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1.
J Clin Invest ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39024569

RESUMO

Intestinal fibrosis, a severe complication of Crohn's disease (CD), is characterized by excessive extracellular matrix (ECM) deposition and induces intestinal strictures, but there are no effective anti-fibrosis drugs available for clinical application. We performed single-cell RNA sequencing (scRNA-seq) of fibrotic and non-fibrotic ileal tissues from CD patients with intestinal obstruction. Analysis revealed mesenchymal stromal cells (MSCs) as the major producers of ECM and the increased infiltration of its subset FAP+ fibroblasts in fibrotic sites, which was confirmed by immunofluorescence and flow cytometry. Single cell transcriptomic profiling of chronic Dextran Sulfate Sodium Salt (DSS) murine colitis model revealed Cd81+Pi16- fibroblasts exhibited transcriptomic and functional similarities to human FAP+ fibroblasts. Consistently, FAP+ fibroblasts were identified as the key subtype with the highest level of ECM production in fibrotic intestines. Furthermore, specific knockout or pharmacological inhibition of TWIST1, which was highly expressed by FAP+ fibroblasts, could significantly ameliorate fibrosis in mice. In addition, TWIST1 expression was induced by CXCL9+ macrophages enriched in fibrotic tissues via IL-1ß and TGF-ß signal. These findings suggest the inhibition of TWIST1 as a promising strategy for CD fibrosis treatment.

2.
Small ; 20(12): e2304433, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37948437

RESUMO

Age-related bone defects are a leading cause of disability and mortality in elderly individuals, and targeted therapy to delay the senescence of bone marrow-derived mesenchymal stem cells (MSCs) has emerged as a promising strategy to rejuvenate bone regeneration in aged scenarios. More specifically, activating the nicotinamide adenine dinucleotide (NAD+)-dependent sirtuin 1 (SIRT1) pathway is demonstrated to effectively counteract MSC senescence and thus promote osteogenesis. Herein, based on an inventively identified senescent MSC-specific surface marker Kremen1, a senescence-targeted and NAD+ dependent SIRT1 activated nanoplatform is fabricated with a dual delivery of resveratrol (RSV) (SIRT1 promoter) and nicotinamide riboside (NR, NAD+ precursor). This targeting nanoplatform exhibits a strong affinity for senescent MSCs through conjugation with anti-Kremen1 antibodies and enables specifically responsive release of NR and RSV in lysosomes via senescence-associated ß-galactosidase-stimulated enzymatic hydrolysis of the hydrophilic chain. Furthermore, this nanoplatform performs well in promoting aged bone formation both in vitro and in vivo by boosting NAD+, activating SIRT1, and delaying MSC senescence. For the first time, a novel senescent MSC-specific surface marker is identified and aged bone repair is rejuvenated by delaying senescence of MSCs using an active targeting platform. This discovery opens up new insights for nanotherapeutics aimed at age-related diseases.


Assuntos
NAD , Sirtuína 1 , Idoso , Humanos , Sirtuína 1/metabolismo , NAD/metabolismo , Senescência Celular , Osteogênese , Resveratrol/farmacologia , Regeneração Óssea
3.
Adv Mater ; 36(9): e2306552, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37848015

RESUMO

Aging exacerbates the dysfunction of tissue regeneration at multiple levels and gradually diminishes individual's capacity to withstand stress, damage, and disease. The excessive accumulation of reactive oxygen species (ROS) is considered a hallmark feature of senescent stem cells, which causes oxidative stress, deteriorates the host microenvironment, and eventually becomes a critical obstacle for aged bone defect repair. Till now, the strategies cannot synchronously and thoroughly regulate intracellular and extracellular ROS in senescent cells. Herein, a multihierarchy ROS scavenging system for aged bone regeneration is developed by fabricating an injectable PEGylated poly(glycerol sebacate) (PEGS-NH2 )/poly(γ-glutamic acid) (γ-PGA) hydrogel containing rapamycin-loaded poly(diselenide-carbonate) nanomicelles (PSeR). This PSeR hydrogel exhibits highly sensitive ROS responsiveness to the local aged microenvironment and dynamically releases drug-loaded nanomicelles to scavenge the intracellular ROS accumulated in senescent bone mesenchymal stem cells. The PSeR hydrogel effectively tunes the antioxidant function and delays senescence of bone mesenchymal stem cells by safeguarding DNA replication in an oxidative environment, thereby promoting the self-renewal ability and enhancing the osteogenic capacity for aged bone repair in vitro and in vivo. Thus, this multihierarchy ROS-regulated hydrogel provides a new strategy for treating degenerative diseases.


Assuntos
Antioxidantes , Hidrogéis , Ratos , Animais , Espécies Reativas de Oxigênio , Hidrogéis/farmacologia , Ratos Sprague-Dawley , Antioxidantes/farmacologia , Estresse Oxidativo
5.
Future Oncol ; 19(40): 2641-2650, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38108112

RESUMO

Conventional laparoscopic-assisted right hemicolectomy requires a small abdominal incision to extract the specimen, which becomes an important source of postoperative complications and impairs perioperative experience. Transvaginal natural orifice specimen extraction surgery (NOSES VIIIA) avoids this small incision by extracting the specimen through the vagina. Here we describe the design of a multicenter, open-label, parallel, noninferior, phase III randomized controlled trial (NCT05495048). The aim of this study is to confirm that the NOSES VIIIA procedure is not inferior to small-incision assisted right hemicolectomy in long-term oncological efficacy. A total of 352 female patients with right colon adenocarcinoma/high-grade intraepithelial neoplasia will be randomly assigned to the NOSES VIIIA arm and the small-incision arm in a 1:1 ratio. The primary end point of this trial is 3 year disease-free survival. Clinical Trial Registration: NCT05495048 (ClinicalTrials.gov).


Assuntos
Adenocarcinoma , Neoplasias do Colo , Laparoscopia , Cirurgia Endoscópica por Orifício Natural , Feminino , Humanos , Adenocarcinoma/cirurgia , Ensaios Clínicos Fase III como Assunto , Colectomia/efeitos adversos , Neoplasias do Colo/cirurgia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Estudos Multicêntricos como Assunto , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Cirurgia Endoscópica por Orifício Natural/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Estudos de Equivalência como Asunto
6.
Adv Sci (Weinh) ; 10(33): e2302622, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37847907

RESUMO

Regenerative medicine in tissue engineering often relies on stem cells and specific growth factors at a supraphysiological dose. These approaches are costly and may cause severe side effects. Herein, therapeutic small extracellular vesicles (t-sEVs) endogenously loaded with a cocktail of human vascular endothelial growth factor A (VEGF-A) and human bone morphogenetic protein 2 (BMP-2) mRNAs within a customized injectable PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel for bone regeneration in rats with challenging femur critical-size defects are introduced. Abundant t-sEVs are produced by a facile cellular nanoelectroporation system based on a commercially available track-etched membrane (TM-nanoEP) to deliver plasmid DNAs to human adipose-derived mesenchymal stem cells (hAdMSCs). Upregulated microRNAs associated with the therapeutic mRNAs are enriched in t-sEVs for enhanced angiogenic-osteogenic regeneration. Localized and controlled release of t-sEVs within the PEGS-A hydrogel leads to the retention of therapeutics in the defect site for highly efficient bone regeneration with minimal low accumulation in other organs.


Assuntos
Osteogênese , Fator A de Crescimento do Endotélio Vascular , Ratos , Humanos , Animais , RNA Mensageiro/genética , Regeneração Óssea/genética , Hidrogéis/farmacologia
7.
Int J Biol Macromol ; 253(Pt 2): 126675, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37660848

RESUMO

Starch plays a pivotal role in food and other industries, necessitating the exploration of new starch sources to cater the substantial requirement. This study delved into the variations in the physicochemical properties, structure attributes and in vitro digestibility of seed starches extracted from five distinct loquat cultivars (Eriobotrya japonica L.). The starch extraction yield of loquat seeds was found to be 45.2 % as an average. Loquat seed starches were designated as having high-amylose starch (>50 %). The starch granules exhibited similar shapes, but granular size significantly varied across the cultivars. Loquat starches presented a C-type crystalline pattern with relative crystallinity from 17.14 % to 21.06 %. The short-range ordered structure of the starches differed with loquat cultivars. The swelling power, solubility and amylose leaching of loquat starches increased with increasing temperature, significantly varying among different cultivars. Gelatinization parameters exhibited significant variations among the loquat starches. Different loquat starches exhibited pronounced variations in paste clarity, water and oil absorption capacity. Marked differences were detected in proportions of rapidly digestible starch (RDS), slowly digestible starch (SDS), and resistant starch (RS) across the five cultivars, with RS being particularly prominent fraction with an average of 84.30 %. These compressive findings offer valuable insights into the potential application of loquat seed starches in the formulation of foods and various industrial products.


Assuntos
Amilose , Eriobotrya , Amilose/química , Amido/química , Sementes , Amido Resistente
8.
Molecules ; 28(9)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37175311

RESUMO

Neohesperidin (NH), a natural flavonoid, exerts multiple actions, such as antioxidant, antiviral, antiallergic, vasoprotective, anticarcinogenic and anti-inflammatory effects, as well as inhibition of tumor progression. In this study, the NH-taro starch complex is prepared, and the effects of NH complexation on the physicochemical properties, structure and in vitro digestibility of taro starch (TS) are investigated. Results showed that NH complexation significantly affected starch gelatinization temperatures and reduced its enthalpy value (ΔH). The addition of NH increased the viscosity and thickening of taro starch, facilitating shearing and thinning. NH binds to TS via hydrogen bonds and promotes the formation of certain crystalline regions in taro starch. SEM images revealed that the surface of NH-TS complexes became looser with the increasing addition of NH. The digestibility results demonstrated that the increase in NH (from 0.1% to 1.1%, weight based on starch) could raise RS (resistant starch) from 21.66% to 27.75% and reduce RDS (rapidly digestible starch) from 33.51% to 26.76% in taro starch. Our work provided a theoretical reference for the NH-taro starch complex's modification of physicochemical properties and in vitro digestibility with potential in food and non-food applications.


Assuntos
Colocasia , Hesperidina , Amido/química , Colocasia/química , Temperatura
9.
Cancer Cell Int ; 23(1): 95, 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37198617

RESUMO

BACKGROUND: Emerging studies have shown that pyroptosis plays a non-negligible role in the development and treatment of tumors. However, the mechanism of pyroptosis in colorectal cancer (CRC) remains still unclear. Therefore, this study investigated the role of pyroptosis in CRC. METHODS: A pyroptosis-related risk model was developed using univariate Cox regression and LASSO Cox regression analyses. Based on this model, pyroptosis-related risk scores (PRS) of CRC samples with OS time > 0 from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database were calculated. The abundance of immune cells in CRC tumor microenvironment (TME) was predicted by single-sample gene-set enrichment analysis (ssGSEA). Then, the responses to chemotherapy and immunotherapy were predicted by pRRophetic algorithm, the tumor immune dysfunction and exclusion (TIDE) and SubMap algorithms, respectively. Moreover, the Cancer Therapeutics Response Portal (CTRP) and PRISM Repurposing dataset (PRISM) were used to explore novel drug treatment strategies of CRC. Finally, we investigated pyroptosis-related genes in the level of single-cell and validated the expression levels of these genes between normal and CRC cell lines by RT-qPCR. RESULTS: Survival analysis showed that CRC samples with low PRS had better overall survival (OS) and progression-free survival (PFS). CRC samples with low PRS had higher immune-related gene expression and immune cell infiltration than those with high PRS. Besides, CRC samples with low PRS were more likely to benefit from 5-fluorouracil based chemotherapy and anti-PD-1 immunotherapy. In novel drug prediction, some compounds such as C6-ceramide and noretynodrel, were inferred as potential drugs for CRC with different PRS. Single-cell analysis revealed pyroptosis-related genes were highly expressed in tumor cells. RT-qPCR also demonstrated different expression levels of these genes between normal and CRC cell lines. CONCLUSIONS: Taken together, this study provides a comprehensive investigation of the role of pyroptosis in CRC at the bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) levels, advances our understanding of CRC characteristics, and guides more effective treatment regimens.

10.
Bioact Mater ; 25: 13-28, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37056256

RESUMO

Clinical therapies developed for estrogen-deficiency-driven postmenopausal osteoporosis (PMO) and related diseases, such as bone degeneration, show multiple adverse effects nowadays. Targeting senescent cells (SnCs) and the consequent senescence-associated secretory phenotype (SASP) with a combination of dasatinib and quercetin (DQ) is a recently developed novel therapy for multiple age-related diseases. Herein, we found that estrogen deficiency induced-bone loss was attributed to a pro-inflammatory microenvironment with SASP secretions and accelerated SnC accumulation, especially senescent mesenchymal stem cells (MSCs) characterized by exhaustion and dysfunction in middle aged rats. Systematically targeting SnCs with DQ strikingly ameliorated PMO and restored MSC function. Local administration of DQ and bone morphogenetic protein 2 (BMP2) in combination promoted osteogenic differentiation of MSCs and rejuvenated osteoporotic bone regeneration. Our results repurposed DQ as an attractive therapy for treating PMO and related diseases.

11.
Adv Sci (Weinh) ; 10(14): e2300373, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36935362

RESUMO

Amorphous oxide semiconductor thin-film transistors (AOS TFTs) are ever-increasingly utilized in displays. However, to bring high mobility and excellent stability together is a daunting challenge. Here, the carrier transport/relaxation bilayer stacked AOS TFTs are investigated to solve the mobility-stability conflict. The charge transport layer (CTL) is made of amorphous In-rich InSnZnO, which favors big average effective coordination number for all cations and more edge-shared structures for better charge transport. Praseodymium-doped InSnZnO is used as the charge relaxation layer (CRL), which substantially shortens the photoelectron lifetime as revealed by femtosecond transient absorption spectroscopy. The CTL and CRL with the thickness suitable for industrial production respectively afford minute potential barrier fluctuation for charge transport and fast relaxation for photo-generated carriers, resulting in transistors with an ultrahigh mobility (75.5 cm2 V-1 s-1 ) and small negative-bias-illumination-stress/positive-bias-temperature-stress voltage shifts (-1.64/0.76 V). The design concept provides a promising route to address the mobility-stability conflict for high-end displays.

12.
Adv Healthc Mater ; 12(18): e2300475, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36892140

RESUMO

On-skin personal electrocardiography (ECG) devices, which can monitor real-time cardiac autonomic changes, have been widely applied to predict cardiac diseases and save lives. However, current interface electrodes fail to be unconditionally and universally applicable, often losing their efficiency and functionality under harsh atmospheric conditions (e.g., underwater, abnormal temperature, and humidity). Herein, an environmentally adaptable organo-ionic gel-based electrode (OIGE) is developed with a facile one-pot synthesis of highly conductive choline-based ionic liquid ([DMAEA-Q] [TFSI], I.L.) and monomers (2,2,2-trifluoroethyl acrylate (TFEA) and N-hydroxyethyl acrylamide (HEAA). In virtue of inherent conductivity, self-responsive hydrophobic barriers, dual-solvent effect, and multiple interfacial interactions, this OIGE features distinct sweat and water-resistance, anti-freezing and anti-dehydration properties with strong adhesiveness and electrical stability under all kinds of circumstances. In contrast to the dysfunction of commercial gel electrodes (CGEs), this OIGE with stronger adhesion as well as skin tolerability can realize a real-time and accurate collection of ECG signals under multiple extreme conditions, including aquatic environments (sweat and underwater), cryogenic (<-20°C) and arid (dehydration) environments. Therefore, the OIGE shows great prospects in diagnosing cardiovascular diseases and paves new horizons for multi-harsh environmental personalized healthcare.


Assuntos
Pele , Água , Água/química , Condutividade Elétrica , Eletrocardiografia , Eletrodos
13.
Front Surg ; 9: 963597, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406345

RESUMO

Background: Laparoscopic colectomy is widely practiced for colon cancer, but many variations exist for anastomosis after laparoscopic colon cancer radical resection. Method: We retrospectively analyzed 226 patients who underwent laparoscopic-assisted radical resection for left colon cancer with knotless hand-sewn end-to-end anastomosis (KHEA) technique with barbed V-loc™ suture material and compared perioperative outcomes, safety, and efficacy to those undergoing stapled anastomosis from 2010 to 2021. Results: After the 1:2 propensity score matching, 123 participants with similar preoperative characteristics (age, body mass index, TNM stage, and tumor location) were enrolled in the study: 41 in the KHEA and 82 in the stapler group. Statistically significant differences were found in time to accomplish the anastomosis (mean 7.9 vs. 11.9 min, p < 0.001) and hospital costs (mean 46,569.71 vs. 50,915.35 CNY, p < 0.05) that differed between the KHEA and stapler group, respectively. No statistically significant difference was found in the mean delay to bowel function recovery (2.6 vs. 2.7 days, p = 0.466), duration of hospital stay (8.6 vs. 7.9 days, p = 0.407), or rate of postoperative complications (14.6% vs. 11.0%, p = 0.563). Anastomotic leakage occurred in 11 patients: 5 (12.2%) vs. 6 (7.3%) (p > 0.05) in the KHEA and stapler group, respectively. Conclusion: KHEA is feasible and safe for anastomosis after laparoscopic left hemicolectomy. The KHEA technique could reduce operation time and hospital costs with complication rates comparable to stapling.

14.
Front Oncol ; 12: 953790, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185248

RESUMO

Background: Although neoadjvuant chemoradiotherapy (CRT) improves the local control rate of locally advanced rectal cancer (LARC), it fails to significantly improve disease-free survival (DFS) and overall survival (OS). We explored the efficacy of prolonged neoadjuvant chemotherapy (pNCT) without radiation and compared this schema with total neoadjuvant therapy (TNT). Material and methods: Patients diagnosed with LARC and received TNT (4 cycles of induction CapeOX/FOLFOX followed with CRT) or pNCT (6~8 cycles of CapeOX/FOLFOX) between June 2016 and October 2021 were retrospective analyzed. All patients underwent total mesorectal excision (TME). A 1:1 propensity score match was performed to adjust baseline potential confounders. The tumor response, toxicity, recurrence-free survival (RFS) and OS were observed. Results: A total of 184 patients with 92 patients in each group were finally enrolled. The median follow-up time was 35 months. TNT showed better pathological complete response (pCR) rate (25.0% vs 16.3%) and objective regression rate (73.9% vs 59.8%) than pNCT. TNT and pNCT produce similar 3-year RFS and OS rates in patients with mid-to-upper rectal cancer. TNT was associated with improved tumor responsiveness in all patients and improved 3-year RFS rates in those with low rectal cancer. Conclusion: pNCT is an option for patients with mid-to-upper rectal cancer, but radiation is still necessary for low rectal cancer. To determine optimal schema for neoadjuvant therapy and patient selection, additional randomized controlled studies are needed.

16.
ACS Appl Mater Interfaces ; 14(33): 38090-38097, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-35969679

RESUMO

Li-CO2 batteries with high theoretical energy densities are recognized as next-generation energy storage devices for addressing the range anxiety and environmental issues encountered in the field of electric transportation. However, cathode catalysts with unsatisfactory activity toward CO2 absorption and reduction/evolution reactions hinder the development of Li-CO2 batteries with desired specific capacities and sufficient cycle numbers. In this work, a multifunctional nanofibrous cathode catalyst that integrates N-rich carbon shells embedded with molybdenum carbide nanoparticles and multiwalled carbon nanotube cores was designed and prepared. The N-rich carbon shell could strengthen the absorption capacity of CO2 and Li2CO3. The molybdenum carbide nanoparticles would improve the catalytic activity of both CO2 reduction and evolution reactions. The carbon nanotube cores would provide an efficient network for electron transportation. The synergistic effect of the cathode catalysts enhances the electrochemical performance of Li-CO2 batteries. A high cycling stability of more than 150 cycles at a current density of 250 mA g-1 with a cutoff capacity of 1000 mAh g-1 and a charge/discharge overpotential of less than 1.5 V is achieved. This work provides a feasible strategy for the design of a high-performance cathode catalyst for lithium-air batteries.

17.
Front Public Health ; 10: 843845, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35655447

RESUMO

Objective: Occupational stress is generally acknowledged as a global phenomenon with significant health and economic consequences. The medical worker is a vulnerable group at a high-level risk for depression symptoms. This study aimed to examine the mediating effect of worker-occupation fit (WOF) in relation to occupational stress and depression symptoms among 1988 medical workers in China. Methods: A multi-center cross-sectional study was conducted during June and October 2020 in Henan Province, China. The participants were medical workers from four targeted hospitals (included one general and three specialized hospitals). The Depression, Anxiety, and Stress Scale (DASS-21 Scale), Worker-Occupation Fit Inventory (WOFI), as well as questions about demographic and occupational information were administered in questionnaires distributed to 1988 medical workers. Hierarchical linear regression analysis was used to examine the mediating role of worker occupation fit. Results: In this study, there are 43.5% (n = 864) of medical workers experienced depression symptoms. The mean score of WOF was 31.6 ± 7.1, characteristic fit, need supply fit and demand ability fit were 11.3 ± 2.5, 10.1 ± 2.7, 12.9 ± 2.2, respectively. The occupational stress was negatively related to worker occupation fit (r = -0.395, P < 0.001), characteristic fit (r = -0.529, P < 0.001), need supply fit (r = -0.500, P < 0.001), and demand ability fit (r = -0.345, P < 0.001). The occupational stress and depression symptoms have a positive relationship (r = 0.798, P < 0.001). The proportion of worker occupation fit mediation was 6.5% of total effect for depression symptoms. Conclusion: Occupational stress has been identified as a risk factor for depression symptoms. Practical strategies for improving medical workers' WOF level would help them better cope with various work-related stressors to reduce depression symptoms. Hospital administrators could reduce medical workers' depression symptoms by taking comprehensive measures to improve the WOF.


Assuntos
Depressão , Estresse Ocupacional , Estudos Transversais , Depressão/epidemiologia , Pessoal de Saúde , Humanos , Estresse Ocupacional/epidemiologia , Ocupações
18.
Nanomaterials (Basel) ; 12(12)2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35745402

RESUMO

Metal-air batteries are considered the research, development, and application direction of electrochemical devices in the future because of their high theoretical energy density. Among them, lithium-carbon dioxide (Li-CO2) batteries can capture, fix, and transform the greenhouse gas carbon dioxide while storing energy efficiently, which is an effective technique to achieve "carbon neutrality". However, the current research on this battery system is still in the initial stage, the selection of key materials such as electrodes and electrolytes still need to be optimized, and the actual reaction path needs to be studied. Carbon tube-based composites have been widely used in this energy storage system due to their excellent electrical conductivity and ability to construct unique spatial structures containing various catalyst loads. In this review, the basic principle of Li-CO2 batteries and the research progress of carbon tube-based composite cathode materials were introduced, the preparation and evaluation strategies together with the existing problems were described, and the future development direction of carbon tube-based materials in Li-CO2 batteries was proposed.

19.
Int J Surg ; 104: 106718, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35724803

RESUMO

BACKGROUND: Recent interest in laparoscopic right colectomy with D3 lymphadenectomy for right colon cancer, has raised renewed attention to the anatomic variations of the gastrocolic trunk of Henlé (GTH). Understanding the vascular structure of the GTH region for individual patients should improve surgical outcomes. The goal of this nationwide multicenter study (Anatomical Classification of Henlé's Trunk in Laparoscopic Right Hemi-colectomy (HeLaRC) trial) was to study the anatomic patterns of the GTH region, to clarify the implications of GTH in laparoscopic right colectomy with D3 lymphadenectomy (D3-RC) and analyze their clinical significance. METHODS: We enrolled 583 patients from 26 centers across China who underwent D3-RC. The number of tributaries, length and types of GTH constitutions and their influence on intra-operative data were investigated. A nomogram score (based on the length of GTH, body mass index (BMI), tumor location, T stage and type of GTH (type I vs. non-type I) was established to assess the potential hazard of bleeding. RESULTS: The GTH was found in 567 patients (97.3%). The distribution of GTH types was 0 (14.1%, n = 80), I (53.3%, n = 302), II (27.0%, n = 153), III (5.6%, n = 32). Of note, the type I GTH, T1 stage and tumor location at ileocecal or ascending colon were correlated with shorter exposure time of the GTH region (P < 0.0001). Short length of GTH (P = 0.002) and tumor location (transverse colon vs. non transverse colon) (P = 0.003) were correlated with the amount of GTH bleeding during the surgery. Nomogram discrimination was good (C-index: 0.72 (95% CI: 0.64, 0.80)). The dissection plane was better in patients with type I GTH than with other types (P = 0.023). CONCLUSION: GTH pattern variations may affect surgical outcomes in patients undergoing D3-RC. Better recognition of GTH anatomy might lead to a safer operation with better oncologic quality.


Assuntos
Colo Transverso , Neoplasias do Colo , Laparoscopia , Colectomia , Humanos , Excisão de Linfonodo
20.
Front Mol Biosci ; 9: 822739, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372503

RESUMO

Background: Inflammatory responses are strongly linked with tumorigenesis and cancer development. This research aimed to construct and validate a novel inflammation response-related risk predictive signature for forecasting the prognosis of patients with LUAD. Methods: Differential expression analysis, univariate Cox, LASSO, and multivariate Cox regression analyses of 200 inflammatory response-related genes (IRRG) were performed to establish a risk predictive model in the TCGA training cohort. The performance of the IRRG model was verified in eight GEO datasets. GSEA analysis, ESTIMATE algorithms, and ssGSEA analysis were applied to elucidate the possible mechanisms. Furthermore, the relationship analysis between risk score, model genes, and chemosensitivity was performed. Last, we verified the protein expression of seven model genes by immunohistochemical staining or Western blotting. Results: We constructed a novel inflammatory response-related 7-gene signature (MMP14, BTG2, LAMP3, CCL20, TLR2, IL7R, and PCDH7). Patients in the high-risk group presented markedly decreased survival time in the TCGA cohort and eight GEO cohorts than the low-risk group. Interestingly, multiple pathways related to immune response were suppressed in high-risk groups. The low infiltration levels of B cell, dendritic cell, natural killer cell, and eosinophil can significantly affect the unsatisfactory prognosis of the high-risk group in LUAD. Moreover, the tumor cells' sensitivity to anticancer drugs was markedly related to risk scores and model genes. The protein expression of seven model genes was consistent with the mRNA expression. Conclusion: Our IRRG prognostic model can effectively forecast LUAD prognosis and is tightly related to immune infiltration.

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