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A Gram-negative, rod-shaped aerobic bacterium designated as strain 2R12T was isolated from the rhizosphere soil of Hosta plantaginea. Phylogenetic analyses based on the 16S rRNA gene revealed that strain 2R12T should be assigned to the genus Chitinophaga with the highest sequence similarity to Chitinophaga arvensicola DSM 3695T (99.1â%) and Chitinophaga ginsengisegetis DSM 18108T (98.6â%). The major fatty acids of strain 2R12T (>10â%) were iso-C15â:â0, C16â:1 ω5c and iso-C17â:â0 3-OH. The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids and five unidentified lipids. The predominant respiratory quinone was MK-7. The genomic DNA G+C content was 46.1âmol%. The average nucleotide identity values of strain 2R12T with C. arvensicola DSM 3695T and C. ginsengisegetis DSM 18108T were 77.9 and 78.8â%, respectively, while in silico DNA-DNA hybridization values for strain 2R12T with these strains were 22.8 and 23.3â%, respectively. Based on comparative analysis of phylogenetic, phylogenomic, phenotypic and chemotaxonomic characteristics, strain 2R12T represents a novel species in the genus Chitinophaga, for which the name Chitinophaga hostae sp. nov. is proposed. The type strain is 2R12T (=ACCC 61757T=JCM 34719T).
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Gammaproteobacteria , Hosta , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Gammaproteobacteria/genética , Hosta/genética , Filogenia , ARN Ribosómico 16S/genética , Rizosfera , Análisis de Secuencia de ADN , Suelo , Microbiología del Suelo , Vitamina K 2RESUMEN
BACKGROUND: Patients with nonmetastatic pT3-4 colon cancers are prone to develop metachronous peritoneal carcinomatosis (mPC). Risk factors for mPC and the influence of mutant kirsten rat sarcoma viral oncogene (KRAS)/neuroblastoma rat sarcoma (NRAS)/v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and DNA mismatch repair (MMR) status on mPC remain to be described in these patients. METHOD: All enrolled patients were identified from the prospectively collected colorectal cancer database of a tertiary referral hospital between 2013 and 2018. Multivariate analysis was used to identify risk factors associated with mPC. RESULTS: Of the 1689 patients with nonmetastatic pT3-4 colon carcinoma, 8.4% (142/1689) progressed to mPC. Endoscopic obstruction (HR = 3.044, p < 0.001), elevated CA125 (HR = 1.795, p = 0.009), pT (T4a vs. T3, HR = 2.745, p < 0.001; T4b vs. T3, HR = 3.167, p = 0.001), pN (N1 vs. N0, HR = 2.592, p < 0.001; N2 vs. N0, HR = 4.049, p < 0.001), less than 12 lymph nodes harvested (HR = 2.588, p < 0.001), mucinous or signet ring cell carcinoma (HR = 1.648, p = 0.038), perineural invasion (HR = 1.984, p < 0.001), and adjuvant chemotherapy (HR = 1.522, p = 0.039) were strongly related to mPC but that mutant KRAS/NRAS/BRAF and MMR status was not associated with mPC. CONCLUSION: This study identified the high-risk factors for mPC in patients with nonmetastatic pT3-4 colon carcinoma, and these factors should be considered in selective preventive therapy and close follow-up for patients subsequently deemed to have high risk for mPC.
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Carcinoma de Células en Anillo de Sello , Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias Peritoneales , Animales , Carcinoma de Células en Anillo de Sello/patología , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Neoplasias Colorrectales/patología , Ratones , Mutación , Estadificación de Neoplasias , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/patología , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Factores de RiesgoRESUMEN
Adenomyosis (ADS) is an estrogen-dependent gynecological disease with unspecified etiopathogenesis. Local hyperestrogenism may serve a key role in contributing to the origin of ADS. Talin1 is mostly identified to be overexpressed and involved in the progression of numerous human carcinomas through mediating cell proliferation, adhesion and motility. Whether Talin1 exerts an oncogenic role in the pathogenesis of ADS and puts an extra impact on the efficacy of estrogen, no relevant data are available yet. Here we demonstrated that the adenomyotic eutopic and ectopic endometrial stromal cells (ADS_Eu_ESC and ADS_Ec_ESC) treated with ß-estradiol (ß-E2) presented stronger proliferative and pro-angiogenetic capacities, accompanied by increased expression of PCNA, Ki67, VEGFB and ANGPTL4 proteins. Meanwhile, these promoting effects were partially abrogated by Fulvestrant (ICI 182780, an estrogen-receptor antagonist). Aberrantly upregulation of Talin1 mRNA and protein level was observed in ADS endometrial specimens and stromal cells. Through performing functional experiments in vitro, we further determined that merely overexpression of Talin1 (OV-Talin1) also enhanced ADS stromal cell proliferation and pro-angiogenesis, while the most pronounced facilitating effects were found in the co-intervention group of OV-Talin1 plus ß-E2 treatment. Results from the xenograft nude mice model showed that the hypodermic endometrial lesions from co-intervention group had the highest mean weight and volume, compared with that of individual OV-Talin1 or ß-E2 treatment. The expression levels of PCNA, Ki67, VEGFB and ANGPTL4 in the lesions were correspondingly elevated the most in the co-intervention group. Our findings unveiled that overexpressed Talin1 might cooperate withß-E2 in stimulating ADS endometrial stromal cell proliferation and neovascularization, synergistically promoting the growth and survival of ectopic lesions. These results may be beneficial to provide a new insight for clarifying the pathogenesis of ADS.
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Adenomiosis/fisiopatología , Endometrio/patología , Células del Estroma/fisiología , Talina/fisiología , Adenocarcinoma , Adenomiosis/genética , Adenomiosis/metabolismo , Animales , División Celular/efectos de los fármacos , Línea Celular Tumoral , Células Cultivadas , Ensayo de Unidades Formadoras de Colonias , Neoplasias Endometriales , Estradiol/farmacología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Miometrio/patología , Neovascularización Patológica/fisiopatología , Neovascularización Fisiológica/efectos de los fármacos , Interferencia de ARN , ARN Interferente Pequeño/genética , Proteínas Recombinantes/metabolismo , Organismos Libres de Patógenos Específicos , Células del Estroma/efectos de los fármacos , Talina/biosíntesis , Talina/genética , Regulación hacia ArribaRESUMEN
BACKGROUND: Let-7a is a small non-coding RNA that has been found to take part in cell proliferation and apoptosis. The hippo-YAP1 axis, known as a tumour suppressor pathway, also plays an important role in cell proliferation and apoptosis. YAP1, TAZ, and phospho-YAP1 play key roles in actions of the hippo-YAP1 axis. Adenomyosis (ADS) is a proliferative disease leading to a large uterus in patients with prolonged illness. Abnormal proliferation of smooth muscle cells (SMCs) in the uterine endometrial-myometrial junctional zone (JZ) is an important reason for developing ADS. This study aimed to explore the expression levels of let-7a and components of the hippo-YAP1 axis in SMCs in the uterine endometrial-myometrial JZ in ADS and to explore the roles of let-7a and the hippo-YAP1 axis of JZ SMC proliferation and apoptosis in ADS. METHODS: We collected JZ tissues for the primary culture of SMCs from 25 women diagnosed with ADS and 27 women without ADS. We used quantitative real-time polymerase chain reaction and western blotting to measure the mRNA and protein expression levels of let-7a, YAP1, TAZ, and phospho-YAP1 in ADS JZ SMCs. A CCK-8 assay and flow cytometry analysis of apoptosis were utilized to test the proliferation and apoptosis of JZ SMCs. The let-7a overexpression lentiviral vector GV280 was used to increase the expression level of let-7a. We added verteporfin to block the phosphorylation of components of the hippo-YAP1 axis. RESULTS: We found that the let-7a level was decreased, while the YAP1 and TAZ levels were increased in ADS JZ SMCs. Upregulated let-7a affected the expression levels of components of the hippo-YAP1 axis, accelerated apoptosis, and inhibited proliferation in JZ SMCs. Furthermore, accumulated YAP1 led to increasing proliferation of JZ SMCs after verteporfin treatment to block the phosphorylation of components of the hippo-YAP1 axis. If components of the hippo-YAP1 axis were unphosphorylated, upregulated let-7a could not inhibit the proliferation of ADS JZ SMCs. Upregulated let-7a could not activate the hippo-YAP1 axis in verteporfin treatment. CONCLUSIONS: Our findings suggest that the let-7a and hippo-YAP1 axis may act as important regulators of JZ SMCs proliferation, and upregulated let-7a may be an effective method to treat ADS.
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Adenomiosis/genética , Endometrio/metabolismo , MicroARNs/genética , Miocitos del Músculo Liso/metabolismo , Miometrio/metabolismo , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ/genética , Proteínas Señalizadoras YAP/genética , Adenomiosis/metabolismo , Adulto , Apoptosis/genética , Estudios de Casos y Controles , Proliferación Celular/genética , Femenino , Vía de Señalización Hippo , Humanos , MicroARNs/metabolismo , ARN Mensajero/metabolismo , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ/metabolismo , Proteínas Señalizadoras YAP/metabolismoRESUMEN
Intussusception in adults is a rare surgical emergency. Unlike in children, most adult intussusceptions arise from a pathological lead point. Ileal intussusception caused by a submucosal liposarcoma is a particularly rare phenomenon. This report describes the diagnosis and management of adult ileal intussusception secondary to submucosal liposarcoma in adult to provide a reference for future clinical work. A 64-year-old female presented to the emergency department with worsening abdominal pain associated with an 8 h history of intermittent vomiting. Based on physical examination, laboratory investigations, and computed tomography, the most likely diagnosis was ileal intussusception secondary to liposarcoma. Thus, emergency laparotomy was performed. During exploration, an ileal invagination was visualised approximately 30 cm from the ileocecal valve, and a flexible polypoid mass was palpable at the lead point of the intussusception. Subsequently, the patient underwent radical resection of pathological tissues with a primary end-to-end ileal anastomosis. Histopathological examination revealed a well-differentiated submucosal liposarcoma. Postoperatively, the patient recovered uneventfully and was doing well at the 6-month follow-up in the outpatient clinic. Thus, clinicians should consider the origin of submucosal liposarcomas in adult with intussusception. Once ileal intussusception secondary to submucosal liposarcoma is diagnosed, timely radical resection is recommended.
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N6-(2-Hydroxyethyl) adenosine, HEA (1), an active ingredient isolated from cultured mycelia of cordyceps species which is a famous traditional tonic in China, showed brain protective, sedative hypnotic activity in pharmacological tests. In order to explore novel non-benzodiazepine sedative-hypnotic agents, HEA was treated as the lead compound. Twenty three target compounds were designed and synthesized. Their chemical structures were characterized by 1H NMR, MS and elemental analysis. Pharmacological test in vivo showed that target compounds 8, 4, 13 were more active than HEA on locomotor and gasping activities of mice. Structure-activity relationships showed that the ribose moiety at N-9 position of adenine base was critical for activity.
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Adenosina/análogos & derivados , Adenosina/síntesis química , Hipnóticos y Sedantes/síntesis química , Adenosina/química , Adenosina/farmacología , Animales , Hipnóticos y Sedantes/química , Hipnóticos y Sedantes/farmacología , Masculino , Ratones , Ratones Endogámicos ICR , Estructura Molecular , Actividad Motora/efectos de los fármacos , Distribución Aleatoria , Relación Estructura-ActividadRESUMEN
Background: The impact of the preoperative carbohydrate antigen 125 (CA125) level on the survival of metastatic colorectal cancer (CRC) patients undergoing primary tumor resection (PTR) remains uncertain. The aim of this study was to assess the prognostic value in overall survival (OS) and cancer-specific survival (CSS) between patients with and without an elevated preoperative CA125 level. Methods: All metastatic CRC patients receiving PTR between 2007 and 2017 at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were retrospectively included. OS and CSS rates were compared between patients with and without elevated preoperative CA125 levels. Results: Among 326 patients examined, 46 (14.1%) exhibited elevated preoperative CA125 levels and the remaining 280 (85.9%) had normal preoperative CA125 levels. Patients with elevated preoperative CA125 levels had lower body mass index, lower preoperative albumin level, lower proportion of preoperative chemotherapy, higher carcinoembryonic antigen and carbohydrate antigen 19-9 (CA19-9) levels, poorer differentiation, and more malignant histopathological type than patients with normal preoperative CA125 levels. In addition, patients with elevated preoperative CA125 levels exhibited more advanced pathological T and N stages, more peritoneal metastasis, and more vessel invasion than patients with normal preoperative CA125 levels. Moreover, the primary tumor was more likely to be located at the colon rather than at the rectum in patients with elevated CA125 levels. Both OS and CSS rates in patients with elevated preoperative CA125 levels were significantly lower than those in patients with normal preoperative CA125 levels. Multivariate Cox regression analysis revealed that an elevated preoperative CA125 level was significantly associated with poor prognosis in metastatic CRC patients undergoing PTR. The hazard ratio (HR) in OS was 2.36 (95% confidence interval [CI], 1.67-3.33, P < 0.001) and the HR in CSS was 2.50 (95% CI, 1.77-3.55, P < 0.001). The survival analysis stratified by peritoneal metastasis also demonstrated that patients with elevated preoperative CA125 levels had lower OS and CSS rates regardless of peritoneal metastasis. Conclusion: Based on an analysis of metastatic CRC patients undergoing PTR, an elevated preoperative CA125 level was associated with poor prognosis, which should be taken into consideration in clinical practice.
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The estrogen 17ßestradiol has been proven to serve an indispensable role in the occurrence and development of adenomyosis (ADS). The let7a/Lin28B axis can control cell proliferation by acting as a tumorinhibiting axis in numerous types of cancer. However, its role in ADS remains unknown. The present study aimed i) to elucidate the role of let7a in regulating the proliferation of human uterine junctional zone (JZ) smooth muscle cells (SMCs) in ADS, ii) to evaluate whether 17ßestradiol modifies the expression levels of let7a and Lin28B in JZ SMCs in ADS, and iii) to establish how 17ßestradiol affects the function of the let7a/Lin28B axis in the proliferation of JZ SMCs in ADS. A total of 36 premenopausal women with ADS were enrolled as the experimental group and 34 women without ADS were recruited as the control group. Reverse transcriptionquantitative PCR was used to evaluate the expression level of let7a, and western blotting was performed to determine the Lin28B expression levels. Lentiviral null vector, let7a overexpression lentiviral vector GV280 and let7a inhibition lentiviral vector GV369 were used to infect cells to alter the expression of let7a for further functional experiments. 17ßestradiol and Cell Counting Kit8 assays were conducted to determine how 17ßestradiol affects the function of the let7a/Lin28B axis in the proliferation of JZ SMCs in ADS. The results demonstrated that let7a was downregulated and Lin28B was upregulated in the JZ SMCs of ADS compared with the control cells (P<0.0001). Moreover, a lower expression of let7a led to faster proliferation of JZ SMCs (P<0.05), and 17ßestradiol affected the let7a/Lin28B axis to accelerate the proliferation of JZ SMCs in ADS (P<0.05). These data suggested that 17ßestradiol collaborates with the let7a/Lin28B axis to affect the development of ADS.
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Adenomiosis/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Estradiol/farmacología , MicroARNs/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Proteínas de Unión al ARN/metabolismo , Útero/efectos de los fármacos , Adenomiosis/genética , Adenomiosis/metabolismo , Adulto , Proliferación Celular/genética , Endometrio/metabolismo , Femenino , Humanos , MicroARNs/genética , Persona de Mediana Edad , Miocitos del Músculo Liso/metabolismo , Miometrio/metabolismo , Cultivo Primario de Células , Proteínas de Unión al ARN/genética , Transducción de Señal/efectos de los fármacos , Útero/metabolismoRESUMEN
Several theories on the origin of adenomyosis (ADS) have been proposed, of which the most widely accepted is the fundamental pathogenic role of uterine eutopic endometrium. Emerging evidence suggests that circular RNAs participate in the multiple tumorgenesis. The vital importance of circular RNA PVT1 (circPVT1) in the pathological progress like malignancies has been well documented. Nevertheless, its underlying correlation with ADS remains elusive yet. The purpose of this study was to investigate the expression pattern, regulatory effect, and internal mechanism of circPVT1 in ADS. qRT-PCR was performed to detect the relative mRNA expression of circPVT1, miR-145, and Talin1 in ADS endometrial tissue and cells. The protein level of Talin1 was measured by Western blot and immunochemistry. Immunofluorescence was used to identify the primary endometrial epithelial and stromal cells. circPVT1 knockdown in vitro was achieved by transfecting with specific lentivirus vector CCK-8, and colony formation assays were utilized to assess cell proliferation; meanwhile, the transwell assay was employed for evaluating cell invasion ability. By conducting bioinformatics, dual-luciferase reporter assay, or RNA immunoprecipitation (RIP) experiment, the interaction between miR-145 and circPVT1 or Talin1 was verified. Rescue experiments further determined the regulatory effect of circPVT1/miR-145/Talin1 axis. We found both circPVT1 and Talin1 were markedly upregulated in ADS endometrial tissue and cells, whereas miR-145 was decreased. Elevated expression of circPVT1 was closely related to the severity of dysmenorrhea, menorrhagia, and uterine enlargement of patients with ADS. Knockdown of circPVT1 inhibited adenomyotic epithelial and stromal cell proliferation and invasion. Further mechanistic experiments revealed that circPVT1 negatively regulated miR-145 through serving as a molecular sponge. And the facilitating effect of circPVT1 was partially reversed by miR-145. Talin1 was demonstrated to be a down target of miR-145 and indirectly affected by circPVT1. Our findings unveiled that enhanced circPVT1 may be involved in the pathogenesis of ADS via stimulating endometrial cell proliferation and invasion. The establishment of circPVT1/miR-145/Talin1 pathway might present a novel therapeutic insight for ADS.
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Adenomiosis/metabolismo , Proliferación Celular , Endometrio/metabolismo , MicroARNs/metabolismo , ARN Circular/biosíntesis , ARN Largo no Codificante/biosíntesis , Transducción de Señal , Talina/metabolismo , Regulación hacia Arriba , Adenomiosis/genética , Adenomiosis/patología , Endometrio/patología , Femenino , Humanos , MicroARNs/genética , ARN Circular/genética , ARN Largo no Codificante/genética , Talina/genéticaRESUMEN
Adenomyosis (ADS) is a commonly encountered benign gynecological disorder. Epithelial-mesenchymal transition (EMT) may serve a pivotal role in the pathogenesis of ADS. Talin1 has been identified to be implicated in multiple human carcinomas, probably through inducing EMT process. However, available data on the precise molecular mechanism of Talin1 in the pathogenesis of ADS remain extremely scanty. In the present study, we aim to investigate the clinical roles of Talin1 and its effects on uterine endometrial cell migration, invasion, and EMT in ADS. Relative mRNA expression of Talin1, microRNA-145-5p (miR-145-5p), and EMT-related markers was determined by qRT-PCR. Immunohistochemistry and immunofluorescence were performed to examine the distribution of Talin1 in ADS endometrium. Protein levels of Talin1, EMT-related markers, and wnt/ß-catenin pathway were measured by western blot. Wound healing assay and transwell assay were utilized for evaluating cell migration and invasion respectively. Dual-luciferase reporter assay was performed to verify the relationship between Talin1 and miR-145-5p. We found Talin1 was markedly overexpressed in ADS endometrial tissue and cells, whereas miR-145-5p was downregulated. Elevated Talin1 mRNA level might be closely related to some clinicopathological features of ADS. Through functional experiments, we demonstrated that overexpression of Talin1 induced EMT and enhanced migration and invasion ability of ADS eutopic and ectopic endometrial epithelial cells (ADS_Eu_EEC and ADS_Ec_EEC) in vitro through activating the canonical wnt/ß-catenin pathway. From a mechanistic perspective, Talin1 was inversely regulated by miR-145-5p as a direct target. Our findings unveiled that under the regulation of miR-145-5p, Talin1 might promote endometrial cell migration and invasion through inducing EMT, presenting a novel insight for elucidating the pathogenesis of ADS.
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Adenomiosis/metabolismo , Movimiento Celular , Endometrio/metabolismo , Transición Epitelial-Mesenquimal , MicroARNs/metabolismo , Talina/metabolismo , Endometrio/citología , Femenino , Humanos , Cultivo Primario de Células , Vía de Señalización WntRESUMEN
BACKGROUND: To investigate dynamic fluctuations of serum viral load and peripheral T-lymphocyte subpopulations of chronic hepatitis B patients and their correlation during entecavir therapy. METHODS: Fifty-five patients received entecavir 0.5 mg/d therapy. Serum HBV DNA load was measured by Real-Time-PCR, and the levels of peripheral T-lymphocyte subpopulations by flow cytometry biweekly, every four weeks and every eight weeks during weeks 1-12, 13-24 and 24-48, respectively. Multilevel modelling was used to analyse the relationship between these variables. RESULTS: Of the 55 patients, all HBeAg positive and with detectable HBV DNA, the majority (81.8%) had serum levels of HBV DNA over 10(7) copies per milliliter. HBV viral load dropped sharply during the first two weeks. In 28 and 43 patients, the level became undetectable from week 24 and 48, respectively. Using pre-therapy level as the reference, a significant decrease in CD8+ T cells and increase in CD4+ T cells were found from week 12. Both parameters and CD4+/CD8+ ratio steadily improved throughout the 48 weeks. Multilevel analyses showed that the level of decrement of HBV DNA was associated with the increment of T-lymphocyte activities only in the later period (4-48 week). After 4 weeks of therapy, for each log10 scale decrement of HBV DNA, the percentage of CD4+ lymphocyte was increased by 0.49 and that of CD8+ decreased by 0.51. CONCLUSION: T-lymphocyte subpopulations could be restored partially by entecavir treatment in patients with chronic hepatitis B concurrently with reduction of viremia.
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Antivirales/uso terapéutico , Guanina/análogos & derivados , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/tratamiento farmacológico , Subgrupos de Linfocitos T/virología , Replicación Viral/efectos de los fármacos , Adolescente , Adulto , Relación CD4-CD8 , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/virología , Estudios de Cohortes , ADN Viral/sangre , Femenino , Guanina/uso terapéutico , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Modelos Biológicos , Análisis Multivariante , Análisis de Regresión , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Carga Viral , Viremia/tratamiento farmacológico , Viremia/inmunología , Viremia/virologíaRESUMEN
AIM: To investigate the peripheral T-lymphocyte subpopulation profile, and its correlations with hepatitis B virus (HBV) replication level in chronic HBV-infected (CHI) individuals with normal liver function tests (LFTs). METHODS: Frequencies of T-lymphocyte subpopulations in peripheral blood were measured by flow cytometry in 216 CHI individuals. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time PCR. Information of age at HBV infection, and maternal HBV infection status was collected. ANOVA linear trend test and linear regression were used in statistical analysis. RESULTS: CHI individuals had significantly decreased relative frequencies of CD3(+), CD4(+) subpopulations and CD4(+)/CD8(+) ratio, and increased CD8(+) subset percentage compared with uninfected individuals (all P < 0.001). There was a significant linear relationship between the load of HBV DNA and the parameters of T-lymphocyte subpopulations (ANOVA linear trend test P < 0.01). The parameters were also significantly worse among individuals whose mothers were known to be HBV carriers, and those having gained infection before the age of 8 years. In multiple regressions, after adjustment for age at HBV infection and status of maternal HBV infection, log copies of HBV DNA maintained its highly significant predictive coefficient on T-lymphocyte subpopulations, whereas the effect of HBeAg was not significant. CONCLUSION: HBV DNA correlates with modification in the relative T-lymphocyte subpopulation frequencies. High viral load is more powerful than HBeAg in predicting the impaired balance of T-cell subsets.
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Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/virología , ADN Viral/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B Crónica/diagnóstico , Pruebas de Función Hepática , Subgrupos Linfocitarios/virología , Adulto , Complejo CD3/análisis , Recuento de Linfocito CD4 , Relación CD4-CD8 , Femenino , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/inmunología , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Replicación ViralRESUMEN
AIM: To investigate peripheral T-lymphocyte sub-population profile and its correlation with hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB). METHODS: Distribution of T-lymphocyte subpopulations in peripheral blood was measured by flow cytometry in 206 CHB patients. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time polymerase chain reaction (PCR). The relationship between HBV replication and variation in peripheral T-cell subsets was analyzed. RESULTS: CHB patients had significantly decreased CD3+ and CD4+ cells and CD4+/CD8+ ratio, and increased CD8+ cells compared with uninfected controls (55.44 +/- 12.39 vs 71.07 +/- 4.76, 30.92 +/- 7.48 vs 38.94 +/- 3.39, 1.01 +/- 0.49 vs 1.67 +/- 0.33, and 34.39 +/- 9.22 vs 24.02 +/- 4.35; P < 0.001, respectively). Univariate analysis showed a similar pattern of these parameters was significantly associated with high viral load, presence of serum hepatitis B e antigen (HBeAg) expression, liver disease severity, history of maternal HBV infection, and young age at HBV infection, all with P < 0.01. There was a significant linear relationship between viral load and these parameters of T-lymphocyte subpopulations (linear trend test P < 0.001). There was a negative correlation between the levels of CD3+ and CD4+ cells and CD4+/CD8+ ratio and serum level of viral load in CHB patients (r = -0.68, -0.65 and -0.75, all P < 0.0001), and a positive correlation between CD8+ cells and viral load (r = 0.70, P < 0.0001). There was a significant decreasing trend in CD3+ and CD4+ cells and CD4+/CD8+ ratio with increasing severity of hepatocyte damage and decreasing age at HBV infection (linear trend test P < 0.01). In multiple regression (after adjustment for age at HBV infection, maternal HBV infection status and hepatocyte damage severity) log copies of HBV DNA maintained a highly significant predictive coefficient on T-lymphocyte subpopulations, and was the strongest predictor of variation in CD3+, CD4+, CD8+ cells and CD4+/CD8+ ratio. However, the effect of HBeAg was not significant. CONCLUSION: T-lymphocyte failure was significantly associated with viral replication level. The substantial linear dose-response relationship and strong independent predictive effect of viral load on T-lymphocyte subpopulations suggests the possibility of a causal relationship between them, and indicates the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients.
Asunto(s)
Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Subgrupos de Linfocitos T/inmunología , Adulto , ADN Viral/sangre , Femenino , Virus de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis B/fisiología , Humanos , Modelos Lineales , Masculino , Estudios Prospectivos , Viremia/inmunología , Viremia/virología , Replicación ViralRESUMEN
BACKGROUND: There are significant variations in the geographical distribution of hepatitis B virus (HBV) genotypes throughout the world, and some genotypes are associated with different clinical outcomes. Eight genotypes of human HBV (designated A-H) have been reported. The present study was designed to examine the distribution of HBV genotypes among patients at various stages of chronic type B liver disease in Yunnan Province, China, and to explore its significance and the relationship of HBV genotype with gender and age, clinical spectrum of chronic HBV infection, and viral replicative activity. METHODS: Serum samples from 126 patients with chronic HBV infection from Yunnan Province, including 26 chronic asymptomatic HBV carriers (ASC), 61 patients with chronic hepatitis B (CHB) (21 mild, 30 moderate and 10 severe), 20 patients with chronic fulminant hepatic failure (CFHF), 12 patients with HBV-related liver cirrhosis (LC) and 7 patients with HBV-related hepatocellular carcinoma (HCC) were analyzed using reverse dot blot (RDB) methodology, which is based on the reverse hybridization principle for HBV genotyping. The relations of HBV genotype with gender and age, clinical patterns, and serological data of the patients were analyzed. RESULTS: In this series, genotypes A, B, C, and D were found. 38.1% patients (48/126) belonged to B, 54.8% (69/126) to C, 0.8% (1/126) to D, 1.6% (2/126) to a mixture of B and C, and 1.6% (2/126) to a mixture of A and C. 3.2% patients (4/126) had unknown genotypes. No other genotypes (E, F, G, and H) were found. Genotypes B and C were predominant. There was a statistically significant difference in the distributions of genotypes C and B (chi(2)=7.04, P=0.008), and C was the dominant genotype in all patient categories. The rate of genotype B in the mild CHB group was significantly higher than that in the moderate and severe groups (chi(2)=12.16, P=0.0001; X2=11.98, P=0.001, respectively), the ASC group (chi(2)=5.46, P=0.02), the CFHF group (chi(2)=5.53, P=0.019), and the LC/HCC group (chi(2)=12.13, P=0.001). The rate of genotype C in the LC/HCC group and the severe CHB group were significantly higher than that in the mild group (chi(2)=9.95, P=0.002; chi(2)=8.78, P=0.003, respectively). HBV DNA positivity and HBeAg positivity were higher in genotype C than in genotype B (chi(2)=9.81, P=0.002; chi(2)=3.85, P=0.05, respectively). The prevalence of genotype C showed an increasing trend in lowest-, middle- and highest-level groups of HBV replication (25.0%, 70.0%, and 55.6%, respectively); in contrast, the prevalence of genotype B showed an opposite trend in the same order (62.5%, 30.0%, and 37.0%, respectively). The rate of genotype C in the highest-level group of HBV replication was higher than genotype B (chi(2)=7.45, P=0.006). The rate of genotype C in the over-30 age group was higher than that in the below-30 age group (chi(2)=3.7, P=0.05). There was no difference between the sexes (P>0.05). More severe liver damage was found in genotype C than in genotype B (P<0.05). CONCLUSIONS: The predominant HBV genotypes in chronic HBV-infected patients are B and C, and C is the most prevalent genotype in Yunnan Province, China. HBV genotype C is associated with the development of more severe liver disease and a higher level of HBV viral replication, and genotype B has a relatively good progress.
Asunto(s)
ADN Viral/genética , Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , Adulto , Factores de Edad , China/epidemiología , Femenino , Genotipo , Hepatitis B Crónica/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Prevalencia , Pronóstico , Estudios Retrospectivos , Población Rural , Índice de Severidad de la Enfermedad , Factores SexualesRESUMEN
OBJECTIVE: To evaluate the safety of metformin in the treatment of elderly type 2 diabetes mellitus (T2DM). METHODS: Two hundred and forty-three cases of elderly T2DM hospitalized from Jan. 1996 to Dec. 2006 were reviewed; the changes of fasting blood glucose(FBG), postprandial blood glucose (PBG), glycosylated hemoglobin (HbA1c), liver and renal function and blood lactic acid were evaluate before and after treatment. RESULTS: The mean time of treatment with metformin was (6.6 +/- 3.9) years (3 months - 21 years) in these 243 cases. The levels of FBG, PBG and HbA1c significantly reduced after treatment with metformin only in 43 cases (17.7%), metformin combined with other oral hypoglycemic drugs in 124 cases (51.0%) and metformin combined with insulin in 76 cases (31.3%). There was only 18.1% of the cases with normal range (> 80 ml/min) of creatinine clearance rate (Ccr), and 25.8% of the cases with Ccr Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico
, Hipoglucemiantes/efectos adversos
, Metformina/efectos adversos
, Anciano
, Anciano de 80 o más Años
, Glucemia
, Contraindicaciones
, Humanos
, Hipoglucemiantes/uso terapéutico
, Metformina/uso terapéutico
, Persona de Mediana Edad
RESUMEN
OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) and smoking have similar mechanisms of promoting colorectal polyps. The potential link between NAFLD and smoking in men and colorectal polyps has not been adequately evaluated. The aim is to investigate this association. METHODS: A retrospective cross-sectional study was conducted on 2409 individuals undergoing a health check. Univariate and multivariate logistic regression were performed for analyzing the association between risk factors and colorectal polyps. Individuals were divided into four groups: Q1: NAFLD (-)/smoking (-); Q2: NAFLD (+)/smoking (-); Q3: NAFLD (-)/smoking (+); Q4: NAFLD (+)/smoking (+). Logistic analyses were used to explore associations for the whole study population and stratified groups. RESULTS: The prevalence of colorectal polyps was 38.8% in males, and that of colorectal polyps in smokers and individuals with NAFLD were 47.0% (428/911) and 42.9% (267/622), respectively. With Q1 as reference, subjects with NAFLD (+) and smoking habits (+) had the highest ORs for colorectal polyps (OR = 2.64, 95% CI: 1.91 - 3.64, P < 0.001), adenomatous polyps (OR = 2.06, 95% CI: 1.38 - 3.05, P < 0.05), non-adenomatous polyps (OR = 1.97, 95% CI: 1.39 - 2.80, P < 0.05), ≥ 3 polyps (OR = 2.05, 95% CI: 1.31 - 3.22, P < 0.05) and proximal polyps (OR = 1.58, 95% CI: 1.02 - 2.45, P < 0.05) after adjusting for confounding variables. CONCLUSIONS: Men with NAFLD and smoking habits have an increasing risk of colorectal polyps.
RESUMEN
AIM: To investigate the relationship between non-alcoholic fatty liver disease (NAFLD) and colorectal adenomatous and hyperplastic polyps. METHODS: A retrospective cross-sectional study was conducted on 3686 individuals undergoing health checkups (2430 males and 1256 females). All subjects underwent laboratory testing, abdominal ultrasonography, colonoscopy, and an interview to ascertain the baseline characteristics and general state of health. Multinomial logistic regression analysis was performed to examine the association between NAFLD and the prevalence of colorectal adenomatous and hyperplastic polyps. Furthermore, the relationship was analyzed in different sex groups. Subgroup analysis was performed based on number, size, and location of colorectal polyps. RESULTS: The prevalence of colorectal polyps was 38.8% in males (16.2% for adenomatous polyps and 9.8% for hyperplastic polyps) and 19.3% in females (8.4% for adenomatous polyps and 3.9% for hyperplastic polyps). When adjusting for confounding variables, NAFLD was significantly associated with the prevalence of adenomatous polyps (OR = 1.28, 95%CI: 1.05-1.51, P < 0.05) and hyperplastic polyps (OR = 1.35, 95%CI: 1.01-1.82, P < 0.05). However, upon analyzing adenomatous and hyperplastic polyps in different sex groups, the significant association remained in males (OR = 1.53, 95%CI: 1.18-2.00, P < 0.05; OR = 1.42, 95%CI: 1.04-1.95, P < 0.05) but not in females (OR = 0.44, 95%CI: 0.18-1.04, P > 0.05; OR = 1.18, 95%CI: 0.50-2.78, P > 0.05). CONCLUSION: NAFLD is specifically associated with an increased risk of colorectal adenomatous and hyperplastic polyps in men. However, NAFLD may not be a significant factor in the prevalence of colorectal polyps in women.
Asunto(s)
Pólipos Adenomatosos/epidemiología , Colon/patología , Pólipos del Colon/epidemiología , Neoplasias Colorrectales/epidemiología , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Pólipos Adenomatosos/diagnóstico , Pólipos Adenomatosos/etiología , Adulto , Colon/diagnóstico por imagen , Pólipos del Colon/diagnóstico , Pólipos del Colon/etiología , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/etiología , Estudios Transversales , Femenino , Humanos , Hiperplasia/diagnóstico , Hiperplasia/epidemiología , Hiperplasia/etiología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , UltrasonografíaRESUMEN
AIM: To observe the efficiency and safety of thymosin-alpha1 treatment in patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis. METHODS: Sixty-two patients were randomly divided into groups A and B. The patients in group A received subcutaneous injection of 1.6 mg thymosin-alpha1, twice a week (T-alpha1 group) for six months, and the patients in group B received 5 MU interferon alpha (IFN-alpha) each day for fifteen days, then three times weekly (IFN-alpha group) for six months. The results between two groups treated with and the group untreated with IFN-alpha which was followed up for 12 mo (historical control group consisting of 30 patients) were compared, and three groups were comparable between each other (P>0.05) at baseline (age, sex, clinical history, biochemical, and serological parameters). RESULTS: At the end of treatment, complete response, which was defined as alanine aminotransferase (ALT) normalization and HBV DNA and HBeAg loss, occurred in 9 of 29 (31.0%) patients in the T-alpha1 group and in 15 of 33 (45.5%) patients in the IFN-alpha group (chi2=1.36, P>0.05). After a follow-up period of six months, a complete response was observed in 14 of 29 (48.3%) patients in the T-alpha1 group and in 9 of 33 (27.3%) patients in the IFN-alpha group (chi2=2.93, P>0.05). Compared with the results observed in the historical control (HC) group untreated with IFN-alpha which was followed up for 12 mo, the rate of complete response was significantly higher in IFN-alpha group at the end of therapy (1 of 30 vs 15 of 33, chi2=14.72, P<0.001) and in the T-alpha1 group at the end of follow-up (1 of 30 vs 14 of 29, chi2=15.71, P<0.001). In T-alpha1 and IFN-alpha treatment groups, the area under (the plasma concentration time) curve (AUC) of negative HBV DNA and HBeAg was 34%, 17%, 31% and 19% smaller than that in the HC group. By the end of the follow-up period, the proportions of ALT normalization and negative HBV DNA in the T-alpha1 group were significantly higher than those in the IFN-alpha and HC groups. The odds of ALT normalization and negative HBV DNA at the end of the follow-up was three-fold higher in the T-alpha1 group than in the IFN-alpha group. Unlike IFN-alpha, T-alpha1 was well tolerated by all patients, and no side effects appeared in T-alpha1 group. CONCLUSION: The results suggest that a 6-mo course of T-alpha1 therapy is effective and safe in patients with chronic hepatitis B. T-alpha1 is able to reduce HBV replication in patients with chronic hepatitis B. Furthermore, T-alpha1 is better tolerated than IFN-alpha and can gradually induce more sustained ALT normalization and HBV DNA and HBeAg loss. However, a response rate of 48.3% is still less ideal. A more effective therapeutic approach warrants further study.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Timosina/análogos & derivados , Adyuvantes Inmunológicos/efectos adversos , Adyuvantes Inmunológicos/farmacología , Adulto , Alanina Transaminasa/sangre , Antivirales/efectos adversos , Antivirales/farmacología , ADN Viral/sangre , Relación Dosis-Respuesta a Droga , Femenino , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B Crónica/sangre , Hepatitis B Crónica/inmunología , Humanos , Interferón-alfa/efectos adversos , Interferón-alfa/farmacología , Masculino , Persona de Mediana Edad , Timalfasina , Timosina/efectos adversos , Timosina/farmacología , Timosina/uso terapéutico , Replicación Viral/efectos de los fármacosRESUMEN
Elaeagnus angustifolia Linn. has various ecological, medicinal and economical uses. An approach was established using RP-HPLC (reversed-phase high-performance liquid chromatography) to classify and analyse the intra-specific genetic relationships of seventeen populations of E. angustifolia, collected from the Xinjiang areas of China. Chromatograms of alcohol-soluble proteins produced by seventeen populations of E. angustifolia, were compared. Each chromatogram of alcohol-soluble proteins came from a single seed of one wild plant only. The results showed that when using a Waters Delta Pak. C18, 5 microm particle size reversed phase column (150 mm x 3.9 mm), a linear gradient of 25%-60% solvent B with flow rate of 1 ml/min and run time of 67 min, the chromatography yielded optimum separation of E. angustifolia alcohol-soluble proteins. Representative peaks in each population were chosen according to peak area and occurrence in every seed. The converted data on the elution peaks of each population were different and could be used to represent those populations. GSC (genetic similarity coefficients) of 41% to 62% showed a medium degree of genetic diversity among the populations in these eco-areas. Cluster analysis showed that the seventeen populations of E. angustifolia could be divided into six clusters at the GSC=0.535 level and indicated the general and unique biochemical markers of these clusters. We suggest that E. angustifolia distribution in these eco-areas could be classified into six variable species. RP-HPLC was shown to be a rapid, repeatable and reliable method for E. angustifolia classification and identification and for analysis of genetic diversity.