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1.
J Food Biochem ; : e14049, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34981522

RESUMO

In the present study, the ameliorative effects of polyphenols from purple potato leaves (PSPLP) on hyperuricemia were investigated. HPLC-MS analysis showed that PSPLP was mainly composed of caffeoylquinic acid derivatives (84%). PSPLP inhibited the levels of cytokines (IL-1ß, IL-6, and TNF-α) in monosodium urate-induced RAW264.7 cells. In vivo, PSPLP significantly inhibited the level of uric acid in hyperuricemia mice from 209.6 to 166.6 µM, and significantly interfered with the activities of xanthine oxidase (XOD) and adenosine deaminase in liver, the activity of XOD decreased from 13.5 to 11.6 U/gprot. PSPLP can decrease serum creatinine level from 105 to 59 µM, and urea nitrogen level from 21.9 to 14.1 mM, which can effectively protect kidney. These results provide a reference for future research and application of PSPLP as a functional food to intervene hyperuricemia and associated inflammation. PRACTICAL APPLICATIONS: This study evaluated the effect of polyphenols from purple potato leaves (PSPLP) on hyperuricemia. The results suggested that PSPLP has an important role in the intervention of hyperuricemia and hyperuricemic-related inflammation or renal injury, and can be used in the application of functional foods. These results provided a basis for further study on the biological activities of polyphenols from purple sweet potato leaves.

2.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(1): 45-51, 2022 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-35038798

RESUMO

Objective: To investigate the effectiveness of transosseous suture in medial patellofemoral ligament (MPFL) double bundle reconstruction. Methods: The clinical data of 75 patients with recurrent patella dislocation who met the selection criteria between January 2014 and December 2017 were retrospectively analyzed. All of them were treated with MPFL double bundle reconstruction, and divided into study group (39 cases, using new transosseous suture technique) and control group (36 cases, using traditional suture anchor fixation) depending on the intraoperative fixation technique. There was no significant difference in gender, age, body mass index, affected knee side, preoperative tibial tuberosity-trochlear groove distance, Insall-Salvati ratio, knee range of motion, Kujala score, International Knee Documentation Committee (IKDC) score, congruence angle, and tilt angle between the two groups ( P>0.05). The operation time, intraoperative blood loss, hospital stay, and postoperative complications were recorded and compared between the two groups. Kujala score, IKDC score, and knee range of motion were used to evaluate the functional improvement of patients before and after operation. The congruence angle and tilt angle were measured on X-ray films. Results: There was no significant difference in operation time, intraoperative blood loss, and hospital stay between the two groups ( P>0.05). Patients in both groups were followed up 24-36 months, with an average of 29.4 months. There was no complication such as incision infection, fat liquefaction, patellar redislocation, and prepatellar pain during follow-up. At last follow-up, the Kujala score, IKDC score, knee range of motion, congruence angle, and tilt angle of two groups significantly improved when compared with those before operation ( P<0.05), while there was no significant difference between the two groups ( P>0.05). Conclusion: The application of suture anchor or transosseous suture to complete MPFL double bundle reconstruction can restore patellar stability, and there is no significant difference in the short-term effectiveness between them.

3.
J Biol Chem ; : 101586, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35032551

RESUMO

Signaling by bone morphogenetic proteins (BMPs) plays pivotal roles in embryogenesis, adult tissue homeostasis, and disease. Recent studies revealed that the well-established WNT agonist R-spondin 2 (RSPO2) is also a BMP receptor (BMPR1A) antagonist, with roles in early Xenopus embryogenesis and human acute myeloid leukemia (AML). To uncouple the BMP antagonist function from the WNT agonist function and to promote development of AML therapeutics, here we identified a 10-mer peptide (RW) derived from the Thrombospondin 1 (TSP1)-domain of RSPO2, which specifically prevents binding between RSPO2 and BMPR1A without altering WNT signaling. We also show a corresponding RW-dendrimer (RWd) exhibiting improved half-life relieves inhibition of BMP receptor signaling by RSPO2 in human AML cells, reducing cell growth and inducing differentiation. Moreover, microinjection of RWd in Xenopus embryos ventralizes the dorsoventral embryonic patterning by upregulating BMP signaling without affecting WNT signaling. Our study corroborates the function of RSPO2 as a BMP receptor antagonist and provides a proof-of-concept for pharmacologically uncoupling BMP antagonist from WNT agonist functions of RSPO2 using the inhibitor peptide RWd with enhanced target selectivity and limited side effects.

4.
J Clin Oncol ; : JCO2101467, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34990291

RESUMO

PURPOSE: Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL. PATIENTS AND METHODS: Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc. RESULTS: Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, -4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life. CONCLUSION: Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.

5.
J Colloid Interface Sci ; 605: 451-462, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34340032

RESUMO

Currently, it is critical but a tricky point to develop economical, high-efficiency, and durable non-precious metal electrocatalysts towards oxygen reduction and oxygen evolution reaction (ORR/OER) in rechargeable Zn-air batteries. Herein, N, Mn-codoped three-dimensional (3D) fluffy porous carbon nanostructures encapsulating FeCo/FeCoP alloyed nanoparticles (FeCo/FeCoP@NMn-CNS) are prepared by one-step pyrolysis of the metal precursors and polyinosinic acid. The optimized hybrid nanocomposite (obtained at 800 °C, named as FeCo/FeCoP@NMn-CNS-800) exhibits outstanding catalytic performance in the alkaline electrolyte with a half-wave potential (E1/2) of 0.84 V for the ORR and an overpotential of 325 mV towards the OER at 10 mA cm-2. Impressively, the FeCo/FeCoP@NMn-CNS-800-assembled rechargeable Zn-air battery presents an open-circuit voltage of 1.522 V (vs. RHE), a peak power density of 135.0 mW cm-2, and long-term durability by charge-discharge cycling for 200 h, surpassing commercial Pt/C + RuO2 based counterpart. This work affords valuable guidelines for exploring advanced bifunctional ORR and OER catalysts in rational construction of high-quality Zn-air batteries.

6.
Neural Regen Res ; 17(5): 1051-1058, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34558532

RESUMO

Repetitive transcranial magnetic stimulation (rTMS) has been shown to effectively improve impaired swallowing in Parkinson's disease (PD) patients with dysphagia. However, little is known about how rTMS affects the corresponding brain regions in this patient group. In this case-control study, we examined data from 38 PD patients with dysphagia who received treatment at Beijing Rehabilitation Medicine Academy, Capital Medical University. The patients received high-frequency rTMS of the motor cortex once per day for 10 successive days. Changes in brain activation were compared via functional magnetic resonance imaging in PD patients with dysphagia and healthy controls. The results revealed that before treatment, PD patients with dysphagia showed greater activation in the precentral gyrus, supplementary motor area, and cerebellum compared with healthy controls, and this enhanced activation was weakened after treatment. Furthermore, before treatment, PD patients with dysphagia exhibited decreased activation in the parahippocampal gyrus, caudate nucleus, and left thalamus compared with healthy controls, and this activation increased after treatment. In addition, PD patients with dysphagia reported improved subjective swallowing sensations after rTMS. These findings suggest that swallowing function in PD patients with dysphagia improved after rTMS of the motor cortex. This may have been due to enhanced activation of the caudate nucleus and parahippocampal gyrus. The study protocol was approved by the Ethics Committee of Beijing Rehabilitation Hospital of Capital Medical University (approval No. 2018bkky017) on March 6, 2018 and was registered with Chinese Clinical Trial Registry (registration No. ChiCTR 1800017207) on July 18, 2018.

9.
J Transl Med ; 19(1): 499, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876185

RESUMO

Chimeric antigen receptor T cell (CAR-T cell) therapy is a relatively new, effective, and rapidly evolving therapeutic for adoptive immunotherapies. Although it has achieved remarkable effect in hematological malignancies, there are some problems that remain to be resolved. For example, there are high recurrence rates and poor efficacy in solid tumors. In this review, we first briefly describe the metabolic re-editing of T cells and the changes in metabolism during the preparation of CAR-T cells. Furthermore, we summarize the latest developments and newest strategies to improve the metabolic adaptability and antitumor activity of CAR-T cells in vitro and in vivo.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34876265

RESUMO

Core-shell structured Ni-ZIF-67@ZIF-8 derived bimetal selenides encapsulating into a 3D interpenetrating dual-carbon framework (Ni3Se4@CoSe2@C/CNTs) have been designed and prepared via carbonization and subsequent selenization processes. In this hierarchical structure, Ni3Se4@CoSe2 nanocrystals were uniformly dispersed into the 3D carbon frameworkstructure/carbon nanotubes networks, which greatly enhanced the electronic conductivity and further enabled ultrafast Na-ion diffusion kinetics. When used as anode materials of sodium ion battery (SIB), The Ni3Se4@CoSe2@C/CNTs electrode delivered the excellent rate capability of 206 mA h g-1 at 3 A g-1 and marvelous cyclic stability with capacity retention of 243 mA h g-1 after 600 cycles at 1 A g-1. This research provides a new way to prepare bimetallic selenide derived from MOF precursor with amazing heterostructure as the advanced anode materials for SIBs.

11.
J Chem Theory Comput ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851637

RESUMO

A protocol that accurately assesses the intestinal permeability of small molecule compounds plays an essential role in decreasing the cost and time in inventing a new drug. This manuscript presents a novel computational method to study the passive permeation of small molecule drugs based on the inhomogeneous solubility-diffusion model. The multidimensional free energy surface of the drug transiting through a lipid bilayer is computed with transition-tempered metadynamics that accurately captures the mechanisms of passive permeation. The permeability is computed by following the diffusion motion of the drug molecules along the minimal free energy path found on the multidimensional free energy surface. This computational method is assessed by studying the permeability of five small molecule drugs (ketoprofen, naproxen, metoprolol, propranolol, and salicylic acid). The results demonstrate a remarkable agreement between the computed permeabilities and those measured with the intestinal assay. The in silico method reported in this manuscript also reproduces the permeability measured from the intestinal assay (in vivo) better than the cell-based assays (e.g., PAMPA and Caco-2) do. In addition, the multidimensional free energy surface reveals the interplay between the structure of the small molecule and its permeability, shedding light on strategies of drug optimization.

12.
Front Oncol ; 11: 764630, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868985

RESUMO

Numerous clinical studies investigated how low expression of CD9 predicts poor prognosis of solid tumor. However, the results were inconclusive. This present meta-analysis was therefore performed to determine the prognostic value of CD9 expression in solid tumors. In this meta-analysis, 25 studies involving 5,555 participants were included; the result showed strong significant associations between declined expression of CD9 and all endpoints: overall survival (OS) (hazard ratio (HR) = 1.88, 95% CI = 1.45-2.43, p < 0.000) and time to progression (TTP) (HR = 2.0, 95% CI = 1.38-2.88, p < 0.000). The subgroup analysis was also performed, which revealed that the associations between CD9 downregulated expression related to poor OS in lung cancer and head and neck cancer. Also, low expression of CD9 was significantly connected with poor TTP in patients with head and neck cancer. The adverse prognostic impact of decreased expression of CD9 was observed in patients of different ethnicities. In conclusion, these results showed that declined expression of CD9 was associated with poor survival in human solid tumors. CD9 may be a valuable prognostic predictive biomarker and a potential therapeutic target in human solid tumors.

13.
Chem Commun (Camb) ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34870644

RESUMO

The dynamically stable global minima M©B7O7+ (M = Ni, Pd, Pt) are interesting in that they possess σ-aromaticity alone within the B7M core moiety, which can be attributed to the strong peripheral localized O → B π back-bonding that leads to the less favourable delocalized M → B π back-bonding over the B7M core moiety.

14.
Acta Biomater ; 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34879291

RESUMO

Minimally invasive repair strategies are a very promising approach for the treatment of intervertebral disc degeneration (IDD). In recent years, small extracellular vesicles (sEVs) secreted from mesenchymal stem cells (MSCs) have been shown great potential in alleviating IDD. However, in vitro experiments, MSCs are usually exposed to a normoxic micro-environment, which differs greatly from the hypoxic micro-environment in vivo. The primary purpose of our research was to determine whether sEVs isolated from MSCs under hypoxic status (H-sEVs) exhibit a more beneficial effect on protecting IDD compared with sEVs derived from MSCs under normoxic status (N-sEVs). A tail IDD rat model and a series of experiments in vitro were conducted to compare the beneficial effects of PBS, N-sEVs, and H-sEVs treatment. Then, to validate the role of sEVs miRNAs in IDD, a miRNA microarray sequencing analysis and a series of rescue experiments were conducted. Luciferase activity, RNA-ChIP and western blot were performed to explore the potential mechanisms. The results indicate that sEVs alleviate IDD by ameliorating the homeostatic imbalance between anabolism and catabolism in vivo and in vitro. Microarray sequencing result shows that miR-17-5p is maximally enriched in H-sEVs. Toll-like receptor 4 (TLR4) was determined to be a target downstream gene of miR-17-5p. Finally, it was found that H-sEVs miR-17-5p may modulate proliferation and synthesis of human nucleus pulposus cells (HNPCs) matrix via TLR4 pathway. In conclusion, H-sEVs miR-17-5p alleviate IDD via promoting HNPCs matrix proliferation and synthesis, providing new therapeutic targets for IDD. STATEMENT OF SIGNIFICANCE: : Intervertebral disc degeneration (IDD) is the primary cause of low back pain (LBP), which is a huge burden to society. Our research demonstrates for the first time that hypoxic pretreatment of small extracellular vesicles (H-sEVs) effectively alleviated the progress of IDD. In short, in the present research, we found that H-sEVs miR-17-5p could modulate proliferation and synthesis of nucleus pulposus cells (NPCs) matrix via TLR4/PI3K/AKT pathway. Therefore, hypoxic pre-treatment is a prospective and efficient method to optimize the therapeutic effect of MSCs-derived sEVs. miRNA and MSCs-derived sEVs combination may be a promising therapeutic approach for IDD.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34882254

RESUMO

Rapid and efficient bispecific antibody (BsAb) production for industrial applications is still facing many challenges. We reported a technology platform for generating bispecific IgG antibodies, "Bispecific Antibody by Protein Trans-splicing (BAPTS)." While the "BAPTS" method has shown potential in high-throughput screening of BsAbs, further understanding and optimizing the methodology is desirable. A large number of BsAbs were selected to illustrate the conversion efficiency and kinetics parameters. The temperature of reaction makes no significant influence in conversion efficiency, which can reach more than 70% within 2 h, and CD3 × HER2 BsAb can reach 90%. By fitting trans-splicing reaction to single-component exponential decay curves, the apparent first-order rate constants at a series of temperatures were determined. The rate constant ranges from 0.02 to 0.11 min-1 at 37 °C, which is a high rate reported for the protein trans-splicing reaction (PTS). The reaction process is activated rapidly with activation energy of 8.9 kcal·mol-1 (CD3 × HER2) and 5.2 kcal·mol-1 (CD3 × EGFR). The BsAbs generated by "BAPTS" technology not only had the similar post-translation modifications to the parental antibodies, but also demonstrated excellent in vitro and in vivo bioactivity. The kinetics parameters and activation energy of the reaction illustrate feasible for high-throughput screening and industrial applications using the "BAPTS" approach. KEY POINTS: • The trans-splicing reaction of Npu DnaE intein in "BAPTS" platform is a rapid process with low reaction activation and high rate. • The BsAb generated by "BAPTS" remained effective in tumor cell killing. • The kinetics parameters and activation energy of the reaction illustrate feasible for high-throughput screening and industrial applications using the "BAPTS" approach.

16.
BMC Cancer ; 21(1): 1320, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34886807

RESUMO

BACKGROUND: To evaluate the prognostic value of the apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (MRI) and monitor the early treatment response to induction chemotherapy (IC) with plasma EBV DNA in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). RESULTS: A total of 307 stage III-IVb NPC patients were prospectively enrolled. All patients underwent MRI examinations to calculate ADC and plasma EBV DNA measurements pretreatment and post-IC. The participants' ADC value of 92.5% (284/307) increased post-IC. A higher percent change in ADC value (ΔADC%high group) post-IC was associated with a higher 5-year OS rate (90.7% vs 74.9%, p < 0.001) than those in the ΔADC%low group. Interestingly, ΔADC% was closely related to the response measured by RECIST 1.1 (p < 0.001) and plasma EBV DNA level (p = 0.037). The AUC significantly increased when post-IC plasma EBV DNA was added to ΔADC% to predict treatment failure. Thus, based on ΔADC% and plasma EBV DNA, we further divided the participants into three new prognostic response phenotypes (early response, intermediate response, and no response) that correlated with disparate risks of death (p = 0.001), disease progression (p < 0.001), distant metastasis (p < 0.001), and locoregional relapse (p < 0.001). CONCLUSION: The percentage change in ADC post-IC is indicative of treatment response and clinical outcome. ΔADC% and plasma EBV DNA-based response phenotypes may provide potential utility for early termination of treatment and allow guiding risk-adapted therapeutic strategies for LA-NPC.

17.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 3791-3794, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34892061

RESUMO

Brain electrical stimulation has shown the capability to modulate neural activities in a variety of ways. Compared with transcranial direct current stimulation(tDCS), transcranial alternating current stimulation (tACS) may affect brain activities differently through a frequency-based mechanism. This pilot study applied tACS to the scalp following the meridian (Jingluo) of traditional Chinese medicine to explore its potential neural modulation effect. A wearable electroencephalogram (EEG) device was used to measure the frontal activity in a female participant before and after tACS longitudinally. A combined method of singular spectrum analysis (SSA)-independent components analysis (ICA) was applied to separate potential artifacts from ocular and other irrelevant sources. The results demonstrated that SSA-ICA could effectively separate signals from different sources especially the ocular artifact. EEG spectrum analysis showed that short-term tACS could increase the power of delta waves. This study has good implications for the use of tACS and SSA-ICA method for the study of brain activities. Future research is needed to refine more optimum parameters of tACS and SSA-ICA to make the evidence more solid.Clinical Relevance- tACS may influence the brain wave oscillations through the frequency-based mechanism. SSA-ICA method helps to broaden the use of wearable EEG devices for various clinical applications.

18.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 6053-6057, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34892497

RESUMO

A valid evaluation of neurological functions after stroke may improve clinical decision-making. The aim of this study was to compare the performance of EEG-related indexes in differentiating stroke patients from control participants, and to investigate pathological EEG changes after chronic stroke. 20 stroke and 13 healthy participants were recruited, and spontaneous EEG signals were recorded during the resting state. EEG rhythms and complexity were calculated based on Fast Fourier Transform and the fuzzy approximate entropy (fApEn) algorithm. The results showed a significant difference of alpha rhythm (p = 0.019) and fApEn (p = 0.003) of EEG signals from brain area among ipsilesional, contralesion hemisphere of stroke patients and corresponding brain hemisphere of healthy participants. EEG fApEn had the best classification accuracy (84.85%), sensitivity (85.00%), and specificity (84.62%) among these EEG-related indexes. Our study provides a potential method to evaluate alterations in the properties of the injured brain, which help us to understand neurological change in chronic strokes.

19.
Biophys J ; 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34968427

RESUMO

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of endogenous lipids that consist of two acyl chains connected through a single ester bond. Being a unique species of FAHFAs, (O-acyl)-ω-hydroxy fatty acids (OAHFAs) differ from other FAHFAs in that their hydroxy fatty acid backbones are ultralong and their hydroxy esterification is believed to be solely at the terminal (ω-) position. Only in recent years with technological advances in lipidomics have OAHFAs been identified as an important component of the tear film lipid layer (TFLL). It was found that OAHFAs account for approximately 4 mol% of the total lipids and 20 mol% of the polar lipids in the TFLL. However, their biophysical function and contribution to the TFLL is still poorly understood. Here we studied the molecular biophysical mechanisms of OAHFAs using palmitic-acid-9-hydroxy-stearic-acid (PAHSA) as a model. PAHSA and OAHFAs share key structural similarities that could result in comparable biophysical properties and molecular mechanisms. With combined biophysical experiments, atomic force microscopy observations, and all-atom molecular dynamics simulations, we found that the biophysical properties of a dynamic PAHSA monolayer under physiologically relevant conditions depend on a balance between kinetics and thermal relaxation. PAHSA molecules at the air-water surface demonstrate unique polymorphic behaviors, which can be explained by configurational transitions of the molecules under various lateral pressures. These findings could have novel implications in understanding biophysical functions that FAHFAs, in general, or OAHFAs, specifically, play in the TFLL.

20.
JAMA Netw Open ; 4(12): e2138470, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34928359

RESUMO

Importance: Nedaplatin-based concurrent chemoradiotherapy (CCRT) regimen at 2 years was noninferior to cisplatin-based regimen in patients with locoregional, stage II to IVB nasopharyngeal carcinoma (NPC) and was associated with fewer late adverse events, but longer-term outcomes and toxicity are unclear. Objective: To evaluate the 5-year outcomes and late toxicity profile of nedaplatin-based CCRT in patients with locoregional, stage II to IVB NPC. Design, Settings, and Participants: This 5-year follow-up secondary analysis of an open-label, noninferiority, multicenter randomized clinical trial enrolled patients with nonkeratinizing stage II to IVB NPC between January 16, 2012, and July 16, 2014, with a median follow-up duration of 78 months (IQR, 3-99 months). Data analysis was conducted from November 10, 2020, to July 8, 2021. Interventions: Patients were randomly assigned (1:1) to receive nedaplatin (100 mg/m2)- or cisplatin (100 mg/m2)-based chemotherapy every 3 weeks for 3 cycles concurrently with intensity-modulated radiotherapy. Main Outcomes and Measures: The primary end point was progression-free survival (PFS). Secondary end points were overall survival, distant metastasis-free survival, and locoregional relapse-free survival. Results: A total of 402 eligible participants were enrolled (median [IQR] age, 45 [18-65] years; 302 [75.1%] male). Patients were randomly assigned to receive nedaplatin- or cisplatin-based CCRT (n = 201 for each): 196 patients (97.5%) started nedaplatin-based CCRT and 197 patients (98.0%) started cisplatin-based CCRT. Intention-to-treat analysis demonstrated a 5-year progression-free survival rate of 81.4% (95% CI, 75.9%-86.9%) for the cisplatin group and 79.8% (95% CI, 74.1%-85.5%) for nedaplatin group, with a difference of 1.6% (95% CI, -6.3% to 9.5%; P = .002 for noninferiority). No significant survival differences were observed between the cisplatin and nedaplatin groups for 5-year overall survival (89.4% vs 88.8%, P = .63), distant metastasis-free survival (85.9% vs 90.4%, P = .17), and locoregional relapse-free survival (92.6% vs 89.6%, P = .17) rates. The cisplatin group had a higher incidence of grade 3 and 4 auditory toxic effects than the nedaplatin group (35 [17.7%] vs 21 [10.5%], P = .04). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, long-term analysis confirmed that nedaplatin-based CCRT could be regarded as an alternative doublet treatment strategy to cisplatin-based CCRT in stage II to IVB NPC. Trial Registration: ClinicalTrials.gov Identifier: NCT01540136.


Assuntos
Quimiorradioterapia/efeitos adversos , Cisplatino/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Compostos Organoplatínicos/uso terapêutico , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Quimiorradioterapia/métodos , Cisplatino/toxicidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/toxicidade , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
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