Objective Serum uric acid (SUA) levels have been identified to be associated with nonalcoholic fatty liver disease (NAFLD) which is often closely linked to obesity. However, few studies have examined the relationship between SUA levels and NAFLD in normal body mass index (BMI) people in whom NAFLD is noted not uncommon. We conducted this study to assess the association of SUA with NAFLD in Chinese normal-BMI people. Methods A total of 2 193 normal-BMI people (1 106 men and 1087 women) who participated in a health check-up were enrolled in this cross-sectional study. NAFLD was defined as a hepatic steatosis examined by liver ultrasonography in the absence of a second cause. Multiple regression analysis was performed to examine the relationship between SUA and NAFLD. Results Compared with people without NAFLD, those with NAFLD had significantly higher level of serum uric acid [males,(339.0±47.6)μmol/L vs.(309.3±53.5)μmol/L, t=3.296, P<0.01;female,(273.6±41.6)μmol/L vs. (243.9 ± 47.6)μmol/L, t=3.178, P<0.01]. Multiple regression analysis revealed that the quartile 3 and 4 of SUA in both sexes had a higher (P<0.05) odds ratio for the presence of NAFLD than the lowest quartile [males,odds ratio:2.508(1.255-3.374)and 3.383(2.058-5.490);females,odds ratio:2.186(1.090-4.384) and 2.420(1.214-4.821),respectively],after adjusting for age, body mass index, blood urea nitrogen, serum creatinine, the liver-function test, metabolic components, high sensitivity C-reactive protein, and smoking status.Conclusions Increased SUA level, even within the normal range, are independently associated with the presence of NAFLD among normal-BMI people.

Objective To study inhibitory effect of serine protease activity by Ulinastatin in vitro .Methods Different chromogenic peptides were designed and synthesized.Highly sensitive fluorescence detection was performed to optimize the concentration of each serine proteases and their chromogenic substrates.Multi-point method was used for the calculation of half maximal inhibitory concentration of Ulinastatin .ResuIts Ulinastain could inhibit Polymorphonuclear leukocyte elastase ( PMNE ) and plasmin with IC50 lower than 100 U/mL.For factor Xa, and Kallikrein, the IC50 of Ulinastatin was higher than 1000U/mL.No thrombin IC50 could be calculated at the present experiments.ConcIusion Similar to Ulinastatin injection from Japan, domestic Ulinastatin shows the strongest inhibitory effects on PMNE among those serine proteases.As important references, this study gives reliable data for dose range of domestic Ulinastatin in anti-inflammation, coagulation/anti-coagulation and anti-shock therapy.

Objective To evaluate the efficacy and safety of hydroxychloroquine combined with butyli flufenamatum ointment and other drugs for the treatment of polymorphous light eruption (PLE).Methods A total of 48 patients with PLE were randomly and equally classified into group 1 and group 2.Both groups took hydroxychloroquine 200 mg twice a day and loratadine 10 mg per day for the initial 4 weeks,then took hydroxychloroquine 100 mg twice a day alone for another 4 weeks.Group 1 also topically applied butyli flufenamatum ointment twice a day during the 8 weeks,while group 2 applied mometasone furoate cream twice a day for the first 2 weeks followed by butyli flufenamatum ointment twice a day for another 6 weeks.Each treatment cycle lasted 2 weeks,and both groups received 4 cycles of treatment.Patients were evaluated for the response rate at the end of each cycle,and for the total symptom score and erythema score before and after the 8-week treatment.Statistical analysis was carried out using t test,chi-square test,Fisher's exact test and repeated-measures analysis of variance with the SPSS17.0 software.Results On day 14,28,42 and 56,the total score improved in 0,3,12 and 19 patients in group 1 respectively,and in 1,4,12 and 20 patients in group 2 respectively;the erythema score improved in 1,5,13 and 18 patients in group 1 respectively,and in 0,5,11 and 17 patients in group 2 respectively.No significant difference was observed between the two groups in response rates at any of the above four time points (P ＞ 0.05).Both the total score and erythema score significantly decreased after the 8-week treatment in both groups compared with the pretreatment scores (both P ＜ 0.05).No serious adverse reaction was observed in either of the two groups.Conclusions Hydroxychloroquine combined with loratadine and butyli flufenamatum ointment shows high efficacy and safety for the treatment of PLE.Topical butyli flufenamatum ointment is highly effective for the treatment of PLE,especially for PLE cases mainly presenting with erythema.

Aim To establish a cell model targeting on GLP-1 R,and evaluate its function by the cAMP assay,for screening the new class of GLP-1 analogues as anti-diabetic candidates. Methods An eukaryotic expression vector pEGFP-GLP-1 R was constructed and transfected into HEK293A cells.After selecting with G41 8,a cell line stably expressing GLP-1 R-GFP was estab-lished.The expression and the cellular distribution of GLP-1 R-GFP fusion protein were investigated by Western blot and fluo-rescence microscopy.Then,the activity of GLP-1 analogue Lira-glutide was evaluated by monitoring the content of cAMP via HTRF using this cell model.Results GLP-1 R-GFP-293A cell line was successfully established.GLP-1 R-GFP fusion proteins were mainly distributed in the cell membrane.The dose-respon-sive relationship experiments revealed that cAMP could be effec-tively stimulated by Liraglutide using this cell model.Conclu-sion This cell model could be used to detect the bioactivity of GLP-1 analogues in vitro,which lays a foundation for the screen-ing of GLP-1 analogues and small GLP-1 R agonists.

Objective To establish reference ranges of venous blood cell parameters in Lanzhou area ,through investigating 1 880 cases of healthy people .Methods Retrospective analysis method was adopted ,and changes of 26 venous blood cell parameters were observed by using Sysmex XE‐5000 automatic hematology analyzer .Results Some parameters ,including platelet(PLT) and hemo‐globin(Hb) ,were close to normal distribution ,while most of parameters were skewed distribution .In the 6 parameters of white blood cells ,except for percentage of lymphocyte and neutrophi ,the 95% CI of the rest of parameters had statistically significant differences between male and female(P<0 .05) .In the 8 parameters of red blood cell ,except for mean corpuscular haemoglobin con‐centration (MCHC) and standard deviation of red blood cell volume distribution width (RDWSD) ,the 95% CI of the rest of parame‐ters had statistically significant differences between male and female (P<0 .05) .The 95% CI of PLT related parameters and per‐centage of juvenile cells had no statistically significant differences between male and female (P>0 .05) .In some parameters ,there were significant differences between 95% CI observed in this study and reference ranges currently used .Conclusion There are sig‐nificant differences between 95% CI of these parameters and original reference ranges ,so the original reference ranges are lack of ac‐curacy and applicability ,which indicates that it is necessary to scientificlly and rationally establish reference ranges of blood cell in region .

Objective:To investigate the characteristics of short-term prognostic factors in very elderly patients with acute coronary syndrome (ACS).Methods:A total of 2 912 ACS patients admitted to Shengjing Hospital of China Medical University from January 1, 2010 to October 31, 2014 and treated with percutaneous coronary intervention (PCI) were enrolled and divided into two groups according to age: very elderly group (≥75 years, 480 cases) and control group (< 75 years, 2 432 cases). The clinical data and coronary artery lesions of the included patients were detected. Major cardiovascular adverse events (MACE) occurred within 30 d after discharge were followed up and recorded. The short-term prognostic factors in very elderly patients with ACS were analyzed by Logistic regression.Results:Compared with control group, the percentage of hypertension, global registry of acute coronary events (GRACE) score, high density lipoprotein cholesterol, N-terminal pro-brain natriuretic peptide, the left main lesion ratio and Gensini score in very elderly group were higher, while the percentage of men, number of smoking, hyperlipidemia proportion, red blood cell count, white blood cell count, blood platelet count, albumin, and long term oral administration of aspirin, clopidogrel, statins, angiotensin receptor inhibitor after discharge were lower, and the differences were statistically significant ( P<0.01 or<0.05). During the follow-up period, the all-cause mortality in very elderly group was higher than that in control group: 2.5%(12/480) vs. 0.9% (21/2 432), and the difference was statistically significant ( P<0.01). Multivariate analysis showed that oral angiotensin converting enzyme inhibitor was a protective factor for elderly ACS patients after discharge ( OR = 0.046, 95% CI 0.006 to 0.383, P = 0.004). The receiver operating characteristic curve analysis showed that Gensini score ≥ 87.75 scores was a threshold value for all-cause mortality. The all-cause mortality ratio in high Gensini score (≥ 87.75 scores) group was higher than that in low Gensini score (<87.75 scores) group: 6.6% (9/137) vs. 0.9% (3/343), and the difference was statistically significant ( P<0.01). Conclusions:Very elderly patients with ACS have their own characteristics from both clinical history and prognostic factors. Patients with Gensini score of ≥ 87.75 scores should be closely observed, and drug treatment during hospitalization should be intensified if necessary. Follow-up should be strengthened for such patients, and oral drug treatment should be continued after discharge.

Objective:To investigate the infection of spotted fever group Rickettsiae (SFGR) and Rickettsia mooseri ( R.mooseri) of wild rodents in the field of plague foci in Western Yunnan. Methods:The DNA of liver samples of 2 512 wild rodents captured from the plague foci in Lianghe County, Jianchuan County and Yulong County in Western Yunnan from 2015 to 2016 was extracted by magnetic bead method, and the heat shock protein groEL gene primers were used for nested PCR amplification. Gene sequence splicing and Blast homology comparison were performed using DNAStar 7.1 software and GenBank of the National Center for Biotechnology Information (NCBI) of the United States, respectively, and DNAStar 7.1 and MEGA 6.0 softwares were used to construct phylogenetic trees.Results:The wild rodents infected with SFGR were Mus pahari, Rattus steini, Crocidura attenuata and Suncus murinus (one for each), with a total infection rate of 0.16% (4/2 512); no R.mooseri infection was detected. The SFGR infection rates of wild rodents in the plague foci of Lianghe County and Jianchuan County were 0.49% (3/611) and 0.10% (1/1 029), respectively; no SFGR infection was detected in the wild rodents in the plague foci of Yulong County. The homology analysis showed that the homology between SFGR positive samples and reference sequences was 95.45%-100.00%; some of the groEL gene sequences were highly similar among the four positive samples, and the homology was 89.60%-97.40%. Sequence evolution analysis showed that the sequences of three SFGR positive samples from the plague focus in Lianghe County were clustered in the same branch, and the homology reached 94.40%-97.40%; one positive sample sequence from the plague focus in Jianchuan County was clustered in one branch. Conclusion:SFGR infection rate of wild rodents in the field of plague foci in Western Yunnan is low, and no R.mooseri infection is found.

Objective:To analyze the epidemiological and clinical characteristics of human brucellosis in Sichuan Province, and to provide a scientific basis for prevention and control of brucellosis.Methods:Retrospective analysis methods were used to collect the data of reported cases of brucellosis in Sichuan Province from 2018 to 2020 from the "Infectious Disease Reporting Information Management System" in the "China Disease Prevention and Control Information System". The distribution (population, time and region) and case investigation data (epidemiological contact history and clinical manifestations) were analyzed by descriptive epidemiological.Results:A total of 309 cases of brucellosis were reported in Sichuan Province in 2018 - 2020, and no deaths occurred. The annual incidence rate was 0.123/100 000. Among the 309 reported cases of brucellosis, the sex ratio of men to women was 2.4 ∶ 1.0 (218 ∶ 91); the age of onset was mainly 20 - 60 years old, accounting for 79.9% (247/309); the occupation was mainly farmers, accounting for 51.8% (160/309). Brucellosis cases were reported in every month of the year, mainly from March to August, accounting for 72.5% (224/309) of the total number of cases. Cases were reported in 21 cities (autonomous prefectures) in Sichuan Province from 2018 to 2020. The top 5 cities (autonomous prefectures) in terms of cumulative number of cases were Chengdu, Liangshan, Zigong, Neijiang and Luzhou in order, accounting for 60.5% (187/309) of the total number of cases. Among the 309 reported cases of brucellosis, 279 case investigations were completed. Among them, 258 cases had a history of contact with livestock and their products, accounting for 92.5%; all contacted livestock were sheep; the main mode of transmission was direct contact, accounting for 88.5% (247/279); the main routes of transmission were sheep farming (50.2%, 140/279), sheep slaughtering (18.6%, 52/279), selling mutton or cutting sheep products in mutton restaurants (11.1%, 31/279); the main clinical manifestations were fever, fatigue, hyperhidrosis, and muscle and joint pain, accounting for 91.4% (255/279), 89.2% (249/279), 80.3% (224/279) and 65.2% (182/279), respectively.Conclusions:The spread of brucellosis in Sichuan Province is increasing, and spring and summer are the epidemic seasons. Brucellosis cases are most common in sheep farms, and the infection method is mainly direct contact infection; the clinical manifestations are diverse and non-specific. Relevant departments should strengthen the prevention and control of the disease in key populations and regions to control the outbreak of brucellosis.

Objective To investigate the effects of polydatin(PD)on the proliferation and apoptosis of pulmonary artery smooth muscle cells(PASMCs)in hypoxic pulmonary hypertension(HPH)neonatal rats,and its mechanism of action.Methods Neonatal rats were randomly separated into six groups:control group,model group,low dose PD group,medium dose PD group,high dose PD group,and high dose PD+Hippo pathway inhibitor(high dose PD+XMU-MP-1)group,with 10 rats in each group.After 2 weeks of hypoxia treatment,the right ventricular systolic blood pressure(RVSP)and right ventricular hypertro-phy index(RVHI)of rats in each group were measured.Hematoxylin-eosin(HE)staining was applied to observe pathological changes in lung tissue,and the percentage of pulmonary artery wall thickness to total thickness(WT)and the percentage of wall area to total area(WA)were calculated.Neonatal rat PASMCs were separated from each group,which were divided into NC group,hypoxia group,low dose PD group,medium dose PD group,high dose PD group,and high dose PD+XMU-MP-1 group.Cell counting kit 8(CCK-8)and 5-ethynyl-2'-deoxyuridine(EdU)were applied to detect cell proliferation.Flow cytometry was applied to detect cell apoptosis.Western blot was applied to detect the expression of Yes-associated protein 1(YAP1),tran-scriptional coactivator with PDZ-binding motif(TAZ),mammalian sterile 20-like kinase 1(MST1),B-cell lymphoma 2(Bcl-2),and Bcl-2 associated protein(Bax)in lung tissue and PASMCs.Results Compared with the control group,the pulmonary artery wall in the model group was significantly thickened,lumen was narrowed,and protein expressions of RVSP,RVHI,WT％,WA％,YAP1,MST1 and TAZ were significantly increased(all P＜0.05).Compared with the model group,pulmonary artery thickening and lumen enlargement were observed in the low,medium and high dose PD groups,and the protein expressions of RVSP,RVHI,WT％,WA％,YAP1,MST1 and TAZ were significantly decreased,which showed a dose-dependent relationship(all P＜0.05).The effect could be reversed by XMU-MP-1.Compared with the NC group,the cell A450nm value,EdU positive rate,the protein expression of YAP1,MST1,TAZ and Bcl-2 in the hydropoxia group were significantly increased.The apoptosis rate and the expression of Bax protein were obviously reduced(all P＜0.05).Compared with the hypoxia group,the cell A450nm value,EdU positive rate,the protein expression of YAP1,MST1,TAZ and Bcl-2 in the low,medium and high dose PD groups were obviously reduced.The apoptosis rate and the expression of Bax were significantly increased,which showed a dose-depend-ent relationship(all P＜0.05).The effect could be reversed by XMU-MP-1.Conclusion PD may inhibit the proliferation of PASMCs in HPH neonatal rats and promote apoptosis by inhibiting YAP1/TAZ signaling pathway.

Objective:To learn about the infection and gene polymorphisms of hepatitis E virus (HEV) in murine-shaped animals of plague foci in Yunnan Province.Methods:From July to August 2019, around 16 natural villages (4 in Mile City, 6 in Mangshi and 6 in Lianghe County), which were the foci of domestic plague in Yunnan Province, the murine-shaped animals were captured by the night-time method. The liver RNA was extracted, and the target gene of rat HEV was detected by one-step real-time fluorescence quantitative PCR, and the positive rate of rat HEV was calculated. The rat HEV positive samples were amplified by PCR for further clone sequencing, and the resulting sequences were compared with the HEV sequences registered in the GenBank and a phylogenetic tree was constructed by using MegAlign and MEGA 7.0.Results:A total of 491 murine-shaped animals were captured from 3 orders, 5 families, 8 genera, 15 species, and the positive rate of rat HEV was 4.89% (24/491). Among them, the positive rate of Rattus tanezumi and Niviventer fulvescens was 9.39% (23/245) and 1/3, respectively; and other species were negative. There was a statistically significant difference in the positive rate of rat HEV between different habitats ( P = 0.014), and the positive rate of rat HEV in the habitats near the dwellings was higher than that in other habitats ( P < 0.05). The sequence comparison analysis showed that the gene sequence of P018 from Lianghe County was 100.0% homologous to the MG813927.1 sequence of the first patient with rat HEV in Hongkong, and it was clustered into the same branch with the sequences of MG813927.1 and LC549185.1 from rat, was the type HEV C. G024 from Mangshi shared a low homology (20.7% - 31.5%) with other virus strains, and it was clustered into the same branch with a HEV sequence from an avian (AY535004.1). Conclusions:Rat HEV is prevalent in murine-shaped animals of plague foci of Yunnan Province, and there may be gene polymorphisms of rat HEV. In addition, the difference infection rate may be related to the habitats.