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Telocytes (TCs), a novel type of interstitial cells, have been found to participate in tissue protection and repair. In this study, we investigated the antioxidative effects of TCs in inflamed lungs of mice. Acute respiratory distress syndrome (ARDS) mice were used as models of inflamed lungs of mice. Gene sequencing was used to screen the differentially expressed miRNAs in TCs after lipopolysaccharide (LPS) stimulation. AntagomiR-146a-5p-pretreated TCs were first injected into mice, and antioxidant activity of TCs was estimated. TCs, RAW264.7 cells, and MLE-12 cells were collected for the detection of expressions of NOX1-4, DUOX1-2, SOD1-3, GPX1-2, CAT, Nrf2, miR-146a-5p, and miR-21a-3p after LPS stimulation. Silencing miRNAs were delivered to examine the involved signaling pathways. Oxidative stress was examined by measuring malondialdehyde (MDA) levels. We found that microRNA-146a-5p and microRNA-21a-3p were upregulated in TCs after LPS stimulation. ARDS mice that were preinfused with TCs had lower lung tissue injury scores, lung wet-dry ratios, white blood cell counts in alveolar lavage fluid and lower MDA concentrations in lung tissue. However, in antagomiR-146a-5p-pretreated ARDS mice, the infusion of TCs caused no corresponding changes. After LPS stimulation, DUOX2 and MDA concentrations were downregulated in TCs, while DUOX2 was restored by antagomiR-146a-5p in TCs. Dual-luciferase reporter assay confirmed that CREB1 was downregulated by miR-146a-5p, while DUOX2 was downregulated by CREB1, which was confirmed by treating TCs with a specific CREB1 inhibitor. This study demonstrates that LPS stimulation upregulates miR-146a-5p in TCs, which downregulates the CREB1/DUOX2 pathway, resulting in a decrease in oxidative stress in cultured TCs. TCs reduce LPS-induced oxidative stress by decreasing DUOX2 in inflamed lungs of mice.
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Oxidasas Duales , Pulmón , Estrés Oxidativo , Síndrome de Dificultad Respiratoria , Telocitos , Animales , Antagomirs/metabolismo , Oxidasas Duales/genética , Oxidasas Duales/metabolismo , Lipopolisacáridos , Pulmón/metabolismo , Pulmón/patología , Ratones , MicroARNs/genética , Telocitos/metabolismoRESUMEN
BACKGROUND: Telocytes (TCs) are newly identified interstitial cells that participate in tissue protection and repair. The present study investigated the mechanisms underlying the protective effect of TCs in a mouse model of respiratory distress. METHODS: The mouse model of acute respiratory distress syndrome (ARDS) was established by intratracheal instillation of lipopolysaccharide (LPS). After instillation of TCs culture medium, lung injury was assessed, and angiogenesis markers, including CD31 and endothelial nitric oxide synthase (eNOS), were detected by immunofluorescence. Bioinformatics analysis was used to screen significantly differentially expressed microRNAs (miRNAs) in cultured TCs stimulated with LPS, and the regulation of downstream angiogenesis genes by these miRNAs was analysed and verified. PI3K subunits and pathways were evaluated by using a PI3K p110α inhibitor to study the involved mechanisms. RESULTS: In ARDS mice, instillation of TCs culture medium ameliorated LPS-induced inflammation and lung injury and increased the protein levels of CD31 and eNOS in the injured lungs. A total of 7 miRNAs and 1899 mRNAs were differentially regulated in TCs stimulated with LPS. Functional prediction analysis showed that the differentially expressed mRNAs were enriched in angiogenesis-related processes, which were highly correlated with miR-21a-3p. Culture medium from TCs with miR-21a-3p inhibition failed to promote angiogenesis in mouse models of LPS-induced ARDS. In cultured TCs, LPS stimulation upregulated the expression of miR-21a-3p, which further targeted the transcription factor E2F8 and decreased Notch2 protein expression. TCs culture medium enhanced hemangioendothelioma endothelial cells (EOMA cells) proliferation, which was blocked by the miR-21a-3p inhibitor. The PI3K p110α inhibitor decreased vascular endothelial growth factor levels in LPS-stimulated TCs and reversed the enhancing effect of TCs culture medium on EOMA cells proliferation. CONCLUSIONS: TCs exerted protective effects under inflammatory conditions by promoting angiogenesis via miR-21a-3p. The PI3K p110α subunit and transcriptional factor E2F8 could be involved in this process.
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MicroARNs/metabolismo , Neovascularización Fisiológica , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Síndrome de Dificultad Respiratoria/genética , Serina-Treonina Quinasas TOR/metabolismo , Telocitos/metabolismo , Animales , Línea Celular , Proliferación Celular/genética , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Inflamación/genética , Inflamación/patología , Lipopolisacáridos , Masculino , Ratones Endogámicos C57BL , Modelos Biológicos , Neovascularización Fisiológica/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reproducibilidad de los Resultados , Síndrome de Dificultad Respiratoria/patología , Transducción de SeñalRESUMEN
Several studies reveal that allergic rhinitis (AR) is a significant risk factor of systemic lupus erythematosus (SLE). However, studies investigating the common pathogenesis linking AR and SLE are lacking. Our study aims to search for the shared biomarkers and mechanisms that may provide new therapeutic targets for preventing AR from developing SLE. GSE50223 for AR and GSE103760 for SLE were downloaded from the Gene Expression Omnibus (GEO) database to screen differentially expressed genes (DEGs). The Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to explore the functions of shared DEGs. Hub genes were screened by cytoHubba (a plugin of Cytoscape) and validated in another two datasets. Gene set enrichment analysis (GSEA) and single-sample Gene set enrichment analysis (ssGSEA) algorithm were applied to understand the functions of hub gene. ENTPD1 was validated as a hub gene between AR and SLE. GSEA results revealed that ENTPD1 was associated with KRAS_SIGNALING_UP pathway in AR and related to HYPOXIA, TGF_BETA_SIGNALING and TNFA_SIGNALING_VIA_NFKB pathways in SLE. The expression of ENTPD1 was positively correlated with activated CD8 T cell in both diseases. Thus, ENTPD1 may be a novel therapeutic target for preventing AR from developing SLE.
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Biomarcadores , Lupus Eritematoso Sistémico , Rinitis Alérgica , Humanos , Lupus Eritematoso Sistémico/genética , Rinitis Alérgica/genética , Ontología de Genes , Perfilación de la Expresión Génica , Bases de Datos Genéticas , Transducción de Señal , Redes Reguladoras de Genes , Biología Computacional/métodosRESUMEN
Background: Premature ovarian failure (POF) is a prevalent and severe condition that impairs female health but there is currently no effective treatment available to restore ovarian function. Human amniotic epithelial cells (hAECs) exhibit ovarian protection in pre-clinical models. Thus, we conducted a single-arm, phase 1 clinical trial to assess the safety and efficacy of allogenic hAECs in treating POF. Methods: A total of 35 patients received 6 × 107 hAECs via ovarian artery and completed a five-month follow-up from December 30, 2020 to January 31, 2022. The follow-up assessments were conducted at various intervals after hAECs treatment, including one month (Visit-1, V-1), three months (Visit-2, V-2), and five months (Visit-3, V-3) post-treatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of transvaginal ultrasound results, sex hormone levels, Menopausal Quality of Life (MENQOL) questionnaire, as well as reproductive indicators. This trial was registered at www.clinicaltrials.gov as NCT02912104. Findings: No serious AEs were observed throughout the five-month follow-up period. The most common AE was hematoma (7/35, 20.00%), and other AEs include pelvic pain (4/35, 11.43%), fever (2/35, 5.71%), anaphylaxis (2/35, 5.71%), and hepatotoxicity (1/35, 2.86%). After hAECs transplantation (hAECT), significant improvements were observed in the levels of endometrial thickness, left ovarian volume, sex hormones (follicle-stimulating hormone (FSH) and estradiol (E2)), and MENQOL scores in all patients during the five-month follow-up period. Among them, 13 participants (37.14%) experienced spontaneous menstrual bleeding, and 20.00% (7/35) reported more than one regular menstrual bleeding post-hAECT. In this response group, significant improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-Müllerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT. Interpretation: hAECT via ovarian artery is safe, well-tolerated and temporarily ameliorates endometrial thickness, ovarian size, hormone levels, and menopausal symptoms in POF patients. Further randomized controlled trial of hAECs with longer follow-up period and a larger sample size is warranted. Funding: National Natural Science Foundation of China (No. 82271664), the Interdisciplinary Program of Shanghai Jiao Tong University (YG2022ZD028), the Shanghai Municipal Health Committee (202240345), Shanghai Key Laboratory of Embryo Original Diseases (No. Shelab2022ZD01), Shanghai Municipal Education Commission (No. 20152236), and National Key Research and Development Program of China (No. 2018YFC1004802), Shanghai Clinical Research Center for Cell Therapy, China (No. 23J41900100).
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The present research on intelligent bearing fault diagnosis assumes that the same feature distribution is used to obtain training and testing data. However, the domain shift (distribution discrepancy) issue generally occurs in both datasets because of different operational conditions. The domain adaptation techniques are preferably applied for fault diagnosis to handle the domain shift issue. Moreover, collecting sufficient testing data or labelled data in real industries is a challenging task. Therefore, the multi-kernel joint distribution adaptation (MKJDA) with dynamic distribution alignment is proposed for bearing fault diagnosis. This method dynamically joins both the marginal and conditional distributions and uses the multi-kernel to solve the non-linear problems to extract the most effective and robust representation for cross-domain issues. Moreover, it runs with the unlabelled task domain to perform the diagnosis by iteratively updating the pseudo code. The experimental results (two public datasets and one experimental dataset) demonstrated that the proposed method (MKJDA) exhibited stable and robust accuracy while conducting bearing fault diagnosis. It can effectively address the most crucial issue: intelligent diagnosis methods must re-train the model when the distribution differs between the source domain (the model is learned) and the target domain (the learned model is applied).
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OBJECTIVE: Macrolide antibiotics are often used to prevent infection and inflammation after functional endoscopic sinus surgery for the treatment of chronic rhinosinusitis (CRS). The purpose of this study was to investigate the anti-inflammatory and antibacterial effects of the clarithromycin-loaded poly(-lactide) (CLA-PLLA) membrane and its mechanism. STUDY DESIGN: Randomized controlled trial. SETTING: Animal Experiment Center. METHODS: We compared the difference between poly(l-lactide) (PLLA) and CLA-PLLA membranes by observing the morphology of fibrous scaffolds, measuring water contact angle, tensile strength, and drug release capacity, and evaluating the antimicrobial activity of CLA-PLLA. Twenty-four rabbits were divided into a PLLA group and a CLA-PLLA group after establishing CRS models. Another 5 normal rabbits comprised the control group. After 3 months, we placed the PLLA membrane in the nasal cavity of the PLLA group and the CLA-PLLA membrane in the CLA-PLLA group. Then, 14 days later, we evaluated the histological and ultrastructural changes in the sinus mucosa, protein, and messenger RNA (mRNA) levels of interleukin (IL)-4, IL-8, tumor necrosis factor-α, transforming growth factor-ß1, α-smooth muscle actin, and type I collagen. RESULTS: The CLA-PLLA membrane showed no significant difference in physical performance to the PLLA membrane, which continuously released 95% of the clarithromycin (CLA) for 2 months. The CLA-PLLA membrane had significant bacteriostatic properties that can improve the morphology of mucosal tissues, and inhibit protein and mRNA expression of inflammatory cytokines. In addition, CLA-PLLA also inhibited the expression of fibrosis-associated marker molecules. CONCLUSION: The CLA-PLLA membrane released CLA slowly and continuously, providing antibacterial, anti-inflammatory, and antifibrotic effects in a rabbit model of postoperative CRS.
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Claritromicina , Sinusitis , Animales , Conejos , Claritromicina/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiinflamatorios/farmacología , Sinusitis/tratamiento farmacológico , Sinusitis/cirugía , ARN MensajeroRESUMEN
Vocal process granuloma is a benign lesion that occurs on the arytenoid cartilage. It tends to recur locally, and there is a great diversity of methods to treat it. Here, we reviewed the effects of zinc sulfate therapy program in 16 patients with vocal process granulomas. Eleven patients had a history of trauma or laryngeal intubation and five patients had unknown origin. Eleven had recurrence after one to three failed surgeries, and the others had no prior treatment. Symptoms included hoarseness, sore throat, lump sensation in the throat and cough that apparently improved. The granulomas did not recur for at least 1 year. No complications occurred. For vocal process granuloma, zinc sulfate therapy is good either as an initial or compensatory treatment.
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Astringentes/uso terapéutico , Granuloma Laríngeo/tratamiento farmacológico , Sulfato de Zinc/uso terapéutico , Adolescente , Adulto , Anciano , Niño , Femenino , Granuloma Laríngeo/patología , Humanos , Laringoscopía , Masculino , Persona de Mediana Edad , Recurrencia , Resultado del Tratamiento , Pliegues Vocales/patologíaRESUMEN
Objectives: Diabetes is an independent risk factor for dementia. Mitochondrial dysfunction is a critical player in diabetes and diabetic complications. The present study aimed to investigate the role of mitochondrial dynamic changes in diabetes-associated cognitive impairment. Methods: Cognitive functions were examined by novel object recognition and T-maze tests. Mice hippocampi were collected for electron microscopy and immunofluorescence examination. Neuron cell line HT22 and primary hippocampal neurons were challenged with high glucose in vitro. Mitotracker-Red CM-H2X ROS was used to detect mitochondrial-derived free radicals. Results: Diabetic mice exhibited memory loss and spatial disorientation. Electron microscopy revealed that diabetic mice had larger synaptic gaps, attenuated postsynaptic density and fewer dendritic spines in the hippocampus. More round-shape mitochondria were observed in hippocampal neurons in diabetic mice than those in control mice. In cultured neurons, high glucose induced a high phosphorylated level of dynamin-related protein 1 (DRP1) and increased oxidative stress, resulting in cell apoptosis. Inhibition of mitochondrial fission by Mdivi-1 and metformin significantly decreased oxidative stress and prevented cell apoptosis in cultured cells. Treatment of Mdivi-1 and metformin restored cognitive function in diabetic mice. Conclusion: Metformin restores cognitive function by inhibiting mitochondrial fission, reducing mitochondrial-derived oxidative stress, and mitigating neuron loss in hippocampi of diabetic mice. The protective effects of metformin shed light on the therapeutic strategy of cognitive impairment.
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Background: This study is aimed at to establish an effective prognostic nomogram for patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI). Methods: The nomogram was based on a retrospective study of 977 patients with AF and ACS who underwent PCI who were admitted to any of the 11 tertiary hospitals in the Beijing area between 2009 and 2015. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index) and calibration curve and were compared using current risk scores such as GRACE, CRUSADE, CHA2DS2-VASc, and HAS-BLED. The results were validated using bootstrap resampling and a retrospective cohort study of 409 patients enrolled in Fuwai Hospital at the same institution. Results: Independent factors derived from multivariable analysis of the primary cohort to predict all-cause mortality were age, pattern of ACS, red blood cell distribution width, N-terminal proBNP, and serum creatinine, all of which were assembled into the nomogram. The calibration curve for the probability of recurrence showed that the nomogram-based predictions were in good agreement with actual observations. The C-index of the nomogram for predicting mortality was 0.764 (95% CI, 0.718-0.810), which was statistically higher than the C-index values for the current risk scores (from 0.573 to 0.681). In the validation cohort, the C-index of the nomogram for predicting all-cause death was 0.706 (95% CI 0.601-0.811), with no significant differences compared with GRACE and CRUSADE, but better than that of CHA2DS2-VASc and HAS-BLED. Conclusions: The nomogram has good prognostic prediction for patients with AF and ACS who underwent PCI.
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TLR4 polymorphisms such as Asp299Gly and Thr399Ile related to Gram-negative sepsis have been reported to result in significantly blunted responsiveness to LPS. Our study group previously screened other TLR4 polymorphic variants by checking the NF-κB activation in comparison to wild type (WT) TLR4 in human embryonic kidney 293T cells. In this study, we found that the Lys694Arg (K694R) polymorphism reduced the activation of NF-κB, and the production of downstream inflammatory factors IL-1, TNF-α and IL-6, representing the K694R polymorphism, led to blunted responsiveness to LPS. Then, we examined the influence of the K694R polymorphism on total and cell-surface TLR4 expression by Western blotting and flow cytometry, respectively, but observed no differences between the K694R polymorphism and WT TLR4. We also used co-immunoprecipitation to determine the interaction of the K694R polymorphism and WT TLR4 with their co-receptor myeloid differentiation factor 2 (MD2) and their downstream signal adaptor MyD88. We found that K694R reduced the recruitment of MyD88 in TLR4 signalling but had no impact on the interaction with MD2.
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Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/metabolismo , Receptor Toll-Like 4/metabolismo , Arginina/genética , Células HEK293 , Humanos , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Neoplasias Renales , Lipopolisacáridos/inmunología , Lisina/genética , Mutación/genética , Polimorfismo Genético , Transducción de Señal , Receptor Toll-Like 4/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVES/HYPOTHESIS: This study explored the feasibility and efficiency of main branch of ansa cervicalis nerve (ACN)-to-recurrent laryngeal nerve (RLN) anastomosis for management of paroxysmal laryngospasm due to unilateral vocal cord paralysis (UVCP). METHODS: Thirteen patients who underwent main branch of ACN-to-RLN anastomosis for management of paroxysmal laryngospasm due to UVCP were enrolled in the present study. Multidimensional assessments, including videostroboscopy, voice assessment, and laryngeal electromyography (LEMG), were performed preoperatively and postoperatively. RESULTS: This series was limited to UVCP with iatrogenic causes, including thyroidectomy, cervical spine surgery, and thoracic surgery. After main branch of ACN-to-RLN anastomosis, all cases showed significant airway improvement, and laryngospasm was completely abolished in 92.3% (12 of 13) of cases. Videostroboscopy showed that the bulging and paradoxical adduction of the affected vocal cord during a sniff were abolished immediately after operation, and there was no significant difference in vocal fold position or glottal closure before versus after the operation. LEMG showed that the postoperative recruitment and amplitude of voluntary motor unit potential in the affected thyroarytenoid muscle during a sniff were significantly decreased compared to preoperative values, and postoperative recruitment showed significant improvement during phonation compared to that preoperatively. Voice assessment showed that there were no significant differences in overall grade, roughness, breathiness, jitter (local), shimmer (local), noise-to-harmonics ratio, or maximum phonation time after the operation compared to the preoperative values. CONCLUSIONS: Main branch of ACN-to-RLN anastomosis could have long-lasting efficacy in the management of paroxysmal laryngospasm due to UVCP, with no apparent compromise of voice quality. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2412-2419, 2020.
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Plexo Cervical/cirugía , Laringismo/etiología , Laringismo/cirugía , Transferencia de Nervios/métodos , Nervio Laríngeo Recurrente/cirugía , Parálisis de los Pliegues Vocales/complicaciones , Adulto , Anastomosis Quirúrgica , Electromiografía , Estudios de Factibilidad , Femenino , Humanos , Enfermedad Iatrogénica , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Endoscopic sinus surgery (ESS) is used to treat chronic rhinosinusitis. However, nasal adhesions often develop postoperatively, triggered by chronic inflammation and local fibrosis. A poly L-lactide (PLLA) electrospun microfibrous membrane is a functional biodegradable material that can be placed on the wound surface to protect the wound and prevent adhesions. METHODS: We divided 24 rabbits randomly into 2 groups, a control operation group (group A) and an operation+PLLA placement group (group B). We investigated the anti-fibrotic effects of the topical biomaterial after sinus surgery. We placed PLLA fibrous membranes in the sinus cavity of group B rabbits after sinus surgery, and then evaluated changes in the mucosa and in the levels of collagen fibers, interleukin 4 (IL-4), IL-8, tumor necrosis factor α (TNF-α), transforming growth factor ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), and collagen I (Col I), using morphological and molecular biological methods. RESULTS: PLLA fibrous membranes did not inhibit the synthesis of messenger RNAs (mRNAs) encoding IL-4, IL-8, or TNF-α, or the protein levels, indicating that the membrane did not have an anti-inflammatory effect. However, the membrane inhibited the synthesis of mRNAs encoding TGF-ß1, α-SMA, and Col I, and reduced collagen production. Thus, the nanostructured membrane inhibited fibroblast proliferation. CONCLUSION: The PLLA membrane had anti-fibrotic effects, and may be used to prevent fibrosis and adhesions after ESS in human patients.
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Colágeno , Factor de Necrosis Tumoral alfa , Animales , Dioxanos , Fibrosis , Humanos , Conejos , Adherencias Tisulares/prevención & control , Factor de Crecimiento Transformador beta1RESUMEN
Systemic antibiotic therapy is the main treatment for acute bacterial rhinosinusitis (ABRS). However, this treatment often causes side effects of dizziness, diarrhea, and drug resistance. In this study, a new polyethylene glycol hydrogel (PEG-H) treatment model is developed to achieve sustained release of drugs at the locality while avoiding those adverse effects. The PEG-H is composed of 4-arm-PEG-SH and silver ions through a high affinity and dynamic reversible coordination bond between the thiol and silver ion. In the initial test, PEG-H is loaded with Clarithromycin (CAM-Lips@Hydrogel) or Clarithromycin and Budesonide liposomes (CAM+BUD-Lips@Hydrogel). The results show that PEG-H maintains the characteristics of self-healing, biodegradability, moderate swelling rate, injectibility and sustained drug release. In in vivo studies, the hydrogel is injected into the maxillary sinus of ABRS rabbit models. In both a single or combined load, the hydrogel not only plays an effective role as an anti-bacterial, but also inhibits inflammatory response of local sinus mucosa. In addition, no other side effects are observed in the ABRS rabbit model through behavioral observation and drug sensitivity tests. Therefore, the injectable self-healing hydrogel with anti-bacterial and anti-inflammatory properties provides a new micro invasive therapeutic method for the clinical treatment of ABRS.
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Hidrogeles , Polietilenglicoles , Animales , Antiinflamatorios/farmacología , Materiales Biocompatibles , Liberación de Fármacos , ConejosRESUMEN
BACKGROUND: To analyze the cardio-protective effects of ticagrelor in patients with acute coronary syndrome with S-T segment elevation. METHODS: The sample was 200 patients who had been diagnosed with acute coronary syndrome accompanied by diabetes Mellitus type II. Only patients having ST segment elevation before the treatment were included. Then, the subjects were further randomly divided into an observation group and a control group. The control group of 100 patients received clopidogrel; the observation group of 100 patients of ticagrelor. The serous creatine kinase CK-MB, functional cardiac indexes of left ventricular end diastolic diameter (LVDD), cardiac troponin I, ventricular ejection fraction, and relevant major adverse cardiovascular events (MACE) were compared between the two groups. RESULTS: One month after a percutaneous coronary intervention (PCI) the observation group showed better results against angina, stent thrombosis, and all-cause mortality compared with those of the control subjects. Six months after treatment, both groups suffered adverse reactions. The number of patients who suffered adverse reactions in respiratory tract in the observation group was higher than in the control group. The inhibition of platelet aggregation IPA of ticagrelor was found to be significantly higher than clopidogrel, having a significant p value. CONCLUSION: Ticagrelor can effectively protect myocardial function for patients with ST-segment elevation acute coronary syndrome accompanied by diabetes and can reduce the incidence of adverse reactions..
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An accurate dosage determination is required in neonates when antibiotics are used. The adult data cannot be simply extrapolated to the pediatric population due to significant individual differences. We aimed to identify factors impacting ceftazidime exposure in neonates and to provide drug dosing guidance to clinicians. Forty-three neonates aged less than 60 days with proven or suspected infections were enrolled in this study. After intravenous administration, blood samples were collected, and plasma ceftazidime concentration was determined using a HPLC method. Pharmacokinetic data were fitted using a nonlinear mixed-effects model approach. One-compartmental model could nicely characterize the ceftazidime in vivo behavior. The covariate test found that the postmenstrual age (day) was strongly associated with systemic drug clearance (L/h), and the effect of body weight (kg) was identified as the covariate on distribution volume (L). Compared with the base model, the addition of covariates improved the goodness-of-fit of the final model. Model validation (bootstrap, visual predictive check, and prediction-corrected visual predictive check) suggested a robust and reliable pharmacokinetic model was developed. Personalized dosage regimens were provided based on model simulations. The intravenous dose should be adjusted according to postmenstrual age, body weight, and minimum inhibitory concentration.
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Antibacterianos/administración & dosificación , Antibacterianos/sangre , Ceftazidima/administración & dosificación , Ceftazidima/sangre , Administración Intravenosa , Peso Corporal , China , Cálculo de Dosificación de Drogas , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Modelos Biológicos , Método de MontecarloRESUMEN
OBJECTIVE: To observe the change in the number of antibodies of preneoplastic hepatocellular carcinoma (HCC) using early treatment by Compound Phyllanthus Urinaria L. (CPUL) on patients with preneoplastic hepatitis B virus (HBV)-associated HCC. METHODS: A total of 102 cirrhosis patients with regenerative or dysplastic nodules whose sera were tested positive for at least one of these six proteins (five up-regulated genes URG4, URG7, URG11, URG12 and URG19, and one down-regulated gene DRG2) were assigned randomly to two groups using continual random codes by SPSS software. Fifty-two patients were in the treatment group and 50 patients were in the control group. CPUL was used in the treatment group for 3 years, while the control group did not receive any treatment. The changes in HBV-DNA level, number of antibodies, and hepatocarcinogenesis occurred were observed. Patients who did not develop HCC were followed up for another 2 years. RESULTS: HBV-DNA levels decreased ⩾2log in 22.2% (10/45) of patients in the treatment group in contrast to only 5.0% (2/40) of patients in the control group (P=0.0228). The number of antibodies that were tested positive in the treatment group (1.08±1.01) was significantly lower compared with the control group (2.11±1.12) after 24 months of drug treatment (P<0.01). Both the positive rates of anti-URG11 (33/52) and anti-URG19 (31/52) were over 60% at baseline in the two groups, and were decreased to 48.1% (25/52) and 46.2% (24/52) respectively at 36 months of drug treatment, while the rates increased to 68.0% (34/50) and 66.0% (33/50) respectively (P=0.0417, P=0.0436) in the control group. The positive rate of anti-DRG2 was increased to 55.8% (29/52) at 36 months of drug treatment, while in the control group was decreased to 36.0% (18/50, P=0.0452). Among the 102 patients who developed HCC, 2 were in the treatment group and 9 were in the control group, meaning that a significant difference between the two groups (P=0.0212). In 11 patients who developed HCC, anti-URG11 and anti-URG19 were always positive, while anti-DRG2 was negative. Patients newly developing HCC were 6 (20.0%) in the control group, and only one (2.5%) in the treatment group (P=0.0441) during 2-year follow-up after the end of the treatment. CONCLUSIONS: Anti-URG11, anti-URG19 and anti-DRG2 could be used as early markers in the prediction of the therapeutic efficacy of CPUL in treating preneoplastic HCC. CPUL is useful in preventing or delaying the development of HBV-associated cirrhosis to HCC.
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Carcinoma Hepatocelular/terapia , Virus de la Hepatitis B/patogenicidad , Neoplasias Hepáticas/terapia , Phyllanthus/química , Extractos Vegetales/uso terapéutico , Lesiones Precancerosas/virología , Anticuerpos Antivirales/sangre , Carcinoma Hepatocelular/virología , ADN Viral/análisis , Células Hep G2 , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Humanos , Neoplasias Hepáticas/virologíaAsunto(s)
Carcinoma Hepatocelular/patología , Hepatitis B/patología , Lesiones Precancerosas/patología , Adulto , Anciano , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/prevención & control , Carcinoma Hepatocelular/terapia , Femenino , Hepatitis B/terapia , Humanos , Masculino , Persona de Mediana Edad , Phyllanthus , Fitoterapia , Lesiones Precancerosas/etiología , Lesiones Precancerosas/prevención & control , Lesiones Precancerosas/terapiaRESUMEN
OBJECTIVE: To observe the efficacy of ursodeoxycholic acid (UDCA) combined with Tongdan: Decoction () on immunological indices and histopathological changes in patients with primary biliary cirrhosis (PBC) of IIor III histological stage. METHODS: Sixty PBC patients were assigned randomly and equally: to the control group treated with UDCA alone and the treatment group treated with UDCA combined with Tongdan Decoction. The immunological indices and histopathological changes were detected before and after 24-week treatment, and the follow-up lasted for 1-3 years. RESULTS: After 24-week treatment, CD4(+)CD28(-) in the peripheral blood was lowered and CD4(+)CD25(+) was increased in both groups, and better effect was shown in the treatment group (P<0.01). The levels of IgM, IgG, and IgA decreased markedly after 96-week treatment in the treatment group (P< 0.05, P< 0.01), while in the control group, only the latter two showed significant decrease after 148 week (all P<0.05). At the end of the 3-year follow-up, the medians of histopathological Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico
, Cirrosis Hepática Biliar/tratamiento farmacológico
, Cirrosis Hepática Biliar/patología
, Ácido Ursodesoxicólico/uso terapéutico
, Antígenos CD/sangre
, Biomarcadores
, Quimioterapia Combinada
, Femenino
, Humanos
, Inmunoglobulina G/sangre
, Inflamación/sangre
, Inflamación/complicaciones
, Cirrosis Hepática Biliar/sangre
, Cirrosis Hepática Biliar/inmunología
, Masculino
, Persona de Mediana Edad
RESUMEN
OBJECTIVE: To present laser surgery techniques to address anterior commissure involvement and evaluate recovery. METHODS: Twelve canines were divided into three groups. In group A the right ventricular band and vocal fold, the anterior third of the left vocal fold, and anterior commissure were cauterized. In group B cauterization was extended to the thyroid cartilage and a 5 mm x 5 mm area of the anterior commissural to half the cartilage thickness. In group C the 5 mm x 5 mm window was extended through the thyroid cartilage. Surgical lesions were observed after surgery and at 1 and 4 weeks post-surgery. RESULTS: Post-operative gross examination confirmed target scopes. One week after surgery, the lesions in group A were completely covered by neo-mucosa, while group B and C wounds were only partially covered. After 4 weeks, a laryngeal web was seen at the anterior commissure and the vocal fold length was shortened. Lesions in all three groups were completely covered by neo-mucosa. Collagen proliferation was most prominent in group C with limited scarring in group A. There were no major complications. CONCLUSIONS: The three operative methods demonstrated satisfactory outcomes; the lesions recovered well over the course of 4 weeks, and no severe complications occurred. The laser surgery protocol was successfully extended into the thyroid cartilage.