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The titer of the microbial fermentation products can be increased by enzyme engineering. l-Sorbosone dehydrogenase (SNDH) is a key enzyme in the production of 2-keto-l-gulonic acid (2-KLG), which is the precursor of vitamin C. Enhancing the activity of SNDH may have a positive impact on 2-KLG production. In this study, a computer-aided semirational design of SNDH was conducted. Based on the analysis of SNDH's substrate pocket and multiple sequence alignment, three modification strategies were established: (1) expanding the entrance of SNDH's substrate pocket, (2) engineering the residues within the substrate pocket, and (3) enhancing the electron transfer of SNDH. Finally, mutants S453A, L460V, and E471D were obtained, whose specific activity was increased by 20, 100, and 10%, respectively. In addition, the ability of Gluconobacter oxidans WSH-004 to synthesize 2-KLG was improved by eliminating H2O2. This study provides mutant enzymes and metabolic engineering strategies for the microbial-fermentation-based production of 2-KLG.
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Proteínas de Bactérias , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Gluconobacter/enzimologia , Gluconobacter/genética , Gluconobacter/metabolismo , Açúcares Ácidos/metabolismo , Açúcares Ácidos/química , Fermentação , Engenharia de Proteínas , Engenharia Metabólica , Desidrogenases de Carboidrato/metabolismo , Desidrogenases de Carboidrato/genética , Desidrogenases de Carboidrato/química , CinéticaRESUMO
This paper reviews the researches on acupuncture preconditioning before surgery in recent years and explores its application value from three aspects, i.e. relieving preoperative anxiety, preventing from postoperative cognitive dysfunction, and preventing from postoperative gastrointestinal dysfunction. As a relatively safe non-drug treatment, acupuncture has the underlying advantages in participating into multidisciplinary coordination in the enhanced recovery after surgery (ERAS). By building up higher-quality medical evidences and revealing the effect mechanism of acupuncture from multi-dimenisonal aspects, it is expected that acupuncture technology can be coordinated with ERAS to optimize the clinical path in the perioperative period, and boost the development of the perioperative medicine ultimately.
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Terapia por Acupuntura , Recuperação Pós-Cirúrgica Melhorada , Humanos , Ansiedade , Transtornos de Ansiedade , Período PerioperatórioRESUMO
This paper reviews the researches on acupuncture preconditioning before surgery in recent years and explores its application value from three aspects, i.e. relieving preoperative anxiety, preventing from postoperative cognitive dysfunction, and preventing from postoperative gastrointestinal dysfunction. As a relatively safe non-drug treatment, acupuncture has the underlying advantages in participating into multidisciplinary coordination in the enhanced recovery after surgery (ERAS). By building up higher-quality medical evidences and revealing the effect mechanism of acupuncture from multi-dimenisonal aspects, it is expected that acupuncture technology can be coordinated with ERAS to optimize the clinical path in the perioperative period, and boost the development of the perioperative medicine ultimately.
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Humanos , Terapia por Acupuntura , Ansiedade , Transtornos de Ansiedade , Recuperação Pós-Cirúrgica Melhorada , Período PerioperatórioRESUMO
[This corrects the article DOI: 10.1107/S1600536813033734.].
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As a new generative model, the generative adversarial network (GAN) has great potential in the accuracy and efficiency of generating pseudoreal data. Nowadays, bearing fault diagnosis based on machine learning usually needs sufficient data. If enough near-real data can be generated in the case of insufficient samples in the actual operating condition, the effect of fault diagnosis will be greatly improved. In this study, a new rolling bearing data generation method based on the generative adversarial network (GAN) is proposed, which can be trained adversarially and jointly via a learned embedding, and applied to solve fault diagnosis problems with insufficient data. By analyzing the time-domain characteristics of rolling bearing life cycle monitoring data in actual working conditions, the operation data are divided into three periods, and the construction and training of the generative adversarial network model are carried out. Data generated by adversarial are compared with the real data in the time domain and frequency domain, respectively, and the similarity between the generated data and the real data is verified.
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Aprendizado de MáquinaRESUMO
The main objective of this study was to evaluate the in vitro antiproliferative effects of isoalantolactone against liver cancer cells (Hep-G2) and also monitor its mechanism of action. The MTT assay was involved in proliferation assessments and phase contrast microscopy was used to check cellular morphology. Acridine orange/ethidium bromide staining along with western blotting was used to evaluate proapoptotic effects of isoalantolactone. DCFH-DA staining was used in ROS measurements. Transwell migration and invasion assay were executed to check the effects of isoalantolactone on migration and invasion of Hep-G2 cells. Western blotting was used to check the expressions of Ras/Raf/MEK signalling pathway in Hep-G2 cells. Results demonstrated that isoalantolactone significantly (*p<0.05 and **p<0.01) inhibited the proliferation of Hep-G2 cells in a concentration and time-reliant fashion. The IC50 value of the tested isoalantolactone molecule was found to be 71.2 µM and 53.4 µM at 12 h and 24 h time intervals respectively. Moreover, the antiproliferative effects of isoalantolactone were mediated through induction of caspase-dependent apoptosis and oxidative stress (ROS mediated). The proapoptotic effects of isoalantolactone were evident from morphological assessments and improved expressions of caspase-3, -8, and -9 and Bax while antiapoptotic Bcl-2 was reduced significantly. Additionally, antiproliferative and proapoptotic effects of isoalantolactone were found to be a consequence of blocking of Ras/Raf/MEK signalling in Hep-G2 cells. Furthermore, isoalantolactone significantly (*p<0.05) targeted the migration and invasion of Hep-G2 cells. In conclusion, these results validated that isoalantolactone shows strong antiproliferative activity against Hep-G2 liver cancer cells. Therefore, it could prove as a leading candidate in liver cancer research, drug discovery and design.
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Apoptose , Neoplasias Hepáticas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por Mitógeno/farmacologia , Espécies Reativas de Oxigênio/metabolismo , SesquiterpenosRESUMO
BACKGROUND AND AIMS: The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. APPROACH AND RESULTS: From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). CONCLUSIONS: MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.
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Carcinoma Hepatocelular , Ablação por Cateter , Laparoscopia , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Hepatectomia , Humanos , Neoplasias Hepáticas/patologia , Micro-Ondas/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Hypoxemia can occur during gastroscopy under intravenous anesthesia. The aim of this randomized controlled trial was to evaluate whether oxygenation using a nasal mask can reduce the incidence of hypoxemia during gastroscopy under intravenous anesthesia compared with a traditional nasal cannula. METHODS: A total of 574 patients scheduled for gastroscopy under intravenous anesthesia were enrolled and randomly assigned to receive either a nasal mask or a traditional nasal cannula for oxygenation. The primary outcome was the incidence of hypoxemia. The secondary outcomes included the incidence of severe hypoxemia, duration of hypoxemia, minimum oxygen saturation, the proportion of emergency airway management, length of procedure, recovery time, and the satisfaction of the anesthetist and gastroenterologists as well as other adverse events (including cough, hiccups, nausea and vomiting, reflux, aspiration, and laryngospasm). RESULTS: A total of 565 patients were included in the analysis: 282 patients in the nasal cannula group and 283 patients in the nasal mask group. The incidence of hypoxemia was lower in the nasal mask group (18.0%) than in the nasal cannula group (27.7%; relative risk [RR] = 0.65; 95% confidence interval [CI], 0.48-0.89; P = .006), and the hypoxemia lasted a median of 18.0 seconds (interquartile range, 10.0-38.8) in the nasal mask group and 32.5 seconds (20.0-53.5) in the nasal cannula group (median difference -14.50; 95% CI, -22.82 to -1.34; P = .047). The proportion of patients requiring emergency airway management was significantly lower in the nasal mask group (8.8%) than in the nasal cannula group (19.1%; RR, 0.46; 95% CI, 0.30-0.73; P < .001). No difference was found in the overall incidence of other adverse events between the 2 groups (nasal mask 20.8%; nasal cannula 17.0%; RR, 1.23; 95% CI, 0.87-1.73; P = .25). Satisfaction was higher with the nasal mask than with the nasal cannula from the perspective of anesthetists (96.1% for nasal mask versus 84.4% for nasal cannula; RR, 1.14; 95% CI, 1.08-1.20; P < .001) and gastroenterologists (95.4% for mask versus 81.9% for cannula; RR, 1.17; 95% CI, 1.10-1.24; P < .001). There were no significant differences in the incidence of severe hypoxemia, minimum oxygen saturation, length of procedure, or recovery time between the 2 groups. CONCLUSIONS: Nasal mask oxygenation reduced the incidence of hypoxemia during anesthesia for gastroscopy under intravenous anesthesia.
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Manuseio das Vias Aéreas/métodos , Anestesia Intravenosa/métodos , Gastroscopia/métodos , Hipóxia/epidemiologia , Máscaras , Nariz , Complicações Pós-Operatórias/epidemiologia , Adulto , Período de Recuperação da Anestesia , Anestesiologistas , Cateterismo , Feminino , Gastroenterologistas , Humanos , Hipóxia/etiologia , Incidência , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Oxigênio/sangue , Resultado do TratamentoRESUMO
Automatically generating an accurate and meaningful description of an image is very challenging. However, the recent scheme of generating an image caption by maximizing the likelihood of target sentences lacks the capacity of recognizing the human-object interaction (HOI) and semantic relationship between HOIs and scenes, which are the essential parts of an image caption. This article proposes a novel two-phase framework to generate an image caption by addressing the above challenges: 1) a hybrid deep learning and 2) an image description generation. In the hybrid deep-learning phase, a novel factored three-way interaction machine was proposed to learn the relational features of the human-object pairs hierarchically. In this way, the image recognition problem is transformed into a latent structured labeling task. In the image description generation phase, a lexicalized probabilistic context-free tree growing scheme is innovatively integrated with a description generator to transform the descriptions generation task into a syntactic-tree generation process. Extensively comparing state-of-the-art image captioning methods on benchmark datasets, we demonstrated that our proposed framework outperformed the existing captioning methods in different ways, such as significantly improving the performance of the HOI and relationships between HOIs and scenes (RHIS) predictions, and quality of generated image captions in a semantically and structurally coherent manner.
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Algoritmos , Idioma , Humanos , SemânticaRESUMO
BACKGROUND: The present study aimed to compare and evaluate the efficacy of antidepressants in remission of esophageal reflux symptoms. METHODS: A comprehensive literature review was performed including sources published on MEDLINE, EMBASE, the Cochrane Central Registry of Controlled Trials (Cochrane), Web of Science, China National Knowledge Infrastructure Database (CNKI), Chinese VIP Information Databases (VIP), Chinese Biology Medicine disc (CBM), and Wan-Fang databases for randomized controlled trials, published up to and including March 31, 2020. We analyzed relevant randomized, placebo-controlled trials reporting the effect of antidepressant therapy in relieving esophageal reflux symptoms ADDIS 1.16.8 was used to perform the network meta-analysis. Furthermore, we performed a split analysis to test inconsistency, and rank probability was complemented for comparison among antidepressants. RESULTS: A total of 10 randomized controlled trials (RCTs) examining the effects of antidepressants, selective 5-HT reabsorption inhibitor (SSRI), 5-HT 1A receptor agonist (5-HT1AA), tricyclic antidepressants (TCAs), and the complex of flupentixol-melitracen (FM) were included. Flupentixol-melitracen and SSRIs exhibited a significantly higher rate of remission than placebo. However, there was no statistically significant difference among different antidepressants compared. Rank probability showed that FM exhibited the highest probability of rank 1 compared with other antidepressants and placebo. CONCLUSION: This network meta-analysis of RCTs supported the use of FM and SSRIs as a potentially effective regimen for symptom remission of gastroesophageal reflux. Furthermore, according to our analysis, FM represents the most efficient antidepressant with highest probability of symptom remission.
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Antidepressivos , Refluxo Gastroesofágico , Antidepressivos/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the best ablative margin (AM) for single hepatocellular carcinoma (HCC) patients with image-guided percutaneous thermal ablation (IPTA) based on MRI-MRI fusion imaging, and to develop and validate a local tumor progression (LTP) predictive model based on the recommended AM. METHODS: Between March 2014 and August 2019, 444 treatment-naïve patients with single HCC (diameter ≤3 cm) who underwent IPTA as first-line treatment from three hospitals were included, which were randomly divided into training (n= 296) and validation (n = 148) cohorts. We measured the ablative margin (AM) by MRI-MRI fusion imaging based on pre-ablation and post-ablation images. Then, we followed up their LPT and verified the optimal AM. Risk factors related to LTP were explored through Cox regression models, the nomogram was developed to predict the LTP risk base on the risk factors, and subsequently validated. The predictive performance and discrimination were assessed and compared with conventional indices. RESULTS: The median follow-up was 19.9 months (95% CI 18.0-21.8) for the entire cohort. The results revealed that the tumor size (HR: 2.16; 95% CI 1.25-3.72; P = 0.003) and AM (HR: 0.72; 95% CI, 0.61-0.85; P < 0.001) were independent prognostic factors for LTP. The AM had a pronounced nonlinear impact on LTP, and a cut-off value of 5-mm was optimal. We developed and validated an LTP predictive model based on the linear tumor size and nonlinear AM. The model showed good predictive accuracy and discrimination (training set, concordance index [C-index] of 0.751; validation set, C-index of 0.756) and outperformed other conventional indices. CONCLUSION: The 5-mm AM is recommended for the best IPTA candidates with single HCC (diameter ≤3 cm). We provided an LTP predictive model that exhibited adequate performance for individualized prediction and risk stratification.
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(1) Background: We aimed to develop a transparent machine-learning (ML) framework to automatically identify patients with a condition from electronic health records (EHRs) via a parsimonious set of features. (2) Methods: We linked multiple sources of EHRs, including 917,496,869 primary care records and 40,656,805 secondary care records and 694,954 records from specialist surgeries between 2002 and 2012, to generate a unique dataset. Then, we treated patient identification as a problem of text classification and proposed a transparent disease-phenotyping framework. This framework comprises a generation of patient representation, feature selection, and optimal phenotyping algorithm development to tackle the imbalanced nature of the data. This framework was extensively evaluated by identifying rheumatoid arthritis (RA) and ankylosing spondylitis (AS). (3) Results: Being applied to the linked dataset of 9657 patients with 1484 cases of rheumatoid arthritis (RA) and 204 cases of ankylosing spondylitis (AS), this framework achieved accuracy and positive predictive values of 86.19% and 88.46%, respectively, for RA and 99.23% and 97.75% for AS, comparable with expert knowledge-driven methods. (4) Conclusions: This framework could potentially be used as an efficient tool for identifying patients with a condition of interest from EHRs, helping clinicians in clinical decision-support process.
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OBJECTIVE: To evaluate the diagnostic efficacy of gastric juice-based genotypic methods for Helicobacter pylori detection and antibiotic resistance testing. METHODS: We used electronic databases including Medline, Embase, Web of Science and the Cochrane Central Register of Controlled Trial for literature survey using keywords such as "gastric juice", "Helicobacter pylori" and their synonyms. The quality of the studies was assessed using QUADAS-2. Summary performance measures (sensitivity, specificity, positive predictive values, negative predictive values, diagnostic odds ratio, and area under the summary receiver operating characteristic curve) and HSROC curves were produced. In addition, fagan plots were applied to illustrate the relationship among the prior test probability, PLR/NLR, and posterior test probability. RESULTS: Our study cohort comprised eight studies with 1235 participants (617 participants of H. pylori infection and 618 participants of non-H. pylori infection). Pooled sensitivity and specificity with a corresponding 95% confidence interval (CI) of gastric juice-based genotypic methods reflected values of 94% (95%CI, 86% - 98%) and 98% (95%CI, 85% - 100%), respectively. The global sensitivity and specificity of clarithromycin resistance were 92% (95%CI, 85% - 96%) and 90% (95%CI, 80% - 95%), respectively. CONCLUSION: Gastric juice-based genotypic methods can be used for diagnostic prediction of H. pylori infection as well as clarithromycin resistance testing.
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Suco Gástrico , Infecções por Helicobacter , Helicobacter pylori , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Suco Gástrico/efeitos dos fármacos , Suco Gástrico/microbiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Técnicas MicrobiológicasRESUMO
Habenaria is one of the largest terrestrial genera in the family Orchidaceae. Most field studies on Habenaria species with greenish-white and nocturnal scented flowers are pollinated by nocturnal hawkmoths and settling moths. However, H. rhodocheila presents reddish flowers lacking a detectable scent and fails to fit the moth pollination syndrome. We investigated the pollinators, breeding system, and functional traits of H. rhodocheila in South China and found that two diurnal swallowtail butterflies Papilio helenus and Papilio nephelus (Papilionidae) were the effective pollinators. When butterflies foraged for nectar in the spur, the pollinia became attached between the palpi. A triangular projected median rostellar lobe was found at the entrance (sinus) of the spur of H. rhodocheila. This lobe divided the spur opening into two entrances forcing butterflies to enter their proboscides through the left or right side. When the projection of median rostellar lobe was removed, the site of pollinium attachment changed to the eyes of the butterflies, leading to a higher rate of pollinium removal but lower rate of pollinium deposition. Our quartz glass cylinder choice experiment suggested that visual rather than olfactory cues provided the major stimuli for butterflies to locate these flowers. Hand pollination experiments suggested this species was self-compatible but pollinator-dependent. However, the proportion of seeds with large embryos produced in self-pollinated fruits was significantly lower than in cross-pollinated fruits, indicating a significant inbreeding depression. Unlike many other orchid species, fruit set was higher than rates of pollinium removal, indicating a high level of pollination efficiency in a species with friable pollinia. Shifts from moth to butterfly pollination in the genus Habenaria parallel other orchid lineages providing insights into the potential for pollinator-mediated floral trait selection.
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PURPOSE: The aim of this review is to explore the effects of the seminar teaching method versus lecture-based learning (LBL) in the education of medical students by meta-analysis. METHOD: Data and information available on PubMed, Cochrane Library, EMBASE, MEDLINE, China National Knowledge Infrastructure, WanFang Data, China Science Periodical Database, and Chinese BioMedical were searched and examined from the inception up to January 2020. Randomized controlled trials (RCTs) that investigated the effects of the seminar teaching method versus LBL in medical education were included. RESULTS: A total of 16 RCTs were included, with a total sample size of 1122 medical students. The seminar teaching method significantly improved knowledge scores (SMD = 1.38, 95%CI 0.92-1.84; p < 0.001) and skill scores (SMD = 1.46, 95%CI 1.00-1.91; p < 0.001) and the seminar teaching method significantly improved teaching effects, including active learning ability, learning interest, scientific innovation, and independent thinking ability, expression and communication ability, clinical thinking ability, teamwork, teacher-student interaction, and classroom atmosphere. CONCLUSIONS: This meta-analysis showed that the seminar teaching method is an effective method for improving knowledge scores, skill scores, active learning ability, student collaboration, classroom atmosphere, and interaction between teachers and students.
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Educação Médica , Estudantes de Medicina , China , Humanos , Aprendizagem Baseada em Problemas , Ensaios Clínicos Controlados Aleatórios como Assunto , EnsinoRESUMO
Tuberculosis remains a global challenge, particularly with a growing number of resistant cases, which may become an obstacle to eliminating this disease. Standardized short-course therapy composed of first-line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF), ethambutol (EMB), and pyrazinamide (PZA) is playing vital roles for curbing the rapid spread of tuberculosis. However, some patients have poor responses to standardized short-course therapy. As the number of drug-resistant tuberculosis increase, some other anti-tuberculous drugs are needed to achieve better treatment outcomes. In this study, we established a UPLC-MS/MS method for simultaneous detection of ten anti-tuberculosis drugs in human plasma including INH, EMB, PZA, RIF, rifampin, rifapentine as well as four second-line antituberculosis drugs, i.e. ethionamide, protionamide, thiosemicarbazone and clofazimine. This study contains almost all the commonly used anti-tuberculosis drugs. The plasma samples were treated with acetonitrile to precipitate proteins, and doped with the isotope internal standard. A Shiseido CAPCELL RAK-ADME (2.1 mm × 50 mm, 3 µm) column was used for chromatographic separation, and acetonitrile-water (containing 0.1% formic acid) was the mobile phase. The separation used gradient elution with a flow rate of 0.4 mL/min. The column temperature was 40 °C, and the sample volume was 1 µL. The electrospray ionization source (ESI) and the positive ion multiple reaction monitoring (MRM) mode were used for the detection. The analysis time was as short as 7 min. The results show a good linear relationship under optimized conditions in the range of 5.00-7.50 × 103, 1.00-1.50 × 103, 5.00-5.00 × 104, 5.00-7.50 × 103, 1.00-3.00 × 103, 1.00 × 101-1.00 × 104, 1.00-3.00 × 103, 1.00-3.00 × 103, 2.00-4.00 × 103, and 1.00 × 10-1-2.00 × 102 ng/mL for INH, EMB PZA, RIF, rifabutin, rifapentine, ethionamide, protionamide, thiosemicarbazone, and clofazimine, respectively, with a linear correlation coefficient of R > 0.99. Finally, 34 patients with pulmonary TB were tested for therapeutic drug monitoring. The results showed that the presented method have significant advances in sensitivity, separation efficiency and simplicity.
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Antituberculosos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Monitoramento de Medicamentos/mortalidade , Espectrometria de Massas em Tandem/métodos , Antituberculosos/uso terapêutico , Monitoramento de Medicamentos/métodos , Humanos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
Calanthe sieboldopsis, a new species, is here described and illustrated from Luoxiao Mountains, Jiangxi Province, eastern China. It is morphologically similar to C. sieboldii Decne. ex Regel, but differs from the latter in having smaller flowers, longer spurs, rectangular mid-lobes with emarginate apex (vs. elliptic mid-lobes with mucronate apex), disc with 3 ridges and the proximal ends of the lateral 2 ridges enlarged with light reddish spots and minute white hairs (vs. disc with 5 ridges and 2 rows of white short hairs at base) and pollinia equal in size (vs. unequal in size). A preliminary risk-of-extinction assessment, according to the IUCN Red List Categories and Criteria, is given for the new species.
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Dual therapy with lopinavir/ritonavir (LPV/r) plus lamivudine (3TC) has been demonstrated to be non-inferior to the triple drug regimen including LPV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) in 48-week studies. However, little is known about the long-term efficacy and drug resistance of this simplified strategy. A randomized, controlled, open-label, non-inferiority trial (ALTERLL) was conducted to assess the efficacy, drug resistance, and safety of dual therapy with LPV/r plus 3TC (DT group), compared with the first-line triple-therapy regimen containing tenofovir (TDF), 3TC plus efavirenz (EFV) (TT group) in antiretroviral therapy (ART)-naïve HIV-1-infected adults in Guangdong, China. The primary endpoint was the proportion of patients with plasma HIV-1 RNA < 50 copies/ml at week 144. Between March 1 and December 31, 2015, a total of 196 patients (from 274 patients screened) were included and randomly assigned to either the DT group (n = 99) or the TT group (n = 97). In the primary intention-to-treat (ITT) analysis at week 144, 95 patients (96%) in the DT group and 93 patients (95.9%) in the TT group achieved virological inhibition with plasma HIV-1 RNA <50 copies/ml (difference: 0.1%; 95% CI, -4.6-4.7%), meeting the criteria for non-inferiority. The DT group did not show significant differences in the mean increase in CD4+ cell count (247.0 vs. 204.5 cells/mm3; p = 0.074) or the CD4/CD8 ratio (0.47 vs. 0.49; p = 0.947) from baseline, or the inflammatory biomarker levels through week 144 compared with the TT group. For the subgroup analysis, baseline high viremia (HIV-1 RNA > 100,000 copies/ml) and genotype BC did not affect the primary endpoint or the mean increase in CD4+ cell count or CD4/CD8 ratio from baseline at week 144. However, in patients with genotype AE, the DT group showed a higher mean increase in CD4+ cell count from baseline through 144 weeks than the TT group (308.7 vs. 209.4 cells/mm3; p = 0.038). No secondary HIV resistance was observed in either group. Moreover, no severe adverse event (SAE) or death was observed in any group. Nonetheless, more patients in the TT group (6.1%) discontinued the assigned regimen than those in the DT group (1%) due to adverse events. Dual therapy with LPV/r plus 3TC manifests long-term non-inferior therapeutic efficacy, low drug resistance, good safety, and tolerability compared with the first-line triple-therapy regimen in Guangdong, China, indicating dual therapy is a viable alternative in resource-limited areas. Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR1900024611].
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In this study, data of 19 climatic factors were downloaded from the World Climate website. A total of 233 Cymbidium kanran distribution data were obtained through online review and field visits. Using MaxEnt model and combined with ArcGIS spatial analysis technology, the potential distribution area and distribution pattern of C. kanran in different periods were simulated, as well as its distribution during the last glacial period and 2070. The results showed that the curve indexes (AUC) value of the model training set was 0.957, and the AUC value of the verification set was 0.953, indicating that the prediction accuracy of the model was very high. The current distribution of C. kanran was mostly affected by the driest quarter precipitation, mean annual precipitation, wettest quarter precipitation, and mean annual temperature range. The contribution rates were 50.3%, 15.9%, 8.4% and 4.4%, respectively, with the total contribution rate being 79.0%. In the last glacial period, C. kanran mainly distributed in Wuyi Mountain, Luojing Mountain, Nanling, Taiwan's five major mountains and some hills in the northern part of Guangxi. From now to 2070, the distribution of C. kanran area will decrease by 22.4%. The southwestern part of Guangxi, the central part of Yunnan, and the junctions of Jiangxi, Fujian and Guangdong provinces will expand, while that in eastern Jiangxi, western Fujian, and the border between these two provinces will shrink.