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Abstract The effect of low‐FODMAPs diet on irritable bowel syndrome (IBS) in Western China has not been reported. We aimed to investigate the effect of low‐FODMAPs diet on IBS patients in the area and whether low‐FODMAPs diet‐induced alterations of microbiota could be improved through probiotics. IBS patients were randomized to the control group, low‐FODMAPs diet group, probiotics group, or combined group. IBS Symptom Severity Score questionnaire (IBS‐SSS) and IBS Quality of Life Score questionnaire (IBS‐QOL) were completed at baseline, 2 and 4 weeks to evaluate the severity of symptoms. Fresh feces were collected for analyses of gut microbiota and short‐chain fatty acids at baseline and 4 weeks after intervention. Seventy‐three patients were included in the per protocol analysis. After intervention, there was significant improvement in IBS‐SSS in the low‐FODMAPs group (37.5%, 44.2%), probiotics group (51.4%, 62.0%), and combined group (34.1%, 40.4%) at both 2 weeks and 4 weeks, compared with the baseline (p

Abstract The purpose of this study is to evaluate loose suture-related inflammation and activation of conjunctiva-associated lymphoid tissue (CALT) in patients after keratoplasty. The patients who were treated with keratoplasty at the First Affiliated Hospital of Harbin Medical University between 2015 and 2022 were recruited into the study. We evaluated the time and location of loose suture development in patients after keratoplasty. In addition, in vivo confocal microscopy was used to evaluate the activation of CALT and the accumulation of inflammatory cells around loose sutures. Meso Scale Discovery assay detection kits were used to evaluate the inflammatory cytokines in the tears of patients before and after the loose suture was removed. In this study, we collected the information from 212 cases (212 eyes) who had PK (126 eyes) and DALK-treated (86 eyes) for corneal transplantation, including 124 males and 88 females, aged 14–84 years old. The average age was 50.65 ± 16.81 years old. Corneal sutures were more prone to loose at 3 months and 6 months after keratoplasty, and the frequent sites were at 5 and 6 o’clock. An increased number of inflammatory cells could be observed around the loose sutures than normal sutures (P

As a rapidly expanding family of 2D materials, MXenes have recently gained considerable attention. Herein, by developing a coating method that enables transfer‐free and layer‐by‐layer film coating, the nonlinear optical absorption (NOA) of Ti3C2Tx MXene films is investigated. Using the Z‐scan technique, the NOA of the MXene films is characterized at ≈800 nm. The results show that there is a strong and layer‐dependent NOA behavior, transitioning from reverse saturable absorption (RSA) to saturable absorption (SA) as the layer number increases from 5 to 30. Notably, the nonlinear absorption coefficient β changes significantly from ≈7.13 × 102 cm GW−1 to ≈−2.69 × 102 cm GW−1 within this range. The power‐dependent NOA of the MXene films is also characterized, and a decreasing trend in β is observed for increasing laser intensity. Finally, the NOA of 2D MXene films at ≈1550 nm is characterized by integrating them onto silicon nitride waveguides, where an SA behavior is observed for the films including 5 and 10 layers of MXene, in contrast to the RSA observed at ≈800 nm. These results reveal intriguing nonlinear optical properties of 2D MXene films, highlighting their versatility and potential for implementing high‐performance nonlinear photonic devices.

Abstract Background Although hepatitis B virus (HBV) infection is a major risk factor for hepatic cancer, the majority of HBV carriers do not develop this lethal disease. Additional molecular alterations are thus implicated in the process of liver tumorigenesis. Since phosphatase and tensin homolog (PTEN) is decreased in approximately half of liver cancers, we investigated the significance of PTEN deficiency in HBV-related hepatocarcinogenesis. Methods HBV-positive human liver cancer tissues were checked for PTEN expression. Transgenic HBV, Alb-Cre and Pten fl/fl mice were inter-crossed to generate WT, HBV, Pten −/− and HBV; Pten −/− mice. Immunoblotting, histological analysis and qRT-PCR were used to study these livers. Gp73 −/− mice were then mated with HBV; Pten −/− mice to illustrate the role of hepatic tumor biomarker golgi membrane protein 73 (GP73)/ golgi membrane protein 1 (GOLM1) in hepatic oncogenesis. Results Pten deletion and HBV transgene synergistically aggravated liver injury, inflammation, fibrosis and development of mixed hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). GP73 was augmented in HBV; Pten −/− livers. Knockout of GP73 blunted the synergistic effect of deficient Pten and transgenic HBV on liver injury, inflammation, fibrosis and cancer development. Conclusions This mixed HCC-ICC mouse model mimics liver cancer patients harboring HBV infection and PTEN/AKT signaling pathway alteration. Targeting GP73 is a promising therapeutic strategy for cancer patients with HBV infection and PTEN alteration.

This is an article in the field of earth sciences. According to insufficient research on the distribution characteristics, genetic mechanism, lithium extraction technology, and economic benefits of high-temperature geothermal water lithium resources in Southern Xizang. Through the analysis of plate tectonics, the test of geothermal water components, the comparative analysis of the applicability of lithium extraction technology in salt lakes, and the establishment of an economic evaluation model for lithium extraction from geothermal water, the following achievements have been achieved: (1) The geothermal water lithium in Southern Xizang is mainly distributed on both sides of the Yarlung Zangbo River deep fault zone and its southern region, Lithium-rich granite wall rock leaching and magmatic hydrothermal solution, it provides rich lithium sources for the formation of lithium-rich geothermal water. (2) In accordance with the characteristics of low concentration and low magnesium/lithium ratio in geothermal water lithium, the extraction method and precipitation method are selected to extract and utilize lithium in geothermal water. (3) Take geothermal well in the Gudui geothermal field as an example, with a lithium concentration of 23.5 mg/L in geothermal water, and the extraction process is used to extract lithium, establishing an economic evaluation model, using cash flow method to evaluate the economy, and the economic evaluation results showed that when the price of lithium carbonate is not less than 250000 yuan/t, the extraction of lithium from geothermal water has good economic benefits.

Abstract. Background:. Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells. Methods:. The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results:. Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts. Conclusions:. The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Zinc (Zn) is a vital micronutrient that strengthens the immune system, aids cellular activities, and treats infectious diseases. A deficiency in Zn can lead to an imbalance in the immune system. This imbalance is particularly evident in severe deficiency cases, where there is a high susceptibility to various viral infections, including COVID-19 caused by SARS-CoV-2. This review article examines the nutritional roles of Zn in human health, the maintenance of Zn concentration, and Zn uptake. As Zn is an essential trace element that plays a critical role in the immune system and is necessary for immune cell function and cell signaling, the roles of Zn in the human immune system, immune cells, interleukins, and its role in SARS-CoV-2 infection are further discussed. In summary, this review paper encapsulates the nutritional role of Zn in the human immune system, with the hope of providing specific insights into Zn research.

Dasatinib-related resistance frequently occurs and may lead to the failure of chemotherapy; thus, dose interruptions are necessary. Cannabidiol (CBD) has potential for integration with orthodox cancer care. In this study, we explored the combination effect of CBD and dasatinib on A549 cells. CBD in combination with dasatinib could induce significant synergistic apoptosis in vitro (ZIP > 10) and in vivo. The combination of CBD and low-dose dasatinib exhibited antiproliferative and proapoptotic effects through up-regulation of caspase-3 and Bax, and down-regulation of Bcl-2 in A549 cells. The xenograft mouse model suggested that the combination was more efficient and safer. In short, CBD and low-dose dasatinib exhibited a synergistic effect on anticancer by targeting the SRC/PI3K/AKT signaling pathway, suggesting a potential therapeutic option for the treatment of lung cancer.

Abstract Purpose This study aims to establish and validate a new diagnosis model called P.Z.A. score for clinically significant prostate cancer (csPCa). Methods The demographic and clinical characteristics of 956 patients were recorded. Age, prostate-specific antigen (PSA), free/total PSA (f/tPSA), PSA density (PSAD), peripheral zone volume ratio (PZ-ratio), and adjusted PSAD of PZ (aPSADPZ) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The nomogram was established, and discrimination abilities of the new nomogram were verified with a calibration curve and area under the ROC curve (AUC). The clinical benefits of P.Z.A. score were evaluated by decision curve analysis and clinical impact curves. External validation of the model using the validation set was also performed. Results The AUCs of aPSADPZ, age, PSA, f/tPSA, PSAD and PZ-ratio were 0.824, 0.672, 0.684, 0.715, 0.792 and 0.717, respectively. The optimal threshold of P.Z.A. score was 0.41. The nomogram displayed excellent net benefit and better overall calibration for predicting the occurrence of csPCa. In addition, the number of patients with csPCa predicted by P.Z.A. score was in good agreement with the actual number of patients with csPCa in the high-risk threshold. The validation set provided better validation of the model. Conclusion P.Z.A. score (including PIRADS(P), aPSADPZ(Z) and age(A)) can increase the detection rate of csPCa, which may decrease the risk of misdiagnosis and reduce the number of unnecessary biopsies. P.Z.A. score contains data that is easy to obtain and is worthy of clinical replication.

Abstract In recommender systems, user reviews on items contain rich semantic information, which can express users’ preferences and item features. However, existing review-based recommendation methods either use the static word vector model or cannot effectively extract long sequence features in reviews, resulting in the limited ability of user feature expression. Furthermore, the impact of different or useless feature interactions between users and items on recommendation performance is ignored. Therefore, we propose an attentional factorization machine with review-based user–item interaction for recommendation (AFMRUI), which first leverages RoBERTa to obtain the embedding feature of each user/item review, and combines bidirectional gated recurrent units with attention network to highlight more useful information in both user and item reviews. Then we adopt AFM to learn user–item feature interactions to distinguish the importance of different user–item feature interactions and further to obtain more accurate rating prediction, so as to promote recommendation. Finally, we conducted performance evaluation on five real-world datasets. Experimental results on five datasets demonstrated that the proposed AFMRUI outperformed the state-of-the-art review-based methods regarding two commonly used evaluation metrics.

Background: Selecting the correct ventilation strategy is crucial for the survival of preterm infants with dyspnea in NICU. Lung ultrasound score (LUSsc) is a potential predictor for respiratory support patterns in preterm infants. Methods: We prospectively included 857 preterm infants. LUS was performed in the first 2 h after admission, and LUSsc was determined by two specialist sonographers. Participants were divided into two categories according to gestational age ( 0.05) for preterm 32+0–36+6 weeks (Kappa value 0.779, P 0.05). Conclusion: The LUSsc showed good reliability in predicting respiratory support mode for preterm infants with dyspnea.Registered at ClinicalTrials.gov (identifier: chiCTR1900023869).

Graph neural networks (GNNs) have shown significant success in graph representation learning. However, the performance of existing GNNs degrades seriously when their layers deepen due to the over-smoothing issue. The node embedding incline converges to a certain value when GNNs repeat, aggregating the representations of the receptive field. The main reason for over-smoothing is that the receptive field of each node tends to be similar as the layers increase, which leads to different nodes aggregating similar information. To solve this problem, we propose an adaptive multi-channel deep graph neural network (AMD-GNN) to adaptively and symmetrically aggregate information from the deep receptive field. The proposed model ensures that the receptive field of each node in the deep layer is different so that the node representations are distinguishable. The experimental results demonstrate that AMD-GNN achieves state-of-the-art performance on node classification tasks with deep models.

The outstanding lubrication of articular cartilage in the major synovial joints such as hips and knees, essential for the joint well-being, has been attributed to boundary layers of lipids at the outer cartilage surfaces, which have very low friction mediated by the hydration lubrication mechanism at their highly hydrated exposed headgroups. However, the role of spontaneously present lipid splays—lipids with an acyl tail in each of the opposing bilayers—in modulating the frictional force between lipid bilayers has not, to date, been considered. In this study, we perform all-atom molecular dynamics simulations to quantitatively assess the significance of splayed molecules within the framework of lubricating lipid bilayers. We demonstrate that, although transient, splayed molecules significantly increase the inter-membrane friction until their retraction back into the lamellar phase, with this effect more steadily occurring at lower sliding velocities that are comparable to the physiological velocities of sliding articular cartilage.

Purpose – Global climate change is a serious threat to the survival and development of mankind. Reducing carbon emissions and achieving carbon neutrality are the keys to reducing greenhouse gas emissions and promoting sustainable human development. For many countries, taking China as an example, the electric power sector is the main contributor to the country’s carbon emissions, as well as a key sector for reducing carbon emissions and achieving carbon neutrality. The low-carbon transition of the power sector is of great significance to the long-term low-carbon development of the economy. Therefore, on the one hand, it is necessary to improve the energy supply structure on the supply side and increase the proportion of new energy in the total power supply. On the other hand, it is necessary to improve energy utilization efficiency on the demand side and control the total primary energy consumption by improving energy efficiency, which is the most direct and effective way to reduce emissions. Improving the utilization efficiency of electric energy and realizing the low-carbon transition of the electric power industry requires synergies between the government and the market. The purpose of this study is to investigate the individual and synergistic effects of China’s low-carbon policy and the opening of urban high-speed railways (HSRs) on the urban electricity consumption efficiency, measured as electricity consumption per unit of gross domestic product (GDP). Design/methodology/approach – This study uses a panel of 289 Chinese prefecture-level cities from the years 1999–2019 as the sample and uses the time-varying difference-in-difference method to test the relationship between HSR, low-carbon pilot cities and urban electricity consumption efficiency. In addition, the instrumental variable method is adopted to make a robustness check. Findings – Empirical results show that the low-carbon pilot policy and the HSR operation in cities would reduce the energy consumption per unit of GDP, and synergies occur in both HSR operated and low-carbon pilot cities. Research limitations/implications – This study has limitations that would provide possible starting points for future studies. The first limitation is the choice of the proxy variable of government and market factors. The second limitation is that the existing data is only about whether the high-speed rail is opened or not and whether it is a low-carbon pilot city, and there is no more informative data to combine the two aspects. Practical implications – The findings of this study can inform policymakers and regulators about the effects of low-carbon pilot city policies. In addition, the government should consider market-level factors in addition to policy factors. Only by combining various influencing factors can the efficient use of energy be more effectively achieved so as to achieve the goal of carbon neutrality. Social implications – From the social perspective, the findings indicate that improving energy utilization is dependent on the joint efforts of the government and market. Originality/value – The study provides quantitative evidence to assess the synergic effect between government and the market in the low-carbon transition of the electric power industry. Particularly, to the best of the authors’ knowledge, it is the first to comprehend the role of the city low-carbon pilot policy and the construction of HSR in improving electricity efficiency.

Abstract Background μ‐opioid receptor agonists (MORAs) are indispensable for analgesia in bladder cancer (BC) patients, both during surgery and for chronic pain treatment. Whether MORAs affect BC progression and metastasis remains largely unknown. This study focused on the effects of MORAs on the formation of circulating tumor cells (CTCs) in BC and aimed to provide potential therapeutic targets, which would retain the pain‐relieving effects of MORAs in BC patients without sacrificing their long‐term prognosis. Methods Different preclinical models were used to identify the effects of MORAs on the progression of BC. A novel immunocapture microfluidic chip was utilized to analyze whether MORAs affected the number of CTCs in mouse models and clinical BC patients. Bioinformatic analyses, total transcriptome sequencing, and molecular biology methods were then used to investigate the underlying mechanisms in these models and in BC cell lines. Results Mouse models of hematogenous metastasis and in situ BC demonstrated that tumor metastasis was significantly increased after MORA treatment. A significant increase in the number of mesenchymal and/or epithelial CTCs was detected after MORA treatment in both the mouse models and clinical trial patients. Mechanistically, MORAs facilitated the formation of CTCs by activating the MOR/PI3K/AKT/Slug signaling pathway, hereby promoting the epithelial‐mesenchymal transition (EMT) of BC cells, as knockdown of MOR, Slug or blockade of PI3K inhibited the EMT process and CTC formation. Conclusion MORAs promoted BC metastasis by facilitating CTC formation. The EMT‐CTC axis could be targeted for preventive measures during MORA treatment to inhibit the associated tumor metastasis or recurrence in BC patients.

Abstract Objectives This study aimed to assess the epidemiological features and explore the potential risk factors for early neurological deterioration (END) in patients with acute single small subcortical infarction (SSSI) who underwent antiplatelet therapy without carotid artery stenosis. Materials & methods Patients with SSSI, as confirmed by cranial magnetic resonance imaging (MRI), who were hospitalized within 48 h after the onset of symptoms were enrolled. END was mainly defined as increment in the National Institutes of Health Stroke Scale (NIHSS) score of ≥ 2 points or any new neurological deficit. Poor functional outcome was defined as modified Rankin Scale (mRS) score of > 2 points at 3-month after the onset. The association of END with multiple indicators was assessed at the early stage of admission using multivariate logistic regression analysis, and adjusted odds ratios (aORs) were calculated. Results A total of 280 patients were enrolled from June 2020 to May 2021, of whom, END occurred in 44 (15.7%) patients (median age, 64 years; 70.5% male), while END occurred during sleep in 28 (63.6%) patients. History of hypertension (aOR: 4.82, p = 0.001), infarction in internal capsule (aOR: 3.35, p = 0.001), and elevated level of low-density lipoprotein cholesterol (LDL-C; aOR: 0.036, p = 0.0016) were significantly associated with the risk of END. Patients with END (aOR: 5.74, p = 0.002), history of diabetes (aOR: 2.61, p = 0.020), and higher NIHSS scores at discharge (per 1-score increase, aOR: 1.29, p = 0.026) were associated with the poor functional outcome at 3-month after the onset. Conclusion Patients with a history of hypertension, infarction in internal capsule or a higher level of LDL-C were found to be at a higher risk of END.

Purpose: Insufficient osseointegration and implant-associated infection are major factors in the failure of Ti-based implants, thus spurring scientists to develop multifunctional coatings that are better suited for clinical requirements. Here, a new biomimetic micro/nanoscale topography coating combined with antibacterial copper was simultaneously designed for Ti-based implant surfaces by adopting a hybrid approach combining plasma electrolytic oxidation and hydrothermal treatment.Results: The biological interactions between this biofunctionalized material interface and stem cells promoted cellular adhesion and spreading during initial attachment and supported cellular proliferation for favorable biocompatibility. Bone marrow mesenchymal stem cells (BMMSCs) on the coating displayed enhanced cellular mineral deposition ability, higher alkaline phosphatase activity, and upregulated expression of osteogenic-related markers without the addition of osteoinductive chemical factors, which improved osseointegration. More interestingly, this new coating reduced the viability of oral pathogens (Fusobacterium nucleatum and Porphyromonas gingivalis)—the primary causes of implant-associated infections as indicated by damage of cellular structures and decreased population. This is the first study investigating the antibacterial property of dental implants modified by a hybrid approach against oral pathogens to better mimic the oral environment.Conclusion: These findings suggest that biofunctionalization of the implant coating by surface modification methods and the incorporation of antibacterial copper (Cu) offer superior osteogenesis capability and effective antibacterial activity, respectively. These strategies have great value in orthopedic and dental implant applications.

Abstract Background Human brucellosis has become one of the major public health problems in China, and increases atypical manifestations, such as fever of unknown origin (FUO), and misdiagnosis rates has complicated the diagnosis of brucellosis. To date, no relevant study on the relationship between brucellosis and FUO has been conducted. Methods We retrospectively reviewed the medical charts of 35 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. The patients were admitted to the Second Affiliated Hospital of Nanchang University between January 01, 2013 and October 31, 2019. Patient data were collected from hospital medical records. Results The percentage of males was significantly higher than that of female in FUO (78.95% vs. 21.05%, P

Background Prolonged spinal surgery in the prone position may lead to postoperative pulmonary complications (PPCs). We aimed to compare the effects of driving pressure-guided ventilation versus conventional protective ventilation on postoperative pulmonary complications in patients undergoing spinal surgery in the prone position. We hypothesized that driving pressure-guided ventilation would be associated with a decreased incidence of PPC. Methods We enrolled 78 patients into this single-center, double-blind, randomized controlled trial. The driving pressure (DP) group (n = 40) received a tidal volume of 6 ml/kg of predicted body weight, individualized positive end-expiratory pressure (PEEP) which produced the lowest driving pressure (plateau pressure-PEEP), and a recruitment maneuver. The protective ventilation (PV) group (n = 38) received the same tidal volume and recruitment maneuver but with a fixed PEEP of 5 cm H2O. Our primary outcome was postoperative pulmonary complications based on Lung Ultrasound Scores (LUS) at the end of the surgery and the simplified Clinical Pulmonary Infection Score (sCPIS) on postoperative days (POD) 1 and 3. Results DP patients had lower LUS and POD1 sCPIS than the PV group (p 0.05). The visual pain score (VAS) in postoperative days, drainage, and lengths of stay (LOS) were also similar between the two groups (p > 0.05). Conclusions Driving pressure-guided ventilation during spinal surgery with a prolonged prone patient position may reduce the incidence of early postoperative pulmonary complications, compared with conventional protective ventilation.

Abstract Tumor immune microenvironment exerts a profound effect on the population of infiltrating immune cells. Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) is frequently overexpressed in a variety of cells, particularly during inflammation and tissue injury. However, its function in cancer and immunity remains enigmatic. In this study, we find that TIMP1 is substantially up-regulated during tumorigenesis through analyzing cancer bioinformatics databases, which is further confirmed by IHC tissue microarrays of clinical samples. The TIMP1 level is significantly increased in lymphocytes infiltrating the tumors and correlated with cancer progression, particularly in GBM. Notably, we find that the transcriptional factor Sp1 binds to the promoter of TIMP1 and triggers its expression in GBM. Together, our findings suggest that the Sp1-TIMP1 axis can be a potent biomarker for evaluating immune cell infiltration at the tumor sites and therefore, the malignant progression of GBM.

ObjectiveThe purpose of this research was to develop a radiomics model that combines several clinical features for preoperative prediction of the pathological grade of bladder cancer (BCa) using non-enhanced computed tomography (NE-CT) scanning images.Materials and methodsThe computed tomography (CT), clinical, and pathological data of 105 BCa patients attending our hospital between January 2017 and August 2022 were retrospectively evaluated. The study cohort comprised 44 low-grade BCa and 61 high-grade BCa patients. The subjects were randomly divided into training (n = 73) and validation (n = 32) cohorts at a ratio of 7:3. Radiomic features were extracted from NE-CT images. A total of 15 representative features were screened using the least absolute shrinkage and selection operator (LASSO) algorithm. Based on these characteristics, six models for predicting BCa pathological grade, including support vector machine (SVM), k-nearest neighbor (KNN), gradient boosting decision tree (GBDT), logical regression (LR), random forest (RF), and extreme gradient boosting (XGBOOST) were constructed. The model combining radiomics score and clinical factors was further constructed. The predictive performance of the models was evaluated based on the area under the receiver operating characteristic (ROC) curve, DeLong test, and decision curve analysis (DCA).ResultsThe selected clinical factors for the model included age and tumor size. LASSO regression analysis identified 15 features most linked to BCa grade, which were included in the machine learning model. The SVM analysis revealed that the highest AUC of the model was 0.842. A nomogram combining the radiomics signature and selected clinical variables showed accurate prediction of the pathological grade of BCa preoperatively. The AUC of the training cohort was 0.919, whereas that of the validation cohort was 0.854. The clinical value of the combined radiomics nomogram was validated using calibration curve and DCA.ConclusionMachine learning models combining CT semantic features and the selected clinical variables can accurately predict the pathological grade of BCa, offering a non-invasive and accurate approach for predicting the pathological grade of BCa preoperatively.

Renal fibrosis, an important pathological change in the development of diabetic kidney disease (DKD), urgently needs new treatment methods clinically. The Jiedu Tongluo Baoshen (JTBF) formula was created based on the theory of toxic damage to the kidney collaterals, and a variety of active ingredients in JTBF have inhibitory effects on epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM). In this study, the Ultra Performance Liquid Chromatography (UPLC) was employed to analyze the effective ingredients in the JTBF formula. After screening in the PubChem database, we identified 94 active compounds of JTBF and predicted the SIRT1 pathway as potential targets through network pharmacology. In addition, in the high fat diet (HFD)+Streptozocin (STZ)-induced DKD rat model and high glucose (HG)-induced NRK-52E cell model, JTBF treatment activates the phosphorylation of LKB1 and AMPK and enhances the autophagy activity of NRK-52E cells, thereby reducing the accumulation of EMT and ECM. These results have been confirmed in vivo and in vitro experiments. JTBF enhances the autophagy activity of renal tubular epithelial cells and inhibits the progression of DKD renal fibrosis by activating the SIRT1/LKB1/AMPK signal pathway. This study provides new insights into the molecular mechanism of JTBF to prevent and treat DKD renal fibrosis.

The engineering of thermo-optic effects has found broad applications in integrated photonic devices, facilitating efficient light manipulation to achieve various functionalities. Here, we perform both an experimental characterization and a theoretical analysis of these effects in integrated microring resonators made from high-index doped silica, which have had many applications in integrated photonics and nonlinear optics. By fitting the experimental results with theory, we obtain fundamental parameters that characterize their thermo-optic performance, including the thermo-optic coefficient, the efficiency of the optically induced thermo-optic process, and the thermal conductivity. The characteristics of these parameters are compared to those of other materials commonly used for integrated photonic platforms, such as silicon, silicon nitride, and silica. These results offer a comprehensive insight into the thermo-optic properties of doped silica-based devices. Understanding these properties is essential for efficiently controlling and engineering them in many practical applications.

Abstract Schizophrenia affects >3.2 million people in the USA. However, its comorbidity patterns have not been systematically characterized in real-world populations. To address this gap, we conducted an observational study using a cohort of 86 million patients in a nationwide health insurance dataset. We identified participants with schizophrenia and those without schizophrenia matched by age, sex, and the first three digits of zip code. For each phenotype encoded in phecodes, we compared their prevalence in schizophrenia patients and the matched non-schizophrenic participants, and we performed subgroup analyses stratified by age and sex. Results show that anxiety, posttraumatic stress disorder, and substance abuse commonly occur in adolescents and young adults prior to schizophrenia diagnoses. Patients aged 60 and above are at higher risks of developing delirium, alcoholism, dementia, pelvic fracture, and osteomyelitis than their matched controls. Type 2 diabetes, sleep apnea, and eating disorders were more prevalent in women prior to schizophrenia diagnosis, whereas acute renal failure, rhabdomyolysis, and developmental delays were found at higher rates in men. Anxiety and obesity are more commonly seen in patients with schizoaffective disorders compared to patients with other types of schizophrenia. Leveraging a large-scale insurance claims dataset, this study identified less-known comorbidity patterns of schizophrenia and confirmed known ones. These comorbidity profiles can guide clinicians and researchers to take heed of early signs of co-occurring diseases.

Abstract. Background:. Till date, the optimal treatment strategy for delivering adjuvant androgen deprivation therapy (ADT) in localized and locally advanced prostate cancer (PCa), as a lower stage in PCa progression compared with metastatic PCa, is still unclear. This study compares the efficacy of castration alone with complete androgen blockade (CAB) as adjuvant ADT in patients with localized and locally advanced PCa undergoing radical prostatectomy (RP). Methods:. Patients diagnosed with PCa, without lymph node or distant metastasis, who received RP in West China Hospital between January 2009 and April 2019, were enrolled in this study. We performed survival, multivariable Cox proportional hazard regression, and subgroup analyses. Results:. A total of 262 patients were enrolled, including 107 patients who received castration alone and 155 patients who received CAB. The survival analysis revealed that there was no significant difference between the two groups (hazard ratios [HR] = 1.07, 95% confidence intervals [95% CI] = 0.60–1.90, P = 0.8195). Moreover, the multivariable Cox model provided similarly negative results before and after adjustment for potential covariant. Similarly, there was no significant difference in the clinical recurrence between the two groups in both non-adjusted and adjusted models. Furthermore, our subgroup analysis showed that CAB achieved better biochemical recurrence (BCR) outcomes than medical castration alone as adjuvant ADT for locally advanced PCa (P for interaction = 0.0247, HR = 0.37, 95% CI = 0.14–1.00, P = 0.0497). Conclusion:. Combined androgen blockade achieved better BCR outcomes compared with medical castration alone as adjuvant ADT for locally advanced PCa without lymph node metastasis.

Background. Acute liver failure (ALF), previously known as fulminant hepatic failure, has become a common, rapidly progressive, and life-threatening catastrophic hepatic disease in intensive care unit (ICU) due to the continuous increase in drug abuse, viral infection, metabolic insult, and auto-immune cause. At present, plasma exchange (PE) is the main effective alternative treatment for ALF in ICU clinical practice, and high-volume plasma exchange (HVP) has been listed as a grade I recommendation for ALF management in the American Society for Apheresis (ASFA) guidelines. However, no existing models can provide a satisfactory performance for clinical prediction on 90-day transplant-free mortality in adult patients with ALF undergoing PE. Our study aims to identify a novel and simple clinical predictor of 90-day transplant-free mortality in adult patients with ALF undergoing PE. Methods. This retrospective study contained adult patients with ALF undergoing PE from the Medical ICU (MICU) in the Second Affiliated Hospital of Harbin Medical University between January 2017 and December 2020. Baseline and clinical data were collected and calculated on admission to ICU before PE, including gender, age, height, weight, body mass index (BMI), etiology, total bilirubin, direct bilirubin, indirect bilirubin, prothrombin activity, model for end-stage liver disease (MELD) score, and sequential organ failure assessment (SOFA) score. Enrolled adult patients with ALF undergoing PE were divided into a survival group and a death group at discharge and 90 days on account of medical records and telephone follow-up. After each PE, decreased rates of total bilirubin and MELD score and increased rates of prothrombin activity were calculated according to the clinical parameters. In clinical practice, different patients underwent different times of PE, and thus, mean decrease rates of total bilirubin and MELD score and mean increase rate of prothrombin activity were obtained for further statistical analysis. Results. A total of 73 adult patients with ALF undergoing 204 PE were included in our retrospective study, and their transplant-free mortality at discharge and 90 days was 6.85% (5/73) and 31.51% (23/73), respectively. All deaths could be attributed to ALF-induced severe and life-threatening complications or even multiple organ dysfunction syndrome (MODS). Most of the enrolled adult patients with ALF were men (76.71%, 56/73), with a median age of 48.77 years. Various hepatitis virus infections, unknown etiology, auto-immune liver disease, drug-induced liver injury, and acute pancreatitis (AP) accounted for 75.34%, 12.33%, 6.85%, 4.11%, and 1.37% of the etiologies in adult patients with ALF, respectively. Univariate analysis showed a significant difference in age, mean decrease rates of total bilirubin and MELD score mean increase rate of prothrombin activity, decrease rates of total bilirubin and MELD score, and increase rate of prothrombin activity after the first PE between the death group and survival group. Multivariate analysis showed that age and mean decrease rates of total bilirubin and MELD score were closely associated with 90-day transplant-free mortality in adult patients with ALF undergoing PE. The 90-day transplant-free mortality was 1.081, 0.908, and 0.893 times of the original value with each one-unit increase in age and mean decrease rates of total bilirubin and MELD score, respectively. The areas under the receiver operatingcharacteristic (ROC) curve of age, mean decrease rates of total bilirubin and MELD score, and the three combined were 0.689, 0.225, 0.123, and 0.912, respectively. The cut-off values of age, mean decrease rates of total bilirubin and MELD score, and the three combined were 61.50, 3.12, 1.21, and 0.33, respectively. The specificity and sensitivity of combined age with mean decrease rates of total bilirubin and MELD score for predicting 90-day transplant-free mortality in adult patients with ALF undergoing PE were 87% and 14%. Conclusion. Combined age with mean decrease rates of total bilirubin and MELD score as a novel and simple clinical predictor can accurately predict 90-day transplant-free mortality in adult patients with ALF undergoing PE, which is worthy of application and promotion in clinical practice, especially in the identification of potential transplant candidates.

Community detection is an extremely important task for complex network analysis. There still remains a challenge of how to improve the performance of community detection in real-world scenario. Some researchers think that the content in networks is helpful to identify communities, and also focus on combining network topology with node contents, alongside the eradication of inauspicious performance. Furthermore, network topology is often sparse, which is reflected in the lack of capability to represent communities. To address the above problems, this study identifies a novel non-negative matrix factorization method which both employs network embedding to enhance the representation power of network topology for communities and also integrates network topology and node contents for further raising the quality of community detection. Furthermore, we then obtain the parameters of the model for finding communities which is based on model inference. Alongside both synthetic and real-world networks with ground-truths, we compare the new method with the state-of-the-art methods. Experimental results show that the new method obtains significant improvement for community detection both by incorporating node contents and by enhancing network topology.

To reduce treatment-related side effects in low-risk prostate cancer (PCa), both focal therapy and deferred treatments, including active surveillance (AS) and watchful waiting (WW), are worth considering over radical prostatectomy (RP). Therefore, this study aimed to compare long-term survival outcomes between focal therapy and AS/WW. Data were obtained and analyzed from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with low-risk PCa who received focal therapy or AS/WW from 2010 to 2016 were included. Focal therapy included cryotherapy and laser ablation. Multivariate Cox proportional hazards models were used to compare overall mortality (OM) and cancer-specific mortality (CSM) between AS/WW and focal therapy, and propensity score matching (PSM) was performed to reduce the influence of bias and unmeasured confounders. A total of 19 292 patients with low-risk PCa were included in this study. In multivariate Cox proportional hazards model analysis, the risk of OM was higher in patients receiving focal therapy than those receiving AS/WW (hazard ratio [HR] = 1.35, 95% confidence interval [CI]: 1.02–1.79, P = 0.037), whereas no significant difference was found in CSM (HR = 0.98, 95% CI: 0.23–4.11, P = 0.977). After PSM, the OM and CSM of focal therapy and AS/WW showed no significant differences (HR = 1.26, 95% CI: 0.92–1.74, P = 0.149; and HR = 1.26, 95% CI: 0.24–6.51, P = 0.782, respectively). For patients with low-risk PCa, focal therapy was no match for AS/WW in decreasing OM, suggesting that AS/WW could bring more overall survival benefits.

The study of community detection in networks has drawn great attention in recent years. To find communities and to understand community semantics, both network topology and network content are utilized. Unfortunately, none of them can explain the driving factors of generating community structure with semantics, which is significant for understanding the mechanisms of community generation. Our observations on a large number of networks show that specific user social behaviors are underlying factors for the generation of community structure. We exploit four types of social behaviors that widely exist in networks, i.e., reciprocity of interactions, posting preference, multitopic preference, and temporal variation of topics. We investigate their impacts on the formation process of links and content in networks, during which communities with topics form. Our analysis shows that they are highly related to community structure. Consequently, a generative community detection model SBCD (social behavior-based community detection) is proposed by combining network topology and content, in which the above social behaviors play a core role. The model is evaluated on two real datasets. The experimental results show that SBCD outperforms state-of-the-art baselines. Finally, a case study illustrates several significant observations with respect to the proposed social behaviors.

Prostate cancer (PCa) is the second-most common cancer among men. Both active surveillance or watchful waiting (AS/WW) and focal laser ablation (FLA) can avoid the complications caused by radical treatment. How to make the choice between these options in clinical practice needs further study. Therefore, this study aims to compare and analyze their effects based on overall survival (OS) and cancer-specific survival (CSS) to obtain better long-term benefits. We included patients with low-risk PCa from the Surveillance Epidemiology and End Results database of 2010–2016. Multivariate Cox proportional hazard analyses were conducted for OS and CSS in the two groups. To eliminate bias, this study applied a series of sensitivity analyses. Moreover, Kaplan–Meier curves were plotted to obtain survival status. A total of 18 841 patients with low-risk PCa were included, with a median of 36-month follow-up. According to the multivariate Cox proportional hazard regression, the FLA group presented inferior survival benefits in OS than the AS/WW group (hazard ratio [HR]: 2.13, 95% confidence interval [CI]: 1.37–3.33, P < 0.05). After adjusting for confounders, the result persisted (HR: 1.69, 95% CI: 1.02–2.81, P < 0.05). According to the results of the sensitivity analysis, the inverse probability of the treatment weighing model indicated the same result in OS. In conclusion, AS/WW and FLA have the advantage of fewer side effects and the benefit of avoiding overtreatment compared with standard treatment. Our study suggested that AS/WW provides more survival benefits for patients with low-risk PCa. More relevant researches and data will be needed for further clarity.

AbstractText style transfer is an important task in natural language generation, which aims to control certain attributes in the generated text, such as politeness, emotion, humor, and many others. It has a long history in the field of natural language processing, and recently has re-gained significant attention thanks to the promising performance brought by deep neural models. In this article, we present a systematic survey of the research on neural text style transfer, spanning over 100 representative articles since the first neural text style transfer work in 2017. We discuss the task formulation, existing datasets and subtasks, evaluation, as well as the rich methodologies in the presence of parallel and non-parallel data. We also provide discussions on a variety of important topics regarding the future development of this task.1

BackgroundIt has been reported for several years that polycyclic aromatic hydrocarbons (PAHs) could disturb human endocrine function. However, there is still a short of consistent conclusion about the relationship between PAH exposure and levels of sexual hormones. The aim of our study is to explore whether exposure to PAHs and how PAHs affect the levels of serum testosterone (T) and estradiol (E2) in adults, hoping to fulfill the knowledge gap.Materials and methodsThis study included adults aged 20 and above who participated in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. We included 10 PAH metabolites in this study. The levels of urinary PAH metabolites were log-transformed and divided into quartiles. The associations between PAH metabolites and both serum T levels of males and E2 levels of females were investigated using multivariate regression models. We furtherly calculated PAHs scores by sum of ranks across 10 PAHs metabolites, which represented the exposure levels of PAHs mixtures, and the association between PAHs scores and serum T and E2 levels were analyzed.ResultsA total of 4,654 subjects were included in this study, including 2,460 males and 2,194 females. After adjusting for confounders, 2-hydroxynapthalene and 3-hydroxyfluorene were positively associated with serum T levels of males (p-value for trend=0.047, and p-value for trend=0.006, respectively), while 1-hydroxyphenanthrene was positively associated with serum E2 levels of females (p-value for trend=0.013). In the adjusted models, no significant association was found between PAHs scores and either T levels of males or E2 levels of females (p-value for trend=0.615, and p-value for trend=0.241, respectively).ConclusionsThis study showed urinary 2-hydroxynapthalene and 3-hydroxyfluorene were associated with increased T levels of males, and urinary 1-hydroxyphenanthrene was associated with increased E2 levels of females. The observed association indicated disrupting effects of PAH exposure on reproductive health.

BackgroundBiomarkers acquired from blood samples are easy to obtain and cost-effective, have attracted considerable interest, and have been widely investigated. Inflammation plays a crucial role in cancer cell initiation, proliferation, and metastasis. We aimed to evaluate the association of the preoperative systemic immune-inflammation index (SII) with the clinical outcomes of patients diagnosed with bladder cancer and who underwent radical cystectomy (RC).Materials and methodsData from patients diagnosed with bladder cancer and who underwent RC from December 2010 to May 2020 in West China Hospital were retrospectively collected according to the inclusion and exclusion criteria. Patients were divided into a low-SII group and a high-SII group according to the SII level. Survival outcomes were obtained during follow-up. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS). Cox proportional hazard models were performed to estimate the effect of SII on OS and RFS and control for potential confoundings. Subgroup analyses were conducted, and the log likelihood ratio test was used to inspect the interaction.ResultsA total of 725 patients who underwent RC were ultimately involved in this study. Of these patients, 621 (85.66%) were men and 104 (14.34%) were women. The median age was 65 years. The median follow-up was 36 months for OS and 33.6 months for RFS. The optimal cutoff value was identified as 554.23 × 109/l. A total of 467 (64.41%) patients were divided into the low-SII group (SII

The Hippo signaling pathway is involved in cell growth, proliferation, and apoptosis, and it plays a key role in regulating organ size, tissue regeneration, and tumor development. The Hippo signaling pathway also participates in the occurrence and development of various human diseases. Recently, many studies have shown that the Hippo pathway is closely related to renal diseases, including renal cancer, cystic kidney disease, diabetic nephropathy, and renal fibrosis, and it promotes the transformation of acute kidney disease to chronic kidney disease (CKD). The present paper summarizes and analyzes the research status of the Hippo signaling pathway in different kidney diseases, and it also summarizes the expression of Hippo signaling pathway components in pathological tissues of kidney diseases. In addition, the present paper discusses the positive therapeutic significance of traditional Chinese medicine (TCM) in regulating the Hippo signaling pathway for treating kidney diseases. This article introduces new targets and ideas for drug development, clinical diagnosis, and treatment of kidney diseases.

PurposeThe aim of this study was to explore a new model of clinical decision-making to predict the occurrence of clinically significant prostate cancer (csPCa).Patients and MethodsThe demographic and clinical characteristics of 152 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), adjusted PSAD of peripheral zone (aPSADPZ), and peripheral zone volume ratio (PZ ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves.ResultsThe AUCs of PSA, PSAD, aPSADPZ, and PZ ratio were 0.521, 0.645, 0.745, and 0.717 for prostate cancer (PCa) diagnosis, while the corresponding values were 0.590, 0.678, 0.780, and 0.731 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of csPCa. The new model significantly improved the diagnostic accuracy of csPCa (0.865 vs. 0.741, p = 0.0284) compared with the base model. In addition, the new model was better than the base model for predicting csPCa in the low or medium probability while the number of patients with csPCa predicted by the new model was in good agreement with the actual number of patients with csPCa in the high-risk threshold.ConclusionsThis study demonstrates that aPSADPZ has a higher predictive accuracy for csPCa diagnosis than the conventional indicators. Including aPSADPZ, PZ ratio, and age can improve csPCa diagnosis and avoid unnecessary biopsies.

Summary: Ferroptosis is a new kind of regulated cell death that is characterized by highly iron-dependent lipid peroxidation. Cancer cells differ in their sensitivity to ferroptosis. Here we showed that the Suppressor of fused homolog (SUFU), a critical component in Hedgehog signaling, regulates ferroptosis sensitivity of breast cancer cells. Ectopic SUFU expression suppressed, whereas depletion of SUFU enhanced the sensitivity of breast cancer cells to RSL3-triggered ferroptosis through deregulation of ACSL4. Moreover, SUFU depletion promoted the activation of Yes-associated protein (YAP), thereby increasing the expression of ACSL4. Mechanistically, SUFU is associated with LATS1. Deletion of a region comprising residues 174–385 in SUFU disrupted SUFU binding to LATS1, thus abrogating SUFU-mediated downregulation of the YAP-ACSL4 axis and sensitivity to ferroptosis. Noteworthy, we showed that vincristine downregulated SUFU, thus increasing breast cancer cell sensitivity to RSL3 in vitro and in vivo. Together, our findings uncover SUFU as a novel regulator in ferroptosis sensitivity.

Abstract Background Validation of the autoverification function is one of the critical steps to confirm its effectiveness before use. It is crucial to verify whether the programmed algorithm follows the expected logic and produces the expected results. This process has always relied on the assessment of human–machine consistency and is mostly a manually recorded and time-consuming activity with inherent subjectivity and arbitrariness that cannot guarantee a comprehensive, timely and continuous effectiveness evaluation of the autoverification function. To overcome these inherent limitations, we independently developed and implemented a laboratory information system (LIS)-based validation system for autoverification. Methods We developed a correctness verification and integrity validation method (hereinafter referred to as the "new method") in the form of a human–machine dialog. The system records personnel review steps and determines whether the human–machine review results are consistent. Laboratory personnel then analyze the reasons for any inconsistency according to system prompts, add to or modify rules, reverify, and finally improve the accuracy of autoverification. Results The validation system was successfully established and implemented. For a dataset consisting of 833 rules for 30 assays, 782 rules (93.87%) were successfully verified in the correctness verification phase, and 51 rules were deleted due to execution errors. In the integrity validation phase, 24 projects were easily verified, while the other 6 projects still required the additional rules or changes to the rule settings. Taking the Hepatitis B virus test as an example, from the setting of 65 rules to the automated releasing of 3000 reports, the validation time was reduced from 452 (manual verification) to 275 h (new method), a reduction in validation time of 177 h. Furthermore, 94.6% (168/182) of laboratory users believed the new method greatly reduced the workload, effectively controlled the report risk and felt satisfied. Since 2019, over 3.5 million reports have been automatically reviewed and issued without a single clinical complaint. Conclusion To the best of our knowledge, this is the first report to realize autoverification validation as a human–machine interaction. The new method effectively controls the risks of autoverification, shortens time consumption, and improves the efficiency of laboratory verification.

Abstract Background Cerebral venous thrombosis (CVT) occurs rarely in the general population and is frequently associated with confused clinical findings and delayed diagnosis. Isolated cerebellar cortical vein thrombosis is a very rare phenomenon. Case presentation This report describes a case with CVT, which is manifested as space-occupying lesions of the cerebellar hemisphere and mimics a cerebellar tumor at the beginning. The diagnosis of CVT was finalized given the laboratory and brain biopsy findings. The etiology may be related to polycythemia vera with Janus Kinase 2 V617F mutation. Conclusion Isolated cerebellar vein thrombosis should be considered when swelling and enhancing cerebellar lesions are detected. Polycythemia vera, especially with a positive JAK2 V617F mutation, may be a rare risk factor for CVT.

Abstract Intestinal epithelium serves as the first barrier against the infections and injuries that mediate colonic inflammation. Colorectal cancer is often accompanied with chronic inflammation. Differed from its well-known oncogenic role in many malignancies, we present here that Golgi membrane protein 1 (GOLM1, also referred to as GP73) suppresses colorectal tumorigenesis via maintenance of intestinal epithelial barrier. GOLM1 deficiency in mice conferred susceptibility to mucosal inflammation and colitis-induced epithelial damage, which consequently promoted colon cancer. Mechanistically, depletion of GOLM1 in intestinal epithelial cells (IECs) led to aberrant Notch activation that interfered with IEC differentiation, maturation, and lineage commitment in mice. Pharmacological inhibition of Notch pathway alleviated epithelial lesions and restrained pro-tumorigenic inflammation in GOLM1-deficient mice. Therefore, GOLM1 maintains IEC homeostasis and protects against colitis and colon tumorigenesis by modulating the equilibrium of Notch signaling pathway.

BackgroundMultiple endocrine neoplasia type 2A (MEN2A) is a rare syndrome that presents as medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. Experience is lacking in the anesthetic management of patients with this syndrome, particularly in those who present with pheochromocytoma receiving nonpheochromocytoma resection. We aimed to share our experience with the anesthetic management of MEN2A patients.MethodWe retrospectively enrolled 24 MEN2A patients who had received different types of surgery at Peking Union Medical College Hospital from January 1, 2015, to December 31, 2021. All the medical records were reviewed and analyzed.ResultIn total, 33 surgeries were performed in 24 MEN2A patients, with 20 surgeries comprising pheochromocytoma resection in 17 patients. Most of these patients who had received pheochromocytoma resection had typical hemodynamic changes during surgery and anesthesia. Regarding the other 13 nonpheochromocytoma resections in 13 patients, 10 were performed in patients without pheochromocytoma, and 3 surgeries were performed with either functional primary (1, bilateral tumor whose patient refused adrenalectomy) or metastatic pheochromocytoma (2, unresectable and malign tumors developed years after bilateral adrenalectomy). Regarding the latter 3 patients, 1 showed hypertension and tachycardia during anesthesia induction, 1 showed tachycardia during surgery and the other showed stability during surgery. Patients who had received pheochromocytoma resection (n=17) required longer postoperative hospital stays than those who had received nonpheochromocytoma resection without pheochromocytoma (n=10) (5.8 ± 1.8 vs. 4.3 ± 1.6; P = 0.031).ConclusionsWhenever MEN2A patients are diagnosed with pheochromocytoma, surgical resection of the pheochromocytoma remains the primary choice for MEN2A treatment. Nonpheochromocytoma surgeries performed with existing pheochromocytoma could be risky and require full caution and preparation.

Hereditary spherocytosis is a common red blood cell disease caused by an inherited red blood cell membrane defect, leading to a spherical shape and propensity for hemolysis. There is a lack of reports on intraoperative autologous blood transfusion for hereditary spherocytosis patients. We hereby report our recent experience with using the Cell Saver® system for intraoperative red blood cell salvage on a hereditary spherocytosis patient. There was a drastic increase in salvaged blood free-hemoglobin compared with the preoperative sample (82.6 mg/dl vs. 6.2 mg/dl) which indicated severe hemolysis. Although our patient recovered smoothly with a normal liver and renal function test and reported no adverse reaction during follow-up, it is noteworthy that severe hemolysis could happen during the cell salvage process for patients with hemolytic anemia, as there are similar reports on sickle cell anemia, beta-thalassemia intermedia, and paroxysmal nocturnal hemoglobinuria. Therefore, more clinical attention and thorough research should be drawn into this perspective, namely, hemolysis during the red blood cell salvage process for patients with hemolytic anemia.

Background: Chronic obstructive pulmonary disease (COPD) has been considered a risk factor for postoperative respiratory failure after general anesthesia. However, the association between COPD severity and postoperative respiratory failure among COPD patients is unknown. Our aim was to compare the prevalence of postoperative respiratory failure in COPD patients according to disease severity after general anesthesia.Methods: We retrospectively reviewed COPD patients undergoing spinal surgery with general anesthesia at our clinical center between January 2016 and January 2021. These subjects were divided into four groups (group I = mild COPD, group II = moderate COPD, group III = severe COPD, and group IV = very severe COPD) according to their preoperative lung function. The primary endpoint was a respiratory failure 1 week after surgery. The diagnosis of respiratory failure was made with the presence of one or more of the following criteria: prolonged ventilator dependence, unplanned postoperative intubation, and partial pressure of arterial oxygen (PaO2) ≤ 50 mmHg while the patient was breathing ambient air in the hospital. The extubation time, perioperative PaO2 and partial pressure of arterial carbon dioxide (PaCO2), postoperative lung infection, and length of hospitalization were also compared.Results: A total of 120 patients who underwent spinal surgery with general anesthesia were included in this retrospective study. Postoperative respiratory failure occurred in 0 (0.0%) patient in group I, 1 (1.5%) patient in group II, 1 (2.5%) patient in group III, and 1 (14.5%) patient in group IV 1 week after surgery (p = 0.219). The duration of anesthesia was 243.3 ± 104.3 min in group I, 235.5 ± 78.8 min in group II, 196.0 ± 66.3 min in group III, and 173.1 ± 63.7 min in group IV (p < 0.001). Preoperative PaO2, PaCO2, intraoperative oxygenation index [a ratio of PaO2 to fraction of inspired oxygen (FiO2)], and postoperative PaO2 were significantly different among the four groups (p < 0.001, 0.001, 0.046,

Abstract Background Brucellosis is a common zoonotic disease that may have a variety of clinical manifestations when it affects the nervous system. Ischemic stroke is a rare clinical symptom, but if it is not diagnosed and treated early, it may cause more severe consequences. Case presentation We report a 38-year-old man presenting with hearing impairment for four years and sudden weakness of the right limb for two years, recurrent aphasia, and gradual weakness of bilateral lower limbs for nine months. He had bilateral positive Babinski’s sign. Cerebrospinal fluid (CSF) showed raised protein and pleocytosis. Magnetic resonance imaging (MRI) showed ischemic infarcts in the pons and extensive enhancement of spinal meninges combined with spinal cord atrophy and ischemia. The tests revealed Brucella Rose Bengal positive in serum and CSF. Brucella culture in CSF was also positive. Next-generation sequencing (NGS) of CSF revealed positive for Brucella with 105 species were detected. He showed significant improvement with antibiotics at five months follow-up. Conclusions Neurobrucellosis may mimic stroke and transverse myelitis like syndromes. NB is a treatable infectious condition and should always be considered in the differentials, especially if there are risk factors, as in our case.

As the core component of electric vehicles， electric drive axles directly determine the performance of electric vehicles. A comprehensive review of the structure of single-speed and multi-speed electric drive axles is carried out. Firstly， the basic structures of single-speed and multi-speed electric drive axles are explained respectively. Then， the research status of multi-speed electric drive axles is summarized. Finally， the advantages and disadvantages of single-speed and multi-speed electric drive axles are compared， and it is clear that multi-speed is the development trend. On this basis， it is pointed out that the focus of future research is that increasing the degree of integration while the multi-speed.

Abstract Background Inactivation of the tumor suppressor p53 is critical for pathogenesis of glioma, in particular glioblastoma multiforme (GBM). MDM2, the main negative regulator of p53, binds to and forms a stable complex with p53 to regulate its activity. Hitherto, it is unclear whether the stability of the p53/MDM2 complex is affected by lncRNAs, in particular circular RNAs that are usually abundant and conserved, and frequently implicated in different oncogenic processes. Methods RIP-seq and RIP-qPCR assays were performed to determine the most enriched lncRNAs (including circular RNAs) bound by p53, followed by bioinformatic assays to estimate the relevance of their expression with p53 signaling and gliomagenesis. Subsequently, the clinical significance of CDR1as was evaluated in the largest cohort of Chinese glioma patients from CGGA (n = 325), and its expression in human glioma tissues was further evaluated by RNA FISH and RT-qPCR, respectively. Assays combining RNA FISH with protein immunofluorescence were performed to determine co-localization of CDR1as and p53, followed by CHIRP assays to confirm RNA-protein interaction. Immunoblot assays were carried out to evaluate protein expression, p53/MDM2 interaction and p53 ubiquitination in cells in which CDR1as expression was manipulated. After AGO2 or Dicer was knocked-down to inhibit miRNA biogenesis, effects of CDR1as on p53 expression, stability and activity were determined by immunoblot, RT-qPCR and luciferase reporter assays. Meanwhile, impacts of CDR1as on DNA damage were evaluated by flow cytometric assays and immunohistochemistry. Tumorigenicity assays were performed to determine the effects of CDR1as on colony formation, cell proliferation, the cell cycle and apoptosis (in vitro), and on tumor volume/weight and survival of nude mice xenografted with GBM cells (in vivo). Results CDR1as is found to bind to p53 protein. CDR1as expression decreases with increasing glioma grade and it is a reliable independent predictor of overall survival in glioma, particularly in GBM. Through a mechanism independent of acting as a miRNA sponge, CDR1as stabilizes p53 protein by preventing it from ubiquitination. CDR1as directly interacts with the p53 DBD domain that is essential for MDM2 binding, thus disrupting the p53/MDM2 complex formation. Induced upon DNA damage, CDR1as may preserve p53 function and protect cells from DNA damage. Significantly, CDR1as inhibits tumor growth in vitro and in vivo, but has little impact in cells where p53 is absent or mutated. Conclusions Rather than acting as a miRNA sponge, CDR1as functions as a tumor suppressor through binding directly to p53 at its DBD region to restrict MDM2 interaction. Thus, CDR1as binding disrupts the p53/MDM2 complex to prevent p53 from ubiquitination and degradation. CDR1as may also sense DNA damage signals and form a protective complex with p53 to preserve p53 function. Therefore, CDR1as depletion may play a potent role in promoting tumorigenesis through down-regulating p53 expression in glioma. Our results broaden further our understanding of the roles and mechanism of action of circular RNAs in general and CDR1as in particular, and can potentially open up novel therapeutic avenues for effective glioma treatment.

Abstract Purpose To study prognostic values of the clinicopathological characteristics and survival outcomes in micropapillary urothelial carcinoma (MPUC) of the urinary bladder. Method We used the national Surveillance, Epidemiology, and End Results database (2004‐2016) to compare MPUC with transitional cell carcinoma (TCC) and to investigate prognostic values of clinicopathological characteristics, as well as survival outcomes, in MPUC of the urinary bladder. A multivariable Cox proportional hazard model, subgroup analyses, and propensity score matching were used. Results In all, 519 patients with MPUC and 154 453 patients with TCC were enrolled. Compared with TCC, patients with MPUC had a higher rate of muscle invasive disease (P

Introduction: We aimed to develop an easy-to-use individual survival prognostication tool based on competing risk analyses to predict the risk of 5-year cancer-specific death after radical prostatectomy for patients with prostate cancer (PCa).Methods: We obtained the data from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2016). The main variables obtained included age at diagnosis, marital status, race, pathological extension, regional lymphonode status, prostate specific antigen level, pathological Gleason Score. In order to reveal the independent prognostic factors. The cumulative incidence function was used as the univariable competing risk analyses and The Fine and Gray's proportional subdistribution hazard approach was used as the multivariable competing risk analyses. With these factors, a nomogram and risk stratification based on the nomogram was established. Concordance index (C-index) and calibration curves were used for validation.Results: A total of 95,812 patients were included and divided into training cohort (n = 67,072) and validation cohort (n = 28,740). Seven independent prognostic factors including age, race, marital status, pathological extension, regional lymphonode status, PSA level, and pathological GS were used to construct the nomogram. In the training cohort, the C-index was 0.828 (%95CI, 0.812–0.844), and the C-index was 0.838 (%95CI, 0.813–0.863) in the validation cohort. The results of the cumulative incidence function showed that the discrimination of risk stratification based on nomogram is better than that of the risk stratification system based on D'Amico risk stratification.Conclusions: We successfully developed the first competing risk nomogram to predict the risk of cancer-specific death after surgery for patients with PCa. It has the potential to help clinicians improve post-operative management of patients.

Immunotherapy has been a milestone for muscle-invasive bladder cancer (MIBC), but only a small portion of patients can benefit from it. Therefore, it is crucial to develop a robust individualized immune-related signature of MIBC to identify patients potentially benefiting from immunotherapy. The current study identified patients from the Cancer Genome Atlas (TCGA) and immune genes from the ImmPort database, and used improved data analytical methods to build up a 45 immune-related gene pair signature, which could classify patients into high-risk and low-risk groups. The signature was then independently validated by a Gene Expression Omnibus (GEO) dataset and IMvigor210 data. The subsequent analysis confirmed the worse survival outcomes of the high-risk group in both training (p < 0.001) and validation cohorts (p = 0.018). A signature-based risk score was proven to be an independent risk factor of overall survival (p < 0.001) and could predict superior clinical net benefit compared to other clinical factors. The CIBERSORT algorithm revealed the low-risk group had increased CD8+ T cells plus memory-activated CD4+ T-cell infiltration. The low-risk group also had higher expression of PDCD1 (PD-1), CD40, and CD27, and lower expression of CD276 (B7-H3) and PDCD1LG2 (PD-L2). Importantly, IMvigor210 data indicated that the low-risk group had higher percentage of “inflamed” phenotype plus less “desert” phenotype, and the survival outcomes were significantly better for low-risk patients after immunotherapy (p = 0.014). In conclusion, we proposed a novel and promising prognostic immune-related gene pair (IRGP) signature of MIBC, which could provide us a panoramic view of the tumor immune microenvironment of MIBC and independently identify MIBC patients who might benefit from immunotherapy.