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Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer often associated with chronic hepatitis B virus infection (CHB) and liver cirrhosis (LC), underscoring the critical need for biomarker discovery to improve patient outcomes. Emerging as a promising avenue for biomarker development, proteomic technology leveraging liquid biopsy from small extracellular vesicles (sEV) offers new insights. Here, we evaluated various methods for sEV isolation and identified polysaccharide chitosan (CS) as an optimal approach. Subsequently, we employed optimized CS-based magnetic beads (Mag-CS) for sEV separation from serum samples of healthy controls, CHB, LC, and HBV-HCC patients. Leveraging data-independent acquisition mass spectrometry coupled with machine learning, we uncovered potential vesicular protein biomarker signatures (KNG1, F11, KLKB1, CAPNS1, CDH1, CPN2, NME2) capable of distinguishing HBV-HCC from CHB, LC, and non-HCC conditions. Collectively, our findings highlight the utility of Mag-CS-based sEV isolation for identifying early detection biomarkers in HBV-HCC.
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Carcinoma Hepatocelular , Quitosana , Vírus da Hepatite B , Neoplasias Hepáticas , Proteômica , Humanos , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/virologia , Proteômica/métodos , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/sangue , Vesículas Extracelulares/metabolismo , Hepatite B Crônica/sangue , Biomarcadores Tumorais/sangue , Cirrose Hepática/sangue , Cirrose Hepática/virologia , Masculino , FemininoRESUMO
BACKGROUND: To compare the impact of tunneled cuffed catheters (TCCs) and arteriovenous fistulas (AVFs) on outcomes in elderly hemodialysis (HD) patients. METHODS: A retrospective matched cohort study was performed. Propensity score matching (PSM) was applied to balance the baseline conditions, and we compared all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCEs), hospitalization, and infection rates between AVF and TCC patients ≥70 years old. Cox survival analysis was used to analyze the risk factors for death. RESULTS: There were 2119 patients from our center in the Chinese National Renal Data System (CNRDS) between 1 January 2010 and 10 October 2023. Among these patients, 77 TCC patients were matched with 77 AVF patients. There was no significant difference in all-cause mortality between the TCC and AVF groups (30.1/100 vs. 33.3/100 patient-years, p = 0.124). Among the propensity score-matched cohorts, no significant differences in Kaplan-Meier curves were observed between the two groups (log-rank p = 0.242). The TCC group had higher rates of MACCEs, hospitalization, and infection than the AVF group (33.7/100 vs. 29.5/100 patient-years, 101.2/100 vs. 79.5/100 patient-years, and 30.1/100 vs. 14.1/100 patient-years, respectively). Multivariate analysis showed that high Charlson comorbidity index (CCI) score was a risk factor for death. CONCLUSIONS: There was no significant difference in all-cause mortality between elderly HD patients receiving TCCs and AVFs. Compared with those with a TCC, elderly HD patients with an AVF have a lower risk of MACCEs, hospitalization, and infection.
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Derivação Arteriovenosa Cirúrgica , Falência Renal Crônica , Pontuação de Propensão , Diálise Renal , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Fatores de Risco , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Idoso de 80 Anos ou mais , Hospitalização/estatística & dados numéricos , China/epidemiologia , Prognóstico , Estimativa de Kaplan-MeierRESUMO
INTRODUCTION: The aberrant up-regulation of meiotic nuclear division 1 (MND1) in somatic cells is considered as one of the driving factors of oncogenesis, whereas its expression and role in breast invasive cancer (BRCA) remain unclear. Hence, this study embarked on a comprehensive evaluation of MND1 across various cancers and identified its roles in BRCA. METHODS: Based on publicly available databases, including but not limited to UCSC Xena, TCGA, GTEx, GEO, STRING, GeneMANIA, and CancerSEA, we evaluated the expression patterns, genomic features, and biological functions of MND1 from a pan-cancer viewpoint and delved into the implications of MND1 in the prognosis and treatment of BRCA. Further molecular biology experiments were undertaken to identify the role of MND1 in proliferation, migration, and apoptosis in BRCA cells. RESULTS: Elevated levels of MND1 were notably observed in a wide array of tumor types, especially in BRCA, COAD, HNSC, LIHC, LUAD, LUSC, STAD, and UCEC. Elevated MND1 expression was markedly associated with shortened OS in several tumors, including BRCA (HR = 1.52 [95%CI, 1.10-2.09], P = 0.011). The up-regulation of MND1 in BRCA was validated in external cohorts and clinical samples. Survival analyses demonstrated that elevated MND1 expression was associated with decreased survival for patients with BRCA. Co-expressed genes of MND1 were identified, and subsequent pathway analyses based on significantly associated genes indicated that MND1 plays key roles in DNA replication, cell cycle regulation, and DNA damage repair. The observed abnormal elevation and activation of MND1 led to increased proliferation and migration, along with decreased apoptosis in BRCA cells. CONCLUSIONS: MND1 emerges as a promising biomarker for diagnostic and therapeutic targeting in various cancers, including BRCA. The abnormal up-regulation and activation of MND1 are linked to carcinogenesis and poor prognosis among BRCA patients, which may be attributed to its involvement in HR-dependent ALT, warranting further scrutiny.
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The development of bacterial resistance significantly contributes to the persistence of infections. Although previous studies have highlighted the benefits of metal-doped positive carbon nanodots in managing bacterial wound infections, their mechanism of action is relatively simple and they may pose potential hazards to human cells. Therefore, it is essential to develop a one-stop carbon dot nanoplatform that offers high biocompatibility, antibacterial properties, and anti-inflammatory activities for wound infection management. This study explores the antibacterial efficacy, without detectable resistance, and wound-healing potential of nitrogen-doped (N-doped) negatively charged carbon dots (TPP-CDs). These carbon dots are synthesized using tannic acid (TA), polyethylene polyamine, and polyethylene glycol (PEG) as precursors, with a focus on their biocompatibility. Numerous systematic studies have shown that TPP-CDs can effectively destroy bacterial biofilms and deoxyribonucleic acid (DNA), while also inducing oxidative stress, leading to a potent antimicrobial effect. TPP-CDs also demonstrate the ability to scavenge excess free radicals, promote cellular proliferation, and inhibit inflammatory factors, all of which contribute to improved wound healing. TPP-CDs also demonstrate favorable cell imaging capabilities. These findings suggest that N-doped negatively charged TPP-CDs hold significant potential for treating bacterial infections and offer practical insights for their application in the medical field.
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The objective of this study was to explore the effects and mechanisms of the combination of isobavachalcone (IBC) and doxorubicin (DOX) on the progression of anaplastic thyroid cancer (ATC). Cell viability of 8505C and CAL62 cells was observed by CCK-8 assay. Kits were used to detect the presence of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and cellular iron. Protein expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was detected using western blot, and CD31 was detected through immunofluorescence. Tumor xenograft models of 8505C cells were constructed to observe the effect of IBC and DOX on ATC growth in vivo. The co-administration of IBC and DOX exhibited a synergistic effect of suppressing the growth of 8505C and CAL62 cells. The concurrent use of IBC and DOX resulted in elevated iron, ROS, and MDA levels, while reducing GSH levels and protein expression of SLC7A11 and GPX4. However, the Fer-1 ferroptosis inhibitor effectively counteracted this effect. In vitro and in vivo, the inhibitory effect on ATC cell proliferation and tumor growth was significantly enhanced by the combination of IBC and DOX. The combination of IBC and DOX can inhibit the growth of ATC by activating ferroptosis, and might prove to be a potent chemotherapy protocol for addressing ATC.
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Chalconas , Doxorrubicina , Sinergismo Farmacológico , Ferroptose , Espécies Reativas de Oxigênio , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Ferroptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/patologia , Carcinoma Anaplásico da Tireoide/metabolismo , Animais , Humanos , Chalconas/farmacologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Progressão da Doença , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Sobrevivência Celular/efeitos dos fármacos , Glutationa/metabolismo , Glutationa/efeitos dos fármacos , Antibióticos Antineoplásicos/farmacologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismoRESUMO
During early pregnancy in mice, the establishment of uterine receptivity and endometrial decidualization require the extensive proliferation and differentiation of endometrial epithelial cells or stromal cells. Pin1 has been suggested to act as a molecular 'timer' of the cell cycle and is involved in the regulation of cellular proliferation and differentiation by binding many cell-cycle regulatory proteins. However, its physiological role during early pregnancy is still not fully understood. Here, we employed immunohistochemistry to determine the spatiotemporal pattern of Pin1 expression during early pregnancy. We found that Pin1 was mainly localized in subluminal stromal cells on day 4, in the decidual zone on days 5 to 8 of pregnancy and in artificial decidualization. Using a uterine stromal cell culture system, we found that progesterone, but not estrogen, induced the expression of Pin1 in a progesterone receptor-dependent manner. Inhibition of Pin1 in the uterus leads to impaired embryo implantation and decidualization in mice. Notably, a decrease in Pin1 activation affected the functional execution of several implantation- or decidualization-related factors. These findings provide new evidence for a previously unknown function of Pin1 in mediating embryo implantation and decidualization during successful pregnancy establishment and maintenance.
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Decídua , Implantação do Embrião , Peptidilprolil Isomerase de Interação com NIMA , Útero , Animais , Feminino , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Peptidilprolil Isomerase de Interação com NIMA/genética , Implantação do Embrião/fisiologia , Camundongos , Gravidez , Decídua/metabolismo , Decídua/citologia , Útero/metabolismo , Útero/citologia , Progesterona/metabolismo , Células Estromais/metabolismo , Receptores de Progesterona/metabolismo , Células Cultivadas , Endométrio/metabolismo , Endométrio/citologiaRESUMO
Breast cancer is the most common malignant tumor worldwide, and mastectomy remains the primary strategy for treating early stage breast cancer. However, the complication rates, surgical variables, and oncologic safety of minimally invasive nipple-sparing mastectomy (MINSM) have not been fully addressed. We systematically searched PubMed, Web of Science, Embase, and the Cochrane Library for randomized-controlled trials (RCTs) and non-RCTs that compared MINSM with conventional nipple-sparing mastectomy (CNSM), both followed by Prosthesis Breast Reconstruction (PBR). The main outcomes observed included overall complications, (Grade III) complications, skin and nipple necrosis, wound dehiscence, infection, seroma, hematoma, implant loss, and oncologic safety (positive margins and recurrence). Secondary outcomes included operation time, blood loss, hospital stay, cost-effectiveness, and patient satisfaction. Binary and continuous variables were compared using odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI). A total of 10 studies involving 2,166 patients were included. There were no statistically significant differences between MINSM and CNSM in terms of skin necrosis, wound dehiscence, infection, seroma, hematoma, implant loss, or oncologic safety. However, MINSM significantly reduced overall complications (OR = 0. 74, 95% CI [0. 58, 0. 94], p = 0. 01) and (Grade III) complications (OR = 0. 47, 95% CI [0. 31, 0. 71], p = 0. 0003). Nipple necrosis events were also significantly reduced in the MINSM group (OR = 0. 49, 95% CI [0. 30, 0. 80], p = 0. 005). Patient satisfaction improved notably in the MINSM group. Additionally, compared with the CNSM group, the MINSM group had longer operating times (MD = 46. 88, 95% CI [19. 55, 74. 21], p = 0. 0008) and hospital stays (MD = 1. 39, 95% CI [0. 65, 2. 12], p < 0. 001), while intraoperative blood loss was significantly reduced (MD = -29. 05, 95% CI [-36. 20, -21. 90], p < 0. 001). Compared with CNSM, MINSM offers advantages in reducing complications and intraoperative blood loss, as well as improving aesthetic outcomes and patient satisfaction. Therefore, MINSM may become a viable option for breast surgery. Nevertheless, a long-term evaluation of the oncologic safety of this approach is necessary to ensure its efficacy and safety for patients.
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Neoplasias da Mama , Mamoplastia , Procedimentos Cirúrgicos Minimamente Invasivos , Mamilos , Complicações Pós-Operatórias , Feminino , Humanos , Implantes de Mama , Neoplasias da Mama/cirurgia , Tempo de Internação/estatística & dados numéricos , Mamoplastia/métodos , Mastectomia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Mamilos/cirurgia , Duração da Cirurgia , Tratamentos com Preservação do Órgão/métodos , Satisfação do Paciente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
PURPOSE: Many T1-2N0-1M0 triple-negative breast cancer (TNBC) patients who undergo neoadjuvant chemotherapy (NAC) do not receive breast-conserving therapy (BCT) due to concerns about non-pCR or lymph node metastasis presence. METHODS: T1-2N0-1M0 TNBC patients who underwent NAC between 2010 and 2017 were collected from the SEER database. Factors affecting surgical modalities were analyzed by multinomial logistic regression. The overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated by Kaplan-Meier curves and Cox proportional hazards models. Further stratified subgroup analyses were performed based on the response to NAC and N-stage. Adjusted-hazard ratios were also calculated to exclude potential bias. RESULTS: A total of 1112 patients were enrolled (median follow-up: 81 months), 58.5% received BCT, 23.6% received reconstruction and 17.9% received mastectomy. Response to NAC and N-stage not only influenced the choice of surgical modality but also were independent predictors for OS and BCSS. The surgery-induced survival differences mainly affect OS. Survival analyses demonstrated that the 10-year OS of BCT was superior or equal to that of mastectomy even in patients with partial response (PR) (77.4% vs. 64.1%, P = 0.013), no response (NR) (44.9% vs. 64.2%, P = 0.33), or N1 stage (75.7% vs. 57.4%, P = 0.0021). In the N1-PR cohort, mastectomy may lead to worse OS (P = 0.0012). Besides, between reconstruction and BCT, there was no statistical difference in OS or BCSS (P > 0.05). CONCLUSION: Our study reveals the necessity of breast surgical de-escalation. Besides, physicians should actively recommend reconstruction for individuals who strongly desire mastectomy.
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Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/cirurgia , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/mortalidade , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Mastectomia/métodos , Estadiamento de Neoplasias , Programa de SEER , Estudos Retrospectivos , Quimioterapia AdjuvanteRESUMO
PURPOSE: To assess the efficacy of neoadjuvant endocrine therapy in female HR-positive/HER2-negative breast cancer patients. DATA AND METHODS: We identified female patients aged ≥18 years with cT1-4N0-XM0, HR(+), and HER2(-) breast cancer from the National Cancer Database. The patients who underwent surgery first were categorized as "surgery-first," while those who received NET before surgery were classified as "NET." Propensity score-matching, Cox proportional-hazard model, variance inflation factors, and interaction analysis were employed to estimate the correlation between NET and survival outcomes. RESULTS: Among 432,387 cases, 2914 NET patients and 2914 surgery-first patients were matched. Compared with the surgery-first group, the NET group received less adjuvant chemotherapy (p < 0.001). Furthermore, the NET group exhibited higher survival probabilities compared with the surgery-first group (3 years: 91.4% vs. 82.1%; 5 years: 82.1% vs. 66.8%). Multivariate Cox analysis indicated that NET was associated with improved OS (surgery-first vs. NET: HR 2.17, 95% CI: 1.93-2.44). Age over 55 years old, having public insurance, higher CDCC score, higher NSBR grade, ER(+)PR(-), and advanced clinical stage were related to worse OS (all p < 0.05). There was an interaction between age, race, income, and home and treatment regimen (all p < 0.05). CONCLUSION: NET may be a more effective treatment procedure than surgery-first in female HR-positive/HER2-negative, non-metastatic breast cancer patients. Future clinical studies with more detailed data will provide higher-level evidence-based data.
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Neoplasias da Mama , Terapia Neoadjuvante , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/mortalidade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Receptor ErbB-2/metabolismo , Idoso , Adulto , Resultado do Tratamento , Antineoplásicos Hormonais/uso terapêutico , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Mastectomia , Quimioterapia Adjuvante/métodosRESUMO
INTRODUCTION: For HR-positive/HER2-negative patients who can undergo breast-conserving surgery (BCS) but have a tumor size of 2-5 cm or 1-3 lymph node metastases, neoadjuvant chemotherapy (NAC) is still controversial. METHODS: Patients with T2N0-1M0 HR-positive/HER2-negative BC who underwent BCS between 2010 and 2017 were selected from the SEER database. Propensity score matching (PSM) was used to minimize the influence of confounding factors. The overall survival (OS) and breast cancer-specific survival (BCSS) of patients were estimated by KaplanâMeier curves and Cox proportional hazard models. Independent prognostic factors were included to construct a nomogram prediction model. RESULTS: A total of 6475 BC patients were enrolled, of whom 553 received NAC and 5922 received adjuvant chemotherapy (AC). In the T2N0-1M0 population and T2N1M0 subgroup, AC patients before PSM had better OS and BCSS than NAC patients. After PSM, there was no significant difference in OS or BCSS between the two groups. However, in the T2N0M0 subgroup, there was no difference in survival between the AC and NAC groups before and after PSM. Stratified analysis revealed that for complete response (CR) patients, survival was roughly equivalent between the NAC and AC groups. However, the survival of no response (NR) and partial response (PR) patients was significantly worse than that of AC patients. Cox analysis revealed that radiotherapy after BCS was an independent protective factor for OS. NAC is an independent risk factor for NR and PR patients. The nomogram has good prediction efficiency. CONCLUSION: NAC before BCS is not necessary for T2N0-1M0 HR-positive/HER2-negative BC patients.
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Neoplasias da Mama , Mastectomia Segmentar , Terapia Neoadjuvante , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Quimioterapia Adjuvante/métodos , Adulto , Idoso , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Estadiamento de Neoplasias , Prognóstico , Programa de SEERRESUMO
Immunotherapy has shown great potential in cancer treatment. However, even with the intervention of techniques such as immune checkpoint inhibitor therapy, tumors can still achieve immune escape, leading to a low response rate. Abnormal glycosylation is a widely recognized hallmark of cancer. The development of a complex "glyco-code" on the surface of tumor cells can potentially influence the immune system's ability to monitor tumors and can impact the anti-tumor immune response. Therefore, abnormal glycosylation has emerged as a promising target for immunotherapy. Many recent studies have shown that targeted glycosylation can reshape the tumor microenvironment (TME) and promote the immune response, thereby improving the response to immunotherapy. This review summarizes how glycosylation affects anti-tumor immune function in the TME and synthesizes the latest research progress on targeted glycosylation in immunotherapy. It is hoped that by elucidating the basic laws and biological connotations of glycosylation, this review will enable researcher to thoroughly analyze the mechanism of its influence on the immune metabolic regulation network, which will provide a theoretical tool for promoting the clinical application of glycosylation codes.
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Imunoterapia , Neoplasias , Microambiente Tumoral , Glicosilação , Humanos , Imunoterapia/métodos , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/metabolismo , Microambiente Tumoral/imunologia , AnimaisRESUMO
Absent, small, or homeotic1-like (ASH1L) is a histone lysine methyltransferase that generally functions as a transcriptional activator in controlling cell fate. So far, its physiological relevance in bone homeostasis and osteoclast differentiation remains elusive. Here, by conditional deleting Ash1l in osteoclast progenitors of mice, we found ASH1L deficiency resulted in osteoporosis and potentiation of osteoclastogenesis in vivo and in vitro. Mechanistically, ASH1L binds the promoter of the Src homology 3 and cysteine-rich domain 2 (Stac2) and increases the gene's transcription via histone 3 lysine 4 (H3K4) trimethylation modification, thus augmenting the STAC2's protection against receptor activator of nuclear factor kB ligand (RANKL)-initiated inflammation during osteoclast formation. Collectively, we demonstrate the first piece of evidence to prove ASH1L as a critical checkpoint during osteoclastogenesis. The work sheds new light on our understanding about the biological function of ASH1L in bone homeostasis, therefore providing a valuable therapeutic target for the treatment of osteoporosis or inflammatory bone diseases.
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Histona-Lisina N-Metiltransferase , Osteoclastos , Osteogênese , Animais , Camundongos , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Diferenciação Celular , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histonas/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoclastos/metabolismo , Osteoporose/metabolismo , Osteoporose/patologia , Osteoporose/genética , Ligante RANK/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
Minimally invasive thyroidectomy (MIT) is increasingly being used for the thyroid tumors. The comparison of bilateral axillo-breast approach robotic thyroidectomy (BABART) with other MIT has not yet led to a unified conclusion with regard to surgical outcomes. To conduct a systematic review and meta-analysis of the literature on the surgical outcomes of BABART compared with MIT. We performed a systematic search in PubMed, Web of Science, Embase and Cochrane Library database for randomized control trials (RCTs) and non-RCTs that compare BABART to MIT. The primary outcomes included perioperative, postoperative complications. The odds ratio (OR) and mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CIs). Nine studies, comprising 3645 patients, were included in the meta-analysis. Our findings indicated that there were no significant differences in hospital stay, number of retrieved lymph nodes, recurrent laryngeal nerve (RLN) injury, and vocal cord dysfunction between BABRT and MIT. However, BABART was associated with a shorter operation time (MD = - 21.45 min, 95% CI [- 47.27, 4.38], p = 0.1) and lower rate of permanent hypoparathyroidism (OR = 0.42, 95% CI [0.20, 0.88], p = 0.02). Additionally, the MIT group had reduced postoperative pain score (MD = 0.45, 95% CI [0.02, 0.88], p = 0.04) and lower rate of hypocalcemia (OR = 2.31, 95% CI [1.04, 5.13], p = 0.04) than the BABART group. In comparison with MIT, BABART exhibits better results in terms of operative time and the rate of permanent hypoparathyroidism, with no significant difference in hospital stay, number of retrieved lymph nodes, RLN injury, and vocal cord dysfunction. However, the postoperative pain score and the rate of hypocalcemia of MIT are slightly better that of BABART.
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Axila , Tempo de Internação , Procedimentos Cirúrgicos Minimamente Invasivos , Duração da Cirurgia , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Robóticos , Tireoidectomia , Humanos , Tireoidectomia/métodos , Tireoidectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Tempo de Internação/estatística & dados numéricos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Mama/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Feminino , Hipoparatireoidismo/prevenção & controle , Hipoparatireoidismo/etiologia , Traumatismos do Nervo Laríngeo Recorrente/prevenção & controle , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Hipocalcemia/etiologia , Hipocalcemia/prevenção & controle , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , MasculinoRESUMO
Designing effective nanomedicines to induce durable anti-tumor immunity represents a promising strategy for improving moderate immune stimulation. In this study, we engineered a multifunctional nanoreactor (named SCGFP NPs) for remodeling the tumor microenvironment (TME) to improve the therapeutic efficacy of immunotherapy. The core of SCGFP NPs consists of CaCO3 loaded with SN38, prepared by the gas diffusion method, and coated with a significant amount of gallic acid-Fe3+-PEG coordination polymer on the surface. In the acidic TME, SCGFP NPs explosively release exogenous Ca2+ and SN38. The SN38-induced intracellular Ca2+ accumulation and exogenous Ca2+ synergistically trigger immunogenic cell death (ICD) through sustained Ca2+ overload. The ablation of tumors with high-intensity photothermal therapy (PTT) by near-infrared (NIR) irradiation of GA-Fe3+ induces tumor cell necrosis, further enhancing ICD activation. Additionally, SN38 upregulates PD-L1, amplifying tumor responsiveness to immune checkpoint inhibitors (ICIs). This study indicates that SCGFP NPs, through the integration of a trimodal therapeutic strategy, hold enormous potential for various types of tumor immunotherapy through distinct mechanisms or synergistic effects.
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Imunoterapia , Neoplasias , Reatores Biológicos , Difusão , Ácido Gálico/uso terapêutico , Polímeros , Microambiente Tumoral , Linhagem Celular TumoralRESUMO
BACKGROUND: Currently, research on the prognostic factors of unilateral breast cancer (UBC) patients receiving contralateral prophylactic mastectomy (CPM) is limited. This study aimed to construct a new nomogram to predict these patients' overall survival (OS). METHODS: In this retrospective study, 88,477 patients who underwent CPM or unilateral mastectomy (UM) were selected from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier curves and Cox regression analyses were used to determine the difference in the impact of the 2 surgical methods on the prognosis. Multivariate Cox analysis was used to determine the best prognostic variable and construct a nomogram. The concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the discrimination capability and clinical effectiveness of the nomogram. RESULTS: The prognosis of patients receiving CPM and UM was significantly different. The DCA curves indicated that the nomogram could provide more excellent clinical net benefits for these patients. The NRI and IDI of the nomogram demonstrated that its performance was better than that of the classical tumor-node-metastasis (TNM) staging system. CONCLUSION: This study developed and validated a practical nomogram to predict the OS of UBC patients undergoing CPM, which provided a beneficial tool for clinical decision-making management.
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Nomogramas , Mastectomia Profilática , Programa de SEER , Humanos , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Mastectomia Profilática/métodos , Mastectomia Profilática/estatística & dados numéricos , Prognóstico , Adulto , Neoplasias da Mama/cirurgia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias Unilaterais da Mama/cirurgia , Neoplasias Unilaterais da Mama/patologia , Idoso , Mastectomia , Estadiamento de Neoplasias , Estimativa de Kaplan-Meier , Curva ROC , Taxa de SobrevidaRESUMO
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/genéticaRESUMO
Aqueous zinc-ion batteries (AZIBs) are considered to be a rising star in the large-scale energy storage area because of their low cost and environmental friendliness properties. However, the limited electrochemical performance of the cathode and severe zinc dendrite of the anode severely hinder the practical application of AZIBs. Herein, a novel 3D interconnected VS2 â¥V4 C3 Tx heterostructure material is prepared via one-step solvothermal method. Morphological and structural characterizations show that VS2 nanosheets are uniformly and dispersedly distributed on the surface of the V4 C3 MXene substrate, which can effectively suppress volume change of the VS2 . Owing to the open heterostructure along with the high conductivity of V4 C3 MXene, the VS2 â¥V4 C3 Tx cathode shows a high specific capacity of 273.9 mAh g-1 at 1 A g-1 and an excellent rate capability of 143.2 mAh g-1 at 20 A g-1 . The V4 C3 MXene can also effectively suppress zinc dendrite growth when used as protective layer for the Zn anode, making the V4 C3 Tx @Zn symmetric cell with a stable voltage profile for ≈1700 h. Benefitting from the synergistic modification effect of V4 C3 MXene on both the cathode and anode, the VS2 â¥V4 C3 Tx ||V4 C3 Tx @Zn battery exhibits a long cycling lifespan of 5000 cycles with a capacity of 157.1 mAh g-1 at 5A g-1 .
RESUMO
Lung adenocarcinoma, the most common histological subtype of non-small cell lung cancer, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Our team uncovers that lncRNA related to chemotherapy resistance in lung adenocarcinoma (lncCRLA) is preferentially expressed in lung adenocarcinoma cells with the mesenchymal phenotype. lncCRLA can not enhance chemotherapy resistance in lung adenocarcinoma due to its binding to RIPK1 in exosomes, which is released into intercellular media and transferred by exosomes from mesenchymal-like to epithelial-like cells. However, plasmatic lncCRLA corresponding to tissue lncCRLA functions as a preferred biomarker to reflect the response to chemotherapy and disease progression of lung adenocarcinoma. Through single-cell sequencing, RNA-Mutect technique and spatial transcriptomics, a handful of hybrid EMT cells with elevated lncCRLA are characterized as the origin of lung adenocarcinoma, which are indiscriminated from hybrid EMT cells by the in-depth sequencing. Plasmatic lncCRLA is properly predictive for the preinvasive lesion of lung adenocarcinoma that would evolve to invasive lesion. That notion is confirmed by a brand-new transgenic mouse model in which EMT is tracked by Cre and Dre system. Dasatinib is potential to hinder the spontaneous progression from preinvasive to invasive lesion of lung adenocarcinoma. Together, plasmatic lncCRLA is defined as a brand-new circulating biomarker to predict the occurrence and evolvement of lung adenocarcinoma, a light for early detection of lung adenocarcinoma.
Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Camundongos , Neoplasias Pulmonares/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Biomarcadores , Pulmão/patologia , Transição Epitelial-Mesenquimal/genética , Linhagem Celular TumoralRESUMO
Purpose: Early judgment of the progress of acute pancreatitis (AP) and timely intervention are crucial to the prognosis of patients. The purpose of this study was to investigate the application value of CT-based radiomics of pancreatic parenchyma in predicting the prognosis of early AP. Materials and methods: This retrospective study enrolled 137 patients diagnosed with AP (95 cases in the progressive group and 42 cases in the non-progressive group) who underwent CT scans. Patients were randomly divided into a training set (n = 95) and a validation set (n = 42) in a ratio of 7: 3. The region of interest (ROI) was outlined along the inner edge of the pancreatic parenchyma manually, and the Modified CT Severity Index (MCTSI) was assessed. After resampling and normalizing the CT image, a total of 2,264 radiomics features were extracted from the ROI. The radiomics features were downscaled and filtered using minimum redundancy maximum correlation (mRMR) and the least absolute shrinkage and selection operator algorithm (LASSO) regression, in turn, and the more optimal subset of radiomics features was selected. In addition, the radiomics score (rad-score) was calculated for each patient by the LASSO method. Clinical data were also analyzed to predict the prognosis of AP. Three prediction models, including clinical model, radiomics model, and combined clinical-radiomics model, are constructed. The effectiveness of each model was evaluated using receiver operating characteristic (ROC) curve analysis. The DeLong test was employed to compare the differences between the ROC curves. The decision curve analysis (DCA) is used to assess the net benefit of the model. Results: The mRMR algorithm and LASSO regression were used to select 13 radiomics features with high values. The rad-score of each texture feature was calculated to fuse MCTSI to establish the radiomics model, and both the clinical model and clinical-radiomics model were established. The clinical-radiomics model showed the best performance, the AUC and 95% confidence interval, accuracy, sensitivity, and specificity of the clinical-radiomics model in the training set were 0.984 (0.964-1.000), 0.947, 0.955, and 0.931, respectively. In the validation set, they were 0.942 (0.870-1.000), 0.929, 0.966, and 0.846, respectively. The Delong test showed that the predictive efficacy of the clinical-radiomics model was higher than that of the clinical model (Z = 2.767, p = 0.005) and the radiomics model (Z = 2.033, p = 0.042) in the validation set. Decision curve analysis demonstrated higher net clinical benefit for the clinical-radiomics model. Conclusion: The pancreatic parenchymal CT clinical-radiomics model has high diagnostic efficacy in predicting the progression of early AP patients, which is significantly better than the clinical or radiomics model. The combined model can help identify and determine the progression trend of patients with AP and improve the prognosis and survival of patients as early as possible.
RESUMO
Since the enhancement of the photonic spin Hall effect (PSHE) is limited around the Brewster's angle, the scientific problem of how to extend the range of incident angles and to keep them unidirectional for the enhanced PSHE remains open. Here, we propose an effective method to achieve the ultrawide angle and unidirectional enhancement of PSHE via the omnidirectional Brewster's effect in a tilted uniaxial crystal. By properly setting the permittivity and the optical axial angle of the uniaxial crystal, the omnidirectional Brewster's effect can be obtained to realize an ultrawide angle enhancement of the PSHE. Then, by appropriately deviating the optical axial angle, the ultrawide enhancement of the PSHE can be achieved within the maximum incident angle range of 60° with unchanged direction. These findings inspire an unprecedented route to facilitate the applications in precision measurement and spin-dependent devices.