Objective:To investigate the outcomes and influencing factors of newly diagnosed prediabetic subjects aged 40 years and above in Guiyang.Methods:A total of 10 015 residents aged 40 years and above were recruited from the Yunyan community, Guiyang, from May to August 2011. Physical examination, laboratory measurements, and questionnaires were conducted. The follow-up survey was conducted in July 2014. A total of 2 530 newly diagnosed prediabetic subjects at baseline were included in the analysis.Results:The 3-year cumulative morbidity of diabetes mellitus was 14.3%, and the risk of diabetes mellitus in combined impaired fasting glucose(IFG)and impaired glucose tolerance(IGT)groups was significantly higher than that in isolated IFG(i-IFG)or isolated IGT(i-IGT)group( P<0.01). High baseline fasting plasma glucose, 2 h plasma glucose, and HbA 1C levels were the independent risk factors for the development of diabetes( OR=1.836, 95% CI 1.374-2.454; OR=1.398, 95% CI 1.261-1.550; OR=2.526, 95% CI 1.804-3.538, all P<0.01)and the inhibitory factors for reversion to normal glucose tolerance( OR=0.511, 95% CI 0.409-0.638; OR=0.715, 95% CI 0.661-0.774; OR=0.638, 95% CI 0.500-0.816, all P<0.01). High level of high density lipoprotein-cholesterol(HDL-C)was an promoting factor for reversion to normal glucose tolerance( OR=1.306, 95% CI 1.017-1.678, P=0.036). Subjects in the highest tertile of baseline HbA 1C level and body mass index(BMI)change before and after follow-up(ΔBMI=follow-up BMI minus baseline BMI)had a higher risk of diabetes mellitus than those in the lowest tertile( OR=2.398, 95% CI 1.733-3.322; OR=2.402, 95% CI 1.859-3.105, both P<0.01). The risk of diabetes mellitus in the significant weight loss group was reduced by 40.4% compared with the non-significant weight loss group when the subjects were divided into two groups according to the cutoff of the lower tertile of ΔBMI( RR=0.596, 95% CI 0.463-0.766, P<0.01). Conclusion:The risk of diabetes mellitus in combined IFG/IGT group was significantly higher than that in i-IFG or i-IGT group. High baseline fasting plasma glucose, 2 h plasma glucose, and HbA 1C levels were the independent risk factors for the development of diabetes. High level of HDL-C was an promoting factor for reversion to normal glucose tolerance. Weight loss can significantly reduce the risk of progression to diabetes in individuals with prediabetes.

Objective:To investigate the correlation between sleep duration, sleep timing and the risk of osteoporosis in postmenopausal women, to identify contributing mechanisms and guide the prevention and treatment of osteoporosis.Methods:A total of 5 449 postmenopausal women were included in this study. All participants completed questionnaires, medical examinations, blood test and the measurement of bone mineral density using calcaneal quantitative ultrasonography. After adjusting for potential confounders, logistic regression model was used to assess the association of sleep duration, sleep timing with the risk of osteoporosis. Results:In postmenopausal women, there were significant differences in sleep duration and timing among groups with different risk of osteoporosis( P<0.05). After controlling ages, BMI, diabetes, hypertension, dyslipidemia, smoking, alcohol consumption and physical activity, sleep duration was correlated with the risk of osteoporosis, long sleep duration(≥9 h)increased the risk of osteoporosis( OR=1.39, 95% CI 1.17-1.65, P<0.05)compared with the group with sleep duration of 7~8 hours. In analysis of the combined effect of sleep duration and sleep time on the risk of osteoporosis, compared with normal sleep duration(7-8 h)and normal sleep timing(22: 00-23: 00), long sleep duration(≥9 h)and normal sleep timing(22: 00-23: 00)increased the risk of osteoporosis( OR=1.38, 95% CI 1.01-1.87, P<0.05), which was higher in the group of long sleep duration(≥9 h)and late sleep timing(≥23: 00; OR=1.43, 95% CI 1.01-2.01, P<0.05). Conclusion:Long sleep duration(≥9 h)and late sleep timing(≥22: 00)are risk factors for the increased risk of osteoporosis in postmenopausal women, the late sleep timing leads to the higher risk.

BACKGROUND: Adenocarcinoma is the most common type of lung cancer. It has been clinically evaluated that therapiestargeting against the epidermal growth factor receptor (EGFR) as the clinical standard first-line treatment. The response and outcome of EGFR-tyrosine kinase inhibitors (TKIs) in patients harboring common mutations in EGFR kinase domain (deletion in exon19 and L858R in exon 21) has been well demonstrated, but not in rare or complex mutations. METHODS: A total of 150 patients that harbored rare or complex mutations in EGFR diagnosed by histopathology were included in this retrospective study. The clinical-pathological characteristics of all 150 patients as well as the response and progression-free survival (PFS) in 48 patients that received EGFR-TKIs in first/second/third line treatments weredescribed and analyzed. RESULTS: Patients were divided into four groups based on the mutation types: single G719X point mutation in exon 18 (n=46, 30.7%), single L861Q point mutation in exon 21 (n=45, 30.0%), other single rare mutation (n=14, 9.3%) and complex mutations (n=45, 30.0%). The result indicated thatthere was no correlation of EGFR mutation typeswith other parameters such as gender, age, clinical stage, pathology and smoking history. For the 48 patients that received EGFR-TKIs treatment, there were no significant differencesamong 4 groups in terms of objective response rate (ORR) and disease control rate (DCR) (54.5% vs 30.0% vs 0.0% vs 35.7%, χ²=3.200, P=0.34; 90.9% vs 85.0% vs 66.7% vs 92.9%, χ²=2.162, P=0.59). The median progress-free survival (mPFS) was 11.0 months (95%CI: 4.4-17.6), and in each group of different EGFR mutation types are 15.8 months (95%CI: 9.5-22.2), 8.0 months (95%CI: 5.1-11.0), 4.9 months (95%CI: 1.4-8.4) and 23.1 months (95%CI: 15.8-30.4)(χ²=7.876, P=0.049). CONCLUSIONS The efficiency of targeting EGFR-TKIs on different types of rare or complex mutations was heterogeneous. The PFS may be better in patients that harbored complex mutations than those with single rare mutations. Further studies with larger sample size are necessary. Moreover, to discover novel therapeutic targets and develop new drugs are imminentfor those patientswith no response to the existing treatments.
Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; Disease-Free Survival ; ErbB Receptors ; antagonists & inhibitors ; genetics ; Exons ; genetics ; Female ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; Male ; Middle Aged ; Mutation ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Retrospective Studies ; Treatment Outcome

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is one of the driver genes of non-small cell lung cancer (NSCLC). Several studies have shown that the efficacy of pemetrexed in HER2-mutant NSCLC is controversial. The aim of this study is to investigate the efficacy of pemetrexed combined with platinum chemotherapy in patients with HER2-mutant and HER2 wild-type lung adenocarcinoma. METHODS: The clinical data of 106 cases of EGFR, ALK, ROS-1, KRAS, BRAF, RET and MET-negative patients with advanced lung adenocarcinoma patients who diagnosed by histopathology in the First Affiliated Hospital of Zhengzhou University were retrospectively reviewed. The relationships between HER2 gene status, clinical characteristics and response and progression-free survival (PFS) were analyzed. RESULTS: All of the 106 patients' HER2 status were determined. HER2 mutations occurred in 32 cases (30.2%), no mutations in 74 cases (69.8%). HER2 mutations were common in young, non-smoking and female patients. All patients received first-line pemetrexed and platinum-based chemotherapy. The objective response rate (ORR) and disease control rate (DCR) of patients with HER2-mutant lung adenocarcinoma were significantly higher than those without HER2 mutations (40.6% vs 14.9%, χ²=8.464, P=0.004; 93.8% vs 68.9%, χ²=6.327, P=0.012), and the difference was statistically significant. According to univariate analysis, the PFS was significantly associated with the brain metastases, maintenance chemotherapy and HER2 gene status (P<0.05), but not with age, gender, smoking history, oligometastases, liver metastases and type of platinum (P>0.05). Cox multivariate analysis indicated that HER2 mutation was an independent positive prognostic factor of PFS (P=0.038). CONCLUSIONS HER2-mutant lung adenocarcinoma patients with first-line pemetrexed combined with platinum chemotherapy have greater clinical benefit than HER2 wild-type patients.
Adenocarcinoma of Lung ; drug therapy ; genetics ; pathology ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Disease-Free Survival ; Female ; Genes, erbB-2 ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Pemetrexed ; therapeutic use ; Platinum ; therapeutic use ; Retrospective Studies ; Treatment Outcome

OBJECTIVES: To investigate the genetic causes of hearing loss with enlarged vestibular aqueduct (EVA) in two children from unrelated two Chinese families. METHODS: Sanger sequencing of all coding exons in SLC26A4 (encoding Pendrin protein) was performed on the two patients, their sibling and parents respectively. To predict and visualize the potential functional outcome of the novel variant, model building, structure analysis, and in silico analysis were further conducted. RESULTS: The results showed that the proband from family I harbored a compound heterozygote of SLC26A4 c.1174A>T (p.N392Y) mutation and c.1181delTCT (p.F394del) variant in exon 10, potentially altering Pendrin protein structure. In family II, the proband was identified in compound heterozygosity with a known mutation of c.919-2A>G in the splice site of intron 7 and a novel mutation of c.1023insC in exon 9, which results in a frameshift and translational termination, consequently leading to truncated Pendrin protein. Sequence homology analysis indicated that all the mutations localized at high conservation sites, which emphasized the significance of these mutations on Pendrin spatial organization and function. CONCLUSION: In summary, this study revealed two compound heterozygous mutations (c.1174A>T/c.1181delTCT; c.919- 2A>G/c.1023insC) in Pendrin protein, which might account for the deafness of the two probands clinically diagnosed with EVA. Thus this study contributes to improve understanding of the causes of hearing loss associated with EVA and develop a more scientific screening strategy for deafness.
Asian Continental Ancestry Group ; Child ; Clinical Coding ; Computer Simulation ; Deafness ; Exons ; Extravehicular Activity ; Frameshift Mutation ; Hearing Loss ; Heterozygote ; Humans ; Introns ; Mass Screening ; Parents ; Sequence Homology ; Siblings ; Vestibular Aqueduct

To improve clinicians'understanding of the diagnosis and treatment of pseudohypoparathyroidism with hypokalemia and hypomagnesemia. The clinical manifestations, laboratory examinations, imaging data, gene results, diagnosis and treatment of a pseudohypoparathyroidism type Ⅰb with hypokalemia and hypomagnesemia patient were retrospectively analyzed. The literatures related to pseudohypoparathyroidism in recent years were also summarized. A young man, mainly manifested as repeated tetany. The physical examination showed short stature, round face, short neck, with positive Trousseau sign. The laboratory examination revealed parathyroid hormone resistance, hypocalcemia, hyperphosphatemia, hypokalemia and hypomagnesemia. The urinary calcium and phosphorus levels were low. Cerebral magnetic resonance imaging ( MRI ) showed bilateral basal ganglia calcification. Genetic screening revealed a hybrid deletion mutation of GNAS-AS1 gene Exon 5E. After the supplement of element calcium 720 mg/d, plain vitamin D 375 U/d, active vitamin D 0.5 μg/d and potassium chloride 3 g/d, the levels of blood potassium and phosphorus rise to normal, the levels of blood calcium and magnesium were close to normal. Pseudohypoparathyroidism typeⅠb may accompany with hypokalemia and hypomagnesemia.

Objective To explore the epidemiological characteristics of the prevalence and incidence of metabolic syndrome(MS) in subjects with different TSH levels, which can provide a certain clinical basis for the prevention and treatment of MS. Methods According to the reference range of the TSH test system in our hospital, the subjects were divided into TSH normal group and TSH elevation group. From May to August of 2011, the whole group sampling method was used to conduct a baseline survey of 10140 permanent residents aged 40 and above in Yunyan district of Guiyang City. A total of 9618 cases were included. The prevalence of MS and its components were calculated with different TSH levels at baseline. After eliminating 3926 MS in 2011, 5692 patients with no MS were followed up for 3 years. Incidence of MS and its components were compared among different TSH levels. The median follow-up was (38. 6 ± 1. 6) months and the completion rate was 75. 40％. Results The total crude and standard prevalence of MS were 40. 82％ and 34. 46％ respectively. The crude and standard prevalence of MS in TSH normal group were 39. 96％ and 33. 90％, respectively, and in TSH elevation group were 44. 3％ and 37. 56％respectively . The comparison of crude prevalence of MS between the two groups was statistically significant (P>0. 05) and the standard prevalence of MS in TSH elevation group was also higher than that in TSH normal group. After 3 years of follow-up, the total crude and standard incidences of MS were 22. 51％ and 20. 64％, respectively. The total crude and standard incidence of MS in TSH normal group were 22. 01％ and 20. 22％, respectively and in TSH elevatlon group were 24. 69％ and 23. 20％, respectively. There was no statistically significant difference between crude incidences of MS in two groups, but the standard incidence of MS in TSH elevation group was higher than that in TSH normal group. Binary Logistic regression analysis showed that there was a positive correlation between TSH and incidence of MS in TSH elevation group. Conclusion Higher than normal levels of TSH may increase the prevalence and incidence of MS and its some components.

Objective To explore the relationship between metabolic syndrome(MS) and glomerular filtration rate(GFR).Methods A total of 10 140 adults aged 40 years and older inhabitants in Zhaiji community of Guiyang urban areas were investigated from May 2010 to August 2010 by adopting stratified cluster sampling method.The venous blood sample was drawn for the measurements of serum creatinine(Cr), fasting plasma glucose(FPG), OGTT 2hPG, fasting insulin, triglyceride(TG), total cholesterol(TC), high-density lipoprotein-cholesterol(HDL-C), low-density lipoprotein-cholesterol(LDL-C), and fasting plasma insulin.The definition of MS in our study was modeled after the Adult Treatment Panel Ⅲ(ATP-Ⅲ).Decreased GFR was defined as an estimated GFR<60 ml·min-1·(1.73 m2)-1.Results The prevalence of GFR less than 60 ml·min-1·(1.73 m2)-1 were 3.0% and 1.2% in participants with and without MS, respectively.The multivariate-adjusted odds ratios[95% confidence interval(CI)] of MS, which were independently associated with decreased GFR, were with elevated blood pressure, higher TG, lower HDL-C, and elevated FPG, their statistically odds ratios were 1.78, 2.96, 1.06, and 1.22, respectively.The prevalence of GFR decreased with the increase of MS components by 0.56%, 1.10%, 1.50%, 2.87%, 3.23%, and the odds ratios were 1.00, 1.57, 1.93, 3.07, and 2.89, respectively.Conclusion With the increase of MS components the risk of GFR decline increased.The occurrence of chronic renal dysfunction(CKD) might integrate multiple different risk factors of MS.

Objective To explore the relationship between risk of stroke and calcaneal quantitative ultrasound(QUS)T score under-2. 5. Methods 5 847 subjects over the age of 40 from Yunyan District, Guiyang City were investigated with questionnaire, physical examination, blood lipids, other metabolic indexes and calcaneus bone density determination from May to October, 2011 by cluster sampling method and were followed up for 3 years. Subjects were divided into stroke group(99 subjects) and non-stroke group(5 748 subjects) according to the occurrence of stroke in the follow-up period. The relationship between risk of stroke and QUS T score under-2. 5 was analyzed. Results Compared to the non-stroke group, the number of subjects with T score under-2. 5 in calcaneal QUS was larger in the stroke group, the difference of which was statistically significant(P<0. 05). T score of bone density under-2. 5 in calcaneal QUS was found to be an independent risk factor for predicting stroke after adjusting for age, sex, and body mass index(HR=1. 467, 95%CI 0. 753-2. 855). The relationship between risk of stroke and T score under-2. 5 in calcaneal QUS remained unchanged after further adjust ment of smoking, diabetes, education, and hypertension(HR=1. 265, 95%CI 0. 647-2. 475). Conclusion The risk of stroke and T score of bone density under-2. 5 in calcaneal QUS was independently associated, and the latter is an independent risk factor for predicting stroke.

Objective To investigate the relationship between changes of ankle brachial index (ABI) and adverse cardiovascular events. Methods Baseline survey was conducted in 4 160 forty-year-old or older citizens living in Yunyan District of Guiyang City from May to August of 2011, which was in the way of cluster sampling to obtain their ABI and to collect information related to physical and blood biochemical examination and disease history. These citizens were conducted a follow-up survey for (39.29±1.47) months from July to December of 2014. Based on the change of ABI (ΔABI) from initial survey to follow-up survey, participants were subsequently divided into three groups: ΔABI>0.15 group,-0.15≤ΔABI≤0.15 group and ΔABI<-0.15 group. The adverse cardiovascular events during follow-up survey were compared between three groups. The risk factors affecting the adverse cardiovascular events were analyzed. Results Follow-up surveys were completed in 3 220 citizens in 3 years. The follow-up rate was 77.4%. Eighty-two new cases (2.5%) of adverse cardiovascular events were found in 3 220 cases in follow-up. The incidence rates of adverse cardiovascular events were higher inΔABI<-0.15 group compared with those of-0.15≤ΔABI≤0.15 group (8.3%vs. 2.4%, P<0.016 7). Logistic regression analysis indicated that age, hypertension history, and ΔABI<-0.15 were risk factors for adverse cardiovascular events. Exercise was the protective factor for adverse cardiovascular events. Conclusion Subjects withΔABI<-0.15 are at high risk for adverse cardiovascular events. The ΔABI can be used as a means of monitoring of adverse cardiovascular event, which provides certain forecast value for determining the possibility of adverse cardiovascular event.