Association between 25 hydroxyvitamin D and serum uric acid level in the Chinese general population: a cross-sectional study.

BACKGROUD: The relationship between serum uric acid (SUA) and 25-hydroxyvitamin D (25(OH)D) has been variably characterized in existing literature, with inconsistent results regarding its nature and implications in the Chinese population. This study aims to clarify this association, considering the potential impact of vitamin D levels on SUA. METHODS: This cross-sectional study involved 7,086 individuals from the Second Affiliated Hospital of Zhejiang University School of Medicine, screened throughout 2020. We collected data on 25(OH)D, SUA, and other metabolic markers. Logistic regression models adjusted for confounding factors were utilized to analyze the relationships. RESULTS: Our findings illustrate a statistically significant inverted U-shaped relationship between 25(OH)D and SUA. The identified threshold effect at 28.82 ng/ml is pivotal; with 25(OH)D levels below this point associated with an increased risk of hyperuricemia (odds ratio: 1.0146, p = 0.0148), and levels above it offering protective benefits (odds ratio: 0.9616, p = 0.0164). CONCLUSIONS: Our findings confirm a nonlinear, inverted U-shaped correlation between 25(OH)D and SUA, emphasizing the importance of maintaining vitamin D levels within a specific range to effectively manage hyperuricemia. These results support the implementation of personalized vitamin D supplementation strategies to optimize metabolic health outcomes, highlighting the complex interplay between vitamin D status and uric acid levels.

Human-like acceleration and deceleration control of a robot astronaut floating in a space station.

The acceleration and deceleration (AD) motions are the basic motion modes of robot astronauts moving in a space station. Controlling the locomotion of the robot astronaut is very challenging due to the strong nonlinearity of its complex multi-body dynamics in a gravity-free environment. However, after training, humans can move well in space stations by pushing the bulkhead, and the motion mechanism of humans is a good reference for robot astronauts. The contribution of this study is modeling the human AD motion in a microgravity environment and proposing a human-like control method for robot astronauts moving in space stations. Specifically, the movement and contact force data of the human body during AD motion were collected on an air-floating platform. Through human AD modeling analysis, the mechanism of human motion is discovered, and semi-sinusoidal primitives of contact forces are proposed for AD motion. Then, a dynamic guidance model of human AD motion is built to complete motion planning under contact constraints, which is used as the expected model for the AD control of robot astronauts. Benefiting from the force primitives, accurate and safe planning of human-like AD motion can be completed. The characteristics and mechanism of human AD motion have been analyzed from the perspective of optimization. Lastly, based on the proposed dynamic guidance model, the AD motion policy is mapped to the robot astronaut system via a system control method based on the equivalent mapping of dynamic responses (force, velocity and pose). Through comparative analysis with real human motion data and simulation results under different conditions, the proposed AD control method can achieve human-like motion efficiently and stably. Even when confronted with errors in the robot's contact velocities and inertia parameters, the method can significantly reduce the motion errors while ensuring stability.

Combined analysis of bulk RNA and single-cell RNA sequencing to identify pyroptosis-related markers and the role of dendritic cells in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by dyspnea caused by airflow limitation. Further development may lead to decreased lung function and other lung diseases. Pyroptosis is a type of programmed cell death that involves multiple pathways. For example, the pathway induced by the NLR family pyrin domain containing 3 (NLRP3) inflammasome is closely associated with COPD exacerbation. Therefore, in this study, various machine learning algorithms were applied to screen for diagnostically relevant pyroptosis-related genes from the GEO dataset, and the results were verified using external datasets. The results showed that deep neural networks and logistic regression algorithms had the highest AUC of 0.91 and 0.74 in the internal and external test sets, respectively. Here, we explored the immune landscape of COPD using diagnosis-related genes. We found that the infiltrating abundance of dendritic cells significantly differed between the COPD and control groups. Finally, the communication patterns of each cell type were explored based on scRNA-seq data. The critical role of significant pathways involved in communication between DCS and other cell populations in the occurrence and progression of COPD was identified.

Network pharmacology mechanisms and experimental verification of licorice in the treatment of ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is widely used in the treatment of ulcerative colitis (UC) and has good antioxidant and anti-inflammatory effects, but its specific active ingredients and mechanisms of action are still unknown. THE PURPOSE OF THE STUDY: To elucidate the specific molecular mechanisms of licorice in the treatment of UC and to experimentally verify its activity. METHODS: Through network pharmacology, the active ingredients of licorice and the molecular targets of UC were identified. A traditional Chinese medicine (TCM)-components-target-disease network diagram was established, and the binding energies of the active ingredient and targets of licorice were verified by molecular docking. A BALB/c mice model of UC was established by treatment with 3% dextran sulfate sodium (DSS). The effect of licorice on colon tissue injury was histologically assessed. The expression of IL-6 and IL-17 in colon tissue was detected by immunohistochemistry (IHC). Transmission electron microscopy (TEM) was used to observe morphological changes in mitochondria in the colon. Caco2 cells were treated with lipopolysaccharide (LPS) for 24 h to establish the cell inflammatory damage model, and cells were exposed to different concentrations of drug-containing serum of Licorice (DCSL) for 24 h. In cells treated with the drug, the contents of oxidation markers were measured and ELISA was used to determine the levels of inflammatory factors in the cells. TEM was used to observe morphological changes in mitochondria. ZO-1 and occludin were detected by Western blotting. DCSL effects on autophagy were evaluated by treating cells with DCSL and autophagy inhibitor for 24 h after LPS injection. Small interfering ribonucleic acid (si-RNA) was used to silence Nrf2 gene expression in Caco2 cells to observe the effects of DCSL on autophagy through the Nrf2/PINK1 pathway. Nrf2, PINK1, HO-1, Parkin, P62, and LC3 were detected by Western blotting. RESULTS: Ninety-one active ingredients and 339 action targets and 792 UC disease targets were identified, 99 of which were overlapping targets. Molecular docking was used to analyze the binding energies of liquiritin, liquiritigenin, glycyrrhizic acid, and glycyrrhetinic acid to the targets, with glycyrrhetinic acid having the strongest binding energy. In the UC mouse model, licorice improved colon histopathological changes, reduced levels of IL-6 and IL-17 and repaired mitochondrial damage. In the LPS-induced inflammation model of Caco2 cells, DCSL decreased MDA, IL-1ß, Il-6, and TNF-α levels and increased those of Superoxide Dismutase (SOD), glutathione peroxidase (GSH-PX), and IL-10, and improved the morphological changes of mitochondria. Increased expression of Nrf2, PINK1, Parkin, HO-1, ZO-1, occludin, P62, and LC3 promoted autophagy and reduced inflammation levels. CONCLUSION: Licorice improves UC, which may be related to the activation of the Nrf2/PINK1 signaling pathway that regulates autophagy.

Characteristics of sodium and water retention in rats with nephrotic syndrome induced by puromycin aminonucleoside.

INTRODUCTION: Nephrotic syndrome (NS) is characterized by renal sodium and water retention. The mechanisms are not fully elucidated. METHODS: The NS rat model was established by single intraperitoneal injection of 100 mg/kg puromycin aminonucleoside (PAN). The plasma electrolyte level and urinary sodium excretion were monitored dynamically. The changes of some sodium transporters, including epithelial Na+ channel (ENaC), Na+/H+ exchanger 3 (NHE3), Na+-K+-2Cl- cotransporter 2 (NKCC2) and Na+-Cl- cotransporter (NCC) in renal cortex at different time points and the level of peripheral circulation factors were detected. RESULTS: The urinary sodium excretion of the model group increased significantly on the first day, then decreased compared with the control group, and there was no significant difference between the model group and the control group on the 12th day. The changes of peripheral circulation factors were not obvious. Some sodium transporters in renal cortex increased in varying degrees, while NKCC2 decreased significantly compared with the control group. CONCLUSIONS: The occurrence of NS edema may not be related to the angiotensin system. The decrease of urinary sodium excretion is independent of the development of albuminuria. During the 18 days of observation, it can be divided into three stages: sodium retention, sodium compensation, and simple water retention. The mechanism is related to the increased expression of α-ENaC, γ-ENaC, NHE3 and NCC in a certain period of time, the compensatory decrease of NKCC2 expression and the continuous increase of aquaporin 2 (AQP2) expression.

Licorice protects against ulcerative colitis via the Nrf2/PINK1-mediated mitochondrial autophagy.

PURPOSE: Study of the effects and mechanisms of licorice in the treatment of ulcerative colitis (UC) from the perspective of mitochondrial autophagy. METHODS: BALB/C mice were induced with 3% dextran sodium sulfate to build an animal model of UC. After 7 days of modeling, different doses of licorice were administered for 7 days. Hematoxylin and eosin staining is used to detect pathological changes in the colon. Mitochondrial membrane potentials and reactive oxygen species (ROS) contents were detected by flow cytometry, and autophagy of mitochondria was observed by transmission electron microscopy. Determination of inflammatory cytokines by enzyme-linked immunosorbent assay. The oxidizing factors are detected by the kits. Western blot analysis was used to detect expressions for nuclear factor called erythropoietin (Nrf2), pten-induced protein kinase 1 (PINK1), Parkin, HO-1, P62, and LC3. RESULTS: Licorice improved the pathological condition of UC mice, increasing the mitochondrial membrane potential and decreasing the ROS content. Promotes the emergence of autophagosomes and autophagosomes. The contents of interleukin (IL)-1ß, IL-6, IL-17, and tumor necrosis factor-alpha were downregulated, the contents of superoxide dismutase and glutathione peroxidase were upregulated and the contents of malondialdehyde were downregulated. In addition, licorice promotes the expression of Nrf2, PINK1, Parkin, HO-1, P62, and LC3. CONCLUSION: Licorice was shown to reduce levels of inflammatory factors and oxidative stress in mice with UC, possibly by promoting mitochondrial autophagy through the activation of the Nrf2/PINK1 pathway.

Sini San ameliorates CCl4-induced liver fibrosis in mice by inhibiting AKT-mediated hepatocyte apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sini San (SNS) is recorded in Zhang Zhongjing's "Treatise on Typhoids" and is used in the treatment of non-alcoholic fatty liver disease, hepatitis, and other liver diseases, with good efficacy in liver fibrosis. However, its anti-liver fibrosis mechanism remains unclear. AIM OF THE STUDY: This study aimed to evaluate the ameliorative effect of SNS on carbon tetrachloride (CCl4)-induced liver fibrosis in mice and the underlying mechanisms. MATERIALS AND METHODS: The active ingredients in the water extract of SNS were determined using high-performance liquid chromatography (HPLC). CCl4-induced liver fibrosis mice were subsequently treated with different doses of SNS for 3 weeks, and AST, ALT, and T-BIL were detected in the serum. The pathological characteristics of the liver were observed using hematoxylin and eosin (H&E) and Masson's staining. Hepatocyte apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The proteins expression of PI3K, p-PI3K, AKT, p-AKT, FXR, caspase-8, Bax, and Bcl-2 was analyzed using western blotting and immunofluorescence. FXR mRNA expression was measured using quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR). Using network pharmacology and bioinformatics to search for active ingredients that regulate PI3K/AKT signaling in the SNS. The material basis for regulating PI3K/AKT signaling in SNS was searched using network pharmacology and bioinformatics. Based on the network pharmacology results, isorhamnetin or SNS-containing serum was added to HepG2 cells stimulated with TNF-α. The Cell Counting Kit (CCK)-8 assay was used to analyze cell viability and apoptosis of HepG2 cells was detected using flow cytometry. RESULTS: SNS reduced serum levels of AST, ALT and T-BIL, down-regulated caspase-8 protein expression and the ratio of Bcl-2/Bax protein expression, and improved apoptosis in liver fibrosis mice. In addition, SNS downregulated the ratio of p-PI3K/PI3K and p-AKT/AKT protein expression and increased FXR expression. Network pharmacology studies showed that quercetin, kaempferol and isorhamnetin in SNS can bind to AKT. In vitro experiments showed that isorhamnetin inhibited HepG2 cell apoptosis, upregulated FXR expression and suppressed AKT activity, whereas AKT inhibitors blocked the effects of isorhamnetin. The effect of the SNS-containing serum was similar to that of isorhamnetin. CONCLUSION: SNS ameliorated the progression of fibrosis and improved hepatocyte apoptosis in liver fibrosis mice. The anti-apoptotic mechanism was related to the inhibition of AKT-mediated down-regulation of FXR expression by its active ingredient, isorhamnetin.

Development and Validation of an Ultrasound-Based Radiomics Nomogram for Identifying HER2 Status in Patients with Breast Carcinoma.

(1) Objective: To evaluate the performance of ultrasound-based radiomics in the preoperative prediction of human epidermal growth factor receptor 2-positive (HER2+) and HER2- breast carcinoma. (2) Methods: Ultrasound images from 309 patients (86 HER2+ cases and 223 HER2- cases) were retrospectively analyzed, of which 216 patients belonged to the training set and 93 patients assigned to the time-independent validation set. The region of interest of the tumors was delineated, and the radiomics features were extracted. Radiomics features underwent dimensionality reduction analyses using the intra-class correlation coefficient (ICC), Mann-Whitney U test, and the least absolute shrinkage and selection operator (LASSO) algorithm. The radiomics score (Rad-score) for each patient was calculated through a linear combination of the nonzero coefficient features. The support vector machine (SVM), K nearest neighbors (KNN), logistic regression (LR), decision tree (DT), random forest (RF), naive Bayes (NB) and XGBoost (XGB) machine learning classifiers were trained to establish prediction models based on the Rad-score. A clinical model based on significant clinical features was also established. In addition, the logistic regression method was used to integrate Rad-score and clinical features to generate the nomogram model. The leave-one-out cross validation (LOOCV) method was used to validate the reliability and stability of the model. (3) Results: Among the seven classifier models, the LR achieved the best performance in the validation set, with an area under the receiver operating characteristic curve (AUC) of 0.786, and was obtained as the Rad-score model, while the RF performed the worst. Tumor size showed a statistical difference between the HER2+ and HER2- groups (p = 0.028). The nomogram model had a slightly higher AUC than the Rad-score model (AUC, 0.788 vs. 0.786), but no statistical difference (Delong test, p = 0.919). The LOOCV method yielded a high median AUC of 0.790 in the validation set. (4) Conclusion: The Rad-score model performs best among the seven classifiers. The nomogram model based on Rad-score and tumor size has slightly better predictive performance than the Rad-score model, and it has the potential to be utilized as a routine modality for preoperatively determining HER2 status in BC patients non-invasively.

Development and validation of an ultrasound-based radiomics nomogram for predicting the luminal from non-luminal type in patients with breast carcinoma.

Introduction: The molecular subtype plays a significant role in breast carcinoma (BC), which is the main indicator to guide treatment and is closely associated with prognosis. The aim of this study was to investigate the feasibility and efficacy of an ultrasound-based radiomics nomogram in preoperatively discriminating the luminal from non-luminal type in patients with BC. Methods: A total of 264 BC patients who underwent routine ultrasound examination were enrolled in this study, of which 184 patients belonged to the training set and 80 patients to the test set. Breast tumors were delineated manually on the ultrasound images and then radiomics features were extracted. In the training set, the T test and least absolute shrinkage and selection operator (LASSO) were used for selecting features, and the radiomics score (Rad-score) for each patient was calculated. Based on the clinical risk features, Rad-score, and combined clinical risk features and Rad-score, three models were established, respectively. The performances of the models were validated with receiver operator characteristic (ROC) curve and decision curve analysis. Results: In all, 788 radiomics features per case were obtained from the ultrasound images. Through radiomics feature selection, 11 features were selected to constitute the Rad-score. The area under the ROC curve (AUC) of the Rad-score for predicting the luminal type was 0.828 in the training set and 0.786 in the test set. The nomogram comprising the Rad-score and US-reported tumor size showed AUCs of the training and test sets were 0.832 and 0.767, respectively, which were significantly higher than the AUCs of the clinical model in the training and test sets (0.691 and 0.526, respectively). However, there was no significant difference in predictive performance between the Rad-score and nomogram. Conclusion: Both the Rad-score and nomogram can be applied as useful, noninvasive tools for preoperatively discriminating the luminal from non-luminal type in patients with BC. Furthermore, this study might provide a novel technique to evaluate molecular subtypes of BC.

Traditional Chinese Medicine in the Treatment of Chronic Kidney Diseases: Theories, Applications, and Mechanisms.

Chronic kidney disease (CKD) is a common and progressive disease that has become a major public health problem on a global scale. Renal fibrosis is a common feature in the pathogenesis of CKD, which is mainly related to the excessive accumulation and deposition of extracellular matrix caused by various inflammatory factors. No ideal treatment has yet been established. In recent years, based on the traditional Chinese medicine (TCM) theory of CKD and its molecular mechanism, clinical evidence or experimental studies have confirmed that a variety of Chinese materia medica (CMM) and their effective components can delay the progress of CKD. TCM believes that the pathogenesis of CKD is the deficiency in the root and excess in the branch, and the deficiency and excess are always accompanied by the disease. The strategies of TCM in treating CKD are mainly based on invigorating Qi, tonifying the kidneys, promoting blood circulation, removing stasis, eliminating heat and dampness, removing turbidity, and eliminating edema, and these effects are multitargeted and multifunctional. This review attempts to summarize the theories and treatment strategies of TCM in the treatment of CKD and presents the efficacy and mechanisms of several CMMs supported by clinical evidence or experimental studies. In addition, the relationship between the macroscopic of TCM and the microscopic of modern medicine and the problems faced in further research were also discussed.

Activation of TRPC6 by Angâ ¡ Induces Podocyte Injury and Participates in Proteinuria of Nephrotic Syndrome.

Background: Nephrotic syndrome (NS) is a common glomerular disease, and podocyte injury is the character of primary NS, usually caused by minimal change disease and membranous nephropathy. Podocytopathy is primarily associated with glomerular proteinuria. Losartan, an angiotensin receptor blocker (ARB), is commonly used in the treatment of NS, and the AngiotensinⅡ (AngⅡ)-transient receptor potential ion channel 6 (TRPC6) axis has been reported to act on podocytes to regulate proteinuria in NS. Therefore, the purpose of this study was to explore the relationship in between AngⅡ-TRPC6, podocyte injury, and proteinuria based on the adriamycin (ADR) NS rat model. Method: All male rats were divided into three groups: control group, model group, and ARB group. The rats in the model group were induced by ADR, and the rats in the ARB group received losartan after induction of renal injury for 4 weeks. The changes in parameters related to renal dysfunction, and glomerular and podocyte structural damage, such as AngⅡ, AngⅡ type I receptor (AT1R), TRPC6, CaN, Caspase-3, Nephrin, and Podocin, were analyzed. Furthermore, the kidneys were isolated for study via transmission electron microscopy (TEM), immunohistochemistry, and western blot (WB) after the rats were sacrificed. In vitro, immortalized mouse MPC5 podocytes were used to investigate the regulatory effect of flufenamic acid (Flu) and SAR7334 (SAR) on the AngⅡ-TRPC6 signaling axis. Flow cytometry and WB were conducted to determine the relationship between podocyte injury and AngⅡ-TRPC6. Results: In vivo results showed that NS rats developed massive albuminuria and abnormal renal function, accompanied by abnormally increased levels of AngⅡ, TRPC6, AT1R, and CaN and a decreased expression of actin molecules in podocytes, extensive fusion of foot processes (FP), loss of glomerular structural integrity, collapse of podocyte structure, and skeletal reorganization. In vitro experiments indicated that both AngⅡ and Flu (the specific agonist of TRPC6) stimulated the expressions of TRPC6, AT1R, and Caspase-3 in podocytes. The AngⅡ receptor-blocker losartan and TRPC6-specific inhibitor SAR blocked the overexpression of the aforementioned proteins. In addition, SAR also attenuated the degradation of podocyte structural proteins and inhibited the fluorescence intensity of intracellular calcium (Ca2+) and cell apoptosis. Conclusion: The involvement of AngⅡ in the occurrence of NS proteinuria may be related to podocyte injury induced by activated TRPC6.

Glycyrrhiza uralensis Fisch. alleviates dextran sulfate sodium-induced colitis in mice through inhibiting of NF-κB signaling pathways and modulating intestinal microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is widely used in traditional Chinese Medicine (TCM) for compound compatibility, which could reduce toxicity and increase efficacy of certain herbal medicine, and its active components prominently effects of inhibit of inflammation and regulate of immunity. AIM OF THE STUDY: The study probed into the mechanism of the anti-inflammatory and immunomodulatory effects of licorice based on the domination of the T helper type 17/regulatory T cells (Th17/Treg) differentiation balance and the composition and structure of the intestinal flora through the nuclear factor kappa B (NF-κB) signaling pathway. MATERIALS AND METHODS: BALB/c mice were inoculated with dextran sulfate sodium (DSS) to establish animal models of ulcerative colitis (UC). For the pharmacodynamic study, UC mice were observed for the anti-inflammatory effect of licorice water extraction (LWE) in vivo, including clinical observation and measurement of colon length. Hematoxylin-eosin (HE) staining was used to evaluate pathological conditions. Immunohistochemistry (IHC) and transmission electron microscopy (TEM) were performed to observe the intestinal barrier of the colons. Inflammatory cytokine levels were measured using with enzyme-linked immunosorbent assay (ELISA) kits. The proportions of T helper (Th) cells in the colons was assessed using flow cytometry. Gut microbiota diversity was detected using 16S ribosomal (r)DNA sequencing. In addition, Western blot (WB) assays were used to verify ROR-γt, Foxp3, TLR4, MyD88 and NF-κB expression according to a standard protocol. RESULTS: LWE exerted a pharmacological anti-inflammatory effect by attenuating inflammation in the colonic tissues through affecting the protein expression of TLR4/MyD88/NF-κB, and increasing the expression of tight junction (TJ) protein in the colons, improving the integrity of the intestinal mucosal barrier in vivo. Moreover, LWE reversed the imbalance in Th17/Treg cells differentiation and influenced the protein expression of ROR-γt and Foxp3 in UC mouse colons. In particular, LWE significantly affected the diversity of the gut microbiota in UC mice, ameliorated the composition of dominant species, and significantly increased the type and quantity of probiotics. CONCLUSION: Licorice tends to reduce inflammation and enhance the protective action of the intestinal mucosal barrier via the TLR4/MyD88/NF-κB signal transduction pathway and alter the imbalance of Th-cell differentiation. Notably, licorice may affect the diversity of intestinal microbiota and the content of beneficial bacteria in the colon, which is a potential mechanism for understanding anti-inflammatory and immunomodulatory effects in UC mice in vivo.

Screening bioactive compounds from Danggui-shaoyao-san for treating sodium retention in nephrotic syndrome using bio-affinity ultrafiltration.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui-shaoyao-san (DSS), a representative formula of Traditional Chinese Medicine (TCM) for promoting blood circulation and diuresis (Huo-Xue-Li-Shui) therapy, has been used to clinically nephrotic syndrome (NS) and relieve nephrotic edema. AIM OF THE STUDY: To explore the effects and mechanisms of DSS in improving sodium retention and to identify the bioactive compounds from DSS. MATERIALS AND METHODS: DSS prescriptions were disassembled into Yangxue-Huoxue (YXHX) and Jianpi-Lishui (JPLS). A nephrotic rat model was induced with puromycin aminonucleoside (PAN), and the effects on urinary sodium excretion, urinary plasmin(gen) content, and plasmin activity of DSS, YXHX, and JPLS extracts were assessed. The inhibitory effects on urokinase-type plasminogen activator (uPA) and plasmin activity of extracts were evaluated in vitro. Bio-affinity ultrafiltration and high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (BAU-UPLC-Q/TOF-MS) were used to rapidly screen and qualitatively analyze the uPA/plasmin affinity compounds from DSS extract. Additionally, uPA/plasmin inhibition assays and molecular docking were used to verify the activity and affinity mechanisms of the potential bioactive compounds. RESULTS: In vivo, DSS, YXHX, and JPLS prevented sodium retention in nephrotic rats. DSS and YXHX treatment decreased urinary plasmin activity but did not alter urinary plasmin(ogen) concentration, and their extracts showed strong uPA and plasmin inhibitory activity in vitro. These results suggested that uPA and plasmin are direct targets of DSS and YXHX in intervening NS sodium retention. Using BAU-UPLC-Q/TOF-MS, gallic acids, methyl gallate, albiflorin, and 1,2,3,4,6-O-pentagalloylglucose (PGG) were screened as uPA or plasmin affinity compounds. Among them, PGG was found to be a uPA and plasmin dual inhibitor, with an IC50 of 6.861 µM against uPA and an IC50 of 149.0 µM against plasmin. The molecular docking results of PGG with uPA and plasmin were consistent with the verification results. CONCLUSION: Intervening in sodium retention by inhibiting uPA-mediated plasmin generation and plasmin activity in the kidneys could be possible mechanisms for DSS, as indicated by the results in PAN-induced nephrotic rats. We conclude that PGG is a potential bioactive compound responsible for the effect of DSS on natriuresis.

Diagnostic value of endobronchial ultrasound elastography for differentiating benign and malignant hilar and mediastinal lymph nodes: a systematic review and meta-analysis.

AIMS: In the present study, a meta-analysis was performed to evaluate the diagnostic value of endobronchial ultrasound (EBUS) elastography for differentiating benign and malignant hilar and mediastinal lymph nodes (LNs). MATERIAL AND METHODS: A comprehensive literature search was carried out through PubMed, Embase, and Cochrane Library. Two authors screened the papers and extracted the data independently and any discrepancies were resolved by discussion. The methodolog-ical quality of each included study was assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the curve were calculated to evaluate the value of EBUS elastography for hilar and mediastinal LNs. RESULTS: Seventeen studies with the number of 2307 LNs were included. There was significant heterogeneity across the included studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio for the diagnosis of hilar and mediastinal LNs by EBUS elastography were 0.90 (95% confidence interval [CI], 0.84-0.94), 0.78 (95% CI, 0.74-0.81), 4.1 (95% CI, 3.4-4.9), 0.12 (95% CI, 0.07-0.21) and 33 (95% CI, 17-64), respectively. Furthermore, area under the curve was calculated to be 0.86 (95% CI, 0.82-0.88). CONCLUSION: EBUS elastography is a valuable technology in the differentiation of benign and malignant hilar and mediastinal LNs and could provide supplementary diagnostic information during endobronchial ultrasound-guided transbronchial needle aspiration. The combination of EBUS elastography and B-mode EBUS could improve the diagnostic accuracy for hilar and mediastinal LNs.

An appendiceal mucinous neoplasm should be considered in the differential diagnosis of giant abdominopelvic tumor.

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The diagnostic accuracy of ultrasound in the detection of foot and ankle fractures: a systematic review and meta-analysis.

AIMS: Foot and ankle injuries are a common presenting complaint in the emergency department. The diagnosis of foot and ankle fractures is conventionally accomplished through X-rays. Whether ultrasound (US) can be considered as a primary scanning modality is still a controversial issue; therefore, we did a meta-analysis to synthesize the diagnostic performance ofultrasound for foot and ankle fractures. MATERIAL AND METHODS: A comprehensive search was carried out to identify studies in which patients with clinically suspected foot and ankle fractures were assessed by US. Two investigators independently screened the literature and extracted the data. Any discrepancies were resolved via discussion. Study quality was assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 tool, and pooled sensitivity and specificity of various US findings were determined. RESULTS: Ten studies with a total of 1065 patients were included. There was significant heterogeneity across the included studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for the diagnosis of foot and ankle fractures by US were 0.96 (95% confidence interval [CI], 0.90-0.99), 0.94 (95% CI, 0.88-0.97), 15.0 (95% CI, 7.9-28.6), 0.04 (95% CI, 0.02-0.11), and 367 (95% CI, 101-1338), respectively. Furthermore, the summary receiver operating characteristic area under the curve was calculated to be 0.99. CONCLUSIONS: Ultrasound has an excellent diagnostic performance for foot and ankle fractures and should be considered as a primary and radiation-free scanning modality in the diagnosis of foot and ankle fractures.

Single-cell RNA-Seq revealed profound immune alteration in the peripheral blood of patients with bacterial infection.

OBJECTIVES: Bacterial infection remains one of the greatest threats to human health. However, how human hosts respond to bacterial infection has not been thoroughly understood. Better understanding of this response will improve human health. METHODS: Here, we conducted an investigation on host response to bacterial infection using unperturbed clinical samples and single-cell RNA-Seq (scRNA-Seq) technology. To evaluate immune alteration upon bacterial infection in scRNA-Seq data of peripheral blood mononuclear cells (PBMCs), we developed a barcode analytical framework named PBMCode. RESULTS: Using this PBMCode framework, we revealed profound immune alteration in peripheral blood under bacterial infection, including the emergence of natural killer T (NKT) cell cluster, reduction of B cell population, and considerable changes in T cells and monocytes. In addition, we also observed a large quantity of low-density neutrophils. CONCLUSIONS: Our investigation on single cells provided unprecedented details in the alteration of both cell population and cell state under bacterial infection. These findings may be relevant to clinical decisions. The complexity of host response to bacterial infection revealed by scRNA-Seq deserves further attention in future studies.

Can acoustic radiation force impulse imaging (ARFI) accurately diagnose renal masses?: A protocol of systematic review and meta-analysis.

BACKGROUND: Renal masses are increasingly being discovered because of the wide accessibility of modern high resolution imaging procedures. Previous clinical studies have reported that acoustic radiation force impulse imaging (ARFI) is used for diagnosis of renal masses. However, no study has investigated this topic systematically. Therefore, this study will evaluate the diagnostic value of ARFI for the diagnosis of renal masses. METHODS: A systematic search using the databases of Cochrane Library, EMBASE, Pubmed, WANGFANG, and China National Knowledge Infrastructure will be performed to identify studies in which patients with renal masses are assessed by ARFI. Two investigators will independently screen the literature and extract the data. Any discrepancies will be resolved via discussion with the senior author. Study quality will be assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 tool, and pooled sensitivity and specificity of various ARFI findings for the diagnosis of renal masses will be determined. Summary receiver operating characteristic curve will be used to assess the overall performance of ARFI. RESULTS: This study will evaluate the diagnostic value of ARFI for the diagnosis of renal masses through sensitivity, specificity, positive and negative likelihood ratio, and diagnostic odds ratio. CONCLUSION: This study will summarize the most recent evidence that focusing on the diagnosis of ARFI for renal masses. STUDY REGISTRATION: INPLASY202060105.

Diagnostic accuracy of contrast-enhanced ultrasound in the detection of small renal masses: A protocol of systematic review and meta-analysis.

BACKGROUND: The small renal masses (SRMs) were defined that the diameter of renal masses measured by enhanced image was ≤4 cm. The diagnostic accuracy of contrast-enhanced ultrasound (CEUS) for SRMs is apparently variable among previous studies. Hence, this study will evaluate the diagnostic accuracy of CEUS in the identification of benign and malignant SRMs. METHODS: A comprehensive search using the databases of Cochrane Library, Embase, PubMed, WANGFANG, and China National Knowledge Infrastructure will be carried out to identify studies in which patients with SRMs are assessed by CEUS. Two investigators will independently screen the literature and extract the data. Any discrepancies will be resolved via discussion with the senior author. Study quality will be assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 tool, and pooled sensitivity and specificity of various CEUS findings for the diagnosis of SRMs will be determined. Summary receiver operating characteristic curve will be used to assess the overall performance of CEUS. RESULTS: This study will evaluate the diagnostic accuracy of CEUS for the diagnosis of SRMs through sensitivity, specificity, positive and negative likelihood ratio, and diagnostic odds ratio. CONCLUSION: This study will summarize the most recent evidence that focusing on the diagnosis of CEUS for SRMs. STUDY REGISTRATION: INPLASY202060040.