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Tuberculosis (TB) stands as the second most fatal infectious disease after COVID-19, the effective treatment of which depends on accurate diagnosis and phenotyping. Metabolomics provides valuable insights into the identification of differential metabolites for disease diagnosis and phenotyping. However, TB diagnosis and phenotyping remain great challenges due to the lack of a satisfactory metabolic approach. Here, a metabolomics-based diagnostic method for rapid TB detection is reported. Serum metabolic fingerprints are examined via an automated nanoparticle-enhanced laser desorption/ionization mass spectrometry platform outstanding by its rapid detection speed (measured in seconds), minimal sample consumption (in nanoliters), and cost-effectiveness (approximately $3). A panel of 14 m z-1 features is identified as biomarkers for TB diagnosis and a panel of 4 m z-1 features for TB phenotyping. Based on the acquired biomarkers, TB metabolic models are constructed through advanced machine learning algorithms. The robust metabolic model yields a 97.8% (95% confidence interval (CI), 0.964-0.986) area under the curve (AUC) in TB diagnosis and an 85.7% (95% CI, 0.806-0.891) AUC in phenotyping. In this study, serum metabolic biomarker panels are revealed and develop an accurate metabolic tool with desirable diagnostic performance for TB diagnosis and phenotyping, which may expedite the effective implementation of the end-TB strategy.
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RATIONALE: Isopsoralen (ISO), a quality control marker (Q-marker) in Psoraleae Fructus, is proven to present an obvious anti-osteoporosis effect. Until now, the metabolism and anti-osteoporosis mechanisms of ISO have not been fully elucidated, greatly restricting its drug development. METHODS: The metabolites of ISO in rats were profiled by using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential anti-osteoporosis mechanism of ISO in vivo was predicted by using network pharmacology. RESULTS: A total of 15 metabolites were characterized in rats after ingestion of ISO (20 mg/kg/day, by gavage), including 2 in plasma, 12 in urine, 6 in feces, 1 in heart, 3 in liver, 1 in spleen, 1 in lung, 3 in kidney, and 2 in brain. The pharmacology network results showed that ISO and its metabolites could regulate AKT1, SRC, NFKB1, EGFR, MAPK3, etc., involved in the prolactin signaling pathway, ErbB signaling pathway, thyroid hormone pathway, and PI3K-Akt signaling pathway. CONCLUSIONS: This is the first time for revealing the in vivo metabolism features and potential anti-osteoporosis mechanism of ISO by metabolite profiling and network pharmacology, providing data for further verification of pharmacological mechanism.
Subject(s)
Furocoumarins , Network Pharmacology , Psoralea , Rats, Sprague-Dawley , Animals , Furocoumarins/pharmacology , Furocoumarins/chemistry , Psoralea/chemistry , Rats , Chromatography, High Pressure Liquid/methods , Male , Osteoporosis/drug therapy , Osteoporosis/metabolism , Quality Control , Biomarkers/analysis , Biomarkers/metabolism , Biomarkers/urine , Fruit/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Mass Spectrometry/methods , Bone Density Conservation Agents/pharmacology , Metabolome/drug effects , Metabolomics/methodsABSTRACT
PURPOSE: The abnormal growth factors-induced epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells was known as a vital pathogenesis of proliferative vitreoretinopathy (PVR). This study aims to explore how survivin inhibition affects EMT induced by epidermal growth factor (EGF) in RPE cells. METHODS: Human primary RPE cells were identified in vitro. EMT in RPE cells was induced by EGF. Inhibition of survivin in RPE cells was accomplished through the use of a survivin inhibitor (YM155) and survivin siRNA. The viability, proliferation and migration of RPE cells was detected by methylthiazol tetrazolium assay, bromodeoxyuridine labeling assay, and wound healing assay, respectively. The EGF receptor /mitogen-activated protein kinase (EGFR/MAPK) proteins and EMT-related proteins were measured by western blot and immunofluorescence assay. RESULTS: EGF induced significant EMT in RPE cells, activated the phosphorylation of EGFR/MAPK signaling proteins, and caused changes to EMT-related proteins. YM155 suppressed RPE cells' viability, proliferation, and migration; induced the phosphorylation of EGFR, JNK, and P38MAPK; and down regulated EGFR and phosphorylated ERK. YM155 also increased expression of E-cadherin and ZO-1 proteins and reduced expression of N-cadherin, Vimentin, and α-SMA proteins. The EGF-induced increase of RPE cell proliferation and migration was constrained by survivin inhibition. Moreover, survivin inhibition in RPE cells suppressed the EGF-caused phosphorylation of EGFR/MAPK proteins and attenuated the EGF-induced reduction of E-cadherin and ZO-1 proteins and increase of N-cadherin, Vimentin, and α-SMA proteins. CONCLUSIONS: Survivin inhibition attenuates EGF-induced EMT of RPE cells by affecting the EGFR/MAPK signaling pathway. Survivin might be a promising target for preventing PVR.
Subject(s)
Cadherins , Cell Movement , Cell Proliferation , Epidermal Growth Factor , Epithelial-Mesenchymal Transition , ErbB Receptors , Imidazoles , MAP Kinase Signaling System , Naphthoquinones , Retinal Pigment Epithelium , Survivin , Humans , Epithelial-Mesenchymal Transition/drug effects , Survivin/metabolism , Survivin/antagonists & inhibitors , ErbB Receptors/metabolism , ErbB Receptors/antagonists & inhibitors , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/cytology , Retinal Pigment Epithelium/drug effects , Epidermal Growth Factor/pharmacology , Naphthoquinones/pharmacology , Cell Proliferation/drug effects , Cell Movement/drug effects , Imidazoles/pharmacology , MAP Kinase Signaling System/drug effects , Cadherins/metabolism , Cell Survival/drug effects , Inhibitor of Apoptosis Proteins/metabolism , Phosphorylation/drug effects , Vimentin/metabolism , Zonula Occludens-1 Protein/metabolism , Cells, Cultured , Actins/metabolism , RNA, Small Interfering/geneticsABSTRACT
Bladder cancer (BC) is one of the most prevalent malignant tumors worldwide, and the incidence is especially higher in males. Extensive evidence has demonstrated the pivotal role of circular RNAs (circRNAs) in BC progression. However, the exact regulatory mechanism of circRNAs in BC remains incompletely elucidated and warrants further exploration. This study screened a novel circRNA-circPGM5 from thousands of circRNAs by high-throughput sequencing. We found that circPGM5, originating from the PGM5 gene, was significantly lower expressed in BC tissues. Quantitative real-time PCR (qRT-PCR) verified that circPGM5 showed relatively low expression in 50 pairs of BC tissues and EJ and T24 cells. Notably, circPGM5 expression was correlated with stage, grade, and lymphatic metastasis of BC. Through RNA-FISH assay, we confirmed that circPGM5 predominantly localized in the cytoplasm. Functionally, overexpression of circPGM5 inhibited the proliferation, migration, and invasion of BC cells in vitro. Remarkably, circPGM5 demonstrated markedly significant tumor growth and metastasis suppression in vivo. Mechanistically, we discovered that circPGM5 upregulated the mitogen-activated protein kinase 10 (MAPK10) expression by influencing the oncogenic miR-21-5p activity through miR-21-5p absorption. This modulation of MAPK10 impacted the phosphorylation of the tumor suppressor Foxo3a in BC. In conclusion, our findings uncovered the tumor-suppressing role of circPGM5 in BC via the miR-21-5p/MAPK10/Foxo3a axis.
Subject(s)
Cell Proliferation , Forkhead Box Protein O3 , MicroRNAs , RNA, Circular , Urinary Bladder Neoplasms , Humans , MicroRNAs/metabolism , MicroRNAs/genetics , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Forkhead Box Protein O3/metabolism , Forkhead Box Protein O3/genetics , RNA, Circular/genetics , RNA, Circular/metabolism , Phosphorylation , Cell Line, Tumor , Male , Animals , Mice , Mice, Nude , Gene Expression Regulation, Neoplastic , Disease Progression , Female , Cell Movement , Middle Aged , Mice, Inbred BALB CABSTRACT
(±)-Hypernumqulins A-H (1-8), eight pairs of enantiomeric quinoline alkaloids fused with an isopentenyl and a germacrane-type sesquiterpenoid, featuring an unprecedented skeleton with 6/6/6/4/10 ring system, were isolated from Hypericum monogynum L. under the guidance of molecular networking strategy. Their structures including absolute configuration were elucidated by NMR spectroscopy analysis, X-ray crystallography and quantum chemical calculation. The proposed [2+2] cycloaddition may play a key biogenic step in building the unexpected skeleton. Most of the isolates exhibited cytotoxicity with IC50 values ranging from 2.82 ± 0.03 to 45.25 ± 1.26 µM against MCF-7, A549 or SGC7901 cells. Furthermore, compounds (±)-1 and (-)-1 could induce apoptosis by upregulating the protein expression level of Bax and downregulating of Bcl-2 in MCF-7 cells. These findings provided the first example of germacrane sesquiterpene quinoline alkaloids, and supported the possibilities for the development of new anti-tumor agents.
Subject(s)
Alkaloids , Antineoplastic Agents, Phytogenic , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Hypericum , Sesquiterpenes , Humans , Alkaloids/chemistry , Alkaloids/pharmacology , Alkaloids/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cycloaddition Reaction , Hypericum/chemistry , Molecular Structure , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/isolation & purification , Stereoisomerism , Structure-Activity Relationship , Quinolines/chemistry , Quinolines/isolation & purification , Quinolines/pharmacologyABSTRACT
Background: Viral diarrhea is one of the major causes of morbidity and mortality in children. This study aimed to conduct etiological surveillance of viral diarrhea in Zhangzhou city, Fujian province, China, from 2017 to 2019 to identify the prevalence, distribution, and characteristics of viral pathogens causing gastrointestinal infections in the region. Methods: Stool samples were collected from patients with acute diarrhea in Zhangzhou city, Fujian province, China, from 2017 to 2019. Rotavirus, norovirus, astrovirus, and adenovirus were detected using fluorescence immunochromatography assay. Results: Of the total 5,627 samples that were collected, at least one of the viruses (rotavirus, norovirus, astrovirus and adenovirus) was found to be positive in 1,422 samples. Rotavirus, norovirus, astrovirus, and adenovirus, were detected in 53.73, 16.68, 15.52, and 14.97%, respectively. Mixed infections were determined in 17.65% of the positive samples. The predominant mixed infections observed were a combination of norovirus and astrovirus, followed by rotavirus and norovirus, and rotavirus and astrovirus. The highest positive rate was observed in the 12-23-month group for rotavirus and adenovirus, while a significantly higher positive rate was observed for norovirus and astrovirus in the 6-11-month group. Conclusion: These findings from this etiological surveillance highlight the significant burden of viral diarrhea in Zhangzhou city, with rotavirus being the predominant pathogen. The identification of common mixed infections provides insights into the complex nature of viral diarrhea transmission. Target interventions and public health strategies should be implemented, particularly during the winter and spring seasons, to prevent and control the spread of viral pathogens causing gastrointestinal infections in this region.
Subject(s)
Diarrhea , Feces , Norovirus , Humans , China/epidemiology , Diarrhea/epidemiology , Diarrhea/virology , Child, Preschool , Infant , Male , Female , Feces/virology , Child , Norovirus/isolation & purification , Rotavirus/isolation & purification , Prevalence , Virus Diseases/epidemiology , Virus Diseases/virology , Adenoviridae/isolation & purification , Adolescent , Infant, Newborn , Seasons , Coinfection/epidemiology , Coinfection/virology , AdultABSTRACT
Although Ru-based materials are among the outstanding catalysts for the oxygen evolution reaction (OER), the instability issue still haunts them and impedes the widespread application. The instability of Ru-based OER catalysts is generally ascribed to the formation of soluble species through the over-oxidation of Ru and structural decomposition caused by involvement of lattice oxygen. Herein, an effective strategy of selectively activating the lattice oxygen around Ru site is proposed to improve the OER activity and stability. Our synthesized spinel-type electrocatalyst of Ru and Zn co-doped Co3O4 showed an ultralow overpotential of 172â mV at 10â mA cm-2 and a long-term stability reaching to 100â hours at 10â mA cm-2 for alkaline OER. The experimental results and theoretical simulations demonstrated that the lattice oxygen site jointly connected with the octahedral Ru and tetrahedral Zn atoms became more active than other oxygen sites near Ru atom, which further lowered the reaction energy barriers and avoided generating excessive oxygen vacancies to enhance the structural stability of Ru sites. The findings hope to provide a new perspective to improve the catalytic activity of Ru-incorporated OER catalysts and the stability of lattice-oxygen-mediated mechanism.
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Low-noise, high-performance long-wave infrared detectors play a crucial role in diverse applications, including in the industrial, security, and medical fields. However, the current performance of long-wave detectors is constrained by the noise associated with narrow bandgaps. Therefore, exploring novel heterostructures for long-wavelength infrared detection is advantageous for the development of compact and high-performance infrared sensing. In this investigation, we present a MoS2/type II superlattice mixed-dimensional van der Waals barrier long-wave infrared detector (Mixed-vdWH). Through the design of the valence band barrier, substantial suppression of device dark noise is achieved, resulting in 2 orders of magnitude reduction in dark current. The device exhibits outstanding performance, with D* reaching 4 × 1010 Jones. This integration approach synergizes the distinctive properties of two-dimensional layered materials (2DLM) with the well-established processing techniques of traditional three-dimensional semiconductor materials, offering a compelling avenue for the large-scale integration of 2DLM.
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BACKGROUND: Farnesoid X receptor (FXR) is a vital receptor for bile acids and plays an important role in the treatment of cholestatic liver disease. In addition to traditional bile acid-based steroidal agonists, synthetic alkaloids are the most commonly reported non-steroidal FXR agonists. Sarmentol H is a nor-sesquiterpenoid obtained from Sedum sarmentosum Bunge, and in vitro screening experiments have shown that it might be related to the regulation of the FXR pathway in a previous study. PURPOSE: To investigate the therapeutic effects of sarmentol H on cholestasis and to determine whether sarmentol H directly targets FXR to mitigate cholestasis. Furthermore, this study aimed to explore the key amino acid residues involved in the binding of sarmentol H to FXR through site-directed mutagenesis. METHODS: An intrahepatic cholestasis mouse model was established to investigate the therapeutic effects of sarmentol H on cholestasis. In vitro experiments, including Co-Ip and FXR-EcRE-Luc assays, were performed to assess whether sarmentol H activates FXR by recruiting the receptor coactivator SRC1. CETSA, SIP, DARTS, and ITC were used to determine the binding of sarmentol H to FXR protein. The key amino acid residues for sarmentol H binding to FXR were analyzed by molecular docking and site-directed mutagenesis. Finally, we conducted in vivo experiments on wild-type and Fxr-/- mice to further validate the anticholestatic target of sarmentol H. RESULTS: Sarmentol H had significant ameliorative effects on the pathological conditions of cholestatic mice induced with ANIT. In vitro experiments suggested that it is capable of activating FXR and regulating downstream signaling pathways by recruiting SRC1. The target validation experiments showed that sarmentol H had the ability to bind to FXR as a ligand (KD = 2.55 µmol/L) and enhance the stability of its spatial structure. Moreover, site-directed mutagenesis revealed that THR292 and TYR365 were key binding sites for sarmentol H and FXR. Furthermore, knockout of the Fxr gene resulted in a significantly higher degree of ANIT-induced cholestatic liver injury than that in wild-type cholestatic mice, and the amelioration of cholestasis or regulatory effects on FXR downstream genes by sarmentol H also disappeared in Fxr-/- cholestatic mice. CONCLUSION: Sarmentol H is an FXR agonist. This is the first study to show that it exerts a significant therapeutic effect on cholestatic mice, and can directly bind to FXR and activate it by recruiting the coactivator SRC1.
Subject(s)
Cholestasis , Nuclear Receptor Coactivator 1 , Receptors, Cytoplasmic and Nuclear , Animals , Humans , Male , Mice , Cholestasis/drug therapy , Disease Models, Animal , Hep G2 Cells , Mice, Inbred C57BL , Molecular Docking Simulation , Mutagenesis, Site-Directed , Receptors, Cytoplasmic and Nuclear/metabolismABSTRACT
Porcine reproductive and respiratory syndrome (PRRS), a highly contagious disease caused by Porcine reproductive and respiratory syndrome virus (PRRSV), results in huge economic losses to the world pig industry. MiRNAs have been reported to be involved in regulation of viral infection. In our study, miR-320 was one of 21 common differentially expressed miRNAs of Meishan, Pietrain, and Landrace pig breeds at 9-h post-infection (hpi). Bioinformatics and experiments found that PRRSV replication was inhibited by miR-320 through directly targeting PRRSV ORF6. In addition, the expression of CCAAT enhancer binding protein beta (CEBPB) was also inhibited by miR-320 by targeting the 3' UTR of CEBPB, which significantly promotes PRRSV replication. Intramuscular injection of pEGFP-N1-miR-320 verified that miR-320 significantly inhibited the replication of PRRSV and alleviated the symptoms caused by PRRSV in piglets. Taken together, miR-320 have significant roles in the infection and may be promising therapeutic target for PRRS.
Subject(s)
MicroRNAs , Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Viral Proteins , Virus Replication , Animals , CCAAT-Enhancer-Binding Protein-beta/metabolism , CCAAT-Enhancer-Binding Protein-beta/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Porcine Reproductive and Respiratory Syndrome/genetics , Porcine Reproductive and Respiratory Syndrome/virology , Porcine respiratory and reproductive syndrome virus/genetics , Porcine respiratory and reproductive syndrome virus/physiology , Swine , Viral Proteins/genetics , Viral Proteins/metabolismABSTRACT
Vertical observations of atmospheric pollutants play crucial roles in a comprehensive understanding of the distribution characteristics and transport of atmospheric pollutants. A hexacopter uncrewed aerial vehicle equipped with miniature monitors was employed to measure the vertical distribution of atmospheric pollutants within a height of 1000 m at a rural site in Xi'an, China, in 2021. The concentrations of carbon monoxide (CO) and particulate matter (PM) showed generally decreasing trends with increasing height. The ozone (O3) concentration showed a general increasing trend with height followed by a gradual decreasing trend. Vertical decrements of PM2.5 and CO from 0 to 1000 m were significantly (p < 0.05) lower on observation days during summer (14.0 ± 8.1 µg m-3 and 8.7 ± 6.6 ppb, respectively), compared with those in winter (78.3 ± 14.1 µg m-3 and 34.8 ± 17.3 ppb, respectively). The horizontal transport of PM and CO mostly occurred in the morning and at night during winter observations at an altitude of 400-500 m. During the winter haze, the PM and CO profile concentrations below 500 m increased substantially with the decrease in the height of the thermal inversion layer. Vertical O3 transportation was observed in the afternoon and evening during summer, and a â¼37.7% (11.6 ppb) increase in ground-level O3 was observed in relation to vertical transport from the upper atmosphere. The results provide insights into the vertical distribution and transport of atmospheric pollutants in rural areas near cities.
Subject(s)
Air Pollutants , Air Pollution , Carbon Monoxide , Environmental Monitoring , Ozone , Particulate Matter , Air Pollutants/analysis , China , Environmental Monitoring/methods , Particulate Matter/analysis , Air Pollution/statistics & numerical data , Ozone/analysis , Carbon Monoxide/analysis , Seasons , Atmosphere/chemistry , AircraftABSTRACT
Utilizing solar energy for photocatalytic CO2 reduction is an attractive research field because of its convenience, safety, and practicality. The selection of an appropriate photocatalyst is the key to achieve efficient CO2 reduction. Herein, we report the synthesis of TiO2/CuPc heterojunctions by compositing CuPc with TiO2 microspheres via a hydroxyl-induced self-assembly process. The experimental investigations demonstrated that the optimal TiO2/0.5CuPc photocatalyst exhibited a significantly enhanced CO2 photoreduction rate up to 32.4 µmol·g-1·h-1 under 300 W xenon lamp irradiation, which was 3.7 times that of the TiO2 microspheres alone. The results of photoelectrochemical experiments indicated that the construction of the heterojunctions by introducing CuPc effectively promoted the separation and transport of photogenerated carriers, thus enhancing the catalytic effect of the photocatalyst.
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Precise implant placement is key to ensuring the success of dental implant surgery. Implant robotic systems have been increasingly adopted for clinical procedures because of their accuracy. Maxillary sinus floor elevation with the Disk-up Sinus Reamer (DSR) may be an effective solution for inadequate posterior maxillary bone height. This clinical treatment combined with an autonomous implant robot with DSR for maxillary sinus floor elevation with simultaneous dental implant surgery may be suitable for clinical practice.
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Previously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016-2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.
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Transjugular intrahepatic portosystemic shunt (TIPS) is a life-saving procedure for patients with severe portal hypertension and persistent variceal bleeding. Stent fracture is a rare and severe complication; however, its cause and mechanisms remain poorly defined. This case helps understand the factors contributing to its occurrence, complications, and subsequent poor outcomes. A 63-year-old male was presented with ruptured bare stent after a TIPS procedure. The upper edge of the bare stent was ruptured, and its fraction subsequently migrated to the entrance of the right atrium. Meanwhile, a mural thrombus was formed in the inferior vena cava. A surgery for the removal of free fracture was planned for preventing the form of pulmonary embolism. Before the surgery, the fracture was shifted to the right inferior pulmonary artery. Therefore, the surgery was canceled for further evaluation. Then, hematemesis suddenly occurred with a high possibility of variceal bleeding and/or gastric ulcer bleeding. Despite comprehensive treatments, the patient symptoms were still worsened with the development of chest tightness, shortness of breath, severe hypoxia, and heart failure. Finally, the patient succumbed to systemic multiorgan failure and death. Taken together, a ruptured unstable stent should be removed as early as the patient is hemodynamically stable, as it is difficult to balance between hemostasis therapy and anticoagulation treatment in patients with liver-cirrhosis-related severe portal hypertension. Physicians should be on high alert of the potential complications of bare stent rapture after TIPS.
Ruptured TIPS stent with a fatal consequence Unstable stent rupture is a life-threatening complication of TIPS and severely complicates the treatment of gastric ulcer bleeding. Early removal of the ruptured stent is necessary to prevent further complications.
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Background: IgA nephropathy (IgAN), a condition posing a significant threat to public health, currently lacks a specific treatment protocol. Research has underscored the potential benefits of traditional Chinese medicine (TCM) for treating IgAN. Nevertheless, the effectiveness of various intervention strategies, such as combining TCM with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), lacks a comprehensive systematic comparison. Therefore, this study aimed to conduct a network meta-analysis to assess the clinical efficacy of ACEIs, ARBs, TCM, and their combinations in treating IgAN to offer novel insights and approaches for the clinical management of IgAN. Methods: A systematic review conducted until November 2023 included relevant literature from databases such as PubMed, Embase, Cochrane, Web of Science, Scopus, CNKI, and Wanfang. Two independent researchers screened and assessed the data for quality. Network and traditional meta-analyses were performed using Stata 18.0 and RevMan 5.3 software, respectively. Outcome measures included 24-h urinary protein quantification (24 hpro), estimated glomerular filtration rate (eGFR), serum creatinine (Scr), blood urea nitrogen (BUN), and adverse event incidence rates (ADRs). Forest plots, cumulative ranking probability curves (SUCRA), and funnel plots generated using Stata 18.0 facilitated a comprehensive analysis of intervention strategies' efficacy and safety. Results: This study included 72 randomized controlled trials, seven interventions, and 7,030 patients. Comparative analysis revealed that ACEI + TCM, ARB + TCM combination therapy, and TCM monotherapy significantly reduced the levels of 24 hpro, eGFR, Scr, and BUN compared to other treatment modalities (p < 0.05). TCM monotherapy demonstrated the most favorable efficacy in reducing eGFR levels (SUCRAs: 78%), whereas the combination of ARB + TCM reduced Scr, 24 hpro, and BUN levels (SUCRAs: 85.7%, 95.2%, and 87.6%, respectively), suggesting that ARB + TCM may represent the optimal intervention strategy. No statistically significant differences were observed among the various treatment strategies in terms of ADR (p > 0.05). Conclusion: The combination of ACEI or ARB with TCM demonstrated superior efficacy compared to ACEI/ARB monotherapy in the treatment of IgAN without any significant ADRs. Therefore, combination therapies can be used to enhance therapeutic outcomes based on individual patient circumstances, highlighting the use of TCM as a widely applicable approach in clinical practice. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023476674.
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Precise reproduction of the preoperatively designed 3-dimensional (3D) implant position is key to seating a prefabricated restoration and restoring esthetics. Static and dynamic computer-aided implant surgery (CAIS) based on the fusion of 3D imaging files have been used to improve implant accuracy. However, both techniques have shortcomings that can be remedied by a robotic system. This clinical report describes the immediate placement of an implant in the anterior esthetic zone by using an autonomous dental implant robotic system (ADIR).
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CA125 (carbohydrate antigen 125) is an important biomarker of ovarian cancer, so developing effective method for its detection is of great significance. In the present work, a novel sandwich-like electrochemical immunosensor (STEM) of CA125 was constructed by preparing nanoribbon-like Ti3C2Tx MXenes (Ti3C2TxNR) to immobilize primary antibody (PAb) of CA125 and UIO-66-NH2 MOFs structure to immobilize second antibody (SAb) and electroactive toluidine blue (Tb) probe. In this designed STEM assay, the as-prepared Ti3C2TxNR nanohybrid offers the advantages in large surface area and conductivity as carrier, and UIO-66-NH2 provided an ideal platform to accommodate SAb and a large number of Tb molecules as signal amplifier. In the presence of CA125, the peak currents of Tb from the formed STEM structure increase with the increase of CA125 level. After optimizing the related control conditions, a wide linear range (0.2-150.0 U mL-1) and a very low detection limit (0.05 U mL-1) of CA125 were achieved. It's thus expected the developed STEM strategy has important applications for the detection of CA125.
Subject(s)
CA-125 Antigen , Electrochemical Techniques , Tolonium Chloride , CA-125 Antigen/analysis , CA-125 Antigen/blood , Immunoassay/methods , Humans , Tolonium Chloride/chemistry , Titanium/chemistry , Biosensing Techniques , Nanotubes, Carbon/chemistry , Limit of Detection , Antibodies, Immobilized/immunology , Antibodies, Immobilized/chemistry , Membrane ProteinsABSTRACT
Japanese encephalitis virus (JEV) infection is considered a global public health emergency. Severe peripheral neuropathy caused by JEV infection has increased disability and mortality rates in recent years. Because there are very few therapeutic options for JEV infection, prompt investigations of the ability of clinically safe, efficacious and globally available drugs to inhibit JEV infection and ameliorate peripheral neuropathy are urgently needed. In this study, we found that high doses of intravenous immunoglobulin, a function inhibitor of acid sphingomyelinase (FIASMA), inhibited acid sphingomyelinase (ASM) and ceramide activity in the serum and sciatic nerve of JEV-infected rats, reduced disease severity, reversed electrophysiological and histological abnormalities, significantly reduced circulating proinflammatory cytokine levels, inhibited Th1 and Th17 cell proliferation, and suppressed the infiltration of inflammatory CD4 + cells into the sciatic nerve. It also maintained the peripheral nerve-blood barrier without causing severe clinical side effects. In terms of the potential mechanisms, ASM was found to participate in immune cell differentiation and to activate immune cells, thereby exerting proinflammatory effects. Therefore, immunoglobulin is a FIASMA that reduces abnormal immune responses and thus targets the ASM/ceramide system to treat peripheral neuropathy caused by JEV infection.