Transition-Metal-Free Radical Relay Cascade Annulation of Amides: Access to Antitumor Active Benzo[b]azepine and Oxindole Derivatives.

Efficient transition-metal-free synthesis of benzo[b]azepines and oxindoles is achieved via a radical relay cascade strategy employing halogen atom transfer (XAT) for aryl radical generation followed by intramolecular hydrogen atom transfer (HAT). Optimization yielded moderate to substantial yields under visible light irradiation. Preliminary biological assessments revealed promising anti-tumor activity for select compounds.

Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial.

Objective: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma.

Design: Phase 3, open label, multicentre, randomised trial.

Setting: Four hospitals located in China between September 2019 and August 2022.

Palladium-catalyzed alkynylation of allylic -difluorides.

Herein, a palladium-catalyzed regioselective alkynylation, esterification, and amination of allylic -difluorides C-F bond activation/transmetallation/β-C elimination or nucleophilic attack has been achieved. This innovative protocol showcases an extensive substrate range and operates efficiently under mild reaction conditions, resulting in high product yields and -selectivity. Particularly noteworthy is its exceptional tolerance towards a wide array of functional groups.

Accessing Benzoazepine Derivatives via Photoinduced Radical Relay Formal [5 + 2] Reaction of Amide/Alkyne Enabled by Palladium Catalysis.

A novel class of alkyne-tethered amides facilitates an unprecedented photoinduced palladium-catalyzed radical relay formal [5 + 2] reaction. This innovative strategy allows for the rapid construction of diverse fused benzoazepine structures, yielding structurally novel and compelling compounds. With a broad substrate scope and excellent functional group tolerance, the methodology synthesizes biologically active compounds.

Camrelizumab and apatinib plus induction chemotherapy and concurrent chemoradiotherapy in stage N3 nasopharyngeal carcinoma: a phase 2 clinical trial.

The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage TN3M0 nasopharyngeal carcinoma were enrolled and received the combination of three cycles of induction chemotherapy, camrelizumab and apatinib followed by chemoradiotherapy.

Palladium-Catalyzed Diversified Synthesis of Monofluorinated Alkenes from Allylic -Difluorides through Pd-OH Intermediate.

Significant advancements in synthesis of monofluoroalkenes via palladium-catalyzed reactions involving allylic -difluorides and diverse nucleophiles have been achieved. This method allows regioselective arylation, alkylation, allylation, alkenylation, and hydrogenation of allylic -difluorides, yielding high selectivity and favorable product yields under mild conditions. Tolerating various functional groups, these transformations utilize a common Pd-OH intermediate.

Efficacy and safety of sintilimab plus bevacizumab in metastatic nasopharyngeal carcinoma after failure of platinum-based chemotherapy: an open-label phase 2 study.

Background: There are limited treatment options for patients with metastatic nasopharyngeal carcinoma (mNPC) after failure of platinum-based chemotherapy. In this trial, we assessed the efficacy and safety of sintilimab plus bevacizumab in patients with mNPC where platinum-based chemotherapy has been ineffective.

Methods: This was a single-centre, open-label, single-arm, phase 2 trial in Guangzhou, China for patients with mNPC progressed after at least one line of systemic therapy.

Effective of metastasis-directed therapy for de novo metastatic nasopharyngeal carcinoma: A propensity score matched analysis.

Objective: Our objective was to establish a prognostic model for patients with de novo metastatic nasopharyngeal carcinoma (NPC) who received chemotherapy followed by locoregional radiotherapy (LRRT) to identify candidates for metastasis-directed therapy (MDT).

Methods: De novo metastatic NPC patients who received chemotherapy followed by LRRT were enrolled. Propensity score matching (PSM) method was used to compare overall survival (OS) for patients receiving LRRT alone and MDT plus LRRT.

Association of Socioeconomic Disparities With Nasopharyngeal Carcinoma Survival in an Endemic Area, China.

Objectives: This retrospective cohort study investigated the association of socioeconomic status with survival outcomes among patients with nasopharyngeal carcinoma in an endemic area of China.

Methods: The primary endpoint was overall survival. Survival outcomes were estimated by the Kaplan-Meier method and compared by the log-rank test, and the multivariate Cox proportional hazards model was used to estimate hazard ratios, 95% CIs, and independent prognostic factors.

Restraint stress induced anxiety and sleep in mice.

In humans and animals, exposure to changes in internal or external environments causes acute stress, which changes sleep and enhances neurochemical, neuroendocrine, and sympathetic activities. Repeated stress responses play an essential role in the pathogenesis of psychiatric diseases and sleep disorders. However, the underlying mechanism of sleep changes and anxiety disorders in response to acute stress is not well established.

Development of a prognostic model to identify the metastatic nasopharyngeal carcinoma patients who may benefit from chemotherapy combination PD-1 inhibitor.

Background: We aimed to establish a prognostic model to identify suitable candidates for chemotherapy combination PD-1 inhibitor in metastatic nasopharyngeal carcinoma (NPC) patients.

Patients And Methods: In this retrospective study, we included 524 patients (192 patients treated with chemotherapy combination PD-1 inhibitor and 332 received chemotherapy alone as first-line regimen) with metastatic NPC between January 2015 and March 2021. We developed a prognostic model to predict progression-free survival (PFS).

Activation of cholinergic basal forebrain neurons improved cognitive functions in adult-onset hypothyroid mice.

Cognitive dysfunction is common in hypothyroid patients, even after undergoing sufficient levothyroxine (LT4) replacement therapy for euthyroid. Our previous studies indicated that cholinergic neurons might contribute to the decline of cognition in adult-onset hypothyroidism. Nevertheless, the role of the cellular and neural control of basal forebrain (BF) cholinergic neurons in hypothyroidism-induced cognitive impairments is unknown.

Plasma Circulating Tumor Epstein-Barr Virus for the Surveillance of Cancer Progression in Bone-Only Metastatic Nasopharyngeal Carcinoma.

Background: Plasma Epstein-Barr virus DNA (EBV-DNA) is a sensitive and specific biomarker for nasopharyngeal carcinoma (NPC). We investigated whether longitudinal monitoring of EBV-DNA could accurately detect clinical disease progression in NPC patients with bone-only metastases.

Methods: In this retrospective study, a total of 105 patients with bone-only metastatic NPC who were treated with platinum-based first-line chemotherapy were enrolled.

gene combined with exercise training attenuates central AngII/AT1 axis function and oxidative stress in a prehypertensive rat model.

Angiotensin-converting enzyme 2 (ACE2) or exercise training (ExT) is beneficial to hypertension, but their combined effects remain unknown. In this study, lentivirus containing enhanced green fluorescent protein (eGFP) and were microinjected into the paraventricular nucleus (PVN) of young male spontaneous hypertensive rats (SHRs), and SHRs were assigned into five groups: sedentary (SHR), SHR-ExT, SHR-eGFP, gene (SHR-ACE2), and gene combined with ExT (SHR-ACE2-ExT). Wistar-Kyoto (WKY) rats were used as a control.

Effect of Induction Chemotherapy With Paclitaxel, Cisplatin, and Capecitabine vs Cisplatin and Fluorouracil on Failure-Free Survival for Patients With Stage IVA to IVB Nasopharyngeal Carcinoma: A Multicenter Phase 3 Randomized Clinical Trial.

Importance: Induction chemotherapy added to concurrent chemoradiotherapy significantly improves survival for patients with locoregionally advanced nasopharyngeal carcinoma, but the optimal induction regimen remains unclear.

Objective: To determine whether induction chemotherapy with paclitaxel, cisplatin, and capecitabine (TPC) improves survival vs cisplatin and fluorouracil (PF) prior to chemoradiotherapy for patients with stage IVA to IVB nasopharyngeal carcinoma.

Design, Setting, And Participants: This randomized, open-label, phase 3 clinical trial recruited 238 patients at 4 hospitals in China from October 20, 2016, to August 29, 2019.

Effect of Capecitabine Maintenance Therapy Plus Best Supportive Care vs Best Supportive Care Alone on Progression-Free Survival Among Patients With Newly Diagnosed Metastatic Nasopharyngeal Carcinoma Who Had Received Induction Chemotherapy: A Phase 3 Randomized Clinical Trial.

Importance: Capecitabine maintenance therapy improves survival outcomes in various cancer types, but data are limited on the efficacy and safety of capecitabine maintenance therapy in metastatic nasopharyngeal carcinoma (NPC).

Objective: To investigate the efficacy and safety of capecitabine maintenance therapy in metastatic NPC.

Design, Setting, And Participants: This randomized phase 3 clinical trial was conducted at Sun Yat-sen University Cancer Center from May 16, 2015, to January 9, 2020, among 104 patients with newly diagnosed metastatic NPC who had achieved disease control after 4 to 6 cycles of induction chemotherapy with paclitaxel, cisplatin, and capecitabine.

Effect of Restricted Feeding on Metabolic Health and Sleep-Wake Rhythms in Aging Mice.

Aging, an irreversible and unavoidable physiological process in all organisms, is often accompanied by obesity, diabetes, cardiovascular diseases, sleep disorders, and fatigue. Thus, older adults are more likely to experience metabolic symptoms and sleep disturbances than are younger adults. Restricted feeding (RF) is a dietary regimen aimed at improving metabolic health and extending longevity, as well as reorganizing sleep-wake cycles.

Assessment of Survival Model Performance Following Inclusion of Epstein-Barr Virus DNA Status in Conventional TNM Staging Groups in Epstein-Barr Virus-Related Nasopharyngeal Carcinoma.

Importance: Nonanatomic prognostic factors complement the traditional anatomic staging system and could be incorporated into the tumor-node-metastasis (TNM) framework. Several diseases have incorporated nonanatomic prognostic factors into the determination of TNM staging groups.

Objective: To refine TNM staging groups for Epstein-Barr virus (EBV)-related nonmetastatic nasopharyngeal carcinoma (NPC) by incorporating EBV DNA status.

Trajectories of EBV DNA and identifying the potential long-term survivors in metastatic nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is highly incident in southern China. Distant metastasis is the leading cause of death in NPC patients. However, the phenotypical feature of this patient population is largely undefined.

A Randomized Controlled Trial Comparing Two Different Schedules for Cisplatin Treatment in Patients with Locoregionally Advanced Nasopharyngeal Cancer.

Purpose: Previous studies suggest that a cumulative cisplatin dose of 200 mg/m might be adequate in the intensity-modulated radiation therapy (IMRT) era for locoregionally advanced nasopharyngeal carcinoma (LANPC). However, two cycles of once-every-3-weeks cisplatin at 100 mg/m has never been prospectively compared with standard once-a-week cisplatin regimen.

Patients And Methods: This trial was conducted at three hospitals from 2011 to 2016.

Prognostic and Predictive Value of Circulating Inflammation Signature in Non-Metastatic Nasopharyngeal Carcinoma: Potential Role for Individualized Induction Chemotherapy.

Purpose: We sought to assess the prognostic and predictive value of a circulating inflammation signature (CISIG) and develop CISIG-based tools for predicting prognosis and guiding individualized induction chemotherapy (ICT) in non-metastatic nasopharyngeal carcinoma (NPC).

Patients And Methods: We retrospectively collected a candidate inflammatory biomarker panel from patients with NPC treated with definitive radiotherapy between 2012 and 2017. We developed the CISIG using candidate biomarkers identified by a least absolute shrinkage and selection operator (LASSO) Cox regression model.

Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial.

Background: 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.