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Exposure to fine particulate matter (PM2.5) during pregnancy has been inversely associated with neonatal neurological development. However, the associations of exposure to specific PM2.5 constituents with neonatal neurological development remain unclear. We investigated these associations and examined the mediating role of meconium metabolites in a Chinese birth cohort consisting of 294 mother-infant pairs. Our results revealed that exposure to PM2.5 and its specific constituents (i.e., organic matter, black carbon, sulfate, nitrate, and ammonium) in the second trimester, but not in the first or third trimester, was inversely associated with the total neonatal behavioral neurological assessment (NBNA) scores. The PM2.5 constituent mixture in the second trimester was also inversely associated with NBNA scores, and sulfate was identified as the largest contributor. Furthermore, meconium metabolome analysis identified four metabolites, namely, threonine, lysine, leucine, and saccharopine, that were associated with both PM2.5 constituents and NBNA scores. Threonine was identified as an important mediator, accounting for a considerable proportion (14.53-15.33%) of the observed inverse associations. Our findings suggest that maternal exposure to PM2.5 and specific constituents may adversely affect neonatal behavioral development, in which meconium metabolites may play a mediating role.
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Exposição Materna , Mecônio , Material Particulado , Humanos , Feminino , Mecônio/química , Gravidez , Estudos de Coortes , Recém-Nascido , Adulto , Poluentes AtmosféricosRESUMO
Streptococcus pneumoniae relies on two-component systems (TCSs) to regulate the processes of pathogenicity, osmotic pressure, chemotaxis, and energy metabolism. The TCS01 system of S. pneumoniae is composed of HK01 (histidine kinase) and RR01 (response regulator). Previous studies have reported that an rr01 mutant reduced the pneumococcal virulence in rat pneumonia, bacteremia, a nasopharyngeal model, and infective endocarditis. However, the mechanism of TCS01 (HK/RR01) regulating pneumococcal virulence remains unclear. Here, pneumococcal mutant strains Δrr01, Δhk01, and Δrr01&hk01 were constructed, and bacterial adhesion and invasion to A549 cells were compared. RNA sequencing was performed in D39 wild-type and Δrr01 strains, and transcript profile changes were analyzed. Differentially expressed virulence genes in the Δrr01 strain were screened out and identified by quantitative real-time PCR (qRT-PCR). Our results showed that pneumococcal mutant strains exhibited attenuated adhesion and invasion to A549 cells and differential transcript profiles. Results of qRT-PCR identification showed that the differential virulence genes screened out were downregulated. Among those changed virulence genes in the Δrr01 strain, the downregulated expression level of choline binding protein pcpA was the most obvious. Complementation of rr01 and overexpression of pcpA in the Δrr01 strain partially restored both pneumococcal adhesion and invasion, and rr01 complementation made the expression of pcpA upregulated. These findings revealed that rr01 influenced pneumococcal virulence by regulating pcpA.
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Peptídeos e Proteínas de Sinalização Intracelular , Infecções Pneumocócicas , Streptococcus pneumoniae , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidade , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Células A549 , Humanos , Infecções Pneumocócicas/metabolismo , Infecções Pneumocócicas/microbiologia , Aderência BacterianaRESUMO
This study aimed to assess the protective effect of nitroglycerin, a commonly used drug in cardiovascular diseases, on mice with acute liver injury induced by carbon tetrachloride (CCl4 ). The mice were randomly divided into three groups: control, CCl4 , and CCl4 + nitroglycerin. They were killed at 0, 6, 12, 24, and 48 h after treatment. Blood and liver tissue samples were collected for analysis. Analysis of the amounts of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), hepatic glutathione (GSH), and malondialdehyde (MDA) showed that nitroglycerin protected against CCl4 -induced acute liver injury. Liver histological analysis provided further evidence of the protective effect of nitroglycerin. Furthermore, we found that nitroglycerin suppressed the increase of T helper 17 (Th17) cells in CCl4 -induced acute liver injury mice. The results indicate that nitroglycerin is a potential candidate for hepatic disease.
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Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Nitroglicerina/uso terapêutico , Células Th17/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Glutationa/metabolismo , Interleucina-17/metabolismo , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos C57BL , Nitroglicerina/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Células Th17/imunologiaRESUMO
INTRODUCTION: Surfactant is usually deficiency in adult acute respiratory distress syndrome(ARDS) patients and surfactant administration may be a useful therapy. The aim of this study was to perform a meta-analysis of the effect of surfactant administration on outcomes of adult patients with acute respiratory distress syndrome. METHODS: PubMed, EMBASE, Medline, Cochrane database, Elsevier, Web of Science and http://clinicaltrials.gov were searched and investigated until December 2017. Randomized controlled trials(RCTs) comparing surfactant administration with general therapy in adult patients with ARDS were enrolled. The primary outcome was mortality (7-10-day, 28-30-day and 90-180-day). Secondary outcome included oxygenation (PaO2/FiO2 ratio). Demographic variables, surfactant administration, and outcomes were retrieved. Sensitivity analyses were used to evaluate the impact of study quality issues on the overall effect. Funnel plot inspection, Egger's and Begger's test were applied to investigate the publication bias. Internal validity was assessed with the risk of bias tool. Random errors were evaluated with trial sequential analysis(TSA). Quality levels were assessed by Grading of Recommendations Assessment, Development, and Evaluation methodology(GRADE). RESULTS: Eleven RCTs with 3038 patients were identified. Surfactant administration could not improve mortality of adult patients [Risk ratio (RR) (95%CI)) = 1.02(0.93-1.12), p = 0.65]. Subgroup analysis revealed no difference of 7-10-day mortality [RR(95%CI)) = 0.89(0.54-1.49), p = 0.66], 28-30-day mortality[RR(95%CI) = 1.00(0.89-1.12), p = 0.98] and 90-180-day mortality [RR(95%CI) = 1.11(0.94-1.32), p = 0.22] between surfactant group and control group. The change of the PaO2/FiO2 ratio in adult ARDS patients had no difference [MD(95%CI) = 0.06(- 0.12-0.24), p = 0.5] after surfactant administration. Finally, TSA and GRADE indicated lack of firm evidence for a beneficial effect. CONCLUSIONS: Surfactant administration has not been shown to improve mortality and improve oxygenation for adult ARDS patients. Large rigorous randomized trials are needed to explore the effect of surfactant to adult ARDS patients.
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Pulmão/fisiopatologia , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório/terapia , Adulto , Humanos , Oxigênio/sangue , Troca Gasosa Pulmonar , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome do Desconforto Respiratório/mortalidadeAssuntos
Doenças Autoimunes , Neoplasias dos Ductos Biliares , Colangiocarcinoma , Colangite Esclerosante , Colangite , Hipofisite , Doença Relacionada a Imunoglobulina G4 , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/diagnóstico , Colangite/diagnóstico , Colangite Esclerosante/complicações , Colangite Esclerosante/diagnóstico , Diagnóstico Diferencial , Humanos , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/diagnósticoRESUMO
Hepatitis B virus (HBV) infection results in different clinical presentation due to different levels of immune response. Our study aimed to characterize HBV full-length genome quasispecies (QS) in patients with different phases of infection to better understand its pathogenesis. Forty treatment-naive HBV-infected patients were enrolled, including 10 cases of acute hepatitis B (AHB), 9 cases of immunotolerant (IT) HBV carriers, 11 cases of chronic hepatitis B (CHB), and 10 cases of acute-on-chronic liver failure (ACLF). The present study was conducted by clone-based sequencing. QS heterogeneity within each open reading frame was calculated. The mutation frequency index (MFI) and amino acid variations within the large HBsAg, HBcAg, and HBxAg regions were analyzed based on the different infection phases. In total, 606 HBV full-length sequences were obtained. HBV QS had higher heterogeneity in ACLF and CHB than that in IT among chronically infected individuals. AHB patients had the lower QS heterogeneity at onset than those with chronic infection. ACLF patients had the highest frequency of mutations in the core promoter and precore region. A triple mutation (A1762T/G1764A/G1896A) was observed more frequently in genotype C than in genotype B. The MFI indicated that specific peptides of the studied regions had more frequent mutations in ACLF. Furthermore, several amino acid variations, known as T- and B-cell epitopes, were potentially associated with the immunoactive phase of infection. More HBV genome mutations and deletions were observed in patients with more severe diseases, particularly in specific regions of the core and preS regions, the clinical significance and mechanism of which need to be further investigated.
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Variação Genética , Genoma Viral , Genótipo , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Hepatite B/virologia , Epitopos/genética , Hepatite B/patologia , Antígenos da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Humanos , Taxa de Mutação , Mutação de Sentido Incorreto , Deleção de SequênciaRESUMO
OBJECTIVES: To evaluate the therapeutic effect of early fluid resuscitation under the guidance of Pulse indicator Continuous Cardiac Output (PiCCO) on patients with severe acute pancreatitis (SAP). METHODS: Clinical data of 18 SAP patients (the study group), who had undergone fluid resuscitation under the guidance of PiCCO from October 2011 to October 2013, were analyzed prospectively. Clinical data of 25 cases (control group) who had undergone fluid resuscitation without the guidance of PiCCO from January 2009 to September 2011 were collected. Then, retrospective and prospective case-control study was carried out. RESULTS: During the first 6 h, 0-24 h, 24-48 h, and 0-72 h of admission, the study group received more volume of fluid than the control group. There were significantly faster decline of APACHE II score and the value of blood lactate in study group, as well as the length of ICU stay and the proportion of renal failure at 72 h of admission. According to the 2012 Atlanta classification, six cases in study group turned into moderate SAP (33.30%), significantly higher than the control group (8.00%) (p = 0.0049). The volume of fluid infusion and clinical parameters were linearly relative. CONCLUSIONS: The PiCCO device may be a useful adjunct for fluid resuscitation monitoring in patients with SAP in the early stage. Early fluid resuscitation under the guidance of PiCCO can improve tissue perfusion, reduce the SIRS persistence time and the length of ICU stay. This program did not increase the risk of respiratory failure and influence the mortality.
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Hidratação/métodos , Pancreatite/terapia , Ressuscitação/métodos , Doença Aguda , Adulto , Idoso , Feminino , Hidratação/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ressuscitação/instrumentação , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: HBV immune escape represents a challenge to prevention, diagnosis, and treatment of hepatitis B. Here, we analyzed the molecular and clinical characteristics of HBV immune escape mutants in a Chinese cohort of chronically infected patients. METHODS: Two hundred sixteen patients with HBsAg and anti-HBs were studied, with one hundred eighty-two HBV carriers without anti-HBs as a control group. Recombinant HBsAg bearing the most frequent N-glycosylation mutations were expressed in CHO and HuH7 cells. After confirming N-glycosylation at the most frequent sites (129 and 131), together with inserted mutations, functional analysis were performed to study antigenicity and secretion capacity. RESULTS: One hundred twenty-three patients had the wild-type HBs gene sequence, 93 patients (43%) had mutants in the major hydrophilic region (MHR), and 47 of the 93 patients had additional N-glycosylation mutations, which were transmitted horizontally to at least 2 patients, one of whom was efficiently vaccinated. The frequency of N-glycosylation mutation in the case group was much higher than that of the control group (47/216 vs. 1/182). Compared with wild-type HBsAg, HBsAg mutants reacted weakly with anti-HBs using a chemiluminescent microparticle enzyme immunoassay. Native gel analysis of secreted virion in supernatants of transfected HuH7 cells indicated that mutants had better virion enveloping and secretion capacity than wild-type HBV. CONCLUSIONS: Our results suggest that specific HBsAg MHR N-glycosylation mutations are implicated in HBV immune escape in a high endemic area.
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Antígenos de Superfície da Hepatite B/genética , Evasão da Resposta Imune , Mutação , Adolescente , Adulto , Idoso , Feminino , Glicosilação , Antígenos de Superfície da Hepatite B/imunologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Masculino , Pessoa de Meia-IdadeRESUMO
Acute respiratory distress syndrome (ARDS) is independently associated with a poor prognosis in patients with sepsis. Macrophage M1 polarization plays an instrumental role in this process. Therefore, the exploration of key molecules affecting acute lung injury and macrophage M1 polarization may provide therapeutic targets for the treatment of septic ARDS. Here, we identified that elevated levels of Ankyrin repeat domain-containing protein 22 (ANKRD22) were associated with poor prognosis and more pronounced M1 macrophage polarization in septic patients by analyzing high-throughput data. ANKRD22 expression was also significantly upregulated in the alveolar lavage fluid, peripheral blood, and lung tissue of septic ARDS model mice. Knockdown of ANKRD22 significantly attenuated acute lung injury in mice with sepsis-induced ARDS and reduced the M1 polarization of lung macrophages. Furthermore, deletion of ANKRD22 in macrophages inhibited M1 macrophage polarization and reduced levels of phosphorylated IRF3 and intracellular interferon regulatory factor 3 (IRF3) expression, while re-expression of ANKRD22 reversed these changes. Further experiments revealed that ANKRD22 promotes IRF3 activation by binding to mitochondrial antiviral-signaling protein (MAVS). In conclusion, these findings suggest that ANKRD22 promotes the M1 polarization of lung macrophages and exacerbates sepsis-induced ARDS.
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BACKGROUND AND AIMS: We aimed to define gender-specific, optimal alanine aminotransferase (ALT) cut-off values for the prediction of significant liver histological changes (SLHC) in Chinese patients with grey zone (GZ) chronic hepatitis B (CHB) and normal ALT. METHODS: In a retrospective study, we included 1101 consecutive patients with GZ CHB and normal ALT assigned to training or internal validation cohorts. We included an independent cohort of 842 patients for external validation. We performed receiver operating characteristic (ROC) curve, smoothed curve fitting, and threshold effect analyses to determine optimal ALT cut-off values. Area under the curve (AUC) values were calculated to assess their predictive performance. RESULTS: A proportion of 79.3% of patients with GZ CHB and normal ALT (≤40 U/L) had SLHC. ROC curve analysis initially identified optimal ALT cut-off values of 29 U/L (male) and 22 U/L (female). After smoothed curve fitting and threshold effect analyses, new optimal cut-off values were 27 U/L for males and 24 U/L for females. AUCs for these values were 0.836 (male) and 0.833 (female) in the internal validation cohort, and 0.849 (male) and 0.844 (female) in the external validation cohort. The accuracy and discriminative ability of the newly defined ALT cut-off values were greater than those of the current recommendations. CONCLUSION: This study established novel optimal ALT cut-off values for more precise prediction of SLHC among Chinese patients with GZ CHB and normal ALT levels. This may help identify individuals who will benefit from timely antiviral therapy.
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Hepatite B Crônica , Humanos , Masculino , Feminino , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/patologia , Estudos Retrospectivos , Cirrose Hepática , Curva ROC , Alanina Transaminase , Vírus da Hepatite B , Antígenos E da Hepatite BRESUMO
BACKGROUND: Only a few cases of chronic hepatitis B (CHB) with primary biliary cholangitis (PBC) have been reported based on histological evidence from liver biopsies. AIM: To observe the clinicopathological features and outcomes of 11 patients with CHB infection complicated by PBC. METHODS: Eleven patients with CHB and PBC who underwent liver biopsy at the Zhenjiang Third Hospital, affiliated with Jiangsu University, and Wuxi Fifth People's Hospital, from January 2005 to September 2020, were selected. All patients initially visited our hospital with CHB and were pathologically diagnosed with CHB and PBC. RESULTS: Only five had elevated alkaline phosphatase levels, nine were positive for anti-mitochondrial antibody (AMA)-M2, and two were negative for AMA-M2. Two had jaundice and pruritus symptoms, 10 had mildly abnormal liver function, and one had severely elevated bilirubin and liver enzyme levels. The pathological characteristics of CHB complicated by PBC overlapped with those of PBC-autoimmune hepatitis (AIH). When necroinflammation of the portal area is not obvious, the pathological features of PBC are predominant, similar to the features of PBC alone. When the interface is severe, biliangitis will occur, with a large number of ductular reactions in zone 3. Unlike the PBC-AIH overlap pathology, this pathology is characterized by a small amount of plasma cell infiltration. Unlike PBC, lobulitis is often observed. CONCLUSION: This is the first large case series to show that the rare pathological features of CHB with PBC are similar to those of PBC-AIH and small duct injury was observed.
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BACKGROUND: Klebsiella variicola (K. variicola) is a member of the Klebsiella genus and is often misidentiï¬ed as Klebsiella pneumoniae. In this report, we present a rare case of invasive liver abscess caused by K. variicola. CASE SUMMARY: We report a rare case of liver abscess due to K. variicola. A 57-year-old female patient presented with back pain for a month. She developed a high-grade fever associated with chills, and went into a coma and developed shock. The clinical examinations and tests after admission confirmed a diagnosis of primary liver abscess caused by K. variicola complicated by intracranial infection and septic shock. The patient successfully recovered following early percutaneous drainage of the abscess, prompt appropriate antibiotic administration, and timely open surgical drainage. CONCLUSION: This is a case of successful treatment of invasive liver abscess syndrome caused by K. variicola, which has rarely been reported. The findings of this report point to the need for further study of this disease.
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Evidence linking O3 exposure and human semen quality is limited and conflicting and the mechanism underlying the association remains unclear. Therefore, we investigated the associations between ambient O3 exposure and sperm quality parameters and explored the mediating role of sperm mitochondrial DNA copy number (mtDNAcn) and sperm telomere length (STL) among 1068 potential sperm donors who provided 5002 repeated semen samples over approximately 90 days. We found that every 10 µg/m3 increase in O3 exposure was associated with a decrease in STL, sperm concentration, total count, total motile sperm number, and semen volume. However, O3 exposure was associated with increased total motility and progressive motility. The association for sperm quality parameters was stronger when exposure was measured at spermatogenesis stages I and II. For STL, the strongest association was observed when exposure was measured at spermatogenesis stage II. Additionally, we found that approximately 9% and 8% of the association between O3 exposure and sperm concentration and count was mediated by STL, respectively. In summary, our findings suggest that O3 pollution may affect sperm telomere length, eventually leading to reduced semen quality.
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Ozônio , Análise do Sêmen , Humanos , Masculino , Análise de Mediação , Indicadores de Qualidade em Assistência à Saúde , Sêmen , Espermatozoides , Telômero , Ozônio/toxicidadeRESUMO
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, poses a significant threat to public health worldwide, and diabetes is considered a risk factor for the rapid progression and poor prognosis of COVID-19. Limited immune function is a clinical feature of COVID-19 patients, and diabetes patients have defects in innate and adaptive immune functions, which may be an important reason for the rapid progression and poor prognosis of COVID-19 in patients with diabetes. We review the possible multiple effects of immune impairment in diabetic patients on the immune responses to COVID-19 to provide guidance for the diagnosis and treatment of diabetic patients with COVID-19.
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OBJECTIVE: To develop a simple model for the noninvasive diagnosis of liver fibrosis in patients with chronic hepatitis B and to testify its diagnostic value. METHODS: One hundred and ninety patients with chronic hepatitis B who had undergone liver biopsy were divided into 2 groups: one for developing the model (n = 110) and one for validation (n= 80). Histological staging of liver fibrosis, assessed blindly and independently by 2 pathologists, was determined according to Scheuer fibrosis score. Twenty markers involved in the study were analyzed initially in the estimation group to derive a predictive model to discriminate the stages of fibrosis. The model created was then assessed with receiver operating characteristic curve (ROC) analysis. It was also applied to the validation group to test its accuracy. RESULTS: Haptoglobin (HPT), gamma-glutamyl transpeptidase (GGT) and platelet were identified by logistic regression analysis as independent factors of fibrosis. A model developed from the above three markers was established to predict the stage of fibrosis(S). In ROC analysis, the area under curve (AUC) for identifying S > or =1, S > or = 2, S > or = 3 and S =4 was 0.832, 0.835, 0.820 and 0.843 respectively. The model had a similar AUC in the validation group without statistically significant difference. Using a cut-off of <0. 18, significant fibrosis (S > or = 2) could be excluded in 27 patients of the total patient population (negative predictive value 90%). Similarly, applying a cut-off > or = 0.70, significant fibrosis could be identified correctly in 67 patients of the total patient population (positive predictive value 82.7%). The model had a high level of diagnostic value in patients with HBeAg-positive chronic hepatitis B as well as in patients with HBeAg-negative chronic hepatitis B (AUC for identifying S > or = 2, 0.857 vs 0.802). Restricting biopsy to patients with intermediate scores ( > or = 0.70 and <0.18) may prevent liver biopsies in 58.4% of the patients while maintaining 84.7% accuracy. CONCLUSIONS: A model including HPT, GGT and platelet is a simple and reliable index for predicting significant fibrosis in patients with HBeAg-positive chronic hepatitis B as well as in patients with HBeAg-negative chronic hepatitis B.
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Hepatite B Crônica/diagnóstico , Cirrose Hepática/diagnóstico , Fígado/patologia , Feminino , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/etiologia , Masculino , Modelos Biológicos , PrognósticoRESUMO
OBJECTIVES: To understand the hepatic pathology, hepatitis B reactivation rates and serological changes in chronic HBV carriers. METHODS: A 5 year dynamic observation and survey of 220 chronic HBV carriers in Wuxi district was taken, analyzing their clinical symptoms, liver histopathology, virology and HBV immunological markers. RESULTS: Thirty-five of the 220 (15.9%) patients, showed hepatitis B reactivation. The hepatitis B reactivation rate of patients with obvious hepatic tissue inflammation (> or = G2) was 27.0% (33/122) and the rate of the patients with mild hepatic tissue inflammation (G0-G1) was 2.0% (2/98), showing significant differences (x2=25.41, P less than 0.01). The reactivation rate of patients with high inflammation was clearly higher than those with mild inflammation. Twenty-seven of the 35 hepatitis B reactivation cases were older than 40 years, showing a significant association between the ages of the patients and hepatitis B reactivation rates (x2=6.72, P less than 0.01), moreover there was no relationship between sex and the hepatitis B reactivation rate. There were differences in the inflammation grades and fibrosis stages between HBeAg positive and anti-HBe positive group cases (Kruskal-Wallis Test, x2=8.68, P less than 0.01, x2=6.84, P less than 0.01), showing inflammation grades and fibrosis stages of the anti-HBe positive group were higher than those of the HBeAg positive group. There were no obvious differences about the inflammation grade between age less than 40 years old and > or = 40 years old group cases (x2=0.62, P more than 0.05), but there were significant statistical differences about the fibrosis stage (x2=7.37, P less than 0.01), showing fibrosis stage of more than 40 years old group cases was clearly higher than the less than 40 years old group cases. Fifty-six cases received a liver biopsy for a second time and 23 for a third time. We found those whose hepatic tissues were normal in their first liver biopsies, then their liver histology continued remaining stable for several years while those with abnormal ones hardly or only recovered slightly. The rate of HBsAg turning to negativity per year was 1.55% and for HBeAg was 5.4%. CONCLUSION: The hepatic tissue pathology for most chronic HBV carriers (55%) had significant abnormalities (inflammation grade > or = G2), and the rates of hepatitis B reactivation were highly relevant to the liver inflammation grades and the ages of the patients.
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Portador Sadio/virologia , Hepatite B Crônica/virologia , Fígado/patologia , Adolescente , Adulto , Criança , Feminino , Seguimentos , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/patologia , Humanos , Inflamação , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Ativação Viral , Replicação Viral , Adulto JovemRESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) derived from bone marrow have potent stabilizing effects for the treatment of acute respiratory distress syndrome (ARDS). However, low efficiency and survival in MSC homing to injured lung tissue remains to be solved. Therefore, the aim of this study was to assess whether large intergenic noncoding RNA (LincRNA)-p21 promote MSC migration and survival capacity through hypoxic preconditioning in vitro. METHODS: MSCs were cultured and divided into the normoxia culture group (20% O2) and hypoxia culture group (1% O2). To determine roles and mechanisms, lentivirus vector-mediated LincRNA-p21 knockdown of MSCs and hypoxia-inducible factor (HIF-1α) inhibitor KC7F2 were introduced. Additionally, MSC migration was analyzed by scratch test and transwell migration assays. MSC proliferation was tested by cell counting kit-8 and trypan blue dye. Apoptosis was detected by Annexin V-PE/7-AAD stained flow cytometry. Moreover, LincRNA-p21 and HIF-1α mRNA was measured by reverse transcription-polymerase chain reaction, and HIF-1α and CXCR4/7 protein were assayed by western blot (WB) or enzyme-linked immunosorbent assay (ELISA). Apoptosis protein caspase-3 and cleaved-caspase-3 were investigated by WB analysis. Considering interactions between VHL and HIF-1α under LincRNA-p21 effect, co-immunoprecipitation was detected. RESULTS: Hypoxic preconditioning MSC promoted migration capacity and MSC survival than normoxia culture group. MSCs induced by hypoxic preconditioning evoked an increase in expression of LincRNA-p21, HIF-1α, and CXCR4/7(both were chemokine stromal-derived factor-1(SDF-1) receptors). Contrarily, blockade of LincRNA-p21 by shRNA and HIF-1α inhibitor KC7F2 abrogated upregulation of hypoxic preconditioning induced CXCR4/7 in MSCs, cell migration, and survival. Furthermore, co-immunoprecipitation assay revealed that hypoxic preconditioning isolated VHL and HIF-1α protein by increasing HIF-1α expression. CONCLUSIONS: Hypoxic preconditioning was identified as a promoting factor of MSC migration and survival capacity. LincRNA-p21 promotes MSC migration and survival capacity through HIF-1α/CXCR4 and CXCR7 pathway under hypoxic preconditioning in vitro.
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Movimento Celular/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Precondicionamento Isquêmico/métodos , Células-Tronco Mesenquimais/metabolismo , RNA Longo não Codificante/genética , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Hipóxia Celular , Sobrevivência Celular , Cultura em Câmaras de Difusão , Dissulfetos/farmacologia , Feminino , Regulação da Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Lentivirus/genética , Lentivirus/metabolismo , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos C57BL , Cultura Primária de Células , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , Receptores CXCR/genética , Receptores CXCR/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Sulfonamidas/farmacologia , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismoRESUMO
Progressive familial intrahepatic cholestasis type 3 is caused by a mutation in the ATP-binding cassette, subfamily B, member 4 (ABCB4) gene encoding multidrug resistance protein 3. A 32-year-old woman with a history of acute hepatitis at age 9 years was found to have jaundice during pregnancy in 2008, and was diagnosed as having intrahepatic cholestasis of pregnancy. In 2009, she underwent cholecystectomy for gallstones and chronic cholecystitis. However, itching and jaundice did not resolve postoperatively. She was admitted to our hospital with fatigue, jaundice, and a recently elevated γ-glutamyl transpeptidase level. Liver biopsy led to the diagnosis of biliary cirrhosis with ductopenia. Genetic testing revealed a pathogenic heterozygous mutation, ex13 c.1531G > A (p.A511T), in the ABCB4 gene. Her father did not carry the mutation, but her mother's brother carried the heterozygous mutation. We made a definitive diagnosis of familial intrahepatic cholestasis type 3. Her symptoms and liver function improved after 3 mo of treatment with ursodeoxycholic acid.
Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/deficiência , Ductos Biliares Intra-Hepáticos/patologia , Colestase Intra-Hepática/diagnóstico , Cirrose Hepática/diagnóstico , Ácido Ursodesoxicólico/uso terapêutico , gama-Glutamiltransferase/sangue , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Biópsia , Colestase Intra-Hepática/tratamento farmacológico , Colestase Intra-Hepática/genética , Colestase Intra-Hepática/patologia , Análise Mutacional de DNA , Feminino , Testes Genéticos , Humanos , Fígado/patologia , Cirrose Hepática/genética , Cirrose Hepática/patologiaRESUMO
Anelloviruses are single-strand circular DNA viruses and ubiquitous within the human population. Although there is no direct evidence, many studies have suggested the anelloviruses may be associated with a variety of diseases. In this study, a novel torque teno mini virus (TTMV) was detected in a child with unexplained encephalitis. The detected virus had a circular genome of 2943 nt in length and 3 open reading frames. It shared 45.4% - 35.9% nucleotide identities with known TTMV species and < 35% with the other species of anellovirus, which suggested it might belong to a new species within the genus Betatorquevirus. Phylogenetic analysis based on the amino acid sequences of ORF1 showed that this virus represented a distinct branch within the diversity of anellovirus. Whether this novel anellovirus strain is associated with encephalitis requires further study.