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Abstract Background Mild autonomous cortisol secretion (MACS) accounts for a significant proportion of adrenal incidentaloma. Current endocrinological screening tests for MACS are complex, particularly in areas with limited medical resources. This study aimed to develop a diagnostic tool based on leukocyte-related parameters to differentiate between MACS and non-functioning adrenal adenoma (NFA). Methods Inthis retrospective case-control study, propensity score-matching was used to select 567 patients from a cohort of 1108 patients (201 MACS, 907 NFA). External validation cohort included 52MACS and 48 NFA from two hospitals, which did not overlap with the modeling cohort patients. Leukocyte-related parameters were evaluated, and the diagnostic efficacy of each parameter was assessed by calculating Youden’s J index (J) and the area under the curve (AUC). The study population was divided into training and testing samples using a 10-fold cross-validation method. Machine learning (ML) and classification and regression tree (CART) model were established. Results After propensity score matching, 567 patients were enrolled, including 197 MACS and 370 NFA. With the exception of basophil percentage, all other parameters differed significantly between the two groups. Lymphocyte count, lymphocyte percentage, eosinophils count, eosinophils percentage, and basophil percentage were lower in the MACS group compared to the NFA group. Eosinophils percentage demonstrated the highest AUC (0.650), with a sensitivity of 51.3% and specificity of 73.2%. The ML model, based on multiple parameters,exhibited better performance in diagnosing MACS (sensitivity 76%, specificity 77.4%, and AUC 0.818). A clinically usable CART model achieved an AUC of 0.872, with a sensitivity of 95% and a specificity of 75.7%. In the validation cohort, the prediction accuracy of the ML model and the CART model were 0.784 and 0.798, respectively. Conclusion TheCART diagnostic model, constructed based on leukocyte-related parameters, could assist clinicians in distinguishing between MACS and NFA.

Recent studies demonstrate that lipid peroxidation-induced ferroptosis participates in 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47)-evoked neurotoxicity and cognitive dysfunction. Melatonin has been indicated to confer neuroprotection against brain diseases via its potent anti-ferroptotic effects. Therefore, this study aims to explore whether melatonin can mitigate BDE-47-elicited cognitive impairment via suppressing ferroptosis, and further delineate the underlying mechanisms. Our results found that melatonin administration effectively inhibited BDE-47-induced ferroptosis in mice hippocampi and murine hippocampal neuronal HT-22 cells. Acyl-CoA synthetase long-chain family member 4 (ACSL4), a key lipid metabolism enzyme dictating ferroptosis sensitivity, accompanied by higher MDA and lipid reactive oxygen species (ROS), was remarkably increased under BDE-47 stress, while melatonin supplementation could suppress the elevated ACSL4 in vivo and in vitro. Furthermore, melatonin facilitated lysosomal ACSL4 degradation through enhancing lysosome-associated membrane protein type 2a (LAMP2a) expression and chaperone-mediated autophagy (CMA) activity, while LAMP2a knockdown abrogated the positive effects of melatonin on ACSL4 elimination in BDE-47-treated HT-22 cells. Moreover, nuclear factor erythroid 2-related factor 2 (Nrf2) activation by melatonin contributed to LAMP2a upregulation and CMA of ACSL4 and subsequent neuronal ferroptosis. Importantly, melatonin, CMA activator CA77.1, and ACSL4 inhibitor rosiglitazone (RSG) administration substantially attenuated neuronal/synaptic injury and cognitive deficits following BDE-47 exposure. Taken together, these findings revealed that melatonin could prevent BDE-47-provoked ferroptosis in the hippocampal neurons and mitigate cognitive dysfunction by facilitating ACSL4 degradation via Nrf2-chaperone-mediated autophagy. Therefore, melatonin might be a potential candidate for treating BDE-47-elicited neurotoxicity and neurobehavioral disorder.

Oxidative stress, caused by an imbalance between the generation of reactive oxygen species (ROS) and the body’s intrinsic antioxidant defenses, plays a critical role in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s. Beyond these conditions, recent evidence indicates that dysregulated redox balance is implicated in neuropsychiatric disorders, including schizophrenia, major depressive disorder, and anxiety disorders. Preclinical and clinical studies have demonstrated the potential of antioxidants, such as N-acetylcysteine, sulforaphane, alpha-lipoic acid, L-carnitine, ascorbic acid, selenocompounds, flavones and zinc, in alleviating neuropsychiatric symptoms by mitigating excitotoxicity, enhancing synaptic plasticity, reducing microglial overactivation and promoting synaptogenesis. This review explores the role of oxidative stress in the pathogenesis of neuropsychiatric disorders. It provides an overview of the current evidence on antioxidant therapy’s pharmacological effects, as demonstrated in animal models and clinical studies. It also discusses the underlying mechanisms and future directions for developing antioxidant-based adjuvant therapies. Given the limitations and side effects of existing treatments for neuropsychiatric disorders, antioxidant therapy presents a promising, safer alternative. Further research is essential to deepen our understanding and investigate the clinical efficacy and mechanisms underlying these therapies.

AIM: To observe the effects of femtosecond laser-assisted excimer laser in situ keratomileusis combined with accelerated corneal cross-linking (FS-LASIK Xtra) on corneal densitometry after correcting for high myopia. METHODS: In this prospectively study, 130 patients underwent FS-LASIK or FS-LASIK Xtra for high myopia. Their right eyes were selected for inclusion in the study, of which 65 cases of 65 eyes in the FS-LASIK group, 65 patients with 65 eyes in the FS-LASIK Xtra group. Patients were evaluated for corneal densitometry at 1, 3, and 6mo postoperatively using Pentacam Scheimpflug imaging. RESULTS: Preoperative differences in corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups in different ranges were not statistically significant (P>0.05). Layer-by-layer analysis revealed statistically significant differences in the anterior (120 μm), central, and total layer corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups at 1 and 3mo postoperatively (all P0.05). CONCLUSION: There is an increase in internal corneal densitometry during the early postoperative period after FS-LASIK Xtra for correction of high myopia. However, the densitometry values decreased to the level of conventional FS-LASIK at 6mo after surgery, with the most significant changes observed in the superficial central zone.

Abstract Background Patients with mood disorders usually require repeated and prolonged hospitalization, resulting in a heavy burden on healthcare resources. This study aims to identify variables associated with length of stay(LOS) of repeatedly hospitalized patients with mood disorders and to provide information for optimizing psychiatry management and healthcare resource allocation. Methods Electronic medical records (EMRs) of repeatedly hospitalized patients with mood disorders from January 2010 to December 2018 were collected and retrospectively analyzed. Chi-square and t-test were adopted to investigate the differences in characteristics between the two groups of short LOS and long LOS. Generalized estimating equation (GEE) was conducted to investigate potential factors influencing LOS. Results A total of 2,009 repeatedly hospitalized patients with mood disorders were enrolled, of which 797 (39.7%) had a long LOS and 1,212 (60.3%) had a short LOS. Adverse effects of treatment, continuous clinical manifestation, chronic onset type, suicide attempt, comorbidity and use of antidepressants were positively associated with long LOS among all repeatedly hospitalized patients with mood disorders (P

Background: Coronary heart disease (CHD) is a common heart disease and a leading cause of death in developed countries and some developing countries such as China. It is recognized as a multifactorial disease, with dyslipidemia being closely associated with the progression of coronary atherosclerosis. Numerous studies have confirmed the relationship between a single indicator of low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C) and CHD. However, the association between LDL-C to HDL-C ratio (LHR) and CHD remains unclear. This study aimed to comprehensively explore the association between LHR and CHD. Methods: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were comprehensively searched up to June 15, 2023, to find the studies that indicated the connection between LHR and CHD. A total of 12 published studies were selected. The random-effects model was used to pool the data and mean difference (MD), and the 95% confidence intervals (CI) were taken as the overall outcome. No language restrictions existed in the study selection. The Review Manager 5.4 and Stata 12 were used to analyze the data. Results: Twelve high-quality clinical studies involving 5544 participants, including 3009 patients with CHD, were enrolled in the meta-analysis. The findings revealed that the LHR was higher by 0.65 in patients with CHD than in those without CHD (MD, 0.65; 95% CI, 0.50–0.80). Conclusion: The LHR was found to be positively correlated with CHD, suggesting that it may serve as a potential indicator of CHD.

BackgroundChimeric antigen receptor T cell (CAR-T) is a promising treatment for aggressive Non-Hodgkin lymphoma (NHL). The aim of the meta-analysis was to determine the association between metabolic tumor volumes (MTV) derived on positron emission tomography before CAR-T infusion and the survival of patients with NHL.MethodsRelevant observational studies pertaining to the purpose of the meta-analysis were obtained through a search of PubMed, Web of Science, and Embase from inception of the databases to April 1, 2024. The data was combined using a random-effects model that accounted for the potential influence of between-study heterogeneity.ResultsFifteen observational studies were included. Pooled results showed that compared to those with a lower MTV, the NHL patients with a higher MTV before CAR-T infusion were associated with a poor progression-free survival (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.48 to 2.02, p < 0.001; I2 = 20%) and overall survival (HR: 2.11, 95% CI: 1.54 to 2.89, p < 0.001; I2 = 58%). Subgroup analysis showed that the association between MTV and survival of NHL patients after CAR-T was not significantly impacted by study design, methods for determination of MTV cutoff, or analytic models (univariate or multivariate, p for each subgroup all < 0.05). Subgroup analysis suggested a stronger association between MTV and poor survival outcomes in patients with median of lines of previous treatment of 2 or 3 as compared to those of 4 (p for subgroup difference < 0.05). Further meta-regression analyses suggested that the association between MTV and survival was not significantly affected by sample size, age, proportion of men, cutoff value of MTV, follow-up duration, or study quality scores (p all > 0.05).ConclusionA high MTV at baseline is associated with a poor survival of NHL patients after CAR-T.Systematic Review Registrationhttps://inplasy.com/, identifier INPLASY (INPLASY202450069).

Traditional denoising methods often lose details or edges, such as Gaussian filtering. Shearlet transform is a multi-scale geometric analysis tool which has the advantages of multi-resolution and multi-directivity. Compared with wavelet, curvelet, and contourlet transforms, it can retain more edge details while denoising, and the subjective vision and objective evaluation indexes are better than other multi-scale geometric analysis methods. Deep learning has made great progress in the field of denoising, such as U_Net, DnCNN, FFDNet, and generative adversarial network, and the denoising effect is better than BM3D, the traditional optimal method. Therefore, we propose a random noise suppression network ST-hFFDNet based on non-subsampled shearlet transform (NSST) and improved FFDNet. It combines the advantages of non-subsampled shearlet transform, Huber norm, and FFDNet, and has three characteristics. 1) Shearlet transform is an effective feature extraction tool, which can obtain the high and low frequency features of a signal at different scales and in different directions, so that the network can learn signal and noise features of different scales and directions. 2) The noise level map can improve the noise reduction performance of different noise levels. 3) Huber norm can reduce the sensitivity of the network to abnormal data and improve the robustness of network. The network training process is as follows. 1) BSD500 datasets are enhanced by flipping, rotating, scaling, and cutting. 2) AWGN with noise level σ∈[0,75] is added to the enhanced datasets to obtain the training datasets. 3) NSST multi-scale and multi-direction decomposition is performed on each pair of samples of the training datasets to obtain high- and low-frequency images of different scales and directions. 4) Based on the decomposed high and low frequency images, the ST-hFFDNet network is trained by Adam algorithm. 5) All samples of the training data set are carried out in steps (3) and (4), and the trained model is thus obtained. Simulation experiments and real seismic data denoising show that for low noise, the proposed method is slightly better than NSST, DnCNN, and FFDNet and that it is superior to NSST, DnCNN, and FFDNet for high noise.

Sugar beet has strong drought resistance and requires a large amount of nitrogen (N) during growth. Can deficit irrigation combined with low N supply of sugar beet improve water productivity (WP) and N use efficiency (NUE)? In this field study in 2020–2021, two irrigation regimes (W1, field capacity (FC) of the 0–60 cm soil layer was not lower than 70% from 45 days after emergence (DAE) to harvest period; W2, FC of the 0–60 cm soil layer was not lower than 50% in 45–90 DAE, but was consistent with that of W1 after 90 DAE) and three N application rates (0 (N0), 150 (N1), and 225 (N2) kg N ha−1) were designed. Then, their impacts on taproot yield (TY), water consumption (WC) and N uptake (NU) were explored. The results showed that there was no significant difference in TY between W2 and W1 treatments under the N1 and N2 levels. Under the N1 and N2 levels, the daily water consumption (DWC, 0.121 and 0.125 mm ℃d−1) and daily N uptake (DNU, 53.6 and 71.6 g N ℃d−1) of W2 treatment were significantly lower than the DWC (0.161 and 0.164 mm ℃d−1) and DNU (60.6 and 86.5 g N ℃d−1) of W1 treatment in 0–90 DAE. The W2N1 treatment had similar WP and higher NUE compared with the W1N2 treatment. In addition, the fertilizer-15N recovery rate in W2N1 treatment was 8.8% higher than that in W1N2 treatment, the fertilizer-15N loss rate was 6.6% lower than that in W1N2 treatment, but there was no difference in the fertilizer-15N residue between the two. This study clarified that implementing W2 deficit irrigation (50% FC at the canopy rapid growth stage (45–90 DAE)) and N1 nitrogen application rate (33% nitrogen reduction based on 225 kg N ha−1) could not reduce TY but improve WP and NUE.

Abstract Maintaining energy balance and economical operation is significant for energy hub (EH) which serves as the central component. Implementing real‐time regulation for heating and cooling equipment within the EH is challenging due to their slow response time in response to the stochastic fluctuation in renewable energy sources and demands while the opposite is true for electric energy storage equipment (EST), a conventional single timescale energy management strategy is no longer sufficient to take into account the operating characteristics of all equipment. With this motivation, this study proposes a deep reinforcement learning based two‐timescale energy management strategy for EH, which controls heating & cooling equipment on a long timescale of 1 h, and EST on a short timescale of 15 min. The actions of the EST are modelled as discrete to reduce the action spaces, and the discrete‐continuous hybrid action sequential TD3 model is proposed to address the problem of handling both discrete and continuous actions in long timescale policy. A joint training approach based on the centralized training framework is proposed to learn multiple levels of policies in parallel. The case studies demonstrate that the proposed strategy reduces the economic cost and carbon emissions by 1%, and 0.5% compared to the single time‐scale strategy respectively.

Abstract Prognostic features in advanced perihilar cholangiocarcinoma (pCCA) patients who received first-line hepatic arterial infusion chemotherapy (HAIC) are unknown. The purpose of our study was to develop an applicable score based on serum inflammatory-tumor biomarkers to predict the survival of advanced pCCA patients who received first-line HAIC. In total, 106 advanced pCCA patients were enrolled as the training cohort. The optimal cutoff values of baseline variables were defined by the receiver operating characteristic method or according to previous publications. According to the results of Cox regression analysis, baseline neutrophil-to-lymphocyte ratio (NLR) > 3.19, carcinoembryonic antigen (CEA) > 10 ng/mL, and carbohydrate antigen 19-9 (CA19-9) > 200 U/mL were identified as independent survival predictors, which were used to develop the NLCECA score (NLR, CEA, and CA19-9). When including the NLCECA score in the multivariate analysis, the NLCECA score was the only independent predictor of survival. The risk of survival decreased by 111.9% for each 1-point increase in the NLCECA score. Additionally, the NLCECA score could also predict survival in another 33 patients in the validation cohort (P

Abstract Objective A comparative study of joint amnesia in patients undergoing total hip arthroplasty with the direct anterior approach and posterior approach was conducted through a comprehensive evaluation. Methods The literature on joint amnesia in postoperative patients who underwent total hip arthroplasty by the direct anterior approach and the posterior approach was systematically searched in PubMed, Embase, Web of Science, Cochrane Library, CNKI, CBM, Wanfang, and VIP databases from the time of library construction until February 13, 2023. Meta-analysis was performed using RevMan 5.3 software after independent searching, screening of the literature, data extraction, and quality assessment of the included studies by two investigators in strict accordance with the guidelines for conducting meta-analyses. Results A total of one RCT and six cohort studies were included in this meta-analysis. Meta-analysis results indicated that at 1 month postoperatively (MD = 2.08, 95% CI (0.20, 3.96), P = 0.03), 3 months (MD = 10.08, 95% CI (1.20, 18.96), P = 0.03), and 1 year (MD = 6.74, 95% CI (1.30, 12.19), P = 0.02), DAA total hip arthroplasty was associated with better FJS compared to PA at 1 year postoperatively. However, there was no statistical significance in FJS between the two groups at 5 years postoperatively (MD = 1.35, 95% CI (− 0.58, 3.28), P = 0.17). Conclusion Current evidence suggests that the degree of joint amnesia after THA for DAA was not found to be superior to that of PA. Further, these findings require confirmation by including a larger number of high-quality randomized controlled studies. Study design Systematic review; Level of evidence, 3.

AIM: To evaluate the efficacy of intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF), photodynamic therapy (PDT), and laser treatment (LT) for anatomical and functional improvement in myopic choroidal neovascularization (mCNV) patients. METHODS: Two researchers independently searched PubMed, Cochrane Library, Web of Science, and other databases to screen studies comparing best-corrected vision acuity (BCVA) and foveal center thickness (FCT) changes after mCNV treatment. Post-treatment chorioretinal atrophy (CRA) is a secondary outcome indicator. The retrieval time limit is from the database construction to January 30, 2023. RESULTS: A total of 1072 eyes in 16 articles were included. In the RCTs, intravitreal bevacizumab (IVB) and intravitreal ranibizumab (IVR) were superior to PDT (MD=0.18, 95%CI: 0.02, 0.40, MD=0.18, 95%CI: 0.01, 0.42) in improving BCVA of mCNV patients (P

Fusarium head blight (FHB), caused by the Fusarium graminearum species complex, causes significant losses in grain yield and quality of wheat (Triticum aestivum) by inducing floret sterility. Grains become contaminated with mycotoxins, especially deoxynivalenol (DON), making them unsuitable for consumption. To clarify the impact of wheat cultivar resistance, infection level, and climate after anthesis on the efficacy of a fungicide for the control of FHB, we treated two moderately susceptible cultivars and 11 susceptible cultivars with fungicide (48% phenamacril + tebuconazole) at anthesis over two years. FHB incidence (INC), disease severity index (DSI), Fusarium-damaged kernels, DON contamination, thousand-kernel weight, and yield were evaluated under artificially inoculated and naturally infected field trials in 2018 and 2021. The results of multi-factor variance analysis show that the control efficacy with respect to INC and DSI is affected by cultivar, fungicide, infection level, and climatic conditions including the average daily temperature, average daily relative humidity, and total rainfall from anthesis to 21 days after anthesis (p < 0.01). Notably, cultivar resistance (deviance = 13.34, 9.55, and 11.22) is more important than fungicide (deviance = 5.77, 6.66, and 6.69) to control the efficacy of INC, DSI, and DON. The results also suggest that infection level appears to be more important than cultivars and fungicide to control the efficacy of INC, and more important than fungicide to control the efficacy of DSI. Total rainfall is more important than other climatic factors. Our results reveal that fungicide is more effective in moderately susceptible cultivars (‘Zhengmai 9023’ and ‘Xinong 979’, 89.5%~98.9%) and some susceptible cultivars than in other susceptible cultivars (‘Zhengmai 7698’ and ‘Zhoumai 27’, 51.9%~67.2%). Thus, integrating cultivar resistance with fungicide application can be an effective strategy for the management of FHB and DON in winter wheat in the Huang-huai-hai Plain of China.

Abstract Objective To systematically evaluate the clinical safety and efficacy of the direct superior approach and the conventional surgical approach. Date sources From PubMed, Embase, the Cochrane Library, and China Knowledge Network up to January 30, 2023. Main results A total of 7 case series involving 4306 patients undergoing total hip arthroplasty were included, including 679 patients with direct superior approach. All outcome measures: Oxford Hip Score [MD = 0.30, 95% CI (− 0.87, 1.47), P = 0.62], Hip Harris Score [MD = − 0.18, 95% CI (− 0.86, 0.49), P = 0.59], intraoperative blood loss [MD = − 54.14, 95% CI (− 102.75,-5.52), P = 0.03], transfusion rate [MD = 0.49, 95% CI (0.29, 0.83), P = 0.008], Limb Length Differences [MD = − 0.21, 95% CI (0.02, 0.39), P = 0.03], Length of Stay [MD = − 0.61, 95% CI (− 0.69, − 0.52), P

Abstract The main goal of integrated energy service providers (IESP) in the future is to pursue profitability and reduce carbon emissions while ensuring sufficient energy supply. However, the multiple uncertainties associated with renewable energy resources and the multi‐energy consumers pose significant challenges in the optimal planning of the integrated energy system (IES) based on energy hubs (EH). This includes the global optimization of device types, EH capacity, and the optional interconnections between adjacent EHs. This study aims to develop a comprehensive mathematical model of EH that considers the temperature limitations on device operation. The thermal bus and associated devices are divided into high and low temperature parts, and a multi‐scenario stochastic programming model is proposed for IES planning. Scenarios are generated using non‐parametric kernel density estimation and the Copula function, a scenario reduction technique is implemented to alleviate computational burden. Additionally, case studies illustrate effectiveness of the proposed approach, the operation and forms of EHs, effect of the interconnections and the trade‐off between carbon emissions and economic costs are further studied by extensive simulations. This study can be a good guide for IESPs to invest in the construction of the EH‐based IES.

Abstract Objective The aim of this study is to conduct a comprehensive evaluation of the effectiveness of the medial parapatellar approach via the vastus medialis obliquus muscle in comparison with the standard medial parapatellar approach for total knee arthroplasty, using a systematic approach. Methods A computer search was conducted on PubMed, EMBASE, Medline, Cochrane libraries, and Web of Science databases to comprehensively collect randomized controlled studies on minimally invasive (MMV) approaches for knee arthroplasty, specifically the vastus and medial parapatellar (MP) approaches. Two authors independently screened the literature based on inclusion and exclusion criteria, evaluated the quality of the included studies using the Cochrane systematic review method, and performed a meta-analysis using RevMan 5.3 software. Results A total of twelve randomized controlled studies were ultimately included, comprising 788 knees. The small incision medial femoral muscle approach (MMV) group consisted of 398 cases, while the traditional parapatellar approach (MP) group consisted of 390 cases. Data analysis showed that in the comparison of KSS, VAS, and ROM score at 3 months after surgery, MMV approach was superior to MP approach [MD = 2.89, 95%CI (0.33, 5.46), P = 0.03], [MD = − 0.22, 95%CI (− 0.36, − 0.09), P = 0.001], and [MD = 1.08, 95%CI (0.04, 2.12), P = 0.04]. However, there was no significant difference in the postoperative KSS, VAS, and ROM score between the MMV and MP approaches at 6 and 12 months after surgery. The operation time of the MMV group was longer than that of the MP group [MD = 8.98, 95%CI (4.64, 13.32), P

Aim: The aim of this study was to confirm the presence of the form deprivation myopia (FDM) guinea pig eye-gut axis and investigate the relationship between serum vasoactive intestinal peptide (VIP), lipopolysaccharides (LPS), specific gut microbiota and their metabolites. Method: 20 specific-pathogen-free (SPF) guinea pigs were divided into the FDM and the control(Con) group. Following model induction, serum levels of VIP and LPS were quantified. A combination of 16S ribosomal ribosomal Ribonucleic Acid (rRNA) gene sequencing, non-targeted metabolomics and bioinformatics analysis were employed to identify disparities in gut microbiota and metabolites between the two groups of guinea pigs. Result: Compared to the control group, FDM guinea pigs exhibited a significant trend towards myopia, along with significantly elevated concentrations of LPS and VIP (p

Background Unicompartmental knee arthroplasty (UKA) is an effective treatment method for knee osteoarthritis. With the development and implementation of enhanced recovery after surgery, UKA is now increasingly performed in outpatient surgical centers. However, there is ongoing debate regarding the safety and effectiveness of performing UKA in outpatient settings. Methods The search was performed to retrieve randomized controlled trials and cohort studies on outpatient UKA from PubMed, Cochrane Library, EMbase, CNKI, and WanFangData databases. The search was conducted from the inception of the databases until August 31, 2023. After independent screening, data extraction, and risk of bias evaluation by two researchers, meta-analysis was performed using RevMan 5.4 software. Results A total of eight studies involving 18,411 patients were included. The results showed that the postoperative transfusion rate in the outpatient group was lower than that in the inpatient group [OR = 0.36, 95%CI (0.24, 0.54), p < 0.00001], and the difference was statistically significant. However, there was no significant difference between the two groups in terms of readmission rate, reoperation rate, surgical site infection, and periprosthetic fracture. The differences were not statistically significant. Conclusion Compared to the traditional inpatient route, the blood transfusion rate for single-condyle replacement in the outpatient operation center is lower, and there is no significant difference in readmission rate, reoperation rate, surgical site infection, and periprosthesis fracture. The outpatient approach to UKA is safe, feasible, and highly satisfactory for patients. However, the results have certain limitations, and a rigorous preoperative complication risk assessment can minimize the risk of UKA in outpatient surgery centers. Trial registration PROSPERO number CRD42023405373.

ABSTRACTEchovirus 5 (E5) belongs to the enterovirus B (EV-B) species, which is one of the pathogens causing respiratory diseases. Only two whole genome sequences (WGSs) of E5 are available in GenBank, and few studies on E5 have been reported worldwide. In this study, human rhabdomyosarcoma (RD) cells were used to isolate E5 from respiratory samples associated with severe acute respiratory infection (SARI). The nucleotide sequence of the VP1 region and the WGSs of two E5 strains were sequenced using Sanger sequencing and high-throughput sequencing technology, respectively. Together with 31 E5 VP1 sequences and 2 WGSs downloaded from GenBank, a total of 33 complete VP1 sequences and 4 WGSs were used for genetic characterization and evolutionary analysis. Phylogenetic analysis revealed five genotypes (A–E) based on complete VP1 sequences. Evolutionary analysis showed that the time to the most recent common ancestor of E5 was approximately 1952 (95% highest posterior density [HPD] range, 1948–1953]), with a mean substitution rate of 7.74 × 10−3 subs/site/year (95% HPD range, 6.44–9.11 × 10−3). In addition, the WGS analyses showed that the nucleotide and amino acid similarities of the coding regions of the two strains obtained in this study with the prototype of the E5 strain Noyce were 80.2% and 97.2%, respectively. Recombination analysis showed that the two E5 strains may have intraspecific recombination with E6, EV-B85, and CVA9 serotypes in the nonstructural region. This study reports the isolation of E5 from SARI cases for the first time, and genetic characterization and evolutionary analysis provide valuable information on global E5 molecular epidemiology.IMPORTANCEThis study is the first report of echovirus 5 (E5) associated with severe acute respiratory infection and obtained the first E5 whole-genome sequence in China. Combined with the sequences available in the GenBank database, the first genotyping, phylogenetic characteristics, recombination, and genetic evolutionary analysis of E5 was performed in this study. Our findings providing valuable information on global E5 molecular epidemiology.

AbstractBackground Pheochromocytomas and paragangliomas (PPGLs) are a group of rare neuroendocrine tumors. Dysglycemia has been observed in patients with PPGLs in some small case series. However, there is limited information available on the factors associated with development and resolution of dysglycemia in these patients.Patients and methods The clinical data of consecutive patients admitted to our hospital with PPGLs between January 2018 and June 2020 were retrospectively analyzed. Clinical characteristics were compared between patients with and without dysglycemia. Logistic regression analysis was used to identify risk factors and receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the variables.Results Among 163 patients, 58.9% had preoperative dysglycemia. Patients with dysglycemia were significantly older at diagnosis (p = 0.01) and were significantly more likely to have hypertension (p = 0.007). White blood cell counts (p = 0.016), 24-hour urinary epinephrine (24hU-E) levels (p

Clarifying the optimal combination of N fertilizer application rate and application method can maximize the yield of drip-irrigated sugar beet in arid areas, which is of great significance for reducing farmland N pollution and achieving sustainable agricultural development. In this three-year field experiment in Xinjiang, China, the effects of three N application rates [75 kg ha−1 (N1), 150 kg ha−1 (N2), and 225 kg ha−1 (N3)] and three N application methods [the proportion of N applied at canopy rapid growth stage, taproot expansion stage, and sugar accumulation stage were (M1) 100%: 0%: 0%, (M2) 70%: 30%: 0%, and (M3) 50%: 30%: 20%] on the dry matter accumulation (DMA) and distribution, leaf senescence, yield, and agronomic N use efficiency (aNUE) of drip-irrigated sugar beet were explored. The results showed that N application (N1, N2, and N3 treatments) increased the shoot DMA by 27.7% (three-year average), 52.6%, and 83.1%, and the taproot DMA by 28.3%, 43.2%, and 61.6%, respectively (p < 0.05), compared with CK (no N supply) treatment. The N application methods M2 and M3 increased the shoot DMA by 5.6% (three-year average) and 1.0% (p > 0.05), respectively, and the taproot DMA by 7.2% and 3.6% (p < 0.05), respectively, compared with M1. In addition, M2 could delay the end of shoot and taproot growth (te) and the occurrence of maximum growth rate (tm). In particular, the N3M2 treatment increased the leaf area index (LAI) by 20.4–75.9% (p < 0.05) compared with other treatments by increasing the leaf area duration (LAD) and decreasing the leaf senescence rate (LSR). The taproot yield and sugar yield of N3M2 treatment reached the maximum at harvest time, but there was no significant difference in taproot yield and sugar yield between N3M2 treatment and N2M2 treatment. The aNUE in N2M2 treatment was the highest (p < 0.05), which was 1.29–7.85 times higher than that of other treatments. Therefore, reducing the N application rate from 225 kg·ha−1 to 150 kg·ha−1 and applying 70% and 30% of 150 kg N ha−1 at the canopy rapid growth stage and the taproot expansion stage, respectively, could achieve the goal of increasing sugar beet yield and N use efficiency. This study will provide an important reference for the sustainable production of sugar beet under drip irrigation in Xinjiang, China.

In order to reduce costs, compress space, and improve system stability under harsh operating conditions, the current vehicle motor drive systems often use position sensorless control methods. However, due to the introduction of filters and the hysteresis of position observers, the position sensorless control has the problem of deteriorating dynamic performance when vehicles start from zero and low speeds or their loads change. Therefore, this article focuses on the problem of position sensorless control applied by permanent magnet synchronous motors when vehicles start and operate at zero and low speed. Combined with high-frequency pulse vibration injection method, the relationship between the types of position observers, parameter selection, and position tracking performance is analyzed and compared. The short-pulse injection method is proposed to locate the initial position of the motor, overcoming the inherent 180° position deviation of pulse vibration high-frequency injections. Subsequently, the impact of the amplitude and frequency of the injected high-frequency signal on the performance of position estimation is focused on. Considering the adverse effects caused by the phase delay of the filter, a design method for filter parameters is proposed to achieve a smooth start and operation of the permanent magnet synchronous motor under position sensorless control. Finally, the rationality of the theoretical analysis and the effectiveness of the adopted methods are fully verified through simulation and experiments.

The Electric Bus Dynamic Wireless Charging (EB-DWC) system is a bus charging system that enables electric buses to receive power wirelessly from ground-based electromagnetic induction devices. In this system, how to optimally configure the charging infrastructures while considering the unpredictable nature of bus movement is a great challenge. This paper presents an optimization problem for an EB-DWC system in urban settings, addressing stochastic elements inherent in the vehicle speed, initial charging state, and dwell time at bus stops. We formulate a stochastic planning problem for the EB-DWC system by integrating these uncertainties and apply Monte Carlo sampling techniques to effectively solve this problem. The proposed method can improve the system’s robustness effectively.

Background: Traditional Chinese medicine (TCM) has been used to prevent and treat type 2 diabetes (T2DM) for thousands of years. The holistic view of TCM and the “multitarget” characteristics of Chinese medicine have unique advantages in the prevention and treatment of T2DM. TCM syndrome differentiation and treatment are effective for T2DM; however, currently, the therapeutic effect of TCM is generally evaluated by asking for patients' subjective feelings, or by checking the changes in relevant indicators. The main problems are that the patient's descriptions are unclear and subjective, and although the self-reported symptoms may have improved significantly, the relevant indicators are sometimes not obvious, which cannot truly reflect the therapeutic effect of TCM. Therefore, it is urgent to develop a novel, sensitive, and noninvasive method to quantitatively evaluate the therapeutic effect of TCM. Methods: In this study, ultra-weak photon emission (UPE) was measured at four sites of hands of T2DM patients with Qi-Yin deficiency before treatment and after 1 and 2 weeks of treatment with TCM. The UPE intensity and spectral distribution were calculated and analyzed using the results measured at these four sites. Spearman's correlation coefficient was used to quantify the correlation between the UPE parameters and the syndrome scores of TCM. Results: The UPE intensity of T2DM patients with Qi-Yin deficiency decreased gradually with the course of the treatment and was significantly lower than that before the treatment. The ratio of photon counts between the wavelength ranges of 495–550 nm and 550–610 nm after the treatment was higher than that before the treatment and negatively correlated with the corresponding syndrome scores so that the degree of symptoms improvement could be characterized by the ratio (495–550 nm/550–610 nm). Conclusions: The therapeutic effect of TCM in T2DM patients with Qi-Yin deficiency can be shown at the level of UPE. UPE is a potential and noninvasive tool for evaluating the therapeutic effect of TCM in patients with T2DM.

BackgroundOsteoarthritis (OA) is a degenerative disease with high prevalence. Some observational studies have shown that patients with osteoarthritis often have co-existing cardiovascular diseases (CVD) such as atrial fibrillation (AF) and coronary atherosclerosis (CA). However, there is still a lack of stronger evidence confirming the association between osteoarthritis and cardiovascular disease. In this study, we used a bidirectional two-sample Mendelian randomization study to investigate the relationship between OA with AF and CA.MethodsOA data from the UK Biobank and arcOGEN (Arthritis Research UK Osteoarthritis Genetics, a study that aimed to find genetic determinants of osteoarthritis and elucidate the genetic architecture of the disease) integration were selected for the study (n = 417,596), AF data were obtained from six studies (n = 1,030,836), and coronary atherosclerosis data were derived from the FinnGen (n = 218,792). MR analysis was performed primarily using the Inverse variance weighted (IVW) method, with MR Egger, weighted median, simple mode, weighted mode as supplements, sensitivity analysis was performed using Cochran Q statistic, and leave-one-out analysis.ResultsWe found that OA and AF were positively associated [IVW: OR (95% CI): 1.11 (1.04, 1.19), P = 0.002], while OA and CA were negatively associated [IVW: OR (95% CI): 0.88 (0.79, 0.98), P = 0.02]. In the reverse MR analysis, no effect of AF on OA was found [IVW: OR (95% CI): 1.00 (0.97, 1.03), P = 0.84], meanwhile, CA and OA were found to be associated negatively [IVW: OR (95% CI): 0.95 (0.92, 0.99), P = 0.01]. No violations of MR assumptions were found in the sensitivity analysis.ConclusionThis research confirms that OA is a risk factor for AF, and there is a mutual protective factor between OA and CA. However, further studies are still necessary to elucidate the underlying mechanisms.

As an important farmed fish, tilapia has poor tolerance to low-temperatures. At the same time, different tilapia strains have apparent differences in low-temperature tolerance. In this study, using the iTRAQ method, the phosphorylated proteomics of two tilapia strains (Oreochromis niloticus and Oreochromis aureus) with different tolerances to low-temperature stress were quantitatively and comparatively analyzed, to clarify the physiological mechanism of tilapia’s response to low-temperature stress. Through the GO and IPR analyses of differentially phosphorylated proteins, a number of similarities in physiological activities and regulatory effects were found between the two tilapias in response to low-temperature stress. Many differentially phosphorylated proteins are mainly involved in lipid metabolism, cell proliferation and apoptosis. However, the difference in endurance of low temperature of these two tilapias might be related to the differences in categories, expression and modification level of genetic products which were involved in the aforementioned physiological processes. And meanwhile, the enrichment results of KEGG showed the changes of multiple immune-related and growth-related phosphorylated proteins in the cytokine-cytokine receptor interaction pathway in O. aureus are more prominent. Furthermore, the significantly enriched pathway of carbohydrate digestion and absorption in O. niloticus may indicate that low-temperature stress exerts a more severe impact on energy metabolism. The relative results would help elucidating the molecular mechanism by which tilapia responds to low-temperature stress, and developing culture of tilapia species.

Abstract Pancreatic cancer has an extremely terrible prognosis and is a common cause of cancer death. In this study, the clinic value, biological function and underlying mechanisms of Zinc finger protein 655 (ZNF655) in human pancreatic cancer were evaluated. The expression level of ZNF655 in pancreatic cancer was determined by immunohistochemistry (IHC) staining. The biological effects of ZNF655 in pancreatic cancer cells was investigated by loss/gain-of-function assays in vitro and in vivo. The downstream molecular mechanism of ZNF655 was explored using co-immunoprecipitation (Co-IP), dual-luciferase reporter and chromatin immunoprecipitation (Ch-IP). ZNF655 expression was significantly elevated in human pancreatic cancer and possessed clinical value in predicting poor prognosis. Functionally, ZNF655 knockdown inhibited the biological progression of pancreatic cancer cells, which was characterized by weaken proliferation, enhanced apoptosis, arrested cell cycle in G2, impeded migration, and suppressed tumor growth. Mechanistically, ZNF655 played an important role in promoting the binding of E2F transcription factor 1 (E2F1) to the cyclin-dependent kinase 1 (CDK1) promoter. Furthermore, knockdown of CDK1 alleviated the promoting effects of ZNF655 overexpression in pancreatic cancer cells. The promotive role of ZNF655 in pancreatic cancer via CDK1 was determined, which drew further interest regarding its clinical application as a promising therapeutic target.

Nitrogen (N), an important element for crop growth, has a great impact on dry matter weight and yield. Currently, improving N fertilizer use rate is an urgent problem to be solved in agricultural production in the world. In this field experiment, a self-developed water-soluble polymer material (PPM) with water retention and slow-release characteristics was combined with different doses of N fertilizer (N300 (100% N), PN300 (PPM + 100% N), PN240 (PPM + 80% N), PN180 (PPM + 60% N), CK (no N and PPM)) to analyze the impacts on N uptake and use efficiency of wheat plants. The results showed that the combined application of PPM and N fertilizer significantly improved yield, plant height, biomass, and N uptake and use efficiency of drip irrigated wheat, and the PN240 group had the highest N use rate. In addition, the PN300 group had the highest yield. N use efficiency in the PN240 group was 40.23% higher than that in the N300 group. Therefore, the combined application of PPM and N fertilizer, especially PN240, can reduce the N fertilizer application rate by increasing N use efficiency. This study provides technical reference for improving the N use efficiency of drip-irrigated wheat in arid areas.

BackgroundPheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors, most of which are characterized by the release of catecholamine, and range in diameters from less than 1 cm to 10 cm or more. However, knowledge of the differences in clinical features between small and large PPGLs is insufficient.MethodsA retrospective analysis of patients with PPGLs treated at our institution between January 2018 and June 2020 was performed. The clinical characteristics of patients were investigated, and comparisons were made between patients with large and small PPGLs. The logistic regression analysis was used to confirm the risk factors, and the receiver operating characteristic curve was used to evaluate the diagnostic performance of the variables.ResultsTotally 263 patients were included, including 110 patients in small tumor group and 153 patients in large tumor group. There were more male patients in the large tumor group (p=0.009). More patients had hypertension (p

Summary: Synaptotagmin III (Syt3) is a Ca2+-dependent membrane-traffic protein that is highly concentrated in synaptic plasma membranes and affects synaptic plasticity by regulating post-synaptic receptor endocytosis. Here, we show that Syt3 is upregulated in the penumbra after ischemia/reperfusion (I/R) injury. Knockdown of Syt3 protects against I/R injury, promotes recovery of motor function, and inhibits cognitive decline. Overexpression of Syt3 exerts the opposite effects. Mechanistically, I/R injury augments Syt3-GluA2 interactions, decreases GluA2 surface expression, and promotes the formation of Ca2+-permeable AMPA receptors (CP-AMPARs). Using a CP-AMPAR antagonist or dissociating the Syt3-GluA2 complex via TAT-GluA2-3Y peptide promotes recovery from neurological impairments and improves cognitive function. Furthermore, Syt3 knockout mice are resistant to cerebral ischemia because they show high-level expression of surface GluA2 and low-level expression of CP-AMPARs after I/R. Our results indicate that Syt3-GluA2 interactions, which regulate the formation of CP-AMPARs, may be a therapeutic target for ischemic insults.

Aim: Myopia is a common chronic eye disease, this study is to investigate the effects of exogenous retinoic acid (RA) on intraocular parameters, especially choroidal thickness (CT) and retinal thickness (RT), in guinea pigs with form deprivation myopia (FDM).Methods: A total of 80 male guinea pigs were divided randomly into 4 groups: Control, FDM, FDM + RA, and FDM + Citral groups. The FDM + RA group was given 24 mg/kg RA dissolved in 0.4 mL peanut oil; the FDM + Citral group was given citral 445 mg/kg dissolved in 0.4 mL peanut oil; The other two groups were given 0.4 mL peanut oil. After 4 weeks, the refractive error (RE), axial length (AL), and intraocular pressure (IOP) of all guinea pigs were measured, and the parameters of RT and CT were obtained using enhanced depth imaging optical coherence tomography (EDI-OCT).Results: After 4 weeks, both the RE and AL in the FDM and FDM + RA groups were increased, and the RT and CT in both groups were smaller than those in the Control group (p < 0.05). Only the IOP of the right eye in the FDM + RA group increased significantly (p < 0.05). The RT of the right eye of the 4 groups was compared: Control group > FDM + Citral group > FDM group > FDM + RA group. Compared with the RT of the left eye and the right eye among the 4 groups, the RT of the right eye in the FDM and FDM + RA groups was significantly less than that in the left eye (p < 0.05). Moreover, the CT of the right eye in the Control group was greater than that in the other three groups (p < 0.0001). There was no significant difference in the CT among the FDM, FDM + RA, and FDM + Citral groups (p > 0.05). In contrast to the RT results, the CT results of the left and right eyes in the FDM + Citral group showed statistically significant differences (p < 0.05).Conclusion: RA participates in the progression of FDM as a regulatory factor. Exogenous RA can increase the RE, AL, and IOP of FDM guinea pigs, and might aggravate the retinal thinning of FDM guinea pigs. Citral can inhibit these changes, but RA might not affect the thickness of the choroid.

Systemic lupus erythematosus (SLE) is an autoimmune illness marked by the loss of immune tolerance and the production of autoantibodies against nucleic acids and other nuclear antigens (Ags). B lymphocytes are important in the immunopathogenesis of SLE. Multiple receptors control abnormal B-cell activation in SLE patients, including intrinsic Toll-like receptors (TLRs), B-cell receptors (BCRs), and cytokine receptors. The role of TLRs, notably TLR7 and TLR9, in the pathophysiology of SLE has been extensively explored in recent years. When endogenous or exogenous nucleic acid ligands are recognized by BCRs and internalized into B cells, they bind TLR7 or TLR9 to activate related signalling pathways and thus govern the proliferation and differentiation of B cells. Surprisingly, TLR7 and TLR9 appear to play opposing roles in SLE B cells, and the interaction between them is still poorly understood. In addition, other cells can enhance TLR signalling in B cells of SLE patients by releasing cytokines that accelerate the differentiation of B cells into plasma cells. Therefore, the delineation of how TLR7 and TLR9 regulate the abnormal activation of B cells in SLE may aid the understanding of the mechanisms of SLE and provide directions for TLR-targeted therapies for SLE.

BackgroundObtaining accurate axial length (AL) is very important for the establishment of animal models of myopia. The purpose of this study is to compare the accuracy of Quantel A-B scan, OD-1 A scan, and vernier caliper in measuring AL in Sprague Dawley (SD) rats.MethodsIn total, 60 5-week-old SD rats were divided into female rat group (n = 30) and male rat group (n = 30). Quantel A-B scan and OD-1 A scan were, respectively, used to measure the AL of both eyes of each living rat, and vernier caliper was used to measure the anterior-posterior diameter of each rat’s eyeball. Besides, the correlation between refractive error (RE) and AL measured by different instruments was evaluated, and the accuracy of the three measurement methods was compared according to gender and left/right eyes.ResultsThere were significant differences in AL and diopter of SD rats at the same age (p < 0.05). the AL of male rats was greater than that of female rats, while diopter (D) was the opposite; There was no significant difference in AL and D between left and right eyes in the same SD rats (p > 0.05); There were statistical differences among the three measurement methods (p < 0.05), AL measured by vernier caliper was the largest, followed by Quantel A-B scan, OD-1 A scan; Difference in AL between male and female was not statistically significant between the results obtained by Quantel A-B scan and vernier caliper (p > 0.05), but there were statistically significant differences between the other two measurement methods (p < 0.05).ConclusionSex is the influencing factor of AL and RE. Imaging measurement can accurately measure the AL in living small rodents. Compared with OD-1 A scan, Quantel A-B scan may be more accurate.

IntroductionNitrogen is a major abiotic stress that affects plant productivity. Previous studies have shown that plant H+-pyrophosphatases (H+-PPases) enhance plant resistance to low nitrogen stress. However, the molecular mechanism underlying H+-PPase-mediated regulation of plant responses to low nitrogen stress is still unknown. In this study, we aimed to investigate the regulatory mechanism of AtAVP1 in response to low nitrogen stress.Methods and ResultsAtAVP1 in Arabidopsis thaliana and EdVP1 in Elymus dahuricus belong to the H+-PPase gene family. In this study, we found that AtAVP1 overexpression was more tolerant to low nitrogen stress than was wild type (WT), whereas the avp1-1 mutant was less tolerant to low nitrogen stress than WT. Plant height, root length, aboveground fresh and dry weights, and underground fresh and dry weights of EdVP1 overexpression wheat were considerably higher than those of SHI366 under low nitrogen treatment during the seedling stage. Two consecutive years of low nitrogen tolerance experiments in the field showed that grain yield and number of grains per spike of EdVP1 overexpression wheat were increased compared to those in SHI366, which indicated that EdVP1 conferred low nitrogen stress tolerance in the field. Furthermore, we screened interaction proteins in Arabidopsis; subcellular localization analysis demonstrated that AtAVP1 and Arabidopsis thaliana receptor-like protein kinase (AtRLK) were located on the plasma membrane. Yeast two-hybrid and luciferase complementary imaging assays showed that the AtRLK interacted with AtAVP1. Under low nitrogen stress, the Arabidopsis mutants rlk and avp1-1 had the same phenotypes.DiscussionThese results indicate that AtAVP1 regulates low nitrogen stress responses by interacting with AtRLK, which provides a novel insight into the regulatory pathway related to H+-pyrophosphatase function in plants.

[This corrects the article DOI: 10.1371/journal.pone.0095259.].

Background. To report the outcomes of phacoemulsification combined with vitrectomy in eyes with extreme myopia (-30 diopters or more). Case Presentation. Three patients with cataract, vitreous opacities, and extreme myopia of more than -30 diopters underwent a combined surgical procedure of cataract extraction combined with vitrectomy. Postoperative refractive correction of the three cases ranged from -1.0 D to -2.5 D spherical equivalent. There was an obvious hyperopic shift of all cases. All patients noted a significant improvement in uncorrected and best-corrected visual acuity from 0.4 to 0.8 in case 1, from CF/70 cm to 1.0 in case 2, and from 0.12 to 0.5 in the right eye and 0.15 to 0.2 in the left eye in case 3. Vitreous floaters disappeared in all cases. No complications were noted during follow-up. Conclusions. To the best of the authors’ knowledge, these represent the first reported clinical cases of combined cataract extraction+vitrectomy surgery in eyes with extreme (>-30 D) myopia. Our results support the notion that phacoemulsification combined with vitrectomy may be a good therapeutic option for cataracts and vitreous floaters in cases with extreme myopia.

Summary: Background: Early detection of gastric cancer (GC) remains challenging. We aimed to examine urine proteomic signatures and identify protein biomarkers that predict the progression of gastric lesions and risk of GC. Methods: A case–control study was initially designed, covering subjects with GC and gastric lesions of different stages. Subjects were aged 40–69 years, without prior diagnosis of renal or urological diseases. We enrolled a total of 255 subjects, with 123 in the discovery stage from Linqu, China, a high-risk area for GC and 132 in the validation stage from Linqu and Beijing. A prospective study was further designed for a subset of 60 subjects with gastric lesions, which were followed for 297–857 days. Findings: We identified 43 differentially expressed urine proteins in subjects with GC vs. mild or advanced gastric lesions. Baseline urinary levels of ANXA11, CDC42, NAPA and SLC25A4 were further positively associated with risk of gastric lesion progression. Three of them, except for SLC25A4, also had higher expression in GC than non-GC tissues. Integrating these four proteins showed outstanding performance in predicting the progression of gastric lesions (AUC (95% CI): 0.92 (0.83–1.00)) and risk of GC (AUC (95% CI): 0.81 (0.73–0.89) and 0.84 (0.77–0.92) for GC vs. mild or advanced gastric lesions respectively). Interpretation: This study revealed distinct urine proteomic profiles and a panel of proteins that may predict the progression of gastric lesions and risk of GC. These biomarkers in a non-invasive approach may have translational significance for defining high-risk populations of GC and its early detection. Funding: Funders are listed in the Acknowledgement.

ObjectiveLenvatinib and sorafenib are first-line oral multikinase inhibitors approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the primary therapeutic agent among these two remains controversial. This meta-analysis aimed to estimate the efficacy and safety of lenvatinib and sorafenib in patients with advanced HCC.MethodsPubMed, Cochrane Library, Web of Science, and Embase databases were searched for relevant research published up to June 30, 2022. After quality assessment and data extraction of the included studies, RevMan 5.3 software was used for analysis. Odds ratio (OR) and hazard ratio (HR) with a 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model.ResultsFifteen studies containing 3908 patients were included after final scrutiny. Our meta-analysis showed that there was no significant difference in overall survival (OS) between the lenvatinib and sorafenib groups (HR = 0.86; 95% CI: 0.72–1.02; p = 0.09); however, the progression-free survival (PFS) (HR = 0.63; 95% CI: 0.53–0.74; p < 0.00001), complete response (CR) (OR = 5.61; 95% CI: 2.71–11.64; p < 0.00001), partial response (PR) (OR = 4.62; 95% CI: 3.06–6.98; p < 0.00001), objective response rate (ORR) (OR = 5.61; 95% CI: 3.90–8.09; p < 0.00001), and disease control rate (DCR) (OR = 2.42; 95% CI: 1.79–3.28; p < 0.00001) in the lenvatinib group were significantly better than those in the sorafenib group. In terms of treatment safety, lenvatinib had similar incidences of any grade adverse events (AEs) (OR = 0.99; 95% CI: 0.47–2.09; p = 0.98) and grade ≥ 3 AEs (OR = 1.17, 95% CI; 1.00–1.37; p = 0.05) compared to sorafenib. Besides, lenvatinib was significantly associated with a higher incidence of hypertension, proteinuria, fatigue, decreased appetite, and weight loss, whereas sorafenib was associated with a higher incidence of diarrhea and hand-foot skin reaction (p < 0.05).ConclusionGiven its potential survival benefit and good tolerability, lenvatinib is an appropriate and promising alternative to sorafenib as first-line systemic therapy in patients with advanced HCC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD 42022327398.

Local recurrence and distant metastasis are the main causes of death in patients with pancreatic adenocarcinoma (PDAC). Microbial content in PDAC metastasis is still not well-characterized. Here, the tissue microbiome was comprehensively compared between metastatic and non-metastatic PDAC patients. We found that the pancreatic tissue microbiome of metastatic patients was significantly different from that of non-metastatic patients. Further, 10 potential bacterial biomarkers (Kurthia, Gulbenkiania, Acetobacterium and Planctomyces etc.) were identified by differential analysis. Meanwhile, significant differences in expression patterns across multiple omics (lncRNA, miRNA, and mRNA) of PDAC patients were found. The highest accuracy was achieved when these 10 bacterial biomarkers were used as features to predict recurrence or metastasis in PDAC patients, with an AUC of 0.815. Finally, the recurrence and metastasis in PDAC patients were associated with reduced survival and this association was potentially driven by the 10 biomarkers we identified. Our studies highlight the association between the tissue microbiome and recurrence or metastasis of pancreatic adenocarcioma patients, as well as the survival of patients.

Abstract Background Left‐sided portal hypertension is usually found in patients undergoing pancreaticoduodenectomy (PD) with spleno‐mesenterico‐portal (S‐M‐P) confluence resection. This study is to explore the outcomes of S‐M‐P confluence reconstruction after resection by using bifurcated allogeneic vein. Methods Clinicopathologic data of patients who underwent extensive PD with S‐M‐P confluence resection for carcinoma of pancreatic head/uncinate process in our hospital between December 2011 and August 2018 were retrospectively reviewed and clinical outcomes of vein reconstruction after resection were analyzed. Results Of the 37 patients enrolled, S‐M‐P reconstruction by bifurcated allogeneic vein was performed in 24 cases (group 1) and simply splenic vein ligation in 13 cases (group 2). Items including pathological results, blood loss, and complications were comparable between the two groups, operation time was longer in group 1 (573.8 vs. 479.2 min, p = 0.018). Significantly decreased platelet count (205.9 vs. 133.1 × 109/L, p = 0.001) and increased splenic volume (270.9 vs. 452.2 ml, p

Abstract Background Vaginal paraganglioma are rare, atypical, solitary tumors which originate from the female genital tract. Sacrococcygeal teratoma are also rare neoplasms which derive from one (or more) primordial germ cell layers. Here we report a unique case of vaginal paraganglioma with sacrococcygeal teratoma. Case presentation A 44-year-old female experienced paroxysmal hypertension, palpitations and dizziness for almost six years. Enhanced CT and MRI highlighted two abnormal soft tissue lesions located in the left vaginal wall and coccyx anteriorly, and Iodine-131 metaiodobenzylguanidine (131I-MIBG) demonstrated abnormal radioactive uptake in perineum area. Endocrine tests showed elevated plasma normetanephrine (NMN) and 24 h urine norepinephrine. There was a well-circumscribed soft tissue lesion of approximately 3.5 cm in the left lateral vaginal wall which could be palpated during bimanual examination, together with a 1.5 cm tumor in the posterior wall of the rectum. We completely resected the two lesions in stages with the support of a senior gynecologist and general surgeons. Postoperative histopathological examinations suggested the vaginal paraganglioma and mature sacrococcygeal teratoma. Targeted sanger sequencing for the 36 mostly common paraganglioma-related genes, with a depth of 1000x, revealed no mutations. Post-operatively, plasma NMN and 24 h urine norepinephrine returned to the normal range and her symptoms completely disappeared. Conclusions We reported an extremely rare case and the successful treatment of functional vaginal paraganglioma coexisting with adult sacrococcygeal teratoma.

Drawing on expectation disconfirmation theory, this study explores the dyadic nature of omni-channel consistency on customer experience. Specifically, we propose a conceptual model that focuses on a brand’s offline channel customer experience relative to that of its online channel, and test the influences of customer experience (in)consistency on customer satisfaction, which then improves repurchase intention and word-of-mouth. The results of polynomial regressions on 265 survey respondents indicate that given omni-channel customer experience inconsistency, customers prefer consistent online and offline experiences. For omni-channel consistency at lower levels of customer experience quality, customers prefer consistency at higher levels of quality. For omni-channel inconsistency where offline customer experience quality is lower than that online, customers prefer omni-channel inconsistency, where offline customer experience quality is higher than that online. These findings produce not only theoretical contributions but also insightful suggestions for how customer experience can be taken into consideration in the promotion of a brand’s omni-channel service success.

In the present study, the Erigeron canadensis L., a typical invasive plant in Southwest China, was utilized as the raw material to prepare original biochar (ECL), a rare earth element La–modified biochar (La–ECL), and a rare earth element La coupling cationic surfactant [cetyltrimethylammonium chloride (CTAC)]–modified biochar (La/CTAC–ECL). These materials were then added to simulated permeable reactive barriers (PRBs) and their nitrate (NO3−) contaminant remediation performances were evaluated in groundwater. The results show that the breakthrough time for NO3− in a simulated PRB column increases as the concentration of the influent NO3− and the flow rate decreases, whereas with the increases of filler particle size and the height of the filler in the column initially increases, and then decreases. Considering an initial NO3− concentration of 50 mg L−1, and a filler particle size range of 0.8–1.2 mm, the maximum adsorption capacity of the La/CTAC–ECL column for NO3− is 18.99 mg g−1 for a filler column height of 10 cm and an influent flow rate of 15 ml min−1. The maximum quantity of adsorbed NO3− of 372.80 mg is obtained using a filler column height of 15 cm and an influent flow rate of 10 ml min−1. The Thomas and Yoon–Nelson models accurately predict the breakthrough of NO3− in groundwater in the simulated PRB column under different conditions, and the results are consistent with those from dynamic NO3− adsorption experiments. TEM, XRD, FTIR, and XPS analyses demonstrate that the modification using the La and CTAC improves the surface structure, porosity, permeability, and configuration of functional groups of the biochar. The mechanisms of NO3− removal from groundwater using the La/CTAC–ECL include pore filling, surface adsorption, ion exchange, and electrostatic adsorption. The composite La/CTAC–ECL exhibits a superior potential for the remediation of NO3− contaminated groundwater.

Depression is a mood disorder which causes a huge economic burden to both families and societies. However, those monoamine-based antidepressants used in clinical practice have been found to have various limitations. Therefore, currently it is very necessary to explore novel antidepressant targets and medications. As a main active component extracted from Scutellariae radix, oroxylin A possesses many pharmacological functions such as anti-cancer, anti-inflammation and neuroprotection. Here, the present study aims to investigate whether oroxylin A possess antidepressant-like actions using the chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) models of depression, forced swim test, tail suspension test, open field test, sucrose preference test, western blotting, immunofluorescence and viral-mediated gene interference. Our results revealed that treatment of oroxylin A fully prevented both the CUMS-induced and CRS-induced depressive-like behaviors in mice. Moreover, the protecting effects of oroxylin A against CUMS and CRS on mice behaviors were accompanied with a significant enhancement on the levels of brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine kinase B (pTrkB), phosphorylated cAMP-response element binding protein (pCREB) and neurogenesis in the hippocampus. Furthermore, genetic knockdown of BDNF and TrkB in the hippocampus remarkably abolished the antidepressant-like efficacy of oroxylin A in both the CUMS and CRS models of depression, proving that the hippocampal BDNF-TrkB system participates in the antidepressant mechanism of oroxylin A. In summary, our findings are the first evidence showing that oroxylin A possesses potential of being an antidepressant candidate.

BackgroundCatecholamine excess arising from pheochromocytomas and paragangliomas (PPGLs) can cause a wide spectrum of cardiac manifestations. Although there are reviews of reported cases, these reviews lack detailed data, which makes it impossible to perform an accurate analysis. In this study, we conducted a comprehensive analysis of cardiovascular complications (CCs), including PPGL-related myocardial injury, cardiogenic shock, and arrhythmias requiring antiarrhythmic therapy, in a large cohort of patients with PPGL.MethodsWe retrospectively analyzed the clinical data of consecutive patients with PPGL admitted between January 2018 and June 2020. The prevalence and the characteristics of patients with CCs were investigated. Moreover, comparisons were made between patients with and without CCs.ResultsCompared with the non-CC group, the percentage of men was significantly lower (14/41 vs.92/175, 34.1% vs. 52.6%, p = 0.034) and the proportion of patients with paroxysmal hypertension was significantly higher (13/41 vs.29/173, 31.7% vs.16.8%, p = 0.03) in the CC group. More patients showed excessive sweating (19/41 vs 64/175, 46.3% vs. 24.0%, p = 0.004) and PPGL crisis (7/41 vs. 10/175, 17.1% vs.5.7%, p=0.035) in the CC group. In terms of laboratory findings, higher white blood cell [7.36 (6.49, 20.23) vs. 5.95 (5.1, 6.97)×109/L, p

BackgroundCombining two immune checkpoint inhibitors (ICIs) instead of using one can effectively improve the prognosis of advanced malignant tumors. At present, ipilimumab alongside nivolumab is the most widely used combinatorial regimen of ICIs. However, the risk of treatment-related adverse events is higher in combinatorial regimens than in single-drug regimens. Thus, this study aimed to evaluate the risks of common adverse events associated with the combinatorial regimen of ipilimumab and nivolumab by using meta-analysis.MethodsWe searched Pubmed, Medline, EMBASE, and Cochrane Library for reports published by 30 September 2021. A randomized controlled study was developed and analyzed using the statistical software R to determine the efficacy of the combinatorial treatment. Risk estimates (hazard ratios, RR) and 95% confidence intervals for various common serious adverse events were used.ResultsA total of 23 randomized control trials (n = 3970 patients) were included. Our meta-analysis indicated the risks of adverse events of any grade and grade ≥ 3 as 90.42% (95%CI: 85.91% ~ 94.18%) and 46.46% (95%CI: 39.37% ~ 53.69%), respectively; the risks of treatment-related death and adverse events leading to discontinuation were estimated at 0.42% (95% CI, 0.18% ~ 0.72%) and 19.11% (95% CI, 14.99% ~ 24.38%), respectively. Classification of 19 common adverse events. The top 5 grade 1-2 adverse events were found to be fatigue (30.92%, 95% CI: 24.59% ~ 37.62%), pruritus (26.05%, 95%CI: 22.29%~29.99%), diarrhea (23.58%, 95% CI: 20.62% ~ 26.96%), rash (19.90%, 95%CI: 15.75% ~ 25.15%), and nausea (17.19%, 95% CI:13.7% ~ 21.57%). The top 5 grade ≥ 3 adverse events were identified as increased alanine aminotransferase(8.12%, 95% CI: 5.90%~10.65%), increased lipase(7.62%, 95% CI: 4.88% ~ 10.89%), and colitis (6.39%, 95%CI: 3.98% ~ 10.25%), increased aspartate aminotransferase (6.30%, 95% CI: 4.61% ~ 8.22%), and diarrhea(5.72%, 95%CI: 3.50% ~ 8.44%). Subgroup analysis revealed some differences in the adverse events between the N1-I3 and N3-I1 subgroups and between subgroups of different cancer types.ConclusionThis study summarized the risks of common adverse events in the co-treatment of malignant-tumor patients with ipilimumab and nivolumab and identified the impacts of various initial administration schemes on the risks of such events, thereby providing an important reference for the toxicity of co-treatment with ipilimumab and nivolumab.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42020181350.

Today’s engineering industries require graduates with a broad range of soft skills, which include teamwork, communication and integrity. Therefore, more accreditation bodies now recommend team-learning activities to be embedded in their engineering programmes. However, hardworking students often find group projects demotivating, especially if their contributions are not accurately reflected in their individual grades. To address these issues, we demonstrate that Electronic Laboratory Notebooks can be used to promote student collaboration and teamwork on a group project. They can also help instructors assess student contributions fairly. During our investigations, we noticed that students have used Electronic Laboratory Notebooks as social interaction tools that enable text, data, images and recorded audio to be exchanged. Consequently, we describe the experiences of 58 transnational undergraduate students in using six different software products for a team-based learning activity. According to our investigations, Electronic Laboratory Notebooks had a positive impact on supporting Team Based Learning in a new electronic engineering course. The outcomes of our investigations can help create effective teaching and learning resources for undergraduate students in Electronic Engineering. They can also help staff members make evidence-based decisions regarding the introduction of Electronic Laboratory Notebooks in undergraduate research activities.

Abstract High vigor seeds have greater yield potential than those with low vigor; however, long-term storage leads to a decline in this trait. The objective of this study was to identify quantitative trait loci (QTLs) for seed vigor-related traits under artificial aging conditions using a high-density genetic linkage map of wheat (Triticum aestivum) and mine the related candidate genes. A doubled haploid population, derived from a cross between Hanxuan 10 × Lumai 14, was used as the experimental material. Six controlled-environment treatments were set up, i.e. the seeds were aged for 0, 24, 36, 48, 60, and 72 h at a high temperature (48 °C) and under high humidity (relative humidity 100%). Eight traits including seed germination percentage, germination energy, germination index, seedling length, root length, seedling weight, vigor index, and simple vigor index were measured. With the prolongation of artificial aging treatment, these traits showed a continuous downward trend and significant correlations were observed between most of them. A total of 49 additive QTLs for seed vigor-related traits were mapped onto 12 chromosomes (1B, 2D, 3A, 3B, 3D, 4A, 4D, 5A, 5B, 5D, 6D, and 7A); and each one accounted for 6.01–17.18% of the phenotypic variations. Twenty-five pairs of epistatic QTLs were detected on all chromosomes, except for 5D, 6A, and 7D, and each epistasis accounted for 7.35–26.06% of the phenotypic variations. Three additive QTL hot spots were found on chromosomes 5A, 5B, and 5D, respectively. 13 QTLs, QGEe5B, QGIe5B, QSLc5B, QSLd5B, QSLf5B, QRLd5B, QRLe5B, QRLf5B, QVId5B, QVIe5B, QVIf5B, QSVId5B, and QSVIe5B, were located in the marker interval AX-94643729 ~ AX-110529646 on 5B and the physical interval 707,412,449–710,959,479 bp. Genes including TRAESCS5B01G564900, TRAESCS5B01G564200, TRAESCS5B01G562600, TraesCS5B02G562700, TRAESCS5B01G561300, TRAESCS5B01G561400, and TRAESCS5B01G562100, located in this marker interval, were found to be involved in regulating the processes of carbohydrate and lipid metabolism, transcription, and cell division during the germination of aging seeds, thus they were viewed as candidate genes for seed viability-related traits. These findings provide the basis for the seed-based cloning and functional identification of related candidate genes for seed vigor.

Abstract Flexible, large-area, and stable perovskite photodetectors have drawn increasing widespread research attention for next-generation wearable and portable optoelectronic devices. However, high mechanical durability coupled with large device area and enhanced environmental stability has not been demonstrated yet to attain practical viability. Herein, a highly bendable, stable, and large-area (3 cm2) flexible polystyrene incorporated perovskite photodetector is presented. Due to the formation of a porous polystyrene-perovskite composite film in a single step it allows unprecedented mechanical stability, maintaining 85% of its original photocurrent value after 10,000 bending cycles at a bending angle of 120°. Equally crucial, the solution-processed self-assembled Pt–Au nanochains were developed to provide a simple and fast method of patterning the conductive and flexible electrodes onto the filter substrate. The optimized polystyrene-perovskite photodetector exhibits a high responsivity up to 2.73 A W−1, a maximum specific detectivity of 6.2 × 1013 Jones, and a superior switching ratio of 1.0 × 104. In addition, the polystyrene-perovskite photodetector yields excellent stability under the combined stresses of moisture, ambient air, and room light, and retains 92% of its original performance for over 30 days. All these results demonstrate that this work provides a facile and cost-effective approach that paves the way to develop high-performance, stable, and highly flexible optoelectronic devices.