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Lateral lymph node metastasis (LLNM) is associated with poor prognosis in patients with papillary thyroid cancer (PTC). The purpose of this study was to determine the risk factors for LLNM and establish prediction models that could individually assessed the risk of LLNM.A total of 619 PTC patients were retrospectively analyzed in our study. Univariate and multivariate analysis were performed for male and female patients, respectively, to assess relationships between clinicopathological features and LLNM. By integrating independent predictors selected by binary logistic regression modeling, preoperative and postoperative nomograms were developed to estimate the risk of LLNM.LLNM was detected in 80 of 216 male patients. Of 403 female patients, 114 had LLNM. The preoperative nomogram of male patients included three clinical variables: the number of foci, tuner size, and echogenic foci. In addition to the above three variables, the postoperative nomogram of male patients included extrathyroidal extension (ETE) detected in surgery, central lymph node metastasis (CLNM) and high-volume CLNM. The preoperative nomogram of female patients included the following variables: age, chronic lymphocytic thyroiditis (CLT), BRAF V600E, the number of foci, tumor size and echogenic foci. Variables such as CLT, BRAF V600E, the number of foci, tumor size, ETE detected in surgery, CLNM, high-volume CLNM and central lymph node ratio were included in the postoperative nomogram. Above Nomograms show good discrimination.Considering the difference in the incidence rate of LLNM between men and women, a separate prediction system should be established for patients of different genders. These nomograms are helpful in promoting the risk stratification of PTC treatment decision-making and postoperative management.

We herein developed a new ICD inducer VC@cLAV, which would induce strong ICD through elevating ROS in cancer cells for the immunotherapy of metastatic tumors while acting as an anti-oxidant in non-cancer cells for cytoprotection.

OBJECTIVE Acute ischemic stroke patients with large-vessel occlusion and good collateral blood flow have significantly better outcomes than patients with poor collateral circulation. The purpose of this study was to evaluate the cost-effectiveness of endovascular thrombectomy (EVT) based on collateral status and, in particular, to analyze its effectiveness in ischemic stroke patients with poor collaterals. METHODS A decision analysis study was performed with Markov modeling to estimate the lifetime quality-adjusted life-years (QALYs) and associated costs of EVT based on collateral status. The study was performed over a lifetime horizon with a societal perspective in the US setting. Base-case analysis was done for good, intermediate, and poor collateral status. One-way, two-way, and probabilistic sensitivity analyses were performed. RESULTS EVT resulted in greater effectiveness of treatment compared to no EVT/medical therapy (2.56 QALYs in patients with good collaterals, 1.88 QALYs in those with intermediate collaterals, and 1.79 QALYs in patients with poor collaterals), which was equivalent to 1050, 771, and 734 days, respectively, in a health state characterized by a modified Rankin Scale (mRS) score of 0–2. EVT also resulted in lower costs in patients with good and intermediate collaterals. For patients with poor collateral status, the EVT strategy had higher effectiveness and higher costs, with an incremental cost-effectiveness ratio (ICER) of $44,326/QALY. EVT was more cost-effective as long as it had better outcomes in absolute numbers in at least 4%–8% more patients than medical management. CONCLUSIONS EVT treatment in the early time window for good outcome after ischemic stroke is cost-effective irrespective of the quality of collateral circulation, and patients should not be excluded from thrombectomy solely on the basis of collateral status. Despite relatively lower benefits of EVT in patients with poor collaterals, even smaller differences in better outcomes have significant long-term financial implications that make EVT cost-effective.

There is growing evidence that partial nephrectomy (PN) and percutaneous cryoablation (PCA) yield comparable outcomes for patients with cT1a renal cell carcinoma (RCC), although the cost-effectiveness of both treatments still needs to be assessed.To perform a cost-effectiveness analysis of PN and PCA for patients with cT1a RCC.A decision analysis was created over a 5-year span from a healthcare payer's perspective computing expected costs and outcomes of PN and PCA in terms of quality-adjusted life-years (QALYs) and incremental cost-effectiveness (ICER). After each treatment, the following states were modelled using data from the recent literature: procedural complications, no evidence of disease (NED), local recurrence, metastases, and death from RCC- or non-RCC-related causes. Probabilistic and deterministic sensitivity analyses were performed.PCA and PN yielded health benefits of 3.68 QALY and 3.67 QALY. Overall expected costs were $20,491 and $26,478 for PCA and PN. On probabilistic sensitivity analysis, PCA was more cost-effective than PN in 84.78% of Monte Carlo simulations. PCA was more cost-effective until its complication risk was at least 38% higher than PN. PCA was more cost-effective than PN when (i) PCAs annual local recurrence risk was3.5% higher than that of PN in absolute values; (ii) PCAs annual metastatic risk was1.0% higher than that of PN; or (iii) PCAs annual cancer-specific mortality risk0.65% higher than that of PN. PCA remained cost-effective until its procedural cost is above $13,875.PCA appears to be more cost-effective than PN for the treatment of cT1a RCC, although the currently available evidence is of limited quality. PCA may be the better treatment strategy in the majority of scenarios varying procedural complications, recurrence, metastatic risk, and RCC-mortality in clinically plausible ranges.• For patients with cT1a RCCs, PCA yields a comparable health benefit at lower costs compared to PN, making PCA the dominant and therefore more cost-effective treatment strategy over PN. • PCA was more cost-effective than PN when (i) PCAs annual local recurrence risk was3.5% higher than PN in absolute values; (ii) PCAs annual metastatic risk was1.0% higher than PN; or (iii) PCAs annual cancer-specific mortality risk0.65% higher than PN. • PCA is more cost-effective than PN for the treatment of cT1a RCC, and it remained so in the majority of scenarios varying procedural complications, recurrence, metastatic risk, and RCC mortality.

Background. Rheumatoid arthritis (RA) is recognized as a chronic inflammatory disease featured by pathological synovial inflammation. Currently, the underlying pathophysiological mechanisms of RA remain unclear. In the study, we attempted to explore the underlying mechanisms of RA and provide potential targets for the therapy of RA via bioinformatics analysis. Methods. We downloaded four microarray datasets (GSE77298, GSE55235, GSE12021, and GSE55457) from the GEO database. Firstly, GSE77298 and GSE55457 were identified DEGs by the “limma” and “sva” packages of R software. Then, we performed GO, KEGG, and GSEA enrichment analyses to further analyze the function of DEGs. Hub genes were screened using LASSO analysis and SVM-RFE analysis. To further explore the differences of the expression of hub genes in healthy control and RA patient synovial tissues, we calculated the ROC curves and AUC. The expression levels of hub genes were verified in synovial tissues of normal and RA rats by qRT-PCR and western blot. Furthermore, the CIBERSORTx was implemented to assess the differences of infiltration in 22 immune cells between normal and RA synovial tissues. We explored the association between hub genes and infiltrating immune cells. Results. CRTAM, CXCL13, and LRRC15 were identified as RA’s potential hub genes by machine learning and LASSO algorithms. In addition, we verified the expression levels of three hub genes in the synovial tissue of normal and RA rats by PCR and western blot. Moreover, immune cell infiltration analysis showed that plasma cells, T follicular helper cells, M0 macrophages, M1 macrophages, and gamma delta T cells may be engaged in the development and progression of RA. Conclusions. In brief, our study identified and validated that three hub genes CRTAM, CXCL13, and LRRC15 might involve in the pathological development of RA, which could provide novel perspectives for the diagnosis and treatment with RA.

Future automotive emission regulations are becoming increasingly dependent on off-cycle (acquired on road and referred to as “real-world”) driving and testing. This was driven in part by the often-observed fact that laboratory emission drive cycles (developed to evaluate a vehicle’s emissions on a chassis dynamometer) may not fully capture the nature of real-world driving. As a result, portable emission measurement systems were developed that could be fit in the trunk of a vehicle, but were relatively large, expensive, and complex to operate. It would be advantageous to have low-cost and simple to operate on-board sensors that could be used in a gasoline powertrain to monitor important criteria emission species, such as NOx. The electrochemical NOx sensor is often used for emissions control systems in diesel powertrains and a proven technology for application to the relatively harsh environment of automotive exhaust. However, electrochemical NOx sensors are nearly equally sensitive to both NOx and NH3, setting up an implicit classification problem that must be solved before they can accurately measure NOx. In this work, we develop a machine-learning model to classify the output of a NOx sensor in a gasoline powertrain. A model generalization study is conducted, and the model is found to be ~96% accurate and able to predict NOx mass emitted over a drive cycle within ~9% of a perfectly classified NOx sensor.

Background. Exenatide is a glucagon-like peptide-1 receptor agonist that can reduce body weight. This study aimed to determine the efficacy of exenatide on body mass index (BMI) reduction in patients with type 2 diabetes mellitus (T2DM) with differing baseline body weight, blood glucose, and atherosclerotic status and to determine if there is a correlation between BMI reduction and cardiometabolic indices in these patients. Methods. This retrospective cohort study used data from our randomized controlled trial. A total of 27 T2DM patients treated with combination therapy of exenatide twice daily and metformin for 52 weeks were included. The primary endpoint was a change in the BMI from the baseline to week 52. The secondary endpoint was a correlation between BMI reduction and cardiometabolic indices. Findings. The BMIs of overweight and obesity patients and those with glycated hemoglobin (HbA1c) ≥ 9% significantly decreased −1.42 ± 1.48 kg/m2 P = 0.015 and −0.87 ± 0.93 kg/m2 P = 0.003 , respectively, at the baseline after 52 weeks of treatment. There was no reduction in BMI in patients with normal weight, HbA1c

Background Migraine is one of the world’s most prevalent and disabling diseases. Despite huge advances in neuroimaging research, more valuable neuroimaging markers are still urgently needed to provide important insights into the brain mechanisms that underlie migraine symptoms. We therefore aim to investigate the regional iron deposition in subcortical nuclei of migraineurs as compared to controls and its association with migraine-related pathophysiological assessments. Methods A total of 200 migraineurs (56 chronic migraine [CM], 144 episodic migraine [EM]) and 41 matched controls were recruited. All subjects underwent MRI and clinical variables including frequency/duration of migraine, intensity of migraine, 6-item Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS), and Pittsburgh Sleep Quality Index (PSQI) were recorded. Quantitative susceptibility mapping was employed to quantify the regional iron content in subcortical regions. Associations between clinical variables and regional iron deposition were studied as well. Results Increased iron deposition in the putamen, caudate, and nucleus accumbens (NAC) was observed in migraineurs more than controls. Meanwhile, patients with CM had a significantly higher volume of iron deposits compared to EM in multiple subcortical nuclei, especially in NAC. Volume of iron in NAC can be used to distinguish patients with CM from EM with a sensitivity of 85.45% and specificity of 71.53%. As the most valuable neuroimaging markers in all of the subcortical nuclei, higher iron deposition in NAC was significantly associated with disease progression, and higher HIT-6, MIDAS, and PSQI. Conclusions These findings provide evidence that iron deposition in NAC may be a biomarker for migraine chronicity and migraine-related dysfunctions, thus may help to understand the underlying vascular and neural mechanisms of migraine. Trial registration ClinicalTrials.gov, number NCT04939922.

Autophagy-lysosome system plays a variety of roles in human cancers. In addition to being implicated in metabolism, it is also involved in tumor immunity, remodeling the tumor microenvironment, vascular proliferation, and promoting tumor progression and metastasis. Transcriptional factor EB (TFEB) is a major regulator of the autophagy-lysosomal system. With the in-depth studies on TFEB, researchers have found that it promotes various cancer phenotypes by regulating the autophagolysosomal system, and even in an autophagy-independent way. In this review, we summarize the recent findings about TFEB in various types of cancer (melanoma, pancreatic ductal adenocarcinoma, renal cell carcinoma, colorectal cancer, breast cancer, prostate cancer, ovarian cancer and lung cancer), and shed some light on the mechanisms by which it may serve as a potential target for cancer treatment.

Diminishing phosphorus resources worldwide requires developing new technologies to recover phosphorus (P) from wastewaters. A lab-scale electrolytic reactor with a magnesium anode was investigated to remove NH

The methodological development of this paper is motivated by the need to address the following scientific question: does the issuance of heat alerts prevent adverse health effects? Our goal is to address this question within a causal inference framework in the context of time series data. A key challenge is that causal inference methods require the overlap assumption to hold: each unit (i.e., a day) must have a positive probability of receiving the treatment (i.e., issuing a heat alert on that day). In our motivating example, the overlap assumption is often violated: the probability of issuing a heat alert on a cooler day is zero. To overcome this challenge, we propose a stochastic intervention for time series data which is implemented via an incremental time-varying propensity score (ItvPS). The ItvPS intervention is executed by multiplying the probability of issuing a heat alert on day $t$ -- conditional on past information up to day $t$ -- by an odds ratio $\delta_t$. First, we introduce a new class of causal estimands that relies on the ItvPS intervention. We provide theoretical results to show that these causal estimands can be identified and estimated under a weaker version of the overlap assumption. Second, we propose nonparametric estimators based on the ItvPS and derive an upper bound for the variances of these estimators. Third, we extend this framework to multi-site time series using a spatial meta-analysis approach. Fourth, we show that the proposed estimators perform well in terms of bias and root mean squared error via simulations. Finally, we apply our proposed approach to estimate the causal effects of increasing the probability of issuing heat alerts on each warm-season day in reducing deaths and hospitalizations among Medicare enrollees in $2,837$ U.S. counties., Comment: 31 pages, 3 figures, 2 tables

Background Immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura are both causes of thrombocytopenia. Recognizing thrombotic thrombocytopenic purpura is crucial for subsequent treatment and prognosis. In clinical practice, corticosteroids and rituximab can be used to treat both immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura; plasma exchange therapy is the first-line treatment in thrombotic thrombocytopenic purpura, while corticosteroids are strongly recommended as first-line treatment in immune thrombocytopenic purpura. The differential diagnosis of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is essential in clinical practice. However, case reports have suggested that immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura can occur concurrently. Case presentation We report the case of a 32-year-old Asian female without previous disease who presented with pancytopenia, concurrent with immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura. The morphology of the megakaryocytes in the bone marrow indicated immune-mediated thrombocytopenia. The patient received glucocorticoid treatment, and her platelet count increased; however, schistocytes remained high during the course of the therapy. Further investigations revealed ADAMTS13 activity deficiency and positive ADAMTS13 antibodies. The high titer of antinuclear antibody and positive anti-U1-ribonucleoprotein/Smith antibody indicated a potential autoimmune disease. However, the patient did not fulfill the current criteria for systemic lupus erythematosus or mixed connective tissue disease. The patient responded well to plasma exchange therapy, and her platelet count remained normal on further follow-up. Conclusions Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is rare, but clinicians should be aware of this entity to ensure prompt medical intervention. Most of the reported cases involve young women. Human immunodeficiency virus infection, pregnancy, and autoimmune disease are the most common underlying conditions.

Impairment of vascular endothelial integrity is associated with various vascular diseases. Our previous studies demonstrated that andrographolide is critical to maintaining gastric vascular homeostasis, as well as to regulating pathological vascular remodeling. Potassium dehydroandrograpolide succinate (PDA), a derivative of andrographolide, has been clinically used for the therapeutic treatment of inflammatory diseases. This study aimed to determine whether PDA promotes endothelial barrier repair in pathological vascular remodeling. Partial ligation of the carotid artery in ApoE−/− mice was used to evaluate whether PDA can regulate pathological vascular remodeling. A flow cytometry assay, BRDU incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay and Matrigel-based tube formation assay were performed to determine whether PDA can regulate the proliferation and motility of HUVEC. A molecular docking simulation and CO-immunoprecipitation assay were performed to observe protein interactions. We observed that PDA induced pathological vascular remodeling characterized by enhanced neointima formation. PDA treatment significantly enhanced the proliferation and migration of vascular endothelial cells. Investigating the potential mechanisms and signaling pathways, we observed that PDA induced endothelial NRP1 expression and activated the VEGF signaling pathway. Knockdown of NRP1 using siRNA transfection attenuated PDA-induced VEGFR2 expression. The interaction between NRP1 and VEGFR2 caused VE-Cad-dependent endothelial barrier impairment, which was characterized by enhanced vascular inflammation. Our study demonstrated that PDA plays a critical role in promoting endothelial barrier repair in pathological vascular remodeling.

Although endoscopic dacryocystorhinostomy (DCR) is a standard procedure for nasolacrimal duct obstruction (NLDO), the failure rate remains approximately 10%. A small lacrimal sac is considered the main reason for surgical failure. We explored the efficacy of endoscopic DCR for the treatment of NLDO with a small lacrimal sac.The clinical data of 72 patients (88 eyes) diagnosed with NLDO and undergoing endoscopic DCR from 2012 to 2020, with at least 24 months of follow-up were retrospectively collected. Intraoperatively, the Rosenmüller valves were fully exposed, mucosal flaps were preserved to cover the naked bone, and a silicone tube was implanted if necessary. Postoperative intervention was performed if necessary. The main outcome measures were symptomatic improvement and objective ostium patency.Eighty-eight eyes of 72 patients were divided into two groups: the refractory group (34 patients, 47 eyes), with a small lacrimal sac (≤ 5 mm in diameter), and the simple group (38 patients, 41 eyes). Patients with small lacrimal sacs were more prone to bilateral eye disease than those in the simple group (P = 0.014) and required a longer postoperative follow-up (P 0.001). Refractory NLDO and simple NLDO had a success rate of 91.5% and 95.1%, respectively, with no significant difference.Endoscopic DCR for refractory NLDO with a small lacrimal sac could achieve a beneficial result by exposing the Rosenmüller valves, preserving mucosal flaps, implanting necessary intubation, and intervening postoperatively. Thus, a small lacrimal sac should not be regarded as a contraindication to surgery.

Oxidative stress is one of the major factors in induction of pancreatic β-cell apoptosis and diabetes. Here, we investigated systematically the roles of a proteoglycan (namely, FYGL) from Ganoderma lucidum in protection and repair of pancreatic β-cells against oxidative stress-induced injury and apoptosis on molecular, cellular and animal basis. FYGL in vitro had antioxidant activity in terms of scavenging of free radicals and reduction power. FYGL improved cells viability, insulin secretion, redox indicator expressions, and mitochondrial membrane potential in H

Carbohydrate metabolism of bacterial pathogens conducts crucial roles in regulating pathogenesis but the molecular mechanisms by which metabolisms and virulence are been modulated and coordinated remain to be illuminated. Here, we investigated in this regard Edwardsiella piscicida, a notorious zoonotic pathogen previously named E. tarda that could ferment very few PTS sugars including glucose, fructose, mannose, N-acetylglucosamine, and N-acetylgalactosamine. We systematically characterized the roles of each of the predicted 23 components of phosphotransferase system (PTS) with the respective in-frame deletion mutants and defined medium containing specific PTS sugar. In addition, PtsH was identified as the crucial PTS component potentiating the utilization of all the tested PTS sugars. Intriguingly, we also found that PtsH while not Fpr was involved in T3SS gene expression and was essential for the pathogenesis of E. piscicida. To corroborate this, His15 and Ser46, the two established PtsH residues involved in phosphorylation cascade, showed redundant roles in regulating T3SS yields. Moreover, PtsH was shown to facilitate mannose uptake and transform it into mannose-6-phosphate, an allosteric substrate established to activate EvrA to augment bacterial virulence. Collectively, our observations provide new insights into the roles of PTS reciprocally regulating carbohydrate metabolism and virulence gene expression. KEY POINTS: • PTS components' roles for sugar uptake are systematically determined in Edwardsiella piscicida. • PtsH is involved in saccharides uptake and in the regulation of E. piscicida's T3SS expression. • PtsH phosphorylation at His15 and Ser46 is essential for the T3SS expression and virulence.

Background The aim of this study was to observe the effectiveness of botulinum toxin type A (BTA) in the treatment of intermittent exotropia (IXT) in children compared with strabismus surgery. Methods One hundred forty-four children with a clear diagnosis of IXT and an indication for surgery were eligible for inclusion. Subjects were divided into two groups based on parental decision: the BTA injection group (injection group) or the conventional surgery group (surgery group). All cases were followed up for 6 months. The primary outcome was a comparison of the success rate (deviation between − 10 and + 10 PD) between the two groups at 6 months after the initial treatment. Secondary outcomes included change in deviation, visual function, and post-surgical complications. Results Seventy-two patients were enrolled in each group. At 6-month follow-up, there was no significant difference in the success rate between the injection and surgery groups (52.8% vs 66.7%, P = 0.13; postoperative deviation − 12.22 ± 10.80 PD vs − 9.17 ± 10.30 PD, P = 0.09). The binocular Visual function, except for near stereoacuity, improved after treatment in both groups, while the fusion recovery rate was higher in the surgical group (68.1% vs 95.8%, P Conclusions BTA is as effective as surgery in the treatment of IXT in children, but the recovery of the fusion is lower than surgery. Trial registration The study has completed the clinical registration on (ChiCTR-INR-17013777).

In this paper, an identical parallel machine scheduling problem with step-deteriorating jobs is considered to minimize the weighted sum of tardiness cost and extra energy consumption cost. In particular, the actual processing time of a job is assumed to be a step function of its starting time and its deteriorating threshold. When the starting time of a job is later than its deteriorating threshold, the job faces two choices: (1) maintaining its status in holding equipment and being processed with a base processing time and (2) consuming an extra penalty time to finish its processing. The two work patterns need different amounts of energy consumption. To implement energy-efficient scheduling, the selection of the pre-processing patterns must be carefully considered. In this paper, a mixed integer linear programming (MILP) model is proposed to minimize the total tardiness cost and the extra energy cost. Decomposition approaches based on logic-based Benders decomposition (LBBD) are developed by reformulating the studied problem into a master problem and some independent sub-problems. The master problem is relaxed by only making assignment decisions. The sub-problems are to find optimal schedules in the job-to-machine assignments given by the master problem. Moreover, MILP and heuristic based on Tabu search are used to solve the sub-problems. To evaluate the performance of our methods, three groups of test instances were generated inspired by both real-world applications and benchmarks from the literature. The computational results demonstrate that the proposed decomposition approaches can compute competitive schedules for medium- and large-size problems in terms of solution quality. In particular, the LBBD with Tabu search performs the best among the suggested four methods.

OBJECTIVE The utility of endovascular thrombectomy (EVT) in patients with acute ischemic stroke, large vessel occlusion (LVO), and low Alberta Stroke Program Early CT Scores (ASPECTS) remains uncertain. The objective of this study was to determine the health outcomes and cost-effectiveness of EVT versus medical management in patients with ASPECTS < 6. METHODS A decision-analytical study was performed with Markov modeling to estimate the lifetime quality-adjusted life-years (QALYs) and associated costs of EVT-treated patients compared to medical management. The study was performed over a lifetime horizon with a societal perspective in the US setting. RESULTS The incremental cost-effectiveness ratios were $412,411/QALY and $1,022,985/QALY for 55- and 65-year-old groups in the short-term model. EVT was the long-term cost-effective strategy in 96.16% of the iterations and resulted in differences in health benefit of 2.21 QALYs and 0.79 QALYs in the 55- and 65-year-old age groups, respectively, equivalent to 807 days and 288 days in perfect health. EVT remained the more cost-effective strategy when the probability of good outcome with EVT was above 16.8% or as long as the good outcome associated with the procedure was at least 1.6% higher in absolute value than that of medical management. EVT remained cost-effective even when its cost exceeded $100,000 (threshold was $108,036). Although the cost-effectiveness decreased with age, EVT was cost-effective for 75-year-old patients as well. CONCLUSIONS This study suggests that EVT is the more cost-effective approach compared to medical management in patients with ASPECTS < 6 in the long term (lifetime horizon), considering the poor outcomes and significant disability associated with nonreperfusion.

Droplets icing has important applications in real life. The icing process of droplets on microstructure is explored based on the MDPDE method in this study. Firstly, the correctness of the heat transfer model was verified by one-dimensional heat conduction simulation, and then the feasibility of the phase change model was verified by investigating the icing process of droplets. The influence of cold surface temperature, droplet volume and contact angle on freezing time of droplets was discussed, and it was found that the temperature of cold surfaces had a greater effect on freezing. We finally explored the influence of different microstructure surfaces on the icing of droplets, and results showed that the presence of microstructures greatly enhanced the anti-icing effect of the surface. In our research, the contact angle is a relatively large factor affecting the icing of droplets. In addition, it was discovered that the droplet had the strongest ability to delay freezing on the surface of triangle microstructures with a contact angle of 157.1°.

Accurate prediction of topographical correlation between craniopharyngiomas (CPs) and hypothalamus is important for treatment. This study sought to develop a predicting tool based on preoperative-MRI through radiological–surgical–pathological–outcome analysis. Third ventricle floor (TVF), mammillary bodies and cerebral peduncle were evaluated through preoperative-MRI. An eagle-head-like sign named “eagle sign” was observed. Normal TVF on sagittal-MRI was defined as the baseline. Variants of the sign were analyzed by comparing with the baseline and corresponding correlations of CPs with hypothalamus were verified using intraoperative records, histopathology and outcome evaluation. A total of 146 CPs patients, who undergone endoscopic endonasal procedure were divided into four groups based on the variants of “eagle sign”. Group A: 24 patients with the upward sign; group B: 81 with the downward sign; group C: 21 with the anterior TVF upward sign and group D: 20 with the unidentifiable sign. Surgical–pathological analysis showed significant correlations between 95.8% CPs in group A and 95.2% in group C with tumor topography and tumor adherence to the hypothalamus. These CPs had their origins beneath the hypothalamus. In contrast, groups B and D, with hypothalamic origin, showed hypothalamic infiltration by tumor in 97.5% and 95% of cases in groups B and D, respectively. Outcomes of groups A and C were relatively better than groups B and D. Predictive sensitivity and specificity of “eagle sign” were more than 90%. “Eagle sign” is an accurate tool for predicting topographic correlations between CPs and hypothalamus with high sensitivity and specificity.

Gastric cancer (GC) is common in East Asia, yet its molecular and pathogenic mechanisms remain unclear. Circular RNAs (circRNAs) are differentially expressed in GC and may be promising biomarkers. Here, we investigated the role and regulatory mechanism of circTMC5 in GC. CircTMC5 expression was detected in human GC and adjacent tissues using microarray assays and qRT-PCR, while the clinicopathological characteristics of patients with GC were used to assess its diagnostic and prognostic value. The circTMC5/miR-361-3p/RABL6 axis was examined in vitro and vivo, and the immune roles of RABL6 were evaluated using bioinformatics analyses and immunohistochemistry (IHC). CircTMC5 was highly expressed in GC tissues, plasma, and cell lines, and was closely related to histological grade, pathological stage, and T classification in patients with GC. CircTMC5 expression was also an independent prognostic factor for GC and its combined detection with carcinoembryonic antigen may improve GC diagnosis. Low circTMC5 expression correlated with good prognosis, inhibited GC cell proliferation, and promoted apoptosis. Mechanistically, circTMC5 overexpression promoted GC cell proliferation, invasion, and metastasis but inhibited apoptosis by sponging miR-361-3p and up-regulating RABL6 in vitro and vivo, whereas miR-361-3p up-regulation had the opposite effects. RABL6 was highly expressed in GC and was involved in immune regulation and infiltration in GC. CircTMC5 promotes GC and sponges miR-361-3p to up-regulate RABL6 expression, thus may have diagnostic and prognostic value in GC. RABL6 also displays therapeutic promise due to its role in the immune regulation of GC.

Mitochondrial dysfunction has been hypothesized to play a central role in the pathobiology of nonalcoholic fatty liver disease (NAFLD). Thus, maintenance of mitochondria homeostasis and function is important for NAFLD treatment. Mitophagy, a process that selectively clears damaged or dysfunctional mitochondria through autophagic machinery, is beneficial for mitochondrial homeostasis. Notably, strategies that regulate mitophagy exert beneficial effects in preclinical experiments. Traditional Chinese medicine (TCM) is a natural product including active ingredients, extracts, and has great potential in the prevention and treatment of liver diseases. Given the importance of mitophagy, this review summarizes mitophagy-related pathways and the latest findings on the regulation of mitophagy in NAFLD. We also highlight the potential of TCM targeting mitophagy for the treatment of NAFLD.

In this study, different micro-aeration (MA) strategies for anaerobic digestion (AD) of poultry litter (PL) and wheat straw (WS) were examined. MA at different stages (pretreatment, middle, pretreatment plus middle, and daily) in batch AD of WS showed that daily MA had the highest increase (16.5 %) of the cumulative methane yield (CMY) compared to the control. Batch co-digestion (Co-AD) of WS and PL with daily MA obtained a furtherly improved (15.1 %) CMY of 225.44 N mL CH

A convenient and rapid detection method for methanol in ethanol remains a major challenge due to their indistinguishable physical properties. Herein, a novel fluorescence probe based on perovskite was successfully designed to overcome this bottleneck. We report a new zero-dimensional (0D) hybrid perovskite of [MP]

The increasing application of carbon nanomaterials has resulted in their inevitable release into the environment. Their toxic effects on plant roots require careful investigation. In the present study, alfalfa (Medicago sativa L.) was exposed to graphene oxide (GO) at levels of 0.2 %, 0.4 %, and 0.6 % (w/w) in potting soil. This study aims to better understand the impact of GO on the root growth, structure, and physiology of alfalfa in the soil matrix. The results demonstrated that GO significantly affected the development and structure of alfalfa roots, and the effect varied with GO level. The highest level of GO (0.6 %) reduced the root length, diameter, volume, dry weight, number of lateral roots, and root activity by 36.1 %, 31.3 %, 60.0 %, 89.6 %, 55.8 %, and 72.3 % (p 0.05), respectively, and the vascular cylinder diameter, periderm thickness, vessel diameter, and phellem thickness decreased by 51.5 %, 50.7 %, 80.9 %, and 49.1 % (p 0.05), respectively. These observations might be associated with GO-induced oxidative stress, which was indicated by the activity of antioxidant enzymes. Furthermore, high GO levels (0.4 % and 0.6 %) inhibited the uptake of N, P, K, Mg, Zn, Fe, Mo, Si, and B in roots. Our findings indicate that GO at high levels has a negative impact on root growth and development by inducing oxidative stress, structural impairment, and nutritional imbalance. Careful soil GO management should be emphasized.

BACKGROUND The aim of this study was to investigate the clinical effect of anti-arcuate suture in treating pernicious placenta previa. MATERIAL AND METHODS We selected 81 patients diagnosed with singleton pregnancy with pernicious placenta previa at Suzhou Municipal Hospital from January 2015 to December 2018. Among them, 41 patients treated with anti-arcuate suture were assigned to the study group, and the other 40 patients were treated with conventional suture were assigned to the control group. RESULTS Compared with traditional suture, anti-arcuate suture significantly reduced blood loss and blood transfusion, and anti-arcuate suture also reduced postoperative complications. In the control group, 7 women underwent hysterectomy, but only 1 woman underwent hysterectomy in the study group. CONCLUSIONS Anti-arcuate suture in pernicious placenta previa can reduce postpartum hemorrhage and reduce postoperative complications.

It is controversial whether there is a different risk of recurrence between two histological subtypes in craniopharyngioma (CP) patients. Some reported that adamantinomatous craniopharyngioma (ACP) had a higher risk of recurrence than papillary craniopharyngioma (PCP), but others reported that there is no significant difference between them. So, we conducted this systematic review and meta-analysis to determine the association between the histological subtype of CP and the rate of recurrence. A comprehensive literature search was undertaken in PubMed, EMBASE, and Web of Science for all English articles published up to November 2020. Recurrence data stratified by ACP and PCP were extracted from studies meeting inclusion criteria. A pooled analysis of the association between the histological subtype of craniopharyngioma and rates of recurrence was performed. Thirteen articles containing 974 patients were included. When stratified by two pathological subtypes, the total recurrence rate of ACP was 26.0% and PCP was 14.1%, which showed ACP associated with a higher risk of tumor recurrence than PCP (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.36, 3.30, P = 0.00). This is the first meta-analysis focusing on histological subtypes of CP. PCP associates with a lower risk of recurrence than ACP, indicating that ACP could act as one of recurrence risk factors for CP patients. Nevertheless, large sample size and well-designed multicenter studies in which the other clinical variables are controlled to determine the histological subtype of CP as an independent recurrence risk factor are needed.

BACKGROUND Cervical cancer is the fourth commonest malignancy in women around the world. It represents the second most commonly diagnosed cancer in South East Asian women, and an important cancer death cause in women of developing nations. Data collected in 2018 revealed 5690000 cervical cancer cases worldwide, 85% of which occurred in developing countries. AIM To assess self-perceived burden (SPB) and related influencing factors in cervical cancer patients undergoing radiotherapy. METHODS Patients were prospectively included by convenient sampling at The Fifth Affiliated Hospital of Sun Yat-Sen University, China between March 2018 and March 2019. The survey was completed using a self-designed general information questionnaire, the SPB scale for cancer patients, and the self-care self-efficacy scale, Strategies Used by People to Promote Health, which were delivered to patients with cervical cancer undergoing radiotherapy. Measurement data are expressed as the mean ± SD. Enumeration data are expressed as frequencies or percentages. Caregivers were the spouse, offspring, and other in 46.4, 40.9, and 12.7%, respectively, and the majority were male (59.1%). As for pathological type, 90 and 20 cases had squamous and adenocarcinoma/adenosquamous carcinomas, respectively. Stage IV disease was found in 12 (10.9%) patients. RESULTS A total of 115 questionnaires were released, and five patients were excluded for too long evaluation time (n = 2) and the inability to confirm the questionnaire contents (n = 3). Finally, a total of 110 questionnaires were collected. They were aged 31-79 years, with the 40-59 age group being most represented (65.4% of all cases). Most patients were married (91.8%) and an overwhelming number had no religion (92.7%). Total SPB score was 43.13 ± 16.65. SPB was associated with the place of residence, monthly family income, payment method, transfer status, the presence of radiotherapy complications, and the presence of pain (P < 0.05). The SPB and self-care self-efficacy were negatively correlated (P < 0.01). In multivariate analysis, self-care self-efficacy, place of residence, monthly family income, payment method, degree of radiation dermatitis, and radiation proctitis were influencing factors of SPB (P < 0.05). CONCLUSION Patients with cervical cancer undergoing radiotherapy often have SPB. Self-care self-efficacy scale, place of residence, monthly family income, payment method, and radiation dermatitis and proctitis are factors independently influencing SPB.

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy with extremely poor prognosis. Gemcitabine resistance is a major challenge in the treatment of PDAC. Here, we showed that LINC00460 was associated with the response to gemcitabine both in PDAC patients and PDAC-PDX. After knocking down LINC00460 in PDAC tumor cells, results of RNA sequencing followed by gene ontology analysis indicated that LINC00460 influenced the activity of growth factors and modified the extracellular matrix. FISH showed that LINC00460 is mostly located in the cytoplasm. Results of RNA pull-down, LC-MS/MS, RIP, and immunoblotting confirmed that LINC00460 could directly bind to PDAP1. Furthermore, we demonstrated that LINC00460 mediated the cellular communication of PDAC tumor cells and CAFs by PDAP1/PDGFA/PDGFR signaling pathway and regulated the gemcitabine-resistance function of CAFs, which could be reversed by treatment with a PDGFR inhibitor (crenolanib). PDAC-PDX tumors with lower expression of LINC00460 showed a better response to gemcitabine plus crenolanib treatment. Our finding supported the application of LINC00460 in precision medicine that uses gemcitabine plus crenolanib to treat PDAC with low expression of LINC00460.

Waterborne ammonia is one of the crucial issues that limited production and animal health in aquaculture. Ammonia-tolerant varieties are highly desired in intensive fish farming. Screening for the key regulatory genes of ammonia tolerance is essential for variety breeding. According to the previous hypothesis, Rh glycoproteins play an important role in ammonia excretion in teleosts. However, the ammonia defensive mechanisms are not well described at present for large-scale loach (Paramisgurnus dabryanus), a typical air-breathing and commercially important fish in East Asia. Here we show that the transcription of Rh glycoprotein-related genes was significantly affected by ammonia exposure in this species. Probit analysis showed that 96 h-LC

ObjectiveTo determine the effects of alanine transaminase (ALT) levels on the screening failure rates or “no calls” due to low fetal fraction (FF) to obtain a result in non-invasive prenatal screening (NIPS).MethodsNIPS by sequencing and liver enzyme measurements were performed in 7,910 pregnancies at 12–26 weeks of gestation. Univariate and multivariable regression models were used to evaluate the significant predictors of screening failure rates among maternal characteristics and relevant laboratory parameters.ResultsOf the 7,910 pregnancies that met the inclusion criteria, 134 (1.69%) had “no calls.” Multiple logistic regression analysis demonstrated that increased body mass index, ALT, prealbumin, albumin levels, and in vitro fertilization (IVF) conception rates were independently associated with screening failures. The test failure rate was higher (4.34 vs. 1.41%; P < 0.001) in IVF pregnancies relative to those with spontaneous conceptions. Meanwhile, the screening failure rates increased with increasing ALT levels from 1.05% at ≤10 U/L to 3.73% at >40 U/L. In particular, IVF pregnancies with an ALT level of >40 U/L had a higher test failure rate (9.52%). Compared with that for an ALT level of ≤10 U/L, the adjusted odds ratio of “no calls” for ALT levels of 10–20, 21–40, and >40 U/L was 1.204 [95% confidence interval (CI), 0.709–2.045], 1.529 (95% CI, 0.865–2.702), and 2.764 (95% CI, 1.500–5.093) (Ptrend < 0.001), respectively.ConclusionsIncreased ALT and IVF conceptions were associated with a higher screening failure rates in NIPS. Therefore, a feasible strategy to adjust these factors to reduce the probability of “no calls” due to low FF would be of great clinical significance.

We aimed to determine the breakpoint of cycloserine (CS) susceptibility in MGIT and to describe the molecular characteristics of CS-resistant Mycobacterium tuberculosis (MTB) isolates.A total of 124 MTB isolates were recruited in our analysis. Minimum inhibitory concentration (MIC) was determined using the MGIT system. The mutations of MTB isolates within alr, ddl, ald, and cycA, potentially conferring CS resistance were analyzed by the whole-genome sequencing.In vitro drug susceptibility testing of isolates with doubling concentrations of CS revealed that the modal MIC values was 4 mg/L for MGIT, accounting for 35.5% (44/124) of isolates tested. Seven isolates harbored mutations conferring CS resistance, consisting of five with alr mutations and two with ald mutations. On the basis of the MIC distributions of wild-type and resistotype populations, we proposed a tentative epidemiologic cut-off value of 16 mg/l. The proportion of CS resistance in extensively drug-resistant TB was significantly higher than that of multidrug-resistant TB.In conclusion, we propose critical concentration for MGIT 960 to properly diagnose CS-resistant MTB and demonstrate that mutations in alr and ald genes are the major mechanism conferring CS resistance in clinical isolates.

We performed this study to investigate the diagnostic performance of prostate-specific antigen density (PSAD) in a multicenter cohort of the Chinese Prostate Cancer Consortium. Outpatients with prostate-specific antigen (PSA) levels ≥4.0 ng ml−1 regardless of digital rectal examination (DRE) results or PSA levels

Our previous study reported that mesenchymal stem cells (MSCs) accelerated the wound healing process through anti-inflammatory, anti-apoptotic, and pro-angiogenetic effects in a rodent skin excision model. NF3 is a twin-herb formula, which presents similar effects in promoting wound healing. Research focusing on the interaction of MSCs and Chinese medicine is limited. In this study, we applied MSCs and the twin-herb formula to the wound healing model and investigated their interactions. Wound healing was improved in all treatment groups (MSCs only, NF3 only, and MSCs + NF3). The combined therapy further enhanced the effect: more GFP-labelled ADMSCs, collagen I and collagen III expression, Sox9 positive cells, and CD31 positive cells, along with less ED-1 positive cells, were detected; the expressions of proinflammatory cytokine IL-6 and TNF-α were downregulated; and the expression of anti-inflammatory cytokine IL-10 was upregulated. In vitro, NF3 promoted the cell viability and proliferation ability of MSCs, and a higher concentration of protein was detected in the NF3-treated supernatant. A proteomic analysis showed there were 15 and 22 proteins in the supernatants of normal ADMSCs and NF3-treated ADMSCs, respectively. After PCR validation, the expressions of 11 related genes were upregulated. The results of a western blot suggested that the TGFβ/Smad and Wnt pathways were related to the therapeutic effects of the combined treatment. Our study suggests for the first time that NF3 enhanced the therapeutic effect of MSCs in the wound healing model and the TGFβ/Smad and Wnt pathways were related to the procedure.

The pancreatic β-cell death or dysfunction induced by oxidative stress plays an important effect on the development and progression of diabetes mellitus. Based on our previous findings, a natural proteoglycan extracted from Ganoderma Lucidum, named FYGL, could treat T2DM in vivo. In this study, we investigated the effects of FYGL on STZ-induced apoptosis of INS-1 cells and its underlying mechanisms. The results showed that FYGL significantly improved the cell viability and alleviated the apoptosis in STZ-treated INS-1 cells. Moreover, FYGL markedly decreased the intracellular ROS accumulation and NO release, and deactivated NF-κB, JNK, and p38 MAPK signaling pathways in STZ-induced INS-1 cells. Furthermore, FYGL improved the insulin secretion through inhibiting the activation of JNK and improving the expression of Pdx-1 in INS-1 cells damaged by STZ. These results indicated that FYGL could protect pancreatic β-cells against apoptosis and dysfunction, and be used as a promising pharmacological medicine for diabetes management.Abbreviations: T2DM: type 2 diabetes mellitus; FYGL: Fudan-Yueyang G. lucidum; ROS: reactive oxygen species; NO: reactive oxygen species; NF-κB: nuclear factor kappa beta; JNK: c-jun N-terminal kinase; MAPK: mitogen-activated protein kinase; Pdx-1: Pancreatic duodenal homeobox 1

The steatosis and resultant oxidative stress and apoptosis play the important roles in the progression of nonalcoholic fatty liver disease (NAFLD), therefore, searching for the effective drugs against NAFLD has been a hot topic. In this work, we investigated a hyperbranched proteoglycan, namely FYGL extracted from Ganoderma lucidum, inhibiting the palmitic acid (PA)-induced steatosis in HepG2 hepatocytes. FYGL compose of hydrophilic polysaccharide and lipophilic protein. Both moieties conclude the reductive residues, such as glucose and cystine, making FYGL capable of anti-oxidation. Herein, we demonstrated that FYGL can significantly inhibit the steatosis, i.e., decrease the contents of triglycerides (TG) and total cholesterol (TC) in hepatic cells on the mechanism of increasing the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), therefore inhibiting the expressions of sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN), furthermore leading to the carnitine palmitoyl transferase-1 (CPT-1) expression increased against steatosis induced by fatty acids oxidation. Meanwhile, FYGL can alleviate reactive oxygen species (ROS) and malondialdehyde (MDA), promote superoxide dismutase (SOD) and total antioxidant capacity (T-AOC). Moreover, FYGL can prevent the cells from apoptosis by regulating the apoptosis-related protein expressions and alleviating oxidative stress. Notably, FYGL could significantly recover the cells activity and inhibit lactate dehydrogenase (LDH) release which were negatively induced by high concentration PA. These results demonstrated that FYGL has the potential functions to prevent the hepatocytes from lipid accumulation, oxidative stress and apoptosis, therefore against NAFLD.

Background and aim This investigation was aimed at disclosing whether SRPX2 affected pancreatic cancer (PC) chemoresistance by regulating PI3K/Akt/mTOR signaling. Methods Totally 243 PC patients were recruited, and they were incorporated into partial remission (PR) group, stable disease (SD) group and progressive disease (PD) group in accordance with their chemotherapeutic response. PC cell lines (i.e. AsPC1, Capan2, VFPAC-1, HPAC, PANC-1, BxPC-3 and SW1990) and human pancreatic ductal epithelial cell lines (hTERT-HPNE) were also collected. Results PC patients of SD + PD group were associated with higher post-chemotherapeutic SRPX2 level than PR group, and their post-chemotherapeutic SRPX2 level was above the pretherapeutic SRPX2 level (P < 0.05). PR population showed lower SRPX2 level after chemotherapy than before chemotherapy (P < 0.05). Besides high serum SRPX2 level and SRPX2 level change before and after chemotherapy were independent predictors of poor PC prognosis. Additionally, si-SRPX2 enhanced chemosensitivity of PC cell lines, and expressions of p-PI3K, p-AKT and p-mTOR were suppressed by si-SRPX2 (P < 0.05). IGF-1 treatment could changeover the impact of si-SRPX2 on proliferation, migration, invasion and chemoresistance of PC cells (P < 0.05). Conclusion The SRPX2-PI3K/AKT/mTOR axis could play a role in modifying progression and chemoresistance of PC cells, which might help to improve PC prognosis.

The medial wall of the cavernous sinus (CS) has a significant role in evaluation and treatment of pituitary adenomas. This study was conducted to clarify the fine architecture of the medial wall and medial compartment of the CS at both macro- and micro-levels in twenty-one human cadaveric heads by using the epoxy sheet plastination technique. The sellar part medial wall is an intact dural layer that separates the CS from the pituitary gland. This dural wall adhered to the diaphragma sellae and the periosteum of the sella turcica to form fibrous triangles. Eight micro-protrusions of the pituitary gland were found at both sides of that wall. The thickness of the sellar part medial wall at its central portion was significantly thinner than that at the other surrounding portions. From the superior view, tortuous intracavernous carotid arteries can be divided into outward bending type and inward bending type. The inward bending intracavernous carotid was apt to bent towards the central part of the sellar part medial wall, where there were usually wide and short fibrous bands with more densely stained connective tissues between them. The micro-protrusion of the pituitary gland in the medial wall of the CS could provide an anatomical basis for the occult tumor invasion and the recurrence of residual tumor. Different bending facing states of tortuous intracavernous carotid arteries in the lateral direction may be a factor of the determination of the direction of growth of pituitary tumors.