The effect of surface roughness on the oxidation behavior of a directionally solidified Ni-based superalloy was investigated by surface mapping microscope,scanning electron microscope and X-ray ...diffraction.It was found that specimens with surface roughness of 0.05 urn exhibit the best oxidation resistance,while specimens with surface roughness of 0.14 μm behave worse than specimens with surface roughness of 0.83 μm.The specimens with surface roughness of 0.05 μm have the best oxidation resistance,which is mainly due to the smallest surface area exposed in air and thinnest work-hardening layer.The Al_2O_3 layer alleviates the oxidation process of the specimens with surface roughness of 0.83 μm,and this is the possible reason for the better oxidation resistance of samples with surface roughness of 0.83 μm than samples with surface roughness of 0.14 μm.
Background DNA repair gene X-ray repair cross complementing group 1 (XRCC1) plays an important role in the maintenance of the genomic integrity and protection of cells from DNA damage. Sequence ...variation in XRCC1 gene may alter head and neck cancer (HNC) susceptibility. However, these results are inconclusive. To derive a more precise estimation of the relationship between XRCC1 polymorphism and HNC risk, we undertook a meta-analysis involving 16,344 subjects. Methods A search of the literature by PubMed, Embase, Web of Science and China National Knowledge Infrastructure was performed to identify studies based on the predetermined inclusion criteria. The odds ratio (OR) with 95% confidence interval (CI) was combined using a random-effects model or a fixed-effects model. Results Twenty-nine studies consisting of 6,719 cases and 9,627 controls were identified and analyzed. Overall, no evidence of significant association was observed between XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln genotypes and the risk of HNC in any genetic models. Subgroup analyses according to ethnicity, tumor site, publication year, genotyping method also detected no significant association in any subgroup, except that oral cancer was associated with Arg194Trp variant in recessive model. Furthermore, no significant effect of these polymorphisms interacted with smoking on HNC risk was detected but Arg194Trp homozygous variant. Conclusion In conclusion, this meta-analysis suggests that the XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism may not involve in HNC susceptibility. Further studies about gene-gene and gene-environment interactions in different populations are required.
Aims
To compare the performance of logistic regression and machine learning methods in predicting postoperative delirium (POD) in elderly patients.
Method
This was a retrospective study of ...perioperative medical data from patients undergoing non‐cardiac and non‐neurology surgery over 65 years old from January 2014 to August 2019. Forty‐six perioperative variables were used to predict POD. A traditional logistic regression and five machine learning models (Random Forest, GBM, AdaBoost, XGBoost, and a stacking ensemble model) were compared by the area under the receiver operating characteristic curve (AUC‐ROC), sensitivity, specificity, and precision.
Results
In total, 29,756 patients were enrolled, and the incidence of POD was 3.22% after variable screening. AUCs were 0.783 (0.765–0.8) for the logistic regression method, 0.78 for random forest, 0.76 for GBM, 0.74 for AdaBoost, 0.73 for XGBoost, and 0.77 for the stacking ensemble model. The respective sensitivities for the 6 aforementioned models were 74.2%, 72.2%, 76.8%, 63.6%, 71.6%, and 67.4%. The respective specificities for the 6 aforementioned models were 70.7%, 99.8%, 96.5%, 98.8%, 96.5%, and 96.1%. The respective precision values for the 6 aforementioned models were 7.8%, 52.3%, 55.6%, 57%, 54.5%, and 56.4%.
Conclusions
The optimal application of the logistic regression model could provide quick and convenient POD risk identification to help improve the perioperative management of surgical patients because of its better sensitivity, fewer variables, and easier interpretability than the machine learning model.
Six prediction models were constructed for POD using logistic regression, RF, AdaBoost, XGBoost, GBM, and stacking ensemble learning based on retrospective analysis of a large sample dataset. The logistic regression model had the same AUC(0.78) with the RF, and performed better than the machine learning models because of its better sensitivity, fewer variables, and easier interpretability.
Summary
The sexine layer of pollen grain is mainly composed of sporopollenins. The sporophytic secretory tapetum is required for the biosynthesis of sporopollenin. Although several enzymes involved ...in sporopollenin biosynthesis have been reported, the regulatory mechanism of these enzymes in tapetal layer remains elusive. ABORTED MICROSPORES (AMS) and MALE STERILE 188/MYB103/MYB80 (MS188/MYB103/MYB80) are two tapetal cell‐specific transcription factors required for pollen wall formation. AMS functions upstream of MS188. Here we report that AMS and MS188 target the CYP703A2 gene, which is involved in sporopollenin biosynthesis. We found that AMS and MS188 were localized in tapetum while CYP703A2 was localized in both tapetum and locule. Chromatin immunoprecipitation (ChIP) showed that MS188 directly bound to the promoter of CYP703A2 and luciferase‐inducible assay showed that MS188 activated the expression of CYP703A2. Yeast two‐hybrid and electrophoretic mobility shift assays (EMSAs) further demonstrated that MS188 complexed with AMS. The expression of CYP703A2 could be partially restored by the elevated levels of MS188 in the ams mutant. Therefore, our data reveal that MS188 coordinates with AMS to activate CYP703A2 in sporopollenin biosynthesis of plant tapetum.
Significance Statement
Sporopollenin in the pollen wall is produced by the tapetum, but how genes encoding the required biosynthetic enzymes are regulated is unclear. Here we show that two transcription factors, MS188 and AMS, positively regulate the gene encoding CYP703A2, a cytochrome P450 required for sporopollenin biosynthesis.
Summary Background Platinum chemotherapy has a role in the treatment of metastatic triple-negative breast cancer but its full potential has probably not yet been reached. We assessed whether a ...cisplatin plus gemcitabine regimen was non-inferior to or superior to paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer. Methods For this open-label, randomised, phase 3, hybrid-designed trial undertaken at 12 institutions or hospitals in China, we included Chinese patients aged 18–70 years with previously untreated, histologically confirmed metastatic triple-negative breast cancer, and an ECOG performance status of 0–1. These patients were randomly assigned (1:1) to receive either cisplatin plus gemcitabine (cisplatin 75 mg/m2 on day 1 and gemcitabine 1250 mg/m2 on days 1 and 8) or paclitaxel plus gemcitabine (paclitaxel 175 mg/m2 on day 1 and gemcitabine 1250 mg/m2 on days 1 and 8) given intravenously every 3 weeks for a maximum of eight cycles. Randomisation was done centrally via an interactive web response system using block randomisation with a size of eight, with no stratification factors. Patients and investigator were aware of group assignments. The primary endpoint was progression-free survival and analyses were based on all patients who received at least one dose of assigned treatment. The margin used to establish non-inferiority was 1·2. If non-inferiority of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine was achieved, we would then test for superiority. The trial is registered with ClinicalTrials.gov , number NCT01287624. Findings From Jan 14, 2011, to Nov 14, 2013, 240 patients were assessed for eligibility and randomly assigned to treatment (120 in the cisplatin plus gemcitabine group and 120 in the paclitaxel plus gemcitabine group). 236 patients received at least one dose of assigned chemotherapy and were included in the modified intention-to-treat analysis (118 per group). After a median follow-up of 16·3 months (IQR 14·4–26·8) in the cisplatin plus gemcitabine group and 15·9 months (10·7–25·4) in the paclitaxel plus gemcitabine group, the hazard ratio for progression-free survival was 0·692 (95% CI 0·523–0·915; pnon-inferiority <0·0001, psuperiority =0·009, thus cisplatin plus gemcitabine was both non-inferior to and superior to paclitaxel plus gemcitabine. Median progression-free survival was 7·73 months (95% CI 6·16–9·30) in the cisplatin plus gemcitabine group and 6·47 months (5·76–7·18) in the paclitaxel plus gemcitabine group. Grade 3 or 4 adverse events that differed significantly between the two groups included nausea (eight 7% vs one <1%), vomiting (13 11% vs one <1%), musculoskeletal pain (none vs ten 8%), anaemia (39 33% vs six 5%), and thrombocytopenia (38 32% vs three 3%), for the cisplatin plus gemcitabine compared with the paclitaxel plus gemcitabine groups, respectively. In addition, patients in the cisplatin plus gemcitabine group had significantly fewer events of grade 1–4 alopecia (12 10% vs 42 36%) and peripheral neuropathy (27 23% vs 60 51%), but more grade 1–4 anorexia (33 28% vs 10 8%), constipation (29 25% vs 11 9%), hypomagnesaemia (27 23% vs five 4%), and hypokalaemia (10 8% vs two 2%). Serious drug-related adverse events were seen in three patients in the paclitaxel plus gemcitabine group (interstitial pneumonia, anaphylaxis, and severe neutropenia) and four in the cisplatin plus gemcitabine group (pathological bone fracture, thrombocytopenia with subcutaneous haemorrhage, severe anaemia, and cardiogenic syncope). There were no treatment-related deaths. Interpretation Cisplatin plus gemcitabine could be an alternative or even the preferred first-line chemotherapy strategy for patients with metastatic triple-negative breast cancer. Funding Shanghai Natural Science Foundation.
Objective
The present study was undertaken to determine the efficacy of coadministration of fingolimod with alteplase in acute ischemic stroke patients in a delayed time window.
Methods
This was a ...prospective, randomized, open‐label, blinded endpoint clinical trial, enrolling patients with internal carotid artery or middle cerebral artery proximal occlusion within 4.5 to 6 hours from symptom onset. Patients were randomly assigned to receive alteplase alone or alteplase with fingolimod. All patients underwent pretreatment and 24‐hour noncontrast computed tomography (CT)/perfusion CT/CT angiography. The coprimary endpoints were the decrease of National Institutes of Health Stroke Scale scores over 24 hours and the favorable shift of modified Rankin Scale score (mRS) distribution at day 90. Exploratory outcomes included vessel recanalization, anterograde reperfusion, and retrograde reperfusion of collateral flow.
Results
Each treatment group included 23 patients. Compared with alteplase alone, patients receiving fingolimod plus alteplase exhibited better early clinical improvement at 24 hours and a favorable shift of mRS distribution at day 90. In addition, patients who received fingolimod and alteplase exhibited a greater reduction in the perfusion lesion accompanied by suppressed infarct growth by 24 hours. Fingolimod in conjunction with alteplase significantly improved anterograde reperfusion of downstream territory and prevented the failure of retrograde reperfusion from collateral circulation.
Interpretation
Fingolimod may enhance the efficacy of alteplase administration in the 4.5‐ to 6‐hour time window in patients with a proximal cerebral arterial occlusion and salvageable penumbral tissue by promoting both anterograde reperfusion and retrograde collateral flow. These findings are instructive for the design of future trials of recanalization therapies in extended time windows. Ann Neurol 2018;84:725–736
Timely diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a prerequisite for treatment and prevention. The serology characteristics and complement diagnosis value ...of the antibody test to RNA test need to be demonstrated.
Serial sera of 80 patients with PCR-confirmed coronavirus disease 2019 (COVID-19) were collected at the First Affiliated Hospital of Zhejiang University, Hangzhou, China. Total antibody (Ab), IgM and IgG antibodies against SARS-CoV-2 were detected, and the antibody dynamics during the infection were described.
The seroconversion rates for Ab, IgM and IgG were 98.8%, 93.8% and 93.8%, respectively. The first detectible serology marker was Ab, followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 days post exposure (d.p.e.) or 9, 10 and 12 days post onset (d.p.o.), respectively. The antibody levels increased rapidly beginning at 6 d.p.o. and were accompanied by a decline in viral load. For patients in the early stage of illness (0-7 d.p.o), Ab showed the highest sensitivity (64.1%) compared with IgM and IgG (33.3% for both; p<0.001). The sensitivities of Ab, IgM and IgG increased to 100%, 96.7% and 93.3%, respectively, 2 weeks later. When the same antibody type was detected, no significant difference was observed between enzyme-linked immunosorbent assays and other forms of immunoassays.
A typical acute antibody response is induced during SARS-CoV-2 infection. Serology testing provides an important complement to RNA testing in the later stages of illness for pathogenic-specific diagnosis and helpful information to evaluate the adapted immunity status of patients.
A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti‐inflammatory properties. However, due to its poor anti‐inflammatory properties, its clinical use is limited. ...Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti‐inflammatory activities in vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)‐induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96 μM. Western blot research revealed that 14 decreased the concentration‐dependent expression of cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation‐associated proteins COX‐2 and INOS to compound 14.
The COVID-19 pandemic is associated with common mental health problems. However, evidence for the association between fear of COVID-19 and obsessive-compulsive disorder (OCD) is limited.
This study ...aimed to examine if fear of negative events affects Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores in the context of a COVID-19-fear-invoking environment.
All participants were medical university students and voluntarily completed three surveys via smartphone or computer. Survey 1 was conducted on February 8, 2020, following a 2-week-long quarantine period without classes; survey 2 was conducted on March 25, 2020, when participants had been taking online courses for 2 weeks; and survey 3 was conducted on April 28, 2020, when no new cases had been reported for 2 weeks. The surveys comprised the Y-BOCS and the Zung Self-Rating Anxiety Scale (SAS); additional items included questions on demographics (age, gender, only child vs siblings, enrollment year, major), knowledge of COVID-19, and level of fear pertaining to COVID-19.
In survey 1, 11.3% of participants (1519/13,478) scored ≥16 on the Y-BOCS (defined as possible OCD). In surveys 2 and 3, 3.6% (305/8162) and 3.5% (305/8511) of participants had scores indicative of possible OCD, respectively. The Y-BOCS score, anxiety level, quarantine level, and intensity of fear were significantly lower at surveys 2 and 3 than at survey 1 (P<.001 for all). Compared to those with a lower Y-BOCS score (<16), participants with possible OCD expressed greater intensity of fear and had higher SAS standard scores (P<.001). The regression linear analysis indicated that intensity of fear was positively correlated to the rate of possible OCD and the average total scores for the Y-BOCS in each survey (P<.001 for all). Multiple regressions showed that those with a higher intensity of fear, a higher anxiety level, of male gender, with sibling(s), and majoring in a nonmedicine discipline had a greater chance of having a higher Y-BOCS score in all surveys. These results were redemonstrated in the 5827 participants who completed both surveys 1 and 2 and in the 4006 participants who completed all three surveys. Furthermore, in matched participants, the Y-BOCS score was negatively correlated to changes in intensity of fear (r=0.74 for survey 2, P<.001; r=0.63 for survey 3, P=.006).
Our findings indicate that fear of COVID-19 was associated with a greater Y-BOCS score, suggesting that an environment (COVID-19 pandemic) × psychology (fear and/or anxiety) interaction might be involved in OCD and that a fear of negative events might play a role in the etiology of OCD.
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