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Hepatocellular carcinoma (HCC) is a common cause of cancer-associated death worldwide. The mitochondrial unfolded protein response (UPRmt) not only maintains mitochondrial integrity but also regulates cancer progression and drug resistance. However, no study has used the UPRmt to construct a prognostic signature for HCC. This work aimed to establish a novel signature for predicting patient prognosis, immune cell infiltration, immunotherapy, and chemotherapy response based on UPRmt-related genes (MRGs). Transcriptional profiles and clinical information were obtained from the TCGA and ICGC databases. Cox regression and LASSO regression analyses were applied to select prognostic genes and develop a risk model. The TIMER algorithm was used to investigate immunocytic infiltration in the high- and low-risk subgroups. Here, two distinct clusters were identified with different prognoses, immune cell infiltration statuses, drug sensitivities, and response to immunotherapy. A risk score consisting of seven MRGs (HSPD1, LONP1, SSBP1, MRPS5, YME1L1, HDAC1 and HDAC2) was developed to accurately and independently predict the prognosis of HCC patients. Additionally, the expression of core MRGs was confirmed by immunohistochemistry (IHC) staining, single-cell RNA sequencing, and spatial transcriptome analyses. Notably, the expression of prognostic MRGs was significantly correlated with sorafenib sensitivity in HCC and markedly downregulated in sorafenib-treated HepG2 and Huh7 cells. Furthermore, the knockdown of LONP1 decreased the proliferation, invasion, and migration of HepG2 cells, suggesting that upregulated LONP1 expression contributed to the malignant behaviors of HCC cells. To our knowledge, this is the first study to investigate the consensus clustering algorithm, prognostic potential, immune microenvironment infiltration and drug sensitivity based on the expression of MRGs in HCC. In summary, the UPRmt-related classification and prognostic signature could assist in determining the prognosis and personalized therapy of HCC patients from the perspectives of predictive, preventative and personalized medicine.
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Carcinoma Hepatocelular , Inmunoterapia , Neoplasias Hepáticas , Mitocondrias , Sorafenib , Respuesta de Proteína Desplegada , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/diagnóstico , Respuesta de Proteína Desplegada/efectos de los fármacos , Pronóstico , Sorafenib/farmacología , Sorafenib/uso terapéutico , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Femenino , Línea Celular TumoralRESUMEN
BACKGROUND: Glechoma longituba, recognized as a medicinal plant, provides valuable pharmaceutical raw materials for treating various diseases. Saline-alkali stress may effectively enhance the medicinal quality of G. longituba by promoting the synthesis of secondary metabolites. To investigate the changes in the primary medicinal components of G. longituba under saline-alkali stress and improve the quality of medicinal materials, Na2CO3 was applied to induce short-term stress under different conditions and the biomass, physiologically active substances and primary medicinal components of G. longituba were measured in this study. RESULTS: Under alkaline salt stress, the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX) were elevated in G. longituba, accompanied by increased accumulation of proline (Pro) and malondialdehyde (MDA). Furthermore, analysis of the medicinal constituents revealed that G. longituba produced the highest levels of soluble sugars, flavonoids, ursolic acid, and oleanolic acid under 0.6% Na2CO3 stress for 48 h, 0.2% Na2CO3 stress for 72 h, 0.4% Na2CO3 stress for 12 h, and 0.4% Na2CO3 stress for 8 h, respectively. CONCLUSIONS: Short-term Na2CO3 stress enhances the synthesis of medicinal components in G. longituba. By manipulating stress conditions, the production of various medicinal substances could be optimized. This approach may serve as a basis for the targeted cultivation of G. longituba, offering potential applications in the treatment of diverse diseases.
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Plantas Medicinales , Estrés Salino , Plantas Medicinales/metabolismo , Plantas Medicinales/química , Carbonatos/metabolismo , Lamiaceae/crecimiento & desarrollo , Lamiaceae/metabolismo , Lamiaceae/fisiología , Lamiaceae/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Malondialdehído/metabolismo , Catalasa/metabolismo , Prolina/metabolismo , Flavonoides/metabolismoRESUMEN
Aqueous rechargeable zinc-ion batteries (ZIBs) are increasingly recognized as promising energy storage systems for mini-grid and mini-off-grid applications due to their advantageous characteristics such as high safety, affordability, and considerable theoretical capacity. However, the long-term cycling performance of ZIBs is hampered by challenges including the uncontrolled dendrite formation, the passivation, and the occurrence of the hydrogen evolution reaction (HER) on the Zn anode. In this study, enhancing ZIB performance by implementing oxide material coatings on Zn metal, serving as a physical barrier at the electrode-electrolyte interfaces to mitigate dendrite growth and suppress the HER is concentrated. Specifically, the mechanisms through which the n-type semiconductor TiO2 coated Zn anode establishes ohmic contact with Zn, and the high-dielectric BaTiO3 (BTO) coated Zn anode fosters Maxwell-Wagner polarization with ferroelectric properties, significantly inhibiting dendrite growth and side reactions, thereby resulting in a highly stable Zn anode for efficient aqueous ZIBs is explored. This advanced BTO/Zn electrode demonstrates an extended lifespan of over 700 h compared to bare Zn and TiO2/Zn anodes. Additionally, full-cell aqueous ZIBs incorporating BTO/Zn//VO2 (B) batteries exhibit superior rate capabilities, high capacity, and sustained cycle life.
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The imperative development of planar on-chip micro-batteries featuring high-capacity electrodes and environmentally safer, cost-effective, and stable systems is crucial for powering forthcoming miniaturized systems-on-chip smart devices. However, research in the area of high-stability micro-batteries is limited due to the complex fabrication process, the stability of micro-electrodes during cycling, and the challenge of maintaining higher capacity within a limited device footprint. In response to this need, this study focuses on providing highly stable and high-capacity micro-electrodes. This involves adding a PEDOT layer between the electrode material and the current collector, applied within a planar polyaniline cathode and zinc anode device structure to enhance charge storage performance. This straightforward strategy not only improves device stability over long-term cycling and reduces charge transfer resistance but also increases charge storage capacities from 17.64 to 19.75 µAh cm- 2 at 0.1 mA cm- 2. Consequently, the Zn-ion micro-batteries achieve notable peak areal energy and power of 18.82 µWh cm- 2 and 4.37 mW cm- 2, respectively. This work proposes an effective strategy to enhance the electrochemical performance of planar micro-batteries, a critical advancement for the development of advanced portable electronics.
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A 3 × 3 coupler multiphase demodulation scheme is proposed to eliminate the impact of working point drifting and the laser relative intensity noise (RIN) on a 3 × 3 coupler interferometric system. An ellipse-fitting algorithm (EFA) is applied to fit the two interference signals of the 3 × 3 coupler in order, then the ATAN algorithm is applied to obtain three noise-containing signals with specific trigonometric relationships. By averaging the three signals, the demodulated phase noise induced from RIN can be effectively eliminated. The experimental results show that compared with the asymmetric demodulation scheme without intensity noise control, the noise floor of the proposed scheme decreases from 4.5 to 1â µrad/âHz at 1â kHz and 2.7 to 0.8â µrad/âHz at 3â kHz. At high frequencies, the average noise floor level is reduced from 10 to 0.9â µrad/âHz, a reduction of about 21â dB. Furthermore, the variation range of the average noise floor is reduced from 5.4 to 0.17â µrad /âHz within 100â s.
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Photocatalytic [3 + 2] cycloadditions and control of stereochemistry have remained a substantial challenge, particularly in the context of heterocycle synthesis; sporadic successful examples have involved enantioselective [3 + 2] photocycloaddition between redox-active direct group-containing cyclopropanes and alkenes for creation of cyclopentanes. Herein, we report a cooperative catalytic system comprising a chiral nickel Lewis acid catalyst and an organic photocatalyst fueled by visible-light irradiation that allows for the hitherto elusive asymmetric [3 + 2] photocycloaddition of ß-keto esters with vinyl azides under redox-neutral conditions. This protocol enables highly enantioselective construction of polycyclic densely substituted 3,4-dihydro-2H-pyrrole heterocycles featuring two contiguous tetrasubstituted carbon stereocenters, including a useful chiral N,O-ketal motif that is not easily accessible with other catalytic methods. Mechanistic studies revealed that the overall reactivity relies on the seamless integration of dual roles of nickel catalysts by the catalytic formation of the substrate/Ni complex, assisting both photoredox event and enantioselective radical addition.
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Zinc metal is a promising candidate for anodes in zinc-ion batteries (ZIBs), but its widespread implementation is hindered by dendrite growth in aqueous electrolytes. Dendrites lead to undesirable side reactions, such as hydrogen evolution, passivation, and corrosion, causing reduced capacity during prolonged cycling. In this study, an approach is explored to address this challenge by directly growing 1D zinc oxide (ZnO) nanorods (NRs) and 2D ZnO nanoflakes (NFs) on Zn anodes, forming artificial layers to enhance ZIB performance. The incorporation of ZnO on the anode offers both chemical and thermal stability and leverages its n-type semiconductor nature to facilitate the formation of ohmic contacts. This results in efficient electron transport during Zn ion plating and stripping processes. Consequently, the ZnO NFs-coated Zn anodes demonstrate significantly improved charge storage performance, achieving 348 mAh g-1 , as compared to ZnO NRs (250 mAh g-1 ) and pristine Zn (160 mAh g-1 ) anodes when evaluated in full cells with V2 O5 cathodes. One significant advantage of ZnO NFs lies in their highly polar surfaces, promoting strong interactions with water molecules and rendering them exceptionally hydrophilic. This characteristic enhances the ability of ZnO NFs to desolvate Zn2+ ions, leading to improved charge storage performance.
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The numerous health benefits of dietary fibers (DFs) justify their inclusion in human diets and biomedical products. Given the short- and long-term human impacts of the COVID-19 virus on human health, the potential of DFs in building immunity against gastrointestinal and respiratory disorders is currently receiving high attention. This paper reviews the physicochemical properties of DFs, together with their immune functions and effects on the gastrointestinal tract and respiratory system mainly based on research in the last ten years. Possible modes of action of DFs in promoting health, especially building immunity, are explored. We seek to highlight the importance of understanding the exact physical and chemical characteristics and molecular behaviors of DFs in providing specific immune function. This review provides a perspective beyond the existing recognition of DFs' positive effects on human health, and offers a theoretical framework for the development of special DFs components and their application in functional foods and other therapeutic products against gastrointestinal and respiratory disorders. DFs enhance immunity from gastrointestinal and respiratory diseases to promote host health.
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BACKGROUND: To explore the role of Trans-rectal Color Doppler Flow Imaging (TR-CDFI) and risk-stratification nomogram in a MRI-directed biopsy pathway and examine its clinical performance, via comparisons between existing four biopsy pathways. METHODS: A Bi-centered retrospective cohort study on biopsy-naïve male population who received ultrasound-guided prostate biopsy from Jan. 2015 to Feb. 2022 was proposed. All enrolled patients should have undergone serum-PSA test, TR-CDFI and multiparametric MRI before biopsy, and subsequently opted for surgical intervention, enabling more accurate pathological grading. We then utilized univariate and multivariate logistic regression analysis to construct a predictive nomogram for risk-stratification. Outcome measurements were overall prostate cancer (PCA) detection rate, clinically significant PCA (csPCA) detection rate, clinically insignificant PCA (cisPCA) detection rate, biopsy avoidance rate and missed csPCA detection rate. Decision curve analysis was used to compare the performances between diagnostic pathways. RESULTS: Under the criteria mentioned above, 752 patients from two centers were included. Reference pathway (biopsy for all) showed that overall PCA detection rate was 46.1%, csPCA and cisPCA detection rates were 32.3% and 13.8% respectively. Risk-based MRI-directed TR-CDFI pathway, which incorporated both TR-CDFI and risk stratification nomogram, exhibited PCA detection rate of 38.7%, csPCA detection rate of 28.7%, cisPCA detection rate of 7.0%, Biopsy avoidance rate of 42.4%, and missed csPCA detection rate of 3.6%. Decision curve analysis revealed that the risk-based pathway held the most net benefit, under the threshold probability level between 0.1 and 0.5. CONCLUSIONS: The risk-based MRI-directed TR-CDFI pathway out-performed other strategies, balancing csPCA detection and biopsy avoidance. This suggested that incorporation of TR-CDFI and risk-stratification nomogram in the early PCA diagnostic procedures could reduce unnecessary biopsies.
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Próstata , Neoplasias de la Próstata , Humanos , Masculino , Próstata/diagnóstico por imagen , Próstata/patología , Nomogramas , Estudios Retrospectivos , Biopsia , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Imagen por Resonancia Magnética/métodos , Biopsia Guiada por Imagen/métodosRESUMEN
INTRODUCTION: To determine the risk factors of hyperlactatemia in pulmonary endarterectomy (PEA) surgery and assess whether elevated blood lactate levels are associated with adverse outcomes. METHODS: In this retrospective observational study, a total of 111 consecutive patients who underwent PEA for chronic thromboembolic pulmonary hypertension at the XXX Hospital between December 2016 and January 2022 were included. We retrospectively evaluated arterial blood samples analyzed intraoperatively. The pre- and intraoperative risk factors for hyperlactatemia and the postoperative outcomes were recorded. RESULTS: Lactate levels gradually increased during surgery. The optimal cut-off lactate level for major postoperative complications, calculated using receiver operating characteristic analysis, was 7.0 mmol/L. Deep hypothermic circulatory arrest (DHCA) duration, nadir hematocrit, and preoperative pulmonary vascular resistance were risk factors for lactate levels >7 mmol/L. Moreover, the intraoperative peak lactate level during PEA under DHCA was found to be a statistically significant predictor of major complications being associated with longer mechanical ventilation time (r = 0.294; p = .003) and intensive care unit length of stay (r = 0.327; p = .001). CONCLUSIONS: Deep hypothermic circulatory arrest duration, nadir hematocrit, and preoperative pulmonary vascular resistance were associated with hyperlactatemia. Increased lactate levels were independent predictors of longer mechanical ventilation time, intensive care unit length of stay, and major complications.
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Ring-opening transformations of donor-acceptor (D-A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium-catalyzed highly diastereo- and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron-withdrawing groups, a subset of D-A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five-membered heterocycles were produced in good yields and with high stereoselectivity (up to 99 % yields, 99 : 1 er and >19 : 1 dr). In-depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H-bonding in stereocontrol.
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Ciclopropanos , Paladio , Paladio/química , Reacción de Cicloadición , Catálisis , Estereoisomerismo , Ciclopropanos/químicaRESUMEN
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by proliferative vascular remodeling. Abnormal vascular smooth muscle cell (VSMC) phenotype switching is crucial to this process, highlighting the need for VSMC metabolic changes to cover cellular energy demand in CTEPH. We report that elevated Wnt family member 5B (WNT5B) expression is associated with vascular remodeling and promotes VSMC phenotype switching via mitochondrial dynamics regulation in CTEPH. Using primary culture of pulmonary artery smooth muscle cells, we show that high WNT5B expression activates VSMC proliferation and migration and results in mitochondrial fission via noncanonical Wnt signaling in CTEPH. Abnormal VSMC proliferation and migration were abolished by mitochondrial division inhibitor 1, an inhibitor of mitochondrial fission. Secreted frizzled-related protein 2, a soluble scavenger of Wnt signaling, attenuates VSMC proliferation and migration by accelerating mitochondrial fusion. These findings indicate that WNT5B is an essential regulator of mitochondrial dynamics, contributing to VSMC phenotype switching in CTEPH.
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Hipertensión Pulmonar , Músculo Liso Vascular , Desdiferenciación Celular , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Células Cultivadas , Humanos , Hipertensión Pulmonar/metabolismo , Dinámicas Mitocondriales/fisiología , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Remodelación Vascular/genética , Proteínas Wnt/metabolismoRESUMEN
BACKGROUND: The global prevalence of ulcerative colitis is increasing, and induction and maintenance of remission is a crucial therapeutic goal. We assessed the efficacy and safety of filgotinib, a once-daily, oral Janus kinase 1 preferential inhibitor, for treatment of ulcerative colitis. METHODS: This phase 2b/3, double-blind, randomised, placebo-controlled trial including two induction studies and one maintenance study was done in 341 study centres in 40 countries. Eligible patients were aged 18-75 years with moderately to severely active ulcerative colitis for at least 6 months before enrolment (induction study A: inadequate clinical response, loss of response to or intolerance to corticosteroids or immunosuppressants, naive to tumour necrosis factor [TNF] antagonists and vedolizumab [biologic-naive]; induction study B: inadequate clinical response, loss of response to or intolerance to any TNF antagonist or vedolizumab, no TNF antagonist or vedolizumab use within 8 weeks before screening [biologic-experienced]). Patients were randomly assigned 2:2:1 to receive oral filgotinib 200 mg, filgotinib 100 mg, or placebo once per day for 11 weeks. Patients who had either clinical remission or a Mayo Clinic Score response at week 10 in either induction study entered the maintenance study. Patients who received induction filgotinib were rerandomised 2:1 to continue their induction filgotinib regimen or to placebo. Patients who received induction placebo continued receiving placebo. The primary endpoint was clinical remission by Mayo endoscopic, rectal bleeding, and stool frequency subscores at weeks 10 and 58. For the induction studies, efficacy was assessed in all randomised patients who received at least one dose of study drug or placebo within that study. For the maintenance study, efficacy was assessed in all patients randomised to any filgotinib treatment group in the induction studies who received at least one dose of study drug or placebo in the maintenance study. Patients who received placebo throughout the induction and maintenance study were not included in the full analysis set for the maintenance study. Safety was assessed in all patients who received at least one dose of the study drug or placebo within each study. This trial is registered with ClinicalTrials.gov, NCT02914522. FINDINGS: Between Nov 14, 2016, and March 31, 2020, we screened 2040 patients for eligibility. 659 patients enrolled in induction study A were randomly assigned to receive filgotinib 100 mg (n=277), filgotinib 200 mg (n=245), or placebo (n=137). 689 patients enrolled into induction study B were randomly assigned to receive filgotinib 100 mg (n=285), filgotinib 200 mg (n=262), or placebo (n=142). 34 patients in induction study A and 54 patients in induction study B discontinued the study drug before week 10. After efficacy assessment at week 10, 664 patients entered the maintenance study (391 from induction study A, 273 from induction study B). 93 patients continued to receive placebo. 270 patients who had received filgotinib 100 mg in the induction study were randomly assigned to receive filgotinib 100 mg (n=179) or placebo (n=91). 301 patients who had received filgotinib 200 mg in the induction study were randomly assigned to receive filgotinib 200 mg (n=202) or placebo (n=99). 263 patients discontinued treatment in the maintenance study. At week 10, a greater proportion of patients given filgotinib 200 mg had clinical remission than those given placebo (induction study A 26·1% vs 15·3%, difference 10·8%; 95% CI 2·1-19·5, p=0·0157; induction study B 11·5% vs 4·2%, 7·2%; 1·6-12·8, p=0·0103). At week 58, 37·2% of patients given filgotinib 200 mg had clinical remission versus 11·2% in the respective placebo group (difference 26·0%, 95% CI 16·0-35·9; p<0·0001). Clinical remission was not significantly different between filgotinib 100 mg and placebo at week 10, but was significant by week 58 (23·8% vs 13·5%, 10·4%; 0·0-20·7, p=0·0420). The incidence of serious adverse events and adverse events of interest was similar between treatment groups. In the induction studies, serious adverse events occurred in 28 (5·0%) of 562 patients given filgotinib 100 mg, 22 (4·3%) of 507 patients given filgotinib 200 mg, and 13 (4·7%) of 279 patients given placebo. In the maintenance study, serious adverse events were reported in eight (4·5%) of 179 patients given filgotinib 100 mg, seven (7·7%) of 91 patients in the respective placebo group, nine (4·5%) of 202 patients in the filgotinib 200 mg group, and no patients in the respective placebo group. No deaths were reported during either induction study. Two patients died during the maintenance study; neither was related to treatment. INTERPRETATION: Filgotinib 200 mg was well tolerated, and efficacious in inducing and maintaining clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. FUNDING: Gilead Sciences.
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Colitis Ulcerosa/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Piridinas/administración & dosificación , Inducción de Remisión , Triazoles/administración & dosificación , Adulto , Método Doble Ciego , Femenino , Humanos , Inhibidores de las Cinasas Janus , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: Elevation of AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) signaling can suppress intracerebral hemorrhage (ICH)-induced neurological impairments. As an isoquinoline alkaloid, Berberine exerts neuroprotective effects in neurological disease models with activated AMPK/PGC1α signaling. AIM: We aim to study the effect of Berberine on ICH-induced brain injury and explore the potential molecular mechanism. METHODS: ICH model was established in mice through intracerebral injection of autologous whole blood, followed by treatment with Berberine. Neurological impairments were assessed by the modified neurological severity score and behavioral assays. Brain edema and blood-brain barrier (BBB) integrity were assessed by water content in the brain, amount of extravasated Evans blue, and BBB tight junction components. Neuroinflammatory responses were assessed by inflammatory cytokine levels. AMPK/PGC1α signaling was examined by AMPK mRNA expression and phosphorylated AMPK and PGC1α protein levels. RESULTS: Berberine (200 mg/kg) attenuated ICH-induced neurological deficits, motor and cognitive impairment, and BBB disruption. Berberine also suppressed ICH-induced inflammatory responses indicated by reduced production of inflammatory cytokines. Finally, Berberine drastically elevated AMPK/PGC1α signaling in the hemisphere of ICH mice. CONCLUSION: Our findings suggest that Berberine plays an important neuroprotective role against ICH-induced neurological impairments and BBB injury, probably by inhibition of inflammation and activation of AMPK/PGC1α signaling.
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Berberina , Barrera Hematoencefálica , Animales , Ratones , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/farmacología , Berberina/farmacología , Berberina/uso terapéutico , Berberina/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Proteínas Quinasas Activadas por AMP/farmacología , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Modelos Animales de Enfermedad , Citocinas/metabolismo , Inflamación/metabolismoRESUMEN
OBJECTIVE: Intracavitary electrocardiography (IC-ECG) has been extensively used for locating the catheter tip of the central venous access devices (CVADs) with favorable safety and accuracy. We aimed to evaluate the efficacy, safety, and cost-effectiveness of IC-ECG-guided catheter tip placement for totally implantable venous access port (TIVAP) by comparing with the standard fluoroscopy method. METHODS: A total of 231 patients who underwent TIVAP implantation from September 2019 to April 2021 were enrolled in the retrospective study. Fluoroscopy and IC-ECG were conducted intraoperatively to confirm the position of catheter tips. Demographic characteristics, surgical data, the catheter tip position, complication rate, and incidence, cost of procedures, and indwelling time were compared between the two groups. Univariate and multivariate analyses were used to identify the risk factors of TIVAP-related complications. RESULTS: There was no significance between the fluoroscopy group and the IC-ECG group in terms of the rate of ideal position (P = 0.733). Nine patients (3.9%) developed TIVAP-related complications. Complication rates and incidence were similar in the fluoroscopy group and the IC-ECG group (3.1% and 0.114/1000 catheter days vs. 4.4% and 0.105/1000 catheter days). The Kaplan-Meier curve showed that there was no significant difference in indwelling time between the 2 groups (Log Rank P = 0.634). Binary logistic regression analysis showed that body mass index (BMI) was an independent risk factor for TIVAP-related complications (OR = 1.334, 95%CI: 1.139 - 1.563, P < 0.001). The IC-ECG group was less costly than the fluoroscopy group (¥9928 ± 362 vs. ¥11762 ± 431, P < 0.001). CONCLUSIONS: IC-ECG-guided catheter tip placement for TIVAP is feasible, safe, and cost-effective, with high accuracy, low risk of complications, and lower cost. It may be considered as an alternative to the standard fluoroscopy method for catheter tip placement of TIVAP.
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Cateterismo Venoso Central , Catéteres Venosos Centrales , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/métodos , Catéteres de Permanencia/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Análisis Costo-Beneficio , Electrocardiografía/métodos , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Acute respiratory and circulatory collapse might occasionally happen after pulmonary endarterectomy (PEA). We aimed to investigate the utilization of extracorporeal membrane oxygenation (ECMO) after PEA and potential risk factors. METHODS: Demographic characteristics, clinical and surgical data were collected for all patients who underwent PEA from December 2016 to June 2022. All factors were compared between patients in the ECMO group and those in the other group. The most characteristic risk factors were obtained by least absolute shrinkage and selection operator regression and support vector machine machine learning, and receiver operating characteristics (ROC) Curve analysis was performed to verify the diagnostic value of the obtained risk factors. RESULTS: A total of 117 patients underwent PEA, and 8 (6.8%) of them received ECMO treatment intraoperatively or postoperatively. There were significant differences between the two groups in terms of cardiac function, pulmonary vascular resistance (PVR), preoperative inflammation and cardiopulmonary bypass time. The PVR and neutrophil-to-lymphocyte ratio (N/L ratio) were the most characteristic risk factors with an area under the ROC curve of 0.847 (95% confidence interval [CI] = 0.7517-0.9420, p = .005) and 0.896 (95% CI = 0.803-0.989, p = .001), respectively. The ECMO group had higher PVR (1549.4 ± 600.7 vs. 952.9 ± 466.9 dyn.s.cm-5 , p = .004) and N/L ratio (6.3 ± 5.6 vs. 2.4 ± 1.7, p = .001). CONCLUSIONS: PVR and N/L ratio can correctly predict who is likely to receive ECMO treatment after PEA. Therefore, addressing the preoperative inflammatory status might be beneficial but further research is needed.
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Oxigenación por Membrana Extracorpórea , Hipertensión Pulmonar , Embolia Pulmonar , Humanos , Oxigenación por Membrana Extracorpórea/efectos adversos , Embolia Pulmonar/cirugía , Embolia Pulmonar/etiología , Arteria Pulmonar/cirugía , Resultado del Tratamiento , Neutrófilos , Hipertensión Pulmonar/terapia , Hipertensión Pulmonar/etiología , Resistencia Vascular , Endarterectomía , Estudios RetrospectivosRESUMEN
BACKGROUND: Deep hypothermic circulatory arrest (DHCA) is nowadays commonly used in pulmonary thromboendarterectomy (PTE). Neurological injury related to DHCA severely impairs the prognosis of patients. However, the risk factors and predictors of neurological injury are still unclear. METHODS: We conducted a prospective observational study, including 82 patients diagnosed as chronic thromboembolic pulmonary hypertension and underwent PTE alone in our center from December 2016 to May 2021. Demographic characteristics, clinical and surgical data, and neurological adverse events were recorded prospectively. Univariate and multivariate analyses were conducted to identify the predictors of neurological injury. RESULTS: Eleven (13.4%) patients exhibited neurological injuries after surgery. Univariate analysis showed that the duration of regional cerebral oxygen saturation (rSO2 ) under 40% (p < .001), the minimum rSO2 (p = .006), and the percentage of decrease in rSO2 (p = .011) were significantly associated with neurological injury. Multivariate analysis showed that the duration of rSO2 under 40% was an independent predictor for postoperative neurological injury (odds ratio = 3.896, 95% confidence interval: 1.812-8.377, p < .001). The receiver operating characteristic curve showed that when the cut-off value was 1.25 min, its sensitivity for predicting neurological injury was 63.6% with a specificity of 88.7%. CONCLUSIONS: The duration of rSO2 under 40% is an independent predictor for neurological injury following PTE. For complicated lesions, more times of circulatory arrest were much safer and more reliable than a prolonged time of a single circulatory arrest. The circulation should be restored as soon as possible, when the rSO2 under 40% is detected, rather than waiting for 5 min.
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Endarterectomía , Saturación de Oxígeno , Circulación Cerebrovascular , Paro Circulatorio Inducido por Hipotermia Profunda/efectos adversos , Endarterectomía/efectos adversos , Humanos , Oxígeno , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: As a marker of the autonomic nervous system, resting heart rate is a predictor of postoperative atrial fibrillation (POAF). However, its predictive value for POAF after pulmonary thromboendarterectomy (PTE) has not been adequately studied. METHODS: We enrolled 97 patients who underwent PTE in our hospital from December 2016 to November 2021 in this retrospective study. Almost all preoperative characteristics, including electrocardiogram, demographics, hematologic and biochemical indices, echocardiography, and pulmonary hemodynamics, were compared between patients with and without POAF. Multivariate logistic regression analysis was used to identify the independent risk factors for POAF after PTE. RESULTS: Overall, 21 patients (21.6%) suffered from POAF after PTE. Compared with patients without POAF, those with POAF were older (p = .049), with a higher resting heart rate (p = .012), and higher platelet count (p = .040). In the binary logistic regression analysis, the resting heart rate (odds ratio [OR] = 1.043, 95% confidence interval [CI] = 1.009-1.078, p = .012) and age (OR = 1.051, 95% CI = 1.003-1.102, p = .037) were independent risk factors for POAF after PTE. The optimal cutoff point of resting heart rate was 89.5 with sensitivity and specificity of 47.6% and 77.6%. When the cutoff value of the age was 54.5, its sensitivity for predicting POAF was 71.4%, with a specificity of 59.2%. CONCLUSIONS: POAF is common after PTE surgery, and the incidence may be underestimated. The resting heart rate and age are independent preoperative risk factors for POAF after PTE. Considering the lower predictive power of the resting heart and age, further large-scale studies are needed.
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Fibrilación Atrial , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/etiología , Puente de Arteria Coronaria/efectos adversos , Endarterectomía , Frecuencia Cardíaca , Humanos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
AIM: It is known that miR-504 can target p53 to promote cancer progression. Our bioinformatics analysis revealed that miR-504 could bind miR-143 host gene (miR143HG), suggesting that miR143HG might also have crosstalk with p53 in cancer progression. This study aimed to analyze the function of miR143HG in glioblastoma (GBM). METHODS: This study selected 64 GBM patients. GBM and non-tumor tissues were obtained from the patients. RT-qPCR was used to analyze gene expression. Survival curve analysis was performed to analyze the prognostic values of miR143HG for GBM. The crosstalk between miR143HG and miR-504 was analyzed by overexpressing them in GBM cells, followed by RT-qPCRs to detect their expression. CCK-8 assay was used to detect the cell proliferation ability. RESULTS: We found that miR143HG was downregulated in GBM and predicted poor survival. The mRNA expression levels of miR143HG and p53 were positively correlated in GBM tissues. Bioinformatics analysis suggested that miR143HG could form base paring with miR-504, which has been reported to target p53. Overexpression experiments revealed that miR143HG overexpression upregulated the expression of p53, while miR-504 overexpression inhibited the effect of miR143HG overexpression on the expression of p53. Moreover, overexpression of miR143HG and p53 decreased GBM cell proliferation, while overexpression of miR-504 increased GBM cell proliferation. In addition, overexpression of miR-504 attenuated the effect of miR143HG overexpression on GBM cell proliferation. CONCLUSION: Therefore, miR143HG may decrease the proliferation of GBM cells by sponging miR-504 to upregulate p53.
Asunto(s)
Glioblastoma , MicroARNs , ARN Largo no Codificante , Humanos , Glioblastoma/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Movimiento Celular , Línea Celular Tumoral , Proliferación Celular/genética , ARN Mensajero , Regulación Neoplásica de la Expresión Génica/genéticaRESUMEN
The synthetic jet piezoelectric air pump is a potential miniature device for electronic cooling. In order to improve the performance of the device, a small-sized synthetic jet piezoelectric air pump is proposed in this work, which is mainly characterized by petal-shaped inlet channels. First, the structure and working principle of the piezoelectric vibrator and the proposed pump are analyzed. Then, three synthetic jet piezoelectric air pumps with different inlet channels are compared. These inlets are the direct channels, the diffuser/nozzle channels, and the petal-shaped channels, respectively. Furthermore, the performance of the synthetic jet piezoelectric air pump with the petal-shaped inlet channels is optimized by orthogonal tests. Finally, the simulation was used to investigate the heat dissipation capability of the synthetic jet piezoelectric pump. The experimental results show that among the three inlet channels, the petal-shaped channel can greatly improve the performance of the pump. The unoptimized pump with petal-shaped channels has a maximum flow rate of 1.8929 L/min at 100 V, 3.9 kHz. Additionally, the optimized pump with petal-shaped channels reaches a maximum flow rate of 3.0088 L/min at 100 V, 3.7 kHz, which is 58.95% higher than the unoptimized one. The proposed synthetic jet piezoelectric air pump greatly improves the output performance and has the advantages of simple structure, low cost, and easy integration. The convective heat transfer coefficient of the synthetic jet piezoelectric pump is 28.8 W/(m2·°C), which can prove that the device has a better heat dissipation capability.