Reirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, ...negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy.
This multicentre, randomised, open-label, phase 3 trial was done in three centres in Guangzhou, China. Eligible patients were aged 18–65 years with histopathologically confirmed undifferentiated or differentiated, non-keratinising, advanced locally recurrent nasopharyngeal carcinoma. Participants were randomly assigned (1:1) to either receive hyperfractionation (65 Gy in 54 fractions, given twice daily with an interfractional time interval of at least 6 h) or standard fractionation (60 Gy in 27 fractions, given once a day). Intensity-modulated radiotherapy was used in both groups. A computer program generated the assignment sequence and randomisation was stratified by treatment centre, recurrent tumour stage (T2–T3 vs T4), and recurrent nodal stage (N0 vs N1–N2), determined at the time of randomisation. The two primary endpoints were the incidence of severe late complications defined as the incidence of grade 3 or worse late radiation-induced complications occurring 3 months after the completion of radiotherapy until the latest follow-up in the safety population, and overall survival defined as the time interval from randomisation to death due to any cause in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02456506.
Between July 10, 2015, and Dec 23, 2019, 178 patients were screened for eligibility, 144 of whom were enrolled and randomly assigned to hyperfractionation or standard fractionation (n=72 in each group). 35 (24%) participants were women and 109 (76%) were men. After a median follow-up of 45·0 months (IQR 37·3–53·3), there was a significantly lower incidence of grade 3 or worse late radiation-induced toxicity in the hyperfractionation group (23 34% of 68 patients) versus the standard fractionation group (39 57% of 68 patients; between-group difference –23% 95% CI –39 to –7; p=0·023). Patients in the hyperfractionation group had better 3-year overall survival than those in the standard fractionation group (74·6% 95% CI 64·4 to 84·8 vs 55·0% 43·4 to 66·6; hazard ratio for death 0·54 95% CI 0·33 to 0·88; p=0·014). There were fewer grade 5 late complications in the hyperfractionation group (five 7% nasal haemorrhage) than in the standard fractionation group (16 24%, including two 3% nasopharyngeal necrosis, 11 16% nasal haemorrhage, and three 4% temporal lobe necrosis).
Hyperfractionated intensity-modulated radiotherapy could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated intensity-modulated radiotherapy could be used as the standard of care for these patients.
Key-Area Research and Development of Guangdong Province, the National Natural Science Foundation of China, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project, and the National Ten Thousand Talents Program Science and Technology Innovation Leading Talents, Sun Yat-Sen University Clinical Research 5010 Program.
Background
Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ...ageing‐related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons.
Methods
A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non‐sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty‐two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre‐intensive and post‐intensive lifestyle interventions, were measured.
Results
The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non‐sarcopenic subjects, serum interleukin (IL)‐6, IL‐18, tumour necrosis factor‐α (TNF‐α), TNF‐like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF‐α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6‐fold and 14.3‐fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4‐fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF‐α, IL‐18, insulin, and adiponectin (all P < 0.05).
Conclusions
High levels of the inflammatory cytokines TWEAK and TNF‐α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could significantly improve muscle mass, reduce inflammation, and restore metabolic hormone levels in sarcopenic patients. This trial was registered at clinicaltrials.gov as NCT02873676.
Xiyanping (XYP) is a Chinese herbal medicine used in the clinic to treat respiratory infection and pneumonia. Recent evidence identified XYP as a potential inhibitor of severe acute respiratory ...syndrome coronavirus 2, implying XYP as a possible treatment for the coronavirus disease 2019 (COVID‐19). Here, we conducted a prospective, multicenter, open‐label and randomized controlled trial to evaluate the safety and effectiveness of XYP injection in patients with mild to moderate COVID‐19. We consecutively recruited 130 COVID‐19 patients with mild to moderate symptoms from five study sites, and randomized them in 1:1 ratio to receive XYP injection in combination with standard therapy or receive standard supportive therapy alone. We found that XYP injection significantly reduced the time to cough relief, fever resolution and virus clearance. Less patients receiving XYP injection experienced disease progression to the severe stage during the treatment process. No severe adverse events were reported during the study. Taken together, XYP injection is safe and effective in improving the recovery of patients with mild to moderate COVID‐19. However, further studies are warranted to evaluate the efficacy of XYP in an expanded cohort comprising COVID‐19 patients at different disease stages.
Objective
Endoscopic nasopharyngectomy (ENPG) with en bloc resection has been well accepted in resectable localized recurrent nasopharyngeal carcinoma (rNPC), but it is a difficult technique to ...master for most otorhinolaryngology head and neck surgeons. Ablation surgery is a new and simplified method to remove tumors. We designed a novel method using low‐temperature plasma radiofrequency ablation (LPRA) and evaluated the survival benefit.
Methods
A total of 56 localized rNPC patients were explained in detail and retrospectively analyzed. The surgery method was ablated from the resection margin to the center of the tumor. The postmetastatic overall survival (OS), local relapse‐free survival (LRFS) rate, progression‐free survival (PFS) and distant metastasis‐free survival (DMFS) were analyzed using the Kaplan–Meier method and compared by the log‐rank test.
Results
All surgeries were successfully performed without any severe postoperative complications or deaths. The median operation time of ablation and harvested NSFF respectively were 29 min (range, 15–100 min) and 101 min (range, 30–180 min). The average number of hospital days postoperation was 3 days (range, 2–5 days). All cases (100.0%) had radical ablation with negative resection margins. The nasopharyngeal defects were completely re‐epithelialized in 54 (96.4%) patients. As of the data cutoff (September 3, 2023), the median follow‐up time was 44.3 months (range, 17.1–52.7 months, 95% CI: 40.4–48.2). The 3‐year OS, LRFS, PFS and DMFS of the entire cohort were 92.9% (95% CI: 0.862–0.996), 89.3% (95% CI: 0.813–0.973), 87.5% (95% CI: 0.789–0.961), and 92.9% (95% CI: 0.862–0.996), respectively. Cycles of radiotherapy were independent risk factors for OS (p = 0.003; HR, 32.041; 95% CI: 3.365–305.064), LRFS (p = 0.002; HR, 10.762; 95% CI: 2.440–47.459), PFS (p = 0.004; HR, 7.457; 95% CI: 1.925–28.877), and DMFS (p = 0.002; HR, 34.776; 95% CI: 3.806–317.799).
Conclusion
Radical endoscopic nasopharyngectomy by using low‐temperature plasma radiofrequency ablation is a novel, safe and simplified method to master and disseminate for treating resectable rNPC. However, further data and longer follow‐up time are needed to prove its efficacy.
This paper investigates the event-triggered predictive control problem for networked nonlinear systems with imperfect premise matching. First, a model of networked nonlinear system is well ...constructed, which has integrated the event-triggered communication scheme (ETCS) and the predictive control together, in which, an ETCS is introduced to alleviate the communication burden by reducing the number of transmitted packets; and a fuzzy predictive controller is designed to predict future states and control signals between two successfully transmitted instants. Therefore, the data dropout induced by the networks can be actively compensated. Second, by using a common Lyapunov theory, a stability criterion and two stabilization criteria are deduced to ensure the asymptotical stability of the studied system and find the controller gains, respectively. Different from the traditional parallel distributed compensation method, the synchronous premise variables between the T-S fuzzy system and the fuzzy event-triggered predictive controller (FETPC) are no longer needed again. Since the imperfect premise matching condition is well considered in the derivation of the main results, the design flexibility and low cost of the FETPC implementation can be expected. Finally, the validity of the method proposed in this paper is demonstrated by a nonlinear mass-spring example.
Summary Background Current staging methods do not accurately predict the risk of disease recurrence and benefit of adjuvant chemotherapy for patients who have had surgery for stage II colon cancer. ...We postulated that expression patterns of multiple microRNAs (miRNAs) could, if combined into a single model, improve postoperative risk stratification and prediction of chemotherapy benefit for these patients. Method Using miRNA microarrays, we analysed 40 paired stage II colon cancer tumours and adjacent normal mucosa tissues, and identified 35 miRNAs that were differentially expressed between tumours and normal tissue. Using paraffin-embedded specimens from a further 138 patients with stage II colon cancer, we confirmed differential expression of these miRNAs using qRT-PCR. We then built a six-miRNA-based classifier using the LASSO Cox regression model, based on the association between the expression of every miRNA and the duration of individual patients' disease-free survival. We validated the prognostic and predictive accuracy of this classifier in both the internal testing group of 138 patients, and an external independent group of 460 patients. Findings Using the LASSO model, we built a classifier based on the six miRNAs: miR-21-5p, miR-20a-5p, miR-103a-3p, miR-106b-5p, miR-143-5p, and miR-215. Using this tool, we were able to classify patients between those at high risk of disease progression (high-risk group), and those at low risk of disease progression (low-risk group). Disease-free survival was significantly different between these groups in every set of patients. In the initial training group of patients, 5-year disease-free survival was 89% (95% CI 77·3–94·4) for the low-risk group, and 60% (46·3–71·0) for the high-risk group (hazard ratio HR 4·24, 95% CI 2·13–8·47; p<0·0001). In the internal testing set of patients, 5-year disease-free survival was 85% (95% CI 74·3–91·8) for the low-risk group, and 57% (42·8–68·5) for the high-risk group (HR 3·63, 1·86–7·01; p<0·0001), and in the independent validation set of patients, was 85% (79·6–89·0) for the low-risk group and 54% (46·4–61·1) for the high-risk group (HR 3·70, 2·56–5·35; p<0·0001). The six-miRNA-based classifier was an independent prognostic factor for, and had better prognostic value than, clinicopathological risk factors and mismatch repair status. In an ad-hoc analysis, the patients in the high-risk group were found to have a favourable response to adjuvant chemotherapy (HR 1·69, 1·17–2·45; p=0·0054). We developed two nomograms for clinical use that integrated the six-miRNA-based classifier and four clinicopathological risk factors to predict which patients might benefit from adjuvant chemotherapy after surgery for stage II colon cancer. Conclusion Our six-miRNA-based classifier is a reliable prognostic and predictive tool for disease recurrence in patients with stage II colon cancer, and might be able to predict which patients benefit from adjuvant chemotherapy. It might facilitate patient counselling and individualise management of patients with this disease. Funding Natural Science Foundation of China.
•Degraded miR-17-3p and raised STAT1 is found in retinal tissues.•Increased miR-17-3p suppressed inflammatory reaction of DR mice.•Elevated exosomal miR-17-3p suppressed antioxidant injury of DR ...mice.•4 There is a target relationship between STAT1 and miR-17-3p.•This study is essential for finding new targets for DR.
Accumulating evidence has reported the role of microRNA (miR) on diabetic retinopathy (DR). Thus, the aim of the study was to investigate the effect of exosomal miR-17-3p targeting signal transducer and activator of transcription 1 (STAT1) on inflammatory reaction and antioxidant injury of DR mice.
A mouse diabetes model was established and injected with miR-17-3p-containing human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes to ascertain the role of exosomal miR-17-3p. The blood glucose, glycosylated hemoglobin (HbAlc), weight, hemoglobin (Hb) content, inflammatory factors, oxidative stress factors, vascular endothelial growth factor (VEGF), apoptosis index and glutamine synthetase (GS) level in serum and/or retinal tissues of DR mice were measured. miR-17-3p and STAT1 expression in retinal tissues as well as the target relationship between miR-17-3p and STAT1 were tested.
miR-17-3p decreased and STAT1 increased in retinal tissues of DR mice, and STAT1 was the target gene of miR-17-3p. Injection of up-regulated exosomal miR-17-3p reduced the blood glucose and HbAlc, increased the weight, Hb content and GS level, decreased contents of inflammatory factors and VEGF, alleviated oxidative injury, and inhibited retinal cell apoptosis in DR mice through inhibiting STAT1.
Functional studies reveal that hucMSCs-derived exosomes shuffle miR-17-3p to ameliorate inflammatory reaction and oxidative injury of DR mice via targeting STAT1.
Background
Intrahepatic cholangiocarcinoma (ICC) is the second most common tumor in primary liver cancer, but the prognostic factors associated with long-term outcomes after surgical resection remain ...poorly defined. This study aimed to develop a novel prognostic classifier for patients with ICC after surgery.
Methods
Using a proteomics approach, we screened tumor markers that up-regulated in ICC tissues, and narrowed down by bioinformatics analysis, western blot and immunohistochemistry. Prognostic markers were identified using Cox regression analyses in primary training cohort and the predictive models for time to recurrence (TTR) were established. The predictive accuracy of predictive model was validated in external validation cohort and prospective validation cohort. MTT assay, clonal formation assay and trans-well assays were used to verify the effect on the proliferation and migration in ICC cell line.
Results
Triosephosphate isomerise (TPI1) was significantly up-regulated in ICC tissues and Kaplan–Meier analysis reveals that higher TPI1 expression was strongly correlated with higher recurrence rate of ICC patients. In the primary training cohort, mean TTR was significantly longer (
p
< 0.0001) than in the low-risk group (26.9 months for TTR, 95% CI 22.4–31.5) than in the high-risk group (14.5 months for TTR, 95% CI 10.6–18.4). Similar results were observed in two validation cohorts. In addition, a nomogram to predict recurrence was developed. Moreover, Knockdown of TPI1 by shRNA inhibited ICC cell growth, colony information, migration, invasion in vitro.
Conclusions
Current prognostic models were accurate in predicting recurrence for ICC patients after surgical resection.
Photovoltaic performance of the hybrid devices consisting of P3HT/CdS/CdSe/TiO2 nanorod array was studied. The dependence of the photovoltaic performance on the CdS/CdSe quantum dots was ...investigated, and it is concluded that the CdS/CdSe quantum dots play an important role in improving charge separation and injection. It has been demonstrated that coating CdS/CdSe quantum dots onto TiO2 nanorods with P3HT to form p–n heterojunctions largely improves the photovoltaic performance of the P3HT/CdSe/CdS/TiO2 nanorod solar cells, exhibiting an energy conversion efficiency of 0.57%.
Rare Earth Elements (REE) are essential to modern society but the origins of many large REE deposits remain unclear. The U-Th-Pb ages, chemical compositions and C, O and Mg isotopic compositions of ...Bayan Obo, the world's largest REE deposit, indicate a protracted mineralisation history with unusual chemical and isotopic features. Coexisting calcite and dolomite are in O isotope disequilibrium; some calcitic carbonatite samples show highly varied δ26 Mg which increases with increasing Si and Mg; and ankerite crystals show decreases in Fe and REE from rim to centre, with highly varied REE patterns. These and many other observations are consistent with an unusual mineralisation process not previously considered; protracted fluxing of calcitic carbonatite by subduction-released high-Si fluids during the closure of the Palaeo-Asian Ocean. The fluids leached Fe and Mg from the mantle wedge and scavenged REE, Nb and Th from carbonatite, forming the deposit through metasomatism of overlying sedimentary carbonate.
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