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Ethnopharmacological relevance: Shizhifang Decoction, a traditional Chinese medicine prescription formulated by Professor Zheng Pingdong of Shuguang Hospital, has been widely utilized in clinical settings for the treatment of hyperuricemia due to its proven safety and efficacy. Objective: In this study, we used network pharmacology, molecular docking technology, and experimental validation to elucidate the therapeutic effects and underlying mechanisms of Shizhifang Decoction in managing hyperuricemia. Methods: Quality control and component identification of the freeze-dried powder of Shizhifang Decoction were conducted using ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry. Active ingredients and their corresponding targets were obtained from Traditional Chinese Medicine Systems Pharmacology, Traditional Chinese Medicine Information Database, The Encyclopedia of Traditional Chinese Medicine, and other databases. Disease-related targets for hyperuricemia were collected from GeneCards and DisGeNET databases. The Venny platform is used to screen common targets for drug active ingredients and diseases. Subsequently, we constructed an active component-target-disease interaction network using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, create a component disease common target network using Cytoscape 3.9.1 software, from which core targets were selected. Import common targets into the Database for Annotation, Visualization and Integrated Discovery (DAVID) for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Molecular docking was then conducted to validate the binding capacity of key active ingredients and their associated targets in Shizhifang Decoction. The theoretical predictions were further confirmed through in vitro and in vivo experiments. Result: A total of 35 active ingredients and 597 action targets were identified, resulting in 890 disease-related targets for hyperuricemia. After comprehensive analysis, 99 common targets were determined. Protein-protein interaction network analysis revealed crucial relationships between these targets and hyperuricemia. Among them, 12 core targets (CASP3, IL1B, IL6, TNF, TP53, GAPDH, PTGS2, MYC, INS, VEGFA, ESR1, PPARG) were identified. Gene Ontology enrichment analysis demonstrated significant associations with the regulation of inflammatory response, cell apoptosis, and the positive regulation of extracellular regulated protein kinases 1 and extracellular regulated protein kinases 2 cascades. Kyoto Encyclopedia of Genes and Genomes pathway analysis highlighted inflammation and apoptosis-related pathways as critical mediators of Shizhifang Decoction's effects on hyperuricemia. Molecular docking studies further supported the interactions between apoptosis-related proteins and active ingredients in the extracellular regulated protein kinases 1/2 signaling pathway. In vitro experiments confirmed the downregulation of apoptosis-related proteins (caspase-3, Bax, Bcl-2) and the inhibition of the extracellular regulated protein kinases 1/2 signaling pathway by Shizhifang Decoction. These findings were also validated in animal models, demonstrating the potential of Shizhifang Decoction to mitigate renal injury induced by hyperuricemia through extracellular regulated protein kinases 1/2-mediated inhibition of renal tubular epithelial cell apoptosis. Conclusion: Our study provides valuable insights into the main mechanism by which Shizhifang Decoction ameliorates hyperuricemia. By targeting the ERK1/2 signaling pathway and modulating cell apoptosis, Shizhifang Decoction exhibits promising therapeutic potential for the treatment of hyperuricemia. These findings support the continued exploration and development of Shizhifang Decoction as a potential herbal remedy for hyperuricemia management.

Background IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and it is characterized by mesangial IgA deposits. Proteinuria is a common clinical feature of IgAN, which has a critical connection to podocyte injury and has been used as a clinical prognostic factor for IgAN. Evidence has shown that TNF-α released from mesangial cells may lead to podocyte apoptosis.Methods Forty male BALB/c mouse were randomly divided into the control group and IgAN group. A mice model of IgAN was developed by oral administration of bovine serum albumin (BSA) combined with Staphylococcus Enterotoxin B (SEB) tail vein injection. Urinary protein concentrations, renal function, renal morphological, IgA deposition, apoptosis situation, and the mRNA and protein expression of nephrin, podocin, TNF-α, TNFR1, caspase-8 and caspase-3, were detected after 12 weeks.Results BSA and SEB can successfully establish an IgAN mouse model, and the main pathological changes are the IgA immune complex deposition in the mesangial area. The gene and protein expression levels of nephrin and podocin were found to be downregulated, and death receptor pathway-related indicators were upregulated, and they were involved in TNF-α-activated podocyte injury and apoptosis in IgAN mice.Conclusion TNF-α may play an important role in the pathogenesis of podocyte apoptosis in IgAN, and its effects may be mediated through the apoptotic death receptor pathway.

Context Diabetic kidney disease (DKD) is a devastating complication of diabetes. Renal functional deterioration caused by tubular injury is the primary change associated with this disease. Calycosin shows protective roles in various diseases.Objectives This study explored the function and underlying mechanism of calycosin in DKD.Materials and methods HK-2 cells were treated with 25 mM high glucose (HG) to establish a renal tubule injury cell model. Then, the viability of cells treated with 0, 5, 10, 20, 40 and 80 μM of calycosin was measured using Cell Counting Kit-8. For the in vivo model, db/db mice were treated with 10 and 20 mg/kg/day of calycosin; db/m mice served as controls. The histomorphology was analyzed via haematoxylin and eosin staining.Results HG-induced decreased expression of glutathione (491.57 ± 33.56 to 122.6 ± 9.78 μmol/mL) and glutathione peroxidase 4 (inhibition rate 92.3%) and increased expression of lactate dehydrogenase (3.85 ± 0.89 to 16.84 ± 2.18 U/mL), malondialdehyde (3.72 ± 0.66 to 18.2 ± 1.58 nmol/mL), lipid ROS (4.31-fold increase) and NCOA4 (7.69-fold increase). The effects induced by HG could be blocked by calycosin. Moreover, calycosin alleviated the HG-induced decrease of cell viability and the increase of lipid ROS, but erastin could block the effects caused by calycosin. The in vivo model showed that calycosin alleviated the renal injury caused by diabetes.Discussion and conclusion Calycosin has a protective effect on diabetic kidney disease; ferroptosis may be involved in this process.

Abstract Background The prevalence rates of gout worldwide have increased annually. Acute gouty arthritis (AGA) accounts for a large proportion of gout patients and causes severe physical and mental pain in patients. Controlling the occurrence and development of gout inflammation is the first step in the treatment of gout. The main treatment drugs in gout are non-steroid anti-inflammatory drugs (NSAIDs), colchicine, and glucocorticoids, but these treatments have many adverse reactions which limit their clinical application. Baihu and Guizhi decoction (BHGZ) is one of the classic prescriptions in the Synopsis of the Golden Chamber and is a good prescription for AGA. Previous clinical studies have shown that BHGZ confers a strong benefit for treating AGA. However, the literature shows a lack of high-quality RCT research on BHGZ with respect to AGA. Therefore, in this study, we use a randomized, double-blind, controlled study with a placebo to evaluate the clinical efficacy and safety of BHGZ on the AGA of moist heat arthralgia spasm syndrome. Methods This study is a randomized, double-blind, controlled clinical trial. A total of 102 adult participants with AGA of moist heat arthralgia spasm syndrome will be enrolled, with balanced treatment allocation (1:1). The experimental intervention will be BHGZ plus the low-dose colchicine, and the control intervention will be placebo plus the low-dose colchicine for 10 days. To study the clinical efficacy (including VAS score; joint tenderness, joint swelling, joint movement disorder; TCM evidence efficacy score) and the changes of inflammatory indexes. At the same time, the improvement of joint inflammation in patients with AGA will be observed from musculoskeletal ultrasound imaging, and the safety evaluation will be carried out. Discussion This study will be the first placebo-controlled RCT to assess whether BHGZ plus low-dose colchicine have beneficial effects on changing reducing inflammation of joints for patients with AGA of moist heat arthralgia spasm syndrome. The results of this trial will help to provide evidence-based recommendations for clinicians. Trial registration Chinese Clinical Trials Register ChiCTR1900024974 . Registered on 5 August 2019

Background: Hyperuricemic nephropathy is a highly prevalent kidney disease induced by excessive accumulation and deposition of monosodium urate in kidney, which contributes to the loss of kidney function. The Jiangniaosuan formulation (JNSF) is a Chinese herbal medicine treatment. The aim of this study is to evaluate its efficacy and safety among patients with hyperuricemic nephropathy at chronic kidney disease (CKD) stages 3–4 and with obstruction of phlegm turbidity and blood stasis syndrome. Methods: Our research is designed as a single-centre, double-blinded, randomized, placebo-controlled trial for 118 patients diagnosed with hyperuricemic nephropathy at CKD stages 3–4 and with obstruction of phlegm turbidity and blood stasis syndrome in mainland China. Patients are to be randomized into two groups: either the intervention group which receives JNSF 20.4 g/day combined with febuxostat 20–40 mg/day, or the control group which receives JNSF placebo 20.4 g/day combined with febuxostat 20–40 mg/day. The intervention will be carried on for 24 weeks. The change in estimated glomerular filtration rate (eGFR) is set as the primary outcome. Secondary outcomes include changes in serum uric acid, serum nitric oxide, urinary albumin/creatinine ratio, urinary N-acetyl-β-D glucosaminidase, urinary β2 microglobulin, urinary retinol binding protein and TCM syndromes in 24 weeks. Statistical analysis will be formulated by SPSS 24.0. Discussion: The trial will conduce to the comprehensive assessment in the efficacy and safety of JNSF among patients diagnosed with hyperuricemic nephropathy at CKD stages 3–4, and provide a clinical method available on systems of the combination of modern medicine and TCM.

Abstract Background Jiangniaosuan formula (JNSF) is commonly used in China for treating hyperuricemia, but there is little research-based evidence to support its use. This randomized controlled trial aims to assess the efficacy and safety of JNSF. Methods A total of 72 patients with hyperuricemia will be selected and randomly assigned in a ratio of 1:2 to receive either Western medicine, i.e., febuxostat 40 mg (WG group; n = 24), or Chinese herbal medicine, i.e., Jiangniaosuan formula + febuxostat 20 mg (WJNSG group; n = 48). After 12 weeks, the WJNSG will be randomly divided into two groups of 24 patients each; one group (WJNSG; n = 24) still will receive febuxostat 20 mg + Jiangniaosuan formula, and the other group (JNSG; n = 24) will continue to receive Jiangniaosuan formula + placebo. Participants will be followed up at 4-week intervals. The primary outcome will be the change in serum uric acid level, and the secondary outcome will be the change in traditional Chinese medicine (TCM) syndrome scores. Serum creatinine, blood glucose, and insulin levels will also be measured. Discussion We hypothesize that patients with hyperuricemia will benefit from JNSF. This study will provide evidence-based recommendations for clinicians. Dissemination The results will be published in a peer-reviewed journal and disseminated by academic conferences. The datasets analyzed during the current study are available from the corresponding author on reasonable request. Trial registration Chinese Clinical Trials Register ChiCTR2000041083 . Registered on 3 May 2021. The protocol version number is V3.0, 20210301.

Abstract Identifying critically ill patients is a key challenge in emergency department (ED) triage. Mis-triage errors are still widespread in triage systems around the world. Here, we present a machine learning system (MLS) to assist ED triage officers better recognize critically ill patients and provide a text-based explanation of the MLS recommendation. To derive the MLS, an existing dataset of 22,272 patient encounters from 2012 to 2019 from our institution’s electronic emergency triage system (EETS) was used for algorithm training and validation. The area under the receiver operating characteristic curve (AUC) was 0.875 ± 0.006 (CI:95%) in retrospective dataset using fivefold cross validation, higher than that of reference model (0.843 ± 0.005 (CI:95%)). In the prospective cohort study, compared to the traditional triage system’s 1.2% mis-triage rate, the mis-triage rate in the MLS-assisted group was 0.9%. This MLS method with a real-time explanation for triage officers was able to lower the mis-triage rate of critically ill ED patients.

This study proposed the use of polyaniline–alkaline copper carbonate composites as anti-corrosion and anti-biofouling concrete additives and established a set of high-dispersion preparation methods for this composite additive. The effects of polyaniline–alkaline copper carbonate composites in concrete were investigated in marine environments via the preparation of concrete specimens, actual sea suspension experiments, concrete mechanical property tests, and biological attachment avoidance tests. The experimental results showed that (1) the yield of the chemical reactions leading to the preparation of the composite was above 96.46% with a good output. The composite was hydrophilic. The addition of ethylene carbonate as a surfactant and the mixing of the composite into the concrete in a suspension form enabled uniform dispersion of the composite. (2) In the sea waters of Zhoushan, China, bio-attachment was mainly dominated by barnacles and sea anemones. Polyaniline–alkaline copper carbonate composites had good anti-bio-attachment properties and could significantly reduce the amount of bio-attachment in concrete. (3) When the additive content was less than 0.20% of the concrete mass, it did not negatively affect the mechanical properties of the concrete specimens and exerted anti-corrosion and anti-biofouling effects. This reduced the strength loss of concrete and increased the service life of the concrete specimens in the ocean. To ensure the best application effect of the compound in concrete, the recommended content of the compound is 0.05–0.15% of the concrete mass.

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common potentially life-threatening inherited kidney diseases. It is the fourth most common cause of end-stage renal disease requiring renal replacement therapy. There are few management options for controlling disease progression. Hence, identification of alternative treatments for patients is important. The Chinese herbal yinang formulation (YNF), which is derived from a Chinese patent medicine, appears to have a satisfactory effect in treating ADPKD. Because a considerable proportion of ADPKD patients presenting with chronic kidney disease (CKD) stages III–IV are diagnosed with the spleen, kidney deficiency, and blood stasis syndrome according to the diagnostic criteria of traditional Chinese medicine (TCM), we hypothesize that YNF may be a complementary drug for ADPKD patients with the corresponding syndrome. Therefore, we have designed a strict clinical trial to evaluate the safety and efficacy of YNF for ADPKD patients with CKD stages III–IV exhibiting the TCM syndrome of spleen, kidney deficiency, and blood stasis. Methods/design This is a multi-center prospective double-blind randomized controlled trial. The total target sample size is planned to be 72 participants, with a balanced treatment allocation (1:1). The experimental intervention will be YNF plus conventional therapy and the control intervention will be a placebo plus conventional therapy for 24 weeks. An additional 24 weeks of follow-up will be conducted after treatment completion. The primary outcome will be the estimated glomerular filtration rate (eGFR). Changes in total kidney volume (TKV), serum creatinine (Scr), blood urea nitrogen (BUN), TCM symptoms, and pain will be the secondary outcomes. Adverse events (AEs) will be monitored throughout the trial. Discussion This study will be the first placebo-controlled randomized controlled trial to assess whether YNF plus conventional therapy has a beneficial effect on eGFR, TKV, Scr, and BUN, and whether it can alleviate TCM clinical symptoms, reduce ADPKD-related pain, and reduce the frequency of AEs for ADPKD patients with CKD stages III–IV with the spleen, kidney deficiency, and blood stasis syndrome. The results of this trial may provide an evidence-based recommendation for clinicians. Trial registration Chinese Clinical Trials Register, ChiCTR-INR-16009914. Registered on 18 November 2016.

Proton exchange membranes exhibiting a well-organized structure were successfully prepared by a novel self-assembling technique using surface-charged latex nanoparticles as building blocks. The nanoparticles were synthesized in water by free-radical copolymerization. Free-standing membranes were obtained by casting the polymer emulsions followed by a cross-linking reaction. The acquired membrane exhibited a high proton conductivity of 0.04 S cm-1 with an ion exchange capacity (IEC) as low as 0.48 mmol g-1. The enhanced proton conductivity is thought to be derived from the formation of a co-continuous ionic network for ion channels by the closely packed surface-charged latex nanoparticles, facilitating proton transportation in the membranes.

BACKGROUND: Sepsis is one of the main causes of mortality in intensive care units (ICUs). Early prediction is critical for reducing injury. As approximately 36% of sepsis occur within 24 h after emergency department (ED) admission in Medical Information Mart for Intensive Care (MIMIC-IV), a prediction system for the ED triage stage would be helpful. Previous methods such as the quick Sequential Organ Failure Assessment (qSOFA) are more suitable for screening than for prediction in the ED, and we aimed to find a light-weight, convenient prediction method through machine learning. METHODS: We accessed the MIMIC-IV for sepsis patient data in the EDs. Our dataset comprised demographic information, vital signs, and synthetic features. Extreme Gradient Boosting (XGBoost) was used to predict the risk of developing sepsis within 24 h after ED admission. Additionally, SHapley Additive exPlanations (SHAP) was employed to provide a comprehensive interpretation of the model's results. Ten percent of the patients were randomly selected as the testing set, while the remaining patients were used for training with 10-fold cross-validation. RESULTS: For 10-fold cross-validation on 14,957 samples, we reached an accuracy of 84.1%±0.3% and an area under the receiver operating characteristic (ROC) curve of 0.92±0.02. The model achieved similar performance on the testing set of 1,662 patients. SHAP values showed that the five most important features were acuity, arrival transportation, age, shock index, and respiratory rate. CONCLUSION: Machine learning models such as XGBoost may be used for sepsis prediction using only a small amount of data conveniently collected in the ED triage stage. This may help reduce workload in the ED and warn medical workers against the risk of sepsis in advance. [ABSTRACT FROM AUTHOR]

The large-distance penetration capability of an annular-shaped charge under multipoint synchronous initiation was experimentally investigated. For different annular charge structures and different multipoint initiation settings, incident angle, collision type of detonation waves, and overpressure on the shaped charge's liner at adjacent initiation points were analyzed using the detonation wave propagation theory. Furthermore, the shaped charge's penetration capability at a standoff distance of 1–15 m from a 20 mm thick 45# steel plate (the target) was determined through penetration experiments. It was found that the annular cutter formed by the 500 mm diameter annular shaped charge (charge width: 100 mm) completely penetrated the target for a large distance, namely a distance of 150 times the charge width. The ratio of the width of the ring gap penetrated by the annular cutter to the liner's initial radial width was about 1.07; this indicated that the annular cutter's width was equivalent to the liner's radial width for the above flight distance, which in turn implied that the annular cutter had superior circular degree. The annular cutter formed in the case of Mach reflection had better circular degree, integrity, and penetration capability than that formed by regular reflection. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease poses a serious health problem worldwide with increasing prevalence and lack of effective treatment. This study aimed to investigate the mechanism of icariin in alleviating chronic renal failure induced by 5/6 nephrectomy in rats. Methods: The chronic renal failure model was established by a two-phased 5/6 nephrectomy procedure. The model rats were given daily doses of water or icariin for 8 weeks. The kidney morphology was checked by HE staining. The levels of blood urea nitrogen, serum creatinine, and serum uric acid were measured by colometric methods. The expression of specified genes was analyzed by quantitative real-time PCR and immunohistochemical staining. The number of renal stem/progenitor cells was analyzed by CD133 and CD24 immunohistochemical staining. Results: Icariin protected against CDK-caused damages to kidney histology and improved renal function, significantly reduced levels of BUN, creatinine, and uric acid. Icariin inhibited the expression level of TGF-β1 whereas upregulated HGF, BMP-7, WT-1, and Pax2 expression. Moreover, ccariin significantly increased the expression of CD24, CD133, Osr1, and Nanog in remnant kidney and the numbers of CD133+/CD24+ renal stem/progenitor cells. Conclusions: These data demonstrated that icariin effectively alleviated 5/6 nephrectomy induced chronic renal failure through increasing renal stem/progenitor cells. [ABSTRACT FROM AUTHOR]

Abstract  We reported proton-conducting membranes with novel microstructure based on partially phosphorylated poly(vinyl alcohol) (P-PVA) and polyethylene glycol (PEG) grafted silica (PEG-SiO2) particles. The PEG-SiO2 particles were synthesized through acid catalyzed hydrolysis and condensation reactions. The membranes were characterized for their mechanical, structural, morphological, and electrical properties by employing tensile test, Fourier transform infrared (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), impedance analyzer, respectively. In these membranes, P-PVA acts as the proton source and PEG act as the proton solvent. The PEG-riched phases in the hybrid membrane form continuous ionic conducting pathways and subsequently give high ionic conductivity. The results suggest that the obtained membrane shows good thermal stability, excellent mechanical property and high ionic conductivity, and the low-cost hybrid membrane can be a promising candidate for intermediate temperature fuel cell systems. [ABSTRACT FROM AUTHOR]