Evaluation of right ventricular performance and impact of continuous positive airway pressure therapy in patients with obstructive sleep apnea living at high altitude.

Obstructive sleep apnea syndrome (OSAS) can lead to alterations in right ventricular (RV) performance and pulmonary vascular haemodynamics. Additionally, altitude-related hypoxia is associated with pulmonary vasoconstriction, and the effect of high-altitude on the pulmonary circulation in OSAS patients can be further altered. We sought to assess alterations in RV morphology and function in OSAS patients living at high altitude by way of 2-dimensional speckle tracking echocardiography (2D-STE), real-time 3- dimensional echocardiography (RT-3DE) and cardiac biomarkers. We also evaluate the impact of continuous positive airway pressure (CPAP) treatment on RV performance. Seventy-one patients with newly diagnosed OSAS and thirty-one controls were included in this study. All individuals were assessed for cardiac biomarkers as well as underwent 2D-STE and RT-3DE. Forty-five OSAS patients underwent CPAP therapy for at least 24 weeks and were studied before and after CPAP treatment. RT-3DE was used to measure RV volume, and calculate RV 3D ejection fraction (3D RVEF). Peak systolic strain was determined. Cardiac biomarkers, including C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide, and cardiac troponin T were also measured. Right atrium volume index, RV volume, RV volume index, systolic pulmonary artery pressure (sPAP), pulmonary vascular resistance (PVR) and level of serum CRP were significantly higher in OSAS group, while OSAS patients showed lower 3D RVEF and RV longitudinal strains. Compared to the patients with sPAP < 40 mmHg, RV longitudinal strains in patients with sPAP ≥ 40 mmHg were lower. Both RV global longitudinal strain and sPAP were associated with apnea-hypopnea index. Patients treated with 6 months of CPAP therapy had significant improvement in RV geometry and performance. RV structural abnormalities and RV function impairments were observed in OSAS patients living at moderate high altitude compared to control highlanders. The reversibility of these changes after application of CPAP were further confirmed.

Presence of thyrotropin receptor in hepatocytes: not a case of illegitimate transcription.

The function of thyrotropin (TSH) in the thyroid gland is mediated by thyrotropin receptor (TSHR). In addition to the thyroid, TSHR expression has been described in some non-thyroidal tissues, although it is uncertain whether TSHR is present in hepatocytes. One study has reported hepatic expression of TSHR mRNA, but this was considered to be because of illegitimate transcription, and there has not been a study investigating its protein expression and function in hepatocytes. Here, we examined the expression of TSHR in human and rat liver tissues, as well as human normal hepatocyte cell line L-02. Our results demonstrated that hepatic TSHR mRNA could be detected and had the same sequence as that of thyroid-derived mRNA. TSHR protein was also expressed and mainly located in the hepatocyte cell membrane. Moreover, bovine TSH and immunoglobulin from sera of patients with Graves' disease stimulated cAMP production in these cells. Taken together, these data show that TSHR is present and functional in hepatocytes, and this expression is not a case of illegitimate transcription. Given the pivotal role of the liver in body metabolism and many human diseases, our findings provide important implications for a potentially novel physiopathological role of TSH via acting on the TSHR in hepatocytes besides its classical role in regulating the thyroid function.

Establishment and biological characteristics of acquired gefitinib resistance in cell line NCI-H1975/gefinitib-resistant with epidermal growth factor receptor T790M mutation.

Non­small cell lung cancer (NSCLC) cells harboring mutations in the epidermal growth factor receptor (EGFR) gene initially respond well to EGFR tyrosine kinase inhibitors (TKI), including gefitinib. However the tumor cells will invariably develop acquired resistance to the drug. The EGFR T790M mutation is generally considered to be the molecular genetic basis of acquired TKI resistance. The present study aimed to explore how the T790M mutation induces tumor cells to escape inhibition by TKI treatment. An acquired gefitinib­resistant cell line (NCI­H1975/GR) was generated from the NCI­H1975 human NSCLC cell line, which harbors the sensitive L858R and resistant T790M mutations of EGFR. The resistant cell line was established by exposing the cells intermittently to increasing concentrations of gefitinib. The mechanisms by which NSCLC acquires resistance to TKIs based on the T790M mutation, were investigated by detecting the protein expression levels of the EGFR/Kirsten rat sarcoma viral oncogene homolog (KRAS)/v­Raf murine sarcoma viral oncogene homolog B (BRAF) transduction pathway, and epithelial­mesenchymal transition (EMT) with immunocytochemistry. The resistance of the NCI­H1975/GR cells to gefitinib was 2.009­fold, as compared with the parent cells; however, the protein expression levels of EGFR, KRAS and BRAF were lower in the resistant cells. Some mesenchymal morphology was observed in the NCI­H1975/GR cells, alongside a decreasing E­cadherin expression and increasing vimentin expression. These results suggest that the reactivation of the EGFR/KRAS/BRAF transduction pathway was not detected in the NCI­H1975/GR cells. EMT may have an important role in the development of acquired resistance to EGFR­TKIs in NSCLC cells with sensitivity and resistance mutations.

Association of ghrelin Leu72Met polymorphism with type 2 diabetes mellitus in Chinese population.

BACKGROUND: Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor, is considered to implicate the development of the type 2 diabetes mellitus (T2DM). The Leu72Met (+408C>A) polymorphism of the preproghrelin, has been linked to obesity, insulin resistance and diabetes. OBJECTIVE: To investigate the distribution of ghrelin gene Leu72Met polymorphism and its association with the type 2 diabetes mellitus in Chinese population. METHODS: We conducted a case-control study on 877 patients with T2DM and 864 controls, which were genotyped by the polymerase chain reaction (PCR) technique, denaturing high performance liquid chromatography (DHPLC) and DNA sequence analysis. Laboratory analyses were carried out in the hospital laboratory. RESULTS: No significant difference in the Leu72Met genotype distributions and allele frequency was observed between type 2 diabetes mellitus and controls (both P>0.05). The polymorphism was not associated with T2DM. However, among the T2DM group, the patients carrying Leu72Leu genotype had significantly increased levels of FPG and serum creatinine compared with variant genotypes (Leu72Met and Met72Met) (P<0.05). In the control group, the subjects with variant genotypes had significantly increased levels of FINS, HOMA-IR compared with Leu72Leu genotype (P<0.05). CONCLUSION: The Leu72Met polymorphism of the preproghrelin gene was not associated with T2DM in Chinese population. However, it may have some roles in the etiology of insulin resistance.

Validation of the association between PSMA6 -8 C/G polymorphism and type 2 diabetes mellitus in Chinese Dongxiang and Han populations.

OBJECTIVE: The aim of our study was to validate association between -8 C/G variant of PSMA6 gene and T2DM in Chinese Dongxiang and Han populations. METHOD: We genotyped PSMA6 gene -8 C/G polymorphism in the control groups and T2DM groups in two populations from China using PCR-RFLP technique. Phenotypes and biochemical indicators were measured by biochemical technique. RESULT: The frequencies of CG+GG genotype were observably different from CC genotype in the T2DM groups and control groups (for Dongxiang population: OR = 1.341, 95% CI: 1.101-1.632, P = 0.004; for Han population: OR = 1.313, 95% CI: 1.085-1.569, P = 0.006 after adjusting for gender, age, and BMI, respectively). In the Dongxiang population, the FPG, HOMA-IR, SBP and TG levels of CG+GG genotype were markedly higher than those of the CC genotype in control group (all P < 0.05). However, in the Han population, we only found that the FPI level of the CC genotype was significantly higher than that of the CG+GG genotype in control group (P < 0.05). CONCLUSION: Our investigation suggests that -8 C/G variant of PSMA6 gene may be associated with T2DM and diabetes-related metabolic traits in Chinese Dongxiang and Han populations.

Association of P213S polymorphism of the L-selectin gene with type 2 diabetes and insulin resistance in Chinese population.

AIMS: L-selectin belongs to selectin family of adhesion molecule and participates in the generation and development of type 2 diabetes (T2D). In this study, we evaluated the relationship between the P213S polymorphism of L-selectin gene and T2D and insulin resistance in the Chinese population. METHODS: We genotyped P213S polymorphism in 801 patients with T2D and 834 healthy controls in the Chinese population using polymerase chain reaction-ligase detection reaction (PCR-LDR) technique. Plasma glucose, insulin, lipid, blood urea nitrogen, creatinine and uric acid levels were measured by biochemical technique. RESULTS: The frequency of 213PP genotype and P allele of the L-selectin gene in patients with T2D was significantly higher than that in controls (P=0.007; P=0.019, respectively). The relative risk of allele P suffered from T2D was 1.191 times higher than that of allele S. Moreover, the levels of FPG and HOMA-IR of PP and PS genotype carriers were significantly higher than those of SS genotype carriers in the T2D group (P<0.05). CONCLUSION: These findings indicated that the P213S polymorphism of L-selectin gene may contribute to susceptibility to T2D and insulin resistance in the Chinese population, and P allele appears to be a risk factor for T2D.

[Retrospective investigation of inpatients with chronic wounds].

OBJECTIVE: To investigate cause of chronic wounds and related status of patients so as to provide strategy for study and treatment of chronic wounds and establishment of health policy. METHODS: A total of twelve thousand one hundred and sixty-one cases hospitalized in our hospital in 2008 were enrolled in the study. A chronic wound was defined as skin tissue defect which could not heal after one month of treatment. Medical records were thus screened. Then a retrospective study was performed on patients with chronic wounds with analysis of age, gender, injury cause, therapy, and average length of hospital stay. Data were processed with chi-square test and one-way analysis of variance. RESULTS: Investigation showed: 397 out of 12 161 cases (accounting for 3.3%) were recognized as having chronic wounds. (1) The main causes for chronic wound were burn, diabetes, and pressure ulcer, accounting for 59.9% (238/397), 15.6% (62/397), 10.8% (43/397), respectively. The other causes were operative injury, infection, varicosity, etc. There was statistical difference among the numbers of patients with chronic wounds with regard to various causes of injury (χ(2) = 136.21, P = 0.001). (2) Among patients with chronic wound, the ratio of male and female was 2.0:1.0 with mean age of (44 ± 23) years, and the highest ratio occurred in patients older than 70 years. There was significant difference in the numbers of patients with chronic wound among different age groups (χ(2) = 24.12, P = 0.025). There was statistical difference among the numbers of patients with chronic wound in different age groups with each cause of injury (with χ(2) values from 7.86 to 28.31, P values all below 0.05). (3) All patients with chronic wounds received traditional dressing. In 60.5% (240/397) and 86.4% (343/397) of patients, operative treatment or antibiotics were given. (4) The average length of hospital stay in patients with chronic wound [(38 ± 27) d] was longer as compared with that of all the inpatients in the same period [(15 ± 7) d, F = 22.82, P = 0.012]. There was obvious difference in the average length of hospital stay among patients with chronic wound caused by different reasons (F = 24.06, P = 0.036), in which burn injury resulted in the longest length of hospital stay [(47 ± 27) d]. CONCLUSIONS: Chronic wounds are mainly caused by diabetes and burn, and characterized by old age and longer length of hospital stay. It is necessary to strengthen translational research and related policy making, so that more rational treatment can be applied for patients with chronic wounds.

Association of sterol regulatory element-binding protein-1c gene polymorphism with type 2 diabetes mellitus, insulin resistance and blood lipid levels in Chinese population.

AIMS: The sterol regulatory element-binding protein (SREBP)-1c gene has been identified as a susceptibility gene in metabolic diseases such as type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and insulin resistance. Previous studies suggest that SNP17 (rs2297508, exon18c and G952G) of SREBP-1c gene and a common SREBP-1c SNP6 (rs11868035) are associated with an increased risk of T2DM. The present study aimed to confirm the previously reported association in a Chinese population and to examine the two SREBP-1c SNPs for their associations with insulin resistance and blood lipid. METHODS: We genotyped two SREBP-1c SNPs in a case-control study (n=327) from Chinese, including 156 patients with T2DM and 171 healthy controls, using polymerase chain reaction-denaturing high-performance liquid chromatography (PCR-DHPLC) and tested for association with type 2 diabetes, insulin resistance and blood lipid, respectively. Genotype and allele distributions and haplotype construction were analysed. RESULTS: The genotype and allele distributions of rs2297508 and rs11868035 polymorphisms were significantly different in type 2 diabetic patients compared to controls (P=0.002 and P=0.013; 0.00 and 0.001, respectively). Haplotype analyses showed significant association with diabetes risk and confirmed the results of the single SNP analyses. The plasma levels of LDL-c of the minor allele-C carriers of the two SNPs were both significantly higher than the noncarriers in the control group (P<0.05). Furthermore, insulin resistance index (HOMA-IRI) of the rare homozygotes C/C of rs11868035 was significantly lower than that of T/T in the T2DM group (P<0.05). CONCLUSIONS: These findings indicate that the SREBP-1c SNPs rs2297508 and rs11868035 are associated with a significantly increased risk of T2DM and dyslipidemia in the Chinese population. Moreover, the SNP (rs11868035) is closely related to insulin resistance (IR) in diabetic patients.

[Study on the determinants of Helicobacter pylori infection among coal miners].

OBJECTIVE: To study the prevalence and determinants of Helicobacter pylori (H. pylori) infection among coal miners and to seek for competent preventive measures. METHODS: 425 coal miners from three coal mines, Tangshan, Daxing, and baodian were chosen under stratified random cluster sampling. Face to face interview was conducted to fill the unified questionnaires by trained interviewers. 306 subjects underwent gastroenduoscopy to detect the situation of the gastroenduodenal diseases, according to the Sydney System of diagnosis. Mucosa biopsies were also undertaken according to the regulated location for culture of H. pylori and for pathological examination. Blood samples were obtained to detect the anti-HpU-IgG by enzyme-linked immunosorbent assay (ELISA). H. pylori infection was determined through culture and ELISA but confirmed under the standards set at the National Congress on Gastroduodenal Diseases in 1999. RESULTS: Among 425 eligible coal miners being tested, 297 (69.9%) were H. pylori positive and the rate for those working underground (74.0%) was higher than that of those working on ground (P=0.004). No difference was found among coal miners between the three mines (P >0.05). Age, living conditions in childhood, number of current family members, the amount of alcohol intake and ways of eating at home were strongly associated with the status of H. pylori infection. CONCLUSIONS: Difference of H. pylori infection prevalences between the underground and the aboveground coal miners was noticed. Determinants that influencing the H. pylori infection would include socioeconomic factors, individual habits and ways of eating at home.