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Chiglitazar (Carfloglitazar) is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes. In this randomized phase 3 trial, we compared the efficacy and safety of chiglitazar with sitagliptin in patients with type 2 diabetes who had insufficient glycemic control despite a strict diet and exercise regimen. Eligible patients were randomized (1:1:1) to receive chiglitazar 32 mg (n = 245), chiglitazar 48 mg (n = 246), or sitagliptin 100 mg (n = 248) once daily for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin A1C (HbA1c) from baseline at week 24 with the non-inferiority of chiglitazar over sitagliptin. Both chiglitazar and sitagliptin significantly reduced HbA1c at week 24 with values of −1.40%, −1.47%, and −1.39% for chiglitazar 32 mg, chiglitazar 48 mg, and sitagliptin 100 mg, respectively. Chiglitazar 32 and 48 mg were both non-inferior to sitagliptin 100 mg, with mean differences of −0.04% (95% confidential interval (CI) −0.22 to 0.15) and −0.08% (95% CI −0.27 to 0.10), respectively. Compared with sitagliptin, greater reduction in fasting and 2-h postprandial plasma glucose and fasting insulin was observed with chiglitazar. Overall adverse event rates were similar between the groups. A small increase in mild edema in the chiglitazar 48 mg group and slight weight gain in both chiglitazar groups were reported. The overall results demonstrated that chiglitazar possesses good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions, thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.

Interface engineering is an effective way to improve the performance of heterojunction photodetectors (PDs). We have constructed p-Si/n-ZnGa2O4 heterojunction solar-blind ultraviolet (UV) PDs with and without an SiO2 interfacial layer and studied the effect of the SiO2 interfacial layer on device performance in detail. At −1 V bias, the dark current of the device from 3.8 × 10−8 A to 5.7 × 10−12 A was greatly reduced, specifically 6.7 × 103 fold, attributed to the high barrier induced by the insertion of the SiO2 interfacial layer. With the introduction of the SiO2 interfacial layer, the photo-to-dark current ratio and the detectivity of the device were greatly improved due to the substantial reduction of dark current. Owing to the insertion of the SiO2 layer reducing the carrier trapping at the interface defects, the rise and decay times of the device were significantly reduced from 0.96 s/0.88 s to 0.12 s/0.08 s, i.e. 8 fold and 11 fold, respectively. Moreover, the large conduction band offset of Si/SiO2 could effectively block visible-light-generated electrons in Si, thereby suppressing the visible-light response and enhancing the UV-visible rejection ratio of the Si/SiO2/ZnGa2O4 PD. Our work has provided a feasible approach for enhancing the performance of Si/wide-bandgap semiconductor heterojunction solar-blind UV PDs.

AIM To evaluate the efficacy and safety of polyethylene glycol loxenatide (PEX168) monotherapy in type 2 diabetes (T2D) patients in China. MATERIALS AND METHODS In a multicentred, randomized, double-blinded, placebo-controlled phase 3a clinical trial, 361 patients with inadequate glycaemic control (HbA1c 7.0%-10.5%, fasting plasma glucose

PURPOSE Differentiating the irinotecan dose on the basis of the uridine diphosphate glucuronosyltransferase 1A1 ( UGT1A1) genotype improves the pathologic complete response (pCR) rate. In this study, we further investigated preoperative irinotecan combined with capecitabine-based chemoradiotherapy for locally advanced rectal cancer. PATIENTS AND METHODS We conducted this randomized, open-label, multicenter, phase III trial in China. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma, UGT1A1 genotype *1*1 or *1*28 were randomly allocated to the control group: pelvic radiation of 50 Gy/25 fractions with concurrent capecitabine, followed by oxaliplatin and capecitabine; or the experimental group: radiation with capecitabine combined with weekly irinotecan 80 mg/m2 for patients with UGT1A1*1*1 or 65 mg/m2 for patients with UGT1A1*1*28, followed by irinotecan and capecitabine. The primary end point was pCR. This trial was registered with ClinicalTrials.gov (ClinicalTrials.gov identifier: NCT02605265). RESULTS Of the 360 patients initially enrolled, 356 were evaluated as the modified intention-to-treat population (n = 178 in both groups). Surgery was performed in 87% and 88% of patients in the control and experimental groups, respectively. The pCR rates were 15% (n = 27 of 178) and 30% (n = 53 of 178) in the control and experimental groups (risk ratio, 1.96; 95% CI, 1.30 to 2.97; P = .001). Four and 6 patients achieved complete clinical response in the control and experimental groups, respectively. Grade 3-4 toxicities were recorded in 11 (6%) and 68 (38%) patients in the control and experimental groups, respectively ( P < .001). The commonest grade 3-4 toxicities were leukopenia, neutropenia, and diarrhea. The overall surgical complication rate was not significantly different between the two groups (11% v 15%; P < .001). CONCLUSION Adding irinotecan guided by UGT1A1 genotype to capecitabine-based neoadjuvant chemoradiotherapy significantly increased complete tumor response in Chinese patients.

Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], −1.04[−1.19, −0.89]%) and BBR-alone group (−0.99[−1.16, −0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (−0.59[−0.75, −0.44]%, −0.53[−0.68, −0.37]%, P, The gut microbiome affects systemic metabolism and is a therapeutic target for type 2 diabetes. Here the authors demonstrate in a randomized controlled trial that effects of berberine, a plant alkaloid known to lower blood glucose, may be explained by the inhibition of Ruminococcus bromii mediated biotransformation of the bile acid deoxycholic acid.

Aims/Introduction Although the efficacy of teneligliptin, a highly selective dipeptidyl peptidase‐4 inhibitor, has been amply studied for the treatment of type 2 diabetes, no clinical trials of teneligliptin have been carried out in China. We evaluated the efficacy and safety of teneligliptin monotherapy compared with a placebo in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. Materials and Methods This multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study, carried out at 42 sites, enrolled type 2 diabetes patients with glycosylated hemoglobin 7.0 to, This multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study evaluated the efficacy and safety of teneligliptin monotherapy compared with a placebo in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. To assess efficacy (primary efficacy end‐point: glycosylated hemoglobin from baseline to week 24) and safety (incidence of adverse events and adverse drug reactions), eligible type 2 diabetes patients were assigned in a 1:1 ratio to treatment with teneligliptin 20 mg or a placebo, administered orally once daily before breakfast for 24 weeks. The least square mean change in glycosylated hemoglobin from baseline to week 24 was −0.95% with teneligliptin versus −0.14% with a placebo, and the least square mean change in fasting plasma glucose from baseline to week 24 was −21.9 mg/dL with teneligliptin versus −1.4 mg/dL with a placebo, with the incidence rates of adverse events and adverse drug reactions being similar in both groups, showing that teneligliptin was effective and generally well tolerated at 24 weeks among Chinese patients with type 2 diabetes inadequately controlled with diet and exercise.

Methimazole (MMI), the first-line anti-thyroid agent used in clinical practice is known to induce hepatotoxicity in patients with Grave's disease (GD), although its exact mechanism remains largely unclear. This cohort study aimed to examine the mechanism of MMI-induced hepatotoxicity using metabolomic approach. A total of 40 GD patients with MMI-induced hepatotoxicity (responders) and 80 GD patients without MMI-induced hepatotoxicity (non-responders) were included in this study and their plasma metabolomics was profiled with targeted gas chromatography-tandem mass spectrometry (GC-MS/MS). The plasma levels of 42 metabolites, including glucuronic acid, some amino acids, fatty acids, ethanolamine and octopamine were found to be significantly different between responders and non-responders. In agreement with our previous genotyping data, the genetic polymorphism of uridine 5'-diphospho-glucuronosyltransferase (UGT)1A1*6, which affects the glucuronidation activity and circulating glucuronic acid level was identified as one of the determinants of MMI-induced hepatotoxicity. Plasma level of ethanolamine has a significant correlation with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. The pathway analyses further revealed that monoamine oxidase (MAO) inhibition, reactive oxygen species (ROS) production, mitochondria dysfunction, and DNA disruption might contribute to MMI-induced hepatotoxicity. Interestingly, the metabolomic data further suggested the responders had a higher risk of developing osteoporosis and fatty liver disease in comparison to the non-responders. This mechanistic study sheds light on the pathogenesis of MMI-induced hepatotoxicity and prompts personalized prescription of MMI based on UGT1A1*6 genotype in the management of GD.

A hybrid perovskite MAPbCl3 (MA = CH3NH3+) single crystal is considered to be one of the most viable candidates for the development of photodetectors because of its outstanding optoelectronic properties. However, the relatively lower crystalline quality of the reported MAPbCl3 single crystals fabricated by the traditional one-step inverse temperature crystallization results in momentous degradation in the performance of their photodetectors. Here, we present a novel two-step temperature process to fabricate high-quality MAPbCl3 single crystals, namely, lower temperature nucleation and higher temperature crystallization. These MAPbCl3 single crystals present low defect density (∼7.9 × 109 cm-3) commensurate with the best-quality crystals of hybrid organic-inorganic lead halide perovskites reported so far. Moreover, a high-performance ultraviolet photodetector was demonstrated on MAPbCl3 single crystals. At 30 V, the peak responsivity at 415 nm of the photodetector is as high as 3.73 A W-1 (light intensity = 1 mW cm-2), ∼2-3 orders of magnitude higher than that of the previously reported MAPbCl3 photodetectors. Meanwhile, the device has an ultrafast response speed with a rise time of 130 ns, which is one of the shortest values of MAPbX3-based photodetectors. Our findings open a new way to obtain high-quality perovskite single crystals and their high-performance photodetectors.

We have demonstrated a self-powered solar-blind ultraviolet (UV) photodetector based on the Au/ZnMgO/ZnO:Al vertical structure. The comb-shaped Au was selected as the Schottky electrode due to its high transmittance (more than 60%) in the wavelength region from 200 nm to 300 nm. At 0 V bias, the detector showed a responsivity of 55 mA/W under 265 nm light illumination with the intensity of 80 nW/cm2, which is larger than that of any other previously reported ZnO-based self-powered UV photodetectors. And a fast response speed can be also clearly observed with 10%–90% rise and 90%-10% decay times of 20 μs and 300 μs, respectively. The excellent self-powered solar-blind UV detection of our Au/ZnMgO/ZnO:Al device should be associated with the high external quantum efficiency, especially for the weak signal detection. Our findings offered new chances in high-performance self-powered photodetectors fabrication.

Background and objective: Circulating tumor cells (CTCs) can be classified into three phenotypes based on epithelial-to-mesenchymal transition (EMT) markers, including epithelial CTCs, mesenchymal CTCs, and mixed phenotypic CTCs. This study is aimed to analyze the correlation between CTC phenotypes and the clinicopathological features of patients with early cervical cancer. Methods: Peripheral blood samples were obtained from 90 patients with early cervical cancer. CTCs were isolated and classified. The correlations of CTC counts and CTC phenotypes with clinicopathological features of patients were analyzed. Results: The positivity rate for CTCs in patients with stage I-IIA cervical cancer was 90%. An increased CTC number was observed in patients with FIGO stage II, pelvic lymph node metastasis, and lymphovascular involvement. There were 38.89% epithelial CTCs, 23.33% mesenchymal CTCs, and 14.44% mixed phenotypic CTCs, Mesenchymal CTCs were more common in patients with FIGO stage II, pelvic lymph node metastasis, lymphovascular involvement, and deep stromal invasion. Conclusion: CTCs with mesenchymal phenotypes are closely related to pelvic lymph node metastasis and lymphatic vascular invasion in stage I-IIA cervical cancer. Detection of circulating tumor cell phenotypes is helpful for the early diagnosis of cervical cancer micro-metastasis and for the assessment of disease status.

Objective Recent studies have shown that neuregulin 4 (Nrg4), a member of the epidermal growth factor (EGF) family of extracellular ligands, plays an important role in the prevention of obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD). Considering that thyroid hormone (TH) has profound effects on whole-body energy metabolism, we speculate that circulating Nrg4 levels might be altered in patients with hyperthyroidism. Design and methods A total of 129 hyperthyroid patients and 100 healthy subjects were recruited. Of them, 39 hyperthyroid patients received thionamide treatment for 3 months until euthyroidism. Serum Nrg4 levels were determined using the ELISA method. To further confirm the relationship between TH and Nrg4, C57BL/6 mice were treated with T3 and quantitative real-time PCR was performed to detect Nrg4 gene expression. Results Serum Nrg4 levels were significantly elevated in hyperthyroid patients as compared with normal controls (3.84 ± 1.63 vs 2.21 ± 1.04 ng/mL, P P 3 was further confirmed by animal and cell culture experiments. Conclusions Serum Nrg4 levels were increased in patients with hyperthyroidism. The liver and white adipose tissue might be primary sources contributing to elevated serum Nrg4 concentrations.

Objective. SLC16a genes encode H + -coupled monocarboxylate transporters (MCTs). MCTs are involved in maintaining interstitial fluids’ pH and regulating insulin’s binding affinity to its receptor, which is a potential mechanism for the onset of diabetes. In this research, we make explorations of the association between the rs312457 genotype of the SLC16a13 gene and diabetes in the Chinese population. Methods. It included 384 type 2 diabetes patients and 1,468 healthy control subjects in total. We measured the anthropometric parameters, glycaemic index, homeostasis model assessment-B cell (HOMA-%B), lipid profile, and homeostasis model assessment-insulin resistance (HOMA-IR). The associations between the rs312457 genotype and type 2 diabetes were analyzed. Results. The rs312457 genotype was markedly in relation to type 2 diabetes ( P = 0.002 ). The frequency of the rs312457 risk allele (G) was 4.8%, higher than that of the wild-type allele (A) in patients of type 2 diabetes, indicating that allele (G)’s presence seemed to make the risk of type 2 diabetes go up. Compared to the GA and AA genotypes, the GG genotype of rs312457 significantly increased the risk of contracting diabetes mellitus ( P ≤ 0.001 ). Moreover, the rs312457 genotype was associated with HOMA-%B. Subjects harbored the GG genotype of rs312457, whose HOMA-%B level went down in comparison with that in subjects harboring the AA genotype ( P = 0.023 ). Conclusion. Our results revealed that the rs312457 genotype of the SLC16a13 gene was correlated with the development of diabetes mellitus in the Chinese population.

The planning of integrated energy system is a very complex multi-objective, multi-constraint, nonlinear, random uncertain hybrid combination optimization problem, its planning and design process should consider not only the system capacity, energy exchange, energy storage, energy and other links between the interdependence, but also the interaction and mixing of cold, hot, electricity and other multi-energy flow, which is essentially a non-deterministic polynomial problem. Based on load prediction technology, combined with scene generation, multi-interconnected energy system modeling and other technologies, around the integrated energy system planning and design, consider the comprehensive evaluation of the whole life cycle, an optimal configuration of the integrated energy system is formed.

The comprehensive energy-saving potential evaluation method of the energy-saving schemes of a distribution network considering the power uncertainty of source and load is studied in this paper. The K-means clustering method is firstly employed to extract typical scenarios of distribution network, and the forward-push back method is used to calculate the power flow in typical scenarios, then energy-saving reconstruction schemes are formulated according to the power flow calculation results. A comprehensive energy saving potential evaluation index system that consists the improvement rate of network loss, line loss rate, transformer loss rate, annual electricity saving cost, annual equipment investment cost, annual maintenance cost and voltage quality improvement rate is built, and the comprehensive evaluation method based on DEMATEL-ANP-TOPSIS mixed decision model is used to evaluate the comprehensive energy-saving potential of the energy-saving reconstruction schemes regarding the index system. Finally, the optimal reconstruction scheme is selected based on the evaluation results of energy saving potential in multiple scenarios. The effectiveness of the proposed method is verified by an example in IEEE-33 node distribution network.

Background. To date, microRNA-21 (miR-21) has been reported to be associated with the prognosis of hepatocellular carcinoma (HCC) in various studies, yet the results were inconsistent. The purpose of this two-part study, consisting of a retrospective cohort study and a meta-analysis, sets out to determine the prognostic role of miR-21 expression among HCC patients who underwent surgical resection. Methods. In this study, we first detected miR-21 expression in HCC patients by quantitative real-time PCR (qRT-PCR). Patients were divided into a high miR-21 expression group and a low miR-21 expression group according to the median level of miR-21 expression in tumor tissues. The survival outcomes of the two groups were analyzed by the Kaplan-Meier method with the log-rank test. Multivariate analysis of the prognostic factors was performed with the Cox regression model. Subsequently, eligible studies were obtained by searching on PubMed, Cochrane Library, and Web of Science, and a meta-analysis was performed to assess the prognostic role of miR-21 expression among HCC. Results. The qRT-PCR analysis results of our cohort study showed miR-21 expression was significantly upregulated in HCC tissues when compared with adjacent nontumor tissues. Multivariate analysis suggested that miR-21 expression was an independent prognostic factor for overall survival (OS) (hazard ratio, HR = 2.361 ) and disease-free survival (DFS) ( HR = 2.024 ) in HCC patients who underwent surgical resection. A total of 10 studies with 969 patients were enrolled in the meta-analysis, consisting of 9 studies from the database search and our cohort study. We observed that elevated miR-21 expression can predict poor OS ( HR = 2.24 , 95 % CI = 1.73 ‐ 2.91 , P < 0.001 ) and DFS/recurrence-free survival (RFS) ( HR = 2.44 , 95 % CI = 1.62 ‐ 3.67 , P < 0.001 ) in surgically resected HCC patients. Conclusions. Our study demonstrated that miR-21 high expression among surgically resected HCC patients is a prognostic factor that indicated adverse survival.

This study explored the changes and predictive value of miR-34a in nasopharyngeal carcinoma (NPC) after concurrent chemoradiotherapy (CCRT), and its association with cognitive function. Fifty NPC patients admitted to Shunde Hospital, and another fifty healthy individuals were assigned into treated group and control group, respectively. Patients in the treated group received 3 courses of CCRT. The relative expression of miR-34a in the two groups was detected, and the cognitive function of patients was assessed. Diagnostic and predictive values of miR-34a in advanced NPC were analyzed. The expression of miR-34a in the control group was significantly higher than that in the treated group (t=13.364, P

Background Atherosclerosis-related cardiovascular diseases are among the leading causes of mortality worldwide. Uptake of modified lipoproteins by monocyte-derived macrophages leads to the formation of foam cells, which by secreting pro-inflammatory cytokines accelerate plaque development. Sorting Nexin 10 (SNX10) plays a critical role in the regulation of macrophage functions as well as in the lipid metabolism. This study aims to explore the precise effects and the underlying molecular mechanisms of SNX10 mediated processes in atherosclerotic diseases. Methods SNX10 knockout mice were generated and bone marrow-derived macrophages (BMDMs) were studied in vitro. Mice were crossed with apolipoprotein E-deficient (ApoE-/-) mice and atherogenesis was monitored for 16 weeks. Results Expression of SNX10 was increased in atherosclerotic plaques from both humans and ApoE-/- mice. SNX10 deficiency decreased foam cell abundance and alleviated atherosclerotic plaque progression in ApoE-/- mice. In addition, high fat, high cholesterol diet fed ApoE-/- mice contained more Ly6ChiCX3CR1lo monocytes than ApoE-/- SNX10-/- (DKO) littermates. ApoE-/- mice showed a higher level of inflammatory macrophages infiltrating into atherosclerotic lesions. SNX10 deficiency reduced the interactions between CD36 and Lyn, thus inhibiting CD36-mediated lipoprotein uptake and foam cell formation. Conclusions Our findings demonstrate CD36-Lyn dependent non-redundant atherogenic role for SNX10 in diet-induced atherogenesis. We propose SNX10 as a potential therapeutic target for the prevention and treatment of atherosclerosis.

Recent investigations indicate that the performance of organic–inorganic perovskite optoelectronic devices can be improved by combining the perovskites and the inorganic materials. However, very few studies have focused on the investigation of perovskites/inorganic semiconductor hybrid UV photodetectors and their detailed performance-enhancement mechanism is still not very clear. In this work, a CH3NH3PbCl3/ZnO UV photodetector has been first demonstrated and investigated. Both the photoresponsivity and response speed of the hybrid device are higher than those of pure CH3NH3PbCl3 and ZnO devices. The photoluminescence and transient absorption spectra indicate that the photoinduced electron transfer between CH3NH3PbCl3 and ZnO should be responsible for the performance enhancement of the hybrid device. In addition, the high crystal quality of CH3NH3PbCl3 on ZnO film is another important reason for the excellent UV detection performance. Our findings in this work provide new insights into the intrinsic photo...

ZnO film was fabricated on p-GaN film using the molecular beam epitaxy technique to form heterojunction light emitting diodes (LEDs). The devices exhibited strong light emission under both forward and reverse bias. The origin of different luminescence peaks has been investigated by comparing electroluminescence (EL) and photoluminescence spectra. When a forward bias is applied to the device, intense ultraviolet emission at ∼376 nm originating from ZnO rather than GaN can be observed, which is associated with the larger hole mobility of p-GaN than the electron mobility of n-ZnO. Under the reverse bias, the device shows broad emission at 520 nm originating from deep level-related recombination in ZnO, emission at 430 nm from GaN, 376 nm from ZnO and weak emission at 408 nm from the interface with a lower injection current of 10 mA. As the injection reverse current increases to 20 mA, the EL emission at 376 nm exhibits a dramatic increase in intensity without a peak shift. The emission mechanism of the heterojunction LED is discussed in terms of interface states and energy band theory. Our findings in this work provide an innovative path for the design and development of ZnO-based ultraviolet diodes.

Background: Our previous study identified irinotecan dose differentiated by UGT1A1 genotype in the neoadjuvant chemoradiotherapy and showed improved pCR. The objective of this phase III study was to further investigate irinotecan combined with capecitabine-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer. Methods: We underwent a randomized, open-label, multicenter, phase 3 trial in China. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly allocated to the control arm (CapRT arm): pelvic radiation of 50 Gy/25 fractions with concurrent capecitabine 825 mg/m2 twice daily 5 days per week, followed by a cycle of XELOX two weeks after the end of CRT; or the experimental arm (CapIriRT arm): radiation with capecitabine 625 mg/m2 twice daily 5 days per week and combined with weekly irinotecan of 80mg/m2 for UGT1A1*1*1 or 65mg/m2 for UGT1A1*1*28, followed by a cycle of XELIRI. The primary endpoint is pathological complete response (pCR). This trial was registered with ClinicalTrials.gov, number NCT02605265. Findings: Of the 360 patients initial enrolled, 356 were evaluated in mITT dataset (both 178 in two arms). Surgery was performed in 87% and 88% of patients in two arms, with 39% and 31% of patients got abdominoperineal resection respectively. The pCR rates were 18% (27/154) in CapRT arm and 34% (53/157) in CapIriRT arm (risk ratio 1.93; 95% CI 1.28–2.89, p=0.001), additional 4 and 6 patients were marked as complete clinical response (cCR). therefore, the overall CR rates were 17% and 33%, respectively. The most common grade 3-4 toxicities during CRT were leukopenia (3% vs. 25%), neutropenia (2% vs. 20%), and diarrhoea (2% vs. 13%). The overall rate of surgical complications were not significantly different between arms (11% vs. 15%). Interpretation: Adding irinotecan guided by UGT1A1 to capecitabine-based neoadjuvant chemoradiotherapy significantly increases complete tumor response. The treatment toxicities were increased but tolerable. Trial Registration: ClinicalTrials.gov, number NCT02605265 Funding Information: This study was funded by grants from Fudan University Shanghai Cancer Center (YJLC201601) and National Natural Science Foundation of China (81773357). We thank the patients, investigators, and institutions involved in this study. Competing Interest Declaration: I/We declare no competing interests. Ethical Approval Statement: The study was approved by the central ethics committee of Fudan University Shanghai Cancer Center (Shanghai, China)

In this paper, a method for welding track correction based on emulational laser and trajectory are introduced. The proposed method is divided into two parts: seam tracking and trajectory correction. In the seam tracking method, by using the prior information of emulational laser stripes which are generated by the simulation software and affine transformation of emulational laser stripes, the real seam point can be detected. And then the trajectory correction method mainly consists of three steps: pre-processing, coarse matching and presice matching by using Iterative Closest Point Matching (ICP). For various conditions and workpieces, the corresponding experiments are conducted in this paper. Experimental results demonstrate that the method can meet the requirement of the internal seams tracking of workpiece and accuracy of welding track correction.

Background: Faced with epidemic conditions, healthcare workers infection (HWI) has become a serious issue which reflects the severity of pandemic conditions and has an important pact on the healthcare system. Hereby, we compared the differences of HWI during the COVID-19 epidemic in two countries, Italy and South Korea, which have similar population and demographic distribution. Methods: We collected the open data updated on the official website about the confirmed cases of healthcare workers (HCWs) and the total population, and then explored the factors contributing to the reduction of HWI, including the basic medical index, initiatives to combat COVID-19, and the changes in healthcare pressure after the outbreak of the disease in the two countries. Finally, we investigated the correlation between indicators on "healthcare pressure" and HWI by computing the death and active cases combined with ICU beds and the number of HCWs. Findings: The results indicated that HWI presented a same trend with total infection in both Italy and South Korea, meanwhile, Italy had a higher proportion of HWI among the general population. And the intensity approach to assess the healthcare pressure was correlated with cumulative HWI (both number and rate) and the magnitude approach performed correlation with increased cases only in Italy. Interpretation: The intensity approach to assess the healthcare pressure expected to be a predictor and had the potential to warn the public of risks of an overload of the healthcare system and the consequent HWI, and that magnitude approach could be correlated to the increased HWI and total cases only when the healthcare system overloaded. This study attempts to explore the current condition of HWI and its related influence factors in two countries, aiming to draw more attention to HWI worldwide and give insight for the policy-making of medical system to provide better protection for HCWs in healthcare emergency. Funding Statement: This article was supported by a grant from National Science and Technology Major Project [Grant Number:2018ZX10101004003003] Declaration of Interests: No potential conflicts of interest were reported.

Methimazole (MMI) has been used for the treatment of Graves’ Disease (GD) for more than half a century. The MMI treatment has been reported to be associated with hepatotoxicity. Previous studies have demonstrated that human leukocyte antigen (HLA) genetic polymorphisms were associated with many drugs-induced liver injuries. To investigate HLA genetic susceptibility to MMI-induced liver injury (MMI-DILI), we characterized both HLA class I and class Ⅱ in a well-characterized phenotypic cohort with 40 MMI-DILI cases and 118 MMI-tolerant controls. Among the 40 MMI-DILI cases, 57.5% were women and 50% were cholestatic liver damage with occurring time from days to months after MMI dosing. The frequency of HLA-C*03:02 was 6.7% (5/75) in the MMI-DILI case patients and 6.4% (4/62) in MMI-induced cholestatic/mixed liver damage, which were significantly different from the percentage of 0.4% (1/231) in the MMI-tolerant patients (odds ratio (OR) = 15.4, 95% confidence interval (CI) = 1.77–133.9, adjusted P = 0.0292; OR=14.9, 95% CI=2.38–182.9, adjusted P = 0.0323; respectively). HLA-A*02:01 was also found to be associated with MMI-induced cholestatic/mixed liver injury (OR = 3.13, 95%CI=1.45–6.91, adjusted P = 0.0464). The present study demonstrated that individuals carrying HLA-C*03:02 allele are at increased risk of developing MMI-induced DILI. These results may assist doctors to prevent the occurrence of hepatotoxicity in GD patients receiving MMI.

Chiglitazar, a novel PPARα/γ/δ pan-agonist, showed favorable effects on glycemic control and lipid modulation with well tolerated safety profile in phase 2 trials. This trial aimed to compare the efficacy and safety of chiglitazar with DPP-4 inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled with diet and exercise (ClinicalTrials.gov NCT02173457). Patients were randomly assigned to receive chiglitazar 32 mg or 48 mg, or sitagliptin 100 mg once daily. The primary endpoint was change in HbA1c from baseline at week 24, with a non-inferiority of each chiglitazar dose versus sitagliptin. Analysis was done in all randomized patients who received at least one dose of study drug (n=739). Chiglitazar showed comparable HbA1c lowering effect compared with sitagliptin at 24 weeks (LS mean difference -0.04% [95% CI -0.22 to 0.15] and -0.08% [95% CI -0.27 to 0.10] for 32 mg and 48 mg, respectively), along with different trends in secondary endpoints. Overall adverse events were comparable across study groups. The incidences of weight gain and edema were generally low but relatively higher in chiglitazar 48 mg. In conclusion, chiglitazar showed non-inferior effect compared with sitagliptin on HbA1c reduction with well tolerated safety profile. Disclosure W. Jia: None. J. Ma: None. H. Miao: None. C. Wang: None. X. Wang: None. Q. Li: None. W. Lu: None. J. Yang: None. L. Zhang: None. J. Yang: None. G. Wang: None. X. Zhang: None. M. Zhang: None. L. Sun: None. X. Yu: None. J. Du: None. B. Shi: None. C. Xiao: None. D. Zhu: None. H. Liu: None. L. Zhong: None. C. Xu: None. Q. Xu: None. G. Liang: None. Y. Zhang: None. G. Li: None. M. Gu: None. J. Liu: None. Z. Ning: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi. Funding Ministry of Science and Technology of the People´s Republic of China (2013ZX09401301)

Methimazole (MMI) has been used in the therapy of Grave's disease (GD) since 1954, and drug-induced liver injury (DILI) is one of the most deleterious side effects. Genetic polymorphisms of drug-metabolizing enzymes and drug transporters have been associated with drug-induced hepatotoxicity in many cases. The aim of this study was to investigate genetic susceptibility of the drug-metabolizing enzymes and drug transporters to the MMI-DILI. A total of 44 GD patients with MMI-DILI and 118 GD patients without MMI-DILI development were included in the study. Thirty-three single nucleotide polymorphisms (SNPs) in twenty candidate genes were genotyped. We found that rs12422149 of SLCO2B1, rs2032582_AT of ABCB1, rs2306283 of SLCO1B1 and rs4148323 of UGT1A1 exhibited a significant association with MMI-DILI; however, no significant difference existed after Bonferroni correction. Haplotype analysis showed that the frequency of SLCO1B1*1a (388A521T) was significantly higher in MMI-DILI cases than that in the control group (OR = 2.21, 95% CI = 1.11-4.39, P = 0.023), while the frequency of SLCO1B1*1b (388G521T) was significantly higher in the control group (OR = 0.52, 95% CI = 0.29-0.93, P = 0.028). These results suggested that genetic polymorphisms of SLCO1B1 were associated with susceptibility to MMI-DILI. The genetic polymorphism of SLCO1B1 may be important predisposing factors for MMI-induced hepatotoxicity.

3603 Background: Adding UGT1A1-guided irinotecan to capecitabine-based neoadjuvant chemoradiotherapy (CRT) significantly increased the pathological complete response (pCR) rate nearly doubling [J Clin Oncol. 2020 Dec 20;38(36):4231-4239]. Here, results of long-term outcome are reported. Methods: Eligible patients with clinical stage II/III rectal adenocarcinoma, UGT1A1 genotype *1*1 or *1*28 were randomized to the control group: pelvic radiation of 50 Gy/25 fractions with concurrent capecitabine, followed by a cycle of oxaliplatin and capecitabine; or the experimental group: radiation with capecitabine combined with weekly irinotecan 80 mg/m2 for patients with *1*1 or 65 mg/m2 for patients with *1*28, followed by a cycle of irinotecan and capecitabine. Surgery was scheduled for 8 weeks after completion of CRT. Five cycles of adjuvant XELOX chemotherapy were administered regardless of the pathologic result. Patients were stratified by UGT1A1 genotype (*1*1 vs. *1*28) clinical T stage (cT3 vs. cT4) and tumor distance from the anal verge (≤5 cm vs. > 5 cm). The primary end point of pCR was reached. Survival time was calculated from the date of randomization to the date of event or the last follow-up. Secondary endpoints were defined as local failure for local control (LC), tumor recurrence or death from any cause for disease-free survival (DFS), and death from any cause for overall survival (OS). Results: Of the 360 patients initially enrolled, 356 were evaluated as the modified intention-to-treat population (n = 178 in both groups). A total of 311 patients underwent surgery and pCR was achieved in 80 patients, another 10 patients undergo a watch-and-wait approach after achieving cCR. With a median follow-up time of 48 months (Q25-Q75, 41-55 months), 57 deaths (33 and 24), 17 local failures (11 and 6) and 69 distant metastases (37 and 32) were observed, respectively. Overall, the 4y LC rate were 93% and 96% in control and experimental groups, with estimated LC HR of 0.53 (95% confidence interval [CI], 0.20-1.43), the 4y DFS rates were 69% and 74% (HR = 0.74, 95% CI 0.49-1.10), and the 4y OS were 80% and 85%, (HR = 0.70, 95% CI 0.42-1.19), respectively. In the subgroup analysis, irinotecan showed a significant improvement in DFS (HR = 0.77, 95% CI 0.61-0.98) and OS (HR = 0.71, 95% CI 0.51-0.98) in UGT1A1 *1*1 patients. Conclusions: The addition of irinotecan to standard capecitabine-based CRT had a tendency towards improving LC, DFS, and OS, but without reaching statistical significance. UGT1A1 *1*1 patients seem to benefit the most from irinotecan. Molecular studies and subsequent therapies should be considered. Clinical trial information: NCT02605265.

3510 Background: It’s presented the results of a phase III trial of short-term radiotherapy (SCRT) combined with chemotherapy versus long-term chemoradiotherapy (LCRT) in patients with locally advanced rectal cancer (LARC). Methods: Patients with distal or middle third, T3-T4 and/or N+ rectal adenocarcinomas diagnosed by MRI, were randomly assigned to experimental group or control group. In experimental group, patients received SCRT (25 Gy / 5 fractions / 5 days), followed by four courses of CAPOX. In control group, patients received LCRT (50 Gy / 25 fractions / 35 days with concurrent capecitabine). Surgery was recommended in both groups and performed 6-8 weeks after preoperative treatment. Two or six courses of CAPOX was prescribed as the postoperative chemotherapy in experimental group and control group, respectively. This trial was a multicenter, open-label, randomized, noninferior, phase III study, and all the patients were from 16 hospitals of China. The primary endpoint for this study was 3-year disease-free survival (DFS). Results: From Aug 30, 2015 to Aug 27, 2018, 599 patients were enrolled and entered random. Finally, 591 intention-to-treat (ITT) populations were included in the analysis, 298 patients assigned to SCRT followed by chemotherapy and 293 to CRT. For the experimental group and control group, cT3 and cT4 accounted for 82.3% vs. 84.6% and 15.4% vs. 12.3%, respectively, and approximately 85% were mrN positive (85.6% vs. 84.0%). As a whole, the completion and full-dose completion rates of preoperative treatment were 82.6% vs. 95.2% (p＜0.001) and 74.8% vs 93.2% (p＜0.001) in the experimental and control groups, respectively. Among the 465 patients who received surgery, 16.6% and 11.8% of them achieved pCR (p=0.134), respectively. Accounting for cCR after preoperative treatment, the total rate of pCR+cCR in experimental group was 22.5% and significantly higher than control group (12.6%, p=0.001). With median follow-up 35.0 months, the HR between experimental and control of DFS was 0.883, with 1-sided noninferiority p-value

Herein, ZnMgO thin film ultraviolet (UV) photodetectors based on metal-semiconductor-metal structure were fabricated on a-plane sapphire substrates by plasma-assisted molecular beam epitaxy. The effect of H2O2 solution treatment on the properties of the ZnMgO thin film and its UV photodetectors was investigated. After immersing the ZnMgO UV photodetector in a H2O2 solution at 100 degrees C for 3 min, the dark current of the device was reduced by more than one order of magnitude under 1 V bias, whereas the responsivity was slightly decreased. More interestingly, the response speed became much quicker and insensitive to the atmosphere after the treatment of the photodetector with H2O2 solution, which can be attributed to the reduction in the oxygen vacancy defects. Our findings may provide a promising approach for improving the performance of photodetectors.

The planning of integrated energy system is a very complex multi-target, multi-constraint, nonlinear, random uncertainty mixed integrated combination optimization problem, its planning and design process should not only consider the interdependence between the system capacity, energy conversion, energy storage, energy use and other links, but also consider the interaction and integration of cold, hot, electricity and other multi-energy flows, which is essentially a non-deterministic polynomial difficult problem. China’s energy continues to develop rapidly, all kinds of sensors and intelligent equipment data is increasing, the data obtained in the equipment and all kinds of sensors collected energy load prediction related factors such as temperature, weather, wind speed and other data volume increased dramatically, the data dimension is also increasing, the scale of data has also increased from GB to TB or even higher, based on the traditional prediction methods and intelligent prediction methods, has been far below the load forecast desired to achieve accuracy and speed requirements, Therefore, the use of big data technology to predict energy demand is an important future direction.

The occupant movement and injury of the new Euro NCAP FAR SIDE test are taken as the research object, with the theoretical analysis, sled test and CAE model. The mathematical model of the far side dummy movement is established, and the main factors affecting the dummy’s displacement are analysed. The injury characteristics of the far side dummy under the sled test are obtained, and the main causes are studied. And finally, the optimization scheme of the FAR SIDE test is proposed.

We have demonstrated the fast-speed and high-rejection-ratio solar-blind ultraviolet (UV) photodetectors based on amorphous Ga2O3 (a-Ga2O3) films grown by atomic layer deposition. The effect of the annealing under oxygen atmosphere on the performance of a-Ga2O3 photodetectors is investigated. By the oxygen annealing at 500 °C, the 90-10% decay time of a-Ga2O3 photodetector can be decreased to ∼150 ns, and the UV/Visible rejection ratio of the photodetector can reach as high as 2.74×105, due to the significant suppression of the visible light response. Moreover, the dark current of the 500 °C-annealed photodetector is only 9.43 pA at 10 V bias. These phenomena can be explained by the decrease in oxygen vacancy concentration of the a-Ga2O3 films after the oxygen annealing. The combination of high rejection ratios and fast operating speeds offers a viable way for facile and scalable fabrication of the oxide semiconductor solar-blind UV detectors.

A novel self-powered solar-blind ZnGa2O4 ultraviolet (UV) photodetector has been constructed by fabricating asymmetric pairs of Au Schottky electrodes on the ZnGa2O4 film. The current-voltage curve of the device exhibits an obvious rectifying characteristic with a rectification ratio of 11.3 at ±8 V. At 0 V bias, the peak responsivity of our device at 246 nm is about 22.2 mA/W with an UV–vis rejection ratio of 1.3× 10 4 , indicating the excellent self-powered solar-blind UV photodetector performance. More interestingly, the rise time and decay time of the device are only 10 ns and 30 ns, respectively, which are much faster than that of any other previously reported self-powered solar-blind UV photodetectors to the best of our knowledge. The ultra-fast response speed of the device should be attributed to the asymmetric Schottky junctions and the high crystalline quality of our ZnGa2O4 film with low trap density. Our work provides a new method to constructing high-performance self-powered solar-blind UV photodetectors.

Background: Accurate clinical staging of patients with cholangiocarcinoma (CCA) has a significant impact on treatment decisions. In this study, we aimed to compare the diagnostic value of magnetic resonance imaging (MRI) and 18-fludeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging of CCA. Methods: We performed comprehensive systematic search in Web of Science (including MEDLINE) and Excerpta Medica Database for relevant diagnostic studies in accordance with the preferred reporting items for systematic reviews and meta-analysis statement. Based on data extracted from patient-based analysis, we calculated the pooled sensitivity and specificity with the 95% confidence intervals (CIs). In addition, the publication bias was assessed by Deek funnel plot of the asymmetry test. The potential heterogeneity was explored by threshold effect analysis and subgroup analyses. Results: Thirty-two studies with 1626 patients were included in present analysis. In T stage, the pooled sensitivity and specificity of MRI were 0.90 (95% CI 0.86–0.93), 0.84 (95% CI 0.73–0.91) respectively. The pooled sensitivity and specificity of 18F-FDG PET/CT were 0.91 (95% CI 0.83–0.95) and 0.85 (0.64–0.95) respectively. In N stage, the pooled sensitivity and specificity of MRI were 0.64 (95% CI 0.52–0.74) and 0.69 (95% CI 0.51–0.87) respectively. The pooled sensitivity and specificity of PET/CT were 0.52 (95% CI 0.37–0.66) and 0.92 (95% CI 0.79–0.97) respectively. In M stage, the pooled sensitivity and specificity of 18F-FDG PET/CT were 0.56 (95% CI, 0.42–0.69) and 0.95 (95% CI, 0.91–0.97) respectively. The Deek test revealed no significant publication bias. No threshold effect was identified. The subgroup analyses showed that pathological type (extrahepatic cholangiocarcinoma vs hilar cholangiocarcinoma/intrahepatic cholangiocarcinoma), country (Asia vs non-Asia) and type of MRI (1.5T vs. 3.0T) were potential causes for the heterogeneity of MRI studies and country (Asia vs non-Asia) was a potential source for 18F-FDG PET/CT studies. Conclusion: The analysis suggested that both modalities provide reasonable diagnostic accuracy in T stage without significant differences between them. We recommend that both modalities be considered based on local availability and practice for the diagnosis of primary CCA tumors. In N stage, the diagnosis of lymph node metastasis (N) of CCA is still limited by MRI and 18F-FDG PET/CT, due to unsatisfactory diagnostic accuracy of both. Nevertheless, 18F-FDG PET/CT can be used to confirm lymph node metastasis while a negative result may not rule out metastasis. Furthermore, 18F-FDG PET/CT have a low sensitivity and a high specificity for detection of distant metastasis.

Data race detection is a method in testing multithreaded programs to ensure their reliability against concurrency errors. In this paper, we present the GBRAD framework to support the initialization of various hybrid race detection techniques, which also supports the evaluation of these strategies at two decision points based on two major design factors of hybrid race detectors. In the GBRAD frame-work, one decision point consists of six skipping strategies and another decision point consists of eight reduction strategies. By combining these strategies, 48 hybrid detection techniques are initialized. We report a controlled experiment on the PARSEC benchmark suite as well as four real-world applications to evaluate these 48 techniques and their strategies in terms of runtime slowdown, memory overhead, and race detection effectiveness. The experiment identified 9 previously unknown techniques that are comparable to the state-of-the-art hybrid race detection technique.

The aim of this study was to compare the treatment outcomes of postoperative chemoradiotherapy (CRT) with radiotherapy (RT) alone in patients with cervical cancer. Based on articles published up to December 2014 a literature search in PubMed and EMBASE was conducted to identify eligible studies. Risk ratio (RR) and its 95% confidence interval (CI) were used as pooled statistics. A total of 4 articles consisting of 461 patients were selected for the meta-analysis. Results revealed that there were a significant overall survival improvements (RR = 1.35, 95% CI: 1.15-1.60, p = 0.0003), a significant reduction of local recurrence (RR = 0.26, 95% CI: 0.14-0.51, p

Diabetic cardiomyopathy, a disorder of the heart muscle in diabetic patients, is one of the major causes of heart failure. We hypothesized that angiotensin-(1-9) [Ang-(1-9)] attenuates cardiomyopathy in streptozotocin (STZ)-induced diabetic rats. Rats were injected with a single intraperitoneal injection of STZ (55 mg/kg body weight) to induced diabetic cardiomyopathy. 4 weeks later, diabetic rats were treated with Ang-(1-9) (200 ng/kg/min), angiotensin type 2 receptor (AT2R) blocker PD123319 (100 ng/kg/min), or Mas antagonist A779 (100 ng/kg/min) for 4 weeks. Although Ang-(1-9) treatment did not affect blood glucose and insulin levels, it significantly attenuated cardiac hypertrophy, reduced cardiac fibrosis and improved ventricular function in STZ-induced diabetic rats. Ang-(1-9) treatment suppressed cardiac NADPH oxidase activity and reduced formation of reactive oxygen species. Ang-(1-9) suppressed NFκB activation and reduced myeloperoxidase (MPO) activity and mRNA levels of TNFα and IL-1β in hearts of diabetic rats. In addition, Ang-(1-9) treatment suppressed activity of ACE and reduced angiotensin II (Ang II) formation in hearts of diabetic rats. The beneficial effect of Ang-(1-9) was blunted by coadministration of PD123319 but not by coadministration of A779. Finally, it was found that Ang-(1-9) treatment could alleviate STZ-induced cardiomyopathy in a dose-dependent manner. In conclusions, Ang-(1-9) attenuates cardiac dysfunction in STZ-induced diabetic rats. The Ang-(1-9)/AT2R axis should be investigated as a novel target for treatment of type 1 diabetic cardiomyopathy.

Background: Gut microbial dysbiosis has been targeted for treating diabetes, and both probiotics and berberine (BBR) have shown gut-regulating properties and hypoglycaemic effect. The combined effects of these two on glycaemic control remain unclear, especially in the elderly. Methods: This multicentre, randomised, double-blind, placebo-controlled trial was conducted in patients with newly diagnosed type 2 diabetes mellitus (T2DM) in 20 medical centers in China. After run-in, participants were randomly assigned (1:1:1:1) to receive probiotics-plus-BBR, BBR-alone, probiotics-alone, or placebo, orally for 12 weeks. The primary outcomes were change in HbA1c from baseline to 13-week follow-up (1) in all participants, and (2) in participants aged ≥ 50 years. Findings: From August 2016, to November 2017, 409 participants (mean [SD] age, 52·5 [9·7] years) were enrolled. Analysis of variance (ANOVA) indicated that change in HbA1c from baseline to 13-week follow-up in the probiotics-plus-BBR group (-1·04[0·79]%) was significantly greater than that in the placebo group (-0·60[0·87]%, p

Human resource departments of large public hospitals in China deal with new challenges caused by multi-campus structure, such as increased labor demand, difficulty in cost management, lack of professional talents, restriction on employing way and etc. Delphi Method and Focus Group were used as the chief methods to analyze the problems. Countermeasures are researched as staffing optimization, performance management, forming Expert Center, establishing HRM Framework based on the positions among campus and restricting the human resource department. The researches break away from traditional human resource practices, develop new application for future trends, and adapt to the changes of business in the country’s public hospital reform.

Taking into account the energy cost, pollution emission, wind power consumption, and other dispatching objectives in the regionally integrated energy system (RIES), the RIES multi-objective optimization model considering the integrated demand response is established. Firstly, the RIES modeling of equipment including electricity-to-gas, energy storage systems, cogeneration units, etc., and the introduction of a comprehensive demand response that specifically considers load reduction, load transfer, and load replacement in the region, aimed at reducing system load peaks and valleys difference. Then, the objective function to minimize the system energy cost, the abandoned wind power, and the pollutant treatment cost was established respectively, and the multi-objective optimization method was adopted—the Pareto front was solved by fuzzy weighted programming traversal weights, and then the decision was made based on evidence Method to find the optimal scheduling strategy. Finally, based on a typical case study, the results show that the proposed multi-objective optimization algorithm can effectively make trade-offs among multiple scheduling objectives, and RIES considering comprehensive demand response has advantages in terms of total energy consumption, environmental friendliness, and wind power consumption.

e15611Background: Colorectal cancer (CRC) is the most common type of gastrointestinal cancer and is the third leading cause of cancer patient’s death worldwide. Long noncoding RNAs (lncRNAs) are a ...

e14063Background: Gliomas are the most common type of primary brain tumors and are the leading cause of cancer-related mortality worldwide. The aquaporins (AQPs) are small hydrophobic integral tran...

A novel modification of the freeform technique selective laser sintering machine via system integration to develop a direct metal laser fabrication machine suitable for both nonmetal and metal materials is put forward in this paper, the aim of which is to establish an experiment platform for studying the direct metal laser fabrication (DMLF) as a variant of selective laser sintering (SLS). The system integration of two machines is realized by use of the low-power SLS Machine (CO2, 50 W) and high-power laser processing machine (CO2, 2,000 W) in our institute after the improvement or rebuilding of light route system, functional units, machinery and electrical system, and control software in the primary SLS machine, which means that direct metal laser fabrication machine with the laser power up to 1,000 W has been developed successfully. Functional tests of two machines and DMLF experiments of a large number of metal powders including Cu-based mixture and 316L-based mixture of powder have been done in detail. The results show that the material suitable for direct metal laser fabrication machine ranges from nonmetal powders to metal powders, including polystyrene, polyamide, polycarbonate, sands, and a large number of metal powders. At the same time, the primary functions or performances of both low-power SLS Machine and high-power laser processing machine are preserved entirely. Metal samples based on copper and 316L powders can be fabricated with the relative density of about 80% and 100%, respectively, by use of developed DMLF machine. The macro appearance and microstructure and processing mechanisms of DMLF are analyzed minutely. The academic application of DMLF machine for metal powders with high melting point has been making its mark.

BACKGROUND The objective of the study was to analyze the association of apelin gene (APLN) single nucleotide polymorphisms (SNPs) and type 2 diabetes mellitus (T2DM). METHODS A total of 1966 subjects were enrolled in this study, including 168 cases (first batch), 330 cases (second batch), and 1468 nondiabetic controls. The SNPs in the HapMap-HCB of APLN were detected using Sequenom MassARRAY SNP technology and included rs2281068, rs3115757, rs2235309, and rs2235310. The related clinical characteristics with glucose metabolism were tested, including the fasting blood glucose (FPG), insulin (INS), C-peptide, glycosylated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C). RESULTS A correlation between rs3115757 and rs2281068 and diabetes was observed in first batch. Thus, we compared the SNPs (rs3115757 and rs2281068) between the cases and controls after more cases were enrolled. In addition, the results showed a significant correlation between APLN rs2281068 and diabetes (p

AIMS To compare the efficacy and safety of liraglutide versus sitagliptin as add-on to metformin after 26 weeks of treatment in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS This 26-week open-label, active comparator trial (NCT02008682) randomized patients (aged 18-80 years) with T2DM inadequately controlled with metformin [glycated haemoglobin (HbA1c) 7.0-10.0% (53-86 mmol/mol)] 1 : 1 to once-daily subcutaneously administered liraglutide 1.8 mg (n = 184) or once-daily oral sitagliptin 100 mg (n = 184), both as add-on to metformin. The primary endpoint was change in HbA1c from baseline to week 26. RESULTS Liraglutide was superior to sitagliptin in reducing HbA1c from baseline [8.1% (65 mmol/mol)] to 26 weeks, as evidenced by estimated mean HbA1c change of -1.65% (-18.07 mmol/mol) versus -0.98% (-10.72 mmol/mol), respectively [estimated treatment difference for liraglutide vs sitagliptin of -0.67% (95% CI -0.86, -0.48) or -7.35 mmol/mol (95% CI -9.43; -5.26); p < 0.0001]. More patients receiving liraglutide (76.5%) than sitagliptin (52.6%) achieved the HbA1c target of

Yujuan Fan,* Yu Zhang,* Xuesong Li,* Hui Zheng, Yuping Song, Ning Zhang, Chunfang Shen, Xiaofang Fan, Fengdong Ren, Jiayi Shen, Guoguang Ren, Jialin Yang Department of Endocrinology, Central Hospital of Minhang District, Minhang Hospital affiliated to Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The objective of this study was to assess the effects of metformin monotherapy or combined treatment with a dipeptidyl peptidase-4 inhibitor (vildagliptin) on apelin levels in patients with type 2 diabetes mellitus. Methods: Twenty-five patients with poor glycemic control (glycosylated hemoglobin >6.5% [48 mmol/mol]) taking 1,000 mg of metformin daily and 25 healthy controls matched for age and body mass index were enrolled in this study. Anthropometric parameters, glycemic and lipid profile, insulin resistance (homeostasis model assessment of insulin resistance index), and apelin levels were measured at baseline and at 12-week and 24-week visits. Results: At baseline, apelin levels were higher in the T2DM patients than in the controls (1.93±1.81 ng/mL versus 6.09±4.90 ng/mL; P

To develop a rat model of type 2 diabetic mellitus that simulated the common manifestation of the metabolic abnormalities and resembled the natural history of a certain type 2 diabetes in human population, male Sprague-Dawley rats (4 months old) were injected with low-dose (15 mg/kg) STZ after high fat diet (30% of calories as fat) for two months (L-STZ/2HF). The functional and histochemical changes in the pancreatic islets were examined. Insulin-glucose tolerance test, islet immunohistochemistry and other corresponding tests were performed and the data in L-STZ/2HF group were compared with that of other groups, such as the model of type 1 diabetes (given 50 mg/kg STZ) and the model of obesity (high fat diet). The body weight of rats in the group of rats given 15 mg/kg STZ after high fat diet for two months increased significantly more than that of rats in the group of rats given 50 mg/kg STZ (the model of type 1 diabetes) (595 +/- 33 g vs. 352 +/- 32 g, p

TPS3632 Background: Irinotecan is an effective drug for rectal cancer. Early small sample size trials have assessed the addition of irinotecan to standard CRT with fluoropyrimidines in neoadjuvant phase of locally advanced rectal cancer, in which pCR rates varied from 13.7 to 37%. ARISTOTLE trial, a multicentre UK-based phase III trial, will complete recruitment in autumn 2016. However, all patients in case group were prescribed with weekly irinotecan dose of 60mg/m2 guided by UGT1A1*28 6/6 and 6/7 genetypes in neoadjuvant chemoradiation. Therefore, this phase III trial was designed to confirm the potential improvement in outcomes seen with the addition of irinotecan to CRT. Methods: Eligible patients are randomly allocated to either radiotherapy 50 Gy with concurrent capecitabine, followed by a cycle of capecitabine and oxaliplatin two weeks after the end of CRT (Control arm) or radiotherapy 50 Gy with concurrent capecitabine and irinotecan, followed by a cycle of capecitabine and irinotecan (Case arm). Capecitabine is prescribed with 825mg/m2 The primary end point is ypCR. The hypothesis is to increase ypCR from 12% in the control group to 25% in the case group. To detect such a difference, with alpha = 0.05 (two-tailed) and belta = 0.15, 360 randomly assigned patients are required. Secondary end points are toxicities, surgical complications, local control, progression-free survival and overall survival. Clinical trial information: NCT02605265.

e17012 Background: There are few studies about epidermal growth factor receptor monoclonal antibody nimotuzumab for the treatment of locally advanced cervical cancer. We aimed to assess the therapeutic efficacy and analyse prognostic factors of chemoradiotherapy combined with nimotuzumab in cervical cancer (stage IIB-IVA) . Methods: We retrospectively analyzed 23 patients with locally advanced cervical cancer(stage IIB-IVA) ,who received concurrent chemoradiotherapy combined with nimotuzumab from 2012 to 2014 (the study group) ,and 30 patients with the similar baseline characteristics who received concurrent chemoradiotherapy alone (the control group). The overall response rates, 5-year overall survival rates, progression-free survival and acute adverse events of the two groups were compared .Multivariate prognostic analysis was performed by a Cox proportional hazards model. Results: The median follow-up time were 46 months (IQR 16-60) in the study group and 42 months (2-60) in the control group.The overall response rates were 87% and 73.3% (P = 0.384) . The 5-year overall survival rates were 63.6% and 36.1% (hazard ratio 2.208,95% CI 0.878-5.557,P = 0.092) .The median progression-free survival in the study group was not achieved (95%CI 9-55) versus 27 months (1-60) in the control group (hazard ratio 2.635, 95% CI 1.030-6.737, P= 0.043).Multivariate prognostic analysis indicated that stage and whether to be combined with nimotuzumab were the influential factors for progression-free survival time.Adverse events were similar between groups.The most common grade 3 or 4 adverse events during treatment in the study group versus the control group were leucopenia(9 [39%] vs 11 [36%]),thrombocytopenia (3 [13%] vs 6 [20%]),anaemia (4 [17%] vs 4 [13%]). Conclusions: Concurrent chemoradiotherapy combined with nimotuzumab in the treatment can improve the progression-free survival time of advanced cervical cancer, while not increasing the incidence of adverse reactions.However, because of the small size of sample in this research, these findings suggest that it is necessary to perform a prospective study with expanded sample size.