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1.
Sci Rep ; 9(1): 12086, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31427625

RESUMO

To identify the factors associated with serum total bilirubin (STB) and determine whether STB is independently associated with diabetic retinopathy (DR) or diabetic kidney disease (DKD), 1,665 Chinese patients with type 2 diabetes (T2DM) (248 outpatients newly diagnosed with T2DM [NDM] and 1,417 inpatients previously diagnosed with T2DM [PDM]) were studied. Clinical and biochemical information was collected, and a single nucleotide polymorphism (rs6704078) of the UGT1A1 gene was genotyped in 1,059 individuals. Multiple linear regression showed that STB was associated with haemoglobin concentration, platelet count, and serum triglyceride concentration in NDM and PDM patients, and with serum albumin, duration of diabetes, and smoking in PDM patients. In patients with PDM, multiple logistic regression revealed that serum albumin was associated with DR (odds ratio [OR] = 0.92, 95% confidence interval [CI]: 0.87-0.96, p = 0.001) and DKD (OR = 0.93, 95% CI: 0.88-0.98, p = 0.005) after adjustment for STB, STB-related factors, and risk factors for DR and DKD. In addition, patients with the T allele of rs6704078 had higher STB (13.2 [10.4-17.9] µmol/L versus 11.8 (9.4-14.8) µmol/L; p < 0.001) and similar risks of DR or DKD to those without the T allele. Thus, serum albumin, but not STB, is associated with DR and DKD.

2.
Clin Transplant ; 33(10): e13692, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31403741

RESUMO

BACKGROUND: Despite significant advances in durable mechanical support survival, infectious complications remain the most common adverse event after ventricular assist device (VAD) implantation and the leading cause of early death after transplantation. In this study, we aim to describe our local infectious epidemiology and review short-term survival and infectious incidence rates in the post-transplantation period and assess risk factors for infectious episodes after transplantation. METHODS: Retrospective single-center study of all consecutive adult heart transplant patients from 2008 to 2017. Survival data were estimated and summarized using the Kaplan-Meier method. We quantified and evaluated the difference in the incidence rate between patients with and without infection using a Fine-Gray model. The outcome of interest is the time to first infection diagnosis with post-transplant death as the competing event. RESULTS: Among 278 heart transplant patients, 74 (26.5%) underwent LVAD implantation. Twenty-one patients (28.3%) developed an infection while supported by an LVAD. When compared to patients supported by an LVAD without a preceding infection, BMI was significantly greater (31.2 vs 27.8 kg/m2 , P = .03). Median follow-up post-transplantation was 3.01 years. Significant risk factors for the competing risk regression for infection after heart transplantation include LVAD infection (HR 1.94, [95% CI] 1.11-3.39, P = .020) and recipient COPD (HR 2.14, [95% CI] 1.39-3.32, P = .001) when adjusted for recipient age, gender, hypertension, diabetes mellitus, and body mass index. CONCLUSIONS: Patients with LVAD-related infection had a significantly increased risk of infectious complications after heart transplantation. Further research on the avoidance of induction agents and reduced maintenance immunosuppression in this patient population is warranted.

3.
Phys Chem Chem Phys ; 21(31): 17087-17095, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31338491

RESUMO

The recent studies of magno-assisted tunnelling in ferromagnetic van der Waals heterostructures formed by graphene and ultrathin CrBr3 films (D. Ghazaryan et al., Nat. Electron., 2018, 1, 344) offer broader opportunities for exploration of novel quantum phenomena, especially for realizing the graphene-based quantum anomalous Hall effect (QAHE). Based on first-principles approaches, we reveal that three types of graphene/CrBr3 (Gr/CrBr3) heterostructures exhibit metallic band behavior due to strong charge-transfer at the interfaces of these heterosystems. Remarkably, the pressure-induced QAHE can be achieved in Gr/CrBr3 and CrBr3/Gr/CrBr3 systems. Further low energy k·p model analyses show that the nontrivial topological properties are mainly attributed to the Rashba spin-orbit coupling (SOC), but not to the intrinsic SOC of graphene. Moreover, a multichannel device prototype is proposed in the superlattices composed of Gr/CrBr3 and normal insulator (such as hexagonal boron nitride) layers. Our work provides an experimentally feasible scheme for realizing the high-temperature and multichannel QAHE in graphene-based heterostructures.

4.
Nanoscale ; 11(29): 13807-13814, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31294742

RESUMO

The search for more types of band inversion-induced topological states is of great scientific and experimental interest. Here, we proposed that the band inversion between px,y and pz orbitals can produce a topological phase transition in honeycomb lattices based on tight-binding model analyses. The corresponding topological phase diagram was mapped out in the parameter space of orbital energy and spin-orbit coupling. Specifically, the quantum anomalous Hall (QAH) effect could be achieved when ferromagnetism was introduced. Moreover, our first-principles calculations demonstrated that the two systems of half-iodinated silicene (Si2I) and one-third monolayer of bismuth epitaxially grown on the Si(111)-√3 ×√3 surface are ideal candidates for realizing the QAH effect with Curie temperatures of ∼101 K and 118 K, respectively. The underlying physical mechanism of this scheme is generally applicable, offering broader opportunities for the exploration of novel topological states and high-temperature QAH effect systems.

5.
Ann Surg Oncol ; 26(8): 2392-2400, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31011907

RESUMO

BACKGROUND: This study aimed to explore adjuvant chemotherapy (ACT) candidates based on a recurrence risk-scoring model in completely lobectomized stage I patients with lung adenocarcinoma (LAD). METHODS: A retrospective study was performed on 4606 patients (non-ACT group: n = 3514; ACT group: n = 1092) who underwent complete lobectomy for LAD at Shanghai Chest Hospital from 2008 to 2014. The nomogram predicting recurrence-free survival (RFS) was developed in the non-ACT group using Cox proportional hazards regression. The nomogram-based risk score was calculated in the entire cohort. Differences of RFS between the non-ACT and ACT groups were compared as stratified by the risk score. The score cut-off points were determined using the X-tile software. RESULTS: Six independent predictors, including age, sex, tumor size, pathological subtype, visceral pleural invasion (VPI), and lymphovascular invasion (LVI) were associated with RFS. The nomogram more accurately predicted RFS than the 8th TNM staging {C-index: 0.784 [95% confidence interval (CI) 0.756-0.812] vs. 0.719 (95% CI 0.689-0.749), p = 0.0017}. A significant RFS difference was observed among the low-, intermediate- and high-risk groups (p < 0.0001), as divided by the optimal cut-points of risk score (203 and 244). ACT did not improve RFS for patients at intermediate-risk, or was even detrimental for low-risk patients; however, improved RFS was observed in ACT receivers at high-risk (p = 0.0416). ACT candidates with a risk score ≥ 245 constituted 2.6% of stage I patients. CONCLUSIONS: The nomogram provided an individual prediction of RFS for stage I LAD following lobectomy. High-risk patients (score ≥ 245) may benefit from postoperative ACT.

6.
Sci Rep ; 9(1): 1087, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30705372

RESUMO

Chitin synthase is responsible for chitin synthesis in the cuticles and cuticular linings of other tissues in insects. We cloned two alternative splicing variants of the chitin synthase 1 gene (SfCHS1) from the white-backed planthopper, Sogatella furcifera. The full-length cDNA of the two variants (SfCHS1a and SfCHS1b) consists of 6408 bp, contains a 4719-bp open reading frame encoding 1572 amino acids, and has 5' and 3' non-coding regions of 283 and 1406 bp, respectively. The two splicing variants occur at the same position in the cDNA sequence between base pairs 4115 and 4291, and consist of 177 nucleotides that encode 59 amino acids but show 74.6% identity at the amino acid level. Analysis in different developmental stages showed that expression of SfCHS1 and SfCHS1a were highest just after molting, whereas SfCHS1b reached its highest expression level 2 days after molting. Further, SfCHS1 and SfCHS1a were mainly expressed in the integument, whereas SfCHS1b was predominately expressed in the gut and fat body. RNAi-based gene silencing inhibited transcript levels of the corresponding mRNAs in S. furcifera nymphs injected with double-stranded RNA of SfCHS1, SfCHS1a, and SfCHS1b, resulted in malformed phenotypes, and killed most of the treated nymphs. Our results indicate that SfCHS1 may be a potential target gene for RNAi-based S. furcifera control.

7.
J Diabetes ; 11(9): 729-743, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30615306

RESUMO

BACKGROUND: Metformin is first-line therapy for patients with diabetes. However, it may lower vitamin B12 concentrations, which could have hematological or neurological implications. This meta-analyses reviewed all available studies on associations between metformin use and vitamin B12 levels, anemia, and neuropathy in diabetic patients. METHODS: PubMed, Web of Knowledge, Cochrane Library, and Embase were searched to identify all relevant studies published in English prior to March 2018. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes and pooled mean differences (MDs) and 95% CIs were calculated for continuous outcomes. RESULTS: Thirty-one studies were included in the meta-analyses. Compared with diabetic patients not taking metformin, patients taking metformin had a significantly higher risk of vitamin B12 deficiency (RR 2.09; 95% CI 1.49, 2.93; P < 0.0001; I2 = 64%) and significantly lower serum vitamin B12 concentrations (MD -63.70; 95% CI -74.35, -53.05] pM; P < 0.00001; I2 = 87%), which depended on dose and duration of treatment. Metformin use was also associated with significantly greater percentage decrease in serum vitamin B12 concentrations from baseline in diabetic patients (MD -14.68%; 95% CI -17.98%, -11.39%; P < 0.00001; I2 = 33%). Analyses revealed no significant association between metformin use and the prevalence of anemia or neuropathy. CONCLUSIONS: Metformin use led to significantly lowered vitamin B12 concentrations and significantly higher risk of vitamin B12 deficiency in diabetic patients. More quality studies are needed to explore the associations between metformin use and anemia and neuropathy in these patients. Annual vitamin B12 assessment in diabetic patients taking metformin is recommended.

8.
J Med Econ ; 22(4): 336-343, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30663458

RESUMO

BACKGROUND AND OBJECTIVE: Dapagliflozin is the first SGLT2 inhibitor available in China, where the disease burden of diabetes and its complications is very heavy. Because a new diabetes treatment strategy for diabetes should consider its cost-effectiveness, compared with an existing treatment, this study aimed to examine the cost-effectiveness between dapagliflozin and metformin treatment in China. METHODS: The Cardiff Diabetes Model (CDM) was used to estimate cost effectiveness and macro- and micro-vascular outcomes of dapagliflozin vs metformin. The CDM effectiveness inputs were derived from indirect comparative efficacy data from meta-analysis of 71 studies comparing monotherapy and add-on therapy of dapagliflozin vs metformin: dapagliflozin or metformin monotherapy, add-on therapy with other oral hypoglycemic agents, and add-on therapy with insulin. Direct medication costs and medical costs on treating diabetes were calculated based on published and local sources. A discount rate of 3% was applied to both costs and health effects. Univariate and probabilistic sensitivity analyses (PSA) were performed to assess uncertainties. RESULTS: The total healthcare costs accumulated over the lifetime on dapagliflozin treatment arm was 8,626 Chinese yuan higher than the metformin treatment arm for an individual patient, and the quality adjusted life years (QALYs) gained with dapagliflozin treatment was 0.8 more than metformin treatment. Therefore, an incremental cost-effectiveness ratio was 10,729 yuan per QALY gained for dapagliflozin treatment arm vs metformin treatment arm. The cost-effectiveness results were robust to various sensitivity analyses. CONCLUSION: Dapagliflozin treatment was more cost-effective compared with metformin treatment for Chinese type 2 diabetes patients. However, the findings of favorable cost-effectiveness results for dapagliflozin are largely driven by the effects of favorable weight profile on clinical, utility, and costs in the Cardiff model.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Hipoglicemiantes/economia , Hipoglicemiantes/uso terapêutico , Metformina/economia , Metformina/uso terapêutico , Administração Oral , Fatores Etários , Idade de Início , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/economia , Peso Corporal , China , Colesterol/sangue , Análise Custo-Benefício , Complicações do Diabetes/economia , Complicações do Diabetes/epidemiologia , Quimioterapia Combinada , Feminino , Glucosídeos/administração & dosagem , Glucosídeos/economia , Hemoglobina A Glicada , Gastos em Saúde , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/administração & dosagem , Metformina/efeitos adversos , Pessoa de Meia-Idade , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida , Índice de Gravidade de Doença , Fatores Sexuais , Fatores Socioeconômicos , Inibidores do Transportador 2 de Sódio-Glicose/economia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
9.
Ann Thorac Surg ; 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30468727

RESUMO

BACKGROUND: At present, there is a significant lack of clinical data for patients with surgically resected stage I squamous lung cancer. The purpose of this study was to investigate the impact of postoperative chemotherapy in this specific population. METHODS: We retrospectively identified patients who had undergone complete squamous lung cancer resection at the Shanghai Chest Hospital between January 2008 and January 2014. RESULTS: A total of 596 patients (236 stage IA, 360 stage IB) were included in this study. Results demonstrated that adjuvant chemotherapy could provide longer overall survival for patients with p-stage IB disease (hazard ratio [HR] = 0.56, 95% confidence interval [CI]: 0.34-0.90, P = 0.017). Among p-stage IB patients, the adjuvant chemotherapy-treated cohort trended towards a benefit (HR = 0.69, 95% CI: 0.45-1.04) in recurrence-free survival, but failed to reach statistical significance (P = 0.076). After propensity score matching, the HRs of recurrence-free survival and overall survival were 0.58 (95% CI: 0.35-0.96, P = 0.033) and 0.49 (95% CI: 0.27-0.88, P = 0.017), respectively. With regards to patients with p-stage IA disease, neither overall survival (HR = 0.87, 95% CI: 0.34-2.27, P = 0.783) nor recurrence-free survival (HR = 0.79, 95% CI: 0.38-1.65, P = 0.534) was significantly different when compared between the patients receiving adjuvant chemotherapy and those who did not. Similar results were also achieved after propensity score matching. CONCLUSIONS: The data presented herein demonstrated that adjuvant chemotherapy might provide survival benefits for squamous lung cancer patients with p-stage IB disease.

10.
J Thorac Cardiovasc Surg ; 156(5): 2006-2015.e2, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30104070

RESUMO

OBJECTIVES: This study explored the prognostic significance and adjuvant chemotherapy benefits in resected patients with stage I non-small cell lung cancer with lymphovascular invasion. METHODS: A total of 2633 patients who received complete resection with pathologic stage I non-small cell lung cancer in the Shanghai Chest Hospital (2008-2012) were enrolled in the study, of whom 222 were diagnosed with lymphovascular invasion. By using the Kaplan-Meier method and Cox proportional hazard regression model, we explored the impact of lymphovascular invasion on prognosis and determined if the use of adjuvant chemotherapy is associated with improved outcomes in patients with lymphovascular invasion. A propensity score-matched analysis was implemented to reduce the selection bias. RESULTS: Patients with lymphovascular invasion had an unfavorable overall survival and recurrence-free survival in stage I non-small cell lung cancer. Multivariate Cox analysis indicated that lymphovascular invasion was an independent poor prognostic factor for recurrence-free survival (hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.58-2.71; P < .001) and overall survival (HR, 2.04; 95% CI, 1.45-2.87; P < .001) in patients with stage I. After using propensity score-matched pairs, analysis of 65 pairs of patients with lymphovascular invasion indicated a beneficial recurrence-free survival (HR, 0.33; 95% CI, 0.16-0.67; P = .002) and overall survival (HR, 0.30; 95% CI, 0.12-0.74; P = .009) from adjuvant chemotherapy. CONCLUSIONS: Lymphovascular invasion was correlated with poor prognosis in patients with stage I non-small cell lung cancer. For such patients, adjuvant chemotherapy was associated with improved survival. Our study suggests that adjuvant chemotherapy might be an appropriate option for patients with stage I non-small cell lung cancer with lymphovascular invasion.

11.
Diabetes Ther ; 9(5): 1995-2014, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30155646

RESUMO

INTRODUCTION: The aim of this study was to evaluate the efficacy and safety of initial combination therapy compared with monotherapy in drug-naïve type 2 diabetes patients. METHODS: MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched for randomized clinical trials of initial combination therapy with hypoglycemic agents compared with monotherapy. Those which satisfied the search criteria were included in the meta-analysis. Weighted mean difference and relative risks were calculated. RESULTS: A total of 36 studies were included in the meta-analysis. Compared with metformin monotherapy, initial combination therapy with metformin plus another anti-diabetes drug exhibited significant reductions in glycated hemoglobin (HbA1c) (p < 0.001). Most of the combination therapies had a similar risk of hypoglycemia (p > 0.05), with the exception of combinations of sulfonylurea/glinide and metformin or combinations of thiazolidinedione and metformin. Compared with dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapy, initial combination therapy with DPP-4 inhibitor plus another anti-diabetes drug showed a significant decrease in HbA1c (p < 0.001) and a similar risk of hypoglycemia (p > 0.05). Compared with monotherapy with other anti-diabetes drugs, initial combination therapies also resulted in significant HbA1c reductions, a similar risk of hypoglycemia and similar risks of other adverse events. CONCLUSION: Compared with monotherapy, all initial combination therapies resulted in significant HbA1c reductions. Compared with metformin monotherapy, initial combination therapies with DPP-4 inhibitors plus metformin, sodium/glucose cotransporter 2 inhibitors and metformin, respectively, were associated with similar risks of hypoglycemia, but initial combination therapies with sulfonylurea plus metformin, thiazolidinedione and metformin, respectively, were associated with higher risks of hypoglycemia. FUNDING: AstraZeneca Ltd. (China). TRIAL REGISTRATION: Registration number CRD42017060717 in PROSPERO.

12.
Endocrine ; 62(2): 299-306, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30128962

RESUMO

PURPOSE: To clarify the relevance between smoking and diabetic retinopathy in patients with type 1 and type 2 diabetes mellitus. METHODS: Published evidence were searched in MEDLINE and EMBASE from the databases began until Feb. 2017. Studies evaluating the association between smoking and diabetic retinopathy or evaluating the risk factors of diabetic retinopathy including smoking were included. RESULTS: Totally 73 studies were identified, among which 19 studies included type 1 diabetes patients and 56 studies included type 2 diabetes patients. In type 1 diabetes, compare with non-smokers, the risk of diabetic retinopathy significantly increased in smokers (risk ratio (RR) = 1.23, 95% CI 1.14, 1.33, P < 0.001), and the risk of proliferative diabetic retinopathy also significantly increased in smokers (RR = 1.48, 95% CI 1.20, 1.81, P < 0.001). In type 2 diabetes, compare with non-smokers, the risk of diabetic retinopathy significantly decreased in smokers (RR = 0.92, 95% CI 0.86, 0.98, P = 0.02) and the risk of proliferative diabetic retinopathy also significantly decreased in smokers (RR = 0.68, 95% CI 0.61, 0.74, P < 0.001). CONCLUSIONS: Compare with non-smokers, the risk of diabetic retinopathy significantly increased in smokers with type 1 diabetes while significantly decreased in smokers with type 2 diabetes. However, this result did not change the importance of smoking cessation for public health.

13.
Diabetes Technol Ther ; 20(10): 704-714, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30095971

RESUMO

BACKGROUND: As initial combination therapy of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitor, the efficacy and safety for the use of high dose of metformin or low dose of metformin and the efficacy and safety for the combination use for Asian and Caucasian patients were not clear. METHODS: Double-blind randomized controlled trials comparing the efficacy of initial combination therapy of metformin and DPP-4 inhibitors with metformin monotherapy were included. The primary outcome was a result of comparisons between high-dose combination therapy and low-dose combination therapy in terms of efficacy and safety. RESULTS: A total of 11 studies were included. The results indicated that the high-dose combination therapy showed significant decreases in hemoglobin A1c (HbA1c) (-0.32%, P < 0.05), fasting plasma glucose (FPG) (-0.63 mmol/L, P < 0.05), and postprandial glucose (PPG) (-0.99 mmol/L, P < 0.05), but less increase in body weight (-0.54 kg, P < 0.05) when compared with low-dose combination therapy, corrected by metformin monotherapy. Moreover, the high-dose combination therapy exhibited significant decreases in HbA1c (-0.24%, P < 0.05), FPG (-0.54 mmol/L, P < 0.05), and PPG (-0.94 mmol/L, P < 0.05) in the Caucasian population than in the Asian population, corrected by metformin monotherapy. CONCLUSION: As an initial treatment, the high dose of metformin in combination with DPP-4 inhibitors not only provided better glycemic control but also had less effect on weight gain compared with the low-dose combination therapy through the correction of metformin monotherapy. Moreover, initial combination therapy in the Caucasian population showed better glycemic control and less increase in body weight compared with the Asian population.

14.
Chin Med J (Engl) ; 131(13): 1605-1612, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29941715

RESUMO

Background: Placebo was defined as any therapy that is used for its nonspecific psychological and physiologic effect but has no specific pharmacologic impact on the condition being treated. Besides medication therapies, studies have found that the optimal dietary approach as well as physical activity and education are useful to control hyperglycemia in patients with type 2 diabetes (T2DM). The aim of this study was to evaluate the placebo effects of antidiabetic therapies in Asian and Caucasian T2DM patients and make a comparison between the two ethnicities. Methods: A search using the MEDLINE database, EMBASE, and Cochrane Database was performed, from when recording began until December 2016. The main concepts searched in English were sulfonylurea (SU); alpha glucosidase inhibitors (AGI); metformin (MET); thiazolidinediones (TZD); dipeptidyl peptidase-4 inhibitors (DPP-4i); sodium-glucose cotransporter 2 inhibitors (SGLT2i); glucagon-like peptide-1 receptor agonist (GLP-1RA); type 2 diabetes (T2DM); placebo controlled; and randomized controlled trials. Using the Cochrane instrument, we evaluated the adequacy of randomization, allocation concealment procedures, and blinding. Results: This study included 63 studies with a total of 7096 Asian patients involved and 262 studies with a total of 27,477 Caucasian patients involved. In Caucasian population, the use of placebo led to significant reductions of glycosylated hemoglobin (HbA1c), -0.683% (P = 0.008) in SU monotherapy treatment, -0.193% (P = 0.001) in DPP-4i treatment, and -0.230% (P < 0.001) in SGLT2i treatment, respectively. In Asian population, the use of placebo resulted in significant decreases of HbA1c, -0.162% (P = 0.012) in DPP-4i treatment and -0.269% (P = 0.028) in GLP-1RA add-on therapy, respectively. The placebo also significantly reduced body weight. In Caucasian population, placebo use resulted in 0.833 kg (P = 0.006) weight loss by SU treatment and 0.953 kg (P = 0.006) weight loss by GLP-1RA treatment. In Asian population, the placebo led to a weight change of 0.612 kg (P < 0.001) by GLP-1RA analog treatment. The changes of HbA1c and weight due to the placebo effect in other treatments were not significant in both Asian and Caucasian population. Comparisons of the placebo effect on HbA1c change and weight change in each treatment group indicated that no significant difference was found between Asian and Caucasian population. Conclusions: The overall differences of the placebo effect on HbA1c changes as well as on body weight changes were not significant between Asian and Caucasian T2DM patients. The placebo effect on HbA1c changes and weight changes was not associated with baseline age, gender, baseline body mass index, baseline HbA1c, duration of diabetes, or study duration.

15.
J Thorac Dis ; 10(Suppl 7): S846-S859, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29780631

RESUMO

Currently, the most effective way of reducing lung cancer mortality is early diagnosis of lung cancer. The National Lung Screening Trial has proved the efficacy of lung cancer screening using low-dose computed tomography to reduce lung cancer mortality. However, many questions remain surrounding lung cancer screening implementation, among which include how to select the optimal risk population, the personalized screening interval based different levels of risk, methods to improve diagnostic discrimination between malignant and benign disease in detected lung nodules, and the roles of biomolecular markers in stratifying risk and in guiding the management of indeterminate nodules. This review concentrates on the latest developments of lung cancer screening and provides an overview of the main unanswered questions on lung nodule detection.

16.
Artigo em Inglês | MEDLINE | ID: mdl-29733998

RESUMO

Chitinases (Chts) and chitin deacetylases (CDAs) are important enzymes required for chitin metabolism in insects. In this study, 12 Cht-related genes (including seven Cht genes and five imaginal disc growth factor genes) and 6 CDA genes (encoding seven proteins) were identified in Bactrocera dorsalis using genome-wide searching and transcript profiling. Based on the conserved sequences and phylogenetic relationships, 12 Cht-related proteins were clustered into eight groups (group I-V and VII-IX). Further domain architecture analysis showed that all contained at least one chitinase catalytic domain, however, only four (BdCht5, BdCht7, BdCht8 and BdCht10) possessed chitin-binding domains. The subsequent phylogenetic analysis revealed that seven CDAs were clustered into five groups (group I-V), and all had one chitin deacetylase catalytic domain. However, only six exhibited chitin-binding domains. Finally, the development- and tissue-specific expression profiling showed that transcript levels of the 12 Cht-related genes and 6 CDA genes varied considerably among eggs, larvae, pupae and adults, as well as among different tissues of larvae and adults. Our findings illustrate the structural differences and expression patterns of Cht and CDA genes in B. dorsalis, and provide important information for the development of new pest control strategies based on these vital enzymes.

17.
Comp Biochem Physiol B Biochem Mol Biol ; 219-220: 10-16, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29555304

RESUMO

Chitin deacetylases (CDAs) are chitin degradation enzymes that strictly regulate growth and development in insects. In this study, we identified and characterized a full-length cDNA of the CDA gene (SpCDA1) in the drugstore beetle, Stegobium paniceum. The open reading frame of SpCDA1 (1614 bp) encoded a 537 amino acid protein, which possessed typical domain structures of CDAs. Phylogenetic comparison to other insect CDAs revealed that SpCDA1 belongs to Group Ib CDAs. Quantitative real-time PCR analyses showed that SpCDA1 was highly expressed in late larval stages. Significant increase of SpCDA1 transcript level in the larvae was observed upon the exposure of 20-hydroxyecdysone. Injection of double-stranded RNA (dsRNA) of SpCDA1 into the late larvae significantly reduced SpCDA1 transcript levels, resulted in larval-pupal molting difficulty and produced high larval mortality. After 15 days, the survival rate of S. paniceum in dsSpCDA1 group was significantly reduced by 72% compared to the control. The results demonstrated that SpCDA1 is essential for successful larval-pupal transition in S. paniceum and this gene may be a potential target for pest control.


Assuntos
Amidoidrolases/biossíntese , Besouros/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Proteínas de Insetos/biossíntese , Interferência de RNA , Amidoidrolases/genética , Animais , Besouros/genética , Proteínas de Insetos/genética , Larva
18.
Cancer ; 124(11): 2399-2406, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29543321

RESUMO

BACKGROUND: Two or more different epidermal growth factor receptor (EGFR) mutations can be detected within a single tumor sample, which represents complex mutations. However, the frequency and efficacy of tyrosine kinase inhibitor (TKI) treatments for patients harboring these mutations are unknown. METHODS: From January 2011 to January 2017, patients diagnosed with EGFR mutations were screened. The effectiveness of TKIs in patients with complex mutations was retrospectively analyzed. RESULTS: A total of 16,840 subjects were screened, and there were 5898 positive patients. One hundred eighty-seven patients (3.2% of all patients with EGFR mutations) had complex EGFR mutations, and 51 of the patients with advanced adenocarcinoma were treated with TKIs as a first-line treatment. The objective response rates for patients who had Del-19+21L858R mutations (n = 15), Del-19/21L858R+atypical mutations (n = 16), double atypical mutations (n = 8), and complex mutations with a primary drug-resistant pattern (n = 12) were 75.0%, 60.0%, 71.0%, and 8.3%, respectively. The median progression-free survival times for the 4 groups were 18.2 months (95% confidence interval [CI], 10.6-25.9 months), 9.7 months (95% CI, 3.3-15.8 months), 9.6 months (95% CI, 3.3-19.0 months), and 1.4 months (95% CI, 0.4-2.3 months), respectively. CONCLUSIONS: These results from the largest sample size suggest that EGFR-TKI therapy is effective in patients with Del-19+21L858R mutations, Del-19/21L858R+atypical mutations, and double atypical mutations but is less effective in patients with a primary drug-resistant pattern. Patients with the Del-19+21L858R mutations may, therefore, benefit more from treatment with first-generation TKIs. Cancer 2018;124:2399-406. © 2018 American Cancer Society.

19.
Lung Cancer ; 117: 20-26, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29496251

RESUMO

OBJECTIVES: To investigate whether low-dose computed tomography (LDCT) screening is capable of enhancing the detection rate of early-stage lung cancer in high-risk population of China with both smoking and non-smoking related factors. METHODS: From 2013-2014, eligible participants with high-risk factors of lung cancer were randomly assigned to a screening group or a control group with questionnaire inquiries. Any non-calcified nodules or masses with longest diameters of ≥4 mm identified on LDCT images were considered as positive. RESULTS: A total of 6717 eligible participants were randomly enrolled to a study group (3550 to LDCT screening and 3167 to standard care). 3512 participants (98.9%) underwent LDCT screening, and 3145 participants (99.3%) received questionnaire inquiries. A positive screening result was observed in 804 participants (22.9%). In the two-year follow-up period, lung cancer was detected in 51 participants (1.5%) in the LDCT group versus 10 (0.3%) in the control group (stage I: 48 vs 2; stage II to IV or limited stage: 3 vs 8), respectively. Early-stage lung cancer was found in 94.1% vs 20%, respectively. CONCLUSIONS: Compared to usual care, LDCT led to a 74.1% increase in detecting early-stage lung cancer. This study provides insights about the non-smoking related risk factors of lung cancer in the Chinese population.

20.
Lung Cancer ; 117: 27-31, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29496252

RESUMO

OBJECTIVES: Occasionally, primary 20 T790M/insertion plus sensitive mutations can be detected within a single tumor sample by routine molecular testing, but the optimal clinical management for these patients is unclear. Herein, we determined the optimal treatment strategy for these patients. MATERIALS AND METHODS: From January 2011 to January 2017, patients diagnosed with epidermal growth factor receptor (EGFR) mutation were screened. For these harboring primary 20 T790M/insertion plus sensitive mutations, the effectiveness of the first or third generation tyrosine kinase inhibitors (TKIs) were retrospectively analyzed. RESULTS: 16,842 individuals were screened during the study period with 5900 positive patients identified. Sixty-one patients were confirmed to have primary 20 T790M/insertion plus sensitive mutations (1% of all EGFR-mutant patients, 95% CI, 0.8%-1.3%). Among them, 31 eligible patients were included for survival analyses. The median progression-free survival (PFS) of the 15 osimertinib-treated patients was 18.0 months (95% CI, 15.1-20.9 months), which was greatly longer than the 16 patients who were treated with first generation TKIs (1.2 months, 95% CI, 0.9-1.6, P < 0.001). Similar results were also observed in overall survival (OS) with 25.1 months (95% CI, not calculable) in the osimertinib group and 17.3 months (95% CI, 9.3-25.4 months) in the first generation TKI group (P = 0.02). CONCLUSIONS: For patients harboring primary resistant and sensitive mutations detected by routine clinical methods, first generation TKIs are ineffective even with the presence of sensitive mutations. However, osimertinib shows great survival benefit, and thus, should be considered during the whole clinical management.

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