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BACKGROUND Currently, proton pump inhibitors (PPIs) are the first-line treatment for ulcers resulting from endoscopic submucosal dissection (ESD). Vonoprazan is a new oral potassium-competitive acid blocker (P-CAB). The aim of this systematic review and meta-analysis was to compare the efficacy, safety, and tolerance of vonoprazan with PPIs in the treatment of peptic ulcers resulting from ESD. MATERIAL AND METHODS Published results of randomized clinical trials (RCTs) comparing vonoprazan with PPIs in the treatment of ulcers resulting from ESD were identified up to March 2018. The main clinical endpoints evaluated were healing rate and adverse events. The meta-analysis included quality assessment of the studies, statistical analysis of endpoints, and sensitivity analysis using Revman version 5.3 meta-analysis software. RESULTS Systematic literature review identified seven published studies that included 548 patients. Five studies were published as full-text manuscripts, and two studies were published as abstracts. Meta-analysis of the vonoprazan treatment, compared with PPI treatment, for ESD showed that the pooled relative risk (RR) of healing rate was 0.64 (95% CI, 0.33-1.22) for the 4-week study group and 0.98 (95% CI, 0.84-1.15) for the 8-week study group. The RR for adverse events was 0.65 (95% CI, 0.31-1.38) (P>0.05). No statistical evidence of publication bias was found. CONCLUSIONS The findings of the systematic review and meta-analysis showed that the efficacy of vonoprazan was comparable with PPIs for the treatment of peptic ulcers following ESD. Further studies are required to support the safety and efficacy of vonoprazan compared with different types of PPIs.
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Úlcera Péptica/tratamento farmacológico , Inibidores da Bomba de Prótons/farmacologia , Pirróis/farmacologia , Sulfonamidas/farmacologia , Ressecção Endoscópica de Mucosa/métodos , Humanos , Complicações Pós-Operatórias , Neoplasias Gástricas , Resultado do Tratamento , CicatrizaçãoRESUMO
BACKGROUND: Hereditary spherocytosis (HS) is a type of hemolytic anemia caused by abnormal red cell membrane skeletal proteins with few unique clinical manifestations in the neonate and infant. An ANK1 gene mutation is the most common cause of HS. CASE PRESENTATION: The patient was a 11-month-old boy who suffered from anemia and needed a regular transfusion therapy at an interval of 2-3 months. Hematological investigations showed moderate anemia (Hb80 g/L). Red cells displayed microcytosis (MCV76.4 fl, MCH25.6 pg, MCHC335 g/L). The reticulocytes were elevated (4.8%) and the spherocytes were increased (10%). Direct antiglobulin test was negative. Biochemical test indicated a slight elevation of bilirubin, mainly indirect reacting (TBIL32.5 µmol/L, IBIL24 µmol/L). The neonatal HS ratio is 4.38, obviously up the threshold. Meanwhile, a de novo ANK1 mutation (exon 25:c.2693dupC:p.A899Sfs*11) was identified by next-generation sequencing (NGS). Thus, hereditary spherocytosis was finally diagnosed. CONCLUSIONS: Gene detection should be considered in some hemolytic anemia which is difficult to diagnose by routine means. We identified a novel de novo ANK1 heterozygous frameshift mutation in a Yi nationality patient while neither of his parents carried this mutation.
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Anquirinas/genética , Mutação , Esferocitose Hereditária/genética , Transfusão de Sangue , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Esferocitose Hereditária/terapiaRESUMO
BACKGROUND AND AIM: Sophocarpine, a tetracyclic quinolizidine alkaloid derived from Sophora alopecuroides L., has been documented that it can suppress pro-inflammatory cytokines synthesis in alleviating nonalcoholic steatohepatitis (NASH) in vivo. Toll-like receptor 4 (TLR4) is a pattern recognition receptor whose activation results in the production of several pro-inflammatory cytokines. It has been reported that TLR4 is upregulated in nonalcoholic fatty liver disease and plays an important role in the pathogenesis of NASH. This study aimed to examine the changes of TLR4 and its signaling pathways in sophocarpine's anti-inflammatory process on experimental NASHâ in vitro. METHODS: Primary hepatocytes were isolated, and oleic acid-induced steatosis model was established. Cell Counting Kit-8 assay was used to detect the number of metabolically active mitochondria and viable cells. Immunocytochemistry analysis was applied to evaluating pro-inflammatory cytokines synthesis. Total RNA and protein were extracted for real-time polymerase chain reaction and Western blot detection. RESULTS: Enhanced expression of TLR4 was observed in oleic acid-induced steatotic hepatocytes. Sophocarpine suppressed pro-inflammatory cytokines synthesis and reduced the expression of TLR4 in steatotic hepatocytes. Expression of TLR4 and pro-inflammatory cytokines recovered after sophocarpine was removed. Moreover, sophocarpine restrained the activation of nuclear factor-kappaB (NF-κB), c-Jun-N-terminal kinase (JNK), and Extracellular regulated protein kinases (ERK) signaling pathways in the anti-inflammatory process. CONCLUSION: Sophocarpine could decrease the expression of TLR4 in steatotic hepatocytes and suppress pro-inflammatory cytokines synthesis. NF-κB, JNK, and ERK signaling pathways were important workable downstream pathways.
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Alcaloides/farmacologia , Citocinas/biossíntese , Hepatócitos/metabolismo , Mediadores da Inflamação , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Ácido Oleico , Reação em Cadeia da Polimerase , Ratos Sprague-Dawley , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Sophora/química , Regulação para Cima/efeitos dos fármacosRESUMO
This study aimed to learn the recurrence rate in the retreatment TB patients with sputum smear and/or culture positive (ss+ and/or c+) two years after they were declared cured, and to explore causes of recurrence in order to improve long-time treatment outcome. 5 cities were selected as research locations. Recurrence of TB was judged by chest X-ray examination together with sputum smear and culture examination. Questionnaire was carried out to collect data on treatment history, demographics and possible risk factors. Chi-square test and logistic regression were conducted using SPSS in this study. As the result, 99 active TB patients were identified and the recurrence rate was 16.67% and irregular medicine and smoking were the causes of the recurrence. The retreatment TB patients with sputum smear and/or culture positive in this study had higher recurrence rate and health education work on regular medication and smoking should be strengthened.
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Antituberculosos/uso terapêutico , Escarro/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologiaRESUMO
High-throughput Illumina RNA-seq was used for deep sequencing analysis of the transcriptome of poly(A)+ RNA from mycelium grown under three different conditions: 30 days darkness (sample 118), 80 days darkness (313W), and 30 days darkness followed by 50 days in the light (313C), in order to gain insight into the molecular mechanisms underlying the process of light-induced brown film (BF) formation in the edible mushroom, Lentinula edodes. Of the three growth conditions, BF formation occurred in 313C samples only. Approximately 159.23 million reads were obtained, trimmed, and de novo assembled into 31,511 contigs with an average length of 1,746 bp and an N 50 of 2,480 bp. Based on sequence orientations determined by a BLASTX search against the NR, Swiss-Prot, COG, and KEGG databases, 24,246 (76.9 %) contigs were assigned putative descriptions. Comparison of 313C/118 and 313C/313W expression profiles revealed 3,958 and 5,651 significantly differentially expressed contigs (DECs), respectively. Annotation using the COG database revealed that candidate genes for light-induced BF formation encoded proteins linked to light reception (e.g., WC-1, WC-2, phytochrome), light signal transduction pathways (e.g., two-component phosphorelay system, mitogen-activated protein kinase pathway), and pigment formation (e.g., polyketide synthase, O-methyltransferase, laccase, P450 monooxygenase, oxidoreductase). Several DECs were validated using quantitative real-time polymerase chain reaction. Our report is the first to identify genes associated with light-induced BF formation in L. edodes and represents a valuable resource for future genomic studies on this commercially important mushroom.
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Perfilação da Expressão Gênica , Luz , Pigmentos Biológicos/biossíntese , Cogumelos Shiitake/genética , Cogumelos Shiitake/efeitos da radiação , Transdução de Sinais , Sequenciamento de Nucleotídeos em Larga Escala , Cogumelos Shiitake/metabolismoRESUMO
The Nernst effect is the transverse mode of thermoelectric transport, in which a longitudinal thermal gradient induces a transverse current in the conductor while under a perpendicular magnetic field. Here the Nernst effect in a mesoscopic topological nodal-line semimetals (TNLSMs) system of four-terminal cross-bar with the spin-orbit coupling under a perpendicular magnetic field is studied. The Nernst coefficientNcin two non-equivalen connection modes (kz-ymode andkx-ymode) is calculated based on the tight-binding Hamiltonian combined with the nonequilibrium Green's function method. When the magnetic field is absent withφ = 0.0, the Nernst coefficientNc=0is exactly regardless of the temperature. When the magnetic field is not zero, the Nernst coefficient exhibits a series of densely oscillating peaks. The height of peak strongly depends on the magnetic field, and the Nernst coefficient is an even function of the Fermi energyEFsatisfying the symmetrical propertyNc(-EF)=Nc(EF). The Nernst coefficient is also closely related to the temperatureT. When the temperature is very low (orTâ0), the Nernst coefficient depends linearly on temperature. In the presence of a strong magnetic field, the Nernst coefficient shows peaks when the Fermi energy crosses the Landau levels. Under the weak magnetic field, the influence of spin-orbit coupling in TNLSMs materials on Nernst effect is very obvious. In the presence of the mass term, thePT-symmetry of the system is destroyed, the nodal ring of TNLSMs is broken and an energy gap will be opened. The Nernst coefficientNchas a large value in the energy gap, which is very promising for the application of the transverse thermoelectric transport.
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BACKGROUND: The use of a colonic stent as a bridge to surgery aims to provide patients with elective one-stage surgical resection while reducing stoma creation and postoperative complications. This study used meta-analytic techniques to compare the outcomes of stent use as a bridge to surgery and emergency surgery in the management of obstructive colorectal cancer. METHODS: A literature search of Medline, Embase, Cochrane controlled trials registry, and the Chinese Biomedical Literature Database was performed on all studies comparing stent as a bridge to surgery and emergency surgery for obstructive colorectal cancer. A meta-analysis of the included studies was carried out to identify the differences in outcomes between the two procedures. RESULTS: Eight studies matched the criteria for inclusion and reported on the outcomes of 601 patients, of whom 232 (38.6%) underwent stent insertion and 369 (61.4%) underwent emergency surgery. Fewer patients in the stent group needed intensive care (risk ratio [RR], 0.42; 95% confidence interval [CI], 0.19-0.93; p = 0.03) and stoma creation (RR, 0.70; 95% CI, 0.50-0.99; p = 0.04). The primary anastomosis rate in the stent group was higher (RR, 1.62; 95% CI, 1.21-2.16; p = 0.001). Overall complications (RR, 0.42; 95% CI, 0.24-0.71; p = 0.001), including anastomotic leakage (RR, 0.31; 95% CI, 0.14-0.69; p = 0.004), were reduced by stent insertion. Stent placement before elective surgery did not adversely affect mortality and long-term survival. CONCLUSIONS: The use of a stent as a bridge to surgery for obstructive left-sided colorectal cancer could increase the chance of primary anastomosis and reduce the need for stoma creation and postprocedural complications. Stent insertion before subsequent surgery has no effect on perioperative mortality and long-term survival.
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Neoplasias Colorretais/cirurgia , Tratamento de Emergência/instrumentação , Obstrução Intestinal/cirurgia , Stents , Colectomia/mortalidade , Colectomia/estatística & dados numéricos , Neoplasias Colorretais/complicações , Neoplasias Colorretais/mortalidade , Colostomia/mortalidade , Colostomia/estatística & dados numéricos , Emergências , Tratamento de Emergência/métodos , Tratamento de Emergência/mortalidade , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/mortalidade , Laparoscopia/mortalidade , Laparoscopia/estatística & dados numéricos , Tempo de Internação , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamanho da AmostraRESUMO
Thermoelectric effects in quantum systems have been focused in recent years. Thermoelectric energy conversion study of systems with edge states, such as quantum Hall insulators and quantum spin Hall insulators, is one of the most important frontier topics in material science and condensed-matter physics. Based on the previous paper (Gresta in Phys Rev Lett 123:186801, 2019), we further investigated the linear and nonlinear thermoelectric transport properties of helical edge states of the quantum spin Hall insulators coupled with double nanomagnet, calculated the Seebeck coefficients [Formula: see text] and the thermoelectrical figure of merit ZT, discussed the influence of the length of the nanomagnet and the relative tilt angle of component of the magnetization perpendicular on the thermoelectric coefficients ([Formula: see text] and ZT), and summarized some meaningful conclusions in the linear response regime. In the nonlinear regime, we calculated the equivalent figure of merit [Formula: see text] and the power-generation efficiency [Formula: see text] in different length of the nanomagnet, obtain the temperature difference of achieving optimal thermoelectricity. The results of this paper further confirm that the setup can indeed be used as a device for achieving high performance thermoelectric.
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Recently discovered topological nodal-line semimetals (TNLSMs) have received considerable research interest due to their rich physical properties and potential applications. TNLSMs have the particular band structure to lead to many novel properties. Here we theoretically study the thermoelectric transport of a two-terminal pristine TNLSM nanowires and TNLSMsp-n-pjunctions. The Seebeck coefficientsScand the thermoelectrical figure of meritZTare calculated based on the Landauer-Büttiker formula combined with the nonequilibrium Green's function method. In pristine TNLSM nanowires, we discuss the effect of the magnetic fieldsφ, the disorderD, the on-site energyµz, and the mass termmon the thermoelectric coefficient and find that the transport gap can lead to a largeScandZT. When transmission coefficient jumps from one integer plateau to another,ScandZTshow a series of peaks. The peaks ofScandZTare determined by the jump of the transmission coefficient plateau and are not associated with the plateau itself. For TNLSMsp-n-pjunctions,ScandZTstrongly depend on the parameterξof potential well. We can get a largeZTby adjusting the parameterξand magnetic fieldφ. In TNLSMsp-n-pjunctions,ZThas the large value and is easily regulated. This setup has promising application prospects as a thermoelectric device.
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BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is one entity in the spectrum of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to explore the prevention and therapeutic effect of sophocarpine on experimental rat NASH. METHODS: Sophocarpine with the dosage of 20 mg/kg/day was injected into NASH rats. At the end of 12 weeks, all rats were killed to detect the degree of fatty degeneration, inflammation and fibrosis. RESULTS: Sophocarpine intervention (in the pro-treated and treated groups) resulted in a significant decrease of liver weight, liver index, serum transaminase and serum lipids. Messenger RNA expressions of leptin, interleukin (IL)-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß1, procollagen-I and α-smooth muscle actin (SMA) and deposition of IL-6, TNF-α and TGF-ß1 in liver decreased, whereas the messenger RNA expression of adiponectin increased significantly compared with that in the model group. Moreover, histological improvement was also observed in the sophocarpine intervention group. In addition, there was no significant difference in any detected indicator between the pro-treated and treated group. CONCLUSIONS: Sophocarpine could decrease the level of serum transaminase, improve lipid metabolism, reduce synthesis of inflammatory cytokines TNF-α, TGF-ß1 and IL-6, activate protective adipocytokine adiponectin, and might be selected as a promising agent for the clinical prevention and therapy of NASH.
Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Fígado/efeitos dos fármacos , Adipocinas/sangue , Adipocinas/genética , Animais , Citocinas/sangue , Citocinas/genética , Citoproteção , Modelos Animais de Doenças , Regulação para Baixo , Fígado Gorduroso/imunologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/prevenção & controle , Mediadores da Inflamação/sangue , Lipídeos/sangue , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Fatores de Tempo , Transaminases/sangueRESUMO
Inflammation is the main contributor for the pathogenesis of nonalcoholic steatohepatitis (NASH). Src homology region 2 domain-containing phosphatase 1 (SHP-1, also known as PTPN6) is regarded as a negative regulator of inflammation, but its role in NASH remains unknown. Here, hepatocyte-specific Ptpn6 knockout mice (Ptpn6HKO ) and adenovirus vector-mediated ectopic expression of SHP-1 (AdSHP1) were used to evaluate the role of SHP-1 in a methionine- and choline-deficient diet-induced NASH model. Compared with the control littermates, Ptpn6HKO mice show exacerbated hepatic steatosis, inflammation, and fibrosis. Additionally, administration of AdSHP1 significantly ameliorates steatohepatitis and inhibits the expression of proinflammatory cytokines, including transforming growth factor-ß, interleukin-6, and tumor necrosis factor-α. Our data indicate that SHP-1 could be a potential therapeutic target for NASH.
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Citocinas/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Animais , Citocinas/genética , Modelos Animais de Doenças , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/patologia , Proteína Tirosina Fosfatase não Receptora Tipo 6/genéticaRESUMO
Background: Thalassemia is an autosomal genetic disorder, found throughout the world. It is still not treatable and create socio economic problems. In this study, we investigated the prevalence and spectrum features of thalassemia in Yunnan Province, the southwestern area of China. During 2014-2018, a total of 3,539 suspected thalassemia children were detected with α- and ß-thalassemia mutations by gap-Polymerase Chain Reaction (PCR) and reverse dot blot (RDB) analysis in Kunming Children's Hospital. Results: Of these patients, 1,130 were diagnosed thalassemia gene carriers with a carrying rate of 31.92%. Among them, α-thalassemia was 43.63%, ß-thalassemia was 53.98%, cases with both α- and ß- thalassemia was 2.39%. In α-thalassemia patients, the most common mutations was -SEA/αα (52.13%), followed by -α3.7/αα (27.79%), hemoglobin H disease (18.46%), and -α4.2/αα (1.62%). Fifteen gene mutations and 30 genotypes were identified in ß-thalassemia patients, with the five most common mutations CD17 (A>T) (29.51%), CD41-42 (-TTCT) (27.87%), IVS-II-654 (C>T) (14.92%), CD26 (G>A) (6.89%), and CD26/CD27 (2.62%) accounting for 81.81% of the ß-globin gene mutations. Furthermore, we founded two rare mutations CD34 (TGG â TAG) and Int in Chinese populations. Conclusions: Our results suggested that the prevalence and gene mutation spectrum of thalassemia display obviously heterogeneity among children in Yunnan Province. The findings provide the valuable information for premarital and pre-pregnancy screening, prenatal diagnostic services, and designing appropriate prevention programs to control thalassemia for future in this area.
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Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.
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Infecções por Coronavirus/mortalidade , Aprendizado de Máquina , Pandemias , Pneumonia Viral/mortalidade , Idoso , Betacoronavirus , COVID-19 , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Medição de Risco , SARS-CoV-2 , Máquina de Vetores de SuporteRESUMO
China is home to rich wild and cultivated strains of Lentinus edodes, an important edible and medicinal mushroom. Artificial selection of L. edodes has a long history, and the widely cultivated strains belong to populations different from those of most wild strains. Internal transcribed spacer (ITS) regions have been used as good markers to identify L. edodes populations. But because ITS regions exhibit incomplete concerted evolution, the use of an ITS to identify L. edodes populations has been questioned. The objective of this study was to determine whether the ITS region is suitable for identifying L. edodes populations and which populations the widely cultivated strains and the most wild strains belong to by investigating intraindividual and differential ITS polymorphisms between 44 cultivars and 44 wild strains of L. edodes in China. Intraindividual ITS polymorphism is common in L. edodes strains, and most strains possessed 2 different ITS sequences, which came from their heterokaryons. The genetic polymorphisms of ITS1, 5.8S, and ITS2 in L. edodes strains are distinct. All strains were divided into one 5.8S type (5.8S-A), 2 ITS1 types (ITS1-A and ITS1-B), and 2 ITS2 types (ITS2-A and ITS2-B), which were subdivided into 2 branches (ITS2-A1 and ITS2-A2; ITS2-B1 and ITS2-B2). ITS1/5.8S/ITS2 could be used as a good marker in preliminary classification of L. edodes strains in China. It not only exhibited classified information of ITS1, 5.8S, and ITS2 for each strain at the same time, it also indicated whether the strain was heterozygous. The 44 cultivated strains were mainly the A/A/A1 type, and the 44 wild strains were mainly the A/A/A2 and other mixed types.
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DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Variação Genética , RNA Ribossômico 5,8S/genética , Análise de Sequência de DNA , Cogumelos Shiitake/classificação , Cogumelos Shiitake/genética , China , Análise por Conglomerados , DNA Fúngico/química , DNA Ribossômico/química , DNA Ribossômico/genética , DNA Espaçador Ribossômico/química , Genótipo , Filogenia , Cogumelos Shiitake/isolamento & purificaçãoRESUMO
Uterine leiomyomata are benign, smooth-muscle tumors. The tumors are very common, affecting approximately 10-15 million women in the United States annually. Uterine leiomyomata are often asymptomatic, but may cause symptoms that range in severity from mild abdominal discomfort to uterine prolapse. Several different chromosomal aberrations have been found in the tumor tissue. Because of the common occurrence of this tumor and the potential severity of associated sequelae, research delineating the different molecular subtypes is needed. Deletions on the long arm of chromosome 7 are believed to be the most common genetic anomaly in uterine leiomyoma. The size of the deletion varies, which makes it difficult to identify the genes that, upon deletion, contribute to tumor growth. The smallest previously defined interval was >12,000 kb. We have narrowed a minimal region to an interval of <500 kb.
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Cromossomos Humanos Par 7 , Leiomioma/genética , Neoplasias Uterinas/genética , Feminino , HumanosRESUMO
AIM: To explore the effect of sophocarpine on experimental liver fibrosis and the potential mechanism involved. METHODS: Sophocarpine was injected intraperitoneally in two distinct rat hepatic fibrosis models induced either by dimethylnitrosamine or bile duct ligation. Masson's trichrome staining, Sirius red staining and hepatic hydroxyproline level were used for collagen determination. Primary hepatic stellate cells (HSCs) were isolated and treated with different concentrations of sophocarpine. Real-time reverse transcription-polymerase chain reaction was used to detect the mRNA levels of fibrotic markers and cytokines. The expression of pathway proteins was measured by Western blot. The Cell Counting Kit-8 test was used to detect the proliferation rate of activated HSCs treated with a gradient concentration of sophocarpine. RESULTS: Sophocarpine decreased serum levels of aminotransferases and total bilirubin in rats under chronic insult. Moreover, administration of sophocarpine suppressed extracellular matrix deposition and prevented the development of hepatic fibrosis. Furthermore, sophocarpine inhibited the expression of α-smooth muscle actin (SMA), interleukin (IL)-6, transforming growth factor-ß1 (TGF-ß1), Toll-like receptor 4 (TLR4), and extracellular-related kinase (ERK) in rats. Sophocarpine also down-regulated the mRNA expression of α-SMA, collagenâ I, collagen III, TGF-ß1, IL-6, tumor necrosis factor-α and monocyte chemoattractant protein-1, and decreased protein levels of TLR4, p-ERK, p-JNK, p-P38 and p-IKK in vitro after Lipopolysaccharide induction. In addition, sophocarpine inhibited the proliferation of HSCs accompanied by a decrease in the expression of Cyclin D1. The protein level of proliferating cell nuclear antigen was decreased in activated HSCs following a gradient concentration of sophocarpine. CONCLUSION: Sophocarpine can alleviate liver fibrosis mainly by inhibiting the TLR4 pathway. Sophocarpine may be a potential chemotherapeutic agent for chronic liver diseases.
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Alcaloides/farmacologia , Cirrose Hepática/patologia , Receptor 4 Toll-Like/metabolismo , Animais , Ductos Biliares/cirurgia , Proliferação de Células , Células Cultivadas , Colágeno/metabolismo , Corantes/química , Dimetilnitrosamina/química , Hidroxiprolina/metabolismo , Fígado/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Transdução de SinaisRESUMO
Sophocarpine, an effective compound derived from foxtail-like sophora herb and seed, has been reported that it can alleviate non-alcoholic steatohepatitis (NASH) in rats and affect adipocytokine synthesis. Meanwhile, adipocytokines could adjust hepatic lipid metabolism through AMPK signaling pathway. In the work presented here, primary hepatocytes were isolated from specific pathogen-free male SD rats and incubated with 200 µmol/L oleic acid for 24h to induce steatotic model, then treated with sophocarpine for 72 h. Oil red staining was performed to evaluate steatosis, total RNA and protein of primary hepatocytes were extracted for real-time RT-PCR and western blot analysis. A cluster of aberrances were observed in the model group, including hepatocyte steatosis, increased leptin and decreased adiponectin mRNA expressions. While sophocarpine treatment resulted in: significant improvement of steatosis (>50% decrease), decrease of leptin expression (<0.57-fold) and increase of adiponectin expression (>1.48-fold). Moreover, compared with the model group, sophocarpine could significantly increase P-AMPKα (>5.82-fold), AMPKα (>1.29-fold) and ACC (>3.27-fold) protein expressions, and reduce P-ACC (<0.30-fold) and HNF-4α (<0.20-fold) protein expression. The mRNA expression of Srebp-1c was downregulated significantly simultaneously (<0.68-fold). We concluded that sophocarpine could alleviate hepatocyte steatosis and the potential mechanism might be the activated signaling pathway of AMPK.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Fígado Gorduroso/tratamento farmacológico , Adipocinas/metabolismo , Adiponectina/metabolismo , Alcaloides/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fígado Gorduroso/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To study the prevalence and trend of tuberculosis for related policy development in Shandong. METHODS: The population under the current study was randomly sampled, using both stratified clustering sampling and proportional population sampling methods, following the national survey protocol. A total of 35 clusters including about 1500 subjects per cluster were established, representing a population of 9.31 million. Questionnaire interview and chest X-ray exam were applied to all inhabitants above 15 years of age. Sputum microscopy and culture were given to all suspected cases with cough longer than 2 weeks or having abnormal X-ray results. RESULTS: In total, 54 279 subjects were interviewed and examined, accounting for 95.78% of eligible population. Of them, 183 active pulmonary tuberculosis cases were identified, with 60.11% asymptomatic. Two of the 35 (5.71%) clusters had no active tuberculosis cases found, and 24 (68.57%) did not show smear positive results. The standardized prevalence rates of active, smear positive and bacteriologic positive pulmonary tuberculosis cases were 270.87/10(5), 17.45/10(5) and 29.57/10(5), with the estimated case numbers as 211 900 (170 100 - 253 600), 13 600 (5800 - 21 500) and 23 100 (13 200 - 33 000) respectively. Compared to the survey in 2000, the rates on smear positive and bacteriologic positive tuberculosis had decreased significantly, at a rate of 81.63%, and 75.56% respectively. The rates in urban areas and in women decreased quickly than those in rural areas and in men. People living in the rural areas, being elderly or males, had significantly higher prevalence rates of tuberculosis. CONCLUSION: Remarkable reduction of tuberculosis prevalence had been achieved despite the fact that tuberculosis remained a major public health problem in Shandong province. Symptomatic patients should be under more serious concern in order to improve the detection of early cases. More efforts should be given to rural population, especially elderly, male population.
Assuntos
Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , China/epidemiologia , Monitoramento Epidemiológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , População Rural , Estudos de Amostragem , Tuberculose/prevenção & controle , População Urbana , Adulto JovemRESUMO
A rapid, inexpensive and reliable method for total RNA extraction from fruiting bodies of Lentinula edodes containing large quantities of polysaccharides and secondary metabolites is described. An initial extraction step using saturated NaCl solution facilitates the separation of nucleic acids from contaminants and, after further extraction with organic solvents and precipitation with 2-propanol, total RNA of high purity and suitable for applications such as cDNA synthesis, RT-PCR and Northern blot hybridization was obtained. The procedure may also have wider applicability for total RNA extraction from the tissues of other mushrooms.