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BACKGROUND: Due to the increasing incidence of ischaemic cerebrovascular diseases, the accurate assessment of internal carotid artery (ICA) stenosis is crucial for the development of treatment plans. This systematic review and meta-analysis aimed to evaluate the diagnostic value of computed tomography angiography (CTA) for severe ICAstenosis, thereby providing support for clinical decision-making and promoting diagnostic updates. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database for Chinese Technical Periodicals (VIP), and Chinese Biomedical Literature (CBM) electronic databases were searched from inception to March 21, 2024, to identify publicly available research literature on the use of CTA to diagnose severe ICA stenosis. Literature screening, data extraction, and quality assessment were conducted based on the inclusion and exclusion criteria as well as the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) standards. Data analysis was performed using Stata 17.0 and Meta-Disc 1.4 software. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of the included studies were calculated using Stata 17.0 software, and forest plots and summary receiver operating characteristic (SROC) curves were generated. The area under the curve (AUC) was calculated, and funnel plots were constructed to assess publication bias. RESULTS: A total of 16 studies with 2368 vascular segments were included. The meta-analysis revealed that the combined sensitivity and specificity of CTA for severe ICA stenosis were 0.93 (95% CI: 0.88 ~ 0.96) and 0.99 (95% CI: 0.96 ~ 1.00), respectively. The combined positive likelihood ratio and negative likelihood ratio were 92.0 (95% CI: 24.2 ~ 349.6) and 0.07 (95% CI: 0.04 ~ 0.13), respectively. The diagnostic odds ratio was 1302 (95% CI: 257 ~ 6606), and the AUC of the SROC curve was 0.98. The Deeks funnel plot suggested no publication bias among the included studies. CONCLUSION: CTA demonstrated high sensitivity and specificity for diagnosing severe ICA stenosis. Therefore, this study provided important evidence for the accurate diagnosis and treatment of severe ICA stenosis. However, there was considerable heterogeneity among the included studies, thus indicating the need for additional high-quality prospective studies to confirm the clinical applicability of CTA.
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Artéria Carótida Interna , Estenose das Carótidas , Angiografia por Tomografia Computadorizada , Sensibilidade e Especificidade , Humanos , Estenose das Carótidas/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Artéria Carótida Interna/diagnóstico por imagem , Curva ROC , Índice de Gravidade de DoençaRESUMO
Pseudobulbus Cremastrae seu Pleiones (PCsP), a traditional Chinese medicine known as â¶Shan-Ci-Guâ³, possesses properties for clearing heat, counteracting toxicity, dissipating phlegm, and resolving masses. As a TCM with multiple bases, the dried pseudobulbs of Pleione bulbocodioides (PB), Pleione yunnanensis (PY) and Cremastra appendiculata (CA) are considered to be the official sources of PCsP. Additionally, several unofficial substitutes are also available in the market. To enhance the quality control of PCsP, an integrated strategy based on Q-marker was proposed. Initially, a study of integrating plant metabolomics, target isolation, structure identification, and activity testing afforded five Q-markers, including three new compounds. Furthermore, a quality evaluation method using a single standard to determine multi-components (SSDMC) based on Q-marker was established, which could effectively distinguish PB from CA and the counterfeit herbs. Finally, the transitivity of Q-markers was explored through a representative Chinese compound prescription containing PCsP. The results indicated that the identified Q-markers together with the established analysis methods could be effectively applied for quality control of PCsP and its preparations.
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Medicamentos de Ervas Chinesas , Controle de Qualidade , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/normas , Cromatografia Líquida de Alta Pressão/métodos , Metabolômica/métodos , Medicina Tradicional Chinesa/normas , Cupressaceae/químicaRESUMO
Four benzophenones, three dihydrocoumarins, and two coumarins were synthesised by a 1-3 step reaction, with yields ranging from 6.2 to 35%. Next, we investigated the in vitro antitumour activity of these compounds. Compounds 1, 8, and 9 exhibited strong antitumour activity and were considered promising candidates in this field. In particular, compound 1 exhibited very strong inhibitory activity against HL-60, A-549, SMMC-7721, and SW480 cells, with IC50 values of 0.48, 0.82, 0.26, and 0.99 µM, respectively. Finally, the antitumour mechanism of compound 1 was investigated through network pharmacology and molecular docking analyses, which identified 22 key genes and 21 tumour pathways. AKT1, ALB, CASP3, ESR1, GAPDH, HSP90AA1, and STAT3 were considered as potential target hub genes for compound 1. These results will enable the future development of benzophenone and its derivatives.
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Mollemycin A (MOMA) is a unique glyco-hexadepsipeptide-polyketide that was isolated from a Streptomyces sp. derived from the Australian marine environment. MOMA exhibits remarkable inhibitory activity against both drug-sensitive and multidrug-resistant malaria parasites. Optimizing MOMA through structural modifications or product enhancements is necessary for the development of effective analogues. However, modifying MOMA using chemical approaches is challenging, and the production titer of MOMA in the wild-type strain is low. This study identified and characterized the biosynthetic gene cluster of MOMA for the first time, proposed its complex biosynthetic pathway, and achieved an effective two-pronged enhancement of MOMA production. The fermentation medium was optimized to increase the yield of MOMA from 0.9 mg L-1 to 1.3 mg L-1, a 44% boost. Additionally, a synergistic mutant strain was developed by deleting the momB3 gene and overexpressing momB2, resulting in a 2.6-fold increase from 1.3 mg L-1 to 3.4 mg L-1. These findings pave the way for investigating the biosynthetic mechanism of MOMA, creating opportunities to produce a wide range of MOMA analogues, and developing an efficient strain for the sustainable and economical production of MOMA and its analogues.
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Objectives: This study was aimed to develop a nomogram that can accurately predict the likelihood of cognitive dysfunction in individuals with abdominal obesity by utilizing various predictor factors. Methods: A total of 1490 cases of abdominal obesity were randomly selected from the National Health and Nutrition Examination Survey (NHANES) database for the years 2011-2014. The diagnostic criteria for abdominal obesity were as follows: waist size ≥ 102 cm for men and waist size ≥ 88 cm for women, and cognitive function was assessed by Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Word Learning subtest, Delayed Word Recall Test, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). The cases were divided into two sets: a training set consisting of 1043 cases (70%) and a validation set consisting of 447 cases (30%). To create the model nomogram, multifactor logistic regression models were constructed based on the selected predictors identified through LASSO regression analysis. The model's performance was assessed using several metrics, including the consistency index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), calibration curves, and decision curve analysis (DCA) to assess the clinical benefit of the model. Results: The multivariate logistic regression analysis revealed that age, sex, education level, 24-hour total fat intake, red blood cell folate concentration, depression, and moderate work activity were significant predictors of cognitive dysfunction in individuals with abdominal obesity (p < 0.05). These predictors were incorporated into the nomogram. The C-indices for the training and validation sets were 0.814 (95% CI: 0.875-0.842) and 0.805 (95% CI: 0.758-0.851), respectively. The corresponding AUC values were 0.814 (95% CI: 0.875-0.842) and 0.795 (95% CI: 0.753-0.847). The calibration curves demonstrated a satisfactory level of agreement between the nomogram model and the observed data. The DCA indicated that early intervention for at-risk populations would provide a net benefit, as indicated by the line graph. Conclusion: Age, sex, education level, 24-hour total fat intake, red blood cell folate concentration, depression, and moderate work activity were identified as predictive factors for cognitive dysfunction in individuals with abdominal obesity. In conclusion, the nomogram model developed in this study can effectively predict the clinical risk of cognitive dysfunction in individuals with abdominal obesity.
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Disfunção Cognitiva , Obesidade Abdominal , Feminino , Humanos , Masculino , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Ácido Fólico , Inquéritos Nutricionais , Obesidade , Obesidade Abdominal/complicações , Obesidade Abdominal/diagnóstico , Obesidade Abdominal/epidemiologiaRESUMO
OBJECTIVE: This study was aimed to create and validate a risk prediction model for the incidence of osteopenia in individuals with abdominal obesity. METHODS: Survey data from the National Health and Nutrition Examination Survey (NHANES) database for the years 2013-2014 and 2017-2018 was selected and included those with waist circumferences ≥102 m in men and ≥88 cm in women, which were defined as abdominal obesity. A multifactor logistic regression model was constructed using LASSO regression analysis to identify the best predictor variables, followed by the creation of a nomogram model. The model was then verified and evaluated using the consistency index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve analysis (DCA). Results Screening based on LASSO regression analysis revealed that sex, age, race, body mass index (BMI), alkaline phosphatase (ALP) and Triglycerides (TG) were significant predictors of osteopenia development in individuals with abdominal obesity (P < 0.05). These six variables were included in the nomogram. In the training and validation sets, the C indices were 0.714 (95 % CI: 0.689-0.738) and 0.701 (95 % CI: 0.662-0.739), respectively, with corresponding AUCs of 0.714 and 0.701. The nomogram model exhibited good consistency with actual observations, as demonstrated by the calibration curve. The DCA nomogram showed that early intervention for at-risk populations has a net positive impact. CONCLUSION: Sex, age, race, BMI, ALP and TG are predictive factors for osteopenia in individuals with abdominal obesity. The constructed nomogram model can be utilized to predict the clinical risk of osteopenia in the population with abdominal obesity.
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Índice de Massa Corporal , Doenças Ósseas Metabólicas , Nomogramas , Inquéritos Nutricionais , Obesidade Abdominal , Circunferência da Cintura , Humanos , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Ósseas Metabólicas/epidemiologia , Adulto , Medição de Risco/métodos , Triglicerídeos/sangue , Curva ROC , Fosfatase Alcalina/sangue , Idoso , Fatores Etários , Fatores de Risco , Fatores Sexuais , Modelos Logísticos , Incidência , Área Sob a CurvaRESUMO
Objective: The purpose of this review is to identify the correlation between ICH and CSVD imaging markers under SMASH-U classification by searching and analyzing a large number of literatures in recent years, laying a theoretical foundation for future clinical research. At the same time, by collecting clinical data to evaluate patient prognosis, analyzing whether there are differences or supplements between clinical trial conclusions and previous theories, and ultimately guiding clinical diagnosis and treatment through the analysis of imaging biomarkers. Methods: In this review, by searching CNKI, Web of Science, PubMed, FMRS and other databases, the use of "spontaneous intracerebral hemorrhage", "hypertensive hemorrhagic cerebral small vessel disease", "cerebral small vessel disease imaging", "Based cerebral small vessel diseases", "SMASH the -u classification" and their Chinese equivalents for the main search term. We focused on reading and analyzing hundreds of relevant literatures in the last decade from August 2011 to April 2020, and also included some earlier literatures with conceptual data sources. After screening and ranking the degree of relevance to this study, sixty of them were cited for analysis and elaboration. Results: In patients with ICH, the number of cerebral microbleeds in lobes, basal ganglia, and the deep brain is positively correlated with ICH volume and independently correlated with neurological functional outcomes; white matter hyperintensity severity is positively correlated with ICH recurrence risk; multiple lacunar infarction independently predict the risk of ICH; severe brain atrophy is an independent risk factor for a poor prognosis in the long term in patients diagnosed with ICH; and the number of enlarged perivascular spaces is correlated with ICH recurrence. However, small subcortical infarct and ICH are the subject of few studies. Higher CSVD scores are independently associated with functional outcomes at 90 days in patients diagnosed with ICH.
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Ten undescribed cardiac glycosides, strasperosides A-J, together with twelve known analogues, were isolated from Streblus asper Lour. Their structures were elucidated on the basis of spectroscopic analysis, electronic circular dichroism data, and chemical methods. These cardiac glycosides showed diversity in steroid skeleton and sugar moiety. Strasperosides A and B are a pair of unusual stereoisomers featuring different orientation of the lactone motif. Ten cardiac glycosides demonstrated potent antiviral effects on HSV-1 in vitro with the IC50 values from 0.19 ± 0.08 to 1.03 ± 0.25 µM and the therapeutic indices from 66.61 ± 5.08 to 326.75 ± 11.75.
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Glicosídeos Cardíacos , Moraceae , Glicosídeos Cardíacos/farmacologia , Glicosídeos Cardíacos/química , Extratos Vegetais/química , Moraceae/química , Antivirais/química , Glicosídeos/farmacologiaRESUMO
Three new formyl phloroglucinol meroterpenoids, eumaidials A-C (1-3), were isolated from the leaves of Eucalyptus globulus subsp. maidenii, along with ten known analogues (4-13). Their chemical structures were determined by various spectral data and electronic circular dichroism calculations. Eumaidial A (1) is the first ß-caryophyllene-based formyl phloroglucinol meroterpenoids from the genus Eucalyptus. Compounds 1-4 and 10 exhibited ATP-citrate lyase inhibitory activities, and compounds 2 and 3 suppressed the hepatocyte lipogenesis.
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Eucalyptus , Complexos Multienzimáticos , Oxo-Ácido-Liases , Estrutura Molecular , Eucalyptus/química , Floroglucinol/farmacologia , Floroglucinol/química , Folhas de Planta/química , Trifosfato de AdenosinaRESUMO
Objective: To report a case of macular injury caused by short-term exposure to a handheld high-intensity light emitting diode (LED) light. Design: Interventional case report. Participant: A patient with macular injury caused by short-term exposure to the light of a handheld high-intensity LED device. Intervention: The patient was examined and followed for 3 months after exposure with ophthalmologic examinations (including funduscopy, optical coherence tomography [OCT], fluorescein angiography [FA], and multifocal electroretinography [mfERG]). The injured eye was treated with one retrobulbar injection of 20 mg triamcinolone acetonide at 5 days after exposure. Main outcome measures: Visual acuity, ophthalmoscopic, and OCT findings. Results: 3 days after exposure, the best corrected visual acuity (BCVA) of the right eye was 6/20. OCT revealed the acute stage of the injury with eminence of the retinal pigment epithelium (RPE). BCVA was improved to 16/20 and 20/20 at 19 and 33 days after exposure, respectively. OCT results of follow-ups at five days, 19 days, 33 days and 3 months after exposure have demonstrated the restoration process of the injury. Conclusions: Short-term exposure to high-intensity LED light may cause damage to the retina. As the expansion of LED use in modern life, education and supervision are of urgent need for public health.
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In a market environment where food safety problems still occur despite repeated prohibitions, food safety problems caused by veterinary drug residues and biological safety problems caused by the transfer of drug resistance have attracted much attention. Herein, a method based on a compound purification system coupled with direct analysis in real time-tandem mass spectrometry (DART-MS/MS) was established to determine 41 different types of veterinary drug residues in livestock and poultry products. First, a single-standard solution sampling method was used to optimize the selection of the best quasi-molecular ion, two daughter ions, and their cone-hole and collision voltages; qualitative and quantitative ion pairs are composed of a quasi-molecular ion and its corresponding daughter ion. The abundance ratios of the drug compounds in standard solutions of the solvent and matrix mixtures were then calculated according to the requirements of the European Union 2002/657 specification. DART-MS/MS was subsequently developed for the accurate characterization and quantitative analysis of the veterinary drugs. Finally, a composite purification pretreatment system was formed by combining the primary secondary amine (PSA) and octadecyl bonded silica gel (C18) of a QuEChERS technology with multiwalled carbon nanotubes (MWCNTs) to achieve the one-step purification of the drug compounds. The influence of the key parameters of the DART ion source on the determination of the drugs was investigated using the peak areas of the quantitative ions as the criterion. The optimum conditions were as follows: ion source temperature of 350 â, 12-Dip-it Samplers module, sample injection speed of 0.6 mm/s, and external vacuum pump pressure of -75 kPa. According to the differences in the dissociation constant (pKa) ranges of the 41 types of veterinary drug compounds and the characteristics of the sample matrixes, the extraction solvent, matrix-dispersing solvent, and purification method were optimized based on the recovery. The extraction solvent was 1.0% acetonitrile formate solution, and the pretreatment column included MWCNTs containing 50 mg of PSA and 50 mg of C18. The three chloramphenicol drugs showed a linear relationship in the ranges of 0.5-20 µg/L with correlation coefficients of 0.9995-0.9997,and the detection and quantification limits of three chloramphenicol drugs were 0.1 and 0.5 µg/kg, respectively. The 38 other drugs, including quinolones, sulfonamides, and nitro-imidazoles showed a linear relationship in the ranges of 2-200 µg/L with correlation coefficients of 0.9979-0.9999, and the detection and quantification limits of the 38 other drugs were 0.5 and 2.0 µg/kg, respectively. The recoveries of the 41 veterinary drugs at low, medium, and high spiked levels in chicken, pork, beef, and mutton samples were 80.0%-109.6%, with intra- and inter-day precisions of 0.3%-6.8% and 0.4%-7.0%, respectively. A total of 100 batches of animal meat (pork, chicken, beef, and mutton; 25 batches each) and known positive samples were simultaneously analyzed using the national standard method and the detection method established in this study. Sulfadiazine (89.2, 78.1, and 105.3 µg/kg) was detected in three batches of pork samples, and sarafloxacin (56.3, 102.0 µg/kg) was detected in two batches of chicken samples and no veterinary drugs were detected in the other samples; both methods yielded consistent results for known positive samples. The proposed method is rapid, simple, sensitive, environmentally friendly, and suitable for the simultaneous screening and detection of multiple veterinary drug residues in animal meat.
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Resíduos de Drogas , Nanotubos de Carbono , Animais , Bovinos , Gado , Aves Domésticas , Espectrometria de Massas em Tandem , Aminas , Galinhas , CloranfenicolRESUMO
Choroidal osteoma is a benign ossifying tumor within the choroid. Complications associated with choroidal osteoma, including disruption of retinal pigment epithelium, atrophy of photoreceptors, subretinal fluid, and choroidal neovascularization, present challenges for clinicians, and management remain controversial. We performed a comprehensive search in the PubMed, EMBASE, and Ovid databases for published studies and case reports relating to the management of choroidal osteoma. Since it was first described in 1978, various case reports of ocular complications associated with choroidal osteoma have been documented, and various therapies have yielded different outcomes. We systematically evaluate the literature published on this rare entity.
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Neoplasias da Coroide , Neovascularização de Coroide , Osteoma , Humanos , Neoplasias da Coroide/diagnóstico , Neoplasias da Coroide/terapia , Neoplasias da Coroide/complicações , Corioide/patologia , Osteoma/diagnóstico , Osteoma/terapia , Osteoma/complicações , Neovascularização de Coroide/tratamento farmacológico , Epitélio Pigmentado da Retina/patologia , Angiofluoresceinografia , Tomografia de Coerência ÓpticaRESUMO
Two enantiomeric pairs of macrocyclic acylphloroglucinols (1a/1b and 2a/2b) with an unprecedented carbon skeleton featuring a bicyclo[12.3.1]octadecane core, together with an undescribed biogenetically related long-chain acylphloroglucinol (3), were isolated from Syzygium szemaoense. Their structures were fully established by spectroscopic method, X-ray crystallographic analysis, and ECD calculation. Compounds 1b and 2a/2b exhibited inhibition against death-associated protein kinase-related apoptosis inducing protein kinase 2 (DRAK2) and ATP citrate lyase (ACLY), respectively.
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Syzygium , Estrutura Molecular , Cristalografia por Raios X , Análise EspectralRESUMO
Five undescribed enantiomeric pairs of acylphloroglucinol-monoterpene meroterpenoids ((+)-/(-)-eucateretins A-E) resolved by chiral-phase HPLC were obtained from the leaves of Eucalyptus tereticornis Smith, along with nine known analogues. Their structures were elucidated by spectroscopic methods and ECD calculations. This is the first report of meroterpenoid enantiomers from this plant. Some of the isolates, (-)-eucateretin A, (+)-/(-)-eucateretins E, 7'α-eucalrobusone X, eucalrobusone X, and robustadial B, exhibited inhibitory effects on ATP citrate lyase, and 7'α-eucalrobusone X significantly suppressed the hepatocyte lipogenesis.
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Eucalyptus , Monoterpenos , Monoterpenos/análise , ATP Citrato (pro-S)-Liase , Eucalyptus/química , Folhas de Planta/química , Aciltransferases , Estrutura MolecularRESUMO
Based on the concept of "smart tourism," this paper designs and implements a tourism management information system based on PSO-optimized NN. The foreground tourism web page of the system adopts DIV + CSS mode for page planning and layout, PHP as the client script language, and SQL server as the database to store and analyze user information. At the same time, the system adds personalized components to the user's search ranking results, so that the routes and scenic spots presented in front of users in the result interface are more in line with users' consumption habits. In order to verify the performance of the model and algorithm constructed in this paper, several experiments were carried out in this paper. Experimental results show that the prediction accuracy of this algorithm is 94.67% and the recall rate is 96.11%. This algorithm can overcome the disadvantages of traditional algorithms and provide some effective suggestions for tourism management. At the same time, this paper applies the concept of "smart tourism" to specific tourism informatization, which can promote the transformation and upgrading of tourism industry structure and further enhance the overall development level of tourism industry.
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Sistemas de Informação Administrativa , Turismo , Algoritmos , Humanos , Gestão da Informação , Redes Neurais de ComputaçãoRESUMO
Objective: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been engendering enormous hazards to the world. We obtained the complete genome sequences of SARS-CoV-2 from imported cases admitted to the Guangzhou Eighth People's Hospital, which was appointed by the Guangdong provincial government to treat coronavirus disease 2019 (COVID-19). The SARS-CoV-2 diversity was analyzed, and the mutation characteristics, time, and regional trend of variant emergence were evaluated. Methods: In total, 177 throat swab samples were obtained from COVID-19 patients (from October 2020 to May 2021). High-throughput sequencing technology was used to detect the viral sequences of patients infected with SARS-CoV-2. Phylogenetic and molecular evolutionary analyses were used to evaluate the mutation characteristics and the time and regional trends of variants. Results: We observed that the imported cases mainly occurred after January 2021, peaking in May 2021, with the highest proportion observed from cases originating from the United States. The main lineages were found in Europe, Africa, and North America, and B.1.1.7 and B.1.351 were the two major sublineages. Sublineage B.1.618 was the Asian lineage (Indian) found in this study, and B.1.1.228 was not included in the lineage list of the Pangolin web. A reasonably high homology was observed among all samples. The total frequency of mutations showed that the open reading frame 1a (ORF1a) protein had the highest mutation density at the nucleotide level, and the D614G mutation in the spike protein was the commonest at the amino acid level. Most importantly, we identified some amino acid mutations in positions S, ORF7b, and ORF9b, and they have neither been reported on the Global Initiative of Sharing All Influenza Data nor published in PubMed among all missense mutations. Conclusion: These results suggested the diversity of lineages and sublineages and the high homology at the amino acid level among imported cases infected with SARS-CoV-2 in Guangdong Province, China.
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COVID-19 , SARS-CoV-2 , Aminoácidos , COVID-19/epidemiologia , Genômica , Humanos , Mutação , Filogenia , SARS-CoV-2/genéticaRESUMO
Three novel dimeric sesquiterpenoids named sarglanoids A-C (1-3), two undescribed monomeric sesquiterpenoids named sarglanoids D (4) and E (5), and seven known compounds (6-12), were isolated and characterized from Sarcandra glabra. Compound 1 represents the first heterodimeric sesquiterpenoid composed of a eudesmane and an eremophilane moiety. Compound 2 possesses two eremophilane monomers featuring an undescribed dimerization pattern. Compound 3 is a symmetric eudesmane dimer with a rare 1,4-epoxy bridge. The structures of 1-5 were fully identified by spectroscopic methods and single-crystal X-ray diffraction experiments. Compounds 3 and 6 suppressed the LPS-triggered inflammatory responses in RAW 264.7 cells.
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Sesquiterpenos de Eudesmano , Sesquiterpenos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Camundongos , Estrutura Molecular , Sesquiterpenos Policíclicos , Células RAW 264.7 , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Eudesmano/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT<2ULN) and early liver fibrosis (F ≤ 2). AIM OF THE STUDY: We aimed to investigate whether monotherapy with AHP improves liver histology in these patients. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT<2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment. RESULTS: Per-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients. CONCLUSIONS: Treatment of CHB patients who had ALT<2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future.
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Hepatite B Crônica , Alanina/uso terapêutico , Alanina Transaminase , Medicamentos de Ervas Chinesas , Hepatite B Crônica/tratamento farmacológico , Humanos , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologiaRESUMO
Rationale: Recent studies have demonstrated that the loss of podocyte is a critical event in diabetic nephropathy (DN). Previously, our group have found that the mitotic arrest deficient protein MAD2B was involved in high glucose (HG)-induced podocyte injury by regulating APC/C activity. However, the exact mechanism of MAD2B implicated in podocyte injury is still lacking. Methods: The experiments were conducted by using kidney tissues from streptozotocin (STZ) induced diabetic mice with or without podocyte-specific deletion of MAD2B and the cultured podocytes exposed to different treatments. Glomerular pathological injury was evaluated by periodic acid-Schiff staining and transmission electron microscopy. The endogenous interaction between MAD2B and Numb was discovered by yeast two-hybrid analysis and co-immunoprecipitation assay. The expressions of MAD2B, Numb and related pathway were detected by western blot, immunochemistry and immunofluorescence. Results: The present study revealed that MAD2B was upregulated in diabetic glomeruli and cultured podocytes under hyperglycemic conditions. Podocyte-specific deletion of MAD2B alleviated podocyte injury and renal function deterioration in mice of diabetic nephropathy. Afterwards, MAD2B was found to interact with Numb, which was downregulated in diabetic glomeruli and HG-stimulated cultured podocytes. Interestingly, MAD2B genetic deletion could partly reverse the decline of Numb in podocytes exposed to HG and in diabetic mice, and the expressions of Numb downstream molecules such as NICD and Hes-1 were decreased accordingly. In addition, overexpression of Numb ameliorated HG-induced podocyte injury. Conclusions: The present findings suggest that upregulated MAD2B expression contributes to Numb depletion and activation of Notch 1 signaling pathway, which ultimately leads to podocyte injury during DN progression.