Summary Background Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is ...non-inferior to gefitinib in patients with non-small-cell lung cancer. Methods In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18–75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov , number NCT01040780 , and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. Findings 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67–1·05; median progression-free survival 4·6 months 95% CI 3·5–6·3 vs 3·4 months 2·3–3·8; p=0·13). The most common adverse events were rash (81 41% of 200 patients in the icotinib group vs 98 49% of 199 patients in the gefitinib group) and diarrhoea (43 22% vs 58 29%). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 61% vs 140 70%; p=0·046), especially drug-related diarrhoea (37 19% vs 55 28%; p=0·033). Interpretation Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer. Funding Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program.
Objectives The purpose of this study was to assess the effects of qili qiangxin capsules in patients with chronic heart failure (CHF). Background Qili qiangxin capsules are a traditional Chinese ...medicine that has been approved in China for the treatment of CHF, but the evidence supporting its efficacy remains unclear. Methods A total of 512 patients with CHF were enrolled and randomly assigned to receive the placebo or qili qiangxin capsules in addition to their standard medications for the treatment of CHF. The primary endpoint was the reduction or percent change in the plasma N-terminal pro–B-type natriuretic peptide (NT-proBNP) level during 12 weeks of treatment. Results At the 12-week follow-up, a significant reduction in the NT-proBNP level from baseline was observed in both groups, but the qili qiangxin capsule group demonstrated a significantly greater reduction than the placebo group (p = 0.002); 47.95% of patients in the qili qiangxin capsule group demonstrated reductions in NT-proBNP levels of at least 30% compared with 31.98% of patients in the placebo group (p < 0.001). Treatment with qili qiangxin capsules also demonstrated superior performance in comparison to the placebo with respect to New York Heart Association functional classification, left ventricular ejection fraction, 6-min walking distance, and quality of life. Conclusions On a background of standard treatment, qili qiangxin capsules further reduced the levels of NT-proBNP. Together, our data suggest that qili qiangxin capsules could be used in combination therapy for CHF.
Purpose To evaluate the use of the buccal fat pad (BFP) in the immediate reconstruction of oncologic palate defects and the influence of postoperative radiotherapy on reconstruction. Patients and ...Methods Patients who were diagnosed with moderate- to high-grade malignancies of the palate underwent partial maxillectomy. The BFP was used as a pedicled flap to reconstruct the defects. All patients received postoperative radiotherapy 4 to 5 weeks after surgery. Results Eighteen patients (9 men and 9 women; age range, 37 to 81 yr) underwent surgery and subsequent radiotherapy. The size of all defects ranged from 7.5 to 19.2 cm2 . Adequate closure of the defects was achieved during surgery and all flaps were epithelialized within 3 weeks after surgery, with no complications of dehiscence or flap failure. Furthermore, there were no complications derived from postoperative radiotherapy. Conclusions This study suggests that BFP grafting is an effective and reliable method for the reconstruction of small to medium-size palate defects. Furthermore, postoperative radiotherapy does not influence the success of reconstruction.
Abstract Background Nasopharyngeal carcinoma is common in China, where the incidence is as high as 2·44 per 100 000 people per year, and usually presents at advanced stage when the prognosis is poor. ...The human Epstein-Barr tumour virus is thought to be an important cause of this cancer. Screening programmes using the Epstein-Barr virus-specific IgA immunoglobulin antibody subtype as the principle screening test can result in early diagnosis, but the long-term effects have not been ascertained. Methods In a mass screening programme between August, 2009, and December, 2014, three townships of Zhongshan city in southern China were randomly assigned: one as the screening town and two as control towns. 16 695 residents of the screening town aged 30–59 years were enrolled, and each was randomly matched for age, sex, and date of enrolment with two residents of the control towns, resulting in 33 390 control participants in total. Participants of the screening group were tested for serum anti-Epstein-Barr virus IgA concentrations using two ELISAs. Those with moderate antibody concentrations or higher (≥0·65 probability of nasopharyngeal carcinoma units logit P) were invited to be retested annually in the following 3 years, and those with high antibody concentrations (≥0·98 logit P) were referred to otorhinolaryngologists for diagnostic work-up. Findings 43 nasopharyngeal carcinoma cases, with two deaths, were reported in the screening group, compared with 52 cases, with eight deaths, in the control group. The sensitivity of the screening triage was 95%, specificity was 94%, positive predictive value was 3·4%, and negative predictive value was 99·9%. Cumulative incidence was 0·26% per person for the screening group and 0·013% for those yielding a negative result, compared with 0·16% for the control group. 35 (82%) cases identified by the screening triage were localised disease, compared with 9 (19%) control cases (p<0·0001). Overall survival in the screening group is significantly greater than that in the control group (95·3% vs 78·8%; p=0·0014). Interpretation By detecting future cases, the screening programme resulted in 1·65 times more diagnosis than the control group and conferred 81% protection against nasopharyngeal carcinoma for 5 years. As a result of early diagnosis, this screening programme significantly increased overall survival. Funding This work was funded by the Eleventh National Science and Technology Support Program of China (2006BAI02A11), the Early Detection of Cancer Project in China (2010–13), and the Science and Technical Support Program of Zhongshan City (20083A183).
Purpose: The molecular etiology of atrial fibrillation (AF) and its treatment are poorly understood. AF involves both electrical and structural features. Vericiguat can ameliorate cardiac remodeling ...in heart failure. The effects of vericiguat on AF, however, are unclear. Here, the actions of vericiguat on atrial structural and electrical remodeling in AF and its possible mechanisms were investigated. Methods and Results: Thirty-six rabbits were randomly allocated to four groups, namely, sham, RAP (pacing with 600 beats/min over three weeks), vericiguat-treated (three weeks’ pacing plus daily oral dose of 1.5 mg/kg of vericiguat), and vericiguat-treated only. HL-1 cells received rapid pacing with or without vericiguat. Parameters including electrophysiology, echocardiography, histology, Ca2+ levels, and ICaL density, as well as levels of TRPC6, CaN, NFAT4, p-NFAT4, Cav1.2, collagen I, collagen III, and ST2 were measured. Significant changes of above proteins expression level, circulating biochemical indices, Ca2+ concentrations, and ICaL density in both animals and cell models, these effects were significantly restored by vericiguat. Vericiguat also reversed the enlarged atrium and significantly reduced myocardial fibrosis, together with preventing reduced atrial effective refractory periods (AERPs) and AF induction rate. Conclusion: Vericiguat thus ameliorated AF-associated structural and electrical remodeling. These findings suggest the potential of vericiguat for treating AF.
Abstract Introduction The aim of the retrospective study was to investigate the therapeutic efficiency of the preoperative intracavitary radiotherapy combined with radical surgery on postoperative ...complications and long-term survival in patients with stage IB2 and IIA2 cervical cancer (CC). Methods From January 1995 to December 2012, a total of 171 patients with stage IB2 or IIA2 CC were recruited into the study. They were divided into two groups according to the treatment modality provided: preoperative radiotherapy followed by radical surgery (n = 80), and radical surgery alone (n = 91). The clinical curative effect, postoperative complications and the postoperative prognosis of patients were evaluated and compared in two groups. The tumor response and survival of patients in two group were observed in follow-up study. Results There were no significant differences in the incidence of postoperative complications, intraoperative blood loss and surgery duration ( P > 0.05) between the two groups. Preoperative radiotherapy did not improve the postoperative prognosis yet. Though patients undergoing preoperative radiotherapy showed the similar 1- (92.50% vs. 84.62%), 3- (85.00% vs. 81.32%) and 5-year (80.00% vs. 74.72%) survival rates, the 3- and 5-year locoregional control rates of them were much higher than those undergoing surgery alone ( P < 0.05). Conclusion Preoperative radiotherapy combined with radical surgery could improve locoregional control rate and would not increase the risk of postoperative complications. It may be a feasible treatment mode for early stage CC carcinoma.
Abstract Background: The objective of this study was to determine the frequency and characteristics of mutations in the RP1 gene and to characterize mutations with the clinical features in the ...Chinese family with autosomal dominant retinitis pigmentosa (ADRP). Methods: Forty-three affected, unrelated Chinese individuals with ADRP were recruited between 2002 and 2006. Polymerase chain reaction and direct DNA sequencing were used to screen in the entire coding region and splice sites of the RP1 gene. Cosegregation analysis and population frequency studies were performed for patients with identified mutations. The clinical features were determined by complete ophthalmologic examinations. Results: The mutation detectable rate of the RP1 gene in Chinese patients with ADRP was 1/43. A missense mutation, N985Y , was identified in exon 4 of the RP1 gene in 8 affected individuals from a Chinese family with ADRP. The ophthalmic findings with an N985Y mutation were similar to those of typical retinitis pigmentosa with delayed onset after age 40 years and slow progression. In addition, a total of 9 distinct variants were detected in our study population, most of which were RP1 gene polymorphisms; the pathological significance of P903L , a novel missense mutation, was unconfirmed. Interpretation: Mutations in the RP1 gene are relatively rare in Chinese patients with ADRP. In our cases, N985Y mutation segregated with the phenotype from 1 Chinese family with mild and late-onset ADRP, a finding that has not been documented in other races.
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