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Abstract Background Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated. Methods Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing. Results CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor. Conclusion A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients.

Abstract Background Scrub typhus is an acute infectious disease caused by Orientia tsutsugamushi. Guillain–Barre syndrome (GBS) is an autoimmune-mediated peripheral neuropathy with a frequent history of prodromal infections, but GBS associated with scrub typhus is very rare. Case presentation We report a 51-year-old male patient who developed dysarthria and peripheral facial paralysis following the cure of scfrub typhus. CSF examination and electrophysiological findings suggested a diagnosis of GBS. After treatment with intravenous immunoglobulin, the patient’s neurological condition improved rapidly. Conclusions Scrub typhus infection is likely to be a potential predisposing factor in GBS, while scrub typhus-associated GBS has a favorable prognosis.

In this work, we focus our attention on the existence of nontrivial solutions to the following supercritical Schrödinger-Poisson type system with $ (p, q) $-Laplacian: $ \begin{equation*} \begin{cases} -\Delta_{p}u-\Delta_{q}u+\phi|u|^{q-2} u = f\left(x, u\right)+\mu|u|^{s-2} u & \text { in } \Omega, \\ -\Delta \phi = |u|^q & \text { in } \Omega, \\ u = \phi = 0 & \text { on } \partial \Omega, \end{cases} \end{equation*} $ where $ \Omega \subset \mathbb{R}^N $ is a bounded smooth domain, $ \mu > 0, N > 1 $, and $ -\Delta_{{\wp}}\varphi = div(|\nabla\varphi|^{{\wp}-2} \nabla\varphi) $, with $ {\wp}\in \{p, q\} $, is the homogeneous $ {\wp} $-Laplacian. $ 1 < p < q < \frac{q^*}{2} $, $ q^*: = \frac{Nq}{N-q} < s $, and $ q^* $ is the critical exponent to $ q $. The proof is accomplished by the Moser iterative method, the mountain pass theorem, and the truncation technique. Furthermore, the $ (p, q) $-Laplacian and the supercritical term appear simultaneously, which is the main innovation and difficulty of this paper.

Abstract Background The cardiometabolic index (CMI) is a new metric derived from the triglyceride-glucose index and body mass index and is considered a potential marker for cardiovascular risk assessment. This study aimed to examine the correlation between the CMI and the presence and severity of arteriosclerosis in patients with type 2 diabetes mellitus (T2DM). Methods This study involved 2243 patients with T2DM. The CMI was derived by dividing the triglyceride level (mmol/L) by the high-density lipoprotein level (mmol/L) and then multiplying the quotient by the waist-to-height ratio. Multivariate logistic regression was used to analyze the correlations between the CMI and BMI blood biomarkers, blood pressure, and brachial-ankle pulse wave velocity (baPWV). Results Patients were categorized into three groups based on their CMI: Group C1 (CMI 1.355; n = 750). Increased BMI, fasting glucose, insulin (at 120 min), total cholesterol (TC), and baPWV values were observed in Groups C2 and C3, with statistically significant trends (all trends P

Summary: Background: Retrograde intrarenal surgery (RIRS) is the main treatments for upper urinary tract stones. The Ureteral Access Sheath (UAS) serves as a supplementary tool, facilitating direct kidney access during RIRS. High quality of evidence comparing tip bendable suction ureteral access sheath (S-UAS) with traditional UAS in RIRS for the treatment of renal and ureteral stones is lacking. The purpose of the study is to compare the efficacy and safety of S-UAS with traditional UAS in RIRS for the treatment of renal or ureteral stones ≤30 mm. Methods: An international, multicenter, and superiority randomized controlled trial included 320 intention-to-treat patients across 8 medical centers in China, the Philippines, Malaysia and Turkey from August 2023 to February 2024. The inclusion criteria were patients ≥18 years old with renal or ureteral stones ≤30 mm. RIRS was performed using either S-UAS or traditional UAS. The primary outcome was the immediately stone-free rate (SFR). Secondary outcomes included SFR 3 months after operation, operating time, hospital stay, auxiliary procedures, complications (using the Clavien–Dindo grading system), and improvement in the Quality of Life (QoL) score. Differences between proportions [risk difference (RD)]/means [mean difference (MD)] and 95% confidence intervals (CI) were presented. This study is registered at ClinicalTrials.gov: NCT05952635. Findings: The S-UAS group demonstrated a significantly higher immediately SFR (81.3% versus 49.4%; RD 31.9%; 95% CI 22.5%–41.7%; p = 0.004) compared to the traditional UAS group, as determined by the one-side superiority test. Additionally, the S-UAS group exhibited a higher SFR at 3 months post-operation (87.5% versus 70.0%; RD 17.5%; 95% CI 8.7%–26.3%; p

Acute myeloid leukemia (AML) is a common hematological malignancy with overall poor prognosis. Exploring novel targets is urgent and necessary to improve the clinical outcome of relapsed and refractory (RR) AML patients. Through clinical specimens, animal models and cell-level studies, we explored the specific mechanism of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 (HMGCS1) in AML and the mechanism of targeting HMGCS1 to attenuate cell proliferation, increase chemotherapy sensitivity and improve the occurrence and development of AML. Here, we reveal that HMGCS1 is overexpressed in RR patients and negatively related to overall survival (OS). Knocking out HMGCS1 in AML cells attenuated cell proliferation and increased chemotherapy sensitivity, while stable overexpression of HMGCS1 had the opposite effects. Mechanistically, we identified that knockout of HMGCS1 suppressed mitogen-activated protein kinase (MAPK) pathway activity, while overexpression of HMGCS1 could remarkably enhance the pathway. U0126, a MEK1 inhibitor, offset the effects of HMGCS1 overexpression, indicating that HMGCS1 promotes RR AML through the MAPK pathway. Further, we verified that hymeglusin, a specific inhibitor of HMGCS1, decreases cell growth both in AML cell lines and primary bone marrow cells of AML patients. Furthermore, combination of hymeglusin and the common chemotherapeutic drug cytarabine and adriamycin (ADR) had synergistic toxic effects on AML cells. Our study demonstrates the important role of HMGCS1 in AML, and targeting this protein is promising for the treatment of RR AML.

The use of animal models for biological experiments is no longer sufficient for research related to human life and disease. The development of organ tissues has replaced animal models by mimicking the structure, function, development and homeostasis of natural organs. This provides more opportunities to study human diseases such as cancer, infectious diseases and genetic disorders. In this study, bibliometric methods were used to analyze organoid-related articles published over the last 20+ years to identify emerging trends and frontiers in organoid research. A total of 13,143 articles from 4125 institutions in 86 countries or regions were included in the analysis. The number of papers increased steadily over the 20-year period. The United States was the leading country in terms of number of papers and citations. Harvard Medical School had the highest number of papers published. Keyword analysis revealed research trends and focus areas such as organ tissues, stem cells, 3D culture and tissue engineering. In conclusion, this study used bibliometric and visualization methods to explore the field of organoid research and found that organ tissues are receiving increasing attention in areas such as cancer, drug discovery, personalized medicine, genetic disease modelling and gene repair, making them a current research hotspot and a future research trend.

Glioma is the most common primary malignant tumor in the brain, characterizing by high disability rate and high recurrence rate. Although low-grade glioma (LGG) has a relative benign biological behavior, the prognosis of LGG patients still varies greatly. Glioma stem cells (GSCs) are considered as the chief offenders of glioma cell proliferation, invasion and resistance to therapies. Our study screened a series of glioma stem cell-related genes (GSCRG) based on mDNAsi and WCGNA, and finally established a reliable single-gene prognostic model through 101 combinations of 10 machine learning methods. Our result suggested that the expression level of TNFAIP6 is negatively correlated with the prognosis of LGG patients, which may be the result of pro-cancer signaling pathways activation and immunosuppression. In general, this study revealed that TNFAIP6 is a robust and valuable prognostic factor in LGG, and may be a new target for LGG treatment.

BackgroundDespite the efficacy of efgartigimod demonstrated in ADAPT phase 3 trial, data specifically derived from Chinese participants are not available. Therefore, we aimed to evaluate the efficacy and safety of efgartigimod in Chinese patients with generalized myasthenia gravis (gMG).MethodsThis is a prospective cohort study conducted in 8 hospitals across China. gMG patients received weekly intravenous infusions of efgartigimod (10 mg/kg) under a named patient program (NPP). The present study is an 8-week study, consisting of 4 consecutive doses of efgartigimod administered over 3 weeks (one cycle), followed by a 5-week follow-up period to assess the tolerability of efgartigimod’s therapeutic effects. The primary outcome was the mean change in MG activities of daily living (MG-ADL) total score from baseline to 4 weeks. MG-ADL responder was defined as a ≥ 2-point improvement that persisted for 4 weeks, starting by week 4. Safety evaluations encompassed the monitoring of adverse events (AE) and serious AE (SAE) throughout the study.ResultsBetween 5 July 2022 and 25 August 2023, a total of 14 gMG patients were included. The mean age was 57.7 years, with a mean MG-ADL score of 10.86 ± 3.32. At week 4, MG-ADL scores showed a mean reduction of 6 points, reaching a maximum decline of 13 points. Among the patients, 85.7% (12/14) achieved MG-ADL responder status after one cycle of treatment. The most significant reduction in quantitative MG (QMG) scores also occurred at week 4, with a mean decrease of 7 points. Notably, the improvements in MG-ADL and QMG scores persisted until week 8. During treatment and follow-up period, only two mild neck rashes occurred and resolved promptly. No infections or SAE were reported.DiscussionA single cycle of efgartigimod treatment demonstrates effectiveness and the tolerability through week 8, with no new safety signals observed in Chinese gMG patients.

Objective(s): The present study investigated the effect and its underlying mechanisms of fucoidan on Type 1 diabetes mellitus (T1DM) in non-obese diabetic (NOD) mice. Materials and Methods: Twenty 7-week-old NOD mice were used in this study, and randomly divided into two groups (10 mice in each group): the control group and the fucoidan treatment group (600 mg/kg. body weight). The weight gain, glucose tolerance, and fasting blood glucose level in NOD mice were detected to assess the development of diabetes. The intervention lasted for 5 weeks. The proportions of Th1/Th2 cells from spleen tissues were tested to determine the anti-inflammatory effect of fucoidan. Western blot was performed to investigate the expression levels of apoptotic markers and autophagic markers. Apoptotic cell staining was visualized through TdT-mediated dUTP nick-end labeling (TUNEL). Results: The results suggested that fucoidan ameliorated T1DM, as evidenced by increased body weight and improved glycemic control of NOD mice. Fucoidan down-regulated the Th1/Th2 cells ratio and decreased Th1 type pro-inflammatory cytokines’ level. Fucoidan enhanced the mitochondrial autophagy level of pancreatic cells and increased the expressions of Beclin-1 and LC3B II/LC3B I. The expression of p-AMPK was up-regulated and p-mTOR1 was inhibited, which promoted the nucleation of transcription factor EB (TFEB), leading to autophagy. Moreover, fucoidan induced apoptosis of pancreatic tissue cells. The levels of cleaved caspase-9, cleaved caspase-3, and Bax were up-regulated after fucoidan treatment. Conclusion: Fucoidan could maintain pancreatic homeostasis and restore immune disorder through enhancing autophagy via the AMPK/mTOR1/TFEB pathway in pancreatic cells.

Abstract Background Aquaculture plays an important role in global protein supplies and food security. The ban on antibiotics as feed additive proposes urgent need to develop alternatives. Gut microbiota plays important roles in the metabolism and immunity of fish and has the potential to give rise to novel solutions for challenges confronted by fish culture. However, our understanding of fish gut microbiome is still lacking. Results We identified 575,856 non-redundant genes by metagenomic sequencing of the intestinal content samples of grass carp. Taxonomic and functional annotation of the gene catalogue revealed specificity of the gut microbiome of grass carp compared with mammals. Co-occurrence analysis indicated exclusive relations between the genera belonging to Proteobacteria and Fusobacteria/Firmicutes/Bacteroidetes, suggesting two independent ecological groups of the microbiota. The association pattern of Proteobacteria with the gene expression modules of fish gut and the liver was consistently opposite to that of Fusobacteria, Firmicutes, and Bacteroidetes, implying differential functionality of Proteobacteria and Fusobacteria/Firmicutes/Bacteroidetes. Therefore, the two ecological groups were considered as two functional groups, i.e., Functional Group 1: Proteobacteria and Functional Group 2: Fusobacteria/Firmicutes/Bacteroidetes. Further analysis revealed that the two functional groups differ in genetic capacity for carbohydrate utilization, virulence factors, and antibiotic resistance. Finally, we proposed that the ratio of “Functional Group 2/Functional Group 1” can be used as a biomarker that efficiently reflects the structural and functional characteristics of the microbiota of grass carp. Conclusions The gene catalogue is an important resource for investigating the gut microbiome of grass carp. Multi-omics analysis provides insights into functional implications of the main phyla that comprise the fish microbiota and shed lights on targets for microbiota regulation. Video Abstract

In this study, the authors propose a model, called the Daily Downward Shortwave Radiation Random Forest Model over Rugged Terrain (DSRMT), to accurately calculate the downward shortwave radiation over a terrain without bright surface on clear days at a daily scale (DSRdaily−rugged). It was built by using the random forest method based on the comprehensive samples from CERES4_SYN1deg_Ed4A within 17 typical mountainous regions. DSRMT could directly estimate DSRdaily-rugged from the instantaneous direct and diffuse solar radiation on a flat surface during 10:30–14:30hrs on each day by comparing with the terrain factors from a digital elevation model, broadband albedo from the Global Land Surface Satellite, and ancillary information. The in-situ validation results showed that it generally delivered superior performance in estimating DSRdaily-rugged at any time during 10:30–14:30hrs, especially at noon, yielding a validated root mean-squared error (RMSE) of 24.90–29.22 Wm−2 and mean absolute error (MAE) of 19.16–22.94 Wm−2, and the average weighted DSRdaily-rugged were usually more accurate with the RMSE and MAE of 21.63 and 17.14 Wm−2. Overall, DSRMT was found to deliver satisfactory performance because of its high accuracy, robustness, ease of implementation, and efficiency, so it has the strong potential to be widely used in practice.

Land surface all-wave net radiation (Rn) is crucial in determining Earth's climate by contributing to the surface radiation budget. This study evaluated seven satellite and three reanalysis long-term land surface Rn products under different spatial scales, spatial and temporal variations, and different conditions. The results showed that during 2000-2018, Global Land Surface Satellite Product (GLASS)-Moderate Resolution Imaging Spectroradiometer (MODIS) performed the best (RMSE=25.54 Wm-2, bias=−1.26 Wm-2), followed by ERA5 (the fifth-generation of European Centre for Medium-Range Weather Forecast Reanalysis) (RMSE=32.17 Wm-2, bias=−4.88 Wm-2) and GLASS-AVHRR (Advanced Very-High-Resolution Radiometer) (RMSE=33.10 Wm-2, bias=4.03 Wm-2). During 1983-2018, GLASS-AVHRR and ERA5 ranked top and performed similarly, with RMSE values of 31.70 and 33.08 Wm-2 and biases of −4.56 and 3.48 Wm-2, respectively. The averaged multi-annual mean Rn over the global land surface of satellite products was higher than that of reanalysis products by about 10∼30 Wm-2. These products differed remarkably in long-term trends variations, particularly pre-2000, but no significant trends were observed. Discrepancies were more frequent in satellite data, while reanalysis products showed smoother variations. Large discrepancies were found in regions with high latitudes, reflectance, and elevation which could be attributed to input radiative components, meteorological variables (e.g., cloud properties, aerosol optical thickness), and applicability of the algorithms used. While further research is needed for detailed insights.

Earth surface longwave radiation (SLR), including downward (DLR), upward (ULR), and net longwave radiation (NLR), significantly impacts the surface radiation budget and global climate evolution. However, the spatiotemporal variation in SLR remains poorly understood. In this study, three satellite products (GLASS-MODIS V40, GLASS-AVHRR, and CERES-SYN) and three reanalysis datasets (ERA5, MERRA-2, and GLDAS) were validated using ground measurements from 288 sites at seven observation networks. The mean biases and root mean square errors of the monthly DLR (ULR, NLR) estimates from the six products were −6.36 (−3.56, −2.86) Wm-2 and 16.63 (14.33, 13.38) Wm-2, respectively. Large differences in the spatial distribution of the SLR were mainly observed at high-latitude, high-altitude and desert/barren-covered regions. Large interannual variability was detected at high latitudes. GLASS-AVHRR and ERA5 better captured the long-term variability in DLR and ULR, whereas GLASS-AVHRR and MERRA-2 better detected trends in NLR. An increasing trend in DLR and ULR was observed between 1982 and 2015, followed by a decreasing trend from 2016 to 2021; the NLR flux did not exhibit a significant trend. Overall, the GLASS-AVHRR and ERA5 SLR estimates were more accurate and stable than those of the other products in accuracy, spatiotemporal distribution, and trend analysis.

Objective: This study aims to investigate the predictive performance of machine learning in predicting the occurrence of systemic inflammatory response syndrome (SIRS) and urosepsis after percutaneous nephrolithotomy (PCNL). Methods: A retrospective analysis was conducted on patients who underwent PCNL treatment between January 2016 and July 2022. Machine learning techniques were employed to establish and select the best predictive model for postoperative systemic infection. The feasibility of using relevant risk factors as predictive markers was explored through interpretability with Machine Learning. Results: A total of 1067 PCNL patients were included in this study, with 111 (10.4 %) patients developing SIRS and 49 (4.5 %) patients developing urosepsis. In the validation set, the risk model based on the GBM protocol demonstrated a predictive power of 0.871 for SIRS and 0.854 for urosepsis. Preoperative and postoperative platelet changes were identified as the most significant predictors. Both thrombocytopenia and thrombocytosis were found to be risk factors for SIRS or urosepsis after PCNL. Furthermore, it was observed that when the change in platelet count before and after PCNL surgery exceeded 30*109/L (whether an increase or decrease), the risk of developing SIRS or urosepsis significantly increased. Conclusion: Machine learning can be effectively utilized for predicting the occurrence of SIRS or urosepsis after PCNL. The changes in platelet count before and after PCNL surgery serve as important predictors.

Nattokinase (NK) and red yeast rice (RYR) are both indicated for their potential in cardiovascular disease prevention and management, but their combined effects especially in coronary artery disease (CAD) are scarcely examined. This 90-day randomized, double-blind trial aims to investigate the effect of NK and RYR supplementations on cardiometabolic parameters in patients with stable CAD. 178 CAD patients were randomized to four groups: NK + RYR, NK, RYR, and placebo. No adverse effects due to the interventions were reported. In comparisons across groups, NK + RYR showed the maximum effect in reducing triglyceride (−0.39 mmol), total cholesterol (−0.66 mmol/L), diastolic blood pressure (−7.39 mmHg), and increase in high-density lipoprotein cholesterol (0.195 mmol/L) than other groups (all p for multiple groups comparison

BackgroundBlood pressure (BP) is a key factor for the clinical outcomes of acute ischemic stroke (AIS) receiving endovascular thrombectomy (EVT). However, the effect of the circadian pattern of BP on functional outcome is unclear.MethodsThis multicenter, retrospective, observational study was conducted from 2016 to 2023 at three hospitals in China (ChiCTR2300077202). A total of 407 patients who underwent endovascular thrombectomy (EVT) and continuous 24-h BP monitoring were included. Two hundred forty-one cases from Beijing Hospital were allocated to the development group, while 166 cases from Peking University Shenzhen Hospital and Hainan General Hospital were used for external validation. Postoperative systolic BP (SBP) included daytime SBP, nighttime SBP, and 24-h average SBP. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), Boruta were used to screen for potential features associated with functional dependence defined as 3-month modified Rankin scale (mRS) score ≥ 3. Nine algorithms were applied for model construction and evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy.ResultsThree hundred twenty-eight of 407 (80.6%) patients achieved successful recanalization and 182 patients (44.7%) were functional independent. NIHSS at onset, modified cerebral infarction thrombolysis grade, atrial fibrillation, coronary atherosclerotic heart disease, hypertension were identified as prognostic factors by the intersection of three algorithms to construct the baseline model. Compared to daytime SBP and 24-h SBP models, the AUC of baseline + nighttime SBP showed the highest AUC in all algorithms. The XGboost model performed the best among all the algorithms. ROC results showed an AUC of 0.841 in the development set and an AUC of 0.752 in the validation set for the baseline plus nighttime SBP model, with a brier score of 0.198.ConclusionThis study firstly explored the association between circadian BP patterns with functional outcome for AIS. Nighttime SBP may provide more clinical information regarding the prognosis of patients with AIS after EVT.

Intestine is responsible for nutrients absorption and plays a key role in defending against various dietary allergens, antigens, toxins, and pathogens. Accumulating evidence reported a critical role of intestine in maintaining animal and human health. Since the use of antibiotics as growth promoters in animal feed has been restricted in many countries, alternatives to antibiotics have been globally investigated, and polysaccharides are considered as environmentally friendly and promising alternatives to improve intestinal health, which has become a research hotspot due to its antibiotic substitution effect. Astragalus polysaccharide (APS), a biological macromolecule, is extracted from astragalus and has been reported to exhibit complex biological activities involved in intestinal barrier integrity maintenance, intestinal microbiota regulation, short-chain fatty acids (SCFAs) production, and immune response regulation, which are critical for intestine health. The biological activity of APS is related to its chemical structure. In this review, we outlined the source and structure of APS, highlighted recent findings on the regulation of APS on physical barrier, biochemical barrier, immunological barrier, and immune response as well as the latest progress of APS as an antibiotic substitute in animal production. We hope this review could provide scientific basis and new insights for the application of APS in nutrition, clinical medicine and health by understanding particular effects of APS on intestine health, anti-inflammation, and animal production.

This study investigated the effects of Lactobacillus rhamnosus fermentation products added to feed on common carp (Cyprinus carpio) on growth, gut and liver health, and gut microbiota. Common carp with an average weight of 1.95±0.4 g were fed five experimental diets: normal diet (normal) and normal diet supplemented with Lactobacillus rhamnosus fermentation products (abbreviation: 0.2% GCC-3, 0.3% GCC-3, 0.4% GCC-3 and 0.5% GCC-3, respectively) for 8 weeks. The results showed that the GCC-3 fermentation product did not affect the growth phenotype of common carp. The diet supplemented with 0.3% GCC-3 significantly reduced the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of common carp compared to the control group. Diets with GCC-3 fermentation products significantly reduced liver triacylglycerol (TAG) levels. Diets supplemented with 0.3% GCC-3 fermentation products significantly downregulated the expression of liver liposynthesis gene (fas) and significantly upregulated the expression of liver lipolysis gene (cpt1). Diets supplemented with GCC-3 significantly reduced the serum lipopolysaccharide (LPS) levels of common carp compared to the control group. In addition, dietary supplementation with 0.3% GCC-3, 0.4% GCC-3, or 0.5% GCC-3 all increased the abundance of Cetobacterium and decreased the abundance of Acinetobacter. In summary, dietary supplementation with 0.3% GCC-3, 0.4% GCC-3, and 0.5% GCC-3 reduced liver lipid deposition, and improved gut microbiota homeostasis of common carp. The best positive effect was observed in common carp fed a 0.3% GCC-3 supplemental diet.

Multiple sclerosis (MS) was defined as a rare disease in China due to its low prevalence. For a long time, interferon β was the only approved disease-modifying therapy (DMT). Since the first oral DMT was approved in 2018, DMT approval accelerated, and seven DMTs were approved within 5 years. With an increasing number of DMTs being prescribed in clinical practice, it is necessary to discuss the standardized MS treatment algorithms depending on the disease activity and DMT availability. In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country.

Abstract Background TFE3 immunohistochemistry (TFE3‐IHC) is controversial in the diagnosis of TFE3‐rearranged renal cell carcinoma (TFE3‐rearranged RCC). This study is to investigate the accuracy and sensitivity of IHC and establish a predictive model to diagnose TFE3‐rearranged RCC. Methods Retrospective analysis was performed by collecting IHC and fluorescence in situ hybridization (FISH) results from 228 patients. IHC results were evaluated using three scoring systems. Scoring system 1 is graded based on nuclear staining intensity, scoring system 2 is graded based on the percentage of stained tumor cell nuclei, and scoring system 3 is graded based on both the nuclear staining intensity and the percentage. We collected patients' IHC results and clinical information. Important variables were screened based on univariate logistic regression analysis. Then, independent risk factors were established through multivariate logistic regression, and a nomogram model was constructed. The model was validated in internal test set and external validation set. The receiver operating characteristic curve (ROC curve), calibration curve, and decision curve analysis (DCA) were generated to assess discriminative ability of the model. Results The accuracy of IHC based on three scoring systems were 0.829, 0.772, and 0.807, respectively. The model included four factors including age, gender, lymph node metastasis and IHC results. Area under the curve (AUC) values were 0.935 for the training set, 0.934 for the internal test set, 0.933 for all 228 patients, and 0.916 for the external validation set. Conclusions TFE3 IHC has high accuracy in the diagnosis of TFE3‐rearranged RCC. Clinical information such as age and lymph node metastasis are independent risk factors, which can be used as a supplement to the results of TFE3 IHC. This study confirms the value of IHC in the diagnosis of TFE3‐rearranged RCC. The accuracy of the diagnosis can be improved by incorporating IHC with other clinical risk factors.

Abstract Introduction During the last decades, the advent of flexible ureteroscopic lithotripsy has revolutionized the management of upper urinary tract stones. We designed a patented tip-bendable ureteral access sheath to facilitate stone clearance. Our current study reported our initial experience of 224 cases. Materials and methods The study is a descriptive, retrospective analysis. The initial 224 cases, operated consecutively by one surgeon during 16 months, were reviewed. The novel tip-bendable ureteral access sheath was applied in the procedure. Demographics, laboratory tests, and peri- and postoperative findings (operation duration, stone-free rate (SFR), utilization of flexible instruments and complications) were analyzed. Resutls The median age of the patients was 56 years and the mean stones size was 2.3 ± 1.3 cm. There were 63 cases of upper ureteral stone, 93cases of renal stone and 68 cases of ureteral-renal stones. The mean operative time was 69.2 ± 65.2 min. The immediate stone-free rate was 76.8% and the 1 month post-operative stone-free rate was 97.3%. Most cases(95.5%)were success in single session. Two patient experienced post-operative fever. There was no unplanned readmission. The frequency of post-operative complications was estimated at 0.89% (Clavien I). Conclusion Flexible ureteroscopic lithotripsy with tip-bendable ureteral access sheath is a safe and effective procedure, which can achieve excellent stone clearance.

Abstract Glioblastoma (GBM) is an aggressive intracranial tumour, and current chemotherapy regimens have limited efficacy. Aloperine (ALO), a natural alkaline compound, has shown potential as an antitumor agent. However, the effect of ALO against GBM remains unclear. This study aimed to investigate the function of ALO in treating GBM. U87, A172, and GL261 cell lines were used for in vitro experiments, and GL261 was also used to establish in vivo models. The results showed that ALO inhibited the proliferation of GBM cells by cell cycle arrest and apoptosis. Furthermore, autophagy was found to play a critical role, suggested by observation of autophagosomes under the transmission electron microscopy. It was discovered for the first time that ALO targeted lysosomes directly in glioma cells, tested by fluo-rescence-labelled ALO and organelle-localizing probes. In addition, ALO inhibited late autophagy and induced paraptosis in GBM, verified by classical gene expression changes in qPCR and western blotting. Also, ALO inhibited tumour growth and acted synergistically with temozolomide in intracranial glioma mice models in vivo. Our findings suggest that ALO targets lysosomes to inhibit late autophagy in GBM, inducing cell cycle arrest, paraptosis, and apoptosis. ALO may therefore be a promising therapeutic agent for the treatment of GBM.

Abstract Background In light of the abnormal expression of microRNA (miR-483-5p) in patients with atherosclerosis (AS), its role in vascular endothelial cell injury was explored. And the mechanisms related to autophagy were also elucidated. Methods Human umbilical vein endothelial cells (HUVECs) were given 100 mg/L ox-LDL to induce endothelial injury. Cell transfection was done to regulate miR-483-5p levels. Cell viability and apoptosis were detected. qRT-PCR was employed for the mRNA levels’ detection. Results Autophagic flux impairment of HUVECs was detected after ox-LDL treatment, along with the upregulation of miR-483-5p. Ox-LDL inhibited cell viability and promoted cell apoptosis, but these influences were changed by miR-483-5p downregulation. MiR-483-5p downregulation decreased the mRNA levels of IL-1β, IL-6, ICAM-1 and VCAM-1. 3-MA, the autophagy inhibitor, reversed the beneficial role of miR-483-5p downregulation in ox-LDL-induced HUVECs’ injury. TIMP2 acts as a target gene of miR-483-5p, and was downregulated in HUVEC models. Conclusion MiR-483-5p downregulation alleviated ox-LDL-induced endothelial injury via activating autophagy, this might be related to TIMP2.

Abstract Contactless bubble manipulation with a high spatiotemporal resolution brings a qualitative leap forward in a variety of applications. Despite considerable advances, light-induced bubble maneuvering remains challenging in terms of robust transportation, splitting and detachment. Here, a photopyroelectric slippery surface (PESS) with a sandwich structure is constructed to achieve the versatile bubble manipulation. Due to the generated dielectric wetting and nonuniform electric field under the irradiation of near infrared (NIR) light, a bubble is subject to both the Laplace force and dielectrophoresis force, enabling a high-efficiency bubble steering. We demonstrate that the splitting, merging and detachment of underwater bubbles can be achieved with high flexibility and precision, high velocity and agile direction maneuverability. We further extend the capability of bubble control to microrobots for cargo transportation, micropart assembly and transmission of gear structures. We envision this robust bubble manipulation strategy on the PESS would provide a valuable platform for various bubble-involved processes, ranging from microfluidic devices to soft robotics.

In this study, the dissipation, terminal residues and dietary risk of the cyazofamid residue in three globally consumed minor crops, turnip (Brassica rapa L.), onion (Allium cepa L.) and romaine lettuce (Lactuca sativa L.) were assessed by supervised field trials at 6 locations of China in 2020. A reliable QuEChERS-LC-MS/MS method was developed for simultaneous analysis of cyazofamid and its primary metabolite, 4-chloro-5-p-tolylimidazole-2-carbonitrile (CCIM). The average recoveries of cyazofamid and CCIM in turnip, onion and romaine lettuce were 79 %–97 % and 77 %–99 %, respectively. The half-lives of cyazofamid in these crops were 5.7–6.5, 5.3–8.7 and 5.8–6.5 days in turnip, onion and romaine lettuce, respectively, with the final cyazofamid residues at harvest all lower than limit of quantitation (LOQ, 0.01 mg/kg). The turnip roots, onion bulbs and romaine lettuce leaves grown in China under Good Agricultural Practices conditions and harvested 10, 14 and 5 days, respectively, after the cyazofamid SC (100 g/L) application, would be reasonably safe for consumption by the general population. The maximum residue limit (MRL) values of cyazofamid could be tentatively set as 10 mg/kg for turnip leaves, 0.3 mg/kg for turnip roots, 0.05 mg/kg for onion bulbs, and 10 mg/kg for romaine lettuce leaves.

Study region: China Study focus: An effective evapotranspiration stress assessment system requires reliable estimates actual evapotranspiration (ETa), and potential evapotranspiration (ETp), and should consider multiple influencing indicators. This study explores the consistency of multiple evaporation reanalysis datasets across mainland China and fuses them with multi-model ensemble method. To address the uncertainty inherent in the traditional evapotranspiration stress index (ESI) that only considers the ETa and ETp relationship, we employ Pearson Correlation Analysis and a Random Forest-based Boruta Algorithm to propose new evapotranspiration stress proxies blending multiple remote sensing indicators, named as MESI-P and MESI-B, respectively. Then, we verified their performance in depicting vegetation production capacity based on Solar-Induced Chlorophyll Fluorescence (SIF) and Gross Primary Productivity (GPP). New hydrological insights for the region: The patterns of ETa from GLDAS, GLEAM, and Harvard Dataverse in China show consistent, but their threshold values differ. The synthesized ETa obtained after using a multi-model ensemble (MME) method is more adaptable in China, with a range of 0.45–1485.31 mm and an increase of 11.34 mm/10a. Following the same pattern as GLDAS and CRU, the synthetic ETp experiences an increasing trend (11.24 mm/10a) during 2000–2019. Compared with the traditional ESI, the MESI-P and MESI-B proposed in this study have superior signal convergence with ETa, SIF, and GPP due to the higher correlation coefficients (＞0.95) in China. Furthermore, during the calculation of MESI-B, soil moisture and solar radiation are identified as dominate factor in Northwest and Southern China respectively.

Summary: Background: The occult lymph node metastasis (LNM) of laryngeal squamous cell carcinoma (LSCC) affects the treatment and prognosis of patients. This study aimed to comprehensively compare the performance of the three-dimensional and two-dimensional deep learning models, radiomics model, and the fusion models for predicting occult LNM in LSCC. Methods: In this retrospective diagnostic study, a total of 553 patients with clinical N0 stage LSCC, who underwent surgical treatment without distant metastasis and multiple primary cancers, were consecutively enrolled from four Chinese medical centres between January 01, 2016 and December 30, 2020. The participant data were manually retrieved from medical records, imaging databases, and pathology reports. The study cohort was divided into a training set (n = 300), an internal test set (n = 89), and two external test sets (n = 120 and 44, respectively). The three-dimensional deep learning (3D DL), two-dimensional deep learning (2D DL), and radiomics model were developed using CT images of the primary tumor. The clinical model was constructed based on clinical and radiological features. Two fusion strategies were utilized to develop the fusion model: the feature-based DLRad_FB model and the decision-based DLRad_DB model. The discriminative ability and correlation of 3D DL, 2D DL and radiomics features were analysed comprehensively. The performances of the predictive models were evaluated based on the pathological diagnosis. Findings: The 3D DL features had superior discriminative ability and lower internal redundancy compared to 2D DL and radiomics features. The DLRad_DB model achieved the highest AUC (0.89–0.90) among all the study sets, significantly outperforming the clinical model (AUC = 0.73–0.78, P = 0.0001–0.042, Delong test). Compared to the DLRad_DB model, the AUC values for the DLRad_FB, 3D DL, 2D DL, and radiomics models were 0.82–0.84 (P = 0.025–0.46), 0.86–0.89 (P = 0.75–0.97), 0.83–0.86 (P = 0.029–0.66), and 0.79–0.82 (P = 0.0072–0.10), respectively in the study sets. Additionally, the DLRad_DB model exhibited the best sensitivity (82–88%) and specificity (79–85%) in the test sets. Interpretation: The decision-based fusion model DLRad_DB, which combines 3D DL, 2D DL, radiomics, and clinical data, can be utilized to predict occult LNM in LSCC. This has the potential to minimize unnecessary lymph node dissection and prophylactic radiotherapy in patients with cN0 disease. Funding: National Natural Science Foundation of China, Natural Science Foundation of Shandong Province.

Whether a basketball player’s movements are standard or not is a key indicator to evaluate a basketball player and a key point for basketball player training. In order to improve the training effect of basketball players, effective and fast accurate recognition of basketball players’ action trajectories is crucial. In order to solve the problems of inadequate extraction of limb action features and loss of detail information due to multiple scales of limb action features caused by traditional recognition algorithms, an action trajectory recognition algorithm based on the improved EfficientDet-D0 is proposed. The algorithm firstly adds a spatial attention mechanism in the backbone network of EfficientDet-D0, where can locate the limb action trajectory features in the image more accurately. Secondly, in the feature fusion network, in order to describe the high-frequency detail information lost by downsampling, the idea of Laplace pyramid is used to fuse the detail feature maps in the top-down fusion path, and cross-level connections are added to make full use of the feature information of different resolutions, so that the acquired high-level feature map information is richer. Finally, the whole network is trained using the migration learning technique and Adam optimizer. The experimental results show that the model achieves a PCP value (percentage correct parts) of 95.6% on the upper limb pose dataset and takes only 5.34 s for 1000 tests. Compared with the traditional algorithm, it has a higher accuracy rate and stronger robustness, with strong practical applicability, realizing the effective and accurate recognition of basketball players’ upper limb action trajectories in real time.

Abstract. Background:. Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting. Methods:. To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks. Results:. A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population (P = 0.005, = 0.026, 50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment (P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. Conclusions:. Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.

Abstract As an important part of the stomach, gastric antrum secretes gastrin which can regulate acid secretion and gastric emptying. Although most cell types in the gastric antrum are identified, the comparison of cell composition and gene expression in the gastric antrum among different species are not explored. In this study, we collected antrum epithelial tissues from human, pig, rat and mouse for scRNA-seq and compared cell types and gene expression among species. In pig antral epithelium, we identified a novel cell cluster, which is marked by high expression of AQP5, F3, CLCA1 and RRAD. We also discovered that the porcine antral epithelium has stronger immune function than the other species. Further analysis revealed that this may be due to the insufficient function of porcine immune cells. Together, our results replenish the information of multiple species of gastric antral epithelium at the single cell level and provide resources for understanding the homeostasis maintenance and regeneration of gastric antrum epithelium.

Objective There is a new medial malleolar fracture classification based on 3D CT reconstruction. However, there is no study assessing the reliability and accuracy of the new classification system and comparison between the new and the classic classification. This study aimed to compare the reliability and accuracy of the medial malleolar fracture classification based on 3D CT reconstruction and the Herscovici classification system. Methods We retrospectively analyzed the consecutive ankle fractures in our hospital from January 2013 to September 2020. Five inexperienced and five experienced orthopedic surgeons were included as observers to assess 68 cases with medial malleolar fractures. Ten evaluators classified the cases according to the two classification systems. The reference results of each case were made by the consensus of three senior trauma surgeons. The interobserver reliability, intraobserver reliability, and accuracy were evaluated at an interval of 6 weeks using Fleiss's kappa (κ) statistics. Results We found substantial interobserver and intraobserver reliability and 81.4% accuracy for the new classification, which was statistically superior to the Herscovici classification (P

Abstract Background Clear cell renal cell carcinoma (ccRCC) is a malignant tumor with heterogeneous morphology and poor prognosis. This study aimed to establish a DNA methylation (DNAm)-driven gene-based prognostic model for ccRCC. Methods Reduced representation bisulfite sequencing (RRBS) was performed on the DNA extracts from ccRCC patients. We analyzed the RRBS data from 10 pairs of patient samples to screen the candidate CpG sites, then trained and validated an 18-CpG site model, and integrated the clinical characters to establish a Nomogram model for the prognosis or risk evaluation of ccRCC. Results We identified 2261 DMRs in the promoter region. After DMR selection, 578 candidates were screened, and was correspondence with 408 CpG dinucleotides in the 450 K array. We collected the DNAm profiles of 478 ccRCC samples from TCGA dataset. Using the training set with 319 samples, a prognostic panel of 18 CpGs was determined by univariate Cox regression, LASSO regression, and multivariate Cox proportional hazards regression analyses. We constructed a prognostic model by combining the clinical signatures. In the test set (159 samples) and whole set (478 samples), the Kaplan–Meier plot showed significant differences; and the ROC curve and survival analyses showed AUC greater than 0.7. The Nomogram integrated with clinicopathological characters and methylation risk score had better performance, and the decision curve analyses also showed a beneficial effect. Conclusions This work provides insight into the role of hypermethylation in ccRCC. The targets identified might serve as biomarkers for early ccRCC diagnosis and prognosis biomarkers for ccRCC. We believe our findings have implications for better risk stratification and personalized management of this disease.

Recent studies have indicated that fucoidan has the potential to improve cognitive impairment. The objective of this study was to demonstrate the protective effect and possible mechanisms of fucoidan in D-galactose (D-gal)-induced cognitive dysfunction. Sprague Dawley rats were injected with D-galactose (200 mg/kg, sc) and administrated with fucoidan (100 mg/kg or 200 mg/kg, ig) for 8 weeks. Our results suggested that fucoidan significantly ameliorated cognitive impairment in D-gal-exposed rats and reversed histopathological changes in the hippocampus. Fucoidan reduced D-gal-induced oxidative stress, declined the inflammation level and improved mitochondrial dysfunction in hippocampal. Fucoidan promoted mitochondrial biogenesis by regulating the PGC-1α/NRF1/TFAM pathway, thereby improving D-gal-induced mitochondrial dysfunction. The regulation effect of fucoidan on PGC-1α is linked to the upstream protein of APN/AMPK/SIRT1. Additionally, the neuroprotective action of fucoidan could be related to maintaining intestinal flora homeostasis with up-regulation of Bacteroidota, Muribaculaceae and Akkermansia and down-regulation of Firmicutes. In summary, fucoidan may be a natural, promising candidate active ingredient for age-related cognitive impairment interventions.

Recent studies in turbomachinery have shown that the phase of acoustic wave reflection within an intake can have either positive or negative effects on the aeroelastic stability of fan rotor blades. However, the typical flow structures, such as the shock wave, within rotor blade passages with acoustic wave reflection remain unclear. The aim of this research was to address this gap by investigating how these flow structures impact blade aeroelastic stabilities with acoustic wave reflections. The focus of this study was the NASA Rotor 67 blade with an extended intake. Moreover, a bump is incorporated on the shroud at different distances from the fan to reflect acoustic waves of varying phases. Utilizing the energy method, variations in the aerodynamic work density on blade surfaces were calculated under different phases of reflected acoustic waves. Analysis indicates that the spatial position of the shock wave undergoes periodic changes synchronized with the phase of acoustic reflection, marking the first instance of such an observation. This synchronization is identified as the primary factor causing variations in the aeroelastic stability of blades due to acoustic wave reflection, contributing to a deeper understanding of the mechanism behind acoustic flutter. The acoustic–vortex coupling at the blade tip leads to unpredictable variations in unsteady pressures on the blade suction surface, although its effect on blade aeroelastic stabilities is relatively limited compared to that of the shock wave.

A nano-structured conjugated polymer with multiple micro-/meso-pores was synthesized by post-crosslinking of an end-functionalized hyperbranched conjugated prepolymer. Firstly, an AB2 monomer 3-((3,5-dibromo-4-(octyloxy)phenyl)ethynyl)-6-ethynyl-9-octyl-9H-carbazole (PECz) was synthesized and polymerized by Sonogashira reaction to give the -Br end-functionalized hyperbranched conjugated prepolymer hb-PPECz. The photophysical and electrochemical properties of hb-PPECz were investigated. The λmax of absorption and emission of hb-PPECz in tetrahydrofuran (THF) solution was 313 and 483 nm, respectively. The optical energy bandgap, highest occupied molecular orbital (HOMO), and lowest unoccupied molecular orbital (LUMO) energy levels of hb-PPECz were 2.98, −5.81, and −2.83 eV, respectively. Then, the prepolymer hb-PPECz was post-crosslinked by Heck reaction with divinylbenzene to give the porous conjugated polymer c-PPECz. The effects of hb-PPECz concentration and added dispersant polyvinylpyrrolidone (PVP K-30) on the morphology and porosity of c-PPECz were investigated. The resulting c-PPECzs showed multiple porous structures mainly constructed by micropores and mesopores. Under a higher hb-PPECz concentration (4 wt/v%), a bulky gel product was obtained. Under lower hb-PPECz concentrations (0.6 wt/v%~2 wt/v%), the resulting c-PPECzs were mainly composed of nano-sized particles. Nearly spheric nanoparticles (200~300 nm) (c-PPECz-5) were obtained under the concentration of 1 wt/v% in the presence of PVP (10 wt% of hb-PPECz). The Brunauer–Emmett–Teller (BET) surface area, pore volume, average pore size, and percentage of pore size below 10 nm of c-PPECz-5 were 10.7781 m2·g−1, 0.0108 cm3·g−1, 4.0081 nm, and 94.47%, respectively.

Biological retention facilities are widely used in the construction of new urban infrastructure because of the increasingly serious problems of urban waterlogging and rainwater pollution. At present, a common method to resolve these problems is to improve the treatment performance of these facilities to improve the soil filling layer. How to evaluate the comprehensive benefits of the improved soil filling layer is a problem that cannot be ignored. In this paper, data from seven groups of soil improvement schemes were collected through laboratory tests, and an evaluation method based on AHP-CRITIC was proposed. Firstly, the evaluation indexes of soil improvement in biological retention facilities were determined, and their subjective and objective weights were determined by the AHP method and CRITIC method, respectively, and the comprehensive weights were further calculated. A comprehensive evaluation model was established by the TOPSISI method. Finally, the AHP-CRITIC evaluation model determined that 10% zeolite-amended soil had the best comprehensive evaluation effect, followed by 20% zeolite-amended soil and 10% gravel-amended soil. The results show that the evaluation model can comprehensively assess the benefits of soil improvement in bioretention facilities from the levels of infiltration, purification, and economy and can then select the optimal program for use in actual engineering practice.

Abstract Background Postoperative nausea and vomiting (PONV) is a common but troublesome complication in patients who undergo laparoscopic bariatric surgery (LBS). Whether sugammadex use is related to the persistent decrease in the occurrence of PONV during postoperative inpatient hospitalization, which is critical for the rehabilitation of patients after LBS, remains unknown. Methods The study was based on a randomized controlled trial conducted in an accredited bariatric centre. A total of 205 patients who underwent LBS were included in the analysis. Univariate analysis and multivariable logistic regression model were used to identify the significant variables related to PONV. Then propensity score matching and inverse probability of treatment weighting (IPTW) were employed to compare outcomes between the sugammadex and neostigmine groups. The primary outcome was the incidence of PONV within 48 h after LBS. The secondary endpoints included the severity of PONV, time to first flatus, need for rescue antiemetic therapy, and water intake. Results The incidence of PONV was 43.4% (89/205) within the first 48 h after LBS. In multivariable analysis, sugammadex use (OR 0.03, 95% CI 0.01–0.09, P

Abstract Background Urolithiasis with high prevalence and recurrence rate, has impacts on kidney injury in patients, becomes a socioeconomic and healthcare problem in worldwide. However, the biology of kidney with crystal formation and proximal tubular injury remains essentially unclear. The present study aims to evaluate the cell biology and immune-communications in urolithiasis mediated kidney injury, to provide new insights in the kidney stone treatment and prevention. Results We identified 3 distinct injured-proximal tubular cell types based on the differentially expression injury markers (Havcr1 and lcn2) and functional solute carriers (slc34a3, slc22a8, slc38a3 and slc7a13), and characterized 4 main immune cell types in kidney and one undefined cell population, where F13a1+/high/CD163+/high monocyte & macrophage and Sirpa/Fcgr1a/Fcgr2a+/high granulocyte were the most enriched. We performed intercellular crosstalk analysis based on the snRNA-seq data and explored the potential immunomodulation of calculi stone formation, and founded that the interaction between ligand Gas6 and its receptors (Gas6-Axl, Gas6-Mertk) was specifically observed in the injured-PT1 cells, but not injured-PT2 and -PT3 cells. The interaction of Ptn-Plxnb2 was only observed between the injured-PT3 cells and its receptor enriched cells. Conclusions Present study comprehensively characterized the gene expression profile in the calculi rat kidney at single nucleus level, identified novel marker genes for all cell types of rat kidney, and determined 3 distinct sub-population of injured-PT clusters, as well as intercellular communication between injured-PTs and immune cells. Our collection of data provides a reliable resource and reference for studies on renal cell biology and kidney disease.

Abstract Background Postoperative nausea and vomiting (PONV) is a common and distressing complication of laparoscopic bariatric surgery (LBS). Penehyclidine hydrochloride has been reported to be effective in preventing PONV. Considering the potential preventive effects of penehyclidine against PONV, we hypothesized that intravenous infusion of penehyclidine may alleviate PONV within the first 48 h in patients scheduled for LBS. Methods Patients who underwent LBS were randomly assigned (1:2) to receive saline (Control group, n = 113) or a single intravenous dose of penehyclidine 0.5 mg (PHC group, n = 221). The primary outcome was incidence of PONV within the first 48 h postoperatively. Secondary endpoints included severity of PONV, need for rescue antiemetic therapy, volume of water intake, and time to first flatus. Results PONV occurred in 159 (48%) patients within the first 48 h postoperatively, including 51% in the Control group and 46% in the PHC group. There was no significant difference in the incidence or severity of PONV between the two groups (P > 0.05). Within the first 24 h and 24–48 h, no significant difference was found in incidence or severity of PONV, postoperative nausea, postoperative vomiting, need for rescue antiemetic therapy, or volume of water intake (P > 0.05). Kaplan–Meier curves showed that penehyclidine was significantly associated with a prolonged time to first flatus (median onset time: 22 h vs. 21 h, P = 0.036). Conclusions Penehyclidine did not decrease incidence and severity of PONV in patients undergoing LBS. However, a single intravenous dose of penehyclidine (0.5 mg) was associated with a slightly prolonged time to first flatus. Trial registration Chinese Clinical Trial Registry (ChiCTR2100052418, http://www.chictr.org.cn/showprojen.aspx?proj=134893 , date of registration: 25/10/2021).

Indices recommendation is a long-standing topic in stock market investment. Predicting the future trends of indices and ranking them based on the prediction results is the main scheme for indices recommendation. How to improve the forecasting performance is the central issue of this study. Inspired by the widely used trend-following investing strategy in financial investment, the indices' future trends are related to not only the nearby transaction data but also the long-term historical data. This article proposes the MSGraph, which tries to improve the index ranking performance by modeling the correlations of short and long-term historical embeddings with the graph attention network. The original minute-level transaction data is first synthesized into a series of K-line sequences with varying time scales. Each K-line sequence is input into a long short-term memory network (LSTM) to get the sequence embedding. Then, the embeddings for all indices with the same scale are fed into a graph convolutional network to achieve index aggregation. All the aggregated embeddings for the same index are input into a graph attention network to fuse the scale interactions. Finally, a fully connected network produces the index return ratio for the next day, and the recommended indices are obtained through ranking. In total, 60 indices in the Chinese stock market are selected as experimental data. The mean reciprocal rank, precision, accuracy and investment return ratio are used as evaluation metrics. The comparison results show that our method achieves state-of-the-art results in all evaluation metrics, and the ablation study also demonstrates that the combination of multiple scale K-lines facilitates the indices recommendation.

Abstract Background To investigate the expression of miR-218-5p in atherosclerosis patients and its effect on ox-LDL induced THP-1-derived macrophage inflammatory response. Methods RT-qPCR detected the expression of serum miR-218-5p, and the diagnostic value of miR-218-5p was analyzed by ROC curve. Pearson correlation coefficient was used to evaluate the correlation between miR-218-5p and CIMT and CRP. THP-1 cells were treated with ox-LDL to construct foam cell model. The expression of miR-218-5p was regulated by in vitro transfection technique, and the effects of miR-218-5p on cell viability, apoptosis and inflammation were investigated. Luciferase reporter genes were used to analyze target genes of miR-218-5p in cell models. Results The expression of miR-218-5p in the atherosclerosis cohort was significantly reduced, and miR-218-5p showed a good ability to distinguish patients from healthy people. Correlation analysis showed that the level of miR-218-5p was negatively correlated with the levels of CIMT and CRP. Cytological studies showed that the expression of miR-218-5p in macrophages decreased after ox-LDL induction. ox-LDL treatment on macrophages resulted in decreased cell viability, increased cell apoptosis and production of inflammatory cytokines, which contributed to the exacerbation of plaque formation. However, the above situation was reversed after upregulation of miR-218-5p. Bioinformatics analysis showed that TLR4 may be the target gene of miR-218-5p, and this hypothesis was proved by luciferase reporter gene assay. Conclusions The expression of miR-218-5p is reduced in atherosclerosis, and it may regulate the inflammatory response of atherosclerotic foam cells by targeting TLR4, suggesting that miR-218-5p may be a promising target for clinical atherosclerosis therapy.

BackgroundIntraoperative hypotension (IOH) is a common complication occurring in surgical practice. This study aims to comprehensively review the collaboration and impact of countries, institutions, authors, journals, keywords, and critical papers on intraoperative hypotension from the perspective of bibliometric, and to evaluate the evolution of knowledge structure clustering and identify research hotspots and emerging topics.MethodsArticles and reviews related to IOH published from 2004 to 2022 were retrieved from the Web of Science Core Collection. Bibliometric analyses and visualization were conducted on Excel, CiteSpace, VOSviewer, and Bibliometrix (R-Tool of R-Studio).ResultsA total of 1,784 articles and reviews were included from 2004 to 2022. The number of articles on IOH gradually increased in the past few years, and peaked in 2021. These publications were chiefly from 1,938 institutions in 40 countries, led by America and China in publications. Sessler Daniel I published the most papers and enjoyed the highest number of citations. Analysis of the journals with the most outputs showed that most journals concentrated on perioperative medicine and clinical anesthesiology. Delirium, acute kidney injury and vasoconstrictor agents are the current and developing research hotspots. The keywords “Acute kidney injury”, “postoperative complication”, “machine learning”, “risk factors” and “hemodynamic instability” may also become new trends and focuses of the near future research.ConclusionThis study uses bibliometrics and visualization methods to comprehensively review the research on intraoperative hypotension, which is helpful for scholars to better understand the dynamic evolution of IOH and provide directions for future research.

Neutrophil extracellular traps (NETs) are composed of chromatin filaments coated with granular and cytosolic proteins, which contribute to the pathogenesis and progression of immune-related diseases. NETs are frequently observed in gouty arthritis, but the related mechanisms remain poorly understood. The aim of our study was to systematically elucidate the molecular mechanisms of self-remitting effects in gouty arthritis, and the causative relationship between neutrophil autophagy and NETs. The air pouch and paw edema model were used to simulate gouty arthritis in mice. Neutrophil infiltration and the formation of NETs were found in gouty arthritis. Interestingly, monosodium urate (MSU) crystals could induce the formation of NETs, degrade inflammatory factors, and alleviate the inflammatory response in gouty arthritis. In addition, MSU crystals resulted in profound molecular alterations in neutrophils using RNA-seq analysis, including autophagy activation. MSU crystals could activate neutrophil autophagy in vitro, and autophagy activators and inhibitors could regulate the formation of NETs. Furthermore, we explored the mechanism of autophagy-induced NETs. Autophagy related protein 7 (ATG7) produced by neutrophils stimulated with MSU crystals worked synergistically with p53 to enter the nucleus, promoting peptidyl arginine deiminase 4 (PAD4) expression, and inducing the formation of NETs. Finally, we substantiated that neutrophil autophagy regulates the severity of gouty arthritis via the formation of NETs in PAD4 -/- mice. Our results indicated that the autophagy of neutrophils regulates the formation of NETs and degrades inflammatory factors. Regulating autophagy and interfering with the formation of NETs represents a potential therapeutic approach against gouty arthritis during clinical practice.

Archives management plays an important role in the current information age. Solving the problem of identifying and classifying archives is essential for promoting the development of archives management. The Least Squares Support Vector Machine (LS-SVM) is obtained by introducing the least squares fitting method into SVM, which is good at solving nonlinear classification. A new wavelet function is used to improve the classifier. At the same time, the cross-validation method is used to optimize the kernel parameters. Finally, the fuzzy theory and LS-SVM are combined to obtain Fuzzy Least Squares Support Vector Machines (FLS-SVM). This FLS-SVM classifier can use the distance between the data points and the classification hyperplane to classify the data in the non-separable region. The performance of FLS-SVM is verified by simulation experiments. The experimental results show that the classification accuracy of FLS-SVM classifier in archive data sets is 98.7%, and the loss rate is only 0.26%. When the wavelet function is used as the kernel function, the average accuracy of the classifier reaches 98.38%. Experiments show that the proposed method has good classification performance. It verifies the feasibility and effectiveness of the least squares fitting method in file management identification and classification.

The lack of social activities in the elderly for physical reasons can make them feel lonely and prone to depression. With the spread of COVID-19, it is difficult for the elderly to conduct the few social activities stably, causing the elderly to be more lonely. The metaverse is a virtual world that mirrors reality. It allows the elderly to get rid of the constraints of reality and perform social activities stably and continuously, providing new ideas for alleviating the loneliness of the elderly. Through the analysis of the needs of the elderly, a virtual social center framework for the elderly was proposed in this study. Besides, a prototype system was designed according to the framework. The elderly can socialize in virtual reality with metaverse-related technologies and human-computer interaction tools. Additionally, a test was jointly conducted with the chief physician of the geriatric rehabilitation department of a tertiary hospital. The results demonstrated that the mental state of the elderly who had used the virtual social center was significantly better than that of the elderly who had not used it. Thus, virtual social centers alleviated loneliness and depression in older adults. Virtual social centers can help the elderly relieve loneliness and depression when the global epidemic is normalizing and the population is aging. Hence, they have promotion value

Convolutional Neural Networks (CNNs) have achieved remarkable results in the computer vision field. However, the newly proposed network architecture has deeper network layers and more parameters, which is more prone to overfitting, resulting in reduced recognition accuracy of the CNNs. To improve the recognition accuracy of the model of image recognition used in CNNs and overcome the problem of overfitting, this paper proposes an improved data augmentation approach based on mosaic algorithm, named Dynamic Mosaic algorithm, to solve the problem of the information waste caused by the gray background in mosaic images. This algorithm improves the original mosaic algorithm by adding a dynamic adjustment step that reduces the proportion of gray background in the mosaic image by dynamically increasing the number of spliced images. Moreover, to relieve the problem of network overfitting, also a Multi-Type Data Augmentation (MTDA) strategy, based on the Dynamic Mosaic algorithm, is introduced. The strategy divides the training samples into four parts, and each part uses different data augmentation operations to improve the information variance between the training samples, thereby preventing the network from overfitting. To evaluate the effectiveness of the Dynamic Mosaic algorithm and the MTDA strategy, we conducted a series of experiments on the Pascal VOC dataset and compared it with other state-of-the-art algorithms. The experimental results show that the Dynamic Mosaic algorithm and MTDA strategy can effectively improve the recognition accuracy of the model, and the recognition accuracy is better than other advanced algorithms.

Objective: To access the level of knowledge, perceptions, and practice towards adverse events following immunization (AEFI) surveillance among vaccination workers in Zhejiang province, China. Methods: This was a cross-sectional survey involving 768 vaccination workers. Data were collected using self-administered questionnaires and analyzed by using SAS 9.3 software. Knowledge, perceptions, and practice on AEFI surveillance were summarized using frequency tables. The mean±SD value was used as the cut-off for defining good (values⩾mean) and poor (values