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1.
Medicine (Baltimore) ; 103(19): e38035, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728451

RESUMO

OBJECTIVE: The objective of this meta-analysis is to evaluate the diagnostic performance of acoustic radiation force impulse (ARFI) in acute pancreatitis (AP) patients. METHODS: PubMed, Web of Science, Embase, Wanfang, Chinese Biological Medicine databases, and Chinese Biomedical Literature Service System were searched for relevant studies to explore the potential diagnostic performance of ARFI in AP from inception to November 2023. STATA 14.0 was used to analyze the standardized mean difference (SMD) with 95% confidence interval (CI), pooled sensitivity, specificity, area under the curve, meta-regression analysis, sensitivity analysis, and publication bias. RESULTS: Nine studies, involving 533 AP patients and 585 healthy controls, were included. AP patients had significantly higher ARFI levels than healthy controls (SMD: 3.13, 95% CI: 1.88-4.39, P = .001). The area under the curve of ARFI for diagnosing AP was 0.99 (95% CI: 0.98-1.00), with 98% sensitivity and 94% specificity. Meta-regression identified the study region and study period as the sources of heterogeneity. Sensitivity analysis showed that the exclusion of any single study did not materially alter the overall combined effect. No evidence of publication bias was observed in the included studies. CONCLUSION: This meta-analysis demonstrated that ARFI exerted satisfactory diagnostic performance in AP.


Assuntos
Técnicas de Imagem por Elasticidade , Pancreatite , Sensibilidade e Especificidade , Humanos , Pancreatite/diagnóstico , Pancreatite/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Doença Aguda
2.
J Pain Res ; 17: 1583-1594, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707266

RESUMO

Objective: Moderate-to-severe pain is the most common clinical symptom in patients with hepatocellular carcinoma (HCC).This trial aimed to analyze the clinical efficacy of Transcutaneous electrical acupoint stimulation (TEAS) in patients of HCC with severe pain and provide a reliable reference for optimizing the clinical diagnostic and therapeutic strategies of HCC. Methods: A total of 104 eligible patients were randomly allocated to experimental and control groups in a ratio of 1:1.The treatment was administered for 1 week continuously. Patients in both groups were followed up 1 week after the end of the treatment.The primary outcome measure was the Numerical Rating Scale (NRS) score, whereas the secondary outcome measures included Brief Pain Inventory BPI-Q3, Q4, Q5 scores, analgesic dose, frequency of opioid-induced gastrointestinal side effects, Karnofsky Performance Status (KPS), Quality of Life Scale - Liver Cancer (QOL-LC), and Brief Fatigue Inventory (BFI) scores. Results: The NRS scores of experimental group was significantly lower after treatment and at the follow-up than baseline (average P<0.01), there were also statistical differences between the groups at the above time points (average P<0.01). BPI-Q3, -Q4, and -Q5 scores in the experimental group were decreased after treatment when compared with those before treatment (average P<0.01). Furthermore, there were significant improvements of gastrointestinal side effects, KPS, QOL-LC and BPI in the experimental group after treatment, and the above results were statistically significant compared to the control group. Conclusion: 7-day TEAS treatment can significantly enhance the analgesic effect and maintain for the following week, also reduce the incidence of gastrointestinal side effects caused by opioids, and improve the quality of life of patients with moderate-to-severe HCC-related pain, which has reliable safety and certain clinical promotion value.

3.
Cancer Manag Res ; 16: 347-359, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707745

RESUMO

Baihe Gujin decoction is one of the most commonly used decoction in traditional Chinese medicine for the treatment of lung cancer. It can nourish yin and moisten the lung as well as prevent phlegm from forming and stop coughing. On the one hand, Baihe Gujin decoction is characterized with extensive application, proven efficacy, a long history, and high safety. On the other hand, Baihe Gujin decoction can induce apoptosis of tumor cells, improve immune function and inhibit inflammation. The main anti-tumor components of this include kaempferol, quercetin, isorhamnetin, glycyrrhizin and ß-sitosterol. Clinically, Baihe Gujin decoction can improve the adverse reactions caused by radiotherapy, chemotherapy and immunotherapy for lung cancer, enhance the quality of life of patients, and prolong their survival time. At present, there are a large number of clinical and basic researches on the treatment of lung cancer with Baihe Gujin decoction. In this paper, we mainly discussed the treatment of lung cancer with Baihe Gujin decoction through analyzing basic and clinical researches at home and abroad in the past 20 years. Through the discussion, we aimed to probe deeper into Baihe Gujin decoction for the treatment of lung cancer, thereby providing a broader idea for clinical diagnosis and treatment of lung cancer.

4.
Arab J Gastroenterol ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38719665

RESUMO

BACKGROUND AND STUDY AIMS: Endoscopic submucosal excavation (ESE) and endoscopic full-thickness resection (EFTR) are common endoscopic minimally invasive methods for treatment of gastric submucosal tumors (SMTs). However, it is sometimes difficult to expose the tumor optimally. This study aimed to explore the safety and effectiveness of tumor traction using orthodontic rubber band (ORB) combined with clips to assist ESE and EFTR of gastric SMTs. PATIENTS AND METHODS: The data of patients with gastric SMTs who underwent ESE or EFR at the Endoscopy Center of the 900th Hospital of PLA from January 2021 to May 2022 were retrospectively analyzed. Baseline characteristics and clinical outcomes, including operation time and postoperative adverse events, were compared between patients receiving ORB-ESE/EFTR and conventional ESE/EFTR. RESULTS: A total of 52 patients were enrolled: 16 patients who underwent ORB-ESE /EFTR and 36 patients who underwent conventional ESE/EFTR. Median procedure time was significantly shorter in the ORB-ESE/EFTR group than in the conventional ESE/EFTR group (32 [IQR, 23.8, 38.0] minutes vs. 39.0 [IQR, 34.6-67.3] minutes, P = 0.002). Baseline characteristics, en bloc resection rate, incidence of postoperative adverse events, and postoperative pathology results were comparable between the two groups (P > 0.05). CONCLUSION: Use of ORB with clips-assisted traction during ESE/EFTR of gastric SMT can shorten the surgical time. Further large prospective studies are needed to confirm the findings of this study.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38733444

RESUMO

Volatile organic compounds (VOCs) frequently pose a threat to the biosphere, impacting ecosystems, flora, fauna, and the surrounding environment. Industrial emissions of VOCs often include the presence of water vapor, which, in turn, diminishes the adsorption capacity and efficacy of adsorbents. This occurs due to the competitive adsorption of water vapor, which competes with target pollutants for adsorption sites on the adsorbent material. In this study, hydrophobic activated carbons (BMIMPF6-AC (L), BMIMPF6-AC (g), and BMIMPF6-AC-H) were successfully prepared using 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6) to adsorb toluene under humidity environment. The adsorption performance and mechanism of the resulting ionic liquid-modified activated carbon for toluene in a high-humidity environment were evaluated to explore the potential application of ionic liquids as hydrophobic modifiers. The results indicated that BMIMPF6-AC-H exhibited superior hydrophobicity. The toluene adsorption capacity of BMIMPF6-AC-H was 1.53 times higher than that of original activated carbon, while the adsorption capacity for water vapor was only 37.30% of it at 27 °C and 77% RH. The Y-N model well-fitted the dynamic adsorption experiments. To elucidate the microscopic mechanism of hydrophobic modification, the Independent Gradient Model (IGM) method was employed to characterize the intermolecular interactions between BMIMPF6 and toluene. Overall, this study introduces a new modifier for hydrophobic modification of activated carbon, which could enhance the efficiency of activated carbon in treating industrial VOCs.

6.
Phytochemistry ; 223: 114120, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38705265

RESUMO

Eleven previously undescribed sesquiterpenoids (8-18), one undescribed jasmonic acid derivative (35) and 28 known compounds were isolated from the leaves of Artemisia stolonifera. Undescribed compounds with their absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction and ECD calculation. Compound 8 was identified as a rare sesquiterpenoid featuring a rearranged 5/8 bicyclic ring system, whereas compound 17 was found to be an unprecedented monocyclic sesquiterpenoid with methyl rearrangement. Evaluation of biological activity showed that compounds 1-5 and 7 displayed cytotoxicity against six tumor cells. In the meantime, compounds 11, 12, 18 and 35 exhibited inhibitory effects against LPS-stimulated NO production in RAW 264.7 macrophage cells and reduced the transcription of IL-6 and IL-1ß in a dose-dependent manner at 25, 50 and 100 µM. Moreover, the anti-inflammatory-based network pharmacology and molecular docking analyses revealed potential target proteins of 11, 12, 18 and 35.

7.
Nat Commun ; 15(1): 3669, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38693119

RESUMO

Oncolytic viruses (OVs) show promise as a cancer treatment by selectively replicating in tumor cells and promoting antitumor immunity. However, the current immunogenicity induced by OVs for tumor treatment is relatively weak, necessitating a thorough investigation of the mechanisms underlying its induction of antitumor immunity. Here, we show that HSV-1-based OVs (oHSVs) trigger ZBP1-mediated PANoptosis (a unique innate immune inflammatory cell death modality), resulting in augmented antitumor immune effects. Mechanistically, oHSV enhances the expression of interferon-stimulated genes, leading to the accumulation of endogenous Z-RNA and subsequent activation of ZBP1. To further enhance the antitumor potential of oHSV, we conduct a screening and identify Fusobacterium nucleatum outer membrane vesicle (Fn-OMV) that can increase the expression of PANoptosis execution proteins. The combination of Fn-OMV and oHSV demonstrates potent antitumor immunogenicity. Taken together, our study provides a deeper understanding of oHSV-induced antitumor immunity, and demonstrates a promising strategy that combines oHSV with Fn-OMV.


Assuntos
Fusobacterium nucleatum , Herpesvirus Humano 1 , Terapia Viral Oncolítica , Vírus Oncolíticos , Proteínas de Ligação a RNA , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 1/genética , Vírus Oncolíticos/genética , Vírus Oncolíticos/imunologia , Animais , Humanos , Terapia Viral Oncolítica/métodos , Camundongos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/imunologia , Linhagem Celular Tumoral , Fusobacterium nucleatum/imunologia , Neoplasias/terapia , Neoplasias/imunologia , Feminino , Imunidade Inata , Camundongos Endogâmicos BALB C
8.
Artigo em Inglês | MEDLINE | ID: mdl-38744667

RESUMO

BACKGROUND AND AIM: False positives (FPs) pose a significant challenge in the application of artificial intelligence (AI) for polyp detection during colonoscopy. The study aimed to quantitatively evaluate the impact of computer-aided polyp detection (CADe) systems' FPs on endoscopists. METHODS: The model's FPs were categorized into four gradients: 0-5, 5-10, 10-15, and 15-20 FPs per minute (FPPM). Fifty-six colonoscopy videos were collected for a crossover study involving 10 endoscopists. Polyp missed rate (PMR) was set as primary outcome. Subsequently, to further verify the impact of FPPM on the assistance capability of AI in clinical environments, a secondary analysis was conducted on a prospective randomized controlled trial (RCT) from Renmin Hospital of Wuhan University in China from July 1 to October 15, 2020, with the adenoma detection rate (ADR) as primary outcome. RESULTS: Compared with routine group, CADe reduced PMR when FPPM was less than 5. However, with the continuous increase of FPPM, the beneficial effect of CADe gradually weakens. For secondary analysis of RCT, a total of 956 patients were enrolled. In AI-assisted group, ADR is higher when FPPM ≤ 5 compared with FPPM > 5 (CADe group: 27.78% vs 11.90%; P = 0.014; odds ratio [OR], 0.351; 95% confidence interval [CI], 0.152-0.812; COMBO group: 38.40% vs 23.46%, P = 0.029; OR, 0.427; 95% CI, 0.199-0.916). After AI intervention, ADR increased when FPPM ≤ 5 (27.78% vs 14.76%; P = 0.001; OR, 0.399; 95% CI, 0.231-0.690), but no statistically significant difference was found when FPPM > 5 (11.90% vs 14.76%, P = 0.788; OR, 1.111; 95% CI, 0.514-2.403). CONCLUSION: The level of FPs of CADe does affect its effectiveness as an aid to endoscopists, with its best effect when FPPM is less than 5.

9.
J Dig Dis ; 25(3): 191-199, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38697920

RESUMO

OBJECTIVE: To compare the detection rate and diagnostic accuracy of cardia polyps using endoscopy with blue laser imaging (BLI) and white-light imaging (WLI). METHODS: Patients were randomly divided into the BLI group and WLI group according to the endoscopic procedures. BLI followed by WLI was conducted in the BLI group, whereas WLI followed by BLI examination was conducted in the WLI group. The number, size, microstructure, and microvascular patterns of cardia polyps detected were recorded. Biopsy of the polyps was then performed. RESULTS: The detection rate of cardia polyps in the BLI group was higher than that in the WLI group (7.87% vs 4.22%, P = 0.018). The rate of overlooked lesions in the BLI group was lower than in the WLI group (0.64% vs 3.38%, P = 0.003). The diagnostic coincidence rate between magnifying BLI and histopathology was 88.16%. The sensitivity, specificity, positive predictive value and negative predictive value for the diagnosis of neoplastic lesions by magnifying endoscopy with BLI were 90.91%, 87.69%, 55.56%, and 98.28%, respectively. The most remarkable patterns for predicting inflammatory polyps were the prolonged and fine network patterns (sensitivity 71.43%, specificity 93.75%). Small round combined with honeycomb patterns were the most common among fundic gland polyps (sensitivity 80.00%, specificity 98.48%). Neoplastic lesions presented as villous or ridge-like combined with core vascular or unclear pattern for both microvascular and microstructure patterns. CONCLUSION: BLI is more effective than WLI in the detection and diagnosis of cardia polyps, and magnifying endoscopy with BLI may help diagnose such lesions.


Assuntos
Cárdia , Estudos de Viabilidade , Neoplasias Gástricas , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Cárdia/patologia , Cárdia/diagnóstico por imagem , Adulto , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Idoso , Pólipos/diagnóstico por imagem , Pólipos/diagnóstico , Gastroscopia/métodos , Sensibilidade e Especificidade , Valor Preditivo dos Testes , Lasers
10.
Sci Rep ; 14(1): 11153, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750224

RESUMO

The Patient-Reported Outcomes Measurement Information System 29-item Profile version 2.1 (PROMIS-29 V2.1) is a widely utilized self-reported instrument for assessing health outcomes from the patients' perspectives. This study aimed to evaluate the psychometric properties of the PROMIS-29 V2.1 Chinese version among patients with hematological malignancy. Conducted as a cross-sectional, this research was approved by the Medical Ethical Committee of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (registration number QTJC2022002-EC-1). We employed convenience sampling to enroll eligible patients with hematological malignancy from four tertiary hospitals in Tianjin, Shandong, Jiangsu, and Anhui province in China between June and August 2023. Participants were asked to complete a socio-demographic information questionnaire, the PROMIS-29 V2.1, and the Functional Assessment of Cancer Therapy-General (FACT-G). We assessed the reliability, ceiling and floor effects, structural, convergent discriminant and criterion validity of the PROMIS-29 V2.1. A total of 354 patients with a mean age of 46.93 years was included in the final analysis. The reliability of the PROMIS-29 V2.1 was affirmed, with Cronbach's α for the domains ranging from 0.787 to 0.968. Except sleep disturbance, the other six domains had ceiling effects, which were seen on physical function (26.0%), anxiety (37.0%), depression (40.4%), fatigue (18.4%), social roles (18.9%) and pain interference (43.2%), respectively. Criterion validity was supported by significant correlations between the PROMIS-29 V2.1 and FACT-G scores, as determined by the Spearman correlation test (P < 0.001). Confirmatory factor analysis (CFA) indicated a good model fit, with indices of χ2/df (2.602), IFI (0.960), and RMSEA (0.067). The Average Variance Extracted (AVE) values for the seven dimensions of PROMIS-29 V2.1, ranging from 0.500 to 0.910, demonstrated satisfactory convergent validity. Discriminant validity was confirmed by ideal √AVE values. The Chinese version of the PROMIS-29 V2.1 profile has been validated as an effective instrument for assessing symptoms and functions in patients with hematological malignancy, underscoring its reliability and applicability in this specific patient group.


Assuntos
Neoplasias Hematológicas , Psicometria , Humanos , Neoplasias Hematológicas/psicologia , Psicometria/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , China , Estudos Transversais , Reprodutibilidade dos Testes , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Inquéritos e Questionários , Idoso , Adulto Jovem , Adolescente
11.
World J Gastrointest Oncol ; 16(5): 2006-2017, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38764815

RESUMO

BACKGROUND: N6-methyladenosine (m6A) modification represents the predominant alteration found in eukaryotic messenger RNA and plays a crucial role in the progression of various tumors. However, despite its significance, the comprehensive investigation of METTL5, a key m6A methyltransferase, in colorectal cancer (CRC) remains limited. AIM: To investigate the role of METTL5 in CRC. METHODS: We assessed METTL5 expression levels in clinical samples obtained from CRC patients as well as in CRC cell lines. To elucidate the downstream targets of METTL5, we performed RNA-sequencing analysis coupled with correlation analysis, leading us to identify Toll-like receptor 8 (TLR8) as a potential downstream target. In vitro functional assessments of METTL5 and TLR8 were conducted using CCK-8 assays, scratch assays, as well as assays measuring cell migration and invasion. RESULTS: Our findings reveal a pronounced upregulation of METTL5 expression in both CRC cells and tissues, which correlated significantly with an unfavorable prognosis. In vitro experiments unequivocally demonstrated the oncogenic role of METTL5, as evidenced by its promotion of CRC cell proliferation, invasion, and migration. Notably, we identified TLR8 as a downstream target of METTL5, and subsequent down-regulation of TLR8 led to a significant inhibition of CRC cell proliferation, invasion, and tumor growth. CONCLUSION: The heightened expression of METTL5 in CRC is strongly associated with clinicopathological features and a poor prognosis, thereby underscoring its potential utility as a critical marker for facilitating early diagnosis and prognostication in CRC.

12.
Biochem Biophys Res Commun ; 717: 150061, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38718570

RESUMO

Epithelial mesenchymal transition (EMT) is a critical process implicated in the pathogenesis of retinal fibrosis and the exacerbation of diabetic retinopathy (DR) within retinal pigment epithelium (RPE) cells. Apigenin (AP), a potential dietary supplement for managing diabetes and its associated complications, has demonstrated inhibitory effects on EMT in various diseases. However, the specific impact and underlying mechanisms of AP on EMT in RPE cells remain poorly understood. In this study, we have successfully validated the inhibitory effects of AP on high glucose-induced EMT in ARPE-19 cells and diabetic db/db mice. Notably, our findings have identified CBP/p300 as a potential therapeutic target for EMT in RPE cells and have further substantiated that AP effectively downregulates the expression of EMT-related genes by attenuating the activity of CBP/p300, consequently reducing histone acetylation alterations within the promoter region of these genes. Taken together, our results provide novel evidence supporting the inhibitory effect of AP on EMT in RPE cells, and highlight the potential of specifically targeting CBP/p300 as a strategy for inhibiting retinal fibrosis in the context of DR.


Assuntos
Apigenina , Transição Epitelial-Mesenquimal , Glucose , Histonas , Epitélio Pigmentado da Retina , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Animais , Apigenina/farmacologia , Acetilação/efeitos dos fármacos , Humanos , Glucose/metabolismo , Glucose/toxicidade , Histonas/metabolismo , Linhagem Celular , Camundongos , Fatores de Transcrição de p300-CBP/metabolismo , Fatores de Transcrição de p300-CBP/antagonistas & inibidores , Camundongos Endogâmicos C57BL , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Retinopatia Diabética/tratamento farmacológico , Proteína p300 Associada a E1A/metabolismo , Masculino , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Proteína de Ligação a CREB/metabolismo , Proteína de Ligação a CREB/genética
13.
Sci Immunol ; 9(95): eadj9730, 2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728414

RESUMO

Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti-B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8+ CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.


Assuntos
Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Análise de Célula Única , Humanos , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologia , Autoimunidade/imunologia , Neuromielite Óptica/imunologia , Neuromielite Óptica/terapia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Sistema Nervoso Central/imunologia
14.
Cancer Immunol Immunother ; 73(7): 132, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753055

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line treatment of metastatic gastric and gastroesophageal adenocarcinomas (GEACs). This study aims to figure out the optimal combined positive score (CPS) cutoff value. METHODS: We searched for randomized phase III trials to investigate the efficacy of ICIs plus chemotherapy for metastatic GEACs compared with chemotherapy alone. Pooled analyses of hazard ratios (HRs) based on PD-L1 expression were performed. RESULTS: A total of six trials (KEYNOTE-062, KEYNOTE-590, KEYNOTE-859, ATTRACTION-04, CheckMate 649, and ORIENT-16) were included, comprising 5,242 patients. ICIs plus chemotherapy significantly improved OS (HR: 0.79, 95% CI 0.72-0.86 in global patients; HR: 0.75, 95% CI 0.57-0.98 in Asian patients) and PFS (HR: 0.74, 95% CI 0.68-0.82 in global patients; HR: 0.64, 95% CI 0.56-0.73 in Asian patients) compared with chemotherapy alone. The differences in OS (ratio of HR: 1.05, 95% CI 0.79-1.40; predictive value: - 5.1%) and PFS (ratio of HR: 1.16, 95% CI 0.98-1.36; predictive value: - 13.5%) were not statistically significant between the global and Asian patients. Subgroup analyses indicated that the optimal CPS threshold was at ≥ 5 for OS and ≥ 10 for PFS with the highest predictive values. CONCLUSIONS: The benefit derived from ICIs plus chemotherapy is similar between Asian and global GEAC patients. However, those with a PD-L1 CPS < 5 or CPS < 10 may not have significant benefits from ICIs therapy. Therefore, it is advisable to routinely assess PD-L1 expression in GEAC patients considered for ICIs treatment.


Assuntos
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Antígeno B7-H1 , Inibidores de Checkpoint Imunológico , Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor ErbB-2/metabolismo , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Ensaios Clínicos Fase III como Assunto , Biomarcadores Tumorais/metabolismo
15.
Ann Hematol ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761184

RESUMO

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38761998

RESUMO

BACKGROUND: Previous study implied that local M2 polarization of macrophage promoted mucosal edema and exacerbates Th2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We thought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: RT-qPCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5 knockout mice were used to establish nasal polyp model with Th2 inflammation and investigate the effects of SIRT5 in macrophages on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophages markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5 deficiency mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages through promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting the alternative polarization of macrophage and thus provides a potential target for CRSwNP interventions.

17.
J Gastrointest Surg ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38670431

RESUMO

BACKGROUND: There are no direct comparisons across different endoscopic therapies for gastroesophageal reflux disease (GERD). This study aimed to evaluate the relative effects of different endoscopic therapies in GERD. METHODS: Five databases were searched until August 2023 for randomized controlled trials (RCTs) that compared the efficacy of endoscopic band ligation (EBL), Stretta, endoscopic fundoplication (transoral incisionless fundoplication [TIF], endoscopic full-thickness plication [EFTP], and EndoCinch plication procedure [EndoCinch, CR BARD, Billerica, Mass., USA]), or proton pump inhibitors (PPIs)/sham procedure for GERD. Bayesian network meta-analysis was performed. RESULTS: A total of 19 trials comprising 1181 patients were included. EBL (mean difference [MD], -7.75; 95% credible interval [CrI], -13.90 to -1.44), Stretta (MD, -9.86; 95% CrI, -19.05 to -0.58), and TIF (MD, -12.58; 95% CrI, -20.23 to -4.91) all significantly improved patients' health-related quality of life score with equivalent efficacy compared with PPIs. TIF and EBL achieved equivalent efficacy in reducing PPIs utility (risk ratio [RR], 0.66; 95% CrI, 0.40-1.05) and both were significantly superior to other endoscopic interventions (Stretta, EFTP, and EndoCinch). Besides, EBL and TIF also could significantly decrease the esophagitis incidence compared with PPIs (EBL [RR, 0.34; 95% CrI, 0.22-0.48] and TIF [RR, 0.38; 95% CrI, 0.15-0.88]). In terms of lower esophageal sphincter (LES) pressure, only TIF could significantly increase the LES pressure (MD, 6.53; 95% CrI, 3.65-9.40) to PPIs. In contrast, TIF was inferior to PPIs in decreasing esophageal acid exposure (MD, 2.57; 95% CrI, 0.77-4.36). CONCLUSION: Combining the evidence, EBL and TIF may have comparable efficacy and both might be superior to Stretta, EFTP, or EndoCinch in GERD treatment.

18.
Front Immunol ; 15: 1378739, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665921

RESUMO

Chimeric antigen receptor (CAR) T cell therapy has transformed cancer immunotherapy. However, significant challenges limit its application beyond B cell-driven malignancies, including limited clinical efficacy, high toxicity, and complex autologous cell product manufacturing. Despite efforts to improve CAR T cell therapy outcomes, there is a growing interest in utilizing alternative immune cells to develop CAR cells. These immune cells offer several advantages, such as major histocompatibility complex (MHC)-independent function, tumor microenvironment (TME) modulation, and increased tissue infiltration capabilities. Currently, CAR products from various T cell subtypes, innate immune cells, hematopoietic progenitor cells, and even exosomes are being explored. These CAR products often show enhanced antitumor efficacy, diminished toxicity, and superior tumor penetration. With these benefits in mind, numerous clinical trials are underway to access the potential of these innovative CAR cells. This review aims to thoroughly examine the advantages, challenges, and existing insights on these new CAR products in cancer treatment.


Assuntos
Imunoterapia Adotiva , Neoplasias , Receptores de Antígenos Quiméricos , Microambiente Tumoral , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Imunoterapia Adotiva/métodos , Animais , Microambiente Tumoral/imunologia , Linfócitos T/imunologia
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124340, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38676986

RESUMO

Three CPs [Zn2(PDA)2(BMIOPE)2·3H2O]n (1), [Co(Br-BDC)(BMIOPE)]n (2) and [Co(MIP)(BMIOPE)]n (3) were synthesized by solvothermal method based on dual-ligand strategy (H2PDA, Br-H2BDC, BMIOPE and H2MIP are 1,3-phenylenediacetic acid, 5-bromo-isophthalic acid, 4,4'-bis(2-methylimidazol-1-yl)diphenyl ether and 5-methylisophthalic acid, respectively). Complexes 1 and 3 exhibit twofold parallel interwoven sql nets. Complex 2 is 2D layer structure. The luminescence property investigations showed that complexes 1-3 could act as multi-responsive fluorescent sensors to detect UO22+, Cr2O72- and CrO42- and nitrofurantoin (NFT) through fluorescence turn-off process, presenting excellent sensitivity and selectivity. Finally, the possible fluorescent quenching mechanisms of complexes 1-3 toward the above pollutants are also further investigated by employing spectroscopic methods and quantum chemical calculations. The fluorescence lifetime measurements manifest the mechanism of fluorescence quenching is static quenching process.

20.
Biochem Pharmacol ; 224: 116234, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38670436

RESUMO

Ionizing radiation, a standard therapeutic approach for lung cancer, often leads to cellular senescence and the induction of epithelial-mesenchymal transition (EMT), posing significant challenges in treatment efficacy and cancer progression. Overcoming these obstacles is crucial for enhancing therapeutic outcomes in lung cancer management. This study investigates the effects of ionizing radiation and gemcitabine on lung cancer cells, with a focus on induced senescence, EMT, and apoptosis. Human-derived A549, PC-9, and mouse-derived Lewis lung carcinoma cells exposed to 10 Gy X-ray irradiation exhibited senescence, as indicated by morphological changes, ß-galactosidase staining, and cell cycle arrest through the p53-p21 pathway. Ionizing radiation also promoted EMT via TGFß/SMAD signaling, evidenced by increased TGFß1 levels, altered EMT marker expressions, and enhanced cell migration. Gemcitabine, a first-line lung cancer treatment, was shown to enhance apoptosis in senescent cells caused by radiation. It inhibited cell proliferation, induced mitochondrial damage, and triggered caspase-mediated apoptosis, thus mitigating EMT in vitro. Furthermore, in vivo studies using a lung cancer mouse model revealed that gemcitabine, combined with radiation, significantly reduced tumor volume and weight, extended survival, and suppressed malignancy indices in irradiated tumors. Collectively, these findings demonstrate that gemcitabine enhances the therapeutic efficacy against radiation-resistant lung cancer cells, both by inducing apoptosis in senescent cells and inhibiting EMT, offering potential improvements in lung cancer treatment strategies.


Assuntos
Antimetabólitos Antineoplásicos , Senescência Celular , Desoxicitidina , Transição Epitelial-Mesenquimal , Gencitabina , Neoplasias Pulmonares , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Senescência Celular/efeitos dos fármacos , Senescência Celular/efeitos da radiação , Animais , Humanos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos da radiação , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Camundongos , Antimetabólitos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Células A549 , Radiação Ionizante , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação
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