Literatures regarding the prevalence and clinical significance of compound EGFR mutations are limited. Until now, none of retrospective or prospective research has focused on in cis compound EGFR mutations except case reports. In this study, we screened a cohort of 3,000 treatment-naïve Chinese advanced NSCLC patients using capture-based ultra-deep targeted sequencing to evaluate the prevalence of EGFR in cis compound mutations and the efficacy of EGFR-TKI in this population. Of the 3,000 patients screened, 1,266 (42.2%) had EGFR mutation; among them, 15 patients (1.2%) harboring in cis compound EGFR mutations, with 10 patients carrying EGFR L858R in combination with a rare mutation and five patients carrying two rare EGFR mutations. No patient with EGFR 19del was observed. Interestingly, no in trans configuration was identified in this cohort. All of the patients harboring in cis compound EGFR mutations were non-smokers, histologically diagnosed with adenocarcinoma and received first-generation EGFR-TKI. Furthermore, our data also revealed that patients with in cis compound EGFR mutations exhibit comparable PFS to first generation EGFR-TKI comparing to patients with single activating EGFR mutation. This observation was further supported by in silico molecular modeling analyses which demonstrated in cis compound mutations do not alter the ATP-binding pocket of EGFR, thus having no effect on the interaction between gefitinib and EGFR.
Abstract Background Coronavirus disease 2019 (COVID-19) broken out and spread rapidly nationwide at the beginning of 2020, which has brought huge impacts to people and work. The current situation of prevention and control is severe and urgent guidance for clinicians, especially for the medical systems. In the hope of providing a reference and recommendation for the prevention and control of the epidemic, we carried out research to improve the quality of patients care and prevention during this epidemic. Methods All of the involved health care personnel were rapidly trained to use personal protection equipment in our department. The managements of the surgery patients and association of two periods were described and analyzed. We reviewed and compared the patients’ discharged records in our database who underwent surgery in the Department of Bone & Joint Surgery at Peking University Shenzhen Hospital, who were discharged between January 1st to March 1st in 2019 and January 1st to March 1st in 2020. Both chi-squared test and Student’s t-test were performed to determine the relationship between the two periods. Results Analysis revealed that gender, surgery class, duration, and anaesthetization had no significantly differences between two periods ( p ༞0.05). However, age and blood loss had significant relationship of the two periods ( p ༜0.05). Conclusions The results of the study imply that we have been benefited from the strict flow charts in management of perioperative for orthopedic patients, which could be a valid tool in routine clinical practice and a consultation during pandemic of the COVID-19.
Aim:The aim of this study was to examine the feasibility and efficacy of nurse-led team management (NLTM) intervention at improving the self-management of patients with type 2 diabetes (T2D) at community settings in Changsha, Hunan, China.Background: China has become the country with the largest number of patients with diabetes, and that number is growing, causing increasing pressure on the health care system.At present, the main diabetes management model in China is teamwork guided by general practitioners.However, the number of general practitioners is insufficient, and their work is overloaded, which leads to poor outcomes of diabetes management.Therefore, it is important to explore alternative methods of diabetes management, such as NLTM.Patients and methods: In a randomized controlled trial, 171 T2D patients were randomized into the control or intervention arm.Participants in the control group received routine management from the community health service center, whereas the intervention group received 12 months NLTM intervention in addition to the standard care.The diabetes selfmanagement scale, fasting blood sugar, and glycosylated hemoglobin A1c (HbA1c) were assessed at baseline and at 6 and 12 months after the start of the intervention.Results: Baseline data were comparable between arms.Repeated-measurement analysis showed that self-management of the intervention group improved compared with the control group after the intervention (P<0.05).There were no significant differences in HbA1c at 6 months, whereas after 12 months of intervention, there was a significant difference in HbA1c between the two groups (F=10.114,P<0.05).The intervention had no significant effect on fasting blood sugar. Conclusion:The NLTM intervention has resulted in an impact of practical significance on T2D self-management, and was beneficial for controlling the level of HbA1c.The study has demonstrated the feasibility and efficacy of using NLTM in the management of T2D in a Chinese community.
The aim of this study was to establish nomograms, based on significant clinicopathologic parameters, for predicting the overall survival (OS) and the cancer-specific survival (CSS) of patients with classical Hodgkin lymphoma (CHL). The data of 43,330 CHL patients, diagnosed between 1983 and 2014, were obtainedfrom the database of the Surveillance, Epidemiology, and End Results (SEER) program. These patients were randomly divided into training (n = 30,339) and validation (n = 12,991) cohorts. The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate the prognostic effects of multiple clinicopathologic parameters on survival. Significant prognostic factors were combined to build nomograms. The predictive performance of nomograms was evaluated using the index of concordance (C-index) and calibration curves. In the training cohort, on univariate and multivariate analyses, age at diagnosis, gender, race, Ann Arbor stage, and histological type significantly correlated with the survival outcomes. These characteristics were used to establish nomograms. The nomograms showed good accuracy in predicting 1-, 5-, and 10-year OS and CSS, with a C-index of 0.794 (95% confidence interval [CI], 0.789-0.799) for OS and 0.760 (95% CI, 0.753-0.767) for CSS. In the validation cohort, the C-index for nomogram-based predictions was 0.787 (95% CI, 0.779-0.795) for OS and 0.769 (95% CI, 0.758-0.780) for CSS. All calibration curves revealed excellent consistency between predicted and actual survival. In summary, novel nomograms were established and validated to predict OS and CSS for patients with CHL. These new prognostic models could aid in improved prediction of survival outcomes leading to reasonable treatment recommendations.
Flavonol Synthase, belongs to 2-oxoglutarate-dependent dioxygenase (2-ODD) superfamily, was involved in flavonol biosynthesis in plants. In this study, we cloned a cDNA encoding flavonol synthase from Ginkgo biloba (designated as GbFLS2).The cDNA of GbFLS2 gene is 1251 bp and contains a 1017 bp open reading frame encoding 338 amino acids. The deduced protein of GbFLS2 displays extensive homology to FLS proteins from other plants such as Pinus radiata, Dioscorea alata, Camellia sinensis and Epimedium sagittatum. Phylogenetic analysis indicated that the GbFLS2 has a closer relationship with FLS from gymnosperm plants than from other plant species. The results suggest that GbFLS2 is a member of the 2-ODD superfamily, and it is from the same ancestor as FLS proteins of other gymnosperm plants.
Purpose: To explore the efficacy and safety of lower-dose decitabine in patients with lower-risk MDS, a prospective multicenter phase II study was conducted to compare decitabine with the best supportive care (BSC).Methods: Patients diagnosed with lower-risk MDS from September 2013 to August 2018 were assigned to the decitabine group or the BSC group.Decitabine (12 mg/m 2 /day) was administered over 1 hour/day for 5 consecutive days in a 4-week cycle.BSC, including growth factors, transfusion, thalidomide, lenalidomide, and immunosuppressive agents were given consecutively.The endpoints included the proportion of patients who achieved overall response (OR) in the first 2 or 3 courses, event-free survival (EFS), and overall survival (OS).Results: A total of recruited 82 patients were analyzed.In the decitabine group, 65.9% (27/41) achieved OR after 2 or 3 cycles of treatment, compared with 22.0% (9/41) in the BSC group (p <0.01).Besides, 44.0% (11/25) in the decitabine group became independent of RBC/Platelets transfusion, compared with 27.8% (5/18) in the BSC group.Patients with gene mutation and treated with decitabine achieved a higher OR rate, compared with those without gene mutation [72.0%(18/25) vs 11.5% (3/26), p <0.01].There was no significant difference in the median EFS between the decitabine and BSC groups (20.6 vs 14.3 months respectively, p = 0.665).In the decitabine group, the most significant adverse events were infections of any grades or neutropenic fever (46.3%, 19/41) and one patient (4.2%) died of acute cerebral infarction within 6 weeks of treatment.Conclusion: Lower-dose decitabine demonstrated promising clinical response with acceptable toxicity profiles in patients with low-and intermediate 1-risk MDS.A higher response rate to decitabine was observed in patients with mutated genes.Therefore, lower-dose decitabine can be advocated for patients with low-risk MDS and mutated genes.
Abstract Background Cell division cycle 6 (CDC6) is a key licensing factor in the assembly of pre-replicative complexes at origins of replication. The role of CDC6 in the pathogenesis of in diffuse larger B-cell lymphoma (DLBCL) remains unknown. We aim to investigate the effects of CDC6 on the proliferation, apoptosis and cell cycle regulation in DLBCL cells, delineate its underlying mechanism, and to correlate CDC6 expression with clinical characteristics and prognosis of patients with DLBCL. Methods Initial bioinformatic analysis was performed to screen the potential role of CDC6 in DLBCL. Lentiviral constructs harboring CDC6 or shCDC6 was transfected to overexpress or knockdown CDC6 in SUDHL4 and OCI-LY7 cells. The cell proliferation was evaluated by CCK-8 assay, cell apoptosis was detected by Annexin-V APC/7-AAD double staining, and cell cycle was measured by flow cytometry. Real time quantitative PCR and western blot was used to characterize CDC6 expression and its downstream signaling pathways. The clinical data of DLBCL patients were retrospectively reviewed, the CDC6 expression in DLBCL or lymph node reactive hyperplasia tissues was evaluated by immunohistochemistry. Results In silico data suggest that CDC6 overexpression is associated with inferior prognosis of DLBCL. We found that CDC6 overexpression increased SUDHL4 or OCI-LY7 cell proliferation, while knockdown of CDC6 inhibited cell proliferation in a time-dependent manner. Upon overexpression, CDC6 reduced cells in G1 phase and did not affect cell apoptosis; CDC6 knockdown led to significant cell cycle arrest in G1 phase and increase in cell apoptosis. Western blot showed that CDC6 inhibited the expression of INK4, E-Cadherin and ATR, accompanied by increased Bcl-2 and deceased Bax expression. The CDC6 protein was overexpressed DLBCL compared with lymph node reactive hyperplasia, and CDC6 overexpression was associated with non-GCB subtype, and conferred poor PFS and OS in patients with DLBCL. Conclusion CDC6 promotes cell proliferation and survival of DLBCL cells through regulation of G1/S cell cycle checkpoint and apoptosis. CDC6 is overexpressed and serves as a novel prognostic marker in DLBCL.
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