Clinical application of high-resolution spiral CT scanning in the diagnosis of auriculotemporal and ossicle.

Precision and intelligence in evaluating the complexities of middle ear structures are required to diagnose auriculotemporal and ossicle-related diseases within otolaryngology. Due to the complexity of the anatomical details and the varied etiologies of illnesses such as trauma, chronic otitis media, and congenital anomalies, traditional diagnostic procedures may not yield accurate diagnoses. This research intends to enhance the diagnosis of diseases of the auriculotemporal region and ossicles by combining High-Resolution Spiral Computed Tomography (HRSCT) scanning with Deep Learning Techniques (DLT). This study employs a deep learning method, Convolutional Neural Network-UNet (CNN-UNet), to extract sub-pixel information from medical photos. This method equips doctors and researchers with cutting-edge resources, leading to groundbreaking discoveries and better patient healthcare. The research effort is the interaction between the CNN-UNet model and high-resolution Computed Tomography (CT) scans, automating activities including ossicle segmentation, fracture detection, and disruption cause classification, accelerating the diagnostic process and increasing clinical decision-making. The suggested HRSCT-DLT model represents the integration of high-resolution spiral CT scans with the CNN-UNet model, which has been fine-tuned to address the nuances of auriculotemporal and ossicular diseases. This novel combination improves diagnostic efficiency and our overall understanding of these intricate diseases. The results of this study highlight the promise of combining high-resolution CT scanning with the CNN-UNet model in otolaryngology, paving the way for more accurate diagnosis and more individualized treatment plans for patients experiencing auriculotemporal and ossicle-related disruptions.

Degradation of edible mushroom waste by Hermetia illucens L. and consequent adaptation of its gut microbiota.

The edible fungus industry is one of the pillar industries in the Yunnan-Guizhou Plateau, China. The expansion of the planting scale has led to the release of various mushroom residues, such as mushroom feet, and other wastes, which are not treated adequately, resulting in environmental pollution. This study investigated the ability of black soldier fly (Hermetia illucens L.) larvae (BSFL) to degrade mushroom waste. Moreover, this study analyzed changes in the intestinal bacterial community and gene expression of BSFL after feeding on mushroom waste. Under identical feeding conditions, the remaining amount of mushroom waste in Pleurotus ostreatus treatment group was reduced by 18.66%, whereas that in Flammulina velutipes treatment group was increased by 31.08%. Regarding gut microbial diversity, compared with wheat bran-treated control group, Dysgonomonas, Providencia, Enterococcus, Pseudochrobactrum, Actinomyces, Morganella, Ochrobactrum, Raoultella, and Ignatzschineria were the most abundant bacteria in the midgut of BSFL in F. velutipes treatment group. Furthermore, Dysgonomonas, Campylobacter, Providencia, Ignatzschineria, Actinomyces, Enterococcus, Morganella, Raoultella, and Pseudochrobactrum were the most abundant bacteria in the midgut of BSFL in P. ostreatus treatment group. Compared with wheat bran-treated control group, 501 upregulated and 285 downregulated genes were identified in F. velutipes treatment group, whereas 211 upregulated and 43 downregulated genes were identified in P. ostreatus treatment group. Using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we identified 14 differentially expressed genes (DEGs) related to amino sugar and nucleotide sugar metabolism in F. velutipes treatment group, followed by 12 DEGs related to protein digestion and absorption. Moreover, in P. ostreatus treatment group, two DEGs were detected for fructose and mannose metabolism, and two were noted for fatty acid metabolism. These results indicate that feeding on edible mushroom waste can alter the intestinal microbial community structure of BSFL; moreover, the larval intestine can generate a corresponding feedback. These changes contribute to the degradation of edible mushroom waste by BSFL and provide a reference for treating edible mushroom waste using BSFL.

A new phenolic compound from Persicaria capitata.

Persicaria capitata was a frequently used Hmong medicinal flora in China. In this study, one new phenolic compound, capitaone A (1) together with 20 known ones, were isolated from the whole herb of P. capitata. Among them, 7 components (4, 9-11, 15-16, 20-21) were discovered from P. capitata for the first time. Their chemical structures were elucidated on the basis of extensive NMR and MS spectrum. Furthermore, three compounds (15, 20, 21) displayed remarkable cytotoxic activities against two human cancer cell lines (A549 and HepG2).

Clinical characteristics and effects of inhaled corticosteroid in patients with post-COVID-19 chronic cough during the Omicron variant outbreak.

BACKGROUND: Chronic cough is a common symptom in patients post the coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the efficacy of inhaled corticosteroids (ICS) and the clinical characteristics of patients with post-COVID-19 chronic cough during the Omicron era. METHODS: An ambispective, longitudinal cohort study was conducted that included patients with post-COVID-19 who attended the respiratory clinic at our hospital between January 1, 2023, and March 31, 2023 with a complaint of persistent cough lasting more than 8 weeks. At 30 and 60 days after the first clinic visit for post-COVID-19 chronic cough, enrolled patients were prospectively followed up. We compared the changes in symptoms and pulmonary function between patients receiving ICS treatment (ICS group) and those not receiving ICS treatment (NICS group) at the two visits. RESULTS: A total of 104 patients with post-COVID-19 chronic cough were enrolled in this study (ICS group, n = 51; NICS group, n = 53). The most common symptoms accompanying post-COVID-19 chronic cough were sputum (58.7%, 61/104) and dyspnea (48.1%, 50/104). Seventy-one (82.6%, 71/86) patients had airway hyperresponsiveness, and 49 patients (47.1%, 49/104) were newly diagnosed with asthma. Most patients (95.2%, 99/104) exhibited improvement at 60 days after the first visit. The pulmonary function parameters of the patients in the ICS group were significantly improved compared to the baseline values (P < 0.05), and the improvement in the FEV1/FVC was significantly greater than that in the NICS group (P = 0.003) after 60 days. CONCLUSIONS: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may contribute to the pathogenesis of asthma, which could be the underlying cause of persistent cough post-COVID-19 infection. Post-COVID-19 chronic cough during the Omicron era was often accompanied by sputum, dyspnea, and airway hyperresponsiveness. ICS treatment did not have a significant impact on symptom management of post-COVID-19 chronic cough; however, it can improve impaired lung function in in these individuals.

Acute upper limb ischemia caused by thrombus shedding during arteriovenous graft thrombolysis: A case report.

Acute upper limb ischemia is a rare, potentially limb- or life-threatening vascular emergency that may lead to limb dysfunction or amputation. We present a patient undergoing maintenance hemodialysis who was hospitalized for arteriovenous graft thrombus complicated by acute upper limb ischemia arising from thrombus shedding to the fingertip arteries during thrombolysis. We successfully restored fingertip arterial patency, avoided amputation, and recovered the function of the arteriovenous graft by precise thrombolysis, anticoagulation, correction of arteriospasm, and percutaneous transluminal angioplasty. This case provides a basis for vascular access surgeons to treat acute upper limb ischemia caused by thromboembolism similarly.

Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection.

OBJECTIVE: Human adenovirus (HAdV) infection is common and can develop to serious conditions with high mortality, yet the mechanism of HAdV infection remains unclear. In the present study, the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection (URTI) were explored. METHODS: In total, 35 patients were enrolled in the study following an outbreak of HAdV-7 in the army, of whom 14 had pneumonia and 21 had URTI. Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics. RESULTS: Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules, including glycerophospholipids, fatty acyls, and sphingolipids. The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways, including sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients, but not between the acute and recovery stages for the URTI patients. Ceramide and lactosylceramide, involved in sphingolipid metabolism, were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities [area under curve (AUC) 0.742 and 0.716, respectively; combination AUC 0.801]. CONCLUSION: Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia, especially the sphingolipid metabolism involving ceramide and lactosylceramide, which might thus be a potential intervention target in the treatment of HAdV infection.

Bile acid metabolomics identifies chenodeoxycholic acid as a therapeutic agent for pancreatic necrosis.

Bile acids are altered and associated with prognosis in patients with acute pancreatitis (AP). Here, we conduct targeted metabolomic analyses to detect bile acids changes in patients during the acute (n = 326) and the recovery (n = 133) phases of AP, as well as in healthy controls (n = 60). Chenodeoxycholic acid (CDCA) decreases in the acute phase, increases in the recovery phase, and is associated with pancreatic necrosis. CDCA and its derivative obeticholic acid exhibit a protective effect against acinar cell injury in vitro and pancreatic necrosis in murine models, and RNA sequencing reveals that the oxidative phosphorylation pathway is mainly involved. Moreover, we find that overexpression of farnesoid X receptor (FXR, CDCA receptor) inhibits pancreatic necrosis, and interfering expression of FXR exhibits an opposite phenotype in mice. Our results possibly suggest that targeting CDCA is a potential strategy for the treatment of acinar cell necrosis in AP, but further verification is needed.

Radiofrequency ablation combined with toripalimab for recurrent hepatocellular carcinoma: A prospective controlled trial.

OBJECTIVE: The effectiveness and security of radiofrequency ablation (RFA) in combination with toripalimab (anti-PD-1) for the treatment of recurrent hepatocellular carcinoma (HCC) was studied in this article. METHODS: Total of 40 patients were enrolled in the study between September 2019 and November 2021. Data follow-up ends in April 2022. The study's main focus is on recurrence free survival (RFS), while the secondary objectives was safety. Chi-square tests, Kaplan-Meier, and Cox proportional hazards models were utilized to analyze the data. RESULTS: The median follow-up period was 21.40 months, and the median RFS was 15.40 months in the group that received combination therapy, which was statistically significantly different (HR: 0.44, p = 0.04) compared with the RFA group (8.2 months). RFS rates (RFSr) at 6, 12 and 18 months in the combination therapy groups and RFA groups were 80% vs 65%, 62.7% vs 35% and 48.7% vs 18.8%, respectively. Between the two groups, significant difference of RFSr was found at 18 months (p = 0.04). No statistical differences were observed between the two groups in terms of safeness (p > 0.05). The subgroup analysis indicated that the combination of RFA and anti-PD-1 led to better RFS than RFA alone. Moreover, patients benefited more from combination therapy in the groups younger than 60 years (HR: 0.26, p = 0.018), male (HR: 0.32, p = 0.028) and Child-Pugh grade A (HR: 0.38, p = 0.032). CONCLUSIONS: Combining RFA with anti-PD-1 showed improved RFS and was deemed safe for patients with recurrent HCC who had previously undergone RFA treatment alone.

Clinical features, microbial spectrum, and antibiotic susceptibility patterns of spontaneous bacterial peritonitis in cirrhotic patients.

BACKGROUND AND AIMS: The microbial spectrum and antimicrobial resistance patterns change over time and vary across regions in patients with spontaneous bacterial peritonitis (SBP). There is an urgent need to clarify the factors associated with in-hospital mortality in these patients. METHODS: In this study, 377 patients with SBP and 794 patients with bacterascites were analyzed for the microbial spectrum, antimicrobial resistance profiles, and laboratory findings. RESULTS: The most common pathogens were Escherichia coli (96, 25.5%), Staphylococcus epidermidis (55, 14.6%), and Enterococcus faecium (42, 11.1%). Multidrug-resistant (MDR) bacteria comprised 49.7% of gram-positive bacteria (GPB) and 48.8% of gram-negative bacteria (GNB). The most sensitive antibiotics were amikacin (91.5%), meropenem (89.8%) and piperacillin/tazobactam (87.6%). Extensively drug-resistant (XDR) (OR=51.457, p < 0.001), neutrophil count (OR=1.088, p < 0.001), and the model for end-stage liver disease (MELD) score (OR=1.124, p < 0.001) were independent predictive factors of in-hospital mortality in patients with SBP. CONCLUSION: MDR represented nearly half of the bacteria isolated from patients with SBP, of which the high prevalence of extended-spectrum ß-lactamase-producing and Carbapenem-resistant bacteria is concerning. The presence of XDR, higher MELD score, and neutrophil count were independent predictive factors associated with higher in-hospital mortality in patients with SBP, indicating that intensive care should be provided to these patients.

The Lin28b/Wnt5a axis drives pancreas cancer through crosstalk between cancer associated fibroblasts and tumor epithelium.

Bidirectional signal transduction between tumor epithelial cells and tumor microenvironment (TME) is important for tumor development. Here we show that Lin28b/let-7 pathway is indispensable for modulating the expression of Wnt5a in tumor epithelium, which could be secreted and then up-regulates Lin28b in cancer-associated fibroblasts (CAFs). Moreover, we demonstrate that Lin28b in CAFs promoted growth of PDAC by inducing cytokine PCSK9's production. Using an orthotopic mouse model of PDAC, we find that depletion of Lin28b in CAFs reduced tumor weight, highlighting the importance of Lin28b in PDAC stroma. Thus, our study shows that the Lin28b-Wnt5a axis plays a critical role in bidirectional crosstalk between pancreatic tumor epithelium and TME and results in a pro-|tumorigenic contexture.

Single-cell mapping reveals several immune subsets associated with liver metastasis of pancreatic ductal adenocarcinoma.

BACKGROUND: Identifying a metastasis-correlated immune cell composition within the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) will help to develop promising and innovative therapeutic strategies. However, the dynamics of immune cell lineages in the TME of advanced PDAC remains elusive. METHODS: Twenty-six samples from 11 patients (including 11 primary tumor tissues, 10 blood, and 5 lymph nodes) with different stages were used to develop a multiscale immune profile. High-dimensional single-cell analysis with mass cytometry was performed to search for metastasis-correlated immune changes in the microenvironment. The findings were further validated by published single-cell RNA sequencing (scRNA-seq) data and multiplex fluorescent immunohistochemistry. FINDINGS: High-dimensional single-cell profiling revealed that the three immune-relevant sites formed a distinct immune atlas. Interestingly, the PDAC microenvironment with the potential for metastatic spread to the liver was characterized by a decreased proportion of CD103+PD-1+CD39+ T cells with cytotoxic and exhausted functional status and an increased proportion of CD73+ macrophages. Analysis of scRNA-seq data of PDAC further confirmed the identified subsets and revealed strong potential interactions via various ligand-receptor pairs between the identified T subsets and the macrophages. Moreover, stratified patients with different immune compositions correlated with clinical outcomes of PDAC. CONCLUSIONS: Our study uncovered metastasis-correlated immune changes, suggesting that ecosystem-based patient classification in PDAC will facilitate the identification of candidates likely to benefit from immunotherapy. FUNDING: This work was supported by the National Key Research and Development Program of China, the Shanghai International Science and Technology Collaboration Program, the Shanghai Sailing Program, and the Key Laboratory of diagnosis and treatment of severe hepato-pancreatic diseases of Zhejiang Province.

Clinical outcomes of indwelling needle-delivered urokinase thrombolysis in the treatment of thrombosed arteriovenous grafts.

BACKGROUND: To investigate the clinical outcomes of indwelling needle-delivered local urokinase thrombolysis, a cost-saving thrombolytic approach, in the treatment of thrombosed arteriovenous grafts (AVGs). METHODS: The clinical data of 71 patients with a first episode of thrombosed AVG were analyzed. Among them, 49 patients underwent urokinase thrombolysis and percutaneous transluminal angioplasty (PTA), and 22 patients underwent thrombectomy and PTA. The operation success rate, operation time, perioperative and postoperative complications, primary patency, and secondary patency were compared. RESULTS: Clinical success was achieved in all 71 PTAs. After thrombolysis, 29 patients achieved complete lysis, and 20 patients achieved partial lysis. All patients achieved thrombus clearance after PTA. The operating room usage time was 37.48 ± 5.33 min for the complete thrombolysis group and 41.70 ± 6.16 min for the incomplete thrombolysis group, and these values were not significantly different (p = 0.853). The operating room usage time of the thrombectomy group was 124.73 ± 5.08 min, which was significantly longer than that of the other groups (p < 0.001). The log-rank test indicated no significant difference in the 90-, 180-, and 360-day primary patency and corresponding secondary patency (all p > 0.05). The Cox regression showed that no significant difference was noted in the changing rate of primary or secondary patency among the groups (all p > 0.05). No major complications occurred in any of the groups, and the difference in the complication incidence was not significant (p = 0.336). CONCLUSIONS: Indwelling needle-delivered urokinase thrombolysis is an acceptable method for the treatment of thrombosed AVGs. Compared with thrombectomy and PTA, thrombolysis and PTA can significantly shorten the time to use the operating room without reducing primary and secondary patency or increasing complications.

Clinical characteristics of hemodialysis patients with left brachiocephalic vein obstruction due to extrinsic compression or prior catheterization.

BACKGROUND: Left brachiocephalic vein (LBCV) stenosis is a common complication in hemodialysis patients and is a heterogenous disorder associated with either prior catheterization or extrinsic compression. This study aimed to characterize patients with LBCV stenosis or occlusion with and without a history of central venous catheterization. METHODS: We performed a retrospective study in 84 hemodialysis patients with LBCV stenosis or occlusion with (n = 22) or without (n = 62) prior catheterization. We compared the clinical features, anatomical factors, restenosis after balloon venoplasty, and patency rates of patients in these two groups. RESULTS: In the cohort of 84 patients with LBCV stenosis or occlusion, 73.8% (62 patients) of them had no history of catheterization. Patients without prior catheterization had more stenotic lesions (p < 0.05) but less occlusive lesions (p < 0.05) than patients with prior catheterization. The space between the sternum and the aorta was narrower in patients without prior catheterization than that in patients with prior catheterization (p < 0.05). Percutaneous venography was performed in 81 patients, and the occurrence of recoil after venoplasty in patients without prior catheterization was significantly higher than that in patients with prior catheterization (p < 0.05). The rate of stent implantation was significantly higher in patients without prior catheterization than patients with prior catheterization (p < 0.05), whereas there was no significant difference in primary patency between the two groups. CONCLUSIONS: LBCV stenosis and occlusion are mainly due to extrinsic compression rather than prior central venous catheterization. Stent implantation is frequently required after venoplasty to treat LBCV obstructive lesions in patients without prior catheterization.

SMYD2 inhibition-mediated hypomethylation of Ku70 contributes to impaired nonhomologous end joining repair and antitumor immunity.

DNA damage repair (DDR) is a double-edged sword with different roles in cancer susceptibility and drug resistance. Recent studies suggest that DDR inhibitors affect immune surveillance. However, this phenomenon is poorly understood. We report that methyltransferase SMYD2 plays an essential role in nonhomologous end joining repair (NHEJ), driving tumor cells adaptive to radiotherapy. Mechanically, in response to DNA damage, SMYD2 is mobilized onto chromatin and methylates Ku70 at lysine-74, lysine-516, and lysine-539, leading to increased recruitment of Ku70/Ku80/DNA-PKcs complex. Knockdown of SMYD2 or its inhibitor AZ505 results in persistent DNA damage and improper repair, which sequentially leads to accumulation of cytosolic DNA, and activation of cGAS-STING pathway and triggers antitumor immunity via infiltration and activation of cytotoxic CD8+ T cells. Our study reveals an unidentified role of SMYD2 in regulating NHEJ pathway and innate immune responses, suggesting that SMYD2 is a promising therapeutic target for cancer treatment.

Interfacial Self-Assembly of Organized Ultrathin Films of Tripodal Metal-Terpyridyl Coordination Polymers as Luminophores and Heterogeneous Catalysts for Photocatalytic CO2 Reduction.

Metal-directed interfacial self-assembly of well-defined coordination polymer (CP) ultrathin films can control the metal complex arrangement and distribution at the molecular level, providing a convenient route for the design and fabrication of novel opto-electrical devices and heterogeneous catalysts. Here, we report the assembly of two series of CP multilayers with the transition-metal ions of Fe2+, Co2+, Zn2+ and Tb3+ as connectors and tripodal terpyridyl ligands of 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tris(1-(4-([2,2':6',2″-terpyridin]-4'-yl)benzyl)pyridin-1-ium) (TerPyTa) and 4,4',4″-(benzene-1,3,5-triyl)tris(1-(4-([2,2':6',2″-terpyridin]-4'-yl)benzyl)pyridin-1-ium) (TerPyBen) as linkers at the air-water interface. The as-prepared Langmuir-Blodgett (LB) films display strong luminescence, with the emission wavelength and relative intensity dependent on both the metal ions and linkers; among them, the Zn-TerPyTa and Zn-TerPyBen CPs give off the strongest luminescent emission centered at about 370 nm with an emission lifetime of approximately 0.2-0.3 ns. The Tb-TerPyTa CPs can give off emission at approximately 490, 546, 586, and 622 nm, attributed to the 5D4 to 7F3-6 electron transitions of typical Tb3+ ions. Finally, these CP LB films can act as efficient heterogeneous photocatalysts for the CO2 reduction to selectively produce CO. The catalytic efficiency can be optimized by adjusting the experimental conditions (light sensitizer, electron donor, and water content) and CP composition (metal ion and ligand) with an excellent yield of up to 248.1 mmol g-1. In particular, it is revealed that, under the same conditions, the catalytic efficiency of the Fe-TerPyTa CP LB film is nearly 2 to 3 orders of magnitude higher than that of the other metalated complexes investigated in the homogeneous system. UV-vis spectroscopy and cyclic voltammetry studies demonstrated that the dual active sites of Fe-terpyridine and TerPyTa units contribute to the enhanced catalytic activity. This work provides an effective method to introduce the earth-abundant metal complexes into CP films to construct efficient noble-metal-free photocatalysts for the CO2 reduction.

A novel type lavandulyl flavonoid from Sophora flavescens as potential anti-hepatic injury agent that inhibit TLR2/NF-κB signaling pathway.

ETHNOPHARMACOLOGY RELEVANCE: Sophora flavescens Aiton, was a crucial source of Traditional Chinese Medicine (TCM) that has benefited human health for hundreds of years. Alkaloids and flavonoids were the major bioactive constituents from S. flavescens, which had been widely used for liver disease treatment in China. However, the liver-protective components of flavonoids from S. flavescens and their mechanism of action were not clear. AIM OF THE STUDY: This work aimed to evaluate the in vitro hepatoprotective activities of 35 flavonoids from S. flavescens and screen active compounds. Furthermore, it was conducted to demonstrate the hepatoprotective effects of a new active compound (kurarinol A, 1) was isolated by authors and the ethyl acetate (EtOAc) extract form S. flavescens against carbon tetrachloride (CCl4)-induced hepatic injury in Kunming (KM) mice, meanwhile revealed the potential mechanism. MATERIALS AND METHODS: The 35 flavonoids from S. flavescens were co-incubated with HepG2 cells and treated with 0.35% CCl4 for 6 h cell viability was measured by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. Then, in vivo animal experiments, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the serum were analyzed, the degree of hepatic injury was examined using hematoxylin-eosin (H&E) staining, the mRNA expression of Superoxide Dismutase 2 (SOD2), Nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α), interleukin-1ß (IL-1ß), and the protein levels of nuclear factor-kappa B p65/p-p65 (NF-κB p65/p-p65), toll-like receptor 2 (TLR2), IL-1ß and cyclooxygenase-2 (COX2) in hepatic tissues were detected. RESULTS: The lavandulyl flavonoid (kurarinol A, 1) and the EtOAc extract from S. flavescens showed protective effects on CCl4-injured HepG2 cells, increasing cell viability from 24.5% to 61.3% and 91.8%, respectively. What's more, we found that treatment with kurarinol A (1) and the EtOAc extract lead to a significant reduction in hepatotoxicity in response to acute CCl4 exposure. Compared with the model group, experimental results exhibited kurarinol A (10 mg/kg, i.p.) and the EtOAc extract (300 mg/kg, i.p.) could decrease the levels of AST, ALT, ALP and tissue damage. Further mechanistic investigations revealed that up-regulated the mRNA expression of SOD2, Nrf2, OH-1 and down-regulated the IL-1ß in liver tissues, respectively. Additionally, Western blot analyses elucidated that inhibition of IL-1ß, TLR2, COX-2, NF-κB (p65/p-p65) via TLR2/NF-κB signaling pathway by kurarinol A and the EtOAc extract contribute to its hepatoprotective activity. CONCLUSION: These findings demonstrated that the novel compound (kurarinol A, 1) possessed notable hepatoprotective activity against CCl4. It was confirmed that kurarinol A had a certain effect on mice with liver damage induced by CCl4, and its mechanism could be include inhibiting inflammation and reducing of oxidative stress reaction by regulating expression of related genes and proteins. Thus, kurarinol A could as a novel active agent that contributes to the hepatoprotective activity of S. flavescens for the treatment of live injury.

Radial artery superficialization for hemodialysis patients with severe heart failure: A case report.

Arteriovenous fistula (AVF) and/or arteriovenous graft (AVG) burdens cardiac load. It is a challenge to create a vascular access (VA) on a patient who suffers severe heart failure and also combines with contraindications of central vein catheter implantation. Superficialized radial artery (RA) could be an available VA as an outflow for continuous hemodialysis. A 57-year-old male had a left arm distal radiocephalic fistula for hemodialysis for 10 months. The patient showed gradual aggravation of heart failure. RA superficialization was performed under anesthesia protocols and surgery steps. Fourteen days after the surgery, the superficialized artery supplied the hemodialysis as an outflow without any uncomfortable and complications. The echocardiographies present the changes of the heart structures and functions during the whole period from the beginning of AVF formation to the 18-month follow-up RA superficialization. RA superficialization technique should be an alternative VA for continuous hemodialysis under suitable conditions.

Graphene electrochemical transistor incorporated with gel electrolyte for wearable and non-invasive glucose monitoring.

With the rapid development of wearable electronic devices, health monitoring is undergoing a fundamental shift from hospital-centered treatment to patient-centered diagnosis. Solution-gated graphene transistors provide an effective platform for developing high-sensitivity wearable devices due to their unique signal amplification, low energy consumption, and compatibility for miniaturization. However, it is still a major challenge to perform real-time sweat composition monitoring directly on the dry skin surface. In this work, a skin-based flexible gel electrolyte graphene transistor (GEGT) was successfully designed and fabricated for glucose detection, consisting of a gate electrode decorated with Au nanoparticles modified reduced graphene oxide (AuNPs/RGO) nanocomposites and a monolayer graphene channel. Glycerin gel was used to replace the traditional liquid electrolyte, not only could better fit the human skin, but also play the role of fluid collection, providing stable testing conditions for the sensor. Based on the high electron mobility of graphene channel and the excellent electrocatalytic performance of AuNPs/RGO nanocomposites, the constructed GEGT sensor exhibits excellent sensing performance for glucose with good selectivity, low operating voltage (0.5 V), wide detection range (10 nM - 25 mM), and low detection limit (10 nM). The device maintains stable performance after up to 1000 bending cycles with a bending radius of 4 mm. In addition, the GEGT sensor displays good accuracy in sweat detection and sensitive dynamic response during actual wearing, which provides a guarantee for the construction of wearable transistor devices and real-time health tracking.

Systematic elucidation of the bioactive alkaloids and potential mechanism from Sophora flavescens for the treatment of eczema via network pharmacology.

ETHNOPHARMACOLOGY RELEVANCE: Sophora flavescens is a frequently used traditional Chinese medicine (TCM) for the treatment of skin disorders, diarrhea, vaginal itching and inflammatory diseases. In particular, the root of S. flavescens combination with other herbs mainly treat eczema ailment in the clinical applications. However, a holistic network pharmacology approach to understanding the mechanism by which alkaloids in S. flavescens treat eczema has not been pursued. AIM OF THE STUDY: To examine the network pharmacological potential effect of S. flavescens on eczema, we studied the alkaloids, performed protein targets prediction and investigated interacting signal pathways. Furthermore, animal experiment was carried out to evaluate its efficacy and real-time quantitative polymerase chain reactions (RT-qPCR) analysis was explored the mechanism of action. MATERIALS AND METHODS: The detail information on alkaloids from S. flavescens were obtained from a handful of public databases on the basis of oral bioavailability (OB ≥ 30%) and drug-likeness (DL ≥ 0.18). Then, correlations between compounds and protein targets were linked using the STRING database, and targets associated with eczema were gathered by the GeneCards database. Human genes were identified and subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) functional enrichment analysis. Particularly, matrine, the crucial alkaloid from S. flavescens, was estimated using a 2,4-dinitrochlorobenzene (DNCB)-induced eczema Kunming (KM) mice model, administered (50 mg/kg and 10 mg/kg) to mice for 22 days. On the last day, the activities of serum tumor necrosis factor α (TNF-α), interleukin-4 (IL-4) and histopathologic examinations were determined. For further to elucidate the mechanisms, the mRNA levels of TNF-α, STAT3, TP53, AKT1, IL-6, JUN and EGFR in dorsal skin tissues were also tested. RESULTS: Network analysis collected and identified 35 alkaloids from S. flavescens. Among them, in total 10 dominating alkaloids, including matrine, oxymatrine, sophoridine, sophocarpine, oxysophocarpine, allomatrine, sophoramine, anagyrine, cytisine and N-methylcytisine. And 71 related targets were provided of alkaloids for the treatment of eczema from S. flavescens. Furthermore, matrine dose-dependently (50 or 10 mg/kg, 22 days, apply to dorsal skin) remarkable decreased the serum levels of TNF-α and IL-4, and significantly alleviated the skin lesions. The effects of 50 mg/kg of matrine were almost identical to those of 200 mg/kg of the positive drug dexamethasone (DXM). The further RT-qPCR analyses could reveal that matrine down-regulate TNF-α, STAT3 and TP53 at transcriptional level in dorsal skin tissues. CONCLUSION: Pharmacological network analysis can utilize to illuminate the pharmacodynamic substances and the potential molecular mechanism of S. flavescens for treating eczema. Matrine, as the crucial alkaloid from S. flavescens, could be a promising drug candidate for the treatment of eczema ailment.