Whole-exome sequencing reveals MYH7 p.R671C mutation in three different phenotypes of familial hypertrophic cardiomyopathy.

Familial hypertrophic cardiomyopathy (HCM) is one of the most common types of genetic heart disorder and features high genetic heterogeneity. HCM is a major cause of sudden cardiac death and also an important cause of heart failure-related disability. A pedigree with suspected familial HCM was recruited for the present study to identify genetic abnormalities. HCM was confirmed by echocardiography and clinical data of the family members were collected. Genomic DNA was extracted from the peripheral blood and sequenced based on standard whole-exome sequencing (WES) protocols. Sanger sequencing was further performed to verify mutation sites and their association with HCM. WES and Sanger sequencing revealed a heterozygous missense mutation (c.2011C>T p.R671C) in myosin heavy chain 7 (MYH7) that was identified in three family members. The Arg671Cys mutation was located in exon 18 and, to the best of our knowledge, has not been previously reported in familial HCM. Furthermore, family members carrying the same mutated gene were of different sexes and clinical phenotypes. They included the proband, a 17-year-old survivor of sudden cardiac arrest with ventricular systolic dysfunction, the proband's maternal uncle, who presented with ventricular diastolic dysfunction and the proband's mother, who had no obvious clinical symptoms and did not present with cardiac dysfunction. However, echocardiology indicated that the proband's mother had an enlarged left atrium, slightly thicker right anterior wall and anterior septum and an expanded atrial septum. Therefore, HCM exhibited obvious genetic and phenotypic heterogeneity. To the best of our knowledge, the present study was the first to report such a mutation in the MYH7 gene in familial HCM. In addition, the present study demonstrated that WES is a powerful tool for identifying genetic variants in HCM.

Stability and Hopf bifurcation in a virus model with self-proliferation and delayed activation of immune cells.

A new mathematical model was proposed to study the effect of self-proliferation and delayed activation of immune cells in the process of virus infection. The global stability of the boundary equilibria was obtained by constructing appropriate Lyapunov functional. For positive equilibrium, the conditions of stability and Hopf bifurcation were obtained by taking the delay as the bifurcation parameter. Furthermore, the direction and stability of the Hopf bifurcation are derived by using the theory of normal form and center manifold. These results indicate that self-proliferation intensity can significantly affect the kinetics of viral infection, and the delayed activation of immune cells can induce periodic oscillation scenario. Along with the increase of delay time, numerical simulations give the corresponding bifurcation diagrams under different self-proliferation rates, and verify that there exists stability switch phenomenon under some conditions.

Protective effect of anisodamine in rats with glycerol-induced acute kidney injury.

BACKGROUND: Anisodamine is used for the treatment of reperfusion injury in various organs. In this study, we investigated the effectiveness and mechanisms of action of anisodamine in promoting recovery from glycerol-induced acute kidney injury (AKI). METHODS: We compared the protective effects of atropine and anisodamine in the rat model of glycerol-induced AKI. We examined signaling pathways involved in oxidative stress, inflammation and apoptosis, as well as expression of kidney injury molecule-1 (KIM-1). Renal injury was assessed by measuring serum creatinine and urea, and by histologic analysis. Rhabdomyolysis was evaluated by measuring creatine kinase levels, and oxidative stress was assessed by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) levels in kidney tissues. Inflammation was assessed by quantifying interleukin 6 (IL-6) and CD45 expression. Apoptosis and necrosis were evaluated by measuring caspase-3 (including cleaved caspase 3) and RIP3 levels, respectively. RESULTS: Glycerol administration resulted in a higher mean histologic damage score, as well as increases in serum creatinine, urea, creatine kinase, reactive oxygen species (ROS), MDA, IL-6, caspase-3 and KIM-1 levels. Furthermore, glycerol reduced kidney tissue SOD activity. All of these markers were significantly improved by anisodamine and atropine. However, the mean histologic damage score and levels of urea, serum creatinine, creatine kinase, ROS and IL-6 were lower in the anisodamine treatment group compared with the atropine treatment group. CONCLUSION: Pretreatment with anisodamine ameliorates renal dysfunction in the rat model of glycerol-induced rhabdomyolytic kidney injury by reducing oxidative stress, the inflammatory response and cell death.

Endometrial breakdown with sustained progesterone release involves NF-κB-mediated functional progesterone withdrawal in a mouse implant model.

Irregular uterine bleeding is a major side effect of long-acting progestogen-only contraceptives in women, and is the primary reason women discontinue their use. In this study, a mouse model of endometrial breakdown was established using a subcutaneous progesterone implant to understand how irregular bleeding begins. Although progestogens sustained decidualization, endometrial breakdown was still observed in this model. We, therefore, hypothesized that endometrial breakdown might involve functional progesterone withdrawal. Using co-immunoprecipitation assays, we observed the constitutive activation of nuclear factor kappa-b (NF-κB) p65 and its interaction with the progesterone receptor (PGR); moreover, transcriptional activity of the PGR was also repressed by NF-κB activity in primary mouse and human decidual stromal cells that mimic progesterone maintenance. Yet the ratio of PGR-B to PGR-A was not increased in the mouse model. In vivo comparison of endometrial breakdown induced by progesterone withdrawal to that seen during sustained progesterone exposure, in the presence of NF-κB inhibitors, revealed that NF-κB-mediated functional progesterone withdrawal is involved in endometrial breakdown in this implant model. These data prompt further studies to determine the homology of this functional progesterone withdrawal mechanism in human endometrium. Mol. Reprod. Dev. 83: 780-791, 2016 © 2016 Wiley Periodicals, Inc.

[Cellphone electromagnetic radiation damages the testicular ultrastructure of male rats].

OBJECTIVE: To investigate the influence of cellphone electromagnetic radiation (CER) on the testicular ultrastructure and the apoptosis of spermatogenic cells in male rats.atability, feasibility, applicability, and controllability in the construction of experimental animal models, we compared the major anatomic features of the penis of 20 adult beagle dogs with those of 10 adult men. Using microsurgical techniques, we performed cross-transplantation of the penis in the 20 (10 pairs) beagle dogs and observed the survival rate of the transplanted penises by FK506+MMF+MP immune induction. We compared the relevant indexes with those of the 10 cases of microsurgical replantation of the amputated penis. METHODS: Thirty adult male SD rats were equally randomized into a 2 h CER, a 4 h CER, and a normal control group, the former two groups exposed to 30 days of 900 MHz CER for 2 and 4 hours a day, respectively, while the latter left untreated. Then the changes in the ultrastructure of the testis tissue were observed under the transmission electron microscope and the apoptosis of the spermatogenic cells was determined by TUNEL. RESULTS: Compared with the normal controls, the rats of the 2 h CER group showed swollen basement membrane of seminiferous tubules, separated tight junction of Sertoli cells, increased cell intervals, apparent vacuoles and medullization in some mitochondria, and increased apoptosis of spermatogenic cells, mainly the apoptosis of primary spermatocytes (P<0.05 ). In comparison with the 2 h CER group, the animals of the 4 h CER group exhibited swollen basement membrane of seminiferous tubules, more separated tight junction of Sertoli cells, wider cell intervals, incomplete membrane of spermatogonial cells, fragments of cytoplasm, nuclear pyknosis and notch, slight dilation of perinuclear space, abnormalities of intracellular mitochondria with vacuoles, fuzzy structure, and fusion or disappearance of some cristae, and increased damage of mitochondria and apoptosis of spermatogenic cells, including the apoptosis of spermatogonial cells, primary spermatocytes, and secondary spermatocytes (P<0.05 ). CONCLUSIONS: CER can damage the testicular ultrastructure and increase the apoptosis of spermatogenic cells of the male rat in a time-dependent manner, and the apoptosis of spermatogenic cells may be associated with the damage to mitochondria.

Effect of 1,25-dihydroxyvitamin D3 on mast cells tryptase in asthmatic guinea pigs.

OBJECTIVE: To explore the effect of 1,25-dihydroxyvitamin D3 on the mast cell tryptase (MCT) in asthmatic guinea pigs. METHODS: A total of 60 male or female healthy guinea pigs were randomly divided into control group (group A), asthmatic group (group B), and 1,25-dihydroxyvitamin D3 group (group C), with 20 cases in each group. To establish asthmatic guinea pig models, 1 mL peanut oil was filled into stomach in the morning in group A and group B, and 1 mL peanut oil with 1,25-dihydroxyvitamin D3 was filled into stomach in group C. Airway resistance (Re) of asthmatic guinea pigs was detected, and the bronchoalveolar lavage fluid (BALF) cells were counted. Lung tissue with HE and MCT immunohistochemical staining were used to observe the pathological changes in lung tissue and the distribution of MCT. RESULTS: After injection of different concentration of acetylcholine chloride, the Re in group B and group C were increased significantly compared with group A (P < 0.05); compared with group B, the Re in group C were decreased significantly (t = -5.385, -5.761, -6.184, -13.574, P < 0.05); the total number of BALF cells and eosinophils were increased significantly in group B and C (t = 19.618, 9.598, 10.854, 5.388, P < 0.05); compared with group B, the total number of BALF cells and eosinophils in group C was decreased significantly (t = -5.555, -5.392, P < 0.05); the number of tryptase positive cells in group B was increased significantly than that in group A (t = 21.312, P < 0.05), and in addition to the alveolar septum and submucosa, the cells were also distributed around blood vessels and outside the cells; the number of tryptase positive cells in group C was decreased significantly compared with group B, and the difference was statistically significant (t = 5.043, P < 0.05). CONCLUSIONS: After the asthmatic guinea pigs are treated with 1,25-dihydroxyvitamin D3, their BALF, Re, infiltration degree of inflammatory cells in the trachea and lung tissue and airway inflammatory reaction are reduced significantly. 1,25-dihydroxyvitamin D3 has a certain inhibiting effect on the activation of mast cells and the release of MCT granules.

[Effects of potato/soybean intercropping on photosynthetic characteristics and yield of three soybean varieties].

The potato/soybean intercropping trials using three soybean varieties including Zhonghuang 30 (early-maturing variety) , Jidou 17 (mid maturing variety) and Qihuang 34 (late maturing variety) with the sole cropping potato as control were carried out to determine the dynamic changes of leaf area index (LAI) of soybean, accumulation of dry matter, photosynthetic characteristics, yield and yield components. The results showed that the LAI, dry matter accumulation, net photosynthesis (Pn), transpiration rate (Tr) and stomatal conduction (g(s)) of soybean in all intercropping systems were lower than in monoculture because of the influence of intensified lower light during earlier growing stage, and the duration from planting to flowering was extended. When the potato was harvested, the LAI, dry matter accumulation, Pn, Tr and g(s) of soybean in all intercropping systems increased, especially for mid-maturing and late-maturing varieties, which became much closer to those in the monoculture. Compared with sole cropping, the pods per plant, seeds per plant and seeds per pod in intercropping system significantly decreased by 22.0%, 36.0% and 17.6% for early-maturing soybean, 5.1%, 13.1% and 8.9% for mid-maturing soybean, 5.7%, 7.6% and 2.1% for late-maturing soybean, respectively. The yields of mid-maturing and late-maturing varieties in intercropping systems were higher than that of the early-maturing, which increased by 92.4% and 163.4%, with the land equivalent ratio (LER) of 1.81 and 1.84, respectively. This suggested that mid-maturing and late-maturing soybean varieties were suitable for intercropping with the potato to improve photosynthetic efficiency, dry matter accumulation and yield of intercropping soybean.

Impacts of exposure to 900 MHz mobile phone radiation on liver function in rats.

OBJECTIVE: To study the impacts of exposure to electromagnetic radiation (EMR) on liver function in rats. METHODS: Twenty adult male Sprague-Dawley rats were randomly divided into normal group and radiated group. The rats in normal group were not radiated, those in radiated group were exposed to EMR 4 h/ d for 18 consecutive days. Rats were sacrificed immediately after the end of the experiment. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and those of malondialdehyde (MDA) and glutathione (GSH) in liver tissue were evaluated by colorimetric method. The liver histopathological changes were observed by hematoxylin and eosin staining and the protein expression of bax and bcl- 2 in liver tissue were detected by immunohistochemical method. Terminal-deoxynucleotidyl transferase mediated nick and labelling (TUNEL) method was used for analysis of apoptosis in liver. RESULTS: Compared with the normal rats, the serum levels of ALT and AST in the radiated group had no obvious changes (P>0.05), while the contents of MDA increased (P < 0.01) and those of GSH decreased (P < 0.01) in liver tissues. The histopathology examination showed diffuse hepatocyte swelling and vacuolation, small pieces and focal necrosis. The immunohistochemical results displayed that the expression of the bax protein was higher and that of bcl-2 protein was lower in radiated group. The hepatocyte apoptosis rates in radiated group was higher than that in normal group (all P < 0.01). CONCLUSION: The exposure to 900 MHz mobile phone 4 h/d for 18 days could induce the liver histological changes, which may be partly due to the apoptosis and oxidative stress induced in liver tissue by electromagnetic radiation.

Genotype distribution of human papillomavirus in women with abnormal cervical cytology in an esophageal carcinoma high incidence area of China.

Infection with human papillomavirus (HPV) could affect genesis of both cervical and esophageal cancers. The type-specific distribution of HPV in cervical cytology abnormalities of women has remained unclear in Shantou, an esophageal cancer high-incidence area of China. Data from 22,617 women who were subjected to cervical HPV DNA testing with simultaneous cervical cytological examination during 2009-2013 were therefore here retrospectively evaluated in a hospital-based study. Overall, 16.2% (3,584/22,114)of women with normal cytology were HR-HPV positive, with HPV-52 (4.07%) as the most common type followed by -16 (3.63%), and -58 (2.46%). Prevalence of HR-HPV was 50.3% (253/503) in women with cervical cytological abnormalities, of which in ASC-H 71.4%, ASC-US 39.1%, HSIL 80.3% and LSIL 73.7%. HPV-58 (14.12%) was the most common type for all cervical cytological abnormalities, followed by HPV-16 (13.72%), and -52 (12.72%), while the more common HPV-16 type in ASC-H (42.9%) and HSIL (36.1%), HPV-52 and -58 were the most common types for ASC-US (10.3%) and LSIL (25%), respectively. Multiple HPV co-infections were identified in 33.2% (84/253) cytology abnormalities with positive HR-HPV, and the highest prevalence of HPV-58/16 combination in HSIL (28.6%, 6/21) was observed. Our data indicated a relative high prevalence of HPV-58 and -52 in women with cervical cytological abnormalities, which should be considered in the development of next-generation vaccines for Shantou.

[Effects of plastic film mulching with double ridges and furrow planting on soil moisture and temperature and soybean yield on a semiarid dryland of Gansu Province, Northwest China].

Taking soybean cultivar Jindou 23 as test object, a field experiment was conducted at the Zhenyuan experimental station of Gansu Academy of Agricultural Sciences to study the effects of various plastic mulching treatments on the soil moisture and temperature and soybean grain yield on a semiarid dryland of Northwest China. Four treatments were installed, i. e., plastic film mulching with double ridges and furrow planting (FMRFC), plastic film mulching without ridges and with furrow planting (FMFC), plastic film mulching with strip planting (FMSC), and no mulch strip planting (NMSC, CK). During the drought year (the precipitation in soybean growth period was 246.3 mm) and wet year (407 mm), the daily soil temperature in 0-20 cm layer in all mulching treatments varied in "S" shape, and its fluctuation became smaller with soybean growth. The mulching treatments raised the daily average soil temperature in 0-20 cm layer by an average of 0.5-2.5 degrees C from the seedling (VE-V3) to seed filling (R6) stage, with the average soil temperature in whole growth period raised by 1.3-1.6 degrees C. Both in dry year and in wet year, mulching treatments promoted the soil moisture consumption in 0-120 cm layer, by soybean, but increased the average soil moisture content and water storage in 0-200 cm layer by 1.2%-1.4% and 62.7-70.3 mm, respectively. As compared to CK, treatments FMRFC and FMFC had significant effects in improving the soil temperature and moisture environment in dry year, and greatly improved the yield-related traits such as plant height, branching number, pods per plant, and 100-seed mass. FMRFC increased the yield by 27.7%-51.1% and raised the water use efficiency (WUE) by 47.7%- 56.3%, whereas FMFC increased the yield by 10.2% -25.2% and raised the WUE by 33.3%-35.4%, as compared to CK. It was suggested that FMRFC and FMFC could be the most efficient planting systems for the soybean production in the dryland farming of Northwest China.

[Genetic characteristics associated with drought tolerance of plant height and thousand-grain mass of recombinant inbred lines of wheat].

A total of 120 recombinant inbred lines (RIL) derived from Chinese winter wheat cultivars Longjian 19xQ9086 and the two parents were taken as test materials to study the quantitative genetics characteristics of their plant height at different development stages, thousand-grain mass, as well as the correlations between the two traits under rainfed (drought stress) and well-watered conditions, and evaluate the genetic variation of the RIL. Under the two water conditions, the target traits of the RIL showed substantial transgressive segregation and great sensitivity to water condition. The drought stress coefficient of the plant height was higher at jointing stage, being up to 0.851. There was a significant positive correlation between the plant height at different development stages and the thousand-grain mass, and comparing with that at other growth stages, the plant height at jointing stage had a higher correlation coefficient with the thousand-grain mass (R2DS = 0.32, R2WW = 0.28). The plant height at both jointing and flowering stages had significant positive and direct effect but negative and indirect gross effect on the thousand-grain mass, while the plant height at heading and maturing stages was in adverse. The target traits showed a lower heritability ranged from 0.27 to 0.60. The numbers of the gene pairs controlling the thousand-grain mass were 10 under rainfed and 13 under well-watered conditions, while those of the gene pairs controlling the plant height at different development stages were 3-7 under rainfed and 4-14 under well-watered conditions, respectively. According to the clustering of the drought stress coefficient of plant height, the RIL could be classified into five subgroups, showing the abundant variation of the RIL in their phe- notypes and in the sensitivity to water condition. It was considered that the test RIL were appropriate for the study of the quantitative genetics of wheat drought resistance.

Agonist-dependent potentiation of vanilloid receptor transient receptor potential vanilloid type 1 function by stilbene derivatives.

Transient receptor potential vanilloid type 1 (TRPV1) is a nonselective cation channel activated by capsaicin, low pH, and noxious heat and plays a key role in nociception. Understanding mechanisms for functional modulation of TRPV1 has important implications. One characteristic of TRPV1 is that channel activity induced by either capsaicin or other activators can be sensitized or modulated by factors involving different cell signaling mechanisms. In this study, we describe a novel mechanism for the modulation of TRPV1 function: TRPV1 function is modulated by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and its analogs. We found that, in rat dorsal root ganglion neurons, although DIDS did not induce the activation of TRPV1 per se but drastically increased the TRPV1 currents induced by either capsaicin or low pH. DIDS also blocked the tachyphylaxis of the low pH-induced TRPV1 currents. 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS), a DIDS analog, failed to enhance the capsaicin-evoked TRPV1 current but increased the low pH-evoked TRPV1 currents, with an effect comparable with that of DIDS. SITS also blocked the low pH-induced tachyphylaxis. DIDS also potentiated the currents of TRPV1 channels expressed in human embryonic kidney 293 cells, with an effect of left-shifting the concentration-response curve of the capsaicin-induced TRPV1 currents. This study demonstrates that DIDS and SITS, traditionally used chloride channel blockers, can modify TRPV1 channel function in an agonist-dependent manner. The results provide new input for understanding TRPV1 modulation and developing new modulators of TRPV1 function.

Meta-analysis of ADH1B and ALDH2 polymorphisms and esophageal cancer risk in China.

AIM: To evaluate whether alcohol dehydrogenase-1B (ADH1B) His47Arg and aldehyde dehydrogenase-2 (ALDH2) Glu487Lys polymorphism is involved in the esophageal squamous cell carcinoma (ESCC) risk in Chinese Han population. METHODS: Seven studies of ADH1B and ALDH2 genotypes in Chinese Han population in 1450 cases and 2459 controls were included for meta-analysis. Stratified analyses were carried out to determine the gene-alcohol and gene-gene interaction with ESCC risk. Potential sources of heterogeneity between studies were explored, and publication bias was also evaluated. RESULTS: Individuals with ADH1B arginine (Arg)/Arg genotype showed 3.95-fold increased ESCC risk in the recessive genetic model [Arg/Arg vs Arg/histidine (His) + His/His: odds ratio (OR) = 3.95, 95% confidence interval (CI): 2.76-5.67]. Significant association was found in the dominant model for ALDH2 lysine (Lys) allele [glutamate (Glu)/Lys + Lys/Lys vs Glu/Glu: OR = 2.00, 95% CI: 1.54-2.61]. Compared with the non-alcoholics, Arg/Arg (OR = 25.20, 95% CI: 10.87-53.44) and Glu/Lys + Lys/Lys (OR = 21.47, 95% CI: 6.44-71.59) were found to interact with alcohol drinking to increase the ESCC risk. ADH1B Arg+ and ALDH2 Lys+ had a higher risk for ESCC (OR = 7.09, 95% CI: 2.16-23.33). CONCLUSION: The genetic variations of ADH1B His47Arg and ALDH2 Glu487Lys are susceptible loci for ESCC in Chinese Han population and interact substantially with alcohol consumption. The individuals carrying both risky genotypes have a higher baseline risk of ESCC.

[Study on the score criteria of severe hand, foot and mouth disease cases].

OBJECTIVE: To explore the score criteria of severe hand, foot and mouth disease (HFMD) cases and to provide evidence for unified criteria and treatment on severe HFMD cases. METHODS: All severe cases and partial mild cases reported by two designated hospitals of HFMD in Fuyang during March to June, 2008 were scored by the methods of criteria constructed in advance. ROC curve was adopted to evaluate the score criteria and the gold standard was defined according to ICU, intubation and clinical outcomes, etc. Sensitivity, specificity and Youden's index were used to determine the division scores on critical, severe and mild cases. RESULTS: 97% of the cases (34 cases) were scored less than 6 points. 88% of cases (24 cases) who were intubated or mechanical ventilated had the scores of 6 points or higher. 79% of deaths (11 cases) were scored 10 points or higher. The area of receiver operation characteristic (ROC) curve was 0.90 (95%CI: 0.83 - 0.98) between severe and mild cases and the area of ROC curve was 0.95 (95%CI: 0.92 - 0.98) between critical and severe, mild cases. When comprehensively considering the sensitivity and specificity, severe cases were best judged when score was 4 points (sensitivity, specificity and Youden's index were 0.94, 0.68 and 0.62 respectively). When score was 6 points, critical cases were judged very well (sensitivity, specificity and Youden's index were 0.92, 0.84 and 0.76 respectively). CONCLUSION: Score criteria could be quantified to determine the degree of seriousness and with high-value for diagnosis on HFMD.

[Synthesis and activity of some new histone deacetylases inhibitors].

To explore novel histone deacetylase (HDAC) inhibitors with anti-tumor activity, twelve target compounds were synthesized, and their structures were confirmed by 1H NMR, MS and elemental analyses. Evaluation results in vitro showed that compound Ia exhibited potent inhibition against HDAC and is worth for further investigation. And compounds IIa, IIb, IIIa-IIIi possessed moderate HDAC inhibitory activity.

[Effect of tumor vascular invasion upon cardio-pulmonary exercise functions in patients with lung cancer].

OBJECTIVE: To investigate the correlation between the tumor vascular invasion and the change of cardio-pulmonary exercise function in patients with lung cancer. METHODS: The cardio-pulmonary exercise test was performed in 405 patients with lung cancer (293 with vascular invasion and 112 without). The peak load indices examined included maximal work power (measured value/predicted value, W%), maximal oxygen uptake per weight (VO(2)/kg), anaerobic threshold (AT), maximal oxygen pulse (measured value/predicted value, VO(2)/HR%), maximal minute ventilation (V(E)), maximal breath reserve (BR), maximal breath frequency (BF) and maximal tidal volume during expiration (VTex). RESULTS: (1) W%, VO(2)/kg, AT, VO(2)/HR% of patients with vascular invasion [(73 +/- 18)%, (17 +/- 5) ml * min(-1) * kg(-1), (51 +/- 14)%, (79 +/- 18)% respectively] decreased than those without vascular invasion [(86 +/- 20)%, (19 +/- 5) ml * min(-1) * kg(-1), (55 +/- 14)%, (88 +/- 20)% respectively, all P < 0.01) while BF increased [(32.1 +/- 6.1)/min vs (30.6 +/- 5.1)/min, P < 0.05). (2) The patients were divided according to TNM stage, number, kind of tumor vascular invasion and its relationship with tumor, W%, VO(2)/HR% decreased in the groups of 1-, 2- and >or= 3-vessel invasion versus the control group (P < 0.01), AT decreased in the groups of 1- and >or= 3-vessel invasion versus the control group (P < 0.05, P < 0.01), VO(2)/kg decreased in the groups of 2- and >or= 3-vessel invasion versus the control group (P < 0.05, P < 0.01), VO(2)/kg decreased in the group of >or= 3-vessel invasion versus 1- and 2-vessel invasion (P < 0.05 or P < 0.01), VO(2)/HR% decreased in the group of >or= 3-vessel invasion versus 1-vessel invasion (P < 0.01), VTex decreased in the group of >or= 3-vessel invasion versus the control group and 1-vessel invasion (P < 0.05). There was correlation between VO(2)/HR% and the number of tumor invaded vessels (r = 0.220, P < 0.01). CONCLUSIONS: The amount of oxygen uptake, exercise ability and cardiac function during exercise decrease in patients of lung cancer with tumor vascular invasion. The main reason is the number of the invaded vessels.

Heredity, diet and lifestyle as determining risk factors for the esophageal cancer on Nanao Island in Southern China.

In this case-control study we evaluated contribution of environmental and genetic factors for risk of esophageal cancer (EC) by studying populations on Nanao Island (highest risk area for EC in China) and Shanwei (low risk region). Data on lifestyle, diet and family history were collected from the 166 newly diagnosed EC patients on Nanao between 2003 and 2004, from their 1450 first degree relatives and from controls on Nanao and Shanwei. Univariate and logistic regression analysis, family aggregation patterns, standardized incidence ratio (SIR), segregation ratio and heritability index were evaluated. The family cancer history was a significant risk factor for the two scenarios; Nanao cases versus Nanao controls, and Nanao controls versus Shanwei controls. Other risk factors included smoking, alcohol and fermented fish sauce. After adjusting for confounding variables, family history was independently associated with the occurrence of EC in Nanao cases versus Nanao controls. The incidence in the first degree relatives of Nanao cases was 0.86%, significantly higher than that of the public (0.12%) and SIR value was 1.44 in the first degree relatives of the 166 EC cases. The segregation ratio was 0.11 and the heritability index among first degree relatives was 40%. Our study indicates that there are steady pathogenic risk factors in the Nanao population's lifestyle but genetic factors also play an important role for EC onset.

Expression of heme oxygenase-1, hypoxia inducible factor-1alpha, and ubiquitin in peripheral inflammatory cells from patients with coronary heart disease.

BACKGROUND: The increased expression of heme oxygenase-1 content, a stress-response protein, directly correlates with the incidence of coronary heart disease. Down-regulation of hypoxia inducible factor-1alpha activity, a major downstream effector of the signaling pathways activated by hypoxia, increases cell survival after hypoxia. The ubiquitin system, a non-lysosomal pathway of protein degradation, is involved in processes of coronary heart disease. The aim of this study was to investigate the expression of heme oxygenase-1, hypoxia inducible factor-1alpha, and ubiquitin in both monocytes and lymphocytes isolated from patients at the mRNA and protein levels in different stages of coronary heart disease and their possible correlation. METHODS: A total of 90 patients with coronary heart disease (30 acute myocardial infarction, 30 unstable angina pectoris, and 30 stable angina pectoris) were selected, and 30 cases with normal coronary artery served as controls. The mRNA and protein expression of heme oxygenase-1, hypoxia inducible factor-1alpha, and ubiquitin in monocytes and lymphocytes were examined by semi-quantitative reverse transcriptase polymerase chain reaction and Western blotting, respectively. RESULTS: The mRNA expression of heme oxygenase-1 and ubiquitin was associated with the severity of coronary heart disease (p<0.05). There was no significant difference in hypoxia inducible factor-1alpha mRNA expression between the coronary heart disease patients and controls. The protein expression of heme oxygenase-1, hypoxia inducible factor-1alpha, and ubiquitin was significantly stronger in patients with coronary heart disease than in controls, and the expression levels increased with the severity of the disease. There was a positive association between heme oxygenase-1 and hypoxia inducible factor-1alpha and ubiquitin, antioxidative therapy with adrenergic receptor blocker, angiotensin-converting enzyme inhibitor or statins up-regulated the expression of heme oxygenase-1 and hypoxia inducible factor-1alpha. CONCLUSIONS: These data suggest that heme oxygenase-1, hypoxia inducible factor-1alpha, and ubiquitin are involved in the development and progression of coronary heart disease and thus may be useful biomarkers for coronary heart disease.

Hypoxia-inducible factor-1alpha induces the coronary collaterals for coronary artery disease.

BACKGROUND: Marked variability exists in coronary artery collaterals in patients with ischemic heart disease. Multiple factors are thought to play a role in collateral development; however, the contribution of hypoxia inducible factor-1alpha (HIF-1alpha), which is a transcriptional activator that functions as a master regulator of oxygen homeostasis, is not completely clear. It could play an important role in modulating collateral development. OBJECTIVE: The objective of this study is to investigate the changes and significance of expression of HIF-1alpha in patients with coronary artery collaterals. METHODS: Collateral vessels were determined in 98 patients with >or=70% narrowing of at least one coronary artery without earlier revascularization, 42 patients with coronary artery collaterals and 56 patients with no coronary artery collaterals. Extent of collaterals was expressed as scores according to the Rentrop scoring system. Another 50 cases with normal coronary arteries were selected as control. The levels of HIF-1alpha protein expression in monocyte and lymphocyte in the participants were tested by immunohistochemistry (IHC) and western blot; mRNA levels were measured using reverse transcriptase PCR technique. RESULTS: Compared with the control with normal coronary artery, the patients had higher expression of HIF-1alpha protein tested by IHC and western blot (52.6+/-10.2 vs. 13.7+/-6.2 by IHC, 50.8+/-4.5 vs. 6.5+/-1.8 by western blot); furthermore, significantly higher HIF-1alpha expression was observed in patients with collaterals compared with patients with no collaterals (81.5+/-11.8 vs. 20.7+/-9.4 by IHC; 87.2+/-6.5 vs. 9.5+/-1.4 by western blot). On the transcriptional levels of HIF-1alpha, the result was the same as the protein, there was significant difference of HIF-1alpha between the three groups. The patients with collaterals were the highest (127.3+/-23.9), followed by patients with no collaterals (35.7+/-12.3), and the control were the lowest (23.5+/-9.3). A highly positive correlation was observed between the expression/transcription of HIF-1alpha and collateral score (P<0.01, IHC: r1=0.78, reverse transcriptase PCR: r2=0.69, western blot: r3=0.84). CONCLUSION: These data suggest that higher inductions of HIF-1alpha are associated with coronary collaterals, thus implying that HIF-1alpha may promote coronary collateral formation. Detection of HIF-1alpha expression might be helpful to predict prognosis of patients with coronary artery disease.