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1.
Cell Commun Signal ; 20(1): 144, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114543

RESUMO

BACKGROUND: Notch signaling is highly conserved and critically involved in cell differentiation, immunity, and survival. Activation of the Notch pathway modulates immune cell functions during the inflammatory response. However, it remains unknown whether and how the macrophage Notch1 may control the innate immune signaling TAK1, and RIPK3-mediated hepatocyte necroptosis in liver ischemia and reperfusion injury (IRI). This study investigated the molecular mechanisms of macrophage Notch1 in modulating TAK1-mediated innate immune responses and RIPK3 functions in liver IRI. METHODS: Myeloid-specific Notch1 knockout (Notch1M-KO) and floxed Notch1 (Notch1FL/FL) mice (n = 6/group) were subjected to 90 min partial liver warm ischemia followed by 6 h of reperfusion. In a parallel in vitro study, bone marrow-derived macrophages (BMMs) were isolated from these conditional knockout mice and transfected with CRISPR/Cas9-mediated ß-catenin knockout (KO) vector followed by LPS (100 ng/ml) stimulation. RESULTS: IR stress-induced Notch1 activation evidenced by increased nuclear Notch intracellular domain (NICD) expression in liver macrophages. Myeloid Notch1 deficiency exacerbated IR-induced liver damage, with increased serum ALT levels, macrophage/neutrophil accumulation, and proinflammatory cytokines/chemokines production compared to the Notch1FL/FL controls. Unlike in the Notch1FL/FL controls, Notch1M-KO enhanced TRAF6, TAK1, NF-κB, RIPK3, and MLKL but reduced ß-catenin activation in ischemic livers. However, adoptive transfer of lentivirus ß-catenin-modified macrophages markedly improved liver function with reduced TRAF6, p-TAK1, RIPK3 and p-MLKL in IR-challenged livers. Moreover, disruption of RIPK3 in Notch1M-KO mice with an in vivo mannose-mediated RIPK3 siRNA delivery system diminished IR-triggered hepatocyte death. In vitro studies showed that macrophage NICD and ß-catenin co-localized in the nucleus, whereby ß-catenin interacted with NICD in response to LPS stimulation. Disruption of ß-catenin with a CRISPR/Cas9-mediated ß-catenin KO in Notch1FL/FL macrophage augmented TRAF6 activation leading to enhanced TAK1 function. While CRISPR/Cas9-mediated TRAF6 KO in Notch1M-KO macrophage inhibited RIPK3-mediated hepatocyte necroptosis after co-culture with primary hepatocytes. CONCLUSIONS: Macrophage Notch1 controls TAK1-mediated innate immune responses and RIPK3-mediated hepatocyte necroptosis through activation of ß-catenin. ß-catenin is required for the macrophage Notch1-mediated immune regulation in liver IRI. Our findings demonstrate that the macrophage Notch1-ß-catenin axis is a crucial regulatory mechanism in IR-triggered liver inflammation and provide novel therapeutic potential in organ IRI and transplant recipients. Video abstract.


Assuntos
Necroptose , Traumatismo por Reperfusão , Animais , Citocinas/metabolismo , Hepatócitos/metabolismo , Isquemia/metabolismo , Lipopolissacarídeos , Fígado/metabolismo , Macrófagos/metabolismo , Manose/metabolismo , Camundongos , Camundongos Knockout , NF-kappa B/metabolismo , RNA Interferente Pequeno/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores , Traumatismo por Reperfusão/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , beta Catenina/metabolismo
2.
Biol Chem ; 401(3): 361-365, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-31655790

RESUMO

CYP20A1 is a well-conserved member of the human cytochrome P450 enzyme family for which no endogenous or xenobiotic substrate is known. We have recently shown that this enzyme has moderate activity towards two proluciferin probe substrates. In order to facilitate the search for physiological substrates we have tested nine additional proluciferins in this study and identified three such probe substrates that give much higher product yields. Using one of these probes, we demonstrate inhibition of CYP20A1 activity by 1-benzylimidazole, ketoconazole and letrozole. Finally, we show that the combination of two common single nucleotide polymorphisms (SNPs) of CYP20A1 leads to an enzyme (CYP20A1Leu97Phe346) with reduced activity.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Imidazóis/farmacologia , Cetoconazol/farmacologia , Letrozol/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Humanos , Estrutura Molecular , Especificidade por Substrato
3.
J Nanosci Nanotechnol ; 12(3): 2534-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22755086

RESUMO

The layered LiNi1/3CO1/3Mn1/3-xMg(x)O2 (x = 0, 0.01, 0.03, 0.05) cathode materials were prepared by solid state reaction, then copper oxide was coated on the product. The structures, morphologies and electrochemical properties of the LiNi1/3Co1/3Mn1/3-xMg(x)O2 and CuO-coated LiNi1/3Co1/3Mn1/3-xMg(x)O2 were characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), and electrochemical tests. The results showed that the electrochemistry properties and cycle performance of magnesium doped LiNi1/3Co1/3Mn1/3O2 and CuO-coated LiNi1/3Co1/3Mn1/3-xMg(x)O2 materials were improved. The optimal doping content of Mg was x = 0.03 in the LiNi1/3Co1/3Mn1/3-xMg(x)O2 samples to achieve high discharge capacity and good cyclic stability, and the first discharge special capacity was 158.5 mAh/g at 0.2 C in the voltage of 2.5-4.3 V, then CuO-coated LiNi1/3Co1/3Mn1/3-0.03Mg0.03O2 was investigated. The electrode reaction reversibility and electronic conductivity were enhanced through Mg-doped and CuO-coated.

4.
BMJ Open ; 12(2): e058461, 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35177466

RESUMO

OBJECTIVE: To evaluate the diagnostic performance of iodine-enhanced multidetector CT and gadoxetic acid-enhanced 3.0 Tesla (T) MRI for detection of hepatocellular carcinoma of patients. DESIGN: Retrospective, multicentre cohort study. SETTING: The Gong'an County People's Hospital, Gong'an County, China and the First People's Hospital of Jingzhou City, China. PARTICIPANTS: Reports of CT, MRI and liver biopsies/histopathology data of a total of 815 patients who at risk were reviewed. PRIMARY AND SECONDARY OUTCOME MEASURES: The lesions that possessed detection in the plain scan phase, enhanced arterial phase and/or enhanced portal phase of CT images and the lesions that possessed enhancements in the plain scan phase, enhanced arterial phase, enhanced portal phase and/or hepatobiliary phases of MRI were considered hepatocellular carcinoma. The decision of hepatocellular carcinoma was made based on the current Liver Imaging and Data Reporting System for diagnosing hepatocellular carcinoma. RESULTS: True positive hepatocellular carcinoma (563 vs 521, p=0.0314), true negative hepatocellular carcinoma (122 vs 91, p=0.0275), false positive hepatocellular carcinoma (88 vs 123, p=0.0121), false negative hepatocellular carcinoma (42 vs 80, p=0.0005), specificity (58.10 vs 42.52, p=0.0478) and negative clinical utility (0.1 vs 0.073, p=0.0386) were superior for gadoxetic acid-enhanced 3.0 T MRI than those of iodine-enhanced multidetector CT. Sensitivity and accuracy for gadoxetic acid-enhanced 3.0 T MRI were 93.06% and 77.40 %, respectively, and those for iodine-enhanced multidetector CT were 86.69% and 75.09 %, respectively. Likelihood to detect hepatocellular carcinoma for gadoxetic acid-enhanced 3.0 T MRI was 0-0.894 diagnostic confidence/lesion, and that for iodine-enhanced multidetector CT was 0-0.887 diagnostic confidence/lesion. CONCLUSION: Gadoxetic acid-enhanced 3.0 T MRI facilitates the confidence of initiation of treatment of hepatocellular carcinoma. LEVEL OF EVIDENCE: III. TECHNICAL EFFICACY STAGE: 4.


Assuntos
Carcinoma Hepatocelular , Iodo , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Meios de Contraste , Gadolínio DTPA , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada Multidetectores/métodos , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade
5.
Asian Spine J ; 16(3): 411-418, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33957742

RESUMO

STUDY DESIGN: This is a multicenter, prospective study. PURPOSE: This study aimed to evaluate the reproducibility of the walking test for patients with lumbar spinal stenosis (LSS). OVERVIEW OF LITERATURE: Walking test is one of the useful procedures to investigate cauda equina syndrome with lumbar spinal stenosis. One the other hands, there were few studies to investigate the reproducibility of this test. METHODS: In this study, we prospectively examined 70 LSS patients with intermittent claudication symptoms at a multicenter outpatient clinic. A walking test was administered at baseline and week 4 to assess patients' walking distance and lower limb pain and numbness. Immediately after the walking test, patients were asked to use the Visual Analog Scale (VAS) to rate their pain and numbness in the front, back, outside, inside, and hip of the lower legs. The reproducibility of the walking test was evaluated using Cohen's κ analysis and intraclass correlation coefficients (ICCs). Meanwhile, the Swiss Spinal Stenosis (SSS) Questionnaire was used to evaluate the severity of the stenosis. RESULTS: The walking distance ICC at baseline and at week 4 remained unchanged at 0.7, with acceptable interobserver reliabilities for lower limb pain and numbness in both legs. The average VAS score for lower leg pain was 23.2±25.2 mm at baseline and 27.4±28.8 mm at week 4, while the corresponding average VAS score for numbness was 23.4±26.7 mm at baseline and 24.8±25.2 mm at week 4. The ICC score was 0.7 for leg pain and 0.7 for numbness. The mean SSS was 30.2±5.5 at baseline and 29.2±5.2 at week 4, and there was no significant difference in the severity. CONCLUSIONS: The walking test for LSS has acceptable reproducibility.

6.
J Tradit Chin Med ; 42(5): 723-731, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36083479

RESUMO

OBJECTIVE: To investigate the effect of Huangqi decoction on renal interstitial fibrosis and its association with the transforming growth factor-ß1 (TGF-ß1) / mitogen-activated protein kinase (MAPK) signaling pathway. METHODS: 120 C57/BL mice were randomly divided into six groups: sham group, Enalapril (20 mg/kg) group, 5/6 nephrectomy model group, and 5/6 nephrectomy model plus Huangqicoction (0.12, 0.36 and 1.08 g/kg respectively) groups. Detecting 24hours urinary protein, blood pressure, serum creatinine, urea nitrogen content changes. Periodic Acid-Schiff stain (PAS) and Masson's trichrome staining was used to observe the renal tissue pathological changes. Protein expression of TGF-ß1, Phosphorylated P38 mitogen activated protein kinases (P-P38), Phosphorylated c-jun N-terminal kinase (P-JNK), Phosphorylated extracellular regulated proteinhnase (P-ERK), Fibroblast-specific protein-1 (FSP-1), Alpha smooth muscle actin (α-SMA), Type III collagen (Collagen III), Connective tissue growth factor (CTGF), Bcl-2 Assaciated X protein (Bax) and B cell lymphoma 2 (Bcl-2) were measured with western blot and immunohistochemical. RESULTS: Both Huangqi decoction and Enalapril improved the kidney function, 24 h urinary protein and the fibrosis in 5/6 nephrectomy mice, Huangqi decoction downregulated the expressions of TGF-ß1, FSP-1, α-SMA, Collagen III and CTGF in a dose-dependent manner, and it has a significant difference ( 0.01) compared with model group.Huangqi decoction downregulated the expressions of P-P38, P-JNK, P-ERK and Bcl-2 in a dose-dependent manner, while upregulated the expression of Bax. CONCLUSIONS: The protective effect of Huangqi decoction for renal interstitial fibrosis in 5/6 nep-hrectomized mice the inhibition of Epithelial-Mesenchymal Transitions and downregulating the TGF-ß1/ MAPK signaling pathway.


Assuntos
Nefropatias , Obstrução Ureteral , Animais , Medicamentos de Ervas Chinesas , Enalapril/metabolismo , Enalapril/farmacologia , Fibrose , Rim , Nefropatias/tratamento farmacológico , Nefropatias/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Nefrectomia , Transdução de Sinais , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Obstrução Ureteral/complicações , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologia , Proteína X Associada a bcl-2/metabolismo
7.
Medicine (Baltimore) ; 101(47): e32059, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36451478

RESUMO

To analyze the pharmacological mechanism of Epimedium in regulating heart failure (HF) based on the network pharmacology method, and to provide a reference for the clinical application of Epimedium in treating HF. Obtaining the main active ingredients and their targets of Epimedium through TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) database. Access to major HF targets through Genecards, OMIM, PharmGKB, Therapeutic Target Database, Drug Bank database. Protein interaction analysis using String platform and construction of PPI network. Subsequently, Cytoscape software was used to construct the "Epimedium active ingredient-heart failure target" network. Finally, the molecular docking is verified through the Systems Dock Web Site. The core active ingredients of Epimedium to regulate HF are quercetin, luteolin, kaempferol, etc. The core targets are JUN, MYC, TP53, HIF1A, ESR1, RELA, MAPK1, etc. Molecular docking validation showed better binding activity of the major targets of HF to the core components of Epimedium. The biological pathways that Epimedium regulates HF mainly act on lipid and atherosclerotic pathways, PI3K-Akt signaling pathway, and chemoattractant-receptor activation. And its molecular functions are mainly DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, and neurotransmitter receptor activity. This study reveals the multi-component, multi-target and multi-pathway mechanism of action of Epimedium in regulating mental failure, and provides a basis for the clinical development and utilization of Epimedium to intervene in HF.


Assuntos
Epimedium , Insuficiência Cardíaca , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Tecnologia , Insuficiência Cardíaca/tratamento farmacológico , Fatores de Transcrição , DNA
8.
Adv Ther ; 39(8): 3749-3765, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35768708

RESUMO

INTRODUCTION: Newer generation bioresorbable scaffolds (BRSs) with thinner struts and improved deliverability are expected to enhance safety and efficacy profiles. Bioheart (Bio-Heart, Shanghai, China) BRS is constructed from a PLLA (poly-l-lactic acid) backbone coated with a PDLLA (poly D-l-lactic acid) layer eluting sirolimus. We report 2-year serial intracoronary imaging findings. METHODS: In this first-in-human study, 46 patients with single de novo lesions in native coronary vessels (vessel size 3.0-3.75 mm, lesion length ≤ 25 mm) were enrolled at a single institution. Baseline intravascular ultrasound (IVUS) and post-implantation IVUS and optical coherence tomography (OCT) examinations were mandatory. After successful implantations of BRS, the 46 patients were randomized to two different follow-up cohorts in a 2:1 ratio. Thirty patients in cohort 1 had to undergo angiography, IVUS, and OCT follow-ups at 6 and 24 months, respectively. The 16 patients in cohort 2 underwent the same types of imaging follow-ups at 12 and 36 months, respectively. Clinical follow-ups were scheduled uniformly in both cohorts at 1, 6, and 12 months and annually up to 5 years for all patients. RESULTS: Between August and November 2016, a total of 54 patients were assessed. However, 8 patients could not meet all the inclusion criteria; thus, the remaining 46 patients (age 57.5 ± 8.7 years, 34.8% female, 50.0% with unstable angina, 26.1% diabetics) with 46 target lesions were enrolled in this study. All patients in both cohorts were required to complete clinical follow-up uniformly and regularly. In cohort 1, one patient had definite scaffold thrombosis within 6 months of follow-up; thus, after 6 months, cohort 1 had 96.7% patients . Imaging follow-up was available in 24 patients, and in-scaffold late loss was 0.44 ± 0.47 mm; intracoronary imaging confirmed the late loss was mainly due to to neointimal hyperplasia, but not scaffold recoil. CONCLUSIONS: Serial 2-year clinical and imaging follow-up results confirmed the preliminary safety and efficacy of Bioheart BRS for treatment of simple coronary lesions.


Assuntos
Fármacos Cardiovasculares , Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Implantes Absorvíveis , Idoso , Fármacos Cardiovasculares/uso terapêutico , China , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Sirolimo/uso terapêutico , Tomografia de Coerência Óptica , Resultado do Tratamento
9.
Environ Technol ; 42(26): 4134-4144, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32188338

RESUMO

Aiming at exploring an effective photocatalytic adsorbent for organic dye removal, a series of heterostructured TiO2@HKUST-1 photocatalysts, by incorporating HKUST-1 with different TiO2 nanoparticles loading, were prepared by single-step hydrothermal method. The morphology and surface characteristics of the as-prepared TiO2@HKUST-1were analyzed using SEM, HRTEM, XRD, FTIR, UV-vis DRS, and Photoluminescence techniques. The adsorption-photocatalytic degradation of the model dye methylene blue (MB) on the catalysts was investigated. It was indicated that the introduction of a certain amount of TiO2 on the surface of HKUST-1 could improve the transfer and separation of the photogenerated charge carriers, resulting in the enhanced photocatalytic activity. The optimal 0.02TiO2@HKUST-1 exhibited the highest MB removal rate with about 4.4 and 19.3 times as high MB removal efficiency as that of HKUST-1 and TiO2, respectively. Heterostructured TiO2@HKUST-1 materials for the removal of MB involved the integrated adsorption and visible light photocatalysis. Meanwhile, the composite exhibited good reusability in the process of cyclic experiments. Therefore, this work provides a potential MOF-based photocatalytic adsorbent for organic dye removal.


Assuntos
Azul de Metileno , Titânio , Adsorção , Estruturas Metalorgânicas
10.
Artigo em Inglês | MEDLINE | ID: mdl-34899954

RESUMO

BACKGROUND: Curcumin, a polyphenolic constituent from Curcuma longa, possesses antioxidant, hypolipidemic, and antidiabetic properties and has been reported to protect against diabetic kidney disease (DKD); however, the effect is inconsistent. OBJECTIVE: This systematic review and meta-analysis aimed to investigate the effect of curcumin supplementation on renal function, lipid profile, blood pressure, and glycemic control in DKD. METHODS: A systematic and comprehensive literature search of interrelated randomized controlled trials (RCTs) was conducted in PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov from inception to July 30, 2021. Two investigators independently extracted data and assessed the risk of bias. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated to describe the effect sizes using a fixed-effect model. Statistical analysis was performed using STATA 14.0 and RevMan 5.3. RESULTS: Five RCTs involving 290 participants with DKD were included. Curcumin supplementation significantly improved the serum creatinine (WMD: -0.16 mg/dL, 95% CI: -0.3 to -0.02, P = 0.029, I 2 = 0%, moderate certainty), total cholesterol (WMD: -10.13 mg/dL, 95% CI: -17.84 to -2.14, P = 0.01, I 2 = 0%, moderate certainty), systolic blood pressure (WMD: 3.94 mmHg, 95% CI: 1.86 to 6.01, P < 0.01, I 2 = 33.5%, moderate certainty), and fasting blood glucose (WMD: -8.29 mg/dL, 95% CI: -15.19 to -1.39, P = 0.019, I 2 = 43.7%, moderate certainty) levels; however, it had no significant effects on blood urea nitrogen, proteinuria, triglyceride, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and diastolic blood pressure levels. CONCLUSIONS: Curcumin may provide great potential effects against DKD. More large-scale and high-quality RCTs are required to confirm these findings.

11.
Artigo em Zh | WPRIM | ID: wpr-1003780

RESUMO

Diabetic kidney disease (DKD) is the main cause of end-stage renal disease. Its high prevalence, mortality rate, and medical cost bring a heavy economic burden to society and families, and DKD has become one of the most important public health problems. Intestinal microecology is the most important and complex micro-ecosystem in the human body, which is involved in important life activities such as material and energy metabolism, immune system regulation, and signal transduction, thereby maintaining the dynamic balance of the human internal environment. The dynamic balance between the intestinal microecology and the body is essentially a Yin-Yang balance. Once this balance is broken, intestinal microbiota imbalance, intestinal mucosal barrier damage, immune dysfunction, and reduction of metabolite short-chain fatty acids (SCFAs) will occur, which play an important role in the progression of DKD. From the perspective of the Yin-Yang theory of traditional Chinese medicine (TCM), the imbalance of intestinal microecology in DKD is equivalent to the excessive or insufficient constraint of Yin and Yang, or Yin deficiency affecting Yang, or Yang deficiency affecting Yin, or waning and waxing of Yin and Yang. For different pathogenesis changes, "Yin disease treated through Yang", "treating Yin for Yang", or "treating Yang for Yin" methods are adopted to regulate intestinal microbiota, inhibit immune inflammation, protect intestinal mucosal barrier, and increase SCFAs through TCM, thereby reconciling Yin and Yang to achieve the condition where "Yin is at peace and Yang is compact". Based on the Yin-Yang theory, this paper intended to interpret the scientific connotation of TCM in the treatment of DKD with intestinal microecology as the target and TCM in the treatment of DKD by regulating intestinal microecology as the breakthrough point to provide a novel insight for the occurrence and development of DKD and the mechanism of TCM.

12.
China Pharmacy ; (12): 101-106, 2024.
Artigo em Zh | WPRIM | ID: wpr-1005222

RESUMO

OBJECTIVE To provide reference for the adjustment of antibiotic treatment regimens, identification of adverse reactions, and individualized pharmaceutical care for melioidosis sepsis (MS). METHODS Clinical pharmacists participated in the intensive and eradicating therapeutic processes for an MS patient by using blood concentration and gene detection. Based on the literature, antibiotic treatment regimens of MS were adjusted by determining the blood concentrations of β-lactam and trimethoprim/ sulfamethoxazole (TMP/SMZ) and calculating PK/PD parameters. The causes of adverse drug reactions were analyzed and addressed by detecting drug-related gene polymorphisms through high-throughput sequencing. RESULTS Clinical pharmacists used blood concentration and genetic testing methods to propose adjustments to imipenem-cilastatin sodium dosage and analyze the causes of various adverse drug reactions. PK/PD targets were calculated by measuring the blood concentrations of β-lactam and TMP/SMZ. Clinical pharmacists explained to clinical doctors the compliance status of patients with melioidosis in sepsis and non- sepsis stages through reviewing guidelines and literature; the results of blood concentration and genetic test were used to analyze the correlation of neurotoxicity of MS patients with B14) IMP cmin, and it was found that nephrotoxicity was not related to the cmax of TMP/SMZ, but to the patient’s water intake. After whole-process antibiotic treatment, the patient’s condition improved and was discharged, and the adverse reactions were effectively treated. CONCLUSIONS Clinical pharmacists use blood concentration and genetic tests to assist clinicians in formulating MS treatment regimens, and provide whole-course pharmaceutical care for a MS patient. This method has improved the safety and effectiveness of clinical drug therapy.

13.
China Occupational Medicine ; (6): 145-149, 2023.
Artigo em Zh | WPRIM | ID: wpr-996538

RESUMO

Objective: To study the relationship between compassion fatigue and overall happiness among firefighters, and the mediating role of psychological stress and positive psychological capital. Methods: A total of 894 firefighters in Shandong Province were selected as the research subjects using purposive sampling method. Questionnaires including the Professional Quality of Life Scale, the Military Psychological Stress Self-Assessment Scale, the Positive Psychological Capital Scale, and the Overall Happiness Scale were used for data collection. Results: The scores of compassion fatigue, psychological stress, positive psychological capital and overall happiness among firefighters were (40.1±13.5), (13.9±3.9), (133.0±26.4) and (84.9±15.2), respectively. There were correlations between compassion fatigue, psychological stress, positive psychological capital and overall happiness (all P<0.01). Psychological stress partially mediated the relationship between compassion fatigue and overall happiness, and the mediating effect accounted for 27.0% of the total effect. Positive psychological capital moderated the front half path and the direct path between compassion fatigue and overall happiness (all P<0.01). Conclusion: Compassion fatigue can directly or indirectly affect the firefighters' overall happiness. Psychological stress plays a partial mediating role and positive psychological capital plays a moderating role between compassion fatigue and overall happiness.

14.
Clinical Medicine of China ; (12): 151-156, 2023.
Artigo em Zh | WPRIM | ID: wpr-992485

RESUMO

Primary biliary cholangitis (PBC), also known as primary biliary cirrhosis, is an autoimmune-mediated chronic intrahepatic cholestatic disease, which is more common in middle-aged and elderly women. Cholestasis can be secondary to hepatic osteodystrophy, with osteoporosis (OP) being the most prominent. OP in PBC patients can increase the risk of fracture and seriously affect the survival and quality of life of patients, thus affecting the prognosis of the disease. In recent years, a large number of studies have shown that with the increase of the incidence and prevalence of PBC, the incidence and prevalence of OP are also on the rise. Therefore, in order to improve the survival and quality of life of patients with PBC combined with OP, how to effectively treat it has become the focus of more and more attention and research.

15.
Chinese Journal of Biotechnology ; (12): 3628-3643, 2023.
Artigo em Zh | WPRIM | ID: wpr-1007982

RESUMO

Small-molecule anticancer drugs inhibited tumor growth based on targeted inhibition of specific proteins, while most of oncogenic proteins are "undruggable". Proteolysis targeting chimeras (PROTAC) is an attractive and general strategy for treating cancer based on targeted degradation of oncogenic proteins. This review briefly describes the peptide-based PTOTAC and small molecule-based PROTAC. Subsequently, we summarize the development of targeted delivery of PROTAC, such as targeting molecule-mediated targeted delivery of PROTAC, nanomaterial-mediated targeted delivery of PROTAC and controllable activation of small-molecular PROTAC prodrug. Such strategies show potential application in improving tumor selectivity, overcoming off-target effect and reducing biotoxicity. At the end, the druggability of PROTAC is prospected.


Assuntos
Humanos , Quimera de Direcionamento de Proteólise , Nanoestruturas , Neoplasias/tratamento farmacológico , Proteólise
16.
Artigo em Zh | WPRIM | ID: wpr-990185

RESUMO

Objective:Based on the core competence of stroke certified registered nurses, this study construct the theoretical raining curriculum system for stroke certified registered nurses and made a preliminary evaluation.Methods:Using Delphi expert consultation method and based on literature research, the first draft of training course for stroke certified registered nurses was formed. In the form of Email, 14 experts in the field of stroke care who met the selection criteria were sent a questionnaire, and two rounds of consultation were conducted. The theoretical raining curriculum system for the training of stroke specialist nurses was constructed; the purpose sampling method was used to evaluate the application effect of the stroke specialist nursing theoretical training curriculum system through the theoretical performance and satisfaction evaluation of 127 trainees who participated in the first phase of the stroke specialist nursing theoretical training curriculum.Results:The recovery rate and effective rate of the two rounds of expert consultation questionnaire were 14/14, the authority coefficient of the second round of expert consultation was 0.94, and the expert Kandall coordination coefficients of the first, second and third-level indexes were 0.356, 0.216, 0.207 respectively ( P<0.05). The training curriculum of stroke specialist nurses finally formed included 5 primary indicators (Professional practice concept, general nursing knowledge, stroke diagnosis and treatment, acute stroke nursing management, secondary prevention of cerebrovascular disease), 21 secondary indicators and 63 tertiary indicators. The Analytic hierarchy process was used to determine the weight coefficients of all levels of indicators, and the consistency Ratio <0.1. Based on the curriculum system as the content framework, theoretical courses were set up to train stroke specialist nurses. 109 trainees completed the post-training assessment. Before training, the qualified rate of theoretical performance of stroke certified registered nurses was 77.95% (99/127), and after training, the qualified rate of theoretical performance of stroke certified registered nurses was 100% (109/109). The difference was statistically significant ( χ 2=27.60, P<0.01). The excellent rate of theoretical performance of stroke certified registered nurses before training was 35.43% (45/127), and 100% (109/109) after training, the difference was statistically significant ( χ 2=24.17, P<0.01).The average score of the trainees′ satisfaction was (38.90±2.55) points. Conclusions:The theoretical raining curriculum system for stroke certified registered nurses setting constructed in this study standardizes the training system of stroke nurses to a certain extent, and provides a basis for the construction of homogeneous training courses in China in the future.

17.
Artigo em Zh | WPRIM | ID: wpr-990172

RESUMO

Objective:To sinicize the Gerontological nursing competence (GeroNursingCom) scale and test its reliability and validity.Methods:This was a cross sectional investigation. The Brislin translation model was used for normal translation and back-translation, cultural adjustment and pre-investigation. The Chinese version of the GeroNursingCom scale was formed according to expert comments. From September to October 2021, a questionnaire survey was conducted by convenient sampling method on 312 nursing undergraduates from 3 undergraduate medical schools in Kunming to test its reliability and validity.Results:The Chinese version of the GeroNursingCom scale included 11 dimensions and a total of 50 items. The overall Cronbach′s α coefficient of the scale was 0.909, the Cronbach′s α coefficient of each dimension was 0.625-0.912, the split-half reliability coefficient was 0.768, and the test-retest reliability was 0.845. The scale-level content validity value was 0.930, and the item-level content validity value was 0.830-1.000. Exploratory factor analysis extracted a total of 11 common factors with eigenvalues>1, and the common interpretation of the results was 68.374%.Conclusions:The Chinese version of GeroNursingCom scale has good reliability and validity, and can be used as a tool to evaluate nursing interns' geriatric nursing ability.

18.
Artigo em Zh | WPRIM | ID: wpr-989234

RESUMO

Objective:To investigate the correlation between serum uric acid to albumin ratio (UAR) and large-artery atherosclerosis (LAA), its severity and short-term outcome.Methods:Patients with acute ischemic stroke admitted to the Department of Neurology, the Affiliated Hospital of Qingdao University from September 2017 to August 2022 were retrospectively enrolled. They were classified into LAA and non-LAA according to the TOAST etiological criteria. Patients with LAA were further divided into mild stroke group (≤8) and moderate to severe stroke group (>8) according to the National Institutes of Health Stroke Scale score at admission, and good outcome group (≤2) and poor outcome group (>2) according to the modified Rankin Scale score at discharge. Multivariate logistic regression analysis was used to determine the correlation between UAR and LAA, its severity and short-term outcome. The predictive value of UAR for poor outcomes in patients with LAA was evaluated by receiver operating characteristic (ROC) curve. Results:A total of 4 178 patients with acute ischemic stroke were enrolled, including 2 751 males (65.8%), aged 61.95±10.73 years. There were 2 000 (47.9%) patients with LAA, including 1 112 (55.6%) mild stroke and 888 (44.4%) moderate to severe stroke; 813 (40.65%) had good short-term outcomes and 1 187 (59.35%) had poor outcomes. UAR in the LAA group was significantly higher than that in the non-LAA group ( P<0.05). In patients with LAA, the UAR of the moderate to severe stroke group and the short-term poor outcome group were significantly higher than that of the mild stroke group and the short-term good outcome group, respectively (all P<0.05). Multivariate logistic regression analysis showed that the UAR was an independent risk factor for LAA (odds ratio [ OR] 1.043, 95% confidence interval [ CI] 1.016-1.071; P=0.002), its severity ( OR 2.000, 95% CI 1.860-2.151; P<0.001), and short-term poor outcomes ( OR 1.456, 95% CI 1.379-1.537; P<0.001). ROC curve analysis showed that the area under the curve of UAR for predicting short-term poor outcomes in patients with LAA was 0.727 (95% CI 0.704-0.750; P<0.001). The optimal cutoff value was 6.62, and the sensitivity and specificity were 86.6% and 56.7%, respectively. The area under the curve of UAR for predicting short-term poor outcomes in patients with LAA was greater than that predicted solely by uric acid and albumin. Conclusions:UAR is associated with LAA, its severity and poor prognosis, and has higher predictive value for poor outcomes in patients with LAA.

19.
Artigo em Zh | WPRIM | ID: wpr-993300

RESUMO

Objective:To analyze the value of laminin γ2 (LAMC2) in the diagnosis of hepatocellular carcinoma (HCC) and the difference in patients with different types of microvascular invasion (MVI).Methods:A cohort of 100 patients with HCC who underwent surgical treatment at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital from January 2021 to March 2022 were prospectively enrolled. There were 80 males and 20 females, aged (55.7±11.1) years. The data of 17 patients with hepatic hemangioma without cirrhosis who underwent operation at the same hospital during the study period were collected to serve as the control group (6 males, 11 females), aged (42.8±9.8) years. LAMC2 in serum was determined by enzyme linked immunosorbent assay. The levels of alpha-fetoprotein (AFP) and LAMC2 were compared between the two groups, and receiver operating characteristic (ROC) curves were drawn to compare these two markers in the diagnosis of HCC. The LAMC2 of different MVI patients were compared.Results:The levels of LAMC2 and AFP were 1 334.2(838.9, 2 656.0) pg/ml and 19.0(4.6, 778.6) μg/L in the HCC group, which were significantly higher than 375.2(221.2, 691.7)pg/ml and 3.3(2.5, 3.5) μg/L in the control group ( Z=-4.32, -4.63, both P<0.001). The areas under the ROC curve were 0.829(95% CI: 0.748-0.892) for LAMC2 and 0.852(95% CI: 0.769-0.910) for AFP, and was 0.949(95% CI: 0.911-0.988) for using both in the diagnoses. The diagnostic efficacy of combining LAMC2 and AFP was significantly better than that of LAMC2 alone and AFP alone (area under ROC: Z=3.15, 3.07, P=0.002, 0.002). When the patients were divided into the M0 group (61 patients), the M1 Group (25 patients) and the M2 Group (14 patients) based on MVIs, the concentrations of LAMC2 were 1 168.6(834.3, 2 521.4) pg/ml, 942.2(614.0, 2 056.6) pg/ml and 3 128.4(1 852.7, 7 191.3) pg/ml, respectively. The level of LAMC2 in the M2 group was significantly higher than that in the M0 and M1 groups ( Z=-3.46, -3.32, P=0.001, 0.004). Conclusion:The diagnostic efficacy of LAMC2 combined with AFP for HCC was significantly higher than that of either LAMC2 alone or AFP alone. Serum LAMC2 levels were significant different among the groups of HCC patients with different types of MVI.

20.
J Orthop Translat ; 14: 57-62, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30035033

RESUMO

BACKGROUND: Surgical masks (SMs) are used to reduce bacterial shedding from the mouth, nose and face. This study aimed to investigate whether SMs may be a potential source of bacterial shedding leading to an increased risk of surgical site infection. METHODS: Bacterial contamination of the SMs was tested by making an impression of the external surface of the mask on sterile culture media immediately. We investigated the difference in bacterial counts between the SMs worn by surgeons and those placed unused in the operating room (OR), and the bacterial count variation with indicated wearing time. Moreover, the difference in bacterial counts on the external surface between the first and second layers of double-layered SMs was also assessed. RESULTS: The bacterial count on the surface of SMs increased with extended operating times; significant difference was found between the 4- to 6-hour and 0-hour groups (p < 0.05). When we analysed the bacterial counts from the same surgeon, a significant increase was noted in the 2-hours group. Moreover, the bacterial counts were significantly higher among the surgeons than the OR. Additionally, the bacterial count of the external surface of the second mask was significantly higher than that of the first one. CONCLUSIONS: The source of bacterial contamination in SMs was the body surface of the surgeons rather than the OR environment. Moreover, we recommend that surgeons should change the mask after each operation, especially those beyond 2 hours. Double-layered SMs or those with excellent filtration function may also be a better alternative. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study provides strong evidence for the identification that SMs as source of bacterial contamination during operative procedures, which should be a cause for alarm and attention in the prevention of surgical site infection in clinical practice.

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