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Mesenchymal stem cells (MSCs), as a stem cell type with multiple differentiation potentials and immune regulatory abilities, have shown broad prospects in the treatment of ischemic stroke in recent years. The main characteristics of MSCs include their self-renewal ability, differentiation potential for different types of cells, and the ability to secrete various bioactive factors such as cytokines, chemokines, and growth factors, which play a key role in tissue repair and regeneration. In the treatment of ischemic stroke, MSCs exert therapeutic effects through various mechanisms, including promoting vascular regeneration of damaged brain tissue, reducing inflammatory responses, and protecting neurons from damage caused by apoptosis. Research have shown that MSCs can promote the repair of ischemic areas by releasing neurotrophic factors and angiogenic factors, while inhibiting immune responses triggered by ischemia, thereby improving neurological function. With the in-depth study of its biological mechanism, MSCs have gradually shown good safety and effectiveness in clinical applications. Therefore, fully exploring and utilizing the potential of MSCs in the treatment of ischemic stroke may provide new ideas and solutions for future neural repair and regenerative medicine.
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BACKGROUND: Cancer stem cells (CSCs) are critical factors that limit the effectiveness of gastric cancer (GC) therapy. Circular RNAs (circRNAs) are confirmed as important regulators of many cancers. However, their role in regulating CSC-like properties of GC remains largely unknown. Our study aimed to investigate the role of circUBA2 in CSC maintenance and the underlying mechanisms. METHODS: We identified circUBA2 as an upregulated gene using circRNA microarray analysis. qRT-PCR was used to examine the circUBA2 levels in normal and GC tissues. In vitro and in vivo functional assays were performed to validate the role of circUBA2 in proliferation, migration, metastasis and CSC-like properties of GC cell. The relationship between circUBA2, miR-144-5p and STC1 was characterised using bioinformatics analysis, a dual fluorescence reporter system, FISH, and RIP assays. RESULTS: CircUBA2 expression was significantly increased in GC tissues, and patients with GC with high circUBA2 expression had a poor prognosis. CircUBA2 enhances CSC-like properties of GC, thereby promoting cell proliferation, migration, and metastasis. Mechanistically, circUBA2 promoted GC malignancy and CSC-like properties by acting as a sponge for miR-144-5p to upregulate STC1 expression and further activate the IL-6/JAK2/STAT3 signaling pathway. More importantly, the ability of circUBA2 to enhance CSC-like properties was inhibited by tocilizumab, a humanised Interleukin-6 receptor (IL-6R) antibody. Thus, circUBA2 knockdown and tocilizumab synergistically inhibited CSC-like properties. CONCLUSIONS: Our study demonstrated the critical role of circUBA2 in regulating CSC-like properties in GC. CircUBA2 may be a promising prognostic biomarker for GC.
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Chimeric antigen receptor (CAR) T cells have shown significant efficacy in hematological diseases. However, CAR T therapy has demonstrated limited efficacy in solid tumors, including glioblastoma (GBM). One of the most important reasons is the immunosuppressive tumor microenvironment (TME), which promotes tumor growth and suppresses immune cells used to eliminate tumor cells. The human transforming growth factor ß (TGF-ß) plays a crucial role in forming the suppressive GBM TME and driving the suppression of the anti-GBM response. To mitigate TGF-ß-mediated suppressive activity, we combined a dominant-negative TGF-ß receptor II (dnTGFßRII) with our previous bicistronic CART-EGFR-IL13Rα2 construct, currently being evaluated in a clinical trial, to generate CART-EGFR-IL13Rα2-dnTGFßRII, a tri-modular construct we are developing for clinical application. We hypothesized that this approach would more effectively subvert resistance mechanisms observed with GBM. Our data suggest that CART-EGFR-IL13Rα2-dnTGFßRII significantly augments T cell proliferation, enhances functional responses, and improves the fitness of bystander cells, particularly by decreasing the TGF-ß concentration in a TGF-ß-rich TME. In addition, in vivo studies validate the safety and efficacy of the dnTGFßRII cooperating with CARs in targeting and eradicating GBM in an NSG mouse model.
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BACKGROUND AND AIM: Obesity and metabolic abnormalities were associated with an increased risk of cardiovascular disease. However, it is unclear how metabolic weight phenotypes relate to cardiovascular diseases in postmenopausal women. This study aimed to explore the relationships in postmenopausal women. METHODS AND RESULTS: We included 15,575 postmenopausal women aged 35-75 years (median age, 60.6) without cardiovascular disease at baseline from a subcohort of the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project. Metabolically unhealthy phenotype was defined as having ≥2 risk factors of metabolic syndrome: blood pressure ≥130/85 mm Hg or current use of antihypertensive drugs, fasting glucose ≥5.6 mmol/L or current use of antidiabetic agents, triglycerides ≥1.7 mmol/L, and high-density lipoprotein cholesterol <1.3 mmol/L. Cox regression analysis was used to evaluate the risks of cardiovascular diseases. Over a median follow-up period of 3.55 (interquartile range, 2.59-4.44) years, a total of 1354 cardiovascular events occurred. Compared to metabolically healthy normal weight, the multivariate-adjusted hazard ratios and their 95% confidence intervals were 1.41 (1.16-1.72) for metabolically unhealthy normal weight, 1.42 (1.16-1.73) for metabolically healthy overweight/obesity, and 1.75 (1.48-2.08) for metabolically unhealthy overweight/obesity. Subdividing overweight/obesity into separate groups revealed higher total cardiovascular disease risk only in metabolically unhealthy individuals across body mass index categories. CONCLUSION: In postmenopausal women, both metabolically healthy overweight/obesity and metabolically unhealthy normal weight were associated with a higher risk of cardiovascular disease compared to metabolically healthy normal weight, and the greatest risk was observed in the metabolically unhealthy overweight/obesity category.
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Enfermedades Cardiovasculares , Síndrome Metabólico , Obesidad , Fenotipo , Posmenopausia , Humanos , Femenino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Anciano , Síndrome Metabólico/epidemiología , Síndrome Metabólico/diagnóstico , China/epidemiología , Adulto , Medición de Riesgo , Obesidad/epidemiología , Obesidad/diagnóstico , Factores de Tiempo , Factores de Riesgo de Enfermedad Cardiaca , Obesidad Metabólica Benigna/epidemiología , Obesidad Metabólica Benigna/diagnóstico , Obesidad Metabólica Benigna/sangre , Obesidad Metabólica Benigna/fisiopatología , Estudios Prospectivos , Pronóstico , Factores de Riesgo , Biomarcadores/sangre , IncidenciaRESUMEN
OBJECTIVE: Textbook outcome (TO) is widely recognized as a comprehensive prognostic indication for patients with gastric cancer (GC). This study aims to develop a modified TO (mTO) for elderly patients with GC. METHODS: Data from the elderly patients (aged ≥ 65 years) in two Chinese tertiary referral hospitals were analyzed. 1389 patients from Fujian Medical University Union Hospital were assigned as the training cohort and 185 patients from Affiliated Hospital of Putian University as the validation cohort. Nomogram was developed by the independent prognostic factors of Overall Survival (OS) based on Cox regression. RESULTS: In the training cohort, laparoscopic surgery was significantly correlated with higher TO rate (P < 0.05). Cox regression analysis revealed that surgical approach was also an independent factor of OS (P < 0.001), distinct from the traditional TO. In light of these findings, TO parameters were enhanced by the inclusion of surgical approach, rendering a modified TO (mTO). Further analysis showed that mTO, tumor size, pTNM staging, and adjuvant chemotherapy were independent prognostic factors associated with OS (all P < 0.05). Additionally, the nomogram incorporating these four indicators accurately predicted 1-, 3-, and 5-year OS in the training cohort, with AUC values of 0.793, 0.814, and 0.807, respectively, and exhibited outstanding predictive performance within the validation cohort. CONCLUSION: mTO holds a robust association with the prognosis of elderly patients with GC, meriting intensified attention in efforts aimed at enhancing surgical quality. Furthermore, the predictive model incorporating mTO demonstrates excellent predictive performance for elderly patients with GC.
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OBJECTIVE: To study the historical global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. METHODS: Incidence data were retrieved from the Cancer Incidence in Five Continents (CI5) volumes I-XI, and mortality data were obtained from the latest update of the World Health Organization (WHO) mortality database. We used join-point regression analysis to examine historical incidence and mortality trends and used the package NORDPRED in R to predict the number of deaths and mortality rates by 2035 by country and sex. RESULTS: More than 1,089,000 new cases of gastric cancer and 769,000 related deaths were reported in 2020. The average annual percent change (AAPC) in the incidence of gastric cancer from 2003 to 2012 among the male population, South Korea, Japan, Malta, Canada, Cyprus, and Switzerland showed an increasing trend (P > 0.05); among the female population, Canada [AAPC, 1.2; (95%Cl, 0.5-2), P < 0.05] showed an increasing trend; and South Korea, Ecuador, Thailand, and Cyprus showed an increasing trend (P > 0.05). AAPC in the mortality of gastric cancer from 2006 to 2015 among the male population, Thailand [3.5 (95%cl, 1.6-5.4), P < 0.05] showed an increasing trend; Malta Island, New Zealand, Turkey, Switzerland, and Cyprus had an increasing trend (P > 0.05); among the male population aged 20-44, Thailand [AAPC, 3.4; (95%cl, 1.3-5.4), P < 0.05] showed an increasing trend; Norway, New Zealand, The Netherlands, Slovakia, France, Colombia, Lithuania, and the USA showed an increasing trend (P > 0.05). It is predicted that the mortality rate in Slovenia and France's female population will show an increasing trend by 2035. It is predicted that the absolute number of deaths in the Israeli male population and in Chile, France, and Canada female population will increase by 2035. CONCLUSION: In the past decade, the incidence and mortality of gastric cancer have shown a decreasing trend; however, there are still some countries showing an increasing trend, especially among populations younger than 45 years. Although mortality in most countries is predicted to decline by 2035, the absolute number of deaths due to gastric cancer may further increase due to population growth.
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Salud Global , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/epidemiología , Masculino , Femenino , Incidencia , Salud Global/estadística & datos numéricos , Mortalidad/tendencias , Predicción , Distribución por SexoRESUMEN
Helicobacter pylori (HP) infection initiates and promotes gastric carcinogenesis. ONECUT2 shows promise for tumor diagnosis, prognosis, and treatment. This study explored ONECUT2's role and the specific mechanism underlying HP infection-associated gastric carcinogenesis to suggest a basis for targeting ONECUT2 as a therapeutic strategy for gastric cancer (GC). Multidimensional data supported an association between ONECUT2, HP infection, and GC pathogenesis. HP infection upregulated ONECUT2 transcriptional activity via NFκB. In vitro and in vivo experiments demonstrated that ONECUT2 increased the stemness of GC cells. ONECUT2 was also shown to inhibit PPP2R4 transcription, resulting in reduced PP2A activity, which in turn increased AKT/ß-catenin phosphorylation. AKT/ß-catenin phosphorylation facilitates ß-catenin translocation to the nucleus, initiating transcription of downstream stemness-associated genes in GC cells. HP infection upregulated the reduction of AKT and ß-catenin phosphorylation triggered by ONECUT2 downregulation via ONECUT2 induction. Clinical survival analysis indicated that high ONECUT2 expression may indicate poor prognosis in GC. This study highlights a critical role played by ONECUT2 in promoting HP infection-associated GC by enhancing cell stemness through the PPP2R4/AKT/ß-catenin signaling pathway. These findings suggest promising therapeutic strategies and potential targets for GC treatment.
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Infecciones por Helicobacter , Helicobacter pylori , Células Madre Neoplásicas , Proteínas Proto-Oncogénicas c-akt , Neoplasias Gástricas , Animales , Femenino , Humanos , Masculino , Ratones , beta Catenina/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/patología , Ratones Endogámicos BALB C , Ratones Desnudos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Fosforilación , Proteína Fosfatasa 2/metabolismo , Proteína Fosfatasa 2/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Neoplasias Gástricas/patología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genéticaRESUMEN
OBJECTIVE: Precancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood. DESIGN: An integrated analysis of genes associated with metaplasia, dysplasia was conducted, verified and characterised in the gastric tissues of patients by single-cell RNA sequencing and immunostaining. Multiple mouse models, including homozygous conditional knockout Klhl21-floxed mice, were generated to investigate the role of Klhl21 deletion in stemness, DNA damage and tumour formation. Mass-spectrometry-based proteomics and ribosome sequencing were used to elucidate the underlying molecular mechanisms. RESULTS: Kelch-like protein 21 (KLHL21) expression progressively decreased in metaplasia, dysplasia and cancer. Genetic deletion of Klhl21 enhances the rapid proliferation of Mist1+ cells and their descendant cells. Klhl21 loss during metaplasia facilitates the recruitment of damaged cells into the cell cycle via STAT3 signalling. Increased STAT3 activity was confirmed in cancer cells lacking KLHL21, boosting self-renewal and tumourigenicity. Mechanistically, the loss of KLHL21 promotes PIK3CB mRNA translation by stabilising the PABPC1-eIF4G complex, subsequently causing STAT3 activation. Pharmacological STAT3 inhibition by TTI-101 elicited anticancer effects, effectively impeding the transition from metaplasia to dysplasia. In patients with gastric cancer, low levels of KLHL21 had a shorter survival rate and a worse response to adjuvant chemotherapy. CONCLUSIONS: Our findings highlighted that KLHL21 loss triggers STAT3 reactivation through PABPC1-mediated PIK3CB translational activation, and targeting STAT3 can reverse preneoplastic metaplasia in KLHL21-deficient stomachs.
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In the realm of e-commerce, personalized recommendations are a crucial component in enhancing user experience and optimizing sales efficiency. To address the inherent sparsity challenge prevalent in collaborative filtering algorithms within personalized recommendation systems, we propose a novel hybrid e-commerce recommendation algorithm based on the User-Nearest-Neighbor model. By integrating the user nearest neighbor model with other recommendation algorithms, this approach effectively mitigates data sparsity and facilitates a more nuanced understanding of the user-product relationship, consequently elevating recommendation quality and enhancing user experience. Taking into account considerations such as data scale and recommendation performance, we conducted experiments utilizing the Spark distributed platform. Empirical findings demonstrate the superiority of our hybrid algorithm over standalone collaborative filtering algorithms across various recommendation indicators.
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The gene encoding the NUAK family kinase 1 (NUAK1) is frequently amplified and its expression is upregulated, activating oncogenic signaling in various cancers. However, little is known about its role in gastric cancer (GC). We investigate the mechanistic links among NUAK1, Hedgehog signaling, and tumorigenesis in GC. NUAK1 overexpression is validated in local and public GC cohorts. Patient-derived xenograft and transgenic mouse models demonstrate that NUAK1 depletion or inhibition dramatically ameliorates gastric tumorigenesis. NUAK1 upregulates GLI1 expression by activating STAT5-mediated transcription and stabilizing GLI1 protein. NUAK1 depletion or inhibition impairs cancer cell expansion, tumor formation, and chemotherapy resistance in in vitro and in vivo models. Clinicopathological analysis confirms that upregulated NUAK1 expression correlates with poor prognosis and chemotherapy resistance in human GC. Our findings demonstrate that the signaling axis NUAK1/STAT5/GLI1 promotes cancer cell expansion and tumorigenesis and indicate that NUAK1 is an attractive therapeutic target and prognostic factor in GC.
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Proliferación Celular , Resistencia a Antineoplásicos , Factores de Transcripción SOXB1 , Factor de Transcripción STAT5 , Transducción de Señal , Neoplasias Gástricas , Proteína con Dedos de Zinc GLI1 , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamiento farmacológico , Humanos , Proteína con Dedos de Zinc GLI1/metabolismo , Proteína con Dedos de Zinc GLI1/genética , Resistencia a Antineoplásicos/genética , Factor de Transcripción STAT5/metabolismo , Factor de Transcripción STAT5/genética , Animales , Línea Celular Tumoral , Ratones , Proliferación Celular/efectos de los fármacos , Factores de Transcripción SOXB1/metabolismo , Factores de Transcripción SOXB1/genética , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Masculino , Femenino , Carcinogénesis/patología , Carcinogénesis/genéticaRESUMEN
BACKGROUND: Intracranial arterial narrowing is a significant factor leading to brief episodes of reduced blood flow to the brain, known as transient ischemic attacks, or full-blown strokes. While atherosclerosis is commonly associated with intracranial arterial narrowing, it is frequently of a non-atherosclerotic nature in younger patients. CASE SUMMARY: Here, we present the case of a young stroke patient with narrowing of the middle cerebral artery (MCA), characterized as non-atherosclerotic lesions, who experienced an ischemic stroke despite receiving standard drug therapy. The patient underwent digital subtraction angiography (DSA) to assess the entire network of blood vessels in the brain, revealing significant narrowing (approximately 80%) in the M1 segment of the right MCA. Subsequently, the patient underwent Drug-Coated Balloon Angioplasty to treat the stenosis in the right MCA's M1 segment. Follow-up DSA confirmed the resolution of stenosis in this segment. Although the remaining branches showed satisfactory blood flow, the vessel wall exhibited irregularities. A review of DSA conducted six months later showed no evident stenosis in the right MCA, with a smooth vessel wall. CONCLUSION: The use of drug-coated balloon angioplasty demonstrated favorable outcomes in repairing and reshaping the blood vessel wall in young patients. Therefore, it may be considered a promising treatment option for similar cases.
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As an antioxidant and antiozonant, N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is predominantly used in the rubber industry to prevent degradation. However, 6PPD can be ozonated to generate a highly toxic transformation product called N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone), which is toxic to aquatic and terrestrial organisms. Thus, 6PPD and 6PPD-quinone, two emerging contaminants, have attracted extensive attention recently. This review discussed the levels and distribution of 6PPD and 6PPD-quinone in the environment and investigated their toxic effects on a series of organisms. 6PPD and 6PPD-quinone have been widely found in air, water, and dust, while data on soil, sediment, and biota are scarce. 6PPD-quinone can cause teratogenic, developmental, reproductive, neuronal, and genetic toxicity for organisms, at environmentally relevant concentrations. Future research should pay more attention to the bioaccumulation, biomagnification, transformation, and toxic mechanisms of 6PPD and 6PPD-quinone.
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Objective: Spinal schwannomas are the most common intradural extramedullary tumors, and their complete removal is recommended to avoid tumor recurrence. Although laminoplasty provides a sufficient window for tumor resection, this approach may increase tissue trauma and cause postoperative instability compared with unilateral hemilaminectomy. This study aimed to compare the efficacy and clinical outcomes of the two approaches. Materials and methods: We included 100 consecutive patients who underwent unilateral hemilaminectomy or laminoplasty for resection of spinal schwannomas between January 2015 and February 2023. The patients' baseline characteristics, including sex, age, tumor location, percentage of tumor occupying the intradural space, operative time, postoperative length of hospital stay, intraoperative bleeding volume, visual analog scale score, and neurologic results, were retrospectively analyzed. Results: Hemilaminectomy patients who underwent unilateral hemilaminectomy had smaller intraoperative bleeding (p = 0.020) volume, shorter operative time (p = 0.012), and shorter postoperative length of hospital stay (p = 0.044). The mean VAS scores at the last follow-up were similar between the two groups (p = 0.658). Although the postoperative McCormick and Karnofsky Performance scores were not significantly different between the laminoplasty and unilateral hemilaminectomy groups (p = 0.687 and p = 0.649, respectively), there was a statistically significant improvement based on postoperative neurological results compared to preoperative neurological results for both groups. The incidence of postoperative complications was 5% and 11.7% in the unilateral hemilaminectomy and laminoplasty groups, respectively (p = 0.308). Conclusions: For spinal schwannoma resection, unilateral hemilaminectomy has more advantages than laminoplasty, including a shorter postoperative hospital stay, faster procedure, and less intraoperative blood loss while achieving the same desired result.
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Importance: Splenic hilar lymphadenectomy has been recommended for locally advanced proximal gastric cancer (APGC) involving the greater curvature. However, it is unclear whether laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) is associated with a long-term survival benefit for APGC without greater curvature invasion. Objective: To present the 5-year follow-up data from a randomized clinical trial that compared laparoscopic total gastrectomy (D2 group) with D2 plus LSPSHL (D2 + No. 10 group) among patients with resectable APGC. Design, Setting, and Participants: This is a post hoc secondary analysis of a randomized clinical trial that enrolled 536 patients with potentially resectable APGC (cT2-4a, N0 or N+, and M0) without greater curvature invasion from January 5, 2015, to October 10, 2018. All patients were tracked for at least 5 years. The final follow-up was on October 30, 2023. Interventions: Patients were randomly assigned in a 1:1 ratio to the D2 + No. 10 or D2 groups. Main Outcomes and Measures: The 5-year disease-free survival (DFS) and overall survival (OS) rates were measured. Recurrence patterns and causes of death were compared. Results: A total of 526 patients (392 men [74.5%]; mean [SD] age, 60.6 [9.6] years) were included in the modified intent-to-treat analysis, with 263 patients in each group. The 5-year DFS rate was 63.9% (95% CI, 58.1%-69.7%) for the D2 + No. 10 group and 55.1% (95% CI, 49.1%-61.1%) for the D2 group (log-rank P = .04). A statistically significant difference was observed in the 5-year OS between the D2 + No. 10 group and the D2 group (66.2% [95% CI, 60.4%-71.9%] vs 57.4% [95% CI, 51.4%-63.4%]; log-rank P = .03). The No. 10 lymph node exhibited a therapeutic value index (TVI) of 6.5, surpassing that of Nos. 8a (TVI, 3.0), 11 (TVI, 5.8), and 12a (TVI, 0.8). A total of 86 patients in the D2 + No. 10 group (cumulative incidence, 32.7%) and 111 patients in the D2 group (cumulative incidence, 42.2%) experienced recurrence (hazard ratio, 0.72; 95% CI, 0.54-0.95; P = .02). The multivariable competing risk regression model demonstrated that D2 + No. 10 remained an independent protective factor for a lower 5-year cumulative recurrence rate after surgery (hazard ratio, 0.75; 95% CI, 0.56-1.00; P = .05). There was a significant difference in the 5-year cumulative recurrence rate at the No. 10 lymph node area between the 2 groups (D2 + No. 10 group vs D2 group: 0% vs 2.3% [n = 6]; P = .01). Conclusions: This post hoc secondary analysis of a randomized clinical trial found that laparoscopic total gastrectomy with LSPSHL can improve the prognosis and reduce recurrence for APGC without greater curvature invasion. Future multicenter studies are warranted to validate these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02333721.
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Gastrectomía , Laparoscopía , Escisión del Ganglio Linfático , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Masculino , Escisión del Ganglio Linfático/métodos , Femenino , Laparoscopía/métodos , Persona de Mediana Edad , Gastrectomía/métodos , Anciano , Bazo/patología , Bazo/cirugía , Tasa de Supervivencia , Estudios de Seguimiento , Invasividad Neoplásica , Tratamientos Conservadores del Órgano/métodos , Supervivencia sin EnfermedadRESUMEN
Robotic surgery may be an alternative to laparoscopic surgery for gastric cancer (GC). However, randomized controlled trials (RCTs) reporting the differences in survival between these two approaches are currently lacking. From September 2017 to January 2020, 300 patients with cT1-4a and N0/+ were enrolled and randomized to either the robotic (RDG) or laparoscopic distal gastrectomy (LDG) group (NCT03313700). The primary endpoint was 3-year disease-free survival (DFS); secondary endpoints reported here are the 3-year overall survival (OS) and recurrence patterns. The remaining secondary outcomes include intraoperative outcomes, postoperative recovery, quality of lymphadenectomy, and cost differences, which have previously been reported. There were 283 patients in the modified intention-to-treat analysis (RDG group: n = 141; LDG group: n = 142). The trial has met pre-specified endpoints. The 3-year DFS rates were 85.8% and 73.2% in the RDG and LDG groups, respectively (p = 0.011). Multivariable Cox regression model including age, tumor size, sex, ECOG PS, lymphovascular invasion, histology, pT stage, and pN stage showed that RDG was associated with better 3-year DFS (HR: 0.541; 95% CI: 0.314-0.932). The RDG also improved the 3-year cumulative recurrence rate (RDG vs. LDG: 12.1% vs. 21.1%; HR: 0.546, 95% CI: 0.302-0.990). Compared to LDG, RDG demonstrated non-inferiority in 3-year DFS rate.
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Gastrectomía , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Gastrectomía/métodos , Laparoscopía/métodos , Masculino , Femenino , Procedimientos Quirúrgicos Robotizados/métodos , Persona de Mediana Edad , Anciano , Escisión del Ganglio Linfático/métodos , Supervivencia sin Enfermedad , Resultado del Tratamiento , Recurrencia Local de Neoplasia , AdultoRESUMEN
Background: Pyroptosis plays a crucial role in immune responses. However, the effects of pyroptosis on tumor microenvironment remodeling and immunotherapy in gastric cancer (GC) remain unclear. Patients and Methods: Large-sample GEO data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory roles of pyroptosis. TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed. The prognostic performance of the PRS was validated using postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=978). Single-cell sequencing and multiplex immunofluorescence were used to elucidate the immune cell infiltration landscape associated with PRS. Patients with GC who received neoadjuvant immunotherapy (n=48) and those with GC who received neoadjuvant chemotherapy (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy. Results: GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful role in immune regulation. PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC. PRSlow is associated with an activated pyroptosis pathway and greater infiltration of anti-tumor immune cells, including more effector and CD4+ T cells, and with the polarization of tumor-associated macrophages in the tumor center. Importantly, PRSlow marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients with combined positive score ≥1 who benefit from neoadjuvant immunotherapy. Conclusion: Our study demonstrated that pyroptosis activates immune processes in the tumor microenvironment. A low PRS correlates with enhanced infiltration of anti-tumor immune cells at the tumor site, increased pyroptotic activity, and improved patient outcomes. The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapeutic strategies for patients with GC.
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Inmunoterapia , Terapia Neoadyuvante , Piroptosis , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patología , Terapia Neoadyuvante/métodos , Microambiente Tumoral/inmunología , Inmunoterapia/métodos , Masculino , Pronóstico , Femenino , Biomarcadores de Tumor/metabolismo , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , MultiómicaRESUMEN
BACKGROUND: Learning curves have been used in the field of robotic gastrectomy (RG). However, it should be noted that the previous study did not comprehensively investigate all changes related to the learning curve. This study aims to establish a learning curve for radical RG and evaluate its effect on the short-term outcomes of patients with gastric cancer. METHODS: The clinicopathological data of 527 patients who underwent RG between August 2016 and June 2021 were retrospectively analyzed. Learning curves related to the operation time and postoperative hospital stay were determined separately using cumulative sum (CUSUM) analysis. Then, the impact of the learning curve on surgical efficacy was analyzed. RESULTS: Combining the CUSUM curve break points and technical optimization time points, the entire cohort was divided into three phases (patients 1-100, 101-250, and 251-527). The postoperative complication rate and postoperative recovery time tended to decrease significantly with phase advancement ( P <0.05). More extraperigastric examined lymph nodes (LN) were retrieved in phase III than in phase I (I vs. III, 15.12±6.90 vs. 17.40±7.05, P =0.005). The rate of LN noncompliance decreased with phase advancement. Textbook outcome (TO) analysis showed that the learning phase was an independent factor in TO attainment ( P <0.05). CONCLUSION: With learning phase advancement, the short-term outcomes were significantly improved. It is possible that our optimization of surgical procedures could have contributed to this improvement. The findings of this study facilitate the safe dissemination of RG in the minimally invasive era.
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Gastrectomía , Curva de Aprendizaje , Procedimientos Quirúrgicos Robotizados , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Procedimientos Quirúrgicos Robotizados/métodos , Gastrectomía/métodos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Tempo Operativo , Adulto , Tiempo de Internación/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Hospitales de Alto Volumen/estadística & datos numéricos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Evidence regarding sex differences in the associations of traditional risk factors with incident heart failure (HF) hospitalization among Chinese general adults is insufficient. This study aimed to evaluate the potential sex differences in the associations of traditional risk factors with HF among Chinese general adults. METHODS AND RESULTS: Data were from a subcohort of the China PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project. The traditional risk factors were collected at baseline, and the study outcome was HF-related hospitalization identified from the Inpatients Registry. A total of 102 278 participants (mean age, 54.3 years; 39.5% men) without prevalent HF were recruited. A total of 1588 cases of HF-related hospitalization were captured after a median follow-up of 3.52 years. The incidence rates were significantly higher in men (2.1%) than in women (1.2%). However, the observed lower risk of HF in women was significantly attenuated or even vanished when several traditional risk factors were poorly controlled (P for sex-by-risk factors <0.05). The selected 11 risk factors collectively explained 62.5% (95% CI, 55.1-68.8) of population attributable fraction for HF in women, which is much higher than in men (population attributable fraction, 39.6% [95% CI, 28.5-48.9]). CONCLUSIONS: Although women had a lower incidence rate of hospitalization for HF than men in this study, the risk for HF increased more remarkably in women than in men when several traditional risk factors were poorly controlled. This study suggests that intensive preventative strategies are immediately needed in China.
Asunto(s)
Insuficiencia Cardíaca , Hospitalización , Humanos , Insuficiencia Cardíaca/epidemiología , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Incidencia , Hospitalización/estadística & datos numéricos , Estudios Prospectivos , Factores Sexuales , Factores de Riesgo , Adulto , Anciano , Medición de Riesgo , Sistema de Registros , Pueblos del Este de AsiaRESUMEN
Quantum telecloning, a pivotal multiuser quantum communication protocol in the realm of quantum information science, facilitates the copy of a quantum state across M distinct locations through teleportation technique. In the continuous-variable regime, the implementation of quantum telecloning necessitates the distribution of multipartite entanglement among the sender and M receiver parties. Following this, the sender carries out optic-electro conversion and transmits information via classical channel to M spatially separated receivers simultaneously. To successfully reconstruct the input state, electro-optic conversion needs to be employed by each receiver. However, due to these conversions, the bandwidth of the optical mode in this process is largely constrained. In this Letter, we present an all-optical version of the 1â2 continuous-variable quantum telecloning scheme, wherein both optic-electro and electro-optic conversions are replaced by optical components. Our scheme allows the two receivers to achieve input state reconstruction solely by utilizing beam splitters, significantly simplifying its complexity. We experimentally demonstrate all-optical 1â2 quantum telecloning of coherent state and achieve the fidelities of 58.6%±1.0% and 58.6%±1.1% for two clones, exceeding the corresponding classical limits (51.9%±0.5% and 51.9%±0.6%). Our results establish a platform for constructing a flexible all-optical multiuser quantum network and promote the field of all-optical quantum information processing.
RESUMEN
Breast cancer (BC) poses a great threat to women's health. Neuronal regeneration related protein (NREP) is a multifunctional protein that is involved in embryonic development, regeneration, and human disease. However, the biological function of NREP in tumors is rarely reported and its role in BC remains unknown. Bioinformatics analysis showed that NREP is highly expressed and closely correlated with poor survival in BC patients. Under hypoxic conditions, NREP was upregulated in BC cells, and this promotion was reversed by hypoxia-inducible factor HIF-1α suppression. Luciferase reporter system and chromatin immunoprecipitation assays confirmed that HIF-1α directly binds to the promoter of NREP to increase the transcriptional activity of NREP. NREP suppression inhibited cell proliferation, arrested the cell cycle at the G1/S phase, and promoted apoptosis and caspase-3 activity in BC cells. Suppression of NREP decreased the tube formation ability of HUVECs. In addition, NREP downregulation showed an inhibition effect on cell migration, invasion, and EMT of BC cells. In NREP overexpressed cells, all these changes were reversed. In vivo, animal experiments also confirmed that NREP promotes BC tumor growth and metastasis. In addition, NREP promoted cellular glycolysis and enhanced the levels of glucose consumption, ATP, lactate production, and glucose transporters expression in NREP-overexpressed BC cells. In summary, our results demonstrated that NREP could be transcriptional activated by HIF-1α, which may aggravate BC tumor growth and metastasis by promoting cellular glycolysis. This result suggested that NREP may play an essential part in BC progression.