RESUMO
Hepatocellular carcinoma (HCC) is defined as a universal malignancy while radiation therapy is the effective treatment for it. This study validated the mechanism of long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed gene (CRNDE) in radiation resistance in HCC. LncRNA CRNDE upregulation was detected in HCC cells. The radiation-resistant cell strains Huh7R and SNU-387R were established. After silencing lncRNA CRNDE, the cell colony formation ability, cell activity, apoptosis, cell cycles, and γ-H2AX positive rate in Huh7R and SNU-387R were detected. Silencing lncRNA CRNDE decreased the cell activity, colony formation ability, and cell number in the G2 phase and facilitated DNA damage and apoptosis. The binding relations of specificity protein 1 (SP1) with lncRNA CRNDE and 3-phosphoinositide dependent protein kinase 1 (PDK1) were verified. LncRNA CRNDE regulated PDK1 transcription by binding to transcription factor SP1. PDK1 overexpression partially reversed the inhibition of silencing lncRNA CRNDE on radiation resistance in HCC cells. The transplanted tumor mouse model was established and showed that silencing lncRNA CRNDE decreased tumor volume and weight and Ki67-positive cells in HCC mice in vivo. Collectively, lncRNA CRNDE was upregulated in HCC cells and promoted PDK1 transcription by binding to SP1, thus enhancing radiation resistance in HCC cells.
Assuntos
Carcinoma Hepatocelular , Neoplasias Colorretais , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/radioterapia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/radioterapia , Camundongos , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
BACKGROUND: Human papillomavirus (HPV) infection causes cervical cancer and premalignant lesions of the cervix. Prevalence of HPV infection and HPV genotypes vary among different regions. However there is no data on the prevalence of HPV infection and HPV genotypes from southwest China. This study was undertaken to determine the prevalence of and risk factors for HR-HPV infection in Qujing of Yunnan province, southwest China to provide comprehensive baseline data for future screening strategies. METHODS: A sample of 5936 women was chosen by the multi-stage stratified cluster sampling method with selection probabilities proportional to size (PPS). An epidemiological questionnaire was conducted via a face-to-face interview and cervical specimens were taken for HPV DNA testing by Digene Hybrid Capture 2 (HC2) test. HPV Genotyping Reverse Hybridization Test was used for HPV genotyping. Proportions were compared by Chi-squared tests, and logistic regression was utilized to evaluate risk factors. RESULTS: The median age was 38 years and the inter-quartile range was from 31 years to 47 years. 97.3% of the study population was Han nationality. Overall prevalence of HR-HPV infection was 8.3% (494/5936) and bimodal age distribution of HPV infection was observed. The five most prevalent HR-HPV genotypes were HPV-16(3.4%), HPV-56(1.7%), HPV-58(1.4%), HPV-33(1.2%) and HPV-52(0.88%). Multiple HPV infections were identified in 50.5% (208/412) of the positive genotyping specimens. Multivariate logistic regression model indicated that parity (OR = 1.35, 95% CI: 1.18-1.53, p < 0.0001) was a risk factor for HR-HPV infection, and age of 50-65 years (OR = 0.60, 95% CI: 0.45-0.80, p = 0.0005), being married or in stable relationship (OR = 0.55, 95% CI: 0.31-0.96, p = 0.035) were protective factors. CONCLUSIONS: This study provided baseline data on HR-HPV prevalence in the general female population in Qujing of Yunnan province, southwest China. The finding of multiple HPV infections and bimodal age distribution revealed that HPV screening is necessary for perimenopausal women in future.
Assuntos
Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Adolescente , Adulto , Fatores Etários , Idoso , Colo do Útero/virologia , China/epidemiologia , Coinfecção/epidemiologia , Coinfecção/virologia , Estudos Transversais , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVE: To evaluate the clinical effects of debridement and bone grafting with internal fixation via anterior approach in treatment of tuberculosis of lower cervical vertebrae. METHODS: The clinical data of 15 patients with tuberculosis of lower cervical vertebrae who accepted the treatment of one-stage debridement and bone grafting with internal fixation from June 2010 to December 2018 were retrospectively analyzed. There were 9 males and 6 females, aged from 39 to 72 years with an average of (54.67±10.75) years. The lesion segment was C4 to C6. Pre- and post-operative neurologic functions were evaluated by ASIA grade. All the patients underwent the X-ray films of positive and lateral of cervical spine before and after the operation and accepted the periodic review of CT to evaluate the bone grafting. RESULTS: All the 15 operations were successful, no neurological or vascular injury occurred during the operation, and all patients were followed up for 18 to 52 months. The clinical symptoms improved significantly during the follow-up period and CT showed good bone grafting fusion. One patient suffered a relapse of the illness 3 years later, but was healed during the follow-up visit by strengthening the anti tuberculosis therapy. CONCLUSION: For the patients with vertebral destruction and loss of cervical stability, one-stage debridement and bone grafting with internal fixation via anterior approach has definite curative effects. On the basis of standard anti tuberculosis treatment before operation, the long-term standard anti-tuberculosis treatment after operation is the key to healing the tuberculosis of lower cervical vertebrae.
Assuntos
Fusão Vertebral , Tuberculose da Coluna Vertebral , Adulto , Idoso , Transplante Ósseo , Vértebras Cervicais , Desbridamento , Feminino , Fixação Interna de Fraturas , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vértebras Torácicas , Resultado do TratamentoRESUMO
OBJECTIVES: Immunosuppressant-related hip pain can greatly affect a patient's mobility and increase the number of total hip arthroplasties. We investigated risk factors and causes of hip pain after orthotopic liver transplant. MATERIALS AND METHODS: The medical records of 175 adult orthotopic liver transplant patients, who were followed-up for more than 2 years, were retrospectively reviewed. Data collected from the records included primary disease, medications, biochemical results, Child-Turcotte-Pugh score, death, rejection, and complications related to liver transplant. RESULTS: A total of 11 patients (6.3%) complained of hip pain, which was diagnosed as calcineurin-inhibitor-induced pain syndrome in 4 patients (2.3%), osteonecrosis of the femoral head in 3 patients (1.7%), and osteoporosis in 2 patients (1.1%). The incidence of calcineurin-inhibitor-induced pain syndrome was related to the dosage of tacrolimus (P > .05) but independent of methylprednisolone use. The occurrence of osteonecrosis of the femoral head was independent of the dosage and early withdrawal of methylprednisolone (P > .05). Patients with methylprednisolone withdrawal within 6 months had significantly longer survival than those using methylprednisolone for more than 6 months (50 ± 15 vs 41 ± 18 mo; P = .007). CONCLUSIONS: Calcineurin-inhibitor-induced pain syndrome and osteonecrosis of the femoral head are main causes of hip pain in adult orthotopic liver transplant patients. Osteonecrosis of the femoral head was not common, but the incidence of hip pain owing to calcineurin-inhibitor-induced pain syndrome was relatively high in orthotopic liver transplant patients. Early withdrawal of methylprednisolone could benefit the patients' survival.
Assuntos
Artralgia/induzido quimicamente , Inibidores de Calcineurina , Articulação do Quadril , Imunossupressores/efeitos adversos , Transplante de Fígado , Tacrolimo/efeitos adversos , Adulto , Idoso , Artralgia/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Incidência , Cirrose Hepática/cirurgia , Falência Hepática/cirurgia , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Osteonecrose/induzido quimicamente , Osteonecrose/epidemiologia , Osteoporose/induzido quimicamente , Osteoporose/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: With the increase of survival in liver transplantation recipients, more patients are at a high risk of developing osteonecrosis, especially in the femoral head, due to immunosuppressive treatment. The purpose of this study was to report the incidence, possible risk factors, and outcome of symptomatic osteonecrosis of the femoral head (ONFH) in adult patients with current immunosuppressive agents and individual protocol after liver transplantation in China. METHODS: A retrospective analysis was performed on 226 adult patients who underwent orthotopic liver transplantation (OLT) at a single liver transplantation institution between January 2004 and December 2008. The posttransplant survival time (or pre-retransplantation survival time) of all the patients were more than 24 months. The possible pre- and post-transplantation risk factors of symptomatic ONFH were investigated and the curative effects of the treatment were also reported. RESULTS: The incidence of ONFH was 1.33% in patients after OLT. ONFH occurred at a mean of (14 ± 6) months (range, 10 - 21 months) after transplantation. Male patients more often presented with osteonecrosis as a complication than female patients. The patients with lower pre-transplantation total bilirubin and direct bilirubin levels (P < 0.05). There was no difference in the cumulative dose of corticosteroids or tacrolimus between the patients with or without symptomatic ONFH. Patients were treated either pharmacologically or surgically. All patients showed a nice curative effect without major complications during the 18 - 63 months post-treatment follow up. CONCLUSIONS: The symptomatic ONFH does not occur commonly after adult OLT in the current individual immunosuppressive protocol in China.
Assuntos
Necrose da Cabeça do Fêmur/epidemiologia , Necrose da Cabeça do Fêmur/etiologia , Transplante de Fígado/efeitos adversos , Osteonecrose/epidemiologia , Osteonecrose/etiologia , Adulto , Idoso , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Feminino , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Metilprednisolona/efeitos adversos , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sirolimo/efeitos adversos , Sirolimo/uso terapêutico , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico , Adulto JovemRESUMO
OBJECTIVE: To synthesize a tumor-targeting cell-penetrating peptide (CPP) and evaluate its biological activity and cytotoxicity in vitro. METHODS: With fluorenylmethyloxycarbonyl (Fmoc) as the protective group of α-amino acid, the tumor-targeting CPP were synthesized with stepwise amino acid extension using solid-phase synthesis method. 5-carboxytetramethylrhodamine was added for fluorescence labeling in the presence of the coupling agents HATU and DMF. The purity of the CPP was measured by high-performance liquid chromatography and its molecular weight measured by mass spectrometry. Fluorescence microscope was used to assess the cell-penetrating activity?of the CPP in hepatocellular carcinoma cell lines SMMC-7721 and normal hepatocellular cell lines LO2. The growth activity of CPP-treated SMMC-7721 cells was measured by MTT assay. RESULTS: With a purity of 96.05% and a relative molecular mass of 3504.9, the synthesized CPP showed no translocation activity in normal hepatocellular cell lines LO2, but showed strong ability to translocate into SMMC-7721 cells without affecting the biological activity of the cells. CONCLUSION: Using Fmoc solid-phase synthesis method, we have successfully synthesized the CPP with tumor-targeting activity.
Assuntos
Peptídeos Penetradores de Células/síntese química , Peptídeos Penetradores de Células/farmacologia , Sistemas de Liberação de Medicamentos , Neoplasias Hepáticas/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Linhagem Celular Tumoral , Desenho de Fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Rodaminas/química , Técnicas de Síntese em Fase SólidaRESUMO
AIMS: Infants less than 35 weeks' gestation age are susceptible to periventricular-intraventricular hemorrhage (PIVH). This may be partially attributable to low concentrations of vitamin K-dependent coagulation factors. The purposes of this study were: (1) to determine the umbilical blood activity levels of vitamin K-dependent coagulation factors II, VII, IX and X; (2) to investigate the change in activities of these factors in premature infants' umbilical blood after prenatal administration of vitamin K1 to the mothers; and (3) to study the prophylactic effects on PIVH after maternal antenatal supplemental vitamin K1. METHODS: Pregnant women in preterm labor at less than 35 weeks of gestation were randomly selected to receive antenatal vitamin K1 10 mg per day injection intramuscularly or intravenously for 2-7 days (vitamin K1 group, n = 40), or no such treatment (control group, n = 50). At the same period, cord blood samples were collected from thirty full-term neonates to compare the factor levels with those of premature infants. Intracranial ultrasound was performed by the same sonographer to determine the presence and severity of PIVH. RESULTS: The activities of vitamin K-dependent coagulation factors in umbilical blood in the control group were: factor II 25.64+/-9.49%, factor VII 59.00+/-17.66%, factor IX 24.67+/-8.88%, and factor X 30.16+/-5.02%. In full-term infants, the respective values were: factor II 36.70+/-4.88%, factor VII 64.54+/-10.62%, factor IX 30.18+/-5.69%, and factor X 34.32+/-12.63%. In vitamin K1 group these factors were: factor II 36.35+/-6.88%, factor VII 69.59+/-16.55%, factor IX 25.71+/-10.88%, and factor X 39.26+/-8.02%. The data suggest the absence of vitamin K-dependent coagulation factors in preterm infants, and antenatal supplement of vitamin K1 may increase the cord blood activity of factor II, VII and factor X (P < 0.001). In addition, the overall rates of PIVH in the vitamin K1 group and in controls were 32.4 and 52.0%, respectively (P = 0.036), and the frequency of severe PIVH was 5.0 and 20.0%, respectively (P = 0.038). CONCLUSIONS: Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation age may result in improved coagulation and may reduce the incidence as well as the severity degree of PIVH.