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OBJECTIVE: This study was designed to examine the association between physical activity (PA) and depression among adult prescription opioid users. METHOD: Data of adults who recently took prescription opioids were collected from NHANES 2007-2018. Participants were divided into two groups according to whether PA in each domain was ≥600 MET-min/week. According to weekly activity frequency, recreational physical activity (RPA) was divided into inactivity, insufficient activity, weekend warrior (WW), and regular activity. PHQ-9 scores ≥10 were identified as depression. RESULTS: RPA of ≥600 MET-min/week was associated with a 40% (OR: 0.60, 95%CI: 0.38-0.96, P = 0.032) reduction in the risk of depression. Restricted Cubic Spline plots found a nonlinear dose-response relationship between RPA and depression (P = 0.045), and the turning point of depression risk was around 600 MET-min/week. There was no significant difference in the risk of depression between the WW and inactivity groups (OR: 0.65, 95%CI: 0.25-1.72, P = 0.382). The regular activity group had an 45% (OR: 0.55, 95%CI: 0.31-0.99, P = 0.046)lower risk for depression than the inactivity group. CONCLUSION: Only regular RPA is associated with a reduced risk of depression, and RPA showed a nonlinear dose-response relationship. The antidepressant effect of the WW is not significant.
Assuntos
Analgésicos Opioides , Depressão , Exercício Físico , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Adulto , Estudos Transversais , Depressão/epidemiologia , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem , Transtornos Relacionados ao Uso de Opioides/epidemiologiaRESUMO
Background: The safety of mastectomy (MT) with immediate reconstruction (IR) in breast cancer patients who have completed neoadjuvant chemotherapy (NAC) is not apparent. This meta-analysis aims to systematically evaluate the differences in surgical complications and postoperative survival rates between MT with IR (MT+IR) and MT alone in post-NAC breast cancer patients. Methods: The PubMed, Embase, Cochrane Library, WanFang Data, and CNKI databases were systematically searched, and cohort studies of post-NAC breast cancer patients with MT+IR or MT surgery were collected from databases inception to May 25, 2023. Two researchers independently executed literature screening, data extraction, and bias risk assessment, and meta-analysis was performed using Revman 5.3 software. Results: A total of 12 studies involving 7378 cases who have accepted NAC were collected for this study. The results showed that compared with the MT group, the relative risk of surgical complications in the MT+IR group was increased by 44%, with no statistical significant [RR=1.44, 95% CI (0.99, 2.09), P=0.06]. While among study subgroups with a median follow-up of less than one year, more surgical complications occurred in the MT+IR group by 23% [RR=1.23, 95% CI (1.00, 1.52), P=0.05]. There was no significant differences in overall survival, disease-free survival, local relapse-free survival, and distant metastasis-free survival between the two groups. Conclusions: Compared with the MT, MT+IR does not affect the postoperative survival rate in post-NAC breast cancer patients, accompanied by a mild increase in short-term surgical complications, but no significant difference in long-term complications. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023421150.
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Immune checkpoint inhibitor-associated adverse reactions (irAEs) are a clinical treatment issue that requires additional attention when ICIs have significant survival benefits in patients with advanced hepatocellular carcinoma (HCC). Among them, ICIs-associated myocarditis (ICIAM) is a kind of severe irAE with a high mortality rate (17%-50%). Despite its low incidence (PD1/PD-L1 related: 0.41%-0.8%), ICIAM can significantly disturb the decision making of therapeutic schemes and even the survival outcomes of patients. ICIAM induced by sintilimab has not been reported in any complete clinical studies yet and understanding the clinical characteristics involved may inform better practices for the management. Here, we reported a 78 y/o patient with advanced HCC, who experienced ICIAM induced by sintilimab within a short course from treatment onset and found that adequate baseline examination before the implementation of the therapeutic scheme, regular monitoring of myocardial enzymonram and cardiac imaging were measures for the early detection, while glucocorticoid pulse therapy is still the best choice with timely and sufficient application. Simultaneously, the combination of other immunosuppressants may lead to better results. New-predictive markers and examination methods are still required to facilitate the early detection.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Miocardite , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
PURPOSE: We aimed to elucidate the applicability of tumor organoids for inherent drug resistance of primary liver cancer (PLC) and mechanisms of acquired drug resistance. METHODS: PLC tissues were used to establish organoids, organoid-derived xenograft (ODX) and patient-derived xenograft (PDX) models. Acquired drug resistance was induced in hepatocellular carcinoma (HCC) organoids. Gene expression profiling was performed by RNA-sequencing. RESULTS: Fifty-two organoids were established from 153 PLC patients. Compared with establishing PDX models, establishing organoids of HCC showed a trend toward a higher success rate (29.0% vs. 23.7%) and took less time (13.0 ± 4.7 vs. 25.1 ± 5.4 days, p = 2.28 × 10-13). Larger tumors, vascular invasion, higher serum AFP levels, advanced stages and upregulation of stemness- and proliferation-related genes were significantly associated with the successful establishment of HCC organoids and PDX. Organoids and ODX recapitulated PLC histopathological features, but were enriched in more aggressive cell types. PLC organoids were mostly resistant to lenvatinib in vitro but sensitive to lenvatinib in ODX models. Stemness- and epithelial-mesenchymal transition (EMT)-related gene sets were found to be upregulated, whereas liver development- and liver specific molecule-related gene sets were downregulated in acquired sorafenib-resistant organoids. Targeting the mTOR signaling pathway was effective in treating acquired sorafenib-resistant HCC organoids, possibly via inducing phosphorylated S6 kinase. Genes upregulated in acquired sorafenib-resistant HCC organoids were associated with an unfavorable prognosis. CONCLUSIONS: HCC organoids perform better than PDX for drug screening. Acquired sorafenib resistance in organoids promotes HCC aggressiveness via facilitating stemness, retro-differentiation and EMT. Phosphorylated S6 kinase may be predictive for drug resistance in HCC.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , alfa-Fetoproteínas/análise , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Resistência a Medicamentos , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Organoides/patologia , Proteínas Quinases S6 Ribossômicas/metabolismo , Sorafenibe/farmacologia , Serina-Treonina Quinases TOR/metabolismoRESUMO
APOBEC3-related somatic mutations are predominant in biliary tract cancers (BTCs). We aimed to elucidate the roles of APOBEC3A/3B functional polymorphisms and their influencing factors on the development of cholangiocarcinoma (CCA) and gallbladder cancer (GBC). Polymorphisms at the promoter regions of APOBEC3A and APOBEC3B were genotyped in 3231 participants using quantitative PCR. Dual-luciferase reporter assay was applied to investigate the promoter activity. The difference in gene accessibility between CCA cells and GBC cells was analyzed through single-cell transposase accessible chromatin sequencing. The effect of APOBEC3A on apoptosis was examined by cytometry. It is found that rs2267401-G at the APOBEC3B promoter decreases CCA risk (age-, gender-adjusted odds ratio [AOR], 0.69; 95% confidence interval [CI], 0.51-0.94) but increases GBC risk (AOR, 2.04; 95% CI, 1.35-3.10). rs2267401-G confers a decreased APOBEC3B promoter activity in CCA cells but an increased activity in GBC cells, possibly because the transcriptional repressor TFAP2A is over-expressed in CCA. Tumor necrosis factor-α (TNF-α) increases the level of APOBEC3B via inhibiting TFAP2A expression rather than directly increasing the accessibility of APOBEC3B promoter. APOBEC3A promoter rs12157810-C decreased the risks of CCA and GBC, with an AOR (95% CI) of 0.80 (0.66-0.97) and 0.75 (0.59-0.95), respectively. rs12157810-C upregulated the promoter activity in both CCA and GBC cells. TNF-α upregulated the activity of the APOBEC3A promoter with rs12157810-C via increasing the accessibility of Ets-1 p68. APOBEC3A overexpression attenuates cancer evolution by causing apoptosis, in contrast to APOBEC3B. The heterogeneity in the transcriptional regulation of APOBEC3B affects the evolutionary potential of cancer cells in the inflammatory microenvironment.
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Neoplasias dos Ductos Biliares , Neoplasias da Vesícula Biliar , Apoptose/genética , Ductos Biliares Intra-Hepáticos , Citidina Desaminase/genética , Neoplasias da Vesícula Biliar/genética , Humanos , Antígenos de Histocompatibilidade Menor/metabolismo , Proteínas , Microambiente TumoralRESUMO
Increasing evidence indicates that dysregulation of microRNAs (miRNAs) contributes to tumorigenesis. MicroRNA-340 (miR-340) is downregulated in several types of cancer. However, the functional mechanism of miR-340 in hepatocellular carcinoma (HCC) remains unclear. Here, we showed that miR-340 was significantly downregulated in HCC tissues and cell lines. Gain-of-function experiments demonstrated that miR-340 overexpression inhibited HCC cell proliferation, migration, and invasion in vitro, and suppressed tumor growth in vivo. Janus kinase 1 (JAK1) was identified as a direct target of miR-340 in HCC cells. Ectopic expression of JAK1 reversed the inhibitory effects of miR-340. Further investigations showed that miR-340 dramatically inhibited the expression of signal transducer and activator of transcription (STAT)3 downstream molecules including Bcl-2, cyclin D1, and matrix metalloprotease (MMP)-2. The present findings indicated that miR-340 suppressed HCC cell proliferation and invasion by regulating the JAK1/STAT3 pathway, suggesting its potential as a novel therapeutic target for HCC.