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BACKGROUND: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a programmed cell death protein 1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1 : 1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by two cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either six cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or six cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in the experimental arm and 118 patients in the control arm, with surgery carried out in 92% and 83.9%, respectively. At data cut-off (11 July 2023), the pCR rates were 39.8% [95% confidence interval (CI) 30.7% to 49.5%] in the experimental arm compared to 15.3% (95% CI 9.3% to 23.0%) in the control arm (difference, 24.6%; odds ratio, 3.7; 95% CI 2.0-6.9; P < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, and grade ≥3 treatment-related adverse events were 29.2% and 27.2%. Three-year EFS rate and OS continue to mature. CONCLUSIONS: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.
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Objective: To develop a simple screening questionnaire for persistent postural-perceptual dizziness (PPPD) and evaluate its screening ability. Methods: A convenience sample of 296 individuals who met the inclusion criteria between November 2021 and January 2023 were prospectively selected for three rounds of screening at the Vertigo Specialty Clinic of the Department of Otorhinolaryngology-Head and Neck Surgery in the First Hospital of Shanxi Medical University. In conjunction with expert opinion and statistical analysis, the first and second rounds of screening were used to modify and finalize the questionnaire entries, and the third round of screening was used to evaluate the questionnaire's screening ability. Independent sample t-test was used for inter group comparison, reliability and validity indicators were employed to screen and evaluate questionnaire entries, and the receiver operating characteristic (ROC) curve was plotted to determine the optimal cut-off value and corresponding sensitivity and specificity. Results: The final PPPD screening questionnaire entries included 21 items. In evaluating the reliability of this questionnaire, the Cronbach's alpha coefficient was 0.831, the half folding coefficient was 0.742, the content validity was 0.86, and the Kaiser-Meyer-Olkin (KMO) value in the structural validity was 0.811. Additionally, there were six factors with characteristic root>1 and a cumulative contribution rate of 62.62%. The area under the ROC curve of the screening questionnaire was 0.935 (95%CI: 0.877-0.992), and the optimal cut-off value was 8.5, with a sensitivity of 85.0%, a specificity of 85.5%, and a Kappa value of 0.653. Conclusion: The PPPD simple screening questionnaire designed in this study has a high sensitivity and specificity, making it a useful tool for identifying PPPD patients.
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Mareo , Humanos , Mareo/diagnóstico , Reproducibilidad de los Resultados , Curva ROC , Sensibilidad y Especificidad , Encuestas y CuestionariosRESUMEN
Objective: To evaluate the application value of reducing tube voltage and iodine delivery rate according to body weight in coronary CT angiography (CCTA). Methods: A prospective randomized controlled study. A total of 297 subjects, 172 males and 125 females, aged [M (Q1, Q3)]60.0 (50.0, 68.0) years, who underwent CCTA examination in Peking University Third Hospital due to clinically suspected coronary heart disease from May to December 2022 were included. According to the odd or even visit dates, the subjects were randomly divided into test group (n=156) and control group (n=141). The subjects in both groups were divided into four sub-groups according to body weight: 50-59 group, 60-69 kg group, 70-79 kg group and 80-89 kg group, respectively. The CCTA images were reconstructed with hybrid iterative algorithm(KARL 3D) with levels of 6 and 8, respectively. 100 kVp and iodine flow rate 1.1, 1.3, 1.4 and 1.5 gI/s recommended by the domestic CCTA application guidelines were used in the control group, while the tube voltage and iodine flow rate were reduced in the test group based on the guidelines and body weight:70 kVp and 0.8 g I/s in 50~59 kg group, 80 kVp and 1.0 gI/s in 60~69 kg group, 80 kVp and 1.1 gI/s in70~79 kg group, and 100 kVp and 1.5 gI/s in 80~89 kg group, respectively. The CT values and standard deviation (SD) of aortic root, proximal left anterior descending branch (LAD) and distal right coronary artery (RCA) luminal CCTA, the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of coronary artery CT images, subjective coronary scores and effective radiation dose (ED) were compared between the both groups. One-way ANOVA or Wilcoxon test was used to analyze the differences of above indicators between the groups to evaluate the application value of low voltage and low iodine flow rate based on weight in coronary CCTA. Results: CT values of aortic root, LAD proximal CT values and SD values of aortic root [411.4 (377.2, 439.8) HU, (366.3±42.9) HU, 26.5±2.3] in the test group were all higher than those in the control group [379.00 (335.2, 415.9) HU, (355.0±46.9) HU and 24.8±2.3]. The differences were statistically significant (all P<0.05), and the other parameters were not statistically significant (all P>0.05). The total subjective image quality score in test group were superior to those in the control group (all P<0.05). The total ED and contrast agent dosage [2.07 (1.52, 3.28) mSv and (38.28±9.68) ml] in CCTA examination in the test group were lower than those in the control group [3.30(2.32, 4.44) mSv and (45.31±5.63) ml], and the differences were statistically significant (all P<0.05). The dosage of ED and contrast agent in the test group was decreased by 37.3% and 15.5%, respectively. Conclusion: Combined with KARL 3D,it is feasible to reduce contrast medium and ED by setting the tube voltage and iodine flow rate of CCTA according to the weight of the subject, which can further reduce the radiation dose and contrast agent dosage of CCTA.
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Angiografía por Tomografía Computarizada , Yodo , Masculino , Femenino , Humanos , Anciano , Angiografía por Tomografía Computarizada/métodos , Medios de Contraste , Estudios Prospectivos , Dosis de Radiación , Angiografía Coronaria/métodos , Tomografía Computarizada por Rayos X/métodos , Peso Corporal , Interpretación de Imagen Radiográfica Asistida por Computador/métodosAsunto(s)
Mareo , Vértigo , Humanos , Mareo/diagnóstico , Encuestas y Cuestionarios , Vértigo/diagnósticoRESUMEN
Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Resultado del TratamientoRESUMEN
A child complained of bilateral congenital non-progressive ptosis for 18 months. According to the clinical characteristics, systemic development and chromosome microarray analysis, the child was diagnosed as 2q37 deletion syndrome related ophthalmo facial malformation. The patient underwent the frontalis aponeurosis flap suspension. After operation, the appearance of eyelids was significantly improved.
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Blefaroplastia , Blefaroptosis , Niño , Humanos , Blefaroptosis/cirugía , Párpados/cirugía , Deleción Cromosómica , Colgajos Quirúrgicos/cirugía , Músculos Oculomotores/cirugíaRESUMEN
Objective: To analyze the effects of the sequence of radiotherapy and chemotherapy on the efficacy of early-stage extranodal NK/T-cell lymphoma (nasal type, ENKTCL) patients, and to provide a quantitative evaluation method for individualized radiotherapy and chemotherapy. Methods: The Chinese Lymphoma Collaborative Group (CLCG) collected the clinical data of 2 008 patients with early-stage â /â ¡ ENKTCL who received radiotherapy and chemotherapy from January 2000 to early September 2019 from 21 hospitals across the country, including 1 417 males and 591 females, aged 2 to 83 (42±14) years. According to the sequence of radiotherapy and chemotherapy, patients were divided into radiotherapy-first group (388 cases) and chemotherapy-first group (1 620 cases). Survival rate was estimated using Kaplan-Meier method, and multivariate Cox proportional risk model was used to screen and identify independent prognostic factors. The prognostic prediction models of the two therapies were constructed separately, and the models were used to predict the individualized mortality risk of all patients to determine the appropriate radiotherapy and chemotherapy regimen for each patient. Results: The 5-year overall survival rate was 74.2% (95%CI: 69.6%-79.2%) in the radiotherapy-first group and 69.7% (95%CI: 67.1%-72.4%) in the chemotherapy-first group. Although the 5-year overall survival rate of patients in the radiotherapy-first group was numerically higher than that of the chemotherapy-first group, the difference was not statistically significant (χ2= 2.26, HR=0.84 (95%CI: 0.68-1.05), P=0.133). Six variables including age, gender, ECOG score, LDH, Ann Arbor staging, and PTI (primary tumor invasion) were screened out as independent prognostic factors (the chemotherapy-first group: HR were 1.01, 1.25, 2.07, 0.77, 1.34, 1.49, respectively, all P<0.05; radiotherapy-first group: HR were 1.02, 1.31, 1.66, 0.78, 1.37, 1.29, all P>0.05). The mean 5-year predicted mortality risk for all patients receiving radiotherapy-first regimen was lower than those receiving chemotherapy-first regimen (26.8% vs 30.2%, P<0.001). There were individualized differences in the predicted mortality risk of patients with different clinical characteristics who received radiotherapy-first regimen or chemotherapy-first regimen. Conclusion: Patients with stage â /â ¡ ENKTCL treated with radiotherapy-first regimen had a better expected prognosis than patients treated with chemotherapy-first regimen. The quantitative assessment of the differential effects of the sequence of radiotherapy and chemotherapy on the mortality risk of individual patients based on their clinical characteristics was helpful for the clinical development of the optimal radiotherapy and chemotherapy plan for each patient.
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Linfoma Extranodal de Células NK-T , Terapia Combinada , Femenino , Humanos , Masculino , Nariz , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
Objective: To explore the hub genes and mechanisms in the pathological process of non-alcoholic steatohepatitis (NASH) by bioinformatics methods. Methods: Microarray datasets GSE89632 were downloaded from the Gene Expression Omnibus (GEO) database, which including 20 simple non-alcoholic fatty liver disease patients, 19 NASH patients and 24 healthy control individuals. The differentially expressed genes (DEGs) in patients with simple non-alcoholic fatty liver disease and NASH were compared with healthy control individuals respectively, and the intersection of the two groups of DEGs was taken. GO functional annotation and KEGG pathway enrichment analysis of DEGs were performed with DAVID 6.8 and KOBAS 3.0 separately. Protein-protein interaction network (PPI) was constructed by STRING database, then the mRNA hub genes were selected by Cytoscape software. The Attie Lab Diabetes database was used to verify the relative expression of hub genes mRNA in the liver of 4 groups of C57BL/6 mice (4-week-old normal group, 4-week-old obese group, 10-week-old normal group and 10-week-old obese group, 5 mice in each group). Spearman's correlation analysis was performed to analyze the correlation between hub gens and prognostic clinical parameters. Results: From the GSE89632 dataset, 365 common DEGs (115 up-regulated genes and 250 down-regulated genes) were identified in patients with simple non-alcoholic fatty liver disease and NASH patients compared with control individuals. GO analysis showed that DEGs were mainly enriched in biological processes such as inflammatory response and immune response. KEGG pathway analysis showed that up-regulated genes were mainly enriched in cholesterol metabolism, bile secretion and fat digestion and absorption signal pathways. Down-regulated genes were mainly enriched in interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, advanced glycation end products and their receptors of diabetic complications. Seven key hub genes were identified by PPI analysis, which were FOS, EGR1, FOSB, JUNB, FOSL1, MYC and NR4A1.The mRNA relative expression levels of EGR1 and JUNB in the liver of 10-week-old obese mice were lower than those of normal mice (P<0.05).The relative expression levels of NR4A1 in the liver of obese mice at 4-and 10-week-old were lower than those of normal mice at the same age (P values<0.05). Spearman's correlation analysis showed that the expression of EGR1 was negatively correlated with the degree of hepatic steatosis (r=-0.785, P<0.001).The expression levels of FOSB, MYC and NR4A1 were negatively correlated with the level of alanine aminotransferase (r=-0.649, -0.597 and-0.580 respectively, all P values<0.001). Conclusion: EGR1, FOSB, MYC, JUNB and NR4A1 might be the hub genes in the pathological process of NASH and the inflammatory and immune response in hepatocytes, IL-17 signaling pathway and TNF signaling pathway might be the key molecular mechanisms in the occurrence and development of NASH.
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Enfermedad del Hígado Graso no Alcohólico , Animales , Expresión Génica , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/genéticaRESUMEN
Objective: To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL). Methods: A total of 557 patients from 2000-2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis. Results: The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 (P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population (P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy (P<0.001). Radiotherapy dose was an independent factor affecting LRC(P<0.05). Conclusions: Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.
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Linfoma Extranodal de Células NK-T , Terapia Combinada , Supervivencia sin Enfermedad , Humanos , Linfoma Extranodal de Células NK-T/patología , Linfoma Extranodal de Células NK-T/radioterapia , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Objective: To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL). Methods: The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis. Results: Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor â ¢~â £ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% (P=0.281), while the PFS rates were 24.8% and 48.3%, respectively (P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival (P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival(P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions: Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.
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Linfoma Extranodal de Células NK-T , China , Humanos , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Linfoma Extranodal de Células NK-T/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: This study evaluated the survival benefit of asparaginase (ASP)-based versus non-ASP-based chemotherapy combined with radiotherapy in a real-world cohort of patients with early-stage extranodal nasal-type natural killer/T-cell lymphoma (ENKTCL). PATIENTS AND METHODS: We identified 376 patients who received combined radiotherapy with either ASP-based (ASP, platinum, and gemcitabine; n = 286) or non-ASP-based (platinum and gemcitabine; n = 90) regimens. The patients were stratified into low-, intermediate-, and high-risk groups using the early stage-adjusted nomogram-revised risk index. Overall survival (OS) and distant metastasis (DM)-free survival (DMFS) between the chemotherapy regimens were compared using inverse probability of treatment weighting (IPTW) and multivariable analyses. RESULTS: ASP-based (versus non-ASP-based) regimens significantly improved 5-year OS (84.5% versus 73.2%, P = 0.021) and DMFS (84.4% versus 74.5%, P = 0.014) for intermediate- and high-risk patients, but not for low-risk patients in the setting of radiotherapy. Moreover, ASP-based regimens decreased DM, with a 5-year cumulative DM rate of 14.9% for ASP-based regimens compared with 25.1% (P = 0.014) for non-ASP-based regimens. The survival benefit of ASP-based chemotherapy and radiotherapy remained consistent after adjusting the confounding variables using IPTW and multivariate analyses; additional sensitivity analyses confirmed these results. CONCLUSIONS: The findings provided support for ASP-based chemotherapy and radiotherapy as a first-line treatment strategy for intermediate- and high-risk early-stage ENKTCL.
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Asparaginasa , Linfoma Extranodal de Células NK-T , Asparaginasa/uso terapéutico , Humanos , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Linfoma Extranodal de Células NK-T/radioterapia , Estadificación de Neoplasias , RiesgoRESUMEN
Lymphoepithelioma-like hepatic carcinoma (LELC) is a rare distinctive variant of liver cancer with unique epidemiological and pathological characteristics, characterized by dense lymphocyte infiltration.It can be divided into lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) and lymphoepithelioma-like cholangiocarcinoma (LEL-CC). The diagnosis is mainly based on pathology, and the treatment is mainly surgery. The prognosis of LELC is good, which may be related to a large number of lymphocyte infiltration. The data of LELC is very limited, only a few case reports and small retrospective studies, which needs further exploration and research. Up to now, 67 cases of LEL-HCC and 34 cases of LEL-CC have been reported. The purpose of this review is to provide a comprehensive overview of the current research situation on LELC in terms of epidemiology, clinical treatment, pathology and research prospects.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Estudios RetrospectivosRESUMEN
Objective: To analyze the relationship between maternal mutations in basal core promoter region of hepatitis B virus (HBV) genotype C and intrauterine transmission. Methods: We collected information on general demographic characteristics and process of delivery among 399 pairs of consecutive HBsAg-positive mothers and their neonates, from the Third People's Hospital of Taiyuan in Shanxi province, China. Fluorescence quantitative polymerase chain reaction (FQ-PCR) and Electro-chemiluminescence immuno-assay (ECLIA) kits were used to detect both maternal and neonatal HBV DNA and serological markers in the peripheral blood. From 113 mothers with HBV DNA load ≥10(6) IU/ml, we selected 22 mothers whose neonates were with intrauterine transmission and randomly selected the same number of mothers whose neonates were without intrauterine transmission, as controls. The whole-length HBV DNA were extracted, amplified, cloned, sequenced and genotyped. Finally, a total of 39 mothers with genotype C of HBV were selected for mutation analysis. Results: Thirty-nine cases of genotype C (88.63%) were finally included in the study, with 19 cases in the intrauterine transmission group and 20 cases as controls. Rates of A1762T/G1764A double mutations were significantly different between the intrauterine transmission group and the control group (7.53% vs. 27.72%, P<0.001). Results from the multivariate analysis showed that the A1762T/G1764A double mutations had reduced the risk of intrauterine transmission (aOR=0.065, 95%CI: 0.006-0.746, P=0.028). Maternal A1762T/G1764A double mutations appeared to be possibly associated with neonatal HBeAg (P=0.050). Conclusion: A1762T/G1764A double mutations of HBV DNA from the genotype C of those HBsAg-positive mothers could reduced the risk of HBV intrauterine transmission during pregnancy.
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Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Mutación , Complicaciones Infecciosas del Embarazo/virología , Regiones Promotoras Genéticas/genética , China , ADN Viral/sangre , Femenino , Genotipo , Humanos , Recién Nacido , EmbarazoRESUMEN
OBJECTIVE: To elucidate the molecular mechanism of Simvastatin on inhibiting malignant progression of lung cancer. PATIENTS AND METHODS: Relative levels of METTL3 and EZH2 in lung cancer tissues and adjacent normal ones were detected by quantitative real-time polymerase chain reaction (qRT-PCR). In addition, their levels in lung cancer patients with different pathological stages were determined as well. A549 cells were induced with different doses of Simvastatin for 24 h. Subsequently, relative levels of METTL3 and EZH2 in cells were detected. Proliferative and metastatic abilities in A549 cells were examined by cell counting kit-8 (CCK-8), 5-Ethynyl-2'- deoxyuridine (EdU) and transwell assay, respectively. RIP assay was conducted to detect the presence of m6A modification on EZH2 mRNA and the interaction between IGF2BP2 and EZH2. Relative levels of EZH2 and epithelial-mesenchymal transition (EMT)-associated genes (E-cadherin and N-cadherin), and metastatic abilities were detected in Simvastatin-induced A549 cells transfected with pcDNA-METTL3. RESULTS: METTL3 and EZH2 levels were upregulated in lung cancer tissues, which were higher in advanced stage lung cancer patients. Their levels, as well as cell proliferative and metastatic abilities, were dose-dependently inhibited in Simvastatin-induced A549 cells. METTL3 positively regulated EZH2 level, and m6A modification on its mRNA. Moreover, the interaction between IGF2BP2 and EZH2 could be inhibited by knockdown of METTL3. Simvastatin could abolish the role of METTL3 in regulating relative levels of EZH2 and EMT-associated genes, as well as metastatic abilities in A549 cells. CONCLUSIONS: Simvastatin induces METTL3 down-regulation in lung cancer tissues, which further influences EMT via m6A modification on EZH2 mRNA and thus inhibits the malignant progression of lung cancer.
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Adenosina/análogos & derivados , Antineoplásicos/farmacología , Proteína Potenciadora del Homólogo Zeste 2/antagonistas & inhibidores , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Metiltransferasas/antagonistas & inhibidores , ARN Mensajero/metabolismo , Simvastatina/farmacología , Células A549 , Adenosina/metabolismo , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Metiltransferasas/metabolismo , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/genética , Células Tumorales CultivadasRESUMEN
Objective: From December 2019, the new coronavirus pneumonia (COVID-19) broke out in Wuhan, Hubei, and spread rapidly to the nationwide. On January 20, 2020, the National Health Committee classified COVID-19 pneumonia as one of B class infectious diseases and treated it as class A infectious disease. During the epidemic period, the routine diagnosis and treatment of tumor patients was affected with varying degrees. In this special period, we performed the superiority of the multi-disciplinary team of diagnosis and treatment, achieved accurate diagnosis and treatment of patients with hepatobiliary malignant tumors, provided support for these patients with limited medical resources, and helped them to survive during the epidemic period.On the basis of fully understanding the new coronavirus pneumonia, the treatment strategy should be changed timely during the epidemic, and more appropriate treatment methods should be adopted to minimize the adverse effect of the epidemic on tumor treatment.
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Infecciones por Coronavirus/prevención & control , Coronavirus , Infección Hospitalaria/prevención & control , Neoplasias Hepáticas/cirugía , Pandemias/prevención & control , Neumonía Viral/prevención & control , Betacoronavirus , Neoplasias del Sistema Biliar/diagnóstico , COVID-19 , China , Control de Enfermedades Transmisibles/métodos , Coronavirus/patogenicidad , Infecciones por Coronavirus/epidemiología , Brotes de Enfermedades , Humanos , Huésped Inmunocomprometido , Neoplasias Hepáticas/diagnóstico , Planificación de Atención al Paciente , Neumonía Viral/epidemiología , Riesgo , SARS-CoV-2RESUMEN
1. This study aimed to investigate the protective effects of Gingko biloba extract EGB761 on heat-stressed chicken heart in vivo and its underlying relevance to Hsp70.2. A total of 50 one-day-old female chicks were randomly divided into five groups: control (Con), heat-stress (HS), 0.1% EGB761 plus heat-stress (0.1%EGB+HS), 0.3%EGB761 plus heat-stress (0.3%EGB+HS) and 0.6%EGB761 plus heat-stress (0.6%EGB+HS) groups. After administration of EGB761 for 45 days, the chickens in each group were exposed to a single heat-stress event at 38 ± 1°C for 3 h.3. EGB761 attenuated the abnormal symptoms and pathological scores of myocardium of heat-stressed chickens. Despite a reduction in the transcription and translation of the Hsp70 gene in heat-stressed myocardium, EGB761 induced the expression of Hsp70 in endothelial cells of the microarteries and venules into the blood, and reduced heat-stress damage in vascular endothelial cells.4. Supplementation with EGB761 before heat-stress exposure protected chicken myocardium from damage by increasing serum Hsp70 protein from myocardial cells and cardiac microvascular endothelial cells and protected the microvascular system from adverse injury.
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Pollos , Ginkgo biloba , Animales , Células Endoteliales , Corazón , Respuesta al Choque Térmico , Calor , Miocardio/metabolismo , Extractos VegetalesRESUMEN
Objective: To investigate the characteristics of different phenotypes of refractory non-erosive gastroesophageal reflux disease (NERD), the types of esophageal motility and the related factors of symptoms. Methods: A retrospective analysis was made of the patients with refractory NERD of Beijing Tongren Hospital affiliated to Capital Medical University from September 2015 to August 2017. All patients underwent electronic gastroscopy, esophageal manometry and 24-hour dynamic esophageal pH impedance monitoring. They were divided into four phenotype groups according to the results. Results: A total of 231 patients were enrolled in the study. There were 111(48.1%)cases in phenotype 1 group, 9 (3.9%)cases in phenotype 2 group, 100 (43.3%)cases in phenotype 3 group and 11 (4.8%) cases in phenotype 4 group. Compared with the other three groups, the number of weak acid reflux [(86±55) vs (37±8), (70±52), (31±9) times] and the number of gas reflux [(86±76) vs (38±13), (58±57), (26±10)] in phenotype 1 group increased significantly (allP<0.005). Dynamics disorders were common in refractory NERD patients (139/231, 60.2%). Mild esophageal dynamics disorder was the main type of dynamics disorder (118/139, 84.9%). There was no significant difference among the phenotype groups. Multivariate unconditional Logistic regression analysis showed that the risk factors for reflux-related symptoms were female ratio, Chicago power classification, gas reflux and weak acid reflux (OR=3.731, 2.452, 1.036 and 1.037, P<0.05). Conclusions: The characteristics of gastroesophageal reflux and the types of motility disorders are different in different phenotype groups of refractory NERD patients. The risk factors of reflux-related symptoms are female ratio, Chicago motility classification, gas reflux and the frequency of weak acid reflux.
Asunto(s)
Esofagitis Péptica , Reflujo Gastroesofágico , Monitorización del pH Esofágico , Femenino , Humanos , Masculino , Fenotipo , Estudios RetrospectivosRESUMEN
Objective: To investigate the value of quantitative dynamic contrast enhancement MR imaging (DCE-MRI) parameters in the prediction and evaluation of the response to neoadjuvant chemotherapy in patients with malignant sinonasal tumors by comparing the parameter values before and after chemotherapy. Methods: DCE-MRI was performed in 14 patients (6 male cases, 8 female cases, 16-83 years) with malignant sinonasal tumors before chemotherapy in Beijing Tongren Hospital from January 2012 to December 2013 in which DCE-MRI was performed in 8 patients on the 7th, 21st and 42nd days after chemotherapy. The values of quantitative parameter including K(trans), K(ep), and V(e) of the tumor were assessed and the change rate of these quantitative parameter values after chemotherapy was calculated. Results: Response to chemotherapy of the tumor was found in 11 patients with malignant sinonasal tumors,whereas no response to chemotherapy of the tumor was confirmed in 3 patients. K(trans) ((0.75±0.28)/min) and K(ep) ((3.23±1.48)/min) values of the tumor before chemotherapy in patients with response to chemotherapy were significantly bigger than those ((0.43±0.41)/min, (1.34±0.42)/min) in patients with no response to chemotherapy (all P<0.01).There was no significant difference in V(e) values between two groups (P=0.165). Compared with K(trans) values of the tumor before chemotherapy,the change rate of K(trans) values decreased more than 40% on the 7th,21st and 42nd days after chemotherapy in the patients with treatment response,whereas the change rate did not decrease significantly in the patients without treatment response. Conclusion: The bigger K(trans) and K(ep) values of the tumor before chemotherapy,the better the treatment response of the tumor to chemotherapy.