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1.
Angew Chem Int Ed Engl ; : e202410900, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010737

RESUMO

MnO2 is commonly used as the cathode material for aqueous zinc-ion batteries (AZIBs). The strong Coulombic interaction between Zn ions and the MnO2 lattice causes significant lattice distortion and, combined with the Jahn-Teller effect, results in Mn2+ dissolution and structural collapse. While proton intercalation can reduce lattice distortion, it changes the electrolyte pH, producing chemically inert byproducts. These issues greatly affect the reversibility of Zn2+ intercalation/extraction, leading to significant capacity degradation of MnO2. Herein, we propose a novel method to enhance the cycling stability of δ-MnO2 through selenium doping (Se-MnO2). Our work indicates that varying the selenium doping content can regulate the intercalation ratio of H+ in MnO2, thereby suppressing the formation of ZnMn2O4 by-products. Se doping mitigates the lattice strain of MnO2 during Zn2+ intercalation/deintercalation by reducing Mn-O octahedral distortion, modifying Mn-O bond length upon Zn2+ insertion, and alleviating Mn dissolution caused by the Jahn-Teller effect. The optimized Se-MnO2 (Se concentration of 0.8 at.%) deposited on carbon nanotube demonstrates a notable capacity of 386 mAh g-1 at 0.1 A g-1, with exceptional long-term cycle stability, retaining 102 mAh g-1 capacity after 5000 cycles at 3.0 A g-1.

2.
BMC Med ; 21(1): 173, 2023 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-37147645

RESUMO

BACKGROUND: Apatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings. METHODS: Patients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan-Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method. RESULTS: Between May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6-5.4%), and DCR was 35.8% (95% CI, 33.7-38.0%). The median PFS was 2.7 months (95% CI 2.2-2.8), and the median OS was 5.8 months (95% CI 5.4-6.1). CONCLUSIONS: The findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.


Assuntos
Adenocarcinoma , Antineoplásicos , Neoplasias Gástricas , Humanos , Antineoplásicos/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Estudos Prospectivos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Junção Esofagogástrica/patologia
3.
Small ; : e2309523, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38072626

RESUMO

The separator located between the positive and negative electrodes not only provides a lithium-ion transmission channel but also prevents short circuits for direct contact of electrodes. The inferior dimension thermostability of commercial polyolefin separators intensifies the thermal runaway of batteries under abuse such as short circuits, overcharge, and so on. a polyvinylidene fluoride/polyether imide (PVDF/PEI) separator with high thermal stability in which the high thermostable PEI microspheres are evenly dispersed in the PVDF film matrix and also located in the micro holes of the PVDF film is developed. They not only function as strong skeleton that enables the rare shrink of the separator at 200 °C avoiding short circuit but also act as ball valve that blocks the lithium ion transmission channel at 150 °C interrupting the further heat aggregation. Thus, the LiNi0.6 Co0.2 Mn0.2 O2 /Li batteries exhibit high cycle stability of 96.5% capacity retention after 100 cycles at 0.2C and 80°C. Further, the LiNi0.6 Co0.2 Mn0.2 O2 /graphite pouch cells are constructed and deliver good safety performance without smoke release and catching fire after the nail penetration test.

4.
Small ; 19(3): e2205489, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319477

RESUMO

Current diabetic wound treatments remain unsatisfactory due to the lack of a comprehensive strategy that can integrate strong applicability (tissue adhesiveness, shape adaptability, fast self-healability, and facile dressing change) with the initiation and smooth connection of the cascade wound healing processes. Herein, benefiting from the multifaceted bonding ability of tannic acid to metal ions and various polymers, a family of tannin-europium coordination complex crosslinked citrate-based mussel-inspired bioadhesives (TE-CMBAs) are specially developed for diabetic wound healing. TE-CMBAs can gel instantly (< 60 s), possess favorable shape-adaptability, considerable mechanical strengths, high elasticity, considerable wet tissue adhesiveness (≈40 kPa), favorable photothermal antimicrobial activity, excellent anti-oxidant activity, biocompatibility, and angiogenetic property. The reversible hydrogen bond crosslinking and sensitive metal-phenolic coordination also confers TE-CMBAs with self-healability, pH-responsive europium ion and TA releasing properties and on-demand removability upon mixing with borax solution, enabling convenient painless dressing change and the smooth connection of inflammatory microenvironment modulation, angiogenesis promotion, and effective extracellular matrix production leveraging the acidic pH condition of diabetic wounds. This adhesive dressing provides a comprehensive regenerative strategy for diabetic wound management and can be extended to other complicated tissue healing scenarios.


Assuntos
Adesivos , Diabetes Mellitus , Humanos , Adesivos/química , Európio , Cicatrização , Bandagens , Concentração de Íons de Hidrogênio , Hidrogéis/química , Antibacterianos/química
5.
Small ; 18(44): e2203347, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36108140

RESUMO

Although rechargeable zinc-ion batteries are promising candidates for next-generation energy storage devices, their inferior performance at subzero temperatures limits their practical application. Here, a strategy to destroy the H-bond network by adding synergistic chaotropic regents is reported, thus reducing the freezing point of the aqueous electrolyte below -90 °C. Owing to the synergistic chaotropic effect between urea and Zn(ClO4 )2 and the thermal release effect on the cathode interface during charging, Zn//VO2 batteries feature a specific capacity of 111.4 mAh g-1 and stability after ≈1000 cycles with 81.9% capacity retention at -40 °C. This work demonstrates that the synergistic chaotropic effect and the thermal effect on the interface can effectively widen the operation range of temperature of aqueous electrolytes and maintain fast kinetics, which provides a new design strategy for all-weather aqueous zinc batteries.

6.
Small ; 16(41): e2003585, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32964658

RESUMO

The practical application of aqueous rechargeable batteries is hampered by the low energy density and poor cycle stability, which mostly arises from the corrosion of cathode current collector, exfoliation of active material, and narrow electrochemical stability window of aqueous electrolyte. A light-weight and low-cost cathode current collector composed of graphite and carbon nanotube coated on nylon membrane exhibiting corrosion resistance and strong adhesion is developed. Also, a modified aqueous electrolyte with the addition of urea whose window is expanded to ≈3.2 V is developed that contributes to the formation of solid-electrolyte interphase on surfaces of electrodes. LiMn2 O4 /NaTi2 (PO4 )3 Li+ /Na+ hybrid ion battery using such aqueous electrolyte and current collector is demonstrated to cycle up to 10 000 times with low cost (60 dollars per kWh) and high energy density (100 Wh kg-1 ) for stationary energy storage and electronic vehicles applications.

7.
Small ; 16(26): e2001228, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32510836

RESUMO

Aqueous rechargeable Zn/birnessite batteries have recently attracted extensive attention for energy storage system because of their low cost and high safety. However, the reaction mechanism of the birnessite cathode in aqueous electrolytes and the cathode structure degradation mechanics still remain elusive and controversial. In this work, it is found that solvation water molecules coordinated to Zn2+ are coinserted into birnessite lattice structure contributing to Zn2+ diffusion. However, the birnessite will suffer from hydroxylation and Mn dissolution with too much solvated water coinsertion. Through engineering Zn2+ primary solvation sheath with strong-field ligand in aqueous electrolyte, highly reversible [Zn(H2 O)2 ]2+ complex intercalation/extraction into/from birnessite cathode is obtained. Cathode-electrolyte interface suppressing the Mn dissolution also forms. The Zn metal anode also shows high reversibility without formation of "death-zinc" and detrimental dendrite. A full cell coupled with birnessite cathode and Zn metal anode delivers a discharge capacity of 270 mAh g-1 , a high energy density of 280 Wh kg-1 (based on total mass of cathode and anode active materials), and capacity retention of 90% over 5000 cycles.

8.
Angew Chem Int Ed Engl ; 56(11): 2937-2941, 2017 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-28185385

RESUMO

A new family of sulfur-rich phosphorus sulfide molecules (P4 S10+n ) and their electrochemical reaction mechanism with metallic Li has been explored. These P4 S10+n molecules are synthesized by the reaction between P4 S10 and S. For Li batteries, the P4 S40 molecule in the series of P4 S10+n molecules provides the highest capacity, which has a first discharge capacity of 1223 mAh g-1 at 100 mA g-1 and stabilizes at approximately 720 mAh g-1 at 500 mA g-1 after 100 cycles. This new class of sulfur-rich P4 S10+n molecules and its electrochemical behavior for room-temperature Li+ storage could provide novel insights for phosphorus sulfide molecules and high-energy batteries.

9.
Hum Mol Genet ; 23(23): 6385-94, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24986923

RESUMO

Pneumoconiosis is the most serious occupational disease in China and its leading cause is occupational silica exposure. Pneumoconiosis takes several years to develop depending on the exposure level of silica. However, individual variation in the susceptibility to pneumoconiosis has been observed among the subjects with similar exposure. We conducted a genome-wide screening with 710,999 single nucleotide polymorphisms (SNPs) in a cohort of 400 coal workers (202 cases and 198 exposed controls) for pneumoconiosis susceptible loci. Seven promising variants were evaluated in an independent cohort of 568 coal workers (323 cases and 245 exposed controls), followed by a second replication on 463 iron ore workers (167 cases and 296 exposed controls). By pooling all of the genome-wide association studies and replication stages together, we found a genome-wide significant (P < 5.0 × 10(-8)) association for rs73329476 (P = 1.74 × 10(-8), OR = 2.17, 95% CI = 1.66-2.85) and two additional replicated associations for rs4320486 (P < 0.05) and rs117626015 (P < 0.05) with combined P-values of 4.29 × 10(-6) and 5.05 × 10(-6), respectively. In addition, the risk allele T of rs73329476 was significantly associated with lower mRNA expression levels of carboxypeptidase M (CPM) in total cellular RNA from whole blood of 156 healthy individuals (P = 0.0252). The identified pneumoconiosis susceptibility loci may provide new insights into the pathogenesis of pneumoconiosis, and may also have some clinical utility for risk prediction for pneumoconiosis and high-risk population screening for workers with occupational silica exposure.


Assuntos
Loci Gênicos , Exposição Ocupacional/efeitos adversos , Pneumoconiose/genética , Dióxido de Silício/toxicidade , Adolescente , Adulto , Estudos de Casos e Controles , China , Estudos de Coortes , Suscetibilidade a Doenças , Proteínas Ligadas por GPI/genética , Estudo de Associação Genômica Ampla , Humanos , Metaloendopeptidases/genética , Mineração , Pneumoconiose/etiologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Adulto Jovem
10.
Small ; 12(43): 6024-6032, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27626894

RESUMO

Much effort has been made to search for high energy and high power density electrode materials for lithium ion batteries. Here, a composite structure among Ge, C and Cu3Ge in Cu3Ge/Ge/C materials with a high rate performance of lithium batteries has been reported. Such Cu3Ge/Ge/C composite is synthesized through the in-situ formation of Ge, C and Cu3Ge by one-pot reaction. Density function theory (DFT) calculations and electrochemical impedance spectroscopy (EIS) suggest a higher electron mobility of the hibrid Cu3Ge/Ge/C composites through the in-situ preparation. As a result, remarkable charge rate over 300 C (fast delithiated capability) and outstanding cycling stability (≈0.02% capacity decay per cycle for 500 cycles at 0.5 C) are achieved for the Cu3Ge/Ge/C composites anode. These Cu3Ge/Ge/C composites demonstrate another perspective to explore the energy storage materials and should provide a new pathway for the design of advanced electrode materials.

11.
Molecules ; 21(12)2016 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-27898008

RESUMO

Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances. Therefore, in this study, toxic substances of Radix Aconiti have been found using UPLC-Q-TOF-MS technology. Then, we used biochemical indicators as a bridge to find the relationships between biomarkers and toxic substances of Radix Aconiti through Pearson correlation analysis and canonical correlation analysis (CCA). Finally, the CCA results showed that LysoPC(22:5) is related to 14-acetyl-talatisamine, mesaconitine, talatisamine and deoxyaconitine in varying degrees; l-acetylcarnitine is negatively correlated with deoxyaconitine and demethyl-14-acetylkaracoline; shikimic acid has a good correlation with karacoline, demethyl-14-acetylkaracoline and deoxyaconitine; and valine is correlated with talatisamine and deoxyaconitine. Research on these relationships provides an innovative way to interpret the toxic mechanism of traditional Chinese medicine, and plays a positive role in the overall study of TCM toxicity.


Assuntos
Aconitum/química , Biomarcadores/sangue , Medicamentos de Ervas Chinesas/toxicidade , Animais , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Ratos
12.
J Proteome Res ; 14(6): 2437-45, 2015 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-25919346

RESUMO

Drug-induced cardiotoxicity seriously affects human health and drug development. However, many conventional detection indicators of cardiotoxicity exhibit significant changes only after the occurrence of severe heart injuries. Therefore, we investigated more sensitive and reliable indicators for the evaluation and prediction of cardiotoxicity. We created rat cardiotoxicity models in which the toxicity was caused by doxorubicin (20 mg/kg), isoproterenol (5 mg/kg), and 5-fluorouracil (125 mg/kg). We collected data from rat plasma samples based on metabolomics using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Following multivariate statistical and integration analyses, we selected 39 biomarker ions of cardiotoxicity that predict cardiotoxicity earlier than biochemical analysis and histopathological assessment. Because drugs with different toxicities may cause similar metabolic changes compared with other noncardiotoxic models (hepatotoxic and nephrotoxic models), we obtained 10 highly specific biomarkers of cardiotoxicity. We subsequently used a support vector machine (SVM) to develop a predictive model to verify and optimize the exclusive biomarkers. l-Carnitine, 19-hydroxydeoxycorticosterone, LPC (14:0), and LPC (20:2) exhibited the strongest specificities. The prediction rate of the SVM model is as high as 90.0%. This research provides a better understanding of drug-induced cardiotoxicity in drug safety evaluations and secondary development and demonstrates novel ideas for verification and optimization of biomarkers via metabolomics.


Assuntos
Biomarcadores/metabolismo , Coração/efeitos dos fármacos , Metabolômica , Animais , Cardiotoxicidade , Doxorrubicina/toxicidade , Fluoruracila/toxicidade , Isoproterenol/toxicidade , Masculino , Modelos Animais , Ratos , Ratos Wistar
13.
Molecules ; 20(12): 21364-72, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26633333

RESUMO

Simiaowan (SMW) is a famous Chinese prescription widely used in clinical treatment of rheumatoid arthritis (RA). The aim of the present study is to determine novel biomarkers to increase the current understanding of RA mechanisms, as well as the underlying therapeutic mechanism of SMW, in RA-model rats. Plasma extracts from control, RA model, and SMW-treated rats were analyzed by gas chromatography coupled with mass spectrometry (GC-MS). An orthogonal partial least-square discriminant analysis (OPLS-DA) model was created to detect metabolites that were expressed in significantly different amounts between the RA model and the control rats and investigate the therapeutic effect of SMW. Metabonomics may prove to be a valuable tool for determining the efficacy of complex traditional prescriptions.


Assuntos
Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Biomarcadores/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metabolômica , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Análise Discriminante , Análise dos Mínimos Quadrados , Masculino , Ratos , Ratos Wistar
14.
Mol Biol Rep ; 41(7): 4171-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24924948

RESUMO

Coal workers' pneumoconiosis (CWP) is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Genetic variations have been recognized to be involved in the multi-factorial susceptibility to CWP, and MUC5B is a candidate lung fibrosis susceptibility gene. In the present study, we investigated possible genetic associations between three single nucleotide polymorphisms in MUC5B promoter region and CWP in a case-control study including 686 CWP patients and 680 controls. Genotyping was carried out by TaqMan method. Only rs2672794 allele and genotype frequencies distributions were significantly different between CWP patients and controls (P = 0.017 and 0.046 for allele and genotype, respectively). The MUC5B rs2672794 CC genotype was associated with a significantly increased risk of CWP, compared with the TT genotype. Moreover, individuals with TC/CC genotype had an obviously increased risk of CWP than those with TT genotype, particularly among subgroups of dust exposure <27 years and smokers. This is the first report showing an association between the MUC5B rs2672794 polymorphism and CWP, and our results suggest that MUC5B rs2672794 CC genotype could increase the risk of CWP. Further studies are warranted to confirm our findings.


Assuntos
Antracose/genética , Mucina-5B/genética , Doenças Profissionais/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Idoso , Alelos , Antracose/diagnóstico , Antracose/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Minas de Carvão , Frequência do Gene , Genótipo , Humanos , Pessoa de Meia-Idade , Doenças Profissionais/diagnóstico , Doenças Profissionais/epidemiologia , Risco , Fumar
15.
ACS Appl Mater Interfaces ; 16(22): 28391-28401, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38768515

RESUMO

Vanadium oxide has been extensively studied as a host of zinc ion intercalation but still suffers from low conductivity, dissolution, and byproduct accumulation during cycling. Here, we hydrothermally synthesize the VO2@MXene Ti3C2 (MV) composite and find that in the MV//3 M Zn(CF3SO3)2//Zn system, the double hydroxide Zn12(CF3SO3)9(OH)15·nH2O (ZCOH) uniformly covers VO2 during the charging process and dissolves reversibly during the discharge process. In situ X-ray diffraction of the MV combined with in situ pH measurements reveals that ZCOH acts as a pH buffer during cycling, which is beneficial to the cycling stability of batteries. And the theoretical calculation indicates that the decomposition energy required by ZCOH on the MV surface is lower than that on pure VO2, which is more conducive to ZCOH dissolution. The coin battery exhibits high-rate performance of 65.1% capacity retention at a current density of 15 A g-1 (compared to 0.6 A g-1) and a long cycling life of 20,000 cycles with a capacity retention of 80.7%. For a 22.4 mA h soft-packaged battery, its capacity remains at 72.1% after 2000 cycles. This work demonstrates the active role of ZCOH in the electrochemical process of VO2 and provides a new perspective for exploiting this mechanism to develop high-performance aqueous zinc-ion battery vanadium oxide cathode materials.

16.
Clin Transl Med ; 14(5): e1674, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685486

RESUMO

BACKGROUND: The current standard of care for locally advanced gastric cancer (GC) involves neoadjuvant chemotherapy followed by radical surgery. Recently, neoadjuvant treatment for this condition has involved the exploration of immunotherapy plus chemotherapy as a potential approach. However, the efficacy remains uncertain. METHODS: A single-arm, phase 2 study was conducted to evaluate the efficacy and tolerability of neoadjuvant camrelizumab combined with mFOLFOX6 and identify potential biomarkers of response through multi-omics analysis in patients with resectable locally advanced GC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included the R0 rate, near pCR rate, progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS). Multi-omics analysis was assessed by whole-exome sequencing, transcriptome sequencing, and multiplex immunofluorescence (mIF) using biopsies pre- and post-neoadjuvant therapy. RESULTS: This study involved 60 patients, of which 55 underwent gastrectomy. Among these, five (9.1%) attained a pathological complete response (pCR), and 11 (20.0%) reached near pCR. No unexpected treatment-emergent adverse events or perioperative mortality were observed, and the regimen presented a manageable safety profile. Molecular changes identified through multi-omics analysis correlated with treatment response, highlighting associations between HER2-positive and CTNNB1 mutations with treatment sensitivity and a favourable prognosis. This finding was further supported by immune cell infiltration analysis and mIF. Expression data uncovered a risk model with four genes (RALYL, SCGN, CCKBR, NTS) linked to poor response. Additionally, post-treatment infiltration of CD8+ T lymphocytes positively correlates with pathological response. CONCLUSION: The findings suggest the combination of PD-1-inhibitor and mFOLFOX6 showed efficacy and acceptable toxicity for locally advanced GC. Extended follow-up is required to determine the duration of the response. This study lays essential groundwork for developing precise neoadjuvant regimens.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Leucovorina/uso terapêutico , Fluoruracila/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Compostos Organoplatínicos/farmacologia , Resultado do Tratamento , Multiômica
17.
Signal Transduct Target Ther ; 9(1): 73, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528050

RESUMO

Patients with advanced gastric cancer typically face a grim prognosis. This phase 1a (dose escalation) and phase 1b (dose expansion) study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma. The primary endpoints included maximum tolerated dose (MTD) in phase 1a and objective response rate (ORR) across phase 1a and 1b. Phase 1a tested three dose regimens of camrelizumab, apatinib, oxaliplatin, and S-1. Dose regimen 1: camrelizumab 200 mg on day 1, apatinib 250 mg every other day, oxaliplatin 100 mg/m² on day 1, and S-1 40 mg twice a day on days 1-14. Dose regimen 2: same as dose regimen 1, but oxaliplatin 130 mg/m². Dose regimen 3: same as dose regimen 2, but apatinib 250 mg daily. Thirty-four patients were included (9 in phase 1a, 25 in phase 1b). No dose-limiting toxicities occurred so no MTD was identified. Dose 3 was set for the recommended phase 2 doses and administered in phase 1b. The confirmed ORR was 76.5% (95% CI 58.8-89.3). The median progression-free survival was 8.4 months (95% CI 5.9-not evaluable [NE]), and the median overall survival (OS) was not mature (11.6-NE). Ten patients underwent surgery after treatment and the multidisciplinary team evaluation. Among 24 patients without surgery, the median OS was 19.6 months (7.8-NE). Eighteen patients (52.9%) developed grade ≥ 3 treatment-emergent adverse events. Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer (ChiCTR2000034109).


Assuntos
Anticorpos Monoclonais Humanizados , Piridinas , Neoplasias Gástricas , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Oxaliplatina , Piridinas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Quimioterapia Combinada/métodos
18.
Nat Med ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956195

RESUMO

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7-18.1, P = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 .

19.
Mol Biol Rep ; 40(5): 3739-47, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23275204

RESUMO

Emerging evidence indicates that microRNAs (miRNAs), a class of small non-coding regulatory RNAs, have important roles in multiple biological processes. To determine the potential contribution of miRNAs to coal workers' pneumoconiosis (CWP), we comprehensively surveyed and identified differentially expressed miRNA profiles in patients with CWP by small RNA sequencing and analysis. Mixed serum samples from the different stages of CWP and the control samples were subjected to deep sequencing by applying next-generation sequencing technology. Samples at different disease stages exhibited inconsistent miRNA expression profiles and differentially expressed miRNA profiles. Generally, these miRNAs were dynamically expressed across the different disease stages and showed various relative expression levels. Some miRNAs (such as miR-18a*, 149, 222 and 671-3p) were consistently up-regulated or down-regulated in the different stages of CWP samples. Most of the aberrantly expressed miRNAs showed a down-regulation trend. Differentially expressed miRNAs were also subjected to pairwise comparison between the different stages. Some miRNAs showed significant inconsistent expression trends across the three stages, although they were not significantly dysregulated based on the control sample. Furthermore, a series of special miRNAs organized into miRNA gene clusters and gene families were also surveyed for aberrant expression (such as mir-200 gene family and mir-222 gene cluster). According to experimentally validated target mRNAs of the aberrantly and abundantly expressed miRNAs, functional enrichment analysis suggests that these miRNAs play important roles in various biological processes, including lung tumorigenesis. In summary, we demonstrated that aberrantly expressed circulating miRNAs showed dynamic expression patterns across diseased samples, which suggests that these miRNAs may have critical roles in the occurrence and development of CWP. In addition, some significantly dysregulated miRNAs may be potential non-invasive diagnosis biomarkers based on further study.


Assuntos
Antracose/sangue , Antracose/genética , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , MicroRNAs/sangue , Estudos de Casos e Controles , Perfilação da Expressão Gênica , Humanos , Família Multigênica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
20.
Artigo em Chinês | MEDLINE | ID: mdl-23905237

RESUMO

OBJECTIVE: To investigate the quality of life ( QOL) of inpatients with coal workers' pneumoconiosis( CWP) and analyse its influential factors, and to provide a theoretical basis for effective control measures. METHODS: Eighty-eight CWP patients in a hospital were included in the study. A questionnaire survey was conducted in them using a self-designed QOL scale. A database was established by software EpiData3.1, and the obtained data were statistically analyzed by software SPSS 16.0. RESULTS: Of the 88 patients, 73( 82.9%) had middle-level QOL, with a mean QOL loss rate of 36.2%; the loss rates of physical function and somatic sensation were the highest ( 44.2% and 41.5%). The patients with stage II CWP had significantly lower physical function than those with stage I and III CWP; the physical function and social function of patients significantly decreased with age; the personal income, household income, and housing condition of the patients had a marked impact on their physical and psychological functions, and the housing condition and education level had a marked impact on their social function. The multivariate analysis showed that old age, low income,and poor housing condition were the main adverse factors for the QOL of inpatients with CWP. CONCLUSION: The QOL of inpatients with CWP declines significantly, and their QOL is related to the age, income, and satisfaction with housing condition.


Assuntos
Antracose , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade
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