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Abstract Objective The objective of this study was to develop and evaluate the performance of machine learning models for predicting the possibility of systemic inflammatory response syndrome (SIRS) following percutaneous nephrolithotomy (PCNL). Methods We retrospectively reviewed the clinical data of 337 patients who received PCNL between May 2020 and June 2022. In our study, 80% of the data were used as the training set, and the remaining data were used as the testing set. Separate prediction models based on the six machine learning algorithms were created using the training set. The predictive performance of each machine learning model was determined by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity using the testing set. We used coefficients to interpret the contribution of each variable to the predictive performance. Results Among the six machine learning algorithms, the support vector machine (SVM) delivered the best performance with accuracy of 0.868, AUC of 0.942 (95% CI 0.890–0.994) in the testing set. Further analysis using the SVM model showed that prealbumin contributed the most to the prediction of the outcome, followed by preoperative urine culture, systemic immune-inflammation (SII), neutrophil to lymphocyte ratio (NLR), staghorn stones, fibrinogen, operation time, preoperative urine white blood cell (WBC), preoperative urea nitrogen, hydronephrosis, stone burden, sex and preoperative lymphocyte count. Conclusion Machine learning-based prediction models can accurately predict the possibility of SIRS after PCNL in advance by learning patient clinical data, and should be used to guide surgeons in clinical decision-making.

Abstract Background Certain occupations may predispose individuals to urolithiasis, a multi-factorial disease. The study aimed to evaluate the prevalence and related factors of nephrolithiasis in medical staff in Qingdao, China. Methods Physical examination results of 5115 in-service medical staff aged 22–60 years old were retrospectively analyzed. Multivariable logistic regression analysis and stratified analyses by age and gender were applied to explore the related factors of nephrolithiasis in these medical staff. Results The overall nephrolithiasis prevalence in medical staff in Qingdao, China was 4.65%. Doctors were more prone to nephrolithiasis than nurses (5.63% vs. 3.96%, P = 0.013) and the peak prevalence (6.69%) was observed in medical staff working in the emergency department (ED). Male gender (OR = 1.615, 95% CI = 1.123–2.323, P = 0.010), overweight or obesity (OR = 1.674, 95% CI = 1.266–2.214, P

Abstract Background Endoscopic spine lumbar interbody fusion (Endo-LIF) is well-regarded within the academic community. However, it presents challenges such as intraoperative disorientation, high rates of nerve damage, a steep learning curve, and prolonged surgical times, often occurring during the creation of the operative channel. Furthermore, the undefined safe operational zones under endoscopy continue to pose risks to surgical safety. We aimed to analyse the anatomical data of Kambin’s triangle via CT imaging to define the parameters of the safe operating area for transforaminal posterior lumbar interbody fusion (TPLIF), providing crucial insights for clinical practice. Methods We selected the L4–L5 intervertebral space. Using three-dimensional (3D), we identified Kambin’s triangle and the endocircle within it, and recorded the position of point ‘J’ on the adjacent facet joint as the centre ‘O’ of the circle shifts by angle ‘β.’ The diameter of the inscribed circle ‘d,’ the abduction angle ‘β,’ and the distances ‘L1’ and ‘L2’ were measured from the trephine’s edge to the exiting and traversing nerve roots, respectively. Results Using a trephine with a diameter of 8 mm in TPLIF has a significant safety distance. The safe operating area under the TPLIF microscope was also clarified. Conclusions Through CT imaging research, combined with 3D simulation, we identified the anatomical data of the L4–L5 segment Kambin’s triangle, to clarify the safe operation area under TPLIF. We propose a simple and easy positioning method and provide a novel surgical technique to establish working channels faster and reduce nerve damage rates. At the same time, according to this method, the Kambin’s triangle anatomical data of the patient’s lumbar spine diseased segments can be measured through CT 3D reconstruction of the lumbar spine, and individualised preoperative design can be conducted to select the appropriate specifications of visible trephine and supporting tools. This may effectively reduce the learning curve, shorten the time operation time, and improve surgical safety.

IntroductionThis study investigates the mutual influence between online medical search and online medical consultation. It focuses on understanding the health information needs that drive these health information-seeking behaviors by utilizing insights from behavioral big data.MethodsWe used actual behavioral data from Chinese internet users on Baidu platform’s “Epidemic Index” from November 26, 2022, to January 25, 2023. Data modeling was conducted to ensure the reliability of the model. Drawing on the logistic model, we constructed a foundational model to quantify the evolutionary patterns of online medical search and online medical consultation. An impact function was defined to measure their mutual influence. Additionally, a pattern detection experiment was conducted to determine the structure of the impact function with maximum commonality through data fitting.ResultsThe analysis allowed us to build a mathematical model that quantifies the nonlinear correlation between online medical search and online medical consultation. Numerical analysis revealed a predation mechanism between online medical consultation and online medical search, highlighting the role of health information needs in this dynamic.DiscussionThis study offers a novel practical approach to better meet the public’s health information needs by understanding the interplay between online medical search and consultation. Additionally, the modeling method used here is broadly applicable, providing a framework for quantifying nonlinear correlations among different behaviors when appropriate data is available.

The through-thickness compressive mechanism of 3D needled nonwoven fiber preforms is complicated due to the complex fiber structure and enormous fiber-to-fiber contacts. This work developed a microscale modeling method to predict compressive behavior of carbon fiber nonwoven preforms. A newly-developed virtual fiber is proposed based on the generalized beam elements, for which the low bending stiffness of the fiber is calibrated by experimental data and decoupled from the high tensile stiffness. The feasibility of the proposed virtual fiber method is demonstrated through a simulation example of three-point bending of 6 k carbon fiber yarn. Influence of modeling parameters including amount of virtual fibers in the yarn and the element length of virtual fibers on the simulations is analyzed. High precision model of 3D needled preform is then generated using the proposed virtual fiber method. Through-thickness and axial compressive deformations of the preform are simulated. The predicted load–displacement curves agreed well with the experimental results.

BackgroundYishen-Tongbi Decoction (YSTB), a traditional Chinese prescription, has been used to improve syndromes of rheumatoid arthritis (RA) for many years. Previous research has shown that YSTB has anti-inflammatory and analgesic properties. However, the underlying molecular mechanism of the anti-RA effects of YSTB remains unclear.Purpose and study designThe purpose of this research was to investigate how YSTB affected mice with collagen-induced arthritis (CIA) and RAW264.7 cells induced with lipopolysaccharide (LPS).ResultsThe findings show that YSTB could significantly improve the clinical arthritic symptoms of CIA mice (mitigate paw swelling, arthritis score, thymus and spleen indices, augment body weight), downregulated expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-17, while upregulated the level of anti-inflammatory like IL-10 and transforming growth factor-β (TGF-β). Meanwhile, YSTB inhibits bone erosion and reduces inflammatory cell infiltration, synovial proliferation, and joint destruction in CIA mice. In addition, we found that YSTB was able to suppress the LPS-induced inflammation of RAW264.7 cells, which was ascribed to the suppression of nitric oxide (NO) production and reactive oxygen species formation (ROS). YSTB also inhibited the production of inducible nitric oxide synthase and reduced the releases of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in LPS-induced RAW264.7 cells. Furthermore, the phosphorylation expression of JAK2, JAK3, STAT3, p38, ERK and p65 protein could be suppressed by YSTB, while the expression of SOCS3 could be activated.ConclusionTaken together, YSTB possesses anti-inflammatory and prevention bone destruction effects in RA disease by regulating the JAK/STAT3/SOCS3 signaling pathway.

Summary: The decline of motor ability is a hallmark feature of aging and is accompanied by degeneration of motor synaptic terminals. Consistent with this, Drosophila motor synapses undergo characteristic age-dependent structural fragmentation co-incident with diminishing motor ability. Here, we show that motor synapse levels of Trio, an evolutionarily conserved guanine nucleotide exchange factor (GEF), decline with age. We demonstrate that increasing Trio expression in adult Drosophila can abrogate age-dependent synaptic structural fragmentation, postpone the decline of motor ability, and maintain the capacity of motor synapses to sustain high-intensity neurotransmitter release. This preservative activity is conserved in transgenic human Trio, requires Trio Rac GEF function, and can also ameliorate synapse degeneration induced by depletion of miniature neurotransmission. Our results support a paradigm where the structural dissolution of motor synapses precedes and promotes motor behavioral diminishment and where intervening in this process can postpone the decline of motor function during aging.

Abstract Cardiac remodeling is manifested by hypertrophy and apoptosis of cardiomyocytes, resulting in the progression of cardiovascular diseases. Long noncoding RNAs (lncRNAs) serve as modifiers of cardiac remodeling. In this study, we aimed to explore the molecular mechanism of H19 shuttled by mesenchymal stem cells (MSC)‐derived extracellular vesicles (EV) in cardiac remodeling upon heart failure (HF). Using the GEO database, H19, microRNA (miR)‐29b‐3p, and CDC42 were screened out as differentially expressed biomolecules in HF. H19 and CDC42 were elevated, and miR‐29b‐3p was decreased after MSC‐EV treatment in rats subjected to ligation of the coronary artery. MSC‐EV alleviated myocardial injury in rats with HF. H19 downregulation exacerbated myocardial injury, while miR‐29b‐3p inhibitor alleviated myocardial injury. By contrast, CDC42 downregulation aggravated the myocardial injury again. PI3K/AKT pathway was activated by MSC‐EV. These findings provide insights into how H19 shuttled by EV mitigates cardiac remodeling through a competitive endogenous RNA network regarding miR‐29b‐3p and CDC42.

Abstract Background The multifactorial aetiology of scoliosis is well known. Physical activity is considered both a treatment and causative factor for idiopathic scoliosis; however, evidence for a causal relationship between physical activity levels and idiopathic scoliosis in adolescents is conflicting. Therefore, we aimed to summarise the current evidence regarding the association between adolescent idiopathic scoliosis and physical activity and further to assess whether the relationship is dose dependent. Methods PubMed, Cochrane, Scopus, and Web of Science databases were searched from 1991 to July 2022 using the following main keywords: adolescent idiopathic scoliosis, physical activity, and risk factors, supplemented with manual searches, secondary citations, and reference searches. The quality of the included literature was evaluated using the Scale for Reporting Observational Studies in Enhanced Epidemiology guidelines. Results Eight studies were included in this review, of which six reported an association between adolescent idiopathic scoliosis and physical activity levels and two reported no association. One British study reported reduced physical function early in life as a new risk factor for scoliosis onset. Conclusions Physical activity is strongly associated with adolescent idiopathic scoliosis. Physical activity should be encouraged as it plays an important role in the prevention of adolescent idiopathic scoliosis. Further research is needed to determine the dose-dependent relationship between physical activity and prevention of adolescent idiopathic scoliosis.

Objective: Pregnancy has been identified as a risk factor for pelvic floor dysfunction (PFD). The aim of this study was to establish primary prevention measures for PFD during pregnancy and reduce the overall incidence of PFD. Methods: We assembled a panel of 36 experts, including gynecologists, obstetricians, and physiotherapists. Through surveys and expert meetings, the panel reviewed and assessed the safety and effectiveness of various clinical interventions. Based on expert comments from Round 1, a revised list of 8 clinical interventions was developed and submitted for a second round of expert review. Results: A consensus was reached on the importance of implementing prevention measures to protect pelvic floor function during pregnancy. Experts particularly emphasized the significance of health education, weight management, pelvic floor muscle training, respiratory training, overall exercise, physical activity, and perineal massage. Conclusion: The expert consensus provides comprehensive clinical measures to safeguard pelvic floor function during pregnancy. This paper represents the initial step toward developing scientific recommendations for pregnant women regarding the primary prevention of PFD. Future research should focus on the implementation of these recommendations in clinical practice.

The crude protein (CP) content is an important determining factor for the quality of alfalfa, and its accurate and rapid evaluation is a challenge for the industry. A model was developed by combining Fourier transform infrared spectroscopy (FTIS) and chemometric analysis. Fourier spectra were collected in the range of 4000~400 cm−1. Adaptive iteratively reweighted penalized least squares (airPLS) and Savitzky–Golay (SG) were used for preprocessing the spectral data; competitive adaptive reweighted sampling (CARS) and the characteristic peaks of CP functional groups and moieties were used for feature selection; partial least squares regression (PLSR) and random forest regression (RFR) were used for quantitative prediction modelling. By comparing the combined prediction results of CP content, the predictive performance of airPLST-cars-PLSR-CV was the best, with an RP2 of 0.99 and an RMSEP of 0.053, which is suitable for establishing a small-sample prediction model. The research results show that the combination of the PLSR model can achieve an accurate prediction of the crude protein content of alfalfa forage, which can provide a reliable and effective new detection method for the crude protein content of alfalfa forage.

Since a scarcity of sufficient grafting materials, several complications can arise after urothelial defect reconstruction surgery, including severe hypospadias. Accordingly, developing alternative therapies, such as urethral restoration via tissue engineering are needed. In the present study, we developed a potent adhesive and repairing material using fibrinogen-poly(l-lactide-co-caprolactone) copolymer (Fib-PLCL) nanofiber scaffold to achieve effective urethral tissue regeneration after seeding with epithelial cells on the surface. The in vitro result found the Fib-PLCL scaffold promoted the attachment and viability of epithelial cells on their surface. The increased expression levels of cytokeratin and actin filaments were observed in Fib-PLCL scaffold than PLCL scaffold. The in vivo urethral injury repairing potential of Fib-PLCL scaffold was evaluated using a rabbit urethral replacement model. In this study, a urethral defect was surgically excised and replaced with the Fib-PLCL and PLCL scaffolds or autograft. As expected, the animals healed well after surgery in the Fib-PLCL scaffold group, and no significant strictures were identified. As expected, the cellularized Fib/PLCL grafts have induced the luminal epithelialization, urethral smooth muscle cell remodelling, and capillary development all at the same time. Histological analysis revealed that the urothelial integrity in the Fib-PLCL group had progressed to that of a normal urothelium, with enhanced urethral tissue development. Based on the results, the present study suggests that the prepared fibrinogen–PLCL scaffold is more appropriate for urethral defect reconstruction.

Polarization imaging and sensing techniques have shown great potential for biomedical and clinical applications. As a novel optical biosensing technology, Mueller matrix polarimetry can provide abundant microstructural information of tissue samples. However, polarimetric aberrations, which lead to inaccurate characterization of polarization properties, can be induced by uneven biomedical sample surfaces while measuring Mueller matrices with complex spatial illuminations. In this study, we analyze the detailed features of complex spatial illumination-induced aberrations by measuring the backscattering Mueller matrices of experimental phantom and tissue samples. We obtain the aberrations under different spatial illumination schemes in Mueller matrix imaging. Furthermore, we give the corresponding suggestions for selecting appropriate illumination schemes to extract specific polarization properties, and then provide strategies to alleviate polarimetric aberrations by adjusting the incident and detection angles in Mueller matrix imaging. The optimized scheme gives critical criteria for the spatial illumination scheme selection of non-collinear backscattering Mueller matrix measurements, which can be helpful for the further development of quantitative tissue polarimetric imaging and biosensing.

Inhibition of glycoside hydrolases has widespread application in the treatment of diabetes. Based on our previous findings, a series of dihydrofuro[3,2-b]piperidine derivatives was designed and synthesized from D- and L-arabinose. Compounds 32 (IC50 = 0.07 μM) and 28 (IC50 = 0.5 μM) showed significantly stronger inhibitory potency against α-glucosidase than positive control acarbose. The study of the structure–activity relationship of these compounds provides a new clue for the development of new α-glucosidase inhibitors.

This study summarizes the latest achievements, challenges, and future research directions in deep learning technologies for the diagnosis of renal cell carcinoma (RCC). This is the first review of deep learning in RCC applications. This review aims to show that deep learning technologies hold great promise in the field of RCC diagnosis, and we look forward to more research results to meet us for the mutual benefit of renal cell carcinoma patients. Medical imaging plays an important role in the early detection of renal cell carcinoma (RCC), as well as in the monitoring and evaluation of RCC during treatment. The most commonly used technologies such as contrast enhanced computed tomography (CECT), ultrasound and magnetic resonance imaging (MRI) are now digitalized, allowing deep learning to be applied to them. Deep learning is one of the fastest growing fields in the direction of medical imaging, with rapidly emerging applications that have changed the traditional medical treatment paradigm. With the help of deep learning-based medical imaging tools, clinicians can diagnose and evaluate renal tumors more accurately and quickly. This paper describes the application of deep learning-based imaging techniques in RCC assessment and provides a comprehensive review.

Public medical facilities that are closely related to the health of residents have been recognised as one of the most crucial elements in sustainable urban planning. For the sake of social equality of medical services (especially for emergency medical conditions), the spatial distributions of medical resources need to be accurately measured and continuously optimized. This study presents an effective method to examine night emergency hospital visit and analyse its spatiotemporal characteristics using float car data (FCD). By extracting the hospital service areas, the two-step floating catchment area (2SFCA) methodology was improved to calculate hospital accessibility. Then, the balance between hospital accessibility and population density was analysed. In addition, we investigated the relationship between individual hospital choice preferences and hospital level and analysed several factors that affect individual choices. These results help us understand the special requirements and need of emergency hospital travel in cities and identify areas where medical resources are scarce. They can be used as guidance for urban hospital planning and construction. And the approach of hospital access behaviour investigation and the improved 2SFCA method can also provide insights for other activity-based travel behaviour research.

Abstract Background Adrenocortical carcinoma (ACC) is a rare endocrine neoplasm, which is characterized by poor prognosis and high recurrence rate. Novel and reliable prognostic and metastatic biomarkers are lacking for ACC patients. This study aims at screening potential prognostic biomarkers and therapeutic targets of ACC through bioinformatic methods and immunohistochemical (IHC) analysis. Methods In the present study, by using the Gene Expression Omnibus (GEO) database we identified differentially expressed genes (DEGs) in ACC and validated these DEGs in The Cancer Genome Atlas (TCGA) ACC cohort. A DEGs-based signature was additionally constructed and we assessed its prognosis and prescient worth for ACC by survival analysis and nomogram. Immunohistochemistry (IHC) was used to verify the relationship between hub gene–GMNN expressions and clinicopathologic outcomes in ACC patients. Results A total of 24 DEGs correlated with the prognosis of ACC were screened from the TCGA and GEO databases. Five DEGs were subsequently selected in a signature which was closely related to the survival rates of ACC patients and GMNN was identified as the core gene in this signature. Univariate and multivariate Cox regression showed that the GMNN was an independent prognostic factor for ACC patients (P

Patients with impaired quality of life associated with xerostomia need long-term treatment, and a nerve stimulator has the advantage of providing natural saliva and long-term management for patients with xerostomia by electrically stimulating the relevant secretory nerves to promote saliva production. A number of clinical trials have preliminarily demonstrated the efficacy of nerve electrical stimulation in the treatment of xerostomia. However, electrical stimulation has not yet become the mainstream treatment for xerostomia. Large prospective randomized controlled clinical trials are still needed to confirm its long-term effectiveness and safety. In addition, the design of nerve stimulators is of great significance for clinical application. The large volume and inconvenient treatment associated with the extra oral nerve stimulator and the first generation intraoral nerve stimulator hinder their clinical application and popularization. The second- and third-generation intraoral nerve stimulator devices are small, convenient to use and have great application prospects. Research on electrical nerve stimulators for xerostomia treatment is mainly concentrated in European and American countries, while there is very little domestic research. It is urgent to master the core technology for the research and development of electrical nerve stimulators. The innovation of miniaturization, efficient power supply, data feedback and packaging will be the key issues of electrical nerve stimulators in the future. In this paper, the treatment and research of electrical nerve stimulation for xerostomia are reviewed to provide a reference for related basic research and the clinical application of electrical stimulators treating xerostomia in China.

Abstract Objective To evaluate the feasibility and accuracy of near-infrared fluorescence imaging technology for assessing margins during breast-conserving surgery for breast cancer. Methods Forty-three breast cancer patients who received surgical treatment at Yijishan Hospital of Wannan Medical College were selected. Before the operation, the patients were administered with an indocyanine green injection of 0.5 mg/kg intravenously 2 h before operation. During and after the operation, all patients underwent surgical margin monitoring with the near-infrared fluorescence imaging system for fluorescence imaging and acquisition of images and quantitative fluorescence intensity. During the operation, the patients’ tissue specimens were collected on the upper, lower, inner, outer, apical, and basal sides of the fluorescence boundary of the isolated lesions for pathological examination. Results Fluorescence was detected in the primary tumor in all patients. The average fluorescence intensities of tumor tissue, peritumoral tissue, and normal tissue were 219.41 ± 32.81, 143.35 ± 17.37, and 105.77 ± 17.79 arbitrary units, respectively (P < 0.05, t test). The signal-to-background ratio of tumor to peritumor tissue and normal tissue was 1.54 ± 0.20 and 2.14 ± 0.60, respectively (P < 0.05, t test). Abnormal indocyanine green fluorescence was detected in 11.6% patients (5/43), including 3 patients with residual infiltrating carcinoma and 2 patients with adenosis with ductal dilatation. Conclusion This study confirms the high sensitivity and specificity of near-infrared fluorescence imaging technology for breast-conserving surgery margin assessment. Near-infrared fluorescence imaging technology can be used as an intraoperative diagnosis and treatment tool to accurately determine the surgical margin and is of important guiding value in breast-conserving surgery for breast cancer.

Abstract Introduction Neobladder urolithiasis is a rare but important delaying complication of orthotopic urinary diversion. We report a case of Hem-o-Lok (HOLC) migration into the neobladder with giant stone formation after orthotopic neobladder cystectomy. Case report We report a case of a 57-year-old man with frequent urination and occasional discharge of stones 3 years after a laparoscopic orthotopic neobladder cystectomy. Computed tomography revealed a large round 3.5 cm calculus. An endoscopic neocystolitholapaxy was performed, and a Hem-o-Lok was found in the center of the stone. Conclusion We described the case presentation, treatment and analysis of etiology of stone formation to avoid such complication.

Tau and the Retromer complex are both linked to Parkinson’s and Alzheimer’s disease. Using Drosophila neurodegeneration models, this study finds that low retromer activity induces a specific increase of a highly toxic truncated form of human Tau.

Background: Functional disorders of mitochondria are closely related to muscle diseases. Many studies have also shown that oxidative stress can stimulate the production of a large number of reactive oxygen species (ROS), which have various adverse effects on mitochondria and can damage muscle cells. Purpose: In this study, based on our previous research, we focused on the PINK1/Parkin pathway to explore the mechanism by which AS-IV alleviates muscle injury by inhibiting excessive mitophagy. Methods: L6 myoblasts were treated with AS-IV after stimulation with hydrogen peroxide (H2O2) and carbonyl cyanide m-chlorophenylhydrazone (CCCP). Then, we detected the related indices of oxidative stress and mitophagy by different methods. A PINK1 knockdown cell line was established by lentiviral infection to obtain further evidence that AS-IV reduces mitochondrial damage through PINK1/Parkin. Results: After mitochondrial damage, the expression of malondialdehyde (MDA) and intracellular ROS in L6 myoblasts significantly increased, while the expression of superoxide dismutase (SOD) and ATP decreased. The mRNA and protein expression levels of Tom20 and Tim23 were decreased, while those of VDAC1 were increased. PINK1, Parkin, and LC3 II mRNA and protein expression increased, and P62 mRNA and protein expression decreased·H2O2 combined with CCCP strongly activated the mitophagy pathway and impaired mitochondrial function. However, abnormal expression of these factors could be reversed after treatment with AS-IV, and excessive mitochondrial autophagy could also be reversed, thus restoring the regulatory function of mitochondria. However, AS-IV-adjusted function was resisted after PINK1 knockdown. Conclusion: AS-IV is a potential drug for myasthenia gravis (MG), and its treatment mechanism is related to mediating mitophagy and restoring mitochondrial function through the PINK1/Parkin pathway.

Ferroptosis and immune infiltration play an important role in the pathogenesis of intervertebral disc degeneration (IDD). However, there is still a lack of comprehensive analysis on the interaction between ferroptosis-related genes (FRGs) and immune microenvironment in IDD patients. Therefore, this study aims to explore the correlation between FRGs characteristics and immune infiltration in the progression of IDD. The expression profiles (GSE56081 and GSE70362) and FRGs were downloaded from the comprehensive gene expression omnibus (GEO) and FerrDb database, respectively, and the differences were analyzed using R. The intersection of IDD related differential genes (DEGs) and FRGs was taken as differentially expressed FRGs (DE-FRGs) and GO and KEGG enrichment analysis was conducted. Then, we used least absolute shrinkage and selection operator (LASSO) regression algorithm and support vector machine (SVM) algorithm to screen feature genes and draw ROC curve judge the diagnostic value of key DE-FRGs. Then CIBERSORT algorithm is used to evaluate the infiltration of immune cells and analyze the correlation between key DE-FRGs and immune infiltration. Based on the analysis results, we conducted single gene GSEA analysis on key DE-FRGs. RT-PCR and immunohistochemistry further verified the clinical value of the results of biochemical analysis and screening. Seven key DE-FRGs were screened, including the upregulated genes NOX4 and PIR, and the downregulated genes TIMM9, ATF3, ENPP2, FADS2 and TFAP2A. Single gene GSEA analysis further elucidates the role of DE-FRGs in IDD associated with ferroptosis. Correlation analysis showed that seven key DE-FRGs were closely related to immune infiltration in the development of IDD. Finally, RT-PCR and immunohistochemical staining showed that NOX4, ENPP2, FADS2 and TFAP2A were statistically significant differences. In this study, we explored the connection between ferroptosis related characteristics and immune infiltration in IDD, and confirmed that NOX4, ENPP2, FADS2, and TFAP2A may become biomarkers and potential therapeutic targets for IDD.

Background Regulatory T (Treg) cells are important immune cells that are regulated by adaptive immunity in the composition of Treg-cell subsets and T-cell receptors (TCRs). Treg cells are related to most autoimmune diseases, such as rheumatoid arthritis (RA). In traditional Chinese medicine (TCM), RA is typically attributed to kidney deficiency (KD) associated with the immunosenescence that causes immune dysfunction and the impaired function of Treg cells. So far, however, no mechanism related to KD and immune repertoires has been identified in RA. Methods Flow cytometry and high-throughput Treg-cell receptor sequencing were used to investigate the amount of different Treg-cell subsets and the diversity of TCRs between RA patients and healthy subjects, as well as between KD RA and non-KD RA patients. RT-qPCR was used to validate the high-throughput sequencing results. Results The data showed that the amount of naïve Treg cells in KD patients was less than in non-KD RA patients (P = 0.004) with no significant differences observed between other subsets. In the TCR of Treg cells, the length of complementarity determining region 3 (CDR3) was low and clonotypes increased in the KD group compared with the non-KD group. The diversity and abundance of Treg TCRs were low, as determined by the Hill number. In addition, several V(D)J combinations, such as T-cell receptor beta variable 7-2 (TRBV7-2), TRBV11-1, TRBV13, TRBV15, and TRBJ2-3, varied significantly between the two groups, indicating that KD causes Treg dysfunction. RT-qPCR shows that FOXP3 expression in peripheral blood Treg is lower in KD than in non-KD. Conclusion The results demonstrate the close correlation between KD and immune repertoires in RA and provide a new evaluation method for RA in TCM.

Abstract Background Mesenchymal stem cell-derived exosomes (MSC-EXO) have emerged as novel therapeutic strategies for myocardial infarction (MI). However, many questions remain untouched and unanswered regarding their roles in myocardial fibrosis. This study aimed to probe the therapeutic effects of MSC-EXO on myocardial fibrosis after MI and possible mechanisms. Methods Myocardial tissues were obtained from MI rats, and myocardial cell viability, fibrosis, apoptosis, and epithelial–mesenchymal transition (EMT) were detected by immunohistochemistry, Masson’s staining, TUNEL, and western blot. Bone marrow-derived MSCs and corresponding EXO were identified, and cardiac function were detected after treatment of MSC-EXO. Bioinformatics analysis and ChIP assay were conducted to detect the downstream genes of EZH2. EZH2 was upregulated alone or with HMGA2 overexpression in myocardial tissues of MI rats upon MSC-EXO treatment, and PI3K/AKT pathway activity in myocardial tissues was detected using western blot. Results The proliferative activity in myocardial tissues of MI rats was significantly decreased, along with accentuated fibrosis, increased collagen volume and EMT. MSC-EXO treatment resulted in partial restoration of cardiac function and reduced EZH2 expression in the myocardium of rats. EZH2 inhibited HMGA2 expression by increasing the H3K27me3 modification. PI3K/AKT pathway was altered under the influence of the EZH2/HMGA2 axis. EZH2 inhibited the effect of MSC-EXO on the recovery of cardiac function and accelerated fibrosis, while HMGA2 reversed the effect of EZH2 to reduce fibrosis and enhance cardiac function. Conclusion MSC-EXO alleviated fibrosis in MI rats via inhibition of EZH2, whereas EZH2 inhibited HMGA2 expression and impaired the PI3K/AKT pathway.

Several monoterpene glycoside compounds were extracted from Paeonia lactiflora Pall. Among them, paeoniflorin, a water-soluble monoterpene glycoside found in the root of Paeonia lactiflora Pall, exhibits excellent antioxidant pharmacological functions. Initially, Sc(CF3SO3)3 was employed as the catalyst for paeoniflorin’s dehydration and rearrangement reactions with alcohols. Subsequently, structural modifications were performed on paeoniflorin through a series of responses, including acetylation, deacetylation, and debenzoylation, ultimately yielding 46 monoterpene glycoside derivatives. The potential inhibitory effects on the pro-inflammatory mediators interleukin-1 beta (IL-1β) and nitric oxide (NO) were assessed in vitro. The results revealed that compounds 29 and 31 demonstrated notable inhibition of NO production, while eight derivatives (3, 8, 18, 20, 21, 29, 34, and 40) displayed substantial inhibitory effects on the secretion of IL-1β. Computational research was also undertaken to investigate the binding affinity of the ligands with the target proteins. Interactions between the proteins and substrates were elucidated, and corresponding binding energies were calculated accordingly. The findings of this study could provide valuable insights into the design and development of novel anti-inflammatory agents with enhanced pharmacological properties.

An economical and effective method is still lacking for cadmium (Cd) toxicity reduction and food product safety improvement in soil–vegetable systems. Therefore, this study aimed to reduce the Cd toxicity to pak choi (Brassica campestris L.) by jointly using passivators and organic fertilizer, highlighting food products’ safety based on pot experiments. The results showed that compared with the control, organic fertilizer decreased the Cd content in edible parts and the soil’s available Cd by 48.4% and 20.9% on average, respectively, due to the 0.15-unit increases in soil pH. Once jointly applied with passivators, the decrements increased by 52.3–72.6% and 32.5–52.6% for the Cd content in edible parts and for the soil’s available Cd, respectively, while the pH increment increased by 0.15–0.46 units. Compared with the control, the transport factor of Cd was reduced by 61.9% and 50.9–55.0% when applying organic fertilizer alone and together with the passivators, respectively. The combination treatment of biochar and organic fertilizer performed the best in decreasing the Cd content in the edible parts and the soil’s available Cd. The combination treatment of fish bone meal and organic fertilizer induced the greatest increases in soil pH. The grey relational analysis results showed that the combination treatment of biochar and organic fertilizer performed the best in reducing the potential Cd pollution risk, thereby highlighting the vegetable food safety. This study provides a potential economical and effective technology for toxicity reduction and food safety in Cd-polluted soil.

Context Yougui pill combined with Buzhong Yiqi decoction (YPBYD) is used to relieve sexual dysfunction in clinical practice. Objective To investigate changes in microbial composition caused by sexual dysfunction and identify dominant bacteria related to YPBYD treatment. Materials and methods Female Sprague-Dawley rats were randomly divided into four groups (n = 6): one group underwent Sham operation (Sham group), while three groups underwent ovariectomy (one model and two treatment groups). The ovariectomized (OVX) rats received oestradiol benzoate (250 µg/kg/week) or YPBYD (3.6 mL/d) via oral gavage for 4 weeks. Vaginal smear assay was performed; the serum levels of cyclic adenosine monophosphate (cAMP) and oestradiol (E2) were measured, followed by collection of stool samples for 16S rRNA sequencing. Results After YPBYD treatment, the levels of E2 and cAMP in OVX rats significantly increased (E2: from 20.45 ± 1.60 ng/L to 24.38 ± 1.70 ng/L; cAMP: from 261.41 ± 9.21 pg/mL to 373.75 ± 17.37 pg/mL). OVX treatment decreased diversity of gut microbiota and YPBYD treatment restored gut microbiota composition. Compared with Sham group, the abundance of Romboutsia significantly increased, while those of Proteobacteria and Staphylococcus markedly decreased in OVX group (all p

This research focuses on the research problem of eliminating COVID-19 vaccine hesitancy through web search. A dynamic model of eliminating COVID-19 vaccine hesitancy through web search is constructed based on the Logistic model, the elimination degree is quantified, the elimination function is defined to analyze the dynamic elimination effect, and the model parameter estimation method is proposed. The numerical solution, process parameters, initial value parameters and stationary point parameters of the model are simulated, respectively, and the mechanism of elimination is deeply analyzed to determine the key time period. Based on the real data of web search and COVID-19 vaccination, data modeling is carried out from two aspects: full sample and segmented sample, and the rationality of the model is verified. On this basis, the model is used to carry out dynamic prediction and verified to have certain medium-term prediction ability. Through this research, the methods of eliminating vaccine hesitancy are enriched, and a new practical idea is provided for eliminating vaccine hesitancy. It also provides a method to predict the quantity of COVID-19 vaccination, provides theoretical guidance for dynamically adjusting the public health policy of the COVID-19, and can provide reference for the vaccination of other vaccines.

ABSTRACT Purpose: Spontaneous intracerebral hemorrhage (ICH) is still a major public health problem, with high mortality and disability. Ulinastatin (UTI) was purified from human urine and has been reported to be anti-inflammatory, organ protective, and antioxidative stress. However, the neuroprotection of UTI in ICH has not been confirmed, and the potential mechanism is unclear. In the present study, we aimed to investigate the neuroprotection and potential molecular mechanisms of UTI in ICH-induced early brain injury in a C57BL/6 mouse model. Methods: The neurological score, brain water content, neuroinflammatory cytokine levels, oxidative stress levels, and neuronal damage were evaluated. Results: UTI treatment markedly increased the neurological score, alleviated brain edema, decreased the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and NF-κB, decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and upregulated the levels of glutathione (GSH), superoxide dismutase (SOD), and Nrf2. This finding indicated that UTI-mediated inhibition of neuroinflammation and oxidative stress alleviated neuronal damage after ICH. The neuroprotective capacity of UTI is partly dependent on the ROS/MAPK/Nrf2 signaling pathway. Conclusions: UTI improves neurological outcomes in mice and reduces neuronal death by protecting against neural neuroinflammation and oxidative stress.

Severe Acute Respiratory Syndrome Coronavirus 2, which is quickly spreading around the world and causes coronavirus disease 2019, may attack the urogenital system. We thought that a summary of the current literature about urogenital disease associated with the virus would be useful for physicians treating patients with coronavirus disease 2019. PubMed was com-prehensively screened for studies published from 2019 to 2020. Studies of coronavirus disease 2019 patients with kidney dis-ease, reproductive system diseases, or urological cancer were included. Through reviewing current literature, we summarized that acute kidney injury is a risk factor for patients with coronavirus disease 2019 and is related to their survival. A diagnosis of chronic kidney disease increases the risk of infection. The therapy for kidney transplant patients should be cautious and implemented on a case-by-case basis. When the public health burden is too heavy to bear, a rational selection of treatment for patients with urological cancer is vital. The male reproductive system is at high risk of being attacked by the virus, which may cause damage to reproductive function, and the long-term effects require further study. So, the complications associated with the urogenital system should not be ignored during the course of infection treatment and more robust evidence of long-term effects on the urogenital system will be proposed as more studies are published.

Synaptic structures disintegrate and fragment as ageing progresses. Here the authors find that miniature neurotransmission is required to maintain adult motor synapse structures in Drosophila and that increasing miniature events can preserve motor ability during ageing.

The marginal soil temperature on the south side of a greenhouse remains at low temperatures in winter for long periods, which affects crop growth and land-use efficiency, it is of great significance to grasp the influencing factors of soil temperature change to improve the marginal soil temperature on the south side of the greenhouse. This study was conducted in at typical greenhouse in the cold and arid area of northern China and used the Grey Relational Analysis (GRA) method, the relational degree between the marginal soil temperature on the south side of the greenhouse and environmental factors under different lining structures was analyzed, and established the soil temperature transfer function. The results show that soil temperature had the greatest correlation with the soil humidity and air humidity inside and outside the greenhouse, and the second greatest correlation was the relation with the air temperature inside and outside the greenhouse and the outdoor soil temperature; the lining structure could effectively reduce the relation between soil temperature and humidity inside and outside the greenhouse. Polystyrene extruded board (PEB) had a greater degree of relational reduction than other lining materials in the test. Through verification analysis, the mean absolute error of soil temperature of 5 cm was less than 0.85 °C, the average absolute error of soil temperature at 15 cm was less than 0.57 °C, and the average absolute error of soil temperature at 25 and 55 cm was less than 0.2 °C. In conclusion, the constructed soil temperature transfer function could be used to predict the variation trend of soil temperature, and the PEB material lining structure had good thermal insulation.

BackgroundEpithelial-mesenchymal transition (EMT), one leading reason of the dismal prognosis of bladder cancer (BLCA), is closely associated with tumor invasion and metastasis. We aimed to develop a novel immune−related gene signature based on different EMT and metabolic status to predict the prognosis of BLCA.MethodsGene expression and clinical data were obtained from TCGA and GEO databases. Patients were clustered based on EMT and metabolism scores calculated by ssGSEA. The immune-related differentially expressed genes (DEGs) between the two clusters with the most obvious differences were used to construct the signature by LASSO and Cox analysis. Time-dependent receiver operating characteristic (ROC) curves and Kaplan–Meier curves were utilized to evaluate the gene signature in training and validation cohorts. Finally, the function of the signature genes AHNAK and NFATC1 in BLCA cell lines were explored by cytological experiments.ResultsBased on the results of ssGSEA, TCGA patients were divided into three clusters, among which cluster 1 and cluster 3 had completely opposite EMT and metabolic status. Patients in cluster 3 had a significantly worse clinical prognosis than cluster 1. Immune-related DEGs were selected between the two clusters to construct the predictive signature based on 14 genes. High-risk patients had poorer prognosis, lower proportions of CD8+ T cells, higher EMT and carbohydrate metabolism, and less sensitivity to chemotherapy and immunotherapy. Overexpression of AHNAK or NFATC1 promoted the proliferation, migration and invasion of T24 and UMUC3 cells. Silencing ANHAK or NFATC1 could effectively inhibit EMT and metabolism in T24 and UMUC3 cells.ConclusionThe established immune signature may act as a promising model for generating accurate prognosis for patients and predicting their EMT and metabolic status, thus guiding the treatment of BLCA patients.

Establishing with precision the quantity and identity of the cell types of the brain is a prerequisite for a detailed compendium of gene and protein expression in the central nervous system (CNS). Currently, however, strict quantitation of cell numbers has been achieved only for the nervous system of Caenorhabditis elegans. Here, we describe the development of a synergistic pipeline of molecular genetic, imaging, and computational technologies designed to allow high-throughput, precise quantitation with cellular resolution of reporters of gene expression in intact whole tissues with complex cellular constitutions such as the brain. We have deployed the approach to determine with exactitude the number of functional neurons and glia in the entire intact larval Drosophila CNS, revealing fewer neurons and more glial cells than previously predicted. We also discover an unexpected divergence between the sexes at this juvenile developmental stage, with the female CNS having significantly more neurons than that of males. Topological analysis of our data establishes that this sexual dimorphism extends to deeper features of CNS organisation. We additionally extended our analysis to quantitate the expression of voltage-gated potassium channel family genes throughout the CNS and uncover substantial differences in abundance. Our methodology enables robust and accurate quantification of the number and positioning of cells within intact organs, facilitating sophisticated analysis of cellular identity, diversity, and gene expression characteristics.

Background: Dihydroarteannuin (DHA), which is extracted from the traditional Chinese herb Artemisia annua L, exhibits potent immunosuppressive activity in rheumatoid arthritis (RA). Strong evidence indicates that B cells act as an essential factor in the pathogenesis of RA, but research on the immunosuppressive function of DHA in regulating B cells is limited.Objective: To investigate the modulatory effects of DHA on joint destruction, proinflammatory cytokine production, activation, apoptosis and proliferation of B cells and to explore the possible associated mechanism in RA treatment.Methods: Collagen-induced arthritis (CIA) model was established. Weight and joint oedema were record weekly, and joint damage was detected by micro-CT scan. Human Burkitt B lymphoma cells lacking endogenous Fc gamma receptor b (FcγRIIb) gene were transfected with a 232Thr loss-of-function mutant to construct a mutant cell model ST486. The proliferation of ST486 cells was assessed with Cell Counting Kit-8. Apoptosis and activation were tested by flow cytometry. The effects of DHA on the activation of FcγRIIb, protein tyrosine kinases (Lyn), and SH2-containing tyrosine phosphatase-1 (SHP-1) signaling pathways were determined by western blotting.Results: In comparison to model group, bone volume/tissue volume (BV/TV) and bone mineral density (BMD) were increased, whereas joint oedema was decreased in both of the DHA and MTX group. The mRNA and protein expression levels of Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-α) were decreased after treatment with DHA. In addition, DHA treatment promoted the apoptosis, inhibited the activation and proliferation of ST486 cells. Furthermore, the protein expression levels of FcγRIIb, SHP-1, and Lyn were increased after treatment with DHA. Moreover, the expression of phosphorylated CD19 was also inhibited by DHA.Conclusion: We provide the first evidence that DHA may alleviate collagen-induced arthritis by activating the FcγRIIb/Lyn/SHP-1 signaling pathway in B cell, indicating that DHA is a novel and valuable candidate for RA therapy.

ABSTRACT Purpose: Spontaneous intracerebral hemorrhage (ICH) is a major public health problem with a huge economic burden worldwide. Ulinastatin (UTI), a serine protease inhibitor, has been reported to be anti-inflammatory, immune regulation, and organ protection by reducing reactive oxygen species production, and inflammation. Necroptosis is a programmed cell death mechanism that plays a vital role in neuronal cell death after ICH. However, the neuroprotection of UTI in ICH has not been confirmed, and the potential mechanism is unclear. The present study aimed to investigate the neuroprotection and potential molecular mechanisms of UTI in ICH-induced EBI in a C57BL/6 mouse model. Methods: The neurological score, brain water content, neuroinflammatory cytokine levels, and neuronal damage were evaluated. The anti-inflammation effectiveness of UTI in ICH patients also was evaluated. Results: UTI treatment markedly increased the neurological score, alleviate the brain edema, decreased the inflammatory cytokine TNF-α, interleukin‑1β (IL‑1β), IL‑6, NF‑κB levels, and RIP1/RIP3, which indicated that UTI-mediated inhibition of neuroinflammation, and necroptosis alleviated neuronal damage after ICH. UTI also can decrease the inflammatory cytokine of ICH patients. The neuroprotective capacity of UTI is partly dependent on the MAPK/NF-κB signaling pathway. Conclusions: UTI improves neurological outcomes in mice and reduces neuronal death by protecting against neural neuroinflammation, and necroptosis.

Abstract Background Bladder cancer (BLCA) is a common malignant tumor of urinary system with high morbidity and mortality. In recent years, immunotherapy has played a significant role in the treatment of BLCA. Tumor mutation burden (TMB) has been reported to be a powerful biomarker for predicting tumor prognosis and efficacy of immunotherapy. Our study aimed to explore the relationship between TMB, prognosis and immune infiltration to identify the key genes in BLCA. Methods Clinical information, somatic mutation and gene expression data of BLCA patients were downloaded from The Cancer Genome Atlas (TCGA) database. Patients were divided into high and low TMB groups according to their calculated TMB scores. Gene Set Enrichment Analysis (GSEA) was performed to screen for significantly enriched pathways. Differentially expressed genes (DEGs) between the two groups were identified. Univariate Cox analysis and Kaplan-Meier survival analysis were applied for screening key genes. Immune infiltration was performed for TMB groups and NTRK3. Results Higher TMB scores were related with poor survival in BLCA. After filtering, 36 DEGs were identified. NTRK3 had the highest hazard ratio and significant prognostic value. Co-expressed genes of NTRK3 were mainly involved in several pathways, including DNA replication, basal transcription factors, complement and coagulation cascades, and ribosome biogenesis in eukaryotes. There was a significant correlation among TMB scores, NTRK3 expression and immune infiltration. Conclusions Our results suggest that NTRK3 is a TMB-related prognostic biomarker, which lays the foundation for further research on the immunomodulatory effect of NTRK3 in BLCA.

A reliable constitutive model is a prerequisite to simulate a new complex forming technique, which is represented by the near-net shape forging process of aluminum wheels in this study. The aim of the present work was to identify the physical-based constitutive model parameters of Al-Zn-Mg alloy via the inverse analysis method based on experimental data and numerical analysis: the stress–strain curves at different temperatures and strain rates were obtained based on hot compression tests. On the basis of the shape of the compressed specimens and experimental force–displacement data, the friction coefficients and the optimized physical-based constitutive model were determined by using two-times inverse analysis techniques. Results showed that the global average error between the predicted and experimental force–displacement curves was only 3.8%. Then, thermo-mechanical finite element models were built in the Deform-3D software to simulate the two-stage forging processes of the near-net shape forging of aluminum alloy wheels, and the results showed that the predicted load–stroke curves were in good agreement with the experimental ones in all forging stages, which verified the prediction accuracy of the optimized physical-based constitutive model. In addition, the identification of the physical-based constitutive model parameters by the inverse analysis method provides a theoretical basis for formulating and optimizing the near-net shape forging process parameters of aluminum alloy wheels.

2A12 aluminum alloy is a high-strength aerospace alloy. During its extrusion process, the extrusion process parameters have a great impact on the microstructure evolution of the extruded products. There are three extrusion process parameters controlled in the actual project, which are the initial temperature of billet, the initial temperature of die and the extrusion speed. Combined with a back propagation (BP) neural network and finite element method (FEM) simulation, based on the constitutive equation and recrystallization evolution process of 2A12 aluminum alloy, this paper establishes a prediction model for the grain size of extruded pipe by these three extrusion process parameters. This paper used a 35MN extruding machine for a production verification of 2A12 pipe. The results show that the predicted grain size is 3% smaller than the actual size.

It is still a clinical challenge to sustain the remission of rheumatoid arthritis (RA); thus, identifying more effective and safer agents for RA treatment remains an urgent demand. We investigated the anti-arthritic activity and potential mechanism of action of sodium Danshensu (SDSS), a structurally representative water-soluble derivative of Danshen, on collagen-induced arthritis (CIA) mice. Our results showed that paw edema, synovium hyperplasia, bone destruction, and the serum levels of both IL-1β and IL-6 were ameliorated by SDSS (40 mg/kg·d) in CIA mice. In addition, there was no difference between SDSS and methotrexate (MTX, 2 mg/kg·3d) treatment in the above indicators. Further mechanism studies illustrated that SDSS inhibited IL-1β secretion by downregulating the HIF-1α/STAT3/NLRP3 pathway in macrophages. On the other hand, HIF-1α accumulation and HIF-1α/STAT3/NLRP3 pathway activation by IOX4 stimulation reduced the therapeutic effect of SDSS. These findings demonstrate that SDSS displays anti-arthritic activity in CIA mice and prevents proinflammatory cytokines secretion in macrophages by suppressing the HIF-1α/STAT3/NLRP3 pathway.

Abstract Programmed death receptor-ligand 1 (PD-L1) plays a crucial role in immune evasion by tumour cells. Most tumour cells exhibit energy dependency and acquire energy from glycolysis. However, the relationship between glucose metabolism and PD-L1 expression remains unclear. In this study, changes in PD-L1 expression in renal carcinoma cells were evaluated during glucose deficiency and recovery, and PD-L1 could inversely regulate glycolysis. In addition, the possible signalling pathways activated by a low level of glucose to regulate PD-L1 were tested experimentally. The results showed that glucose deficiency could upregulate PD-L1 expression in two renal cancer cell lines, 786-O and OS-RC-2. Although the native levels of PD-L1 differed in the two cell lines, the upregulated PD-L1 expression was repristinated after glucose recovery. Moreover, epidermal growth factor receptor (EGFR) expression was upregulated in both cell lines with glucose deficiency. The use of an EGFR inhibitor reversed the upregulation of PD-L1 expression induced by glucose deficiency and inhibited the phosphorylation of extracellular regulated protein kinases 1 and 2 (ERK1/2). EGFR activated by epidermal growth factor (EGF) induced PD-L1 expression and ERK1/2 phosphorylation. Furthermore, an ERK1/2 inhibitor inhibited the phosphorylation of c-Jun and decreased the elevated PD-L1 expression induced by glucose deficiency. In addition, this study also showed that 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFK-2/FBPase 3 or PFKFB3) mediated upregulation of the level of glycolysis to improve the adverse environment through PD-L1 induction. Therefore, glucose metabolism can regulate the expression of PD-L1 through the EGFR/ERK/c-Jun pathway in renal cancer, and elevated PD-L1 can also regulate glycolysis by improving the expression of PFKFB3. The findings of this study could provide a new multiple target treatment for renal cell carcinoma (RCC) therapy.

It is important to model the flow behavior of materials before the design and optimization of the forming process. In this work, the TC6 titanium alloy was subjected to a temperature range of 800 °C to 1000 °C and a strain range of 0.01 s−1 to 10 s−1 in isothermal compression experiments, after which friction and temperature corrections were performed. Based on the corrected data, three metamodeling methods—the response surface method, the Kriging method, and the BP neural network—were used to model the constitutive relationships of the TC6 titanium alloy. The results show that the three models can better predict the flow stress of the TC6 titanium alloy than the Arrhenius model. In addition, by comparing the fitting accuracy of the three methods using different numbers of training samples, we found that the accuracy of the BP neural network method is very dependent on the number of training samples, while the fitting accuracy of the response surface method and the Kriging method is always maintained at a high level; when the number of training samples is between 30 and 240, the curved surfaces fitted by these two methods do not change significantly. Compared with the Arrhenius model, the response surface method and the Kriging method can reach higher accuracy with fewer training samples, which is significant for reducing the number of experiments and calculation time required to model the constitutive relationship.

Dihydroarteannuin (DHA), the primary element of artemisinin extracted from the traditional Chinese herb Artemisia annua L., has been used in malaria treatment for a long time. Recently, many studies have indicated that DHA also exhibits potent anti-rheumatoid arthritis (RA) activity. In this study, collagen-induced arthritis (CIA) in DBA/1J mice and inflammatory model in THP-1 cells were established to evaluate the modulatory effects of DHA on joint destruction and to explore the underlying mechanisms. Our results showed that DHA decreased the serum levels of IL-1β and IL-6, alleviated paw oedema, and reduced bone destruction in DBA/1J mice with CIA. Further exploration with the inflammatory model in THP-1 cells indicated that DHA reduced the protein expression of hypoxia‐inducible factor (HIF)‐1α and the phosphorylation in Janus kinase (JAK) 3 and signal transducer and activator of transcription (STAT) 3 protein, which resulted in a decrease in NOD-like receptor protein (NLRP) 3 expression and interleukin (IL)-1β release. Consequentially, the inflammatory activation in THP-1 cells was inhibited. Therefore, we concluded that DHA efficiently alleviated the inflammation and arthritic symptoms in CIA mice and downregulated inflammation in part by inhibiting NLRP3 expression via the HIF‐1α and JAK3/STAT3 signaling pathway. Thus, DHA may be considered as a potential therapeutic agent in RA treatment.

BackgroundPatients with renal cell carcinoma are often troubled by metastases, but masseter muscle metastases are particularly rare.Case PresentationWe reported a 76-year-old male who did not show any recurrence and metastasis after the nephrectomy until 5 years later. The metastatic mass was found with the protrusion of masseter muscle area. Computed tomography and ultrasonography indicated a hypervascular mass, and pathology confirmed the masseter muscle metastasis of renal cell carcinoma. Complete metastasectomy was performed with the preserval of facial function and appearance. No local recurrence or distant metastasis was found in follow-up.ConclusionOur report indicates masseter muscle can be a metastatic site of renal cell carcinoma, regardless of its rarity. Long-term comprehensive surveillance is needed for patients with renal cell carcinoma. Muscle metastases can disguise as benign mass, while multiple imaging and pathology are important in identifying their sources. If possible, complete metastasectomy with function retention is recommended for masseter muscle metastases.

ChinaPurpose: To compare the diagnostic efficiency of 68Gallium labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET) and magnetic resonance imaging (MRI) for staging the lymph node metastases (LNMs) in the prostate cancer. Materials and Methods: A broad search of scientific databases including PubMed, EMBASE, Web of Science, Cochrane Database, and Chinese Biomedicine Literature Database (updated prior to November 1st, 2018) was conducted systematically by two reviewers. In this paper, we evaluated the methodological quality of each included article independently and performed a systematic review and meta-analysis to reveal the summary of the diagnostic performance of 68Ga-PSMA PET and MRI in properly identifying LNMs of intermediate- and/or high-risk prostate cancer.Results: Thirteen eligible articles comprising 1,597 patients were included. For LNMs detection, the pooled sensitivity and specificity of 68Ga-PSMA PET were 0.65 (95% confidence interval [CI]: 0.49–0.79) and 0.94 (95% CI: 0.88–0.97), respectively, while the corresponding values of MRI were 0.41 (95% CI: 0.26–0.57) and 0.92 (95% CI: 0.86–0.95). The area under the symmetric receiver-operating characteristic (SROC) curve for 68Ga-PSMA PET and MRI were 0.92 and 0.83, respectively. Conclusions: In intermediate- or high-risk pre-treatment prostate cancer, 68Ga-PSMA PET had a higher sensitivity and a slightly different specificity in probing the LNMs when comparing with MRI. Moreover, the area under the SROC curve indicated that 68Ga-PSMA PET was a more effective weapon for predicting the LNMs prior to radical surgery.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

BackgroundClinical practice guidelines recommend that exercise is essential in the self-management of ankylosing spondylitis (AS). Attending supervised interventions requiring periodic medical center visits can be difficult and patients may decline participation, whereas effective home-based exercise interventions that do not require regular medical center visits are likely to be more accessible for AS patients. ObjectiveThe goal of the research was to investigate the adherence, efficacy, and safety of a wearable technology–assisted combined home-based exercise program in AS. MethodsThis was a 16-week investigator-initiated, assessor-blinded, randomized, pilot controlled trial conducted at Chinese People’s Liberation Army General Hospital. We enrolled patients with AS who had no regular exercise habits and had been stable in drug treatment for the preceding month. Patients were randomly assigned (1:1) using a computer algorithm. An exercise program consisting of moderate-intensity aerobic exercise and functional exercise was given to the patients in the intervention group. The exercise intensity was controlled by a Mio FUSE Heart Rate Monitor wristband, which uses photoplethysmography to measure heart rate. Patients in the control group received usual care. The primary outcome was the difference in the Ankylosing Spondylitis Disease Activity Score (ASDAS). The secondary outcomes were patient global assessment (PGA), physician global assessment (PhGA), total pain, nocturnal pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BAS Functional Index (BASFI), BAS Metrology Index (BASMI), Spondyloarthritis International Society Health Index (ASAS HI), 36-item Short Form Survey (SF-36), maximal oxygen uptake (VO2) max, body composition, range of motion of joints, and muscle endurance tests. Retention rate, adherence rate, barriers to being active, and adverse events were also assessed. ResultsA total of 77 patients were screened, of whom 55 (71%) patients were enrolled; 2% (1/55) withdrew without treatment after randomization. Patients were assigned to the intervention (n=26) or control group (n=28). The median adherence rate of the prescribed exercise protocol was 84.2% (IQR 48.7%-97.9%). For the primary outcome, between-group difference of ASDAS was significant, favoring the intervention (–0.2, 95% CI –0.4 to 0.02, P=.03). For the secondary outcomes, significant between-group differences at 16 weeks were detected in PGA, PhGA, total pain, BASDAI, BASDAI-fatigue, BASDAI–spinal pain, BASDAI–morning stiffness intensity, BASFI, and BASMI. Moreover, the frequency of difficulty in ASAS HI-motivation at 16 weeks was less in the intervention group (P=.03). Between-group difference for change from baseline were also detected in VO2 max, SF-36, back extensor endurance test, and the range of motion of cervical lateral flexion at 16 weeks. Lack of time, energy, and willpower were the most distinct barriers to being active. Incidences of adverse events were similar between groups (P=.11). ConclusionsOur pilot study suggests that this technology-assisted combined home-based exercise program can improve the clinical outcomes of patients with AS who have no exercise habit, with good adherence and safety profile. Trial RegistrationChinese Clinical Trial Registry ChiCTR1900024244; http://www.chictr.org.cn/showproj.aspx?proj=40176

Dess–Martin periodinane (DMP) is a broadly applicable oxidant in chemical synthesis. In this work, an efficient and convenient synthesis of N-substituted isoquinolinone derivatives mediated by DMP was achieved through the oxidative coupling reaction of functionalized isoquinoline with readily available benzyl bromide, which is a metal-free, mild, and practical method for synthesizing isoquinoline-1,3-dione or isoquinoline-1,3,4-trione derivatives in excellent yields. The H2O18-labeling experiment was performed to gain insight into the possible mechanism for this reaction.