Objective To investigate the expression of circulating microRNA (miRNA) of rats with hypobaric hypoxia‐induced pulmonary hypertension (HPH) .Methods Commercial rat miRNA microarray was employed to detect and analyze the circulating miRNA profile in the serum samples of Sprague‐Dawley rats with hypobaric hypoxia‐induced HPH and controls .Furthermore ,differentially expressed candidate circulating miRNAs between HPH and control groups were validated by Real‐time quantitative PCR based on the case‐control study ,and receiver operating characteristic curve (ROC ) analysis was used to test the performance of four differentially expressed circulating miRNAs in discriminating HPH and control groups .Results Compared with those in the control group ,13 upregulated miRNAs and 10 downregulated miRNAs were identified in hypobaric hypoxia‐induced HPH rats by using miRNA microarray . And differentially expressed miR‐451 , miR‐505 , let‐7d and miR‐214 were validated by using RT‐PCR .ROC analysis showed that the area under the curve of miR‐451 ,miR‐505 and let‐7d was 0 .979 ,0 .938 and 0 .993 in discriminating HPH and control groups ,respectively .Conclusion The aberrant expression of circulating miR‐451 ,miR‐505 and let‐7d in serum may be correlated with the pathogenesis of HPH .

Animals ; Calcium Channel Blockers ; therapeutic use ; Dogs ; Hypothermia ; complications ; Male ; Nimodipine ; therapeutic use ; Ventricular Fibrillation ; etiology ; prevention & control

OBJECTIVETo study the mechanism of male infertility caused by varicocele by evaluating the effects of hyperbaric oxygenation (HBO) therapy on the testicular tissue morphology and function of rabbit model with varicocele(VC).

METHODSTwenty-four mature male rabbits were randomly divided into three groups: pseudo-operation, VC model and VC model administered by HBO. Experimental varicocele was induced by partial ligation of the left "lumbotesticular" trunk vein in rabbits. HBO was administered to one of the two groups of VC model rabbits after the operation. Weight and volume of both testes, parameters of seminal fluid, histological changes of testicular tissues, MTDs, TFI, and Sertoli cell index (SI) of seminiferous tubules were studied.

RESULTSThe average weight and volume of the left testes significantly increased in the rabbits treated by HBO. The semen quality was improved, and MTDs increased significantly compared with VC group(P < 0.0001). The testicular tissue morphology became nearly normal in VC + HBO group.

CONCLUSIONS1. Both the structure and spermatogenetic function of testes can be damaged by the presence of varicocele; 2. Chronic ischemia, anoxia and microcircular dysfunction may be the key process and essential factor that make varicocele contributive to testicular damage and spermatogenetic dysfunction; 3. HBO can effectively alleviate, even eliminate, chronic ischemia, anoxia and microcircular dysfunction in testicular tissues with varicocele, and thus protect the structure and functions of testes.

Animals ; Hyperbaric Oxygenation ; Male ; Rabbits ; Testis ; blood supply ; pathology ; Varicocele ; pathology ; physiopathology ; therapy

Objective To explore the distribution of water with high level arsenic and prevalence of arsenism along Huai'he River and the surrounding area of Hong'ze lake in Huai'an of Jiangsu. Methods Wate rsamples were collected and tested in 2008 from 18 villages of 6 towns according to history data in 3 counties like Xuyi,Jinhu and Hongze. Samples having arsenic level higher than 0.05 mg/L were investigated by epidemiological method and the patients were diagnosed by Standard of Diagnosis for Endemic Arsenism. Results All 5199 water samples were determined,and 260 water samples were exceeding the national drinking water quality level (0.05 mg/L) in 3 counties,the rates of exceeding diagnosis were 5.6%(247/4454),0.7%(4/597),6.0%(9/148) respectively. Total detected rate of endemic arsenic disease was 5.94%(128/2155). The detected rates of age group of 0 ～ ,20 ～,30 ～ ,40 ～ ,50 ～ ,60 ～ ,70 ～ ,80 ～ were 2.86%(1/35),2.11%(2/95),1.26%(3/239),3.10%(16/516),5.53% (32/579),10.07%(41/407),11.84%(27/228),10.71%(6/56) respectively. The detected rate of male (9.10%,78/857) was higher than that of female(3.85%,50/1298,χ~2 = 25.46,P < 0.01). Conclusions Huai'he River and the surrounding areas of Hong'ze lake like Xuyi,Jinhu and Hongze are identified existing endemic arsenic disease area. The prevention of arsenism should be strengthened in these areas.

OBJECTIVETo explore apoptosis-inducing effects of realgar nanoparticle (nano-realgar) on drug-sensitive leukemia cells.

METHODPreparation of nano-realgar was mechanical milled using a high-energy planetary ball mill. Using drug-sensitive leukemia cells (K562) as target cells, MTT assay was used to detect the proliferating activity of K562 cells, and the cellular apoptosis was investigated with double staining of FITC-Annexin V and propidium iodide (PI) by flow cytometry. Flow cytometry (FCM) was employed to detect expression of intracellular Bax, Bcl-2, P-53 protein and the activity of Caspase-3.

RESULTThe raw realgar was made to ultra-fine powder by ball milling, and the average diameter of the nanoparticle was (72.72 +/- 22.18) nm measured with electron microscopes. Nano-realgar significantly inhibited the proliferation of K562 cells, Treated for 24, 48 and 72 hours, the 50% inhibitory concentration (IC50) was 43.48, 20.52, 16.07 mg x L(-1). After exposure to 20 mg x L(-1) and 50 mg x L(-1) nano-realgar for 48 hours, the apoptosis of K562 cells detected by Annexin V/PI staining was increased, the apoptotic rate of K562 cells was 10. 52% and 73.25%. After the target cells were treated with 20 mg x L(-1) and 50 mg x L(-1) nano-realgar for 48 h, the expression of P-53, Bax, Bcl-2 markedly increased in a time and dose-dependent manner. After administration of 20 mg x L(-1) and 50 mg x L(-1) nano-realgar for 48 h, the percentage of BCRP+, P-gp+ and co-expressing P-gp and BCRP cell population in K562 cells incrased dramatically.

CONCLUSIONNano-Realgar significantly induced apoptosis of drug-sensitive leukemia cells.

Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Cell Proliferation ; drug effects ; Humans ; K562 Cells ; Leukemia ; drug therapy ; pathology ; Nanotechnology ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Sulfides ; pharmacology ; Tumor Suppressor Protein p53 ; analysis

To investigate the inhibition of cyclosporin A (CsA) on neutrophil adhesion to human umbilical vein endothelial cells (HUVECs, ECV-304) induced by hypoxia/reoxygenation and further explore its mechanism, a 1 h hypoxia/4 h reoxygenation model was reproduced using ECV-304. The adhesion rate of neutrophils to ECV-304 was determined by measuring the activity of endogenous hexosaminidase. The expression of endothelial cell adhesion molecules of E-selectin and ICAM-1 was measured by flow cytometry. The expression of cyclophilin A (CyPA) and the activation of ERK1/2 was compared among experimental groups by Western blot. The content of reactive oxygen species (ROS) was measured by Fenton reaction. After being stimulated with 1 h hypoxia/4 h reoxygenation, ECV-304 showed an enhanced neutrophil adhensiveness in association with an increased surface expression of E-selectin and ICAM-1. In parallel, the content of ROS was also increased. These effects were significantly suppressed by the addition of CsA. Most importantly, the expression of CyPA was significantly increased following 1 h hypoxia/4 h reoxygenation, which was accompanied with an increased activation of ERK1/2. Treatment with CyPA inhibitor CsA and CyPA antisense oligonucleotides significantly inhibited the activation of ERK1/2 and decreased the adhesion of neutrophils to ECV-304. The specific ERK1/2 inhibitor PD98059 caused an inhibition of neutrophil adhesion to hypoxia/reoxygenation-stimulated ECV-304. Our data confirm that CsA inhibits neutrophil adhesion to hypoxia/reoxygenation stimulated ECV-304 by a mechanism involving inhibition of the signal transduction of ROS, CyPA and ERK1/2.
Cell Adhesion ; Cell Hypoxia ; Cells, Cultured ; Cyclophilins ; biosynthesis ; genetics ; Cyclosporine ; pharmacology ; Endothelium, Vascular ; cytology ; Humans ; Intercellular Adhesion Molecule-1 ; biosynthesis ; genetics ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Neutrophils ; cytology ; Reactive Oxygen Species ; metabolism ; Reperfusion Injury ; physiopathology ; Signal Transduction ; Umbilical Veins ; cytology

AIMTo investigate the impact of CYP2C9 * 3 on the pharmacokinetics of glibenclamide and lornoxicam.

METHODSCYP2C9 * 3 was measured in 83 non-related Chinese subjects by PCR-RFLP. The pharmacokinetics of lornoxicam and glibenclamide were investigated in 18 subjects (7 with CYP2C9 * 1/* 3 genotype and 11 with * 1/* 1 genotype). Glibenclamide and lornoxicam in plasma were determined by the sensitive liquid chromatography-tandem mass spectrometry, separately.

RESULTSAfter a single oral dose of 2.5 mg glibenclamide, C(max) was (70.0 +/- 11.5) microg x L(-1) in CYP2C9 * 1/ * 3 subjects and (51.9 +/- 12.3) microg x L(-1) in * 1/ *1 subjects. AUC(0-infinity) were (435 +/- 47) vs (287 +/- 95) microg x h x L(-1) (in * 1/ * 3 vs * 1/ *1 subjects), and CL/F were (96 +/- 9.3) vs (160 +/- 51) mL x min(-1), respectively. Statistic analysis results indicated that glibenclamide AUC(0-infinity) was significantly higher (1.5-fold) and subsequently CL/F was significantly lower (40%) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.01). After a single oral dose of 8 mg lornoxicam, C(max) was (1.54 +/- 0.24) mg x L(-1) in CYP2C9 * 1/ * 3 subjects and (1.19 +/- 0.37) mg x L(-1) in * 1/ * 1 subjects. AUC(o-infinity were (14.9 +/- 2.2) vs (6.92 +/- 1.48) mg x h x L(-1) (in * 1/ *3 vs * 1/ * 1 subjects), and CL/F were (9.1 +/- 1.2) vs (20.1 +/- 4.6) mL x min(-1), respectively. Statistic analysis results indicated that lornoxicam AUC(0-infinity) was significantly higher (2. 2-fold) and subsequently CL/F was significantly lower (55% ) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.001).

CONCLUSIONCYP2C9 * 3 greatly affects both the pharmacokinetic profiles of glibenclamide and lornoxicam. The elimination of these drugs significantly decreased in subjects with CYP2C9 * 1/ * 3 genotype, especially lornoxicam.

Adult ; Alleles ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacokinetics ; Area Under Curve ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; China ; Cytochrome P-450 CYP2C9 ; Genotype ; Glyburide ; pharmacokinetics ; Humans ; Hypoglycemic Agents ; pharmacokinetics ; Male ; Piroxicam ; analogs & derivatives ; pharmacokinetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

BACKGROUNDIntratracheal instillation of blood induces self-repaired acute lung injury. However, the mechanism of repair has been unclear. Heme-oxygenase (HO)-1, which catalyzes heme breakdown, acts as an inducible defense against oxidative stress and plays an important role in inflammation. The objective of this study was to test the role of HO-1 in lung injury caused by intratracheal instillation of red cells.

METHODSForty healthy, male Sprague-Dawley rats were randomly divided into five groups: normal group, saline group, erythrocyte group, erythrocyte+zinc-protoporphyrin (ZnPP, HO-1 inhibitor) group and saline+ZnPP group. At 2 days after intratracheal instillation of red cells, lung tissues and lavage samples were isolated for biochemical determinations and histological measurements.

RESULTSHistological analysis revealed that administration of ZnPP worsened the acute lung injury induced by instilled erythrocytes. HO-1 was over-expressed in the erythrocyte group and in the erythrocyte + ZnPP group. Compared with the erythrocyte + ZnPP group, the levels of total protein, lactate dehydrogenase and tumor necrosis factor-alpha in the lavage were lower (P < 0.01), while the level of interleukin-10 was higher in the erythrocyte group (P < 0.01).

CONCLUSIONHO-1 protects against erythrocyte-induced inflammatory injury in lung.

Animals ; Erythrocytes ; physiology ; Heme Oxygenase (Decyclizing) ; analysis ; physiology ; Interleukin-10 ; analysis ; Lung ; pathology ; Lung Injury ; prevention & control ; Male ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; analysis

Objecctive To explore the construction and effect of the Doctor-nurse integrative medical care mode for domestic analgesia in middle and late stage cancer patients.Me thods From september 2016 to February 2017, 120 Cancer patients in The People's hospitalof Du Jiang Yan were included, and randomly divided into experimental group (n=60) and observation group (n=60). The observation group received routine outpatient follow-up after discharge.The experimental group was treated with the Doctor-nurse integrative medical care mode.The analgesic modes included psychological support, immediate morphine and morphine sustained release tablets for personalized home titration. The Net bottom-hospitals were responsible for the follow-up and intervention, the training and guidance were bore by Hub hospitals. The patients were followed up at the first and twelfth weeks, followed by telephone follow-up at fourth and eighthweek, after discharge. The quality of life, the degree of depression and the degree of anxiety of caregiver were compared between the two groups at the beginning of the study and the twelfth weeks after discharge. Re s ults In experimental group, the scores of in the life quality of patints before and after intervention were (62.43±12.83) and (50.33 ±9.04), respectively, the scores of depression before and after intervention were (50.33± 6.59) and (47.37±4.97), respectively, the scores of anxiety before and after intervention were (55.05 ±8.82) and (52.22 ±5.37). There was statistically significant difference between the two groups (P＜0.05). Conclus ions Doctor-nurse integrative medical care mode can improve the quality of life of patients with advanced cancer, reduce the degree of depression, and reduce the degree of anxiety of patients.

The DNA fragments of ag85b、esat-6、hsp65、mpb64 and ag85b-esat-6、hsp65-esat-6、mpb64-esat-6 were amplified by PCR and SOE technique.These seven fragments were inserted into pCDNA3.1(+)vector to construct recombinant plasmids pCA、pCE6、pCH、pCM、pCAE、pCHE and pCME.The seven plasmids were transfected into SP2/0 cell in vitro to detect the expression of target genes.BALB/c mice were intramuscularly vaccinated with the seven plasmids and the control vector pCDNA3.1(+)and PBS respectively.The serum antibodies and the spleen lymphocyte proliferation(SLP)and secreted IFN～? of spleen were tested.The results of indirect ELISA showed the levels of antibodies in all recombinant plasmids groups were significantly higher than the two control groups(P