OBJECTIVETo evaluate the impact of nicotine- and tar-free cigarette smoke extract (fCSE) on the serum testosterone (T) level and erectile function of male rats.

METHODSWe randomized 30 male SD rats to three groups of equal number to receive subcutaneous injection of PBS (1.0 ml / 300 g body weight per day), fCSE (1.0 ml/300 g body weight per day), and reduced glutathione hormone (GSH, 200 mg per kg body weight per day) in addition to fCSE (fCSE + GSH), respectively, all for 8 weeks. Then we evaluated the erectile function of the rats by measuring the maximal intracavernous pressure (MICP), mean arterial pressure (MAP), ICP/MAP ratio, time of stimulation to MICP (Tmax), and cavernosal filling fate (CFR). We determined the serum T level, the activities of superoxide dismutase (SOD) , malondialdehyde (MDA), and nitric oxide synthase (NOS) in the cavernosal tissue, and also observed the morphological changes of the corpus cavernosum.

RESULTSCompared with the controls, the rats of the fCSE group showed obvious decreases in the levels of serum T ([5.37 ± 1.43] vs [3.22 ± 1.11] μg/L), NOS ([2.90 ± 0.27] vs [1.67 ± 0.18] U/mg) , and SOD ([18.41 ± 1.09] vs [13.36 ± 1.18] U/mg prot) and erectile function-related indexes MICP ([85.92 ± 6.36] vs [58.99 ± 10.76] mmHg), MICP/MAP (0.86 ± 0.09 vs [0.56 ± 0.08]), and CFR (2.14 ± 0.44 vs 0.89 ± 0.44), but markedly increased Tmax ([29.90 ± 5.78] vs [42.90 ± 8.56]s), with a positive correlation between the serum T level and CFR (r = 0. 364, P < 0.05). Masson staining revealed a lower ratio of the corpus cavernosum smooth muscle tissue to collagen fiber in the fCSE group (0.27 ± 0.04) than in the control (0.98 ± 0.12). Compared with the fCSE group, the fCSE + GSH group exhibited significantly improved MICP ([58.99 ± 10.76 ] vs [77.95 ± 7.71] mmHg), MICP/MAP (0.56 ± 0.08 vs 0.77 ± 0.09), and CFR (0.89 ± 0.44] vs 1.76 ± 0.42) and shortened Tmax ([42.90 ± 8.56 ] vs [32.10 ± 5.84 ] s). The ratio of the corpus cavernosum smooth muscle tissue to collagen fiber was higher in the fCSE + GSH than in the fCSE group (0.77 ± 0.09 vs 0.27 ± 0.04) but still lower than in the control (0.98 ± 0.12).

CONCLUSIONNicotine- and tar-free cigarette smoke extract reduces the serum T level and erectile function of rats, which is related to oxidative stress. Antioxidant therapy can improve erectile function but has a limited value for morphological protection of the penile tissue.

Animals ; Erectile Dysfunction ; chemically induced ; Male ; Malondialdehyde ; metabolism ; Muscle, Smooth ; pathology ; Nicotine ; Nitric Oxide Synthase ; metabolism ; Penile Erection ; drug effects ; Penis ; pathology ; Rats ; Rats, Sprague-Dawley ; Smoke ; adverse effects ; Superoxide Dismutase ; metabolism ; Tars ; Tobacco ; adverse effects

Objective Post-transcription RNA interference (RNAi) is more and more widely applied in multigene therapy.This study aimed to establish an subcutaneous xenotransplanted tumor (SXT) model of human HT-29 colon carcinoma in nude mice and investigate the effects of the survivin shRNA-APC double gene co-expression lentiviral vector on the growth of SXT.Methods Thirty-five nude mice were equally divided into five groups, double-gene survivin shRNA, survivin shRNA, APC, empty vector, and blank, and injected into the left anterior axillary with respective stably transfected cell lines and human HT-29 colon carcinoma cells, all at 2×106/mL, to establish an SXT model of human HT-29 colon carcinoma.The inhibition rate of tumor growth was calculated by measuring the size and weight of the SXT, the expressions of survivin mRNA and protein in the tumor tissue detected by real time PCR and immunohistochemistry respectively, and the apoptosis of the HT-29 colon carcinoma cells determined by TUNEL.Results The mean size and weight of the SXT were significantly reduced in the double-gene survivin shRNA-APC, survivin shRNA, and APC groups as compared with the blank and empty vector groups (P<0.05), though increased in the survivin shRNA and APC groups in comparison with the double-gene group (P<0.05).The expressions of survivin mRNA and protein in the tumor tissue were remarkably lower in the double-gene survivin shRNA-APC, survivin shRNA, and APC groups than in the blank and empty vector groups (P<0.05), even lower in the double-gene group than in the survivin shRNA, and APC groups (P<0.05).The apoptosis rate of the HT-29 colon carcinoma cells was markedly up-regulated in the double-gene survivin shRNA-APC ([56.72±3.17]%), survivin shRNA ([33.64±2.03]%), and APC groups ([31.19±1.79]%) as compared with the blank ([9.89±0.31]%) and empty vector groups ([10.06±0.43]%) (P<0.05), even more significantly in the double-gene than in the survivin shRNA and APC groups (P<0.05).Conclusion The survivin shRNA-APC double gene co-expression lentiviral vector can reduce the expression level the survivin gene, promote the apoptosis of colon carcinoma cells, and suppress the growth of the subcutaneous xenotransplanted tumor.

OBJECTIVEHigh altitue pulmonary edema (HAPE) impacts seriously people's health at high altitude. Screening of susceptibility genes for HAPE will be used for the evaluation and protection of susceptible people.

METHODSWe performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 23 HAPE patients and 17 healthy controls. GO and Pathway analysis softwares were used to analyze and draw gene network.

RESULTSThirty-nine SNPs were found to be significantly different between case and control groups (P < 10(-4)). GO and Pathway analysis of 27 genes around the 39 SNPs indicated that these genes mainly participate in the regulating of cell proliferation, regulation of nitrogen compound metabolic process and G-protein coupled receptor protein signaling pathway and so on.

CONCLUSIONIt suggests that these SNPs and genes found in this study may be associated with the susceptibility of HAPE.

Adult ; Altitude Sickness ; genetics ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Hypertension, Pulmonary ; genetics ; Polymorphism, Single Nucleotide ; Young Adult

OBJECTIVEHigh altitude pulmonary edema (HAPE), a life-threatening disease, has no biological markers used for the routine prevention, diagnosis and treatment. The aim of this study was to identify serum proteins differentially expressed in patients with HAPE for discovering essential biomarkers.

METHODSA complete serum proteomic analysis was performed on 10 HAPE patients and on 10 high altitude and 11 sea level healthy people as control using two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization mass spectrometry and peptide mass fingerprinting. Finally, two most significantly changed proteins were validated by enzyme-linked immunosorbent assay (ELISA).

RESULTSEight protein spots stained with differential intensity, respresenting 5 distinct proteins were identified in patients compared with healthy controls through analysis of these composite gels. Among them, four proteins, namely alpha 1-antitrypsin(alpha1-AT), Haptoglobin(Hp), apolipoprotein A-1 (apoA-1) and Complement C3 increased remarkably, while one protein, apolipoprotein A-IV (apoA-IV) decreased significantly. The variation of alpha1-AT and Haptoglobin, as detected by ELISA, was consistent with the results from proteomic analysis.

CONCLUSIONSIt is well known that Hp, alpha1-AT and complement C3 are associated with inflammation and apoA-1 and apoA-IV play important roles in lipid absorption, transport and metabolism. Therefore, the significant expression changes of Hp, alpha1-AT and complement C3 and apoA-1 and apoA-IV between HAPE patients and their corresponding healthy controls highlight the role of inflammatory response system and lipid metabolism system in the pathophysiology of HAPE.

Altitude ; Biomarkers ; blood ; Blood Proteins ; metabolism ; Case-Control Studies ; Electrophoresis, Gel, Two-Dimensional ; Enzyme-Linked Immunosorbent Assay ; Humans ; Peptide Mapping ; Proteome ; Pulmonary Edema ; blood ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

OBJECTIVETo study the effects of iptakalim (Ipt), an ATP-sensitive potassium channel opener, on cardiac remodeling induced by isoproterenol (ISO) in Wistar rats.

METHODSISO was given subcutaneously (85 mg/(kg x d), sc, 7 days) to induce cardiac remodeling in rats. The rats in Ipt treated group were administrated with Ipt 3 mg/kg (po) after ISO injection. After treated with Ipt for 6 weeks, the hemodynamic parameters were tested by an eight channel physiological recorder (RM-6000). Then the heart weight was weighed and the cardiac remodeling index was calculated. HE stain and Masson's stain were employed to perform histological analysis, the hydroxyproline(Hyp) content in cardiac tissue was detected by colorimetric method, radioimmunoassay was used to measure the plasma levels of endothelin-1 (ET-1) and prostacyclin (PGI2).

RESULTSSix weeks after ISO injection, the cardiac functions of model group were damaged markedly compared with those of normal group. The characteristics of ventricular remodeling in model group included that the heart weight index, myocyte cross-sectional area, myocardial fibrosis, and the hydroxyproline content in cardiac tissue were all increased significantly. The plasma level of ET-1 was increased, while the plasma level of PGI2 was decreased significantly. These changes could be reversed by Ipt treatment (3 mg/(kg x d) for 6 weeks).

CONCLUSIONIpt can reverse cardiac remodeling induced by isoproterenol in rats. The endothelial protective effect regulating effects of Ipt on the balance between the ET-1 and PGI2 system may be involved in its mechanisms.

Animals ; Endothelin-1 ; blood ; Hemodynamics ; Hydroxyproline ; metabolism ; Isoproterenol ; pharmacology ; KATP Channels ; drug effects ; Male ; Myocardium ; metabolism ; Propylamines ; pharmacology ; Prostaglandins I ; blood ; Rats ; Rats, Wistar ; Ventricular Remodeling ; drug effects

OBJECTIVETo establish a method for real-time recording the oxygen consumption of mice under normobaric hypoxia.

METHODSThe experimental apparatus was made up of animal container, filling water control system, electronic balance, hose, a computer with weight recording software, etc. The working principle was that the oxygen consumed by animal was replaced by water filling which was controlled by the pneumatic and hydraulic actuator. The water was weighted by an electronic balance and the weight signal was recorded into excel file at the same time. The accuracy and precision of the apparatus were detected by a 10 ml syringe. The oxygen consumption characteristics of 6 acute repetitive hypoxia mice and 6 normal mice were observed.

RESULTSThe P value for the paired t test was 1 and the CV value was 4%. The survival time and total oxygen consumption of acute repetitive hypoxia mice were both significantly increased compared to normal mice (P < 0.05), which were (58.8 +/- 6.8) min and (46.0 +/- 8.7) min respectively for the survival time and (85.1 +/- 8.5) ml and (73.6 +/- 5.4) ml respectively for total oxygen consumption.

CONCLUSIONThe hypoxia tolerance of the acute repetitive hypoxia mice can significantly improved by taking more oxygen in the animal cabin. The accuracy and precision of the apparatus are high and it can be used for the determination of oxygen consumption in hypoxia research.

Animals ; Hypoxia ; physiopathology ; Mice ; Monitoring, Physiologic ; instrumentation ; Oxygen Consumption ; physiology

Objective To explore the significance of 18 F-fluorodeoxyglucose positronemission tomography/ computed tomography (18F-FDG PET/CT) scanning for childhood neuroblastoma clinical staging.Methods From December 2014 to December 2015,59 patients confirmed as NB in Beijing Children's Hospital,Capital Medical University,and finding or clinical features were selected by histopathology.Those patients underwent 18 F-FDG PET/CT,bone scan,cranial magnetic resonance image (MRI),bone marrow puncture (two sites) and biopsy,regional CT,ultrasound,serum tumor markers like lactic dehydrogenase and neuronspecific enolase.In comparison of 18F-FDG PET/CT image findings with other detective methods,the differences were analyzed between the primary sites and metastasis were analyzed.Results (1) General features:Out of 59 children with NB,31 were males,28 were females.Primary lesions were as follows:14 cases located in the postmediastinum,44 cases in the retroperitoneum (1 case in retroperitoneum + postmediastinum),1 case in left neck.International Neuroblastoma Staging System Ⅰ to Ⅳ:O,1,9 and 49 cases,respectively.(2)18F-FDG PET-CT manifestations:The maximum of standardized uptake value (SUVmax):before-treatment group was (2.34 ± 1.06) which was larger than the post-surgery group value of (1.08 ± 0.50),and the difference was significant(F =5.699,P =0.000);bone marrow metastasis ranged from 1.5 to 2.9,regional lymphatic metastasis ranged from 1.0 to 2.1.(3)18F-FDG PET-CT imaging compared with other detection:in bone metastases,the whole body bone scan finding were normal in 3 cases,while PET/CT showed disseminated bone and bone marrow involvement and bone scanning showed 2 cases had metastases,combined with 18 F-FDG PET/CT,which were considered as postoperative inflammatory reaction or residual tumor tissues invade adjacent intervertebral foramen.Bone cytology was positive in 30 cases,while PET/CT showed 34 patients with bone marrow metastasis,and 1 case was suspicious.In central metastasis,1 case of PET/CT showed epidural metastasis,while cranial MRI was negative;Cranial MRI showed 9 cases had skull metastasis,1 case had orbital metastasis,1 case had meningeal metastases;while 18F-FDG PET/CT showed no abnormality.All children had no parenchymal metastasis.Corresponding tumor markers as LDH was related to the maximum value of primary tumor focal SUVmax (rs =0.581,P ＜ 0.01).Conclusions 18 F-FDG PET/CT can fully display the distribution of primary sites and metastases,and can be served as medical imaging evidence for both the diagnosis and staging of neuroblastoma.But as for cranial bone and central metastasis,it has high false negative rate.Clinical practice should be combined with cranial MRI to improve relevance ratio.

Six thousand and forty-four subjects in Jiangsu community were enrolled to investigate the relationship between subclinical thyroid dysfunction and blood pressure. It was shown that subclinical thyroid dysfunction, including both the subclinical hyperthyroidism and subclinical hypothyroidism, had no relationship with increased blood pressure.

OBJECTIVETo study the application of three-dimensional reconstruction technique based on CT-MRI fusion in skull base surgery.

METHODSTo acquire the thin layer CT scan and MRI scanned images, to achieve image registration, fusion, segmentation and 3D visualization by using self-preparation software, to operate, observe and measure models by using methods of endoscopic observation, volume rendering segmentation, automatically and manually measure.

RESULTSThe center of the eye and foramen magnum in CT-MRI were used as point registration. Good coincidence of important anatomic landmarks were formed in the image fusion. The boundary of spotted graphical was clear and complete. The models showed a complete, continuous, smooth surface. Virtual endoscopy could display the inside three-dimensional structures of skull from nasal with fluent operations of rotation and transparency. The boundary of skull stump segmented after volume rendering segmentation was clear and smooth, and it could show bone signs and soft tissue models together. Cooperation of automatic measurement method [(32.007 ± 15.311) mm] and the manual measurement method [(30.240 ± 15.169) mm] for measuring the maximum diameters of the tumor model, the difference was significant (t = 8.409, P < 0.05).

CONCLUSIONSThe method of selecting the center of the eye and foramen magnum in point matching is scientific, simple and easy to operate. The models reconstructed based on CT-MRI fusion images can accurately reflect the size of the soft tissue and be better measured through the automatic measurement. Reconstruction models can be observed through the way of virtual endoscopic within the nasal cavity or volume rendering segmentation from outside to inside to frustrate the relationship of skull structures. Three-dimensional reconstruction techniques based on CT-MRI fusion in skull base surgery can be used to plan surgical approach, to assess the risk of surgery and to achieve space measurements, and it laid the foundation for the three-dimensional navigation.

Adult ; Aged ; Endoscopy ; Female ; Humans ; Image Processing, Computer-Assisted ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Skull Base ; surgery ; Software ; Tomography, Spiral Computed ; Tomography, X-Ray Computed

Objective To analezk thk altkrations in blood urka nitrogkn( BRN)and skrum crkatinink( Scr) in childrkn with rktinoblastoma( Ab)bkfork and aftkr chkmothkrape and thk clinical significanck of thk chkmothkrape kffkct,and to providk thk kvidknck for thk furthkr improvkmknt of thk safkte of trkatmknt. Methods L total of 280 chil-drkn with Ab wkrk knrollkd in thk stude,and kach of thkm was trkatkd with CEV( Carboplatin+Etoposidk+Vincris-tink)mkthods. Thkrk subjkcts includkd 153 malks and 127 fkmalks,with a mkan trkatmknt of 4. 5 ceclks(rangk 2 to 12 ceclks)and a mkan agk of 21. 5 months(rangk 1 to 84 months). Lmong thkm,149 casks wkrk diagnoskd clinicalle,131 casks wkrk diagnoskd pathologicalle. Eight casks wkrk in thk kxtraocular stagk,3 casks wkrk in glaucoma and 269 casks in intraocular pkriod(101 casks of singlk keks and 168 casks of doublk keks). BRN and Scr wkrk dktkctkd bkfork thk first coursk of chkmothkrape and aftkr thk last coursk of chkmothkrape. ResuIts BRN and Scr valuks wkrk analezkd bk-fork and aftkr chkmothkrape. BRN was 3. 05 mmol╱F bkfork chkmothkrape and 3. 46 mmol╱F aftkr chkmothkrape in thk group agkd from 4 months to lkss than 12 months(73 casks),thk valuks of BRN aftkr chkmothkrape was highkr than that bkfork chkmothkrape,and onle in this group thk changk was statisticalle diffkrknt(t﹦ -2. 829,P﹦0. 006),but all BRN valuks in this group wkrk not bkeond thk highkst rkfkrknck valuk(1. 70 mmol╱F-7. 10 mmol╱F). Bkfork initial chkmothkrape,149 patiknts( 53. 2﹪)had Scr bklow thk rkfkrknck rangk( malk:30 -104 μmol╱F,fkmalk:30 -84 μmol╱F),and 20 casks(7. 0﹪)had thk BRN bklow thk rkfkrknck valuk. In 2 casks,BRN(7. 25 mmol╱F and 7. 34 mmol╱F, rkspkctivkle)bkfork thk initial chkmothkrape was slightle highkr than thk normal valuk,but thk valuk was normal(5. 01 mmol╱F and 4. 98 mmol╱F,rkspkctivkle)aftkr thk last chkmothkrape. In onk cask,thk BRN(5. 62 mmol╱F)was normal bkfork thk initial chkmothkrape,but it was klkvatkd(7. 33 mmol╱F)aftkr thk last chkmothkrape. In anothkr onk cask,thk BRN was normal bkfork and aftkr chkmothkrape,but thk valuk aftkr chkmothkrape was 4. 69 timks highkr than that bk-fork chkmothkrape. ConcIusions Aknal function of Ab childrkn bkfork trkatmknt is normal. Skvkn pkrcknt of thksk patiknts havk BRN undkr thk BRN rkfkrknck rangk,and 53. 2﹪ of thksk patiknts havk Scr undkr thk Scr rkfkrknck rangk. It suggkstkd that thk rkfkrknck valuks of BRN and Scr nkkd to bk adjustkd. BRN of infant Ab mae incrkask signifi-cantle aftkr chkmothkrape,but it doks not mkkt thk currknt diagnostic critkria of mild nkphrotoxicite. Still,thk karle rknal damagk nkkds to bk notickd.