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PURPOSE: The purpose of this study was to explore the significance of the neuregulin-1/ErbB signaling pathway and its effect on Sox10 expression in the course of the differentiation of mouse bone marrow mesenchymal stem cells into Schwann-like cells in vitro. MATERIALS AND METHODS: The experiment was conducted with three groups-control, TAK 165, and HRG-off. In the control group, we used the classical induction method of adding ß-ME, RA, FSK, b-FGF, PDGF, and neuregulin (HRG); the cells were collected on the 7th day. Using the same basic protocol as the control group, the specific ErbB2 inhibitor mubritinib (TAK 165) was added to block the neuregulin-1/ErbB pathway in the TAK 165 group, while HRG was not added in the HRG-off group. We detected the degree of differentiation of stem cells into Schwann-like cells by using RT-PCR to examine the expression of Sox10, NRG-1, ErbB2, ErbB3, and ErbB4 and by using immunofluorescence staining to examine the Schwann cell marker S100B, Glial Fibrillary Acidic Protein (GFAP) and P75. RESULTS: Our results showed that the proliferation of Schwann cells was reduced and apoptosis was increased in the TAK 165 group and the HRG-off group. Sox10 was stably expressed and NRG-1, ErbB2, and ErbB3 increased in the control group. However, the expression of Sox10 in the TAK 165 group was obviously decreased at the end of induced differentiation; meanwhile, the degree of stem cell differentiation also decreased. CONCLUSIONS: the neuregulin-1/ErbB signaling pathway plays an important role in the differentiation of bone marrow mesenchymal stem cells into Schwann-like cells and can promote the maintenance of Sox10 ã.
Assuntos
Neuregulina-1 , Células de Schwann , Animais , Diferenciação Celular , Camundongos , Neuregulina-1/metabolismo , Receptor ErbB-4/metabolismo , Fatores de Transcrição SOXE/genética , Fatores de Transcrição SOXE/metabolismo , Transdução de SinaisRESUMO
In areas where hepatitis B virus (HBV) is endemic, mother-to-child transmission (MTCT) is the major route of infection of children. Blocking MTCT of HBV therefore would reduce its prevalence. The China Foundation of Hepatitis Prevention and Control organized a team of specialists in infectious diseases, hepatology, immunology, obstetrics, and public health to develop an algorithm for interrupting MTCT of HBV, based on the most recent hepatitis B guidelines and latest evidence. This algorithm comprises 10 steps and has been adopted in clinical practice in China. Four aspects (screening, antiviral intervention during pregnancy, immunoprophylaxis, and postvaccination serologic testing) are the core components of preventing MTCT. Although the combination of passive and active immunization in newborns of hepatitis B surface antigen-positive mothers reduces MTCT of HBV, this immunoprophylaxis cannot completely eradicate MTCT. In the past decade, administration of antiviral agents to pregnant women has been shown to be safe and effective in reducing MTCT of HBV in combination with immunoprophylaxis. Aiming to achieve zero MTCT, this algorithm recommends the use of antivirals during pregnancy by women with high viral loads. Preventing MTCT is key to achieving the goal of eliminating HBV as a public health threat by 2030. Implementation and enhancement of the standardized algorithm for pregnant women with chronic HBV infection and their infants is urgently needed to prevent MTCT.
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Antivirais/uso terapêutico , Vacinas contra Hepatite B/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Imunoglobulinas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Algoritmos , Aleitamento Materno , Feminino , Vírus da Hepatite B/imunologia , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/prevenção & controle , Humanos , Imunização Passiva , Recém-Nascido , Programas de Rastreamento , Guias de Prática Clínica como Assunto , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Tenofovir/uso terapêutico , Vacinação , Carga ViralRESUMO
BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is the leading cause of liver diseases including cirrhosis and hepatocellular carcinoma. In China, it is a major national health problem that demands nationwide coordinated emphasis on prevention and treatment. To inform these initiatives, a nationwide survey was conducted from January to April 2015 to evaluate the knowledge, awareness, and perceived obstacles to HCV care. METHODS: A sample of 1000 HCV specialists across mainland China were recruited. Respondents were asked a series of 30 open-ended single or multiple response and Likert-scale questions about their HCV treatment knowledge, experience, assessment of HCV care status in China, and perceptions about treatment barriers. RESULTS: Sixty percent of the respondents answered incorrectly to more than half of the questions on basic HCV treatment principles. Over half of them incorrectly believed that maintenance therapy should be prescribed for non-responders (72%) and longer treatment duration improved sustained viral response rates (62%), regardless of HCV RNA level changes. Sixty-six percent of them believed that HCV treatment would still be interferon-based therapy in the next 5 years in China. Patient-related barriers, in particular lack of disease awareness, were considered to be the most significant barriers to HCV care. Payer and medical-provider barriers included affordability issues, lack of reimbursement coverage for testing and treatments, and lack of referral to HCV specialists. CONCLUSIONS: Focused and intense patient and provider education should be carried out to increase awareness. More effective direct-acting antivirals should be made available and affordable in China.
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Antivirais/uso terapêutico , Atitude do Pessoal de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Acessibilidade aos Serviços de Saúde , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Padrão de Cuidado , Antivirais/efeitos adversos , China , Competência Clínica , Quimioterapia Combinada , Pesquisas sobre Atenção à Saúde , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Humanos , Interferons/efeitos adversos , Educação de Pacientes como Assunto , Polietilenoglicóis/efeitos adversos , Padrões de Prática Médica , Ribavirina/efeitos adversos , Resultado do TratamentoRESUMO
STUDY DESIGN: Retrospective, observational study. OBJECTIVE: To evaluate the ability and value of metagenomic next-generation sequencing (mNGS) in detecting pathogens from spinal infections. BACKGROUND: The pathogenic diagnosis of primary spinal infection is challenging. The widespread application of mNGs in clinical practice makes it particularly useful in detecting rare, emerging, and atypical complex infectious diseases. METHODS: From January 2019 to December 2023, a retrospective collection of 120 samples was obtained from patients suspected of spinal infections and undergoing treatment. Pairwise comparisons between traditional laboratory tests and mNGS were conducted for all cases. RESULTS: Among the 120 cases, 95 were diagnosed as spinal infections, while 25 were classified as non-infectious. Microbiological evidence was found in 59 cases, while 36 cases were clinically diagnosed as spinal infection without definitive microbiological evidence. Rare microorganisms such as Aspergillus fumigatus, Taifanglania major, and Coxiella burnetii were detected by mNGS. The positive rate of mNGS was significantly higher at 88.42% compared to microbiological culture (43.16%), P<0.001. At the genus level, mNGS exhibited a consistency rate of 86.44% (51/59) with confirmed microorganisms. MNGS demonstrated very good agreement with clinically confirmed microorganisms at the genus level (kappa=0.833). The sensitivity, specificity, positive predictive value, and negative predictive value of mNGS were 86.44%, 92.00%, 96.23%, and 74.19%, respectively. CONCLUSIONS: The mNGS test exhibits rapidity, efficiency, and accuracy, rendering it of immense diagnostic and therapeutic value in the realm of spinal infection diseases.
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Growing evidence indicates that gut microbiota is involved in the regulation of the host's sex hormone levels, such as through interfering with the sex hormone metabolism in the intestine. However, if gut microbiota or its metabolites directly influence the sex hormone biosynthesis in the gonad remains largely unknown. Our previous study showed that colistin, as a narrow-spectrum antibiotic, can significantly downregulate the serum testosterone levels and thus enhance the antitumor efficiency of anti-PD-L1 in male mice; however, the underlying mechanism for the regulation of the host's testosterone levels remains uninvestigated. In the present study, we analyzed the impact of colistin on the immune microenvironment of the testis as well as the composition and metabolism of gut microbiota in male mice. Our results showed that colistin has an impact on the immune microenvironment of the testis and can downregulate serum testosterone levels in male mice through inhibition of Akkermansia, leading to destroyed inosine metabolism. Supplement with inosine can restore testosterone secretion probably by prompting the recovery of the intestinal mucus barrier and the serum lipopolysaccharides levels. All these findings reveal a new pathway for the regulation of the host's sex hormone levels by gut microbiota.IMPORTANCEThis study demonstrates that exposure to even narrow-spectrum antibiotics may affect the host's testosterone levels by altering the gut microbiota and its metabolites. Our findings provide evidence that some specific gut bacteria have an impact on the sex hormone biosynthesis in the testis.
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Microbioma Gastrointestinal , Masculino , Camundongos , Animais , Testículo , Colistina , Testosterona , Hormônios Esteroides GonadaisRESUMO
The World Health Organization (WHO) has set the goal of eliminating hepatitis as a threat to public health by 2030. Blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is not only the key to eliminating viral hepatitis, but also a hot issue in the field of hepatitis B prevention and treatment. To standardize the clinical management of preventing MTCT of HBV and achieve zero HBV infection among infants, the Chinese Foundation for Hepatitis Prevention and Control organized experts to compile a management algorithm for prevention of MTCT of HBV based on the latest research progress and guidelines, including 10 steps of pregnancy management and postpartum follow-up, among which screening, antiviral treatment, and infant immunization are its core components.
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BACKGROUND: Ideal surgical treatment for thoracic disc herniation (TDH) is controversial due to variations in patient presentation, pathology, and possible surgical approach. Althougth discectomy may lead to improvements in neurologic function, it can be complicated by approach related morbidity. Various posterior surgical approaches have been developed to treate TDH, but the gold standard remains transthoracic decompression. Certain patients have comorbidities and herniation that are not optimally treated with an anterior approach. A transfacet pedicle approach was first described in 1995, but outcomes and complications have not been well described. The aim of this work was to evaluate the clinical effect and complications in a consecutive series of patients with symptomatic thoracic disc herniations undergoing thoracic discectomy using a modified transfacet approach. MATERIALS AND METHODS: 33 patients with thoracic disc herniation were included in this study. Duration of the disease was from 12 days to 36 months, with less than 1 month in 13 patients. Of these, 15 patients were diagnosed with simple thoracic disc herniation, 6 were associated with ossified posterior longitudinal ligament, and 12 with ossified or hypertrophied yellow ligament. A total of 45 discs were involved. All the herniated discs and the ossified posterior longitudinal ligaments were excised using a modified transfacet approach. Laminectomy and replantation were performed for patients with ossified or hypertrophied yellow ligament. The screw-rod system was used on both sides in 14 patients and on one side in l9 patients. RESULTS: 29 patients were followed up for an average of 37 months (range 12-63 months) and 4 patients were lost to followup. Evaluation was based on Epstein and Schwall criteria.5 15 were classified as excellent and 10 as good, accounting for 86.21% (25/29); 2 patients were classified as improved and 2 as poor. All the patients recovered neurologically after surgery. A total of 25 patients had significantly improved motor function from 3 to 6 months after surgery and 10 patients had slow recovery 6 months after surgery.. Of the three patients with postoperative complications, two had exacerbated preexisting defects and one had implant failure. Postoperative computed tomography or magnetic resonance imaging showed that all patients had well fused replanted lamina and completely decompressed canal. CONCLUSION: Thoracic discectomy using a modified transfacet approach can significantly improve the clinical outcomes.