Objective To study the efficacy and safety of low-dose azithromycin with tiotropium bromide in the treatment of stable chronic obstructive pulmonary disease.Methods A hundred and ten patients were randomized into three groups:tiotropium bromide group (36 cases,group A),azithromycin with tiotropium bromide group(38 cases,group B)and control group(36 cases,group C).Patients in group A were given tiotropium bromide (18 μg,q,d )in addition to conventional treatment.The patients in group B were given lowdose azithromycin (250 mg,twice a week) in combined with tiotropium bromide.The patients in control group were given the conventional treatment only.The courses of treatment lasted for six months.Results Compared with the control group,the frequency of acute exacerbation in patients treated with azithromycin and tiotropium bromide was reduced remarkably ( 2.1 ± 0.6 and 4.9 ± 0.7,t =18.5061,P ＜ 0.05 ).The severity of clinic symptoms ( Cough 1.3 ± 0.5 vs.2.2 ± 0.6,P ＜ 0.05 ),expectoration ( 1.0 ± 0.2 vs.1.7 ± 0.3,P ＜ 0.05 ),anhelation ( 1.5 ± 0.8 vs.2.1 ± 0.6,t =3.6342,P ＜ 0.001 ) ],life quality ( 29 ± 8 vs.42 ± 11,P ＜ 0.05 ) and six-minutes walking distance( [ 370.00 ± 14.26 ] m vs.[ 290.00 ± 12.85 ] m,P ＜ 0.05 ) of the azithromycin with tiotropium bromide group were improved significantly when compared with control.Compared with the tiotropium bromide group,the frequency of acute exacerbation ( 2.1 ± 0.6 vs.3.2 ± 0.8,P ＜ 0.05 ),the severity of clinic symptoms (Cough 1.3 ±0.5 vs.1.8 ±0.4,P＜0.05),expectoration( 1.0 ±0.2 vs.1.3 ±0.3,P ＜0.05) and anhelation( 1.5 ±0.8 vs.1.9 ± 0.6,P ＜ 0.05 ) ],life quality ( 29 ± 8 vs.36 ± 10,P ＜ 0.05 ) and six-minutes walking distance ( [ 370.00 ± 14.26 ] m vs.[ 330.00 ± 13.76 ] m,P ＜ 0.05 ) were improved over those of tiotropium bromide group.Conclusion The long-term low-dose azithromycin in combinned with tiotropium bromide is good and safe in treating stable COPD.Therefore,it is worth of further clinical evaluation.

Objective To investigate the significance of optimization of bedside Gram staining of sputum smear in the early diagnosis and antimicrobial treatment for ventilator-associated pneumonia(VAP)patients. Methods The data of patients with VAP undergoing mechanical ventilation over 48 hours in the Department of Critical Care Medicine of Tianjin Fourth Central Hospital from June 2009 to June 2014 were analyzed. The patients were divided into two groups according to whether or not bedside Gram staining of sputum smear was used or not. The sputum samples from lower respiratory tract of all VAP patients were collected daily with tracheal catheter. In empirical examination group(from June 2009 to December 2011,n=43),the patients received antibiotics at the time of onset of VAP, selection of antibiotics depended on the information of bacterial epidemiology of the intensive care unit(ICU),and also existence of high risk factors of multi-drug resistant bacteria. In target treatment group(from January 2012 to June 2014,n=43),the patients received antibiotics according to the results of bedside instant sputum smear examination and empirical antibiotic regime. The correlation between the results of sputum smear examination and culture result was analyzed. The levels of body temperature,white blood cell(WBC)count,procalcitonin(PCT)level,and high sensitivity C-reactive protein(hs-CRP)were measured on the 1st day and 3rd day. The length of antibiotics treatment, duration of mechanical ventilation,and the time of ICU stay were recorded for both groups. Results There were 512 qualified sputum specimens for culture,from which 336 pathogens were found,and 358 strains of pathogenic bacteria were found from microscopic examination of 512 qualified sputum smear. The coincidence rate of results of bedside examination of sputum smear and that of sputum culture was 78.32%(401/512). The diagnostic acumen of the former was 85.42%(287/336),specificity was 64.77%(114/176),positive predictive value was 80.17%(287/358),and negative predictive value was 74.03%(114/154). On the 1st day,no statistical differences in infection index between the two groups could be found,but on the 3rd day,the results were significantly improved in both groups. Compared with the empirical treatment group,the body temperature,WBC,PCT and hs-CRP in the target treatment group were significantly lower〔body temperature(℃):36.83±0.69 vs. 37.64±0.71,WBC(×109/L):7.91±2.75 vs. 9.66±3.39,PCT(μg/L):7.14±3.89 vs. 10.14±4.32,hs-CRP(mg/L):12.24±6.28 vs. 15.54±5.94,P<0.05 or P<0.01〕. Compared with the empirical treatment group,the time of antibiotics use(days:6.00±2.55 vs. 9.20±3.46), the duration of mechanical ventilation(days:5.00±1.73 vs. 7.00±1.94),and the length of ICU stay(days:7.43±1.72 vs. 12.57±4.16)were significantly shortened(P<0.05 or P<0.01). Conclusions The results of bedside sputum examination and sputum culture showed a good correlation,and the former is helpful in early diagnosis and treatment of VAP. The result of high quality sputum smear in significant in guiding the first choice of antibiotics,reduce the time of antibiotic use,shorten the duration of mechanical ventilation and the length of ICU stay,and improve the outcome of the patients.

Animals ; Carbon Radioisotopes ; Diabetes Mellitus, Experimental ; genetics ; metabolism ; Diabetes Mellitus, Type 1 ; genetics ; metabolism ; Gene Expression Regulation ; Glucose ; administration & dosage ; metabolism ; Lipid Metabolism ; Liver ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Transcriptome

OBJECTIVETo investigate the distributive path and proliferative rule of marrow mesenchymal stem cells (MSCs) in the rat transplanted via caudal vein from male rat to female rats model of chronic aristolochic acid nephropathy (CAAN).

METHODSCells taken from femoral bone marrow of male Wistar rats were made into single cell suspension, cultured, purified and identified as MSCs. MSCs were transplanted via caudal vein into 50 female Wistar CAAN model rats allocated in the test group, they were killed, 10 rats in a batch, at various time points (6 h, 48 h, 10 d, 30 d and 60 d after transplantation). Besides, 10 rats allocated in the control group were killed on the 30th day after received sham-transplantation. Kidney tissue of all rats was taken for detecting cells originated from the donors by fluorescence in situ hybridization test with FAM-labeled sex determining region of Y chromosome (SRY FISH) probe, and their number in SRY was counted using SRY PCR.

RESULTSMSCs were mainly distributed in the glomerular capillaries at the time points of 6 h and 48 h, but the number of MSCs in glomerular capillaries decreased and those in renal mesenchyma increased at the time points from 10 d to 60 d gradually, then tended to a steady state, meanwhile it showed a stable increasing trend in renal tubule. Cell colony of MSCs could be found in mesenchyma with a slowed down increasing between 30 d to 60 d, but the increasing in tubule was still steady.

CONCLUSIONMSCs originated from the donor can enter the kidney of acceptor and distribute from blood capillary to renal mesenchyma and tubule, and they can long time inhabit there and make propagation.

Animals ; Aristolochic Acids ; toxicity ; Bone Marrow Cells ; cytology ; Cell Proliferation ; Female ; Kidney ; pathology ; Kidney Diseases ; chemically induced ; pathology ; Male ; Mesenchymal Stromal Cells ; cytology ; Rats ; Rats, Wistar

Aim Study the interaction between metho-trexate and levetiracetam after oral administration and hepatorenal toxicity in rats, to provide theoretical basis for the clinical rational use of two drugs. Methods Male SD rats ( 250 ± 20 ) g were selected as experi-mental animals. Rats were randomly divided into 3 groups ( 1 mg·kg-1methotrexate group, 180 mg· kg-1 levetiracetam group, combined group), 5 rats in each group. The following experiment was carried out:(1) pharmacokinetic parameters study; (2) renal ex-cretion study; (3) liver and kidney toxicity study. All samples were determined by ultra performance liquid chromatography-tandem mass spectrometry ( UPLC/MS/MS) . Results After the combination of two drugs, the Cmax, AUC0-t and Tmax of methotrexate in-creased, T1/2, Cl and MRT of methotrexate decreased, the differences was statistically significant. The Tmax, T1/2, Cl, MRT of levetiracetam had a certain upward trend, AUC0-t had a certain downward trend, the differences has no statistically significant. After combi-nation of two drugs, the renal excretion of methotrexate increased significantly, the renal excretion of levetirac-etam decreased significantly and hepatorenal toxicity increased significantly. Conclusion After combina-tion of two drugs by oral administration, Levetiracetam significantly increased methotrexate absorption in rats. Levetiracetam increased the plasma concentration and renal excretion of methotrexate and caused hepatorenal toxicity significantly. It is suggested that dose adjust-ment is necessary for combination of two drugs.

This study was designed to investigate the effect of hypoxia on preeclampsia(PE)by modulating the Src/Siglec-6/SHP2 signaling pathway in the cytoplasm of trophoblast cells.Mouse model of PE was established in normal control and Siglec-6 knockdown mice by L-NAME administration,with aims of studying the changes in vascular diameter of spiral arteries in vivo and examining the expression levels of Siglec-6,p-Src,p-Shp2 and p-ERK1/2 proteins in mouse uterine vascular tissues.While,the effect of Src/Siglec-6/SHP2 on the invasive proliferation of trophoblast cells was explored by culturing human chorionic trophoblast cells HTR-8/SVneo with hypoxia in vitro.In vivo experimental assays showed that the diameter of spiral arteries was reduced in the Siglec-6 knockdown group of mice,and the expression levels of Siglec-6,p-Src,p-SHP2 and p-ERK1/2 proteins were significantly reduced.In vitro hypoxic HTR-8/SVneo cell model results revealed that Siglec-6 overexpression could promote trophoblast cell invasion and proliferation by regulating p-Src,p-SHP2,p-ERK1/2,MMP2,P53 and P21.While,suppression of Src and SHP2 eliminated Siglec-6 overexpression-mediated Siglec-6,p-Src,p-SHP2 and p-ERK1/2 expression,and inhibited the ability of Siglec-6 overexpression to mediate trophoblast invasion and proliferation.Taken together,Siglec-6 plays an important role in preeclampsia,and can alleviate preeclampsia by promoting trophoblast invasion and proliferation through the Src/SHP2 signalling pathway.

OBJECTIVETo determine the correlation of the CYP1A1 (rs4646422) gene polymorphisms with male infertility in the Chinese Han population.

METHODSUsing the Mass ARRAY iPLEX GOLD technique, we conducted a case-control study on theCYPlA1 (rs4646422) gene polymorphisms in 636 infertile males aged 21-49 years (case group) and 442 normal healthy men aged 23-47 years (control group) of the Chinese Han population. We analyzed the genotypes and allele frequencies in the two groups ofsubjects with the SPSS 20.0 software.

RESULTSCompared with the wild homozygous genotype GG, the heterozygous genotype AG (OR = 1.06, 95% CI 0.81-1.38) and homozygous genotype AA (OR = 1.11, 95% CI 0.56-2.21) showed no correlation with male infertility, nor did the mutant allele A (OR = 1.06, 95% CI 0.85-1.32) in comparison with the wild allele G.

CONCLUSIONThe CYP1A1 (rs4646422) gene polymorphisms might not be correlated with male infertility in the Chinese Han population.

Adult ; Alleles ; Case-Control Studies ; China ; Cytochrome P-450 CYP1A1 ; genetics ; Gene Frequency ; Genotype ; Homozygote ; Humans ; Infertility, Male ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Young Adult

This article describes the preparation of the N-tert-butyl-alpha-phenylnitrone (PBN) liposomes and their related characteristics. The PBN liposomes were prepared by film dispersion-supersonic method and the formula of liposomes was optimized by orthogonal uniform design. RP-HPLC was used to qualify the amount of PBN that entered into the hepatoma cells. Necrosis rate was also investigated by fluorescence activated cell sorter (FACS) after PBN liposomes transfection. Result showed that the mean particle size, entrapment efficiency, and polydispersity of the resulting PBN-liposome were 137.5 nm, 71.52% and 0.286, respectively. PBN liposomes can enter into the tumor cell stably and they have higher affinity to hepatoma cell compared with free PBN resulting in a higher necrosis rate after transfection. These results provide a potential method for early diagnosis and treatment of cancer using specific spin trapping probe targeting tumor cells.
Carcinoma, Hepatocellular ; pathology ; Cyclic N-Oxides ; chemistry ; Electron Spin Resonance Spectroscopy ; Humans ; Nanoparticles ; chemistry ; Spin Labels ; Spin Trapping ; methods ; Tumor Cells, Cultured

Objective:To determine the safety and efficacy of controlled first hepaticportal blood flow occlusion in hepatectomy.Methods:Patients who underwent hepatectomy from 1 September 2018 to 1 September 2020 at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Anhui Medical University were studied. There were 133 males and 70 females, with age of (52.9±19.2) years old. They were prospectively randomized into three groups: the intermittent Pringle’s maneuver group ( n=72), the controlled first hepaticportal blood flow occlusion group ( n=66) and the selective portal vein occlusion group ( n=65). The clinical data of these three groups before, during and after operation were analysed. Results:The amount of intraoperative bleeding in the selective portal vein occlusion group was significantly more than the intermittent Pringle’s maneuver group [(226.7±117.9) vs. (115.7±84.2) ml, P<0.05] and the controlled first hepaticportal blood flow occlusion group [(226.7±117.9) vs. (128.1±103.6) ml, P<0.05]. The total duration of operation in the selective portal vein occlusion group was significantly longer than the intermittent Pringle’s maneuver group [(173.6±51.7) vs. (128.4±36.5) min, P<0.05] and the controlled first hepaticportal blood flow occlusion group [(173.6±51.7) vs. (136.1±40.7) min, P<0.05]. The postoperative data showed the AST indexes on day 1 after surgery to be significantly different between the intermittent Pringle’s maneuver group with the controlled first hepaticportal blood flow occlusion group [(587.5±189.2) vs. (361.2±158.3) U/L, P<0.05], and the selective portal vein occlusion group [(587.5±189.2) vs. (358.2±162.7) U/L, P<0.05]. The ALT indexes on day 1 after surgery were significantly different between the intermittent Pringle’s maneuver group with the controlled first hepaticportal blood flow occlusion group [(609.4±172.5) vs. (414.8±162.2) U/L, P<0.05], and the selective portal vein occlusion group[(609.4±172.5) vs. (395.6±158.7) U/L, P<0.05]. The AST and ALT indexes on day 3 after surgery were significantly different between the intermittent Pringle’s maneuver group the controlled first hepaticportal blood flow occlusion group, and the selective portal vein occlusion group. Other liver functions, postoperative complications and recovery indexes showed no significantly differences among the three groups. Conclusions:All the three methods of hepatic blood flow occlusion were safe and efficacious. The controlled first hepaticportal blood flow occlusion method was simple to use and it provided some protective effect in alleviating hepatic ischemia reperfusion injury.

Objective To establish a HPLC method for determining the concentration of voriconazole (VRC) in human plasma.Methods The analysis was conducted using a ZORBAX Eclipse Plus C18 column and the column temperature was 40 ℃.The mobile phase consisted of methanol and water (55∶45).The flow rate was 1 mL · min-1 and the detection was performed at 254 nm.And the internal standard substance was p-Chloroacetanilide.The specificity,lower limit of quantitation (LLOQ),standard curve,precision,accuracy,recovery and stability were investigated.Results Endogenous impurities did not interfere with the determination of the samples in plasma.The standard curve was linear in the range of 0.1-10.0 μg · mL-1 (r =0.999 2),LLOQ was 0.1 μg · mL-1.The RSDs of inter-day and intra-day were all less than 10％ in the plasma and the extraction recovery was 89％-92％.Conclusion This method was simple,sensitive,accurate,efficient and suitable for routine determination of the concentration of VRC in human plasma.