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1.
Artigo em Inglês | MEDLINE | ID: mdl-38753724

RESUMO

In China, non-nucleoside reverse transcriptase inhibitors (NNRTIs) are integral to the antiretroviral therapy (ART) regimen for persons living with HIV (PWH), comprising over 80% of such treatments. To broaden treatment options and improve therapeutic effectiveness, Ainuovirine (ANV), a new NNRTI, was authorized for ART in 2021. Nevertheless, the clinical efficacy of ANV and its impact on blood biochemical markers remain somewhat underexplored. This study seeks to evaluate ANV's clinical performance in ART and its influence on relevant treatment parameters. A retrospective analysis was performed on 208 patients treated with an ANV-based regimen from July 2021 to July 2023, monitoring indicator changes from baseline to week 24. The primary endpoint was the proportion of participants achieving HIV-1 RNA levels of less than 50 copies/mL by week 24. Secondary endpoints involved assessing variations in CD4+ T cell counts and blood biochemical markers from baseline. These outcomes were also compared with data from 241 patients treated with an Efavirenz (EFV)-based regimen in the same time frame. The findings suggest that the ANV-based regimen is as effective as the EFV-based regimen in viral suppression (p > .05) and offers superior improvements in lipid profiles, liver function, and immune system indicators, alongside fewer adverse reactions. These results affirm ANV's efficacy and safety as an antiretroviral therapy option, offering Acquired Immune Deficiency Syndrome patients a wider array of treatment possibilities and the potential for better treatment outcomes.

2.
Psychol Res Behav Manag ; 17: 1611-1624, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628983

RESUMO

Background: Although structured clinical interviews are considered the gold standard for assessing binge eating disorder (BED), the self-administered Binge Eating Scale (BES) has been widely used as a screening tool for BED in clinical research. However, the psychometric properties of the BES among Chinese young adults remain unclear. This study aimed to examine the validity of a Chinese version of the BES with a large sample. Methods: A total of 2182 young adult college students were tested using the Simplified Chinese version of BES (SCBES), the 7-Item Binge-Eating Disorder Screener (BEDS-7), the Zung Self-Rating Depression Scale (SDS), the Generalized Anxiety Disorder Scale (GAD-7), and the Dual-Modes of Self-Control Scale (DMSC). The frequency of objective binge-eating episodes was used as a measure of severity. Validity and reliability of the SCBES were assessed through multiple analyses, along with the item analysis. Results: The data revealed that the SCBES demonstrated reasonable reliability and validity. The Cronbach's α value was 0.813, with a one-month test-retest reliability of 0.835. The exploratory factor analysis (EFA) extracted three first-order factors, which explained a total of 53.82% of the variance. The confirmatory factor analysis (CFA) confirmed the three-factor model (ie, Binge-eating behaviors, Lack of control, Negative affects related to overeating), with a good model fit. The SCBES also demonstrated excellent concurrent and criterion validity, significantly correlating with the BEDS-7 and frequency of objective binge-eating episodes (r=0.760-0.782, p<0.001). Gender, body mass index, depression, anxiety, impulsivity, and self-control were significantly associated with the total score of SCBES. Conclusion: The SCBES demonstrated sound psychometric properties and exhibited good cross-cultural adaptability in Chinese young adults, with a novel three-factor model fitting the data best. This scale could serve as a useful screening tool for identifying the severity of binge eating behaviors among Chinese youths.

3.
Thorac Cancer ; 15(14): 1132-1137, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38572623

RESUMO

BACKGROUND: The simultaneous (synchronous) presence of primary breast cancer and primary lung cancer diagnosed in a single individual is not an uncommon phenomenon. However, reference data for treatment strategy is scarce and "chaotic". In the present study we discuss the management strategy for this group of patients. METHODS: We retrospectively reviewed patients in the primary breast cancer database of the Breast Center and the primary lung cancer database of the Thoracic Surgery Department I of Peking University Cancer Hospital. Patients with synchronous primary breast cancer and primary lung cancer who underwent surgery between December 2010 and December 2023 were included in the study. The sequence of outpatient visits, recommendations of multidisciplinary teams, perioperative treatment, and surgical procedures were reviewed. Meanwhile, survival analysis based on propensity score matching with 1:1 ratio was performed between the 31 patients and those with lung cancer only during the same period. RESULTS: A total of 31 patients with synchronous primary breast cancer and primary lung cancer were identified; all of the patients were women. The average age was 61 years. A total of 24 of the patients had visited the breast center first, and routine chest computed tomography (CT) showed evidence of primary lung cancer. The other seven patients had visited the thoracic surgery clinic first, and routine positron emission tomography (PET)-CT revealed the coexistence of primary breast cancer. All the patients had multidisciplinary team consultations, after which 20 patients were recommended to have preoperative treatment for breast cancer, two patients were recommended to have preoperative treatment for lung cancer, and nine patients were recommended to undergo surgery directly. After surgery, 23 patients received postoperative adjuvant treatment for breast cancer, and no patients needed postoperative adjuvant treatment for lung cancer. Survival analysis showed that there was no significant difference between the 31 patients and those with lung cancer only. CONCLUSION: Routine chest CT is needed for breast cancer patients before surgery, and PET-CT is required for the accurate staging of lung cancer patients. A multidisciplinary expert team should manage synchronous primary breast cancer and primary lung cancer. Emphasis should be placed on patients who need preoperative treatment before surgery. Particularly, for patients who need preoperative chemotherapy, a regimen should be chosen that balances the treatment of lung cancer and breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Neoplasias Primárias Múltiplas , Humanos , Feminino , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Neoplasias da Mama/cirurgia , Estudos Retrospectivos , Neoplasias Primárias Múltiplas/terapia , Neoplasias Primárias Múltiplas/patologia , Idoso , Adulto
4.
Phys Chem Chem Phys ; 26(4): 3159-3167, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38190261

RESUMO

A superior piezoelectric coefficient and diminutive lattice thermal conductivity are advantageous for the application of a two-dimensional semiconductor in piezoelectric and thermoelectric devices, whereas an imperfect piezoelectric coefficient and large lattice thermal conductivity limit the practical application of the material. In this study, we investigate how the equibiaxial strain regulates the electronic structure, and mechanical, piezoelectric, and thermal transport properties. Tensile strain can deduce the bandgap of the monolayer CrX2 (X = S, Se, Te), whereas compressive strain has an opposite effect. Additionally, the transition from a semiconductor to a metal state and the transition between direct and indirect band gaps will occur at appropriate strain values, so the electronic structure can be effectively regulated. The reason is the different sensitivities of the energy corresponding to K and Γ on the valence band to the strain due to the changes in different orbital overlaps. The tensile strain can effectively improve the flexibility of monolayers CrX2, which provides a possibility for the application of flexible electronic devices. Furthermore, the tensile strain can improve the piezoelectric strain coefficient of monolayers CrX2. Using Slacks formulation, we calculate the lattice thermal conductivity, and the tensile biaxial strain can reduce the lattice thermal conductivity. Our research provides a strategy to enhance the piezoelectric and flexible electronic applications and decrease the lattice thermal conductivity, which can benefit the thermoelectric applications.

5.
Ann Surg Oncol ; 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172446

RESUMO

BACKGROUND: The higher pathologic complete response (pCR) after neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) has not translated into significant gains in overall survival. Data on the long-term survival of patients who obtained a pCR after neoadjuvant chemotherapy are scarce. Therefore, this study aimed to evaluate the long-term prognosis and recurrence patterns in these patients. METHODS: The study enrolled patients with locally advanced ESCC after neoadjuvant chemotherapy followed by surgery in the authors' hospital between January 2007 and December 2020. The factors predictive of pCR were analyzed. Furthermore, propensity score-matching was performed for those who did and those who did not have a pCR using 1:5 ratio for a long-term survival analysis. Finally, the survival and recurrence patterns of patients obtaining pCR after neoadjuvant chemotherapy were analyzed. RESULTS: A pCR was achieved for 61 (8.70%) of the 701 patients in the study. Univariate analysis showed that the patients without alcohol drinking had a higher possibility of obtaining a pCR, although multivariate analysis failed to confirm the difference as significant. After propensity score-matching, the 5-year overall survival was 84.50% for the patients who had a pCR and 52.90% for those who did not (p < 0.001). Among the 61 patients with a pCR, 9 patients (14.80%) experienced recurrence, including 6 patients with locoregional recurrence and 3 patients with distant metastasis. CONCLUSION: Advanced ESCC patients with pCR after neoadjuvant chemotherapy had a favorable prognosis, yet some still experienced recurrence, particularly locoregional recurrence. Therefore, for this group of patients, regular follow-up evaluation also is needed.

6.
Artigo em Inglês | MEDLINE | ID: mdl-37995811

RESUMO

BACKGROUND: Compulsivity represents the performance of persistent and repetitive acts despite negative consequences and is considered one of the critical mechanisms for drug addiction. Although compulsivity-related neurocognitive impairments have been linked to addiction, it remains unclear whether these deficits might have predated drug abuse as potential familial susceptibilities. METHODS: A large sample of 213 adult participants were recruited, including 70 abstinent individuals addicted to heroin (HAs), 69 unaffected biological siblings of the HAs (siblings), and 74 unrelated healthy control participants. Compulsivity-related neurocognitive functions were evaluated using the intradimensional/extradimensional set-shift task and a probabilistic reversal learning task. Compulsive traits were measured by the Obsessive-Compulsive Inventory-Revised. Inhibitory control was assessed using the stop signal task and Stroop Color and Word Test. Network models for group recognition were conducted using multilayer perceptron neural networks. RESULTS: Data indicated that both HAs and siblings performed worse than healthy control participants on compulsivity-related aspects (i.e., shifting and reversal learning functions) and inhibitory control and had higher levels of self-reported compulsive traits. Furthermore, neural models revealed that a possible 3-facet clustering of neurocognitive deficits was linked to both HAs and siblings. CONCLUSIONS: Our findings suggest that deficits in shift reversal and inhibitory control aspects and elevated compulsive traits, shared by HAs and their unaffected siblings, may putatively represent conceivable markers associated with familial vulnerabilities implicated in the development of heroin dependence.


Assuntos
Comportamento Aditivo , Dependência de Heroína , Humanos , Adulto , Dependência de Heroína/psicologia , Comportamento Impulsivo , Irmãos , Autorrelato
7.
CNS Neurosci Ther ; 30(4): e14465, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37830163

RESUMO

PURPOSES: To identify potent DNA methylation candidates that could predict response to temozolomide (TMZ) in glioblastomas (GBMs) that do not have glioma-CpGs island methylator phenotype (G-CIMP) but have an unmethylated promoter of O-6-methylguanine-DNA methyltransferase (unMGMT). METHODS: The discovery-validation approach was planned incorporating a series of G-CIMP-/unMGMT GBM cohorts with DNA methylation microarray data and clinical information, to construct multi-CpG prediction models. Different bioinformatic and experimental analyses were performed for biological exploration. RESULTS: By analyzing discovery sets with radiotherapy (RT) plus TMZ versus RT alone, we identified a panel of 64 TMZ efficacy-related CpGs, from which a 10-CpG risk signature was further constructed. Both the 64-CpG panel and the 10-CpG risk signature were validated showing significant correlations with overall survival of G-CIMP-/unMGMT GBMs when treated with RT/TMZ, rather than RT alone. The 10-CpG risk signature was further observed for aiding TMZ choice by distinguishing differential outcomes to RT/TMZ versus RT within each risk subgroup. Functional studies on GPR81, the gene harboring one of the 10 CpGs, indicated its distinct impacts on TMZ resistance in GBM cells, which may be dependent on the status of MGMT expression. CONCLUSIONS: The 64 TMZ efficacy-related CpGs and in particular the 10-CpG risk signature may serve as promising predictive biomarker candidates for guiding optimal usage of TMZ in G-CIMP-/unMGMT GBMs.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Metilação de DNA , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Glioma/genética , Metilases de Modificação do DNA/genética , Fenótipo , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Proteínas Supressoras de Tumor/genética , Enzimas Reparadoras do DNA/genética
8.
Plant Dis ; 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38085241

RESUMO

Cowpea (Vigna unguiculata L.), a significant vegetable crop in China, holds particular prominence in the tropical island of Hainan. This region serves as the primary production area for the winter cultivation of cowpea. Phytoplasmas are an idiopathic parasitic pathogen and cannot be cultured in vitro. It is mainly transmitted by the insect vectors with the piercing and sucking mouthparts, such as leafhoppers, plant hoppers, and psyllids. (Kumari et al. 2019). On September 11, 2023, typical characteristics of phytoplasma diseases on cowpeas were observed in the experimental base of Hainan Academy of Agricultural Sciences (20°0'38.6964″N, 110°21'35.4024″E, Haikou City, Hainan Province, China), including reduced leaf size, chlorosis, and the development of broom-like branch deformities reminiscent, as depicted in Figure 1. At the same time, we found a large number of leafhoppers near the diseased plants, and we speculated that leafhoppers are the insect carriers that spread the disease. Following an on-site investigation, it was determined that the disease incidence ranges from 10% to 15%, leading to a consequential decrease of about 10% in yield, which is a potential disease that seriously threatens the cowpea industry in Hainan. Ten disease and healthy samples were meticulously collected and subsequently preserved at -80°C within the laboratory refrigerator. Three disease samples denoted as HNNKY-1, HNNKY-2, and HNNKY-3, were randomly chosen, and total DNA extraction was carried out employing the NuClean Plant Genomic DNA Kit (CWBIO, Taizhou, China), while three healthy samples were randomly selected as control. The 16S rRNA gene was amplified by PCR using the primer pairs P1/P7 (Schneider et al. 1995) and R16F2n / R16R2 (Lee et al. 1993) and the secA gene was amplified by PCR using the primer pairs secAfor1/secArev3 (Hodgetts et al. 2008). After agarose gel electrophoresis analysis, no DNA fragments were observed in the healthy leaf samples, whereas all three disease samples yielded amplification products. The PCR products were subsequently sequenced by Hainan Nanshan Biotech Co., Ltd., Haikou, China. After sequence analysis, it was found that the 16S rRNA gene and secA gene sequences HNNKY-1, HNNKY-2, and HNNKY-3 were identical to each other. We selected two gene sequences of strain HNNKY-3 to submission to the GenBank database, The length of the 16S rRNA gene sequence is 1193 base pairs, identified by the accession number OR666421, while the secA gene sequence is 825 base pairs in length, associated with the accession number OR661282. The phytoplasma strain HNNKY-3 was named 'Vigna unguiculata' witches'-broom phytoplasma. A BLAST analysis of the 16S rRNA gene revealed that strain HNNKY-3 displayed a 100% sequence match with 'Emilia sonchifolia' witches'-broom phytoplasma (MT420682), Peanut witches'-broom phytoplasma (OR239773), and 'Raphanus sativus' witches'-broom phytoplasma (OK491387). All of these phytoplasmas were classified within the 16SrII group. Based on the BLAST analysis of partial secA gene sequences, it was discerned that sequence homogeneity ranged from 99.27% to 99.74% among the studied sequences. These sequences were collectively classified as members of the 16SrII group. In addition, a phylogenetic tree was constructed by MEGA 11 (version 11.0.13) based on the 16Sr RNA gene and secA gene by the neighbor-joining method (Tamura et al. 2004). The results demonstrated the clustering of HNNKY-3 phytoplasma strains within the 16SrII group, as illustrated in Figures 2 and 3. A virtual RFLP analysis based on the 16S rRNA gene fragment of HNNKY-3 was conducted using the interactive online phytoplasma classification tool, iPhyClassifier (Zhao et al. 2009). The results indicated that the phytoplasma strain was the same as the reference pattern of the onion yellows phytoplasma of 16SrII-A (GenBank accession: L33765), and the similarity coefficient was 1.00. To best of our knowledge, this is the inaugural documentation of 16SrII Group-related phytoplasma infecting cowpea in Hainan, China, and lays the groundwork for further research on the dissemination of cowpea phytoplasma disease within China.

9.
Psychol Res Behav Manag ; 16: 4737-4748, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38024662

RESUMO

Background: Similar to addictive disorders, deficits on cognitive control might be involved in the onset and development of Binge Eating Disorder (BED). However, it remains unclear whether general or food-related inhibitory control impairments would be basically linked to overeating and binge eating behaviors. This study thus aimed to investigate behavioral performance and electrophysiological correlates of food-related inhibitory control among individuals with binge eating behavior. Methods: Sixty individuals with probable BED (pBED) and 60 well-matched healthy controls (HCs) were assessed using the typical Stop-Signal Task, a revised Go/No Go Task, and a food-related Go/No Go Task. Besides, another separate sample, including 35 individuals with pBED and 35 HCs, completed the food-related Go/No Go Task when EEG signals were recorded with the event-related potentials (ERPs). Results: The data revealed that the pBED group performed worse with a longer SSRT on the Stop-Signal Task compared with HCs (Cohen's d = 0.58, p = 0.002). Moreover, on the food-related Go/No Go Task, the pBED group had a lower success rate of inhibition in no-go trials (Cohen's d = 0.47, p = 0.012). The ERPs data showed that in comparison with HCs, the pBED group exhibited increased P300 latency (FC1, FC2, F3, F4, FZ) in the no-go trials of the food-related Go/No Go Task (Cohen's d 0.56-0.73, all p < 0.05). Conclusion: These findings suggested that individuals with binge eating could be impaired in both non-specific and food-related inhibitory control aspects, and the impairments in food-related inhibitory control might be linked to P300 abnormalities, implying a behavioral-neurobiological dysfunction mechanism implicated in BED.

11.
Environ Pollut ; 336: 122425, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37604393

RESUMO

The antibiotic pollution emerged in different environments has raised a great concern. Adsorption is an effective method to solve the problem. However, conventional adsorbents are not always efficient for antibiotic removal with interferences. Therefore, in this study, molecularly imprinted polymer (EMIP) with selective adsorption ability was prepared to remove a typical antibiotic-erythromycin (ERY) at environmentally relevant concentration. The specific surface area of EMIP was 265.62 m2/g with large pore volume, small pore size and hydrophobic surface. The adsorption capacity of EMIP was increased from 211.08 to 4015.51 µg/g when the concentration of ERY was increased from 5.00 to 100.00 µg/L. The isothermal adsorption process was fitted well with the Langmuir model. The adsorption kinetic could be well described by the pseudo-second-order model. With co-existing of interferences, the imprinting factor for ERY was 2.57, which demonstrated EMIP had good adsorption selectivity. After five consecutive adsorption-desorption experiments, the adsorption capacity of EMIP was still over 80%. The results of molecular dynamic simulation showed the adsorption energy between ERY and EMIP was high, which was favorable for ERY adsorption removal. Hopefully, the results of this study could provide new insights for trace antibiotic removal by molecular imprinting polymers in different aqueous environments.

12.
J Med Chem ; 66(16): 11335-11350, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37552639

RESUMO

Artemisinin, a prominent anti-malaria drug, is being investigated for its potential as a repurposed cancer treatment. However, its effectiveness in tumor cell lines remains limited, and its mechanism of action is unclear. To make more progress, the PROteolysis-TArgeting chimera (PROTAC) technique has been applied to design and synthesize novel artemisinin derivatives in this study. Among them, AD4, the most potent compound, exhibited an IC50 value of 50.6 nM in RS4;11 cells, over 12-fold better than that of its parent compound, SM1044. This was supported by prolonged survival of RS4;11-transplanted NOD/SCID mice. Meanwhile, AD4 effectively degraded PCLAF in RS4;11 cells and thus activated the p21/Rb axis to exert antitumor activity by directly targeting PCLAF. The discovery of AD4 highlights the great potential of using PROTACs to improve the efficacy of natural products, identify therapeutic targets, and facilitate drug repurposing. This opens a promising avenue for transforming other natural products into effective therapies.


Assuntos
Artemisininas , Quimera de Direcionamento de Proteólise , Animais , Camundongos , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Reposicionamento de Medicamentos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteólise
13.
BMC Psychiatry ; 23(1): 512, 2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-37452290

RESUMO

OBJECTIVES: Non-suicidal self-injury (NSSI) behavior is a severe public health issue in adolescents. This study investigated the possible impact of the coronavirus disease 2019 (COVID-19) and analyzed psychological risk factors on adolescent NSSI. METHODS: A one-year follow-up study was conducted in September 2019 (Time 1) and September 2020 (Time 2) among 3588 high school students. The completed follow-up participants (N = 2527) were classified into no NSSI (negative at both time points), emerging NSSI (negative at Time 1 but positive at Time 2), and sustained NSSI (positive at both time points) subgroups according to their NSSI behaviors before and during the COVID-19 pandemic. Perceived family functioning, perceived school climate, negative life events, personality traits (neuroticism, impulsivity, and self-control) were assessed using self-report scales. RESULTS: The data indicated an increase (10.3%) in the incidence of NSSI. Compared to no NSSI subjects, the emerging NSSI and sustained NSSI subgroups had lower perceived family functioning, higher neuroticism, higher impulse-system but lower self-control scores, and more negative life events. Logistic regressions revealed that after controlling for demographics, neuroticism and impulse-system levels at Time 1 positively predicted emerging NSSI behavior, and similarly, higher neuroticism and impulsivity and lower self-control at Time 1 predicted sustained NSSI behavior. CONCLUSIONS: These findings highlighted the aggravated impact of the COVID-19 on NSSI, and suggested that individual neuroticism, impulsivity, and self-control traits might be crucial for the development of NSSI behavior among adolescent students.


Assuntos
COVID-19 , Comportamento Autodestrutivo , Adolescente , Humanos , Seguimentos , Pandemias , COVID-19/epidemiologia , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/psicologia , Estudantes/psicologia , Fatores de Risco
14.
Phys Chem Chem Phys ; 25(15): 10827-10835, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37013675

RESUMO

In this paper, the electronic band structure, Rashba effect, hexagonal warping, and piezoelectricity of Janus group-VIA binary monolayers STe2, SeTe2, and Se2Te are investigated based on density functional theory (DFT). Due to the inversion asymmetry and spin-orbit coupling (SOC), the STe2, SeTe2 and Se2Te monolayers exhibit large intrinsic Rashba spin splitting (RSS) at the Γ point with the Rashba parameters 0.19 eV Å, 0.39 eV Å, and 0.34 eV Å, respectively. Interestingly, based on the k·p model via symmetry analysis, the hexagonal warping effect and a nonzero spin projection component Sz arise at a larger constant energy surface due to nonlinear k3 terms. Then, the warping strength λ was obtained by fitting the calculated energy band data. Additionally, in-plane biaxial strain can significantly modulate the band structure and RSS. Furthermore, all these systems exhibit large in-plane and out-of-plane piezoelectricity due to inversion and mirror asymmetry. The calculated piezoelectric coefficients d11 and d31 are about 15-40 pm V-1 and 0.2-0.4 pm V-1, respectively, which are superior to those of most reported Janus monolayers. Because of the large RSS and piezoelectricity, the studied materials have great potential for spintronic and piezoelectric applications.

15.
Signal Transduct Target Ther ; 8(1): 76, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36823150

RESUMO

EMERGING-CTONG 1103 showed improved progression-free survival (PFS) with neoadjuvant erlotinib vs. chemotherapy for patients harbouring EGFR sensibility mutations and R0 resected stage IIIA-N2 non-small cell lung cancer (NSCLC) (NCT01407822). Herein, we report the final results. Recruited patients were randomly allocated 1:1 to the erlotinib group (150 mg/day orally; neoadjuvant phase for 42 days and adjuvant phase to 12 months) or to the GC group (gemcitabine 1250 mg/m2 plus cisplatin 75 mg/m2 intravenously; 2 cycles in neoadjuvant phase and 2 cycles in adjuvant phase). Objective response rate (ORR), complete pathologic response (pCR), PFS, and overall survival (OS) were assessed along with safety. Post hoc analysis was performed for subsequent treatments after disease recurrence. Among investigated 72 patients (erlotinib, n = 37; GC, n = 35), the median follow-up was 62.5 months. The median OS was 42.2 months (erlotinib) and 36.9 months (GC) (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.47-1.47; p = 0.513). The 3- and 5-year OS rates were 58.6% and 40.8% with erlotinib and 55.9% and 27.6% with GC (p3-y = 0.819, p5-y = 0.252). Subsequent treatment was administered in 71.9% and 81.8% of patients receiving erlotinib and GC, respectively; targeted therapy contributed mostly to OS (HR, 0.35; 95% CI, 0.18-0.70). After disease progression, the ORR was 53.3%, and the median PFS was 10.9 months during the EGFR-TKI rechallenge. During postoperative therapy, grade 3 or 4 adverse events (AEs) were 13.5% in the erlotinib group and 29.4% in the GC group. No serious adverse events were observed. Erlotinib exhibited clinical feasibility for resectable IIIA-N2 NSCLC over chemotherapy in the neoadjuvant setting.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Cloridrato de Erlotinib , Cisplatino , Gencitabina , Terapia Neoadjuvante , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases , Receptores ErbB/genética , Desoxicitidina , Análise de Sobrevida
16.
Dis Esophagus ; 36(6)2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-36533426

RESUMO

Chylothorax is an important complication after esophagectomy. Ligation of the injured thoracic duct is the main method to prevent chylothorax after esophagectomy, but may be associated with adverse effects. Whether ligation of the injured tributary alone, keeping the main trunk intact, may suffice to prevent post-operative chylothorax is not well known. Since March 2017, 40 mL of olive oil was administered to patients posted for esophagectomy. We compared patients admitted between March 2017 and December 2019 with patients admitted between July 2014 and February 2017, who had not received pre-operative oil. The outcome measures were the need for thoracic duct main trunk or tributary ligation, development of chylothorax and missed ligation. There were 371 patients in the oil ingestion group and 308 patients in the standard control group. Chylothorax in the oil ingestion group was significantly lower than that in the standard control group (1.3% vs. 4.5%, P = 0.012). Chyle leak from thoracic duct tributaries was diagnosed in a significantly higher percentage (5.7% vs. 0.0%, P < 0.001) and missed ligation of the injured thoracic duct was significantly lower (0.3% vs. 3.9%, P = 0.002) in the oil ingestion group compared with the standard control group. The incidence of post-operative chylothorax was not statistically different (6.3% vs. 10.0%, P = 1.000) between the tributary and the trunk ligation group. Pre-operative oil ingestion can help visualize the thoracic duct trunk and its tributaries during esophagectomy. Thus, non-selected thoracic duct trunk ligation and missed ligation during esophagectomy can be reduced. Precise ligation of the injured tributary while the main trunk is intact can also prevent post-operative chylothorax.


Assuntos
Quilotórax , Neoplasias Esofágicas , Humanos , Ducto Torácico/cirurgia , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/cirurgia , Neoplasias Esofágicas/complicações , Probabilidade , Quilotórax/etiologia , Quilotórax/prevenção & controle , Quilotórax/cirurgia , Ingestão de Alimentos
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-982062

RESUMO

OBJECTIVE@#To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML).@*METHODS@#The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored.@*RESULTS@#The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients.@*CONCLUSION@#VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.


Assuntos
Adulto , Humanos , Estudos Retrospectivos , Neoplasia Residual/tratamento farmacológico , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Recidiva , Leucemia Mieloide Aguda/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
18.
Journal of Clinical Hepatology ; (12): 552-561, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-971892

RESUMO

Objective To investigate the association between the polymorphism of the microsomal triglyceride transport protein (MTTP) gene at rs1800591 locus and the risk of nonalcoholic fatty liver disease (NAFLD) in the elderly population. Methods The clinical cohort of this study was established in Menkuang Hospital, Beijing Jingmei Group General Hospital. A total of 1098 healthy elderly volunteers were recruited for physical examination in communities in Mentougou District of Beijing, China, from January 11, 2020 to September 30, 2021, among whom there were 614 patients with NAFLD and 484 individuals without NAFLD. Gene microarray was used to determine the genotypes of MTTP rs1800591; demographic data were collected, and blood biochemical parameters were measured. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The chi-square test was used to investigate whether the distribution of genotype frequency was in accordance with Hardy-Weinberg equilibrium. The unconditional logistic regression model was used to calculate odds ratio ( OR ) and its 95% confidence interval ( CI ) to investigate the association of gene polymorphism with the risk of NAFLD and other comorbidities. Results There were significant differences in sex and age between the two groups ( P < 0.05). Compared with the non-NAFLD group, the NAFLD group had significantly higher levels of body mass index (BMI), waist-hip ratio, triglyceride, alanine aminotransferase, aspartate aminotransferase, controlled attenuation parameter (CAP), and liver stiffness measurement and a significantly lower level of high-density lipoprotein (HDL) (all P < 0.05). Compared with the non-NAFLD group, the NAFLD group had a significantly higher proportion of patients with hypertension, diabetes, obesity, and metabolic syndrome (all P < 0.05). The distribution of genotype frequency at MTTP rs1800591 locus was in accordance with Hardy-Weinberg equilibrium in the control group ( χ 2 =1.097, P =0.29). There were a significant differences in the genotype and the distribution of alleles at MTTP rs1800591 locus between the patients with NAFLD and the control group (all P < 0.001). In the total population, there was a significantly lower carrying rate of T allele (GT+TT, n =351) in male individuals, and the individuals carrying T allele had significantly higher BMI and CAP than those carrying GG allele ( n =747) ( P < 0.001). Compared with the individuals who did not carry T allele, the individuals carrying T allele (GT+TT, n =232) had a significantly higher proportion of patients with obesity and a significantly lower NFS score ( P < 0.05). As for the individuals with NAFLD, the individuals carrying T allele had a significantly lower proportion of male individuals, a significantly lower waist-hip ratio, and a significantly higher level of HDL compared with those who did not carry T allele (GG, n =382), and the GT+TT group had a significantly lower NFS score than the GG group (all P < 0.05). The non-conditional logistic regression analysis showed that after adjustment for the confounding factors of sex, age, and BMI, the GT+TT genotype at MTTP rs1800591 locus significantly increased the risk of NAFLD ( OR =1.643, 95% CI : 1.226-2.203, P =0.001), and carrying T allele also increased the risk of obesity in the total population ( OR =1.371, 95% CI : 1.051-1.788, P =0.02). Conclusion MTTP rs1800591 polymorphism is associated with the development of NAFLD in the elderly population, and carrying T allele may promote hepatic steatosis and increase the risk of obesity in NAFLD, while it may inhibit the progression of liver fibrosis.

19.
Ecotoxicol Environ Saf ; 241: 113826, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36068753

RESUMO

Endometriosis is a chronic, inflammatory, estrogen-dependent gynecological disease characterized by the growth of endometrial stromal cells and glands outside the uterine cavity in response to hormones, which commonly occurs in reproductive-age women. Zearalenone (ZEA) is a toxic metabolite produced by Fusarium, which acts as estrogen activity because of the similarity of its structure to estrogen. In this study, we used an endometriosis mouse model: 15 days after ovariectomy, endometrial fragments were sutured on the pelvic wall, and exogenous estrogen was supplied using an estrogen-releasing silicone tube embedded subcutaneously. Mice were treated with different doses of ZEA by gavage for 21 days. The results show that ZEA significantly inhibited the growth of ectopic endometrium in a dose-dependent manner. The proliferation of cells decreased while apoptosis increased in the ectopic tissues of ZEA-treated mice compared to the vehicle group. The expression of estrogen receptor-α and its downstream targets MUC1 and p-AKT decreased, indicating an impaired estrogen signaling activity by ZEA treatment. In addition, the decreased expression of pro-inflammatory cytokine Tnf-α, Il-1ß, and Il-6, the lower number of macrophages and neutrophils cells, and the inhibited NF-κB signaling pathway suggest the inflammatory response in the ectopic endometrium was also suppressed by ZEA treatment. However, when the exogenous estrogen supply is removed, ZEA, in turn, plays an estrogen-like role that promotes cell proliferation in the ectopic endometrium. In summary, our data suggest ZEA acts as an antagonist in endometriotic tissue when estrogen is sufficient but turns to estrogenic activity in the absence of estrogen in the development of endometriosis. ZEA also inhibits ectopic tissue growth by inhibiting inflammatory response in the endometriosis model.


Assuntos
Endometriose , Zearalenona , Animais , Endometriose/tratamento farmacológico , Endometriose/metabolismo , Endométrio/metabolismo , Estrogênios/metabolismo , Estrogênios/toxicidade , Feminino , Humanos , Camundongos , Transdução de Sinais , Zearalenona/toxicidade
20.
Front Psychiatry ; 13: 838700, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35479492

RESUMO

Background: Binge eating disorder (BED) as a public health problem has been included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Akin to addictive disorders, impulsivity-related neuropsychological constructs might be potentially involved in the onset and development of BED. However, it remains unclear which facets of impulsivity are connected to overeating and binge eating behaviors among non-clinical populations. The present study aimed to detect the relationship between impulsivity and binge eating both on the personality-trait and behavioral-choice levels in undiagnosed young adults. Methods: Fifty-eight individuals with probable BED and 59 healthy controls, matched on age, gender, and educational level, were assessed by using a series of self-report measurements, including the Barratt Impulsiveness Scale (BIS-11), UPPS-P Impulsive Behaviors Scale (UPPS-P), Delay Discounting Test (DDT), and Probability Discounting Test (PDT). Results: Multivariate analysis of variance models revealed that compared with healthy controls, the probable BED group showed elevated scores on the BIS-11 Attentional and Motor impulsiveness, and on the UPPS-P Negative Urgency, Positive Urgency, and Lack of Perseverance. However, the probable BED subjects had similar discounting rates on the DDT and PDT with healthy controls. Regression models found that Negative Urgency was the only positive predictor of binge eating behavior. Conclusions: These findings suggested that typical facets of trait impulsivity, which have been recognized in addictive disorders, were associated with binge eating in young adults, whereas choice impulsivity was not aberrantly seen in the same probable BED sample. This study might promote a better understanding of the pathogenesis of BED.

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