases in 2018-2019. Among the elderly people hospitalized due to four different diseases, the vaccination rate of the patients aged 70-79 years was higher than that of the other age groups and that of the patients aged 60-69 years was the lowest. Among the elderly people hospitalized due to respiratory diseases, the vaccination rate of men was higher than that of women, while the situation reversed among the elderly people hospitalized due to cardiovascular diseases and diabetes mellitus. Vaccination rates decreased among the older adults with poor hospitalization outcomes. Among the elderly people hospitalized due to diabetes mellitus, those with 0 comorbidity had the lowest vaccination rate (7.9%). CONCLUSION The trend of influenza vaccine coverage rates among the elderly people in Beijing from 2013 to 2019 was downward. We should pay more attention to influenza vaccination in elderly people with diabetes mellitus and aged 60-69 years, and carry out more research on the protective effects of influenza vaccine to promote influenza vaccine coverage among people with chronic diseases.
Aged ; Beijing ; Cardiovascular Diseases ; Female ; Hospitalization ; Humans ; Influenza Vaccines ; Influenza, Human/prevention & control* ; Male ; Middle Aged ; Vaccination

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.

Pluripotent stem cells (PSCs) can be expanded in vitro in different culture conditions, resulting in a spectrum of cell states with distinct properties. Understanding how PSCs transition from one state to another, ultimately leading to lineage-specific differentiation, is important for devel-opmental biology and regenerative medicine. Although there is significant information regarding gene expression changes controlling these transitions, less is known about post-translational modifi-cations of proteins. Protein crotonylation is a newly discovered post-translational modification where lysine residues are modified with a crotonyl group. Here, we employed affinity purification of crotonylated peptides and liquid chromatography–tandem mass spectrometry (LC–MS/MS) to systematically profile protein crotonylation in mouse PSCs in different states includ-ing ground, metastable, and primed states, as well as metastable PSCs undergoing early pluripotency exit. We successfully identified 3628 high-confidence crotonylated sites in 1426 proteins. These crotonylated proteins are enriched for factors involved in functions/processes related to pluripotency such as RNA biogenesis, central carbon metabolism, and proteasome function. Moreover, we found that increasing the cellular levels of crotonyl-coenzyme A (crotonyl-CoA) through crotonic acid treatment promotes proteasome activity in metastable PSCs and delays their differentiation, consis-tent with previous observations showing that enhanced proteasome activity helps to sustain pluripo-tency. Our atlas of protein crotonylation will be valuable for further studies of pluripotency regulation and may also provide insights into the role of metabolism in other cell fate transitions.

AIM:To observe the expression of microRNA-126-5p during myocardial injury and its role in myo-cardial cell injury induced by adriamycin(also called doxorubicin, DOX).METHODS: The BALB/c mouse model of DOX-induced acute and chronic myocardial injury was established via intraperitoneal injection of DOX.HE staining was applied to observe the morphological changes of myocardial tissues.Lactate dehydrogenase(LDH)in serum was detected and PowerLab system was used to detect the influence of DOX on the changes of ±dp/dtmax.The expression of microRNA-126-5p in injured myocardial tissues and the H 9c2 cells exposed to DOX was detected by real-time PCR.Gain-and loss-of-function experiments were conducted to detect the role of microRNA-126-5p in H9c2 cells treated with DOX on LDH release and caspase-3 activation.RESULTS:In acute and chronic DOX myocardial damage models in mice,HE staining showed disarranged myocardial fibers, dissolved myofibril and inflammatory cell infiltration.Higher serum LDH level and lower ±dp/dtmaxin DOX-treated mice than those in normal mice were found.Compared with the normal mice, the expression level of microRNA-126-5p was significant increased in the myocardium with DOX-induced injury.Similarly,the expression level of microRNA-126-5p was significant increased in the H9c2 cells treated with DOX.In addition, over-expression of microRNA-126-5p decreased cell viability and promoted apoptosis,while microRNA-126-5p ablation promoted the viability and inhibited the apoptosis of H9c2 cells.CONCLUSION:The microRNA-126-5p expression is up-regulated in myocar-dial injury induced by DOX,and microRNA-126-5p inhibits cell viability and promotes apoptosis induced by DOX.

Objective To investigate the constituents of water and ethanol extracts from the stems and leaves ofAucklandia lappa and their effect on gastric emptying and intestinal propulsion of gastrointestinal normal,hyperthyroidism and inhibited mice.Methods The water,ethanol and aether petrolei extracts from stems and leaves of A.lappa were prepared,and the chemical constituents of the stems and leaves were identified by chemical reaction.The hyperthyroidism state was induced by neostigmine and inhibiting state was induced by atropine.Mice were ig administered with water and ethanol extracts (0.5 g/kg),with the improved phenol red method to determine gastric emptying and intestinal propulsion in gastrointestinal normal,hyperthyroidism and inhibited mice.Results Both water and ethanol extracts significantly improved intestinal propulsion in normal mice (P ＜ 0.05 and 0.01),while significantly decreased the intestinal propulsion in hyperthyroidism mice (P ＜ 0.05) and ethanol extract showed a stronger decreasing effect than that of water extract.The inhibitory effect of atropine on intestinal propulsion was intensified by these two extracts (P ＜ 0.05).The restrained gastric emptying of normal,hyperthyroidism and inhibited mice was also observed.Chemical composition analysis indicated that many kinds of chemical components including protein,sugar,essential oil,flavonoids,lactones,alkaloids,saponins and tannins existed in the leaves and stems of A.lappa.Conclusion The leaves and stems of A.lappa could promote the intestinal propulsion of normal mice and restrain the intestinal propulsion of hyperthyroidism and inhibited mice while inhibit the gastric emptying in any condition tested,and its promoting effect on the gut may be related to the M cholinergic receptor.

The application of prostate-specific antigen (PSA) in the screening and diagnosis of prostate cancer (PCa) has improved the clinical management of PCa patients.However,the PSA assay has been faced with criticism due to its potential association with over-diagnosis and subsequent overtreatment of indolent patients.Matrix metalloproteinase-26 (MMP26) is a member of matrix metalloproteinases (MMPs) and has been reported to be highly expressed in many cancers.This investigation evaluated the potential of serum MMP26 as a biomarker for PCa.The level of serum MMP26 was measured by enzyme-linked immunosorbent assay (ELISA) in 160 subjects including PCa group (n=80),benign prostatic hyperplasia (BPH) group (n=40) and control group (n=40).Furthermore,we evaluated the expression of MMP26 in tissues by immunohistochemistry.The results showed the serum MMP26 levels were significantly higher in PCa group than in BPH group and control group.Similarly,the MMP26 protein was positive in PCa tissues and negative in BPH tissues and control tissues.In conclusion,these results suggested MMP26 could be used as a potential serum biomarker in the diagnosis of PCa.

Objective:To investigate the effectiveness of immunoFISH technology in detecting tumor cells in cerebrospinal fluid (CSF) for adjuvant diagnosis of meningeal metastasis from lung cancer. Methods:Circulating tumor cells (CTCs) were detected by im-munoFISH technology in CSF samples from 16 patients with meningeal metastasis from lung cancer and 8 patients with non-tumorous brain diseases. Meningeal metastasis from lung cancer was diagnosed on the basis of neurological symptoms and confirmed by en-hanced magnetic resonance imaging and CSF cytological examination. Results:The number of CTCs was significantly greater in pa-tients with meningeal metastasis from lung cancer than in those with non-tumorous brain diseases (P<0.01). The critical point of the maximum correct diagnosis index (Youden index) was regarded as the judging criterion for the positive tumor cells in CSF based on the receiver operating characteristic curve. When one tumor cell existed in 7.5 mL of CSF, the area under the curve was 0.875, and the 95%confidence interval ranged from 0.705 to 1.000. The diagnostic sensitivity, specificity, effectiveness, positive predictive values, and neg-ative predictive values were 75.0%, 100.0%, 83.3%, 100.0%, and 66.7%, respectively. Conclusion:ImmunoFISH technology provides great significance in detecting CTCs in CSF to diagnose meningeal metastasis from lung cancer.

Objective To evaluate the antibacterial activities of severalβ-lactam/β-lactam inhibitor combinations in vitro.Methods All the clinical isolates were Enterobacteriaceae collected from hospitals and the susceptibility tests were performed using agar dilution method recom-mended by CLSI.The minimum inhibitory concentration ( MIC ) results were interpreted according to the breakpoints of CLSI (2014) guideline.The data was analyzed by software SPSS17.0.Results A total of 2166 Enterobacteriaceae were collected and were performed MIC tests.Based on the MIC results, the MIC50 and MIC90 of piperacillin to Escherichia coli were 256 , 512 μg · mL-1 , while piperacillin/tazobactam were 2 , 8μg· mL-1 , respectively.The sensitive rates of piperacillin/tazobactam to ESBLs -producing Escherichia coli and Klebsiella pneumoniae were 93.7% and 86.1%, cefoperazone/tazobactam were 91.5% and 82.5%, while cefoperazone /sulbactam were 74.4% and 58.39%. Among ESBLs -non -producing Escherichia coli and Klebsiella pneumoniae, there is not much difference between using β-lactam/β-lactam inhibitor combinations and β-lactams alone.β-lactam antibiotics have higher sensitive rates to Proteus vulgaris than Proteus mirabilis, butβ-lactam/β-lactam inhibitor combinations have no difference against them.The sensitive rate of mezlocillin/sulbactam to Morganella spp.was 97.4%, significantly higher than mezlocillin alone with sensitive rate 76.3%.The MIC90 of cefotaxime/tazobactam and ceftriaxone/tazobactam were lower than using cefotaxime and ceftriaxone alone.Conclusion β-lactam/β-lactam inhibitor combinations have greater antimicrobial activity to Enterobacteriaceae than β-lactams alone, especially for ESBLs-producing Escherichia coli and Klebsiella pneumoniae.Among them, piperacillin/tazobactam has the greatest antimicrobial activity.

Objective To investigate the distribution and antimicrobial resistance of clinical isolates derived from intensive care unit(ICU) pa-tients in China in 2012.Methods A total of 94178 non -duplicate clinical isolates from ICU of 557 tertiary hospitals were collected from January 2012 to December 2012.Antimicrobial susceptibility testing was carried out according to a unified using disc diffusion test ( Kirby-Bauer method ) or automated systems.The data were analyzed by WHONET 5.6 software according to Clinical and Laboratory Standards Institute ( CLSI) 2012 breakpoints.Results Among these 94178 non-duplicate clinical isolates, gram-negative organisms and gram-positive organisms accounted for 75.6% and 24.4%, respectively.The 5 most common pathogens in ICU were Acinetobacter baumannii ( 15.8%) , Klebsiella pneumoniae ( 14.7%) , Pseudomonas aeruginosa ( 12.8%) , Escherichia coli ( 12.5%) and Staphylococcus aureus (8.5%).Methicillin -resistant Staphylococcus aureus ( MRSA ) strains and coagulase -negative Staphylococcus ( MRCNS) accounted for 57.5% and 83.7%, respectively.However, 69.2% of Staphylococcus aureus strains were still susceptible to trimethoprim -sulfamethoxazole, while 83.9% of CNS strains were susceptible to rifampin.No Staphylococcus aureus strain was resistant to vancomycin, teicoplanin and linezolid.2.1% of the CNS strains were found resistant to teicoplanin.The resistant rates of Enterococcus faecalis and Enterococcus faecium to vancomycin, teicoplanin and linezolid were 1.8%, 3.1%,2.3% and 5.9%,5.9%1.4%, respectively.Extended spectrum β-lactamases ( ESBLs)-producing strains accounted for 67.5%, 45.4%, 32.5%and 39.5%in Escherichia coli, Kleb-siella pneumoniae, Klebsiella oxytoca and Proteus mirabilis, respectively.Overall, 2.2%-10.4%of the Enterobacteria-ceae strains were resistant to carbapenems.The resistance rates of Acinetobacter baumannii to imipenem and meropenem were 70.8 and 69.2%, respectively.The resistance rates of Pseudomonas aeruginosa to imipenem and meropenem were 38.5%and 37.4%, respectively.Conclusion Bacterial resistance is still an serious problem in ICU in China, espe-cially the carbapenem resistant Enterbacteriaceae and Acinetobacter baumannii.It is mandatory to take effective hospital infection contral measures and rational use antibiotics.