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This study aimed to determine the effectiveness of brachytherapy in post-operative cervical cancer patients with risk factors other than positive stump, and to identify the candidates most likely to benefit.Newly diagnosed, non-metastatic cervical cancer patients treated in our hospital between January 2012 and November 2015 were retrospectively reviewed. Early stage patients receiving radical surgery and needing adjuvant external radiotherapy were included, but those with positive stump were excluded. All patients received external radiotherapy. They were divided into two groups: one group received vaginal brachytherapy and the other did not. The 5-year local-regional recurrence free survival (LRRFS) and overall survival (OS) rates in the two groups were compared.Two hundred and twenty-five patients were included in this study; while 99 received brachytherapy, 126 did not. The brachytherapy group had significantly superior 5-year LRRFS (87.7% vs. 72.5%, p = 0.004), but did not show a significant overall survival benefit (78.4% vs. 75.3%, p = 0.055). In multivariate analysis, brachytherapy, pathological type, high-risk factors, duration of radiotherapy, and transfusion were independent prognostic factors for 5-year LRRFS. In stratified analysis, the brachytherapy group showed superior LRRFS in those meeting Sedlis criteria (p = 0.017).The combination of external beam radiation therapy and brachytherapy can improve LRRFS in post-operative cervical cancer patients with risk factors other than positive stump. Therefore, brachytherapy should be considered for these patients.

Cu7S4 nanosheets enriched with Cu–S bond can facilitate the kinetics of CO2 electroreduction to HCOO− and suppress the formation of *CO as a result of the high FE of HCOO− (82.7%) and high partial current density (456 mA cm−2).

Reducing the bidentate ether species formed from the chemisorption between PO and acid sites in the TS/H2O2 system is key to achieving stable operation of the HPPO process.

A protic solvent (ROH/H2O) acts as a mediator to promote the proton transfer during H2O2 activation.

Objective. A target of low-density lipoprotein cholesterol (LDL-C)

The frequency of the pathogenic allele of the autosomal recessive deafness gene GJB2 varies among different populations in the world, and accumulates to a sufficiently high frequency in certain population. The purpose of this study is to investigate the origin and evolution of GJB2 pathogenic alleles in Chinese deaf patients. Children with non-syndromic hearing loss, and their parents, from 295 families were recruited. Customized capture probes targeted at 943 single nucleotide polymorphisms (SNPs) related to GJB2 gene were designed for sequencing of genomic DNA in blood samples. Haplotypes carrying pathogenic allele were analyzed through linkage disequilibrium block building, ancestry tracing, and extended haplotype heterozygosity calculation. Two pathogenic GJB2 alleles, c.235delC (18.41%) and c.109G A (15.57%), were observed in 867 donors. For c.235delC allele, three different core haplotypes with one major haplotype (97.32%) were found, and their core SNPs were 100% conserved. For c.109G A allele, six different haplotypes with one major haplotype (93.28%) were found and the major c.109G A allele evolved from a specific ancestral haplotype. Geographical origins of donors carrying GJB2 c.109G A and c.235delC core haplotypes centered between Qinghai and Neimenggu. GJB2 c.235delC has long-range linkage disequilibrium. No positive selection signature was found for GJB2 c.235delC or c.109G A in the studied population. In conclusion, we discovered a single origin of GJB2 c.235delC allele and multiple independent origins of GJB2 c.109G A allele. Alternative to positive selection or multiple independent recurrent mutation event, population bottleneck effect might account for the observed high population frequency of these pathogenic alleles.

The removal of three inverted triangular parallel cannulated screws after the femoral neck fracture healing is sometimes accompanied by osteonecrosis of the femoral head (ONFH) or its refracture. The purpose of this study was to determine the biomechanical changes of the femur before and after the screw removal using a finite element analysis.The CT data of the femurs were obtained from a 69-year-old healthy female to establish the femur models. The established finite element models consisted of N, C, and R groups: N group, the normal femur; C group (to simulate the femoral neck fracture healing after the internal fixation), the normal femur with three inverted triangular parallel cannulated screws (C1) or with two upper parallel screws (C2). For the R1 or R2 groups, the screws in the model of the C1 or C2 individuals were gradually removed in seven or three types of different screw combinations, respectively. The stresses and displacements of the femur were determined.(1) Compared with the N group, a uniform stress distribution was stopped by the addition of three screws in the C1 group; in contrast, all screw removals resulted in the stress concentration on the screw holes and the disappearance of stress shielding. Moreover, the average stress of the femoral head in C1 group increased by 37.85%, while that of the femoral neck decreased by 23.03%. (2) Compared with the C1 group, while only the lowest femoral calcar screw was removed, there was a similar stress distribution in the proximal femur, and the average stress of the femoral head increased only by 0.35% although that of the femoral neck increased by 63.62%; however, removal by any other means resulted in a significant stress concentration in the proximal femur and a significant increase in the average stresses of the femoral head and neck (5.96-40.95% and 12.82-75.46%, respectively). (3) Compared with the N or C1 group, there was a significant stress concentration on the screws and its surrounding proximal femur in the C2 group. (4) Compared with the C2 group, the simultaneous removal of two upper screws not only did not cause a significant stress concentration on the proximal femur but also significantly reduced the average stresses of the femoral head and neck by 87.49% and 65.51% respectively. On the contrary, the gradual removal of two screws caused a significant stress concentration on the screw and its surrounding proximal femur although the average stresses of the femoral head and neck decreased by 88.79-89.06% and 67.00-67.22%, respectively. (5) Compared with the N group, the average displacements of the femoral head and neck in the C1 group increased only by 3.12% and 3.37%, respectively. Additionally, compared with the C1 group, while three, two, or one screw was simultaneously removed, the average displacements of the femoral head and neck only fluctuated - 5.51-1.65% and 1.78-9.03%, respectively.Residual internal fixation after femoral neck fracture healing may lead to stress concentration on screws and stress shielding around screws. The first removal of the lowest femoral calcar screw and then the second removal of two upper residual screws have a minimum effect on the stress concentration on the proximal femur and the average stress on the femoral head. The incorrect screw removal and resulting femoral load may well be closely related to occurrence in ONFH or its refracture.

Intercropping orchards with cover crops is an important practice for achieving sustainable soil management. However, little research has addressed the development of a soil quality index (SQI) to evaluate cover crop effects on orchard soil quality. The aim of this study was to ascertain whether cover cropping improves soil quality and fruit yield of Goji (Lycium barbarum L.) while reducing or replacing organic fertilizer application. The main treatments were the traditional management of L. barbarum as a monocrop (M) and intercropping Goji with radish (Raphanus sativus L.) as an annual cover crop (I). Within the main treatments, different levels of organic fertilizer were applied at 0 kg·plant−1 (M0), 2 kg·plant−1 (M1), and 4 kg·plant−1 (M2). After six years of planting, we analyzed the changes in soil quality caused by cover cropping with different organic fertilizer levels based on the SQI method. Goji yields were used for validation of the SQI derived from a minimum data set of soil quality indicators. In contrast with traditional monocropping, cover cropping increased soil total nitrogen, available nitrogen, and available phosphorus contents (by 78.60%, 30.30%, and 138.08%, respectively). There were also increased microbial biomass carbon and nitrogen contents (by 79.01% and 184.01%, respectively), enhanced urease and sucrase activities (by 41.02% and 56.81%, respectively), and reduced bulk density (by 1.92%) in the soil as a result of cover cropping. Compared with IM0 treatment, soil microbial biomass carbon and nitrogen contents considerably increased under IM1 treatment, whereas soil available nitrogen and potassium contents as well as electrical conductivity increased under IM2 treatment. The SQI, which varied among treatments in the order IM1 > IM2 > MM2 > MM1 > IM0 > MM0, was positively correlated with Goji yield. From the soil quality and Goji yield perspective, cover cropping with a medium level of organic fertilizer is the optimal soil management practice for the L. barbarum planting system in arid areas of Ningxia, Northwest China.

The widespread use of pesticides poses significant risks to food and environmental safety. Imidacloprid is one of the most effective neuroactive neonicotinoid insecticides and is effective against a broad spectrum of piercing–sucking pests. A rapid, efficient, and high-throughput analysis method for the determination of imidacloprid was developed in four minor crops with six matrices (bamboo shoot, winter jujube, fresh and dry D. officinale, and fresh and dry Fritillaria) by solid-phase extraction and HPLC-MS/MS. The procedure showed satisfying recoveries (72~111%) and RSDs (1~13%). A total of 288 samples were tested in China (Aba and Luan). Imidacloprid residues were 100% detected in fresh and dry D. officinale and winter jujube, with concentrations ranging from 0.048 to 1.550 mg·kg−1. Imidacloprid residues were also abundant in fresh and dry Fritillaria (maximal concentration of 0.021 and 0.063 mg·kg−1, respectively), followed by bamboo shoot, which had the lowest detection rate of imidacloprid (6%). Using the risk quotient (RQ) method, the long-term (RQc) and short-term (RQa) dietary risks of imidacloprid in bamboo shoot, winter jujube, fresh and dry D. officinale, and fresh and dry Fritillaria were further monitored. Based on the imidacloprid residues in this paper, the RQc and RQa were 15.03% and 0.0008~1.7604%, respectively. The RQ values were far less than 100%, showing that Chinese consumers face little health risk as a result of imidacloprid intake.

Background. Type 2 diabetes was associated with a higher risk for permanent pacemaker (PPM) treatment. The difference in cardiovascular outcomes between patients with and without diabetes receiving PPM treatment remains unexplored. Method. Between January 2003 and December 2017, 1742 patients receiving naïve PPM treatment comprised this retrospective cohort study and were categorized into two groups by the diagnosis of diabetes: group with diabetes ( n = 632 , 36.3%) and group without diabetes ( n = 1110 , 63.7%). The primary outcome was cardiovascular events including heart failure (HF) hospitalization and acute myocardial infarction (AMI). The secondary outcomes of this study included pacemaker infection, pacing-induced cardiomyopathy, cerebrovascular accident, cardiovascular mortality, and all-cause mortality. Propensity score matching (PSM) was applied to reduce selection bias between the study groups. Result. During a mean follow-up period of 7.8 ± 4.8 years, 264 patients had a cardiovascular event. Before PSM, the incidence of cardiovascular events was higher in patients with diabetes compared to patients without diabetes (19.8% vs. 12.5%, P < 0.001 ), and the incidences of pacing-induced cardiomyopathy, cardiovascular mortality, and all-cause mortality were all higher in patients with diabetes compared to patients without diabetes. After PSM, the incidence of cardiovascular events was higher in patients with diabetes compared to patients without diabetes (18.8% vs. 12.3%, P = 0.015 ). The incidence of HF hospitalization was higher in patients with diabetes compared to patients without diabetes (15.3% vs. 10.2%, P = 0.037 ), whereas the incidence of AMI did not differ between the two groups. Moreover, after PSM, patients with diabetes had higher cumulative incidences of pacing-induced cardiomyopathy and all-cause mortality compared to patients without diabetes. Conclusions. The prevalence of diabetes was over one-third of naïve PPM recipients of this cohort, and diabetes increased the risk of cardiovascular events in PPM recipients, especially for HF hospitalization.

Next generation sequencing technologies enable the analysis of the transcriptomes of individual cells, providing a higher resolution of gene expression and function at the single cell level. Various single-cell data are continuously generated every year, covering fields from scientific research to clinical development. The fast-growing public datasets are collected by distinctive platforms, which are designed to facilitate biological discoveries, disease diagnosis, and new treatments. However, these platforms are hard to meet the urgency of having a unified data integration pipeline to improve comparability between datasets. Here we present SynEcoSys, an online multifunctional platform for single-cell transcriptomic data analysis, visualization, and exploration. SynEcoSys by Singleron Biotechnologies currently provides a massive collection of publicly available single-cell sequencing dataset, involving 46,326,175 cells from 731 datasets across multiple platforms and species. All datasets are generated with a strict and uniform data analysis pipeline and cell marker-based manual annotation, thus facilitating more comprehensive and reliable data mining. SynEcoSys is available at:https://www.synecosys.com.

Background Impaired renal function is frequently observed in patients with heart failure and reduced ejection fraction (HFrEF). The differential effect of sacubitril/valsartan and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEIs/ARBs) on the clinical and renal outcomes in patients with HFrEF and chronic kidney disease (CKD) remains unknown. Aims This study aimed to explore the differential effect of sacubitril/valsartan and ACEI/ARB on the clinical and renal outcomes as well as renal function over a 12-month follow-up period in HFrEF patients with and without CKD. Methods Patients with HfrEF (LVEF ≤35%) and NYHA class ≥II were enrolled from the Chang Gung Research Database between 2017 and 2020. Baseline characteristics were compared between patients prescribed sacubitril/valsartan and ACEI/ARB. After propensity score matching, the following clinical and renal outcomes were compared between the two groups in patients with and without CKD over a 12-month follow-up period: acute kidney injury (AKI), emergent dialysis/renal death, HF hospitalization, cardiovascular mortality, and all-cause mortality. Results This study enrolled 3735 HFrEF patients with a mean left ventricular EF of 27.56 ± 5.86%, who had been prescribed sacubitril/valsartan (N = 1708) or ACEI/ARB (N = 2027). After propensity score matching, the clinical and renal outcomes did not differ between the sacubitril/valsartan and ACEI/ARB groups in patients without CKD. In patients with CKD, the ACEI/ARB group had a significantly higher incidence of all-cause mortality than the sacubitril/valsartan group (14.89% vs. 10.50%; hazard ratio 1.46; 95% confidence interval 1.06–2.00; p = 0.02), and the incidence of AKI, HF hospitalization, and CV mortality did not differ between the two groups. Conclusions Sacubitril/valsartan had a lower all-cause mortality compared to ACEI/ARB in symptomatic HFrEF patients with CKD. Further prospective randomized studies are warranted to confirm our findings.

Metalaxyl is frequently used to protect a variety of crops from fungal diseases. This study aims to establish a method for the determination of metalaxyl in Chinese bayberry, fresh Dendrobium officinale (D. officinale), and dried D. officinale by gas chromatography-tandem mass spectrometry (GC-MS/MS) and further assess dietary risk. The samples were extracted with acetonitrile and purified by the dispersed solid phase extraction method. Chinese bayberry, fresh D. officinale, and dried D. officinale samples were collected from Hangzhou and Zhangzhou in 2021 to clarify metalaxyl residue levels. The metalaxyl was quantitated by the external standard method. In the range of 0.001–0.1 mg L−1, there was good linearity under the optimal conditions. The recoveries ranged from 83.90% to 110.47%, with relative standard deviations ranging from 0.86% to 5.81%. The detection rates in Chinese bayberry, fresh D. officinale, and dried D. officinale were 97.92%, 49.29%, and 50.71%, respectively. The dietary risk of metalaxyl residues in Chinese bayberry, fresh D. officinale, and dried D. officinale was acceptable for consumers.

Objective. The study aimed to compare the clinical outcomes between the patients receiving coronary artery bypass surgery (CABG) or percutaneous coronary intervention (PCI) for the patients with symptomatic severe left ventricular (LV) dysfunction and coronary artery disease (CAD). Methods. Between February 2007 and February 2020, a total of 745 patients who received coronary artery angiography for reduced LV ejection fraction (LVEF) 22, who received CABG (N = 47) and PCI (N = 69), were recruited for this study.Results. There was no significant difference in the incidence values of in-hospital course and those of in-hospital mortality, acute kidney injury, and postprocedural hemodialysis. There was no significant difference in the 1-yearfollow-up of recurrent MI, revascularization, or stroke between the groups. The 1-year heart failure (HF) hospitalization rate was significantly lower in the CABG group than in all patients of the PCI group (13.2% vs. 33.3%; p = 0.035 ); however, there was no significant difference in the same variable between the CABG group and the complete revascularization subgroup (13.2% vs. 28.2%; p = 0.160 ). The revascularization index (RI) was significantly higher in the CABG group than in all patients of the PCI group or complete revascularization subgroup (0.93 ± 0.12 vs. 0.71 ± 0.25; p < 0.001 ) and (0.93 ± 0.12 vs. 0.86 ± 0.13; p = 0.019 ). The 3-year HF hospitalization rate was significantly lower in the CABG group than in all patients of the PCI group (16.2% vs. 42.2%; p = 0.008 ); however, there was no difference in the same variable between the CABG group and the complete revascularization subgroup (16.2% vs. 35.1%; p = 0.109 ). Conclusions. In patients with symptomatic (NYHA class ≥ 3) severe LV dysfunction and CAD, CABG brought less HF admission when compared to patients in the PCI group, but this did not differ when compared to the complete revascularization subgroup. Therefore, an extensive revascularization, achieved by CABG or PCI, is associated with a lower HF hospitalization rate during the 3-yearfollow-up period in such populations.

The distribution of titanium (Ti) active sites in the framework of TS-1 zeolite is one of the critical factors affecting its catalytic performance, since it can influence accessibility of the Ti active sites and the catalytic utilization of Ti atoms. Here, TS-1 zeolite with homogeneous distribution of titanium atoms in the framework (named BUS-TS-1) is successfully synthesized via bottom-up strategy at high basicity conditions, and BUS-TS-1 zeolite exhibits better catalytic performance for both olefin and alkane oxidation. The comprehensive explorations on the crystallization behavior of BUS-TS-1 zeolite show that, the gripper-like silicon species, as condensed matter in Q2 and Q3 states (detected by 29Si NMR), can be obtained by the condensation of tetraethyl orthosilicate (TEOS) at high alkalinity conditions. The gripper-like silicon species can condense with Ti-OH to form stable and isolated Si-O-Ti species, so that the phase transfer rates of Si and Ti species match during the entire crystallization process, resulting in the homogeneous distribution of Ti atoms. This work offers a useful strategy for the synthesis of high-performance catalysts by regulating the distribution of Ti active-site within TS-1 framework.

In this paper, potential energy curves of Λ

The development of high-performance catalysts with high activity, selectivity, and stability are essential for the practical applications of H

Background Vitamin K antagonists and different direct oral anticoagulants (DOACs) have different renal clearance rates. However, the impact of different stages of chronic renal impairment on the efficacy and safety of warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban in atrial fibrillation (AF) patients remains unclear. Methods This study enrolled AF patients from the Chang Gung Research Database. The study endpoints included thromboembolic events, major/fatal bleeding, gastrointestinal (GI) bleeding and intracranial hemorrhage (ICH). The risks of time to study endpoints between groups were compared using a Cox proportional hazards regression model with adjustment. Results This study enrolled 3525 patients with moderate renal impairment (30 ≤ creatinine clearance (CrCl) Conclusion There did not appear to be major differences in bleeding or thromboembolic risk compared to warfarin in AF patients across a range of degree of renal failure when appropriate dose reductions of the DOACs are made.

Experiments confirmed that circular RNAs contributed to the pathogenesis of diabetic foot ulcers (DFUs). CircHIPK3 was upregulated in type 2 diabetes mellitus (T2DM), but its role in DFU remained unknown. Our study aimed to investigate the regulatory functions of exosomal circHIPK3 and its potential mechanisms in DFU.Exosomal size and distribution, marker proteins, and circHIPK3 levels were evaluated by transmission electron microscope, ExoView R200, western blot, and qRT-PCR. Flow cytometry, MTT, Wound healing assays, and tube formation assays were used to assess the roles of exosomal circHIPK3 in high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). The relationships between Nrf2/VEGFA/circHIPK3 and miR-20b-5p, and between Nrf2 and VEGFA were determined by luciferase reporter assay and RNA immunoprecipitation. We used cell and mice models to investigate the mechanisms of exosomal circHIPK3 under diabetic conditions.CircHIPK3 was significantly upregulated in exo-circHIPK3 rather than exo-vector. Exo-circHIPK3 remarkably inhibited cell apoptosis but promoted cell proliferation, migration, and tube formation in HG-treated HUVECs. Luciferase reporter and RIP assays showed that miR-20b-5p targeted and inhibited Nrf2 and VEGFA, and circHIPK3 acted as a ceRNA of miR-20b-5p to inhibit the binding to its downstream genes Nrf2 and VEGFA. Mechanistically, circHIPK3 promoted cell proliferation, migration, and angiogenesis via downregulating miR-20b-5p to upregulate Nrf2 and VEGFA. However, the overexpressed miR-20b-5p could abolish the promoting effects of circHIPK3 overexpression on cell proliferation, migration, and tube formation under HG conditions.UCMSCs-derived exosomal circHIPK3 protected HG-treated HUVECs via miR-20b-5p/Nrf2/VEGFA axis. The exosomal circHIPK3 might be a therapeutic candidate to treat DFU.

The timely selection of severe heart failure (HF) patients for cardiac transplantation and advanced HF therapy is challenging. Peak oxygen consumption (VOWe retrospectively selected 377 acute HF patients discharged from the hospital. The primary outcome was a composite of all-cause mortality, or urgent cardiac transplantation. We divided these patients into the more GDMT (two or more types of GDMT) and less GDMT groups (fewer than two types of GDMT) and compared the performance of their peak VOOptimizing the cutoff value of peak VO

Purpose To assess the effectiveness and toxicity of radiation dose escalation in treating local advanced nasopharyngeal carcinoma patients (LA-NPCs) who have locally and/or regionally residual lesion(s) after standard treatment. Methods and materials: From November 2011 to November 2020, 259 LA-NPCs with residual local and/or regional lesion(s) after receiving induction chemotherapy followed by concurrent chemoradiotherapy (IC + CCRT) from our hospital were included. The total dose of primary radiotherapy (RT) was 68.1-74.25 Gy (median, 70.4 Gy). The boost doses were 4.0–18.0 Gy (median, 9 Gy), 1.8-2.0 Gy/fraction. Results Five-year local relapse-free survival (LRFS), regional relapse-free survival (RRFS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), failure-free survival (FFS) and overall survival (OS) for all patients were 90.2%, 89.1%, 79.5%, 87.9%, 69.0%, 86.3%, respectively. LRRFS, DMFS, FFS, and OS in patients with age ≤ 65 versus > 65, plasma EBV-DNA ≤ 500 versus > 500, T1 − 2 versus T3 − 4, N0 − 1 versus N2 − 3, and stage III versus stage IV showed no statistically significant differences. The interval between primary RT and boost was not a prognostic factor for LRRFS, DMFS, FFS, and OS. Males had a lower 3-year FFS rate than females (72.9% vs. 83.7%, P = 0.024). LA-NPCs with locally and regionally residual lesion(s) had the worst 3-year DMFS and OS rates compared with locally or regionally residual lesion(s) (77.7% vs. 98.8% vs. 87.4%, P = 0.014; 75.9% vs. 94.5% vs. 82.4%, P = 0.002). Conclusion Boost radiation was an option for LA-NPCs with locally and/or regionally residual lesions after receiving IC + CCRT. It warrants further prospective study.

An asymmetric organocatalyzed three-component Povarov reaction to construct azaspirocycles has been developed. A chiral phosphoric acid

Background To assess the effectiveness and toxicity of radiation dose escalation for locally advanced nasopharyngeal carcinoma (LA-NPC) in patients with local and/or regional residual lesion(s) after standard treatment. Methods From November 2011 to November 2020, 259 LA-NPC patients who had local and/or regional residual lesion(s) after induction chemotherapy followed by concurrent chemoradiotherapy (IC + CCRT) from our hospital were included. The total dose of primary radiotherapy (RT) was 68.1–74.25 Gy (median, 70.4 Gy). The boost doses were 4.0–18.0 Gy (median, 9 Gy), 1.8–2.0 Gy/fraction. Results For all patients, the 5-year local relapse-free survival was 90.2%, regional relapse-free survival was 89.1%, locoregional relapse-free survival (LRRFS) was 79.5%, distant metastasis-free survival (DMFS) was 87.9%, failure-free survival (FFS) was 69.0%, and overall survival (OS) was 86.3%. LRRFS, DMFS, FFS, and OS in patients with age ≤ 65 versus > 65, plasma Epstein-Barr virus-deoxyribonucleic acid ≤ 500 versus > 500, T1–2 versus T3–4, N0–1 versus N2–3, and stage III versus stage IV showed no statistically significant differences. The interval between primary RT and boost was not a prognostic factor for LRRFS, DMFS, FFS, and OS. Males had a lower 3-year FFS rate than females (72.9% vs. 83.7%, P = 0.024). LA-NPCs with locally and regionally residual lesion(s) had the worst 3-year DMFS and OS rates compared with locally or regionally residual lesion(s) (77.7% vs. 98.8% vs. 87.4%, P = 0.014; 75.9% vs. 94.5% vs. 82.4%, P = 0.002). Conclusion Boost radiation was an option for LA-NPCs with locally and/or regionally residual lesions after receiving IC + CCRT. It warrants further prospective study. Trial registration: Retrospectively registered.

Originally considered to be a plant pathogen, reports of phaeohyphomycosis due to

The unique optical properties of two-dimensional layered materials are attractive for achieving increased functionality in integrated photonics. Owing to the van der Waals nature, these materials are ideal for integrating with nanoscale photonic structures. Here we report on carefully designed air-mode silicon photonic crystal nanobeam cavities for efficient control through two-dimensional materials. By systematically investigating various types and thickness of two-dimensional materials, we are able to show that enhanced responsivity allows for giant shifts of the resonant wavelength. With atomically precise thickness over a macroscopic area, few-layer flakes give rise to quantization of the mode shifts. We extract the dielectric constant of the flakes and find that it is independent of the layer number down to a monolayer. Flexible reconfiguration of a cavity is demonstrated by stacking and removing ultrathin flakes. With an unconventional cavity design, our results open up new possibilities for photonic devices integrated with two-dimensional materials., Comment: 8 pages, 5 figures

Objective To explore the associations of obstructive sleep apnea(OSA) and gender with estimated glomerular filtration rate(eGFR) in hypertensive populations.Methods From February 2005 to August 2010,2064 hypertensive patients who were treated in the Department of Hypertension Center underwent overnight polysomnographic monitoring.According to the apnea-hypopnea index(AHI),they were assigned into an hypertension combined with OSA group and a hypertension group.The clinical characteristics and sleep monitoring indicators were compared between different genders and between the two groups.Multivariate Logistic regression was employed to analyze the influencing factors of eGFR.Results Among the 2064 hypertensive patients,there were 1537 males(including 1221 patients with OSA) and 527 females(including 350 patients with OSA).The males had higher prevalence of OSA(

Aims: The current study investigated the effects of first language (L1) congruency, word frequency, collocational frequency, second language (L2) proficiency, and their combined effects on L2 collocational processing. Methodology: Twenty English native speakers and 60 adult Chinese–English bilinguals (intermediate and advanced) completed an online phrasal decision task. They made a judgment about whether target word pairs (congruent collocations, incongruent collocations, and non-collocational baseline items) were commonly used in English. Data and analysis: Response time and accuracy data were analyzed with mixed-effects models, with focus on the interactions of the variables of interest. Findings: Results demonstrated differential effects for the response time and accuracy data: (1) both L2 groups were significantly more accurate but not significantly faster in judging the congruent collocations than the incongruent collocations, and unexpectedly similar patterns were observed with the L1 group; (2) all participants were sensitive to word frequency and collocational frequency, but they differed in the manner and degree of such sensitivity; and (3) the processing of incongruent collocations showed greater combined effects of word frequency and collocational frequency than did the processing of congruent collocations. Originality: We specifically investigated the effects of multiple influencing factors and their combined effects. In addition, we addressed a methodological limitation regarding stimuli control by using congruent and incongruent collocational pairs that differed in only one constituent word. Implications: Our findings highlight the non-colinear relationship of L2 proficiency and (explicit and implicit) collocational knowledge as well as the semantic aspects of cross-language differences, and they also support the usage-based models.

Objective: To explore the gene biomarkers related to the diagnosis and prognosis of adrenocortical carcinoma (ACC) by bioinformatics. Methods: GEPIA online analysis tool was used to screen differentially expressed genes for sequencing data from patients with ACC and normal adrenal cortex. The overall survival rate and disease-free survival method were used to conduct batch survival analysis on differentially expressed genes, and the top 100 genes with HR values calculated by the two methods were obtained respectively. The intersection method is used to obtain core genes that play a key role in both overall survival and diseasefree survival. GEPIA online analysis tool was used again to explore the relationship between the above-mentioned survival-related genes and the pathological stage of ACC. Use UALCAN online analysis tool to verify the survival-related genes again and draw the Kaplan-Meier survival curve. Finally, GSE33371 chip dataset of the GEO database was used to evaluate the diagnostic value of the above-mentioned survival-related genes. Results: 514 differentially expressed genes were obtained by limma method. Batch analysis of differential genes was performed to obtain the top 100 genes most related to overall survival and disease-free survival, of which 13 genes were closely related to overall survival and disease-free survival. 9 hub genes including TP73, SNHG1, PDE6D, GPC2, SUV39H2, HELLS, CLK2, COPS7B and CEP164 were finally obtained by exploring the relationship between their expression levels and pathological stage and resurvival analysis. At the same time, the results of ROC analysis suggest that the above hub genes have high diagnostic value for patients with adrenocortical carcinoma. Conclusion: By using GEPIA, UALCAN and the gene chip retrieved from GEO database, combined with the bioinformatics method, we analyzed and verified the new biomarkers that can be used to evaluate the prognosis of patients with ACC and to differential diagnosis of ACC, and provided the theoretical support of bioinformatics for exploring the occurrence, development of molecular mechanism and potential target of treatment of ACC.

Background: With respect to total mortality and cardiovascular mortality, the feature and impact of guideline-directed medication (GDM) prescriptions for heart failure with reduced ejection fraction (HFrEF) with chronic kidney disease (CKD) are unknown. Therefore, we aimed to determine these aspects. Methods: GDM prescriptions and their impact on discharged patients with and without CKD were analyzed. To analyze differences in one-year clinical outcomes, propensity score matching was conducted on a cohort of patients with concomitant HFrEF and CKD who received more and fewer GDM prescriptions. Results: A total of 1509 patients were enrolled in Taiwan's HFrEF registry from May 2013 to October 2014, and 1275 discharged patients with complete one-year follow-up were further analyzed. Of these patients, 468 (36.7%) had moderate CKD, whereas 249 (19.5%) had advanced CKD. Patients with advanced CKD received fewer prescribed GDMs than other patients. Multivariate analysis revealed that peripheral arterial occlusive disease, thyroid disorder, advanced HF at discharge, diastolic blood pressure, digoxin use, and fewer prescribed GDMs were independent predictors of one-year total mortality. After propensity score matching, patients with fewer prescribed GDMs had higher one-year total mortality rate than those with more prescribed GDMs (P=0.036). Conclusions: CKD at discharge from HF hospitalization was associated with fewer GDM prescriptions, particularly in patients with more advanced CKD. The propensity-matched analysis indicated that more GDM prescriptions led to better clinical outcomes in HFrEF patients with CKD. Careful interpretation of changes in renal function during HF hospitalization may improve GDM prescriptions.

Surface-enhanced Raman spectroscopy (SERS) is an optical technique for molecule identification. However, fabrication of flexible and structured SERS substrates for performance improvement in a facile and cost-effective manner is challenging. In this work, we reported a polytetrafluoroethylene (PTFE)-based flexible SERS substrate by femtosecond laser direct writing (FsLDW) technology. The femtosecond laser-treated PTFE surface is 3D hierarchical micro-/nano-structures, and the structured PTFE-based SERS chip shows excellent performance enhancement. As a result, 10−7 M can be detected, which shows excellent potentials in developing flexible SERS for wearable electronics.

Metformin, the first line pharmacotherapy for type 2 diabetes has demonstrated favourable effects in prostate cancer (PCa) across a range of studies evaluating PCa patient outcomes amongst metformin users. However, a lack of rigorously conducted prospective studies has stalled clinical use in this setting. Despite multiple studies evaluating the mechanisms underpinning antitumour effects of metformin in PCa, to date, no reviews have compared these findings. This systematic review and meta-analysis consolidates the mechanisms accounting for the antitumour effect of metformin in PCa and evaluates the antitumour efficacy of metformin in preclinical PCa studies. Data were obtained through Medline and EMBASE, extracted by two independent assessors. Risk of bias was assessed using the TOXR tool. Meta-analysis compared in vivo reductions of PCa tumour volume with metformin. In total, 447 articles were identified with 80 duplicates, and 261 articles excluded based on eligibility criteria. The remaining 106 articles were assessed and 71 excluded, with 35 articles included for systematic review, and eight included for meta-analysis. The mechanisms of action of metformin regarding tumour growth, viability, migration, invasion, cell metabolism, and activation of signalling cascades are individually discussed. The mechanisms by which metformin inhibits PCa cell growth are multimodal. Metformin regulates expression of multiple proteins/genes to inhibit cellular proliferation, cell cycle progression, and cellular invasion and migration. Published in vivo studies also conclusively demonstrate that metformin inhibits PCa growth. This highlights the potential of metformin to be repurposed as an anticancer agent, warranting further investigation of metformin in the setting of PCa.

Background: Acute decompensated heart failure (ADHF) is a life-threatening condition with a high mortality rate. Levosimendan is an effective inotropic agent used to maintain cardiac output and a long-lasting effect. However, only few studies have compared the clinical outcomes, after levosimendan therapy, among etiologies of ADHF. Methods: Between July 2014 and December 2019, 184 patients received levosimendan therapy for ADHF at our hospital. A total of 143 patients had ischemic cardiomyopathy (ICM), and 41 patients had non-ICM (NICM). Data on comorbidities, echocardiographic findings, laboratory findings, use of mechanical devices, consumption of other inotropic or vasopressor agents, frequency of HF hospitalization, cardiovascular (CV) mortality, and all-cause mortality were compared between the ICM and NICM groups. Results: Patients with ICM were older with higher prevalence of diabetes mellitus when compared to patients with NICM. Patients with NICM had a poorer left ventricular ejection fraction (LVEF) and higher left ventricular end-systolic volume when compared to patients with ICM. At the 30 day follow-up period, a lower CV mortality (ICM vs. NICM: 20.9% vs. 5.1%; log-rank p = 0.033) and lower all-cause mortality (ICM vs. NICM: 28.7% vs. 9.8%; log-rank p = 0.018) was observed in the NICM patients. A significantly lower all-cause mortality was noted at 180 day (ICM vs. NICM: 39.2% vs. 22.0%; log-rank p = 0.043) and 1 year (ICM vs. NICM: 41.3% vs. 24.4%; log-rank p = 0.046) follow up in the NICM subgroup. NICM (hazard ratio (HR): 0.303, 95% confidence interval (CI): 0.108–0.845; p = 0.023) and ECMO use (HR: 2.550, 95% CI: 1.385–4.693; p = 0.003) were significant predictors of 30 day all-cause mortality. Conclusions: In our study on levosimendan use for ADHF patients, better clinical outcomes were noted in the NICM population when compared to the ICM population. In the patients with cardiogenic shock or ventilator use, significantly lower incidence of 30 day mortality presented in the NICM population when compared with the ICM population.

On 17 June 2019, an Ms6.0 earthquake occurred in Changning, Sichuan, China (Changning event), which was the largest earthquake on record within 50 km of the area. It attracted great attention as the area has the largest shale gas production in China as well as significant mineral salt production. Using the Interferometric Synthetic Aperture Radar (InSAR), we extract the coseismic deformation of the Changning event and two earlier Ms > 5.0 earthquakes which occurred in the same region (16 December 2018 Ms5.7 and 3 January 2019 Ms5.3) from the Sentinel-1 and ALOS2 data. We use nonlinear and linear methods to invert the fault models of the three earthquakes based on the deformation fields. The final model shows that the Changning event was caused by a fault with left-lateral strike and thrust slip. The strike is 124.3° with a dip angle of 43.4°. The seismic moment obtained by inversion is 5.28 × 1017 Nm, corresponding to Mw 5.78. Based on the fault models, we analyze the cause of the Changning earthquake considering the local tectonic setting, Coulomb stress change, mining, and fluid injection. We consider that the event may be related to salt mining. The two earlier Ms > 5.0 earthquakes may also play an important role in advancing the Changning earthquake.

PurposeSnoring or obstructive sleep apnea, with or without uncontrolled hypertension, is common and significantly increases the risk of coronary heart disease (CHD). The aim of this study was to develop and validate a prognostic model to predict and identify high-risk patients for CHD among snorers with uncontrolled hypertension.MethodsRecords from 1,822 snorers with uncontrolled hypertension were randomly divided into a training set (n = 1,275, 70%) and validation set (n = 547, 30%). Predictors for CHD were extracted to construct a nomogram model based on multivariate Cox regression analysis. We performed a single-split verification and 1,000 bootstraps resampling internal validation to assess the discrimination and consistency of the prediction model using area under the receiver operating characteristic curve (AUC) and calibration plots. Based on the linear predictors, a risk classifier for CHD could be set.ResultsAge, waist circumference (WC), and high- and low-density lipoprotein cholesterol (HDL-C and LDL-C) were extracted as the predictors to generate this nomogram model. The C-index was 0.720 (95% confidence interval 0.663–0.777) in the derivation cohort and 0.703 (0.630–0.776) in the validation cohort. The AUC was 0.757 (0.626–0.887), 0.739 (0.647–0.831), and 0.732 (0.665–0.799) in the training set and 0.689 (0.542–0.837), 0.701 (0.606–0.796), and 0.712 (0.615–0.808) in the validation set at 3, 5, and 8 years, respectively. The calibration plots showed acceptable consistency between the probability of CHD-free survival and the observed CHD-free survival in the training and validation sets. A total of more than 134 points in the nomogram can be used in the identification of high-risk patients for CHD among snorers with uncontrolled hypertension.ConclusionWe developed a CHD risk prediction model in snorers with uncontrolled hypertension, which includes age, WC, HDL-C, and LDL-C, and can help clinicians with early and quick identification of patients with a high risk for CHD.

In this study, an analytical method for the simultaneous determination of the novel insecticide flupyradifurone and its two metabolites in a variety of traditional Chinese herbal medicines was developed for the first time using high-performance liquid chromatography-tandem mass spectrometry. A simple and efficient method using dispersive solid-phase extraction was employed for the pretreatment of the samples. Several extractions and cleanup strategies were evaluated. The recoveries (n = 15) of flupyradifurone and its metabolites at three spiking levels were in the range 71.3%–101.7%, with corresponding intraday and interday relative standard deviations of 1.1%–14.8%. The limits of quantitation were 0.01 mg/kg for flupyradifurone and 0.1 mg/kg for its two metabolites. Overall, our developed method was sensitive and reliable for the fast screening of flupyradifurone and its two metabolites in traditional Chinese herbal medicine samples.

Earthquakes rarely occur at extremely shallow depths, for example, less than 2 km. Even for induced earthquakes that are typically shallower than tectonic events, only very small ones have been reported in such depths. The ML 4.9 earthquake (Mw 4.3) that struck the Rongxian County, Sichuan, China on 25 February 2019 was an extremely shallow event. Seismological and geodetic data constrained the mainshock depth at ∼1 km with a thrust-faulting mechanism, consistent with the Molin fault orienting northwest. Two foreshocks with magnitudes larger than 4 occurred on an unmapped fault striking northeast, right next to an injection well where hydraulic fracturing (HF) was conducted. The focal depths of the two foreshocks were at ∼2.7 km, coinciding with the depth of HF. Coulomb failure stresses of the two foreshocks on the Molin fault was ∼3 kPa, smaller than typical static triggering threshold (10 kPa), and thus their triggering effects were mild. As the fault was hydraulically sealed from HF, we suggested that the ML 4.9 earthquake was possibly triggered by nearby HF activities through poroelastic stress transfer. Such findings held significant implications for shale gas development by considering seismic hazard associated with shallow faults.

Objective: The aim of this study was to analyze the risk factors of type 2 diabetes in 5 years in Chinese population, and to construct the prediction model of nomogram and verify its validity. Methods: The physical examination and follow-up data of the participants who received physical examination at 32 sites in 11 cities in China from 2010 to 2016 were collected from the Dryad digital repository database. Randomly divided into modeling group (n = 22936) and validation group (n = 9830). In the modeling group, the independent risk factors were determined by single factor and multi factor analysis based on Cox regression model, and the nomogram prediction model was constructed by R software. The accuracy and performance of the model were evaluated by AUC value, C-index and calibration curve. Results: The multivariate regression model suggested that fasting blood glucose, triglyceride, smoking history and drinking history were independent risk predictors of 5-year risk of type 2 diabetes in Chinese population. In the modeling group, AUC was 0.776 (95%CI: 0.699-0.849), and C-index was 0.783 (95%CI: 0.706-0.856). Similarly, in the validation group, the AUC value was 0.743 (95%CI:0.665-0.824), and the C-index was 0.764 (95%CI: 0.667-0.846), suggesting that the model had a good discrimination ability. The 5-year adjusted risk curve of type 2 diabetes in Chinese population suggests a good consistency between the predicted value and the actual value. Conclusion: The nomogram model can predict the 5-year risk of type 2 diabetes in Chinese population intuitively and accurately.

Background With the recent emergence of immune checkpoint inhibitors, microsatellite instability (MSI) status has become an important biomarker for immune checkpoint blockade therapy. There are growing technical demands for the integration of different genomic alterations profiling including MSI analysis in a single assay for full use of the limited tissues. Methods Tumor and paired control samples from 64 patients with primary colorectal cancer were enrolled in this study, including 14 MSI-high (MSI-H) cases and 50 microsatellite stable (MSS) cases determined by MSI-PCR. All the samples were sequenced by a customized NGS panel covering 2.2 MB. A training dataset of 28 samples was used for selection of microsatellite loci and a novel NGS-based MSI status classifier, USCI-msi, was developed. NGS-based MSI status, single nucleotide variant (SNV) and tumor mutation burden (TMB) were detected for all patients. Most of the patients were also independently detected by immunohistochemistry (IHC) staining. Results A 9-loci model for detecting microsatellite instability was able to correctly predict MSI status with 100% sensitivity and specificity compared with MSI-PCR, and 84.3% overall concordance with IHC staining. Mutations in cancer driver genes (APC, TP53, and KRAS) were dispersed in MSI-H and MSS cases, while BRAF p.V600E and frameshifts in TCF7L2 gene occurred only in MSI-H cases. Mismatch repair (MMR)-related genes are highly mutated in MSI-H samples. Conclusion We established a new NGS-based MSI classifier, USCI-msi, with as few as 9 microsatellite loci for detecting MSI status in CRC cases. This approach possesses 100% sensitivity and specificity, and performed robustly in samples with low tumor purity.

We propose a novel end-to-end deep learning framework, the Joint Matting Network (JMNet), to automatically generate alpha mattes for human images. We utilize the intrinsic structures of the human body as seen in images by introducing a pose estimation module, which can provide both global structural guidance and a local attention focus for the matting task. Our network model includes a pose network, a trimap network, a matting network, and a shared encoder to extract features for the above three networks. We also append a trimap refinement module and utilize gradient loss to provide a sharper alpha matte. Extensive experiments have shown that our method outperforms state-of-theart human matting techniques; the shared encoder leads to better performance and lower memory costs. Our model can process real images downloaded from the Internet for use in composition applications.