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Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma. In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18–60 years with previously untreated, non-keratinising stage III–IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1–5 and 22–26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1–5 and 22–26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68–70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62–68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30–32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed. From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9–81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7–80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69–1·39; log-rank p=0·92), with a difference of 0·5% (95% CI −7·1 to 8·1; pnon-inferiority=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (−6·1 to 9·3; pnon-inferiority=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3–4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported. Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma. National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. For the Chinese translation of the abstract see Supplementary Materials section.

Objectives This study aimed to investigate the incidence, consequences, and predictors of serious chemotherapy‐induced thrombocytopenia (CIT) in nasopharyngeal carcinoma (NPC). Materials and Methods We retrospectively reviewed the clinical records of patients with NPC between 2013 and 2015. Multivariate Cox proportional hazards regression model and propensity score matching were used to estimate the effect of serious CIT on overall survival. Univariate and multivariate logistic regression analyses were applied to identify the predictors of serious CIT. Results and Conclusion The incidence of serious CIT was 5.21% in patients with NPC. Patients who experienced serious thrombocytopenia had a worse long‐term prognosis, while the difference in short‐term survival rate was slight. Chemotherapy regimens of gemcitabine and platinum, 5‐fluorouracil and platinum, taxane and platinum, serum potassium ion concentration, serum lactate dehydrogenase levels, platelet count, red blood cell count, and estimated glomerular filtration rate were predictors of serious CIT.

Background Dysregulation of lipid metabolism is closely associated with cancer progression. The study aimed to establish a prognostic model to predict distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC), based on lipidomics. Methods The plasma lipid profiles of 179 patients with locoregionally advanced NPC (LANPC) were measured and quantified using widely targeted quantitative lipidomics. Then, patients were randomly split into the training (125 patients, 69.8%) and validation (54 patients, 30.2%) sets. To identify distant metastasis-associated lipids, univariate Cox regression was applied to the training set ( P  < 0.05). A deep survival method called DeepSurv was employed to develop a proposed model based on significant lipid species ( P  < 0.01) and clinical biomarkers to predict DMFS. Concordance index and receiver operating curve analyses were performed to assess model effectiveness. The study also explored the potential role of lipid alterations in the prognosis of NPC. Results Forty lipids were recognized as distant metastasis-associated ( P  < 0.05) by univariate Cox regression. The concordance indices of the proposed model were 0.764 (95% confidence interval (CI), 0.682–0.846) and 0.760 (95% CI, 0.649–0.871) in the training and validation sets, respectively. High-risk patients had poorer 5-year DMFS compared with low-risk patients (Hazard ratio, 26.18; 95% CI, 3.52–194.80; P  < 0.0001). Moreover, the six lipids were significantly correlated with immunity- and inflammation-associated biomarkers and were mainly enriched in metabolic pathways. Conclusions Widely targeted quantitative lipidomics reveals plasma lipid predictors for LANPC, the prognostic model based on that demonstrated superior performance in predicting metastasis in LANPC patients.

Background Locoregional recurrence remains the challenge for long‐term survival of non‐small cell lung cancer (NSCLC) patients after radical surgery, and curative‐intent radiotherapy could be a treatment choice. This study aimed to assess the survival and prognostic factors of patients with postoperative locoregionally recurrent NSCLC treated with radical radiotherapy. Methods We reviewed medical records of 74 NSCLC patients with postoperative locoregional recurrence who received radical radiotherapy between April 2012 and February 2016 at Sun Yat‐sen University Cancer Center (Guangzhou, China). The efficacy and safety of radical radiotherapy were analyzed. The probability of survival was estimated using the Kaplan–Meier method and compared using the log‐rank test. The Cox proportional hazards model was used to identify prognostic factors. Results Grade 3/4 adverse events included neutropenia (8 cases, 10.8%), esophagitis (7 cases, 9.5%), pneumonitis (1 case, 1.4%), and vomiting (1 case, 1.4%). The 2‐year overall survival, progression‐free survival, local recurrence‐free survival (LRFS), and distant metastasis‐free survival (DMFS) rates of all patients were 84.2, 42.5, 70.0, and 50.9%, respectively. Univariate and multivariate analyses showed that a higher biological effective dose (BED) of radiation was associated with longer LRFS [hazard ratios (HR) = 0.317, 95% confidence interval (CI) = 0.112–0.899, P = 0.016] and that wild‐type epidermal growth factor receptor (EGFR) was associated with longer DMFS compared with EGFR mutation (HR = 0.383, 95% CI = 0.171–0.855, P = 0.019). Conclusions Radical radiotherapy is effective and well‐tolerated in NSCLC patients with postoperative locoregional recurrence. High BED is a predictor for long LRFS, and the presence of wild‐type EGFR is a predictor for long DMFS.

Background We aimed to comprehensively investigate the optimal cumulative cisplatin dose during concurrent chemoradiotherapy (CC-CCD) for locoregionally advanced nasopharyngeal carcinoma (CA-LANPC) with different tumor responses after neoadjuvant chemotherapy (NAC). Methods Patients with CA-LANPC who underwent NAC followed by cisplatin-based concurrent chemoradiotherapy were retrospectively analyzed. Evaluation of tumor response in patients was conducted by Response Evaluation Criteria for Solid Tumor (RECIST) 1.1 after two to four cycles NAC. Multivariate Cox proportional hazards models were used for prognosis. Recursive partitioning analysis (RPA) was conducted to classify participates and predict disease-free survival (DFS). Results One hundred and thirty-two patients with favorable response after NAC were included. The median CC-CCD was 163 mg/m 2 (IQR, 145–194 mg/m 2 ), and 160 mg/m 2 was selected as the cutoff point to group patients into low and high CC-CCD groups (< 160 vs. ≥ 160 mg/m 2 ). There was significant improvement in 5-year DFS (91.2% vs. 72.6%; P = 0.003) for patients receiving high CC-CCD compared to those receiving low CC-CCD. Multivariate analysis revealed that CC-CCD, T stage, and Epstein–Barr virus (EBV) DNA were independent prognostic factors for DFS (P < 0.05 for all). Patients were further categorized into two prognostic groups by RPA: the low-risk group (T1-3 disease with regardless of EBV DNA, and T4 disease with EBV DNA < 4000 copy/mL), and the high-risk group (T4 disease with EBV DNA ≥ 4000 copy/mL). Significant 5-year DFS improvement was observed for the high-risk group (P = 0.004) with high CC-CCD. However, DFS improvement was relatively insignificant in the low-risk group (P = 0.073). Conclusions CC-CCD was a positive prognostic factor for responders after NAC in CA-LANPC. Furthermore, CC-CCD ≥ 160 mg/m 2 could significantly improve DFS in the high-risk group with CA-LANPC, but the benefit of high CC-CCD in the low-risk group needs further study.

BackgroundDespite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC plus cisplatin CCRT ) for LANPC patients.MethodsFrom January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors.ResultsAfter PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3–4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064).ConclusionAdditiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Liver, as an immune and detoxification organ, represents an important line of defense against bacteria and infection and a vulnerable organ that is easily injured during sepsis. Artesunate (ART) is an anti-malaria agent, that also exhibits broad pharmacological activities including anti-inflammatory, immune-regulation and liver protection. In this study, we investigated the cellular responses in liver to sepsis infection and ART hepatic-protective mechanisms against sepsis. Cecal ligation and puncture (CLP)-induced sepsis model was established in mice. The mice were administered ART (10 mg/kg, i.p.) at 4 h, and sacrificed at 12 h after the surgery. Liver samples were collected for preparing single-cell RNA transcriptome sequencing (scRNA-seq). The scRNA-seq analysis revealed that sepsis-induced a dramatic reduction of hepatic endothelial cells, especially the subtypes characterized with proliferation and differentiation. Macrophages were recruited during sepsis and released inflammatory cytokines ( Tnf , Il1b , Il6 ), chemokines ( Ccl6 , Cd14 ), and transcription factor ( Nfkb1 ), resulting in liver inflammatory responses. Massive apoptosis of lymphocytes and abnormal recruitment of neutrophils caused immune dysfunction. ART treatment significantly improved the survival of CLP mice within 96 h, and partially relieved or reversed the above-mentioned pathological features, mitigating the impact of sepsis on liver injury, inflammation, and dysfunction. This study provides comprehensive fundamental proof for the liver protective efficacy of ART against sepsis infection, which would potentially contribute to its clinical translation for sepsis therapy. Single cell transcriptome reveals the changes of various hepatocyte subtypes of CLP-induced liver injury and the potential pharmacological effects of artesunate on sepsis.

The Cu/SAPO-34 zeolite serves as an efficient active component for the selective catalytic reduction (SCR) of nitrogen oxides (NO x ) in flue gas by ammonia. Despite its commendable high-temperature hydrothermal stability, the application of Cu/SAPO-34 zeolite is limited due to low-temperature hydrothermal deactivation issues in the steam environment. In this paper, we provide a systematic review on the denitration mechanism, low-temperature hydrothermal deactivation mechanism, factors influencing its low-temperature hydrothermal stability, and the corresponding improvement measures of Cu/SAPO-34 zeolite. Additionally, the advantages and disadvantages of different methods are analyzed to offer valuable insights for future research.

This paper analyzes the industrial structure of Zhenjiang city with multiple perspectives in Jiangsu province in China, such as: input structure, output structure and their contributions to GDP. The study focuses on the industrial structures themselves and the relations among them with the drawing of industrial economics theory, regional economics and priority economic growth theory. The shifting mode about Zhenjiang's industrial structures during the 10th Five-Year and the 11th Five-Year plans are presented in detail and in depth in this paper. The contribution to economic growth caused by upgrading of industrial structures in low-carbon emission economic model is analyzed. Finally, it is proposed an economic model system based on the transformation and upgrading of industrial structures.

Purpose Chidamide (CS055/HBI-8000) is a new benzamide class of histone deacetylase inhibitor with marked anti-tumor activity. This study reports the phase I results. Methods Patients with advanced solid tumors or lymphomas received oral doses of 5, 10, 17.5, 25, 32.5, or 50 mg chidamide either twice (BIW) or three times (TIW) per week for 4 consecutive weeks every 6 weeks. Safety, characteristics of pharmacokinetics (PK) and pharmacodynamics (PD), and preliminary efficacy were evaluated. Results A total of 31 patients were enrolled. No DLTs were identified in the BIW cohorts up to 50 mg. DLTs were grade 3 diarrhea and vomiting in two patients in the TIW cohort at 50 mg, respectively. PK analysis revealed t 1/2 of 16.8–18.3 h, T max of 1–2 h in most cases, and a dose-related increase in C max and AUC. Significant induction of histone H3 acetylation in peripheral white blood cells was observed after a single dose of chidamide. Four patients with T-cell lymphomas and 1 patient with submandibular adenoid cystic carcinoma achieved a partial response. Conclusions Chidamide was generally well tolerated in patients with advanced solid tumors or lymphomas in the tested regimens. Favorable PK and PD profiles, as well as encouraging preliminary anti-tumor activity, were demonstrated.