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Macroautophagy/autophagy is a fundamental cellular catabolic process that delivers cytoplasmic components into double-membrane vesicles called autophagosomes, which then fuse with lysosomes and their contents are degraded. Autophagy recycles cytoplasmic components, including misfolded proteins, dysfunctional organelles and even microbial invaders, thereby playing an essential role in development, immunity and cell death. Autophagosome formation is the main step in autophagy, which is governed by a set of ATG (autophagy related) proteins. ATG16L1 interacts with ATG12-ATG5 conjugate to form an ATG12-ATG5-ATG16L1 complex. The complex acts as a ubiquitin-like E3 ligase that catalyzes the lipidation of MAP1LC3/LC3 (microtubule associated protein 1 light chain 3), which is crucial for autophagosome formation. In the present study, we found that ATG16L1 was subject to S-palmitoylation on cysteine 153, which was catalyzed by ZDHHC7 (zinc finger DHHC-type palmitoyltransferase 7). We observed that re-expressing ATG16L1 but not the S-palmitoylation-deficient mutant ATG16L1C153S rescued a defect in the lipidation of LC3 and the formation of autophagosomes in ATG16L1-KO (knockout) HeLa cells. Furthermore, increasing ATG16L1 S-palmitoylation by ZDHHC7 expression promoted the production of LC3-II, whereas reducing ATG16L1 S-palmitoylation by ZDHHC7 deletion inhibited the LC3 lipidation process and autophagosome formation. Mechanistically, the addition of a hydrophobic 16-carbon palmitoyl group on Cys153 residue of ATG16L1 enhances the formation of ATG16L1-WIPI2B complex and ATG16L1-RAB33B complex on phagophore, thereby facilitating the LC3 lipidation process and autophagosome formation. In conclusion, S-palmitoylation of ATG16L1 is essential for the lipidation process of LC3 and the formation of autophagosomes. Our research uncovers a new regulatory mechanism of ATG16L1 function in autophagy.
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Efficiently handling huge data amounts and enabling processing-intensive applications to run in faraway areas simultaneously is the ultimate objective of 5G networks. Currently, in order to distribute computing tasks, ongoing studies are exploring the incorporation of fog-cloud servers onto satellites, presenting a promising solution to enhance connectivity in remote areas. Nevertheless, analyzing the copious amounts of data produced by scattered sensors remains a challenging endeavor. The conventional strategy of transmitting this data to a central server for analysis can be costly. In contrast to centralized learning methods, distributed machine learning (ML) provides an alternative approach, albeit with notable drawbacks. This paper addresses the comparative learning expenses of centralized and distributed learning systems to tackle these challenges directly. It proposes the creation of an integrated system that harmoniously merges cloud servers with satellite network structures, leveraging the strengths of each system. This integration could represent a major breakthrough in satellite-based networking technology by streamlining data processing from remote nodes and cutting down on expenses. The core of this approach lies in the adaptive tailoring of learning techniques for individual entities based on their specific contextual nuances. The experimental findings underscore the prowess of the innovative lightweight strategy, LMAED2L (Enhanced Deep Learning for Earth Data Analysis), across a spectrum of machine learning assignments, showcasing remarkable and consistent performance under diverse operational conditions. Through a strategic fusion of centralized and distributed learning frameworks, the LMAED2L method emerges as a dynamic and effective remedy for the intricate data analysis challenges encountered within satellite networks interfaced with cloud servers. The empirical findings reveal a significant performance boost of our novel approach over traditional methods, with an average increase in reward (4.1 %), task completion rate (3.9 %), and delivered packets (3.4 %). This report suggests that these advancements will catalyze the integration of cutting-edge machine learning algorithms within future networks, elevating responsiveness, efficiency, and resource utilization to new heights.
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BACKGROUND: Herein, the effect of pre-use of Dexmedetomidine(Dex) on the half-effective dose (ED50) and 95%-effective dose (ED95) of Remimazolam tosilate(RT) in inhibiting the positive cardiovascular response(CR) which means blood pressure or heart rate rises above a critical threshold induced by double-lumen bronchial intubation was evaluated. METHODS: Patients who underwent video-assisted thoracic surgery were divided into groups A (0), B (0.5 µg/kg), and C (1 µg/kg) based on different Dex doses. Group A included subgroups comprising young (A-Y) and elderly (A-O) patients. Neither groups B nor C included elderly patients due of the sedative effect of Dex. Based on the previous subject's CR, the dose of RT was increased or decreased in the next patient using the sequential method. This trial would be terminated when the seventh crossover occurred, at which point the sample size met the stable estimate of the target dose. Heart rate (HR) and mean arterial pressure (MAP) were monitored throughout the trial, and sedation was assessed using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. HR and MAP were recorded at baseline (T1), the end of Dex (T2), and the end of RT (T3), the maximum HR and MAP were recorded within 3 min of intubation from beginning to end (T4). There was a positive CR when the T4 levels rose above 15% of the baseline. The ED50/ED95 and corresponding confidence interval were calculated using probability regression. RESULTS: In total, 114 patients completed the trial. Without the use of Dex, the ED50/ED95 of TR inhibiting the positive CR caused by double-lumen bronchial intubation was 0.198/0.227 and 0.155/0.181 mg/kg in groups A-Y and A-O, respectively. The changes in vital signs from T1 to T3 were similar in the subgroups, indicating that the elderly patients were more sensitive to the dose of RT. The ED50/ED95 of RT inhibiting the positive CR caused by double-lumen endobronchial intubation was 0.122/0.150 and 0.068/0.084 mg/kg in groups B and C, respectively. And, the fluctuation of blood pressure from T3 to T4 was reduced by using Dex. RT was 100% effective in sedation with no significant inhibition of circulation. Apart from one case of hypotension occurred in group A-Y, two cases of low HR in group B, and one case of low HR in group C, no other adverse events were noted. CONCLUSIONS: The optimal dose of RT to inhibit positive CR induced by double-lumen bronchial intubation in elderly patients was 0.18 mg/kg and 0.23 mg/kg in younger patients. When the pre-use dose of Dex was 0.5 µg/kg, the optimal dose to inhibit positive CR of RT was 0.15 mg/kg. And, when the pre-use dose of Dex was 1 µg/kg, the optimal dose of RT was 0.9 mg/kg. CLINICAL TRIAL REGISTRATION: NCT05631028.
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Anestesia , Dexmedetomidina , Humanos , Idoso , Dexmedetomidina/farmacologia , Hipnóticos e Sedativos , Intubação IntratraquealRESUMO
Lung transplantation is the last effective treatment for end-stage respiratory failure, however, with ischemia-reperfusion injury (IRI) inevitably occurring in postoperative period. IRI is the major pathophysiologic mechanism of primary graft dysfunction, a severe complication that contributes to prolonged length of stay and overall mortality. The understanding of pathophysiology and etiology remain limited and the underlying molecular mechanism, as well as novel diagnostic biomarkers and therapeutic targets, urgently require exploration. Excessive uncontrolled inflammatory response is the core mechanism of IRI. In this research, a weighted gene co-expression network was established using the CIBERSORT and WGCNA algorithms in order to identify macrophage-related hub genes based on the data downloaded from the GEO database (GSE127003, GSE18995). 692 differentially expressed genes (DEGs) in reperfused lung allografts were identified, with three genes recognized as being related to M1 macrophages and validated as differentially expressed using GSE18995 dataset. Of these putative novel biomarker genes, TCRα subunit constant gene (TRAC) were downregulated, while Perforin-1 (PRF1) and Granzyme B (GZMB) were upregulated in reperfused vs. ischemic lung allografts. Furthermore, we obtained 189 potentially therapeutic small molecules for IRI after lung transplantation from the CMap database among which PD-98059 was the top molecule with the highest absolute correlated connectivity score (CS). Our study provides the novel insights into the impact of immune cells on the etiology of IRI and potential targets for therapeutic intervention. Nevertheless, further investigation of these key genes and therapeutic drugs is needed to validate their effects.
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Transplante de Pulmão , Traumatismo por Reperfusão , Humanos , Traumatismo por Reperfusão/genética , Perfilação da Expressão Gênica , Biomarcadores , Algoritmos , Macrófagos , TranscriptomaRESUMO
BACKGROUND: Recent development in tau-sensitive tracers has sparkled significant interest in tracking tauopathies using positron emission tomography (PET) biomarkers. However, the ability of 18 F-florzolotau PET imaging to topographically characterize tau pathology in corticobasal syndrome (CBS) remains unclear. Further, the question as to whether disease-level differences exist with other neurodegenerative tauopathies is still unanswered. OBJECTIVE: To analyze the topographical patterns of tau pathology in the living brains of patients with CBS using 18 F-florzolotau PET imaging and to examine whether differences with other tauopathies exist. METHODS: 18 F-florzolotau PET imaging was performed in 20 consecutive patients with CBS, 20 cognitively healthy controls (HCs), 20 patients with Alzheimer's disease (AD), and 16 patients with progressive supranuclear palsy-Richardson's syndrome (PSP-RS). Cerebrospinal fluid (CSF) levels of ß-amyloid biomarkers were quantified in all patients with CBS. 18 F-florzolotau uptake was quantitatively assessed using standardized uptake value ratios. RESULTS: Of the 20 patients with CBS, 19 (95%) were negative for CSF biomarkers of amyloid pathology; of them, three had negative 18 F-florzolotau PET findings. Compared with HCs, patients with CBS showed increased 18 F-florzolotau signals in both cortical and subcortical regions. In addition, patients with CBS were characterized by higher tracer retentions in subcortical regions compared with those with AD and showed a trend toward higher signals in cortical areas compared with PSP-RS. An asymmetric pattern of 18 F-florzolotau uptake was associated with an asymmetry of motor severity in patients with CBS. CONCLUSIONS: In vivo 18 F-florzolotau PET imaging holds promise for distinguishing CBS in the spectrum of neurodegenerative tauopathies. © 2023 International Parkinson and Movement Disorder Society.
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Degeneração Corticobasal , Tomografia por Emissão de Pósitrons , Tauopatias , Humanos , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Degeneração Corticobasal/diagnóstico por imagem , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons/métodos , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Paralisia Supranuclear Progressiva/patologia , Proteínas tau/metabolismo , Tauopatias/diagnóstico por imagemRESUMO
Background: Extracorporeal membrane oxygenation (ECMO) is a versatile tool associated with favorable outcomes in the field of lung transplantation (LTx). Here, the clinical outcomes and complications of patients who underwent LTx with ECMO support, mainly prophylactically both intraoperatively and post-operatively, in a single center in China are reviewed. Methods: The study cohort included all consecutive patients who underwent LTx between January 2020 and January 2022. Demographics and LTx data were retrospectively reviewed. Perioperative results, including complications and survival outcomes, were assessed. Results: Of 86 patients included in the study, 32 received ECMO support, including 21 who received prophylactic intraoperative use of ECMO with or without prolonged post-operative use (pro-ECMO group), while the remaining 54 (62.8%) received no external support (non-ECMO group). There were no significant differences in the incidence of grade 3 primary graft dysfunction (PGD), short-term survival, or perioperative outcomes and complications between the non-ECMO and pro-ECMO groups. However, the estimated 1- and 2-year survival were superior in the pro-ECMO group, although this difference was not statistically significant (64.1% vs. 82.4%, log-rank P = 0.152; 46.5% vs. 72.1%, log-rank P = 0.182, respectively). After regrouping based on the reason for ECMO support, 30-day survival was satisfactory, while 90-day survival was poor in patients who received ECMO as a bridge to transplantation. However, prophylactic intraoperative use of ECMO and post-operative ECMO prolongation demonstrated promising survival and acceptable complication rates. In particular, patients who initially received venovenous (VV) ECMO intraoperatively with the same configuration post-operatively achieved excellent outcomes. The use of ECMO to salvage a graft affected by severe PGD also achieved acceptable survival in the rescue group. Conclusions: Prophylactic intraoperative ECMO support and post-operative ECMO prolongation demonstrated promising survival outcomes and acceptable complications in LTx patients. Particularly, VV ECMO provided safe and effective support intraoperatively and prophylactic prolongation reduced the incidence of PGD in selected patients. However, since this study was conducted in a relatively low-volume transplant center, further studies are needed to validate the results.
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BACKGROUND: Internal jugular vein catheterization (IJVC) and subclavian vein catheterization (SCVC) have been the most preferred central venous catheterizations (CVC) clinically. Individual preference and institutional routine dominate the traditional CVC choice; however, it is lack of high-level evidence. We sought to provide better clinical strategy for CVC site choice based on anatomical landmark technique between IJVC and SCVC. METHODS: We systematically reviewed eligible studies from PubMed, OVID, Cochrane and ClinicalTrials.Gov till February 2020. The primary outcomes were catheterization time and overall success rate, and the secondary outcomes were the first-attempt success rate and the instant mechanical complications. Ethical problems are not applicable. RESULTS: A total of 3378 patients from 7 studies were included in the analyses. Neither difference was found on the catheterization time (SMD 95% CI: -0.095-0.124, p = 0.792), nor any difference on the overall success rate (RR = 1.017, 95% CI: 0.927-1.117, p = 0.721, I2 = 89.6%) between the 2 procedures. However, subgroup analyses showed overall success rate of IJVC was significantly lower than that of SCVC (RR = 0.906, 95% CI: 0.850-0.965, p = 0.002) in adults. The first-attempt success rate of IJVC group was higher in the adults (RR = 1.472, 95% CI: 1.004-2.156, p = 0.047). No significance was detected in arterial injury (RR = 1.137, 95% CI: 0.541-2.387, p = 0.735) and pneumothorax (RR = 0.600, 95% CI: 0.32-1.126, p = 0.112) between the two procedures. Hematoma was significantly more in IJVC group than that in SCVC group (RR = 2.824, 95% CI: 1.181-6.751, p = 0.02). CONCLUSIONS: Compared with IJVC, SCVC shows a higher overall success rate while a lower first-attempt success rate in adults, and has involved with less hematoma. PROSPERO REGISTRATION: CRD42020165444.
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Cateterismo Venoso Central , Pneumotórax , Adulto , Humanos , Veias Jugulares , Pneumotórax/terapiaRESUMO
For bronchial sleeve and carinal resection and reconstruction during uniportal video-assisted thoracic surgery (VATS), ventilation technique remains a demanding challenge for the anesthesiologists. The ventilation techniques require maintaining adequate gas exchange while providing a good surgical exposure. The case we present was a 58-year-old female with carcinoma in the right upper lobe involving the right main bronchus and the lower trachea. Right upper sleeve lobectomy, carinal resection and reconstruction was performed under uniportal VATS. A modified double-lumen tube (DLT) was inserted to achieve one-lung ventilation, and high-frequency jet ventilation (HFJV) was passed through the DLT to provide oxygenation during the anastomosis without interfering with the surgical procedure. The whole procedure was uneventful. We suggest that the double lumen tube could be modified being a simple and safe option for one-lung ventilation in carinal resection and reconstruction under uniportal VATS.
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OBJECTIVES: Pulmonary carcinosarcoma (PCS) is a rare neoplasm. This study explored the clinicopathological characteristics and survival outcomes of PCS. METHODS: The Surveillance, Epidemiology and End Results (SEER) database (1988-2014) was queried for PCS. Overall survival (OS) was evaluated by multivariable Cox regression and nomograms were constructed to predict 3-year OS for PCS. Prognostic performance was evaluated using concordance index and area under the curve analysis. In M0 surgically treated patients, interaction assessments were performed using likelihood ratio tests. Subgroup analysis was performed according to patient age. The clinical features of PCSs were further compared to other non-small-cell lung cancers (NSCLCs). RESULTS: Multivariable analysis identified age [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.04], surgery (HR 0.53, 95% CI 0.36-0.77) and chemotherapy (HR 0.51, 95% CI 0.36-0.73) as significantly associated with OS. The nomogram had a concordance index of 0.747 and an area under the curve of 0.803. The association between age and OS was stronger in those receiving pneumonectomy (P = 0.04 for interactions) compared to those that did not (HR 5.14, 95% CI 1.64-16.07), and was associated with a poorer outcome compared to lobectomy amongst the elderly (age ≥ 70 years). Patients with PCS were more likely to receive surgical treatment and had lower lymphatic metastasis compared to adenocarcinoma, squamous cell carcinoma and large cell carcinoma (all P < 0.05). CONCLUSIONS: PCS had unique clinical features compared to common types of NSCLCs in terms of lymphatic invasion and surgical treatment. Pneumonectomy was associated with poorer survival in elderly patients.
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Carcinossarcoma/mortalidade , Neoplasias Pulmonares/mortalidade , Idoso , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nomogramas , Pneumonectomia/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Programa de SEERRESUMO
BACKGROUND: Lung resection after previous contralateral pneumonectomy is rare. We present a case of right anterior segmentectomy despite previous left pneumonectomy, demanding special airway management strategy. CASE PRESENTATION: A 48-year-old woman who had left pneumonectomy 2 years ago was scheduled to have the right anterior segmentectomy through uniportal video-assisted thoracoscopy (VATS). A 32-French (Fr) left-sided double-lumen endobronchial tube (DLT) was chosen and adapted. The DLT was intubated into the bronchus intermedius. And the upper lobe can be isolated from the ventilation in the middle and lower lobes when the bronchial cuff's inflated. The perioperative period was uneventful and the pathological diagnosis was adenocarcinoma. CONCLUSION: Lung cancer radical resection was discouraged after previous contralateral pneumonectomy partly due to the challenging ventilation and isolation. With this new DLT adapting and intubation technique showed in this case, the challenging ventilation and isolation that deter the implementation of the operation mentioned above could be solved.
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Manuseio das Vias Aéreas/métodos , Intubação Intratraqueal/métodos , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Manuseio das Vias Aéreas/instrumentação , Feminino , Humanos , Intubação Intratraqueal/instrumentação , Neoplasias Pulmonares/diagnóstico por imagem , Pneumonectomia/instrumentação , Cirurgia Torácica Vídeoassistida/instrumentaçãoRESUMO
The behavior of the pathological subtypes of tracheal glomus tumor (benign, uncertain malignant potential UMP, malignant) is vague. In a 51-year-old gentleman, suffering from cough for 4 months, computed tomography scan showed a mass at lower third of the trachea and the bronchoscope revealed exophytic mass at the tracheal lumen. Segmental tracheal resection was done using special modified endotracheal tube for the distal lung ventilation. The tracheal glomus tumor was also diagnosed based on the immunohistochemical staining. The tumor was 2 cm in diameter, deeply located, mitotic phase was difficult to identify, and a diagnosis of UMP subtype was made. There was no recurrence after 2 years follow-up. This is the first reported case of UMP subtype in lower trachea and we studied the treatment options with the clinic-pathological behavior of this tumor and its sequel by regular follow-up.
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Tumor Glômico/patologia , Tumor Glômico/cirurgia , Neoplasias da Traqueia/patologia , Neoplasias da Traqueia/cirurgia , Tumor Glômico/diagnóstico por imagem , Humanos , Intubação Intratraqueal/instrumentação , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Neoplasias da Traqueia/diagnóstico por imagemRESUMO
Tracheal resection and anastomosis for benign and malignant tracheal disease are a well-described procedure. Intra-thoracic tracheal lesions used to be addressed through sternotomy, thoracotomy, or via combined techniques. In the recent decade, minimal invasive surgical techniques have become an innovative trend in treatment of surgical thoracic conditions. Some recent papers have described and proven the feasibility and safety of tracheal and carinal surgeries via 3-4 port video-assisted thoracoscopic surgery (VATS) approaches. Even better results regarding morbidity and mortality were achieved using these new techniques. In this article, we publish a video that demonstrates our technique in tracheal resection and reconstruction using two portal thoracoscopic techniques.
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BACKGROUND: Extracellular histones were recently identified as an inflammatory mediator involved in the pathogenesis of various organ injuries. This study aimed to examine extracellular histone levels and their clinical implications in acute respiratory distress syndrome (ARDS) patients and to explore histone-mediated effects through ex-vivo investigations. METHODS: Extracellular histones, cytokine profiles and clinical data from 96 ARDS patients and 30 healthy volunteers were obtained. Human bronchial epithelial cells (BEAS-2B), human pulmonary artery endothelial cells (HPAEC), and human monocytic U937 cells were exposed to bronchoalveolar lavage fluid (BALF) collected from ARDS patients, and cellular damage and cytokine production were assessed. Furthermore, the effect of histone-targeted interventions by heparin or anti-histone antibody was evaluated. RESULTS: Plasma and BALF extracellular histone levels were much higher in ARDS patients than in healthy controls. There was a significant association between extracellular histones and ARDS severity and mortality. In addition, extracellular histones correlated with an evident systemic inflammation detected in ARDS patients. Ex-vivo analysis further showed that ARDS patient's BALF remarkably induced epithelial and endothelial cell damage and stimulated cytokine production in the supernatant of U937 cells. The adverse effects on these cells could be abrogated by heparin or anti-histone antibody. CONCLUSIONS: Extracellular histones in ARDS patients are excessively increased and may contribute to disease aggravation by inducing cellular damage and promoting systemic inflammation. Targeting extracellular histones may provide a promising approach for treating ARDS.
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Líquido Extracelular/metabolismo , Histonas/metabolismo , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/metabolismo , Mucosa Respiratória/metabolismo , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Histonas/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Mucosa Respiratória/citologia , Células U937RESUMO
OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is commonly used for clinical diagnosis of mediastinal lymphadenectasis. This study aimed to evaluate the diagnostic significance of EBUS-TBNA for mediastinal lymphadenectasis in a large single center. METHODS: A total of 846 patients who were not definitively diagnosed with mediastinal lymphadenectasis underwent EBUS-TBNA were retrospectively analyzed in this study. RESULTS: In total, 842 patients underwent EBUS-TBNA successfully. There were 589 patients with malignancy, including squamous carcinoma (118 cases; 20.6%), adenocarcinoma (187 cases; 32.7%) and small cell carcinoma (88 cases; 15.4%). A total of 253 patients were diagnosed with benign disease, including tuberculosis (111 cases; 43.9%) and sarcoidosis (93 cases; 36.7%). The diagnostic sensitivity of lung cancer, tuberculosis and sarcoidosis were 94.4%, 81.1% and 51.6%, respectively. The overall sensitivity of EBUS-TBNA was 92.0%. N2 stage in lung cancer patients who were diagnosed by EBUS-TBNA was significantly higher than other stages. The positive rate of targeted puncture is high for the lymph nodes whose short-axis diameters were larger than 1 cm. CONCLUSION: The operation risk of EBUS-TBNA is relatively small. In diseases complicated by mediastinal lymphadenectasis, malignant diseases are most, and benign diseases mainly are granulomatous. EBUS-TBNA is a valuable diagnostic technique in patients with mediastinal lymphadenectasis whose diagnosis have not been determined.
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Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Neoplasias Pulmonares/diagnóstico , Linfonodos/patologia , Sarcoidose/diagnóstico , Tuberculose/diagnóstico , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Masculino , Mediastino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
The objective of this work was to develop a simple, selective, and sensitive LC-MS/MS method for the quantitation of the mepivacaine in Chinese biological matrix. The calibration curve of mepivacaine ranged from 0.5 to 2000 ng/mL with the lower limit of quantitation being 0.5 ng/mL. This sensitivity was high enough to describe the profile of blood mepivacaine level versus time. Thereby it was very desirable for the pharmacokinetic study because of its high sensitivity and accuracy. The study used a single-dose two-period crossover design principle. For the pharmacokinetic analysis of plasma, the mean (SD) values obtained were as follows: t1/2, 1.63 (0.43) h; Cmax, 435.3 (67.4) ng/ml; AUC0-t, 1546.9 (339.7) ng/ml·h; AUC0-∞, 1982.3 (421.4) ng/ml·h; Tmax, 0.62 (0.31) h. The validated method has been successfully applied to assess the pharmacokinetic study of mepivacaine after a single administration to Chinese volunteers.
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Análise Química do Sangue/métodos , Cromatografia Líquida/métodos , Voluntários Saudáveis , Mepivacaína/sangue , Mepivacaína/farmacocinética , Espectrometria de Massas em Tandem/métodos , Calibragem , Humanos , Limite de Detecção , Modelos Lineares , Masculino , Distribuição TecidualRESUMO
OBJECTIVE: To observe the curative effect of different duration of mild moxibustion in superficial gastritis patients with deficiency cold pattern of spleen and stomach. METHODS: A total of 84 superficial gastritis patients were randomly divided into moxibustion-20 min group, moxibustion-40 min group and medication (Ranitidine) group, with 28 cases in each group. Mild moxibustion was applied to bilateral Zusanli (ST 36) and Zhongwan (CV 12, odd days), Pishu (BL 20) and Weishu (BL 21, even-numbered days) for 20 min and 40 min respectively, once daily for 20 days. The symptom integrative score of superficial gastritis patients and the therapeutic effects were assessed according to "The Scoring Table for Symptoms and Signs of Gastrointestinal Disorders of Chinese Medicine", etc. RESULTS: Following 20 days' treatment, of the three 28 gastrititis patients in the medication, moxibustion-20 min and moxibustion-40 min groups, 0, 1, and 0 cases were cured, 5, 7 and 12 experienced marked improvement in their symptoms, 15, 16 and 12 had an improvement, and 8, 4 and 4 were invalid, with the effective rates being 71.4%, 85.7% and 85.7%, respectively. After one month's follow up, of the three 28 cases in the medication, moxibustion-20 min and moxibustion-40 min groups, 0, 4 and 0 cases were cured, 4, 8, and 13 experienced marked improvement, 15, 16 and 13 had an improvement, 9, 0 and 2 were ineffective, with the effective rates being 67.9%, 100% and 92.9%, respectively. Self-comparison of each group showed that the integrative scores of symptoms were all decreased significantly after the treatment and one-month's follow up in the three groups (P < 0.01). The effective rates of both moxibustion-20 min and -40 min were significantly higher than that of the medication group after one month's follow up (P < 0.01, P < 0.05). The therapeutic effect of moxibustion-20 min group was significantly superior to that of the medication group in lowering the integrative score of symptoms after one month's follow up (P < 0.01). No significant differences were found among the three groups in the therapeutic effects and in reducing integrative scores of symptoms after 20 days' treatment (P > 0.05). CONCLUSION: Mild moxibustion is significantly superior to medication in long-term therapeutic effects in the treatment of superficial gastritis patients with spleen-stomach deficiency-cold pattern.