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1.
Langenbecks Arch Surg ; 409(1): 154, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714551

RESUMO

BACKGROUND: In recent years, there has been an increasing prevalence of patients with papillary thyroid microcarcinoma (PTMC) without lymph node involvement in medical centers worldwide. For patients who are unable to undergo active surveillance (AS) and are afraid of postoperative complications, conformal thyroidectomy may be a suitable option to ensure both preservation of function and complete removal of the tumor. METHODS: The patients in the cohort during 2010 to 2015 were retrospectively enrolled strictly following the inclusion and exclusion criteria. The observation and control groups were defined based on the surgical approach, with patients in the observation group undergoing conformal thyroidectomy and patients in the control group undergoing lobectomy. Event-free survival (EFS), the interval from initial surgery to the detection of recurrent or metastatic disease, was defined as the primary observation endpoint. RESULTS: A total of 319 patients were included in the study, with 124 patients undergoing conformal thyroidectomy and 195 patients undergoing lobectomy. When compared to lobectomy, conformal thyroidectomy demonstrated reduced hospital stays, shorter operative times, and lower rates of vocal cord paralysis and hypoparathyroidism. Furthermore, the mean bleeding volume during the operation and the rate of permanent hypothyroidism were also lower in the conformal thyroidectomy group than in the lobectomy group. However, there was no statistically significant difference observed in the 5- and 10-year EFS between the two groups. CONCLUSIONS: Conformal thyroidectomy had advantages in perioperative management and short-term complication rates, with an EFS that was not inferior to that of lobectomy. Thus, conformal thyroidectomy is a feasible option for low-risk PTMC patients.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Tireoidectomia/métodos , Tireoidectomia/efeitos adversos , Feminino , Masculino , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/mortalidade , Estudos Retrospectivos , Pessoa de Meia-Idade , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Carcinoma Papilar/mortalidade , Adulto , Seguimentos , Estudos de Viabilidade , Estudos de Coortes , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Duração da Cirurgia
2.
J Nanobiotechnology ; 22(1): 253, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755600

RESUMO

Improving cancer therapy by targeting the adverse tumor microenvironment (TME) rather than the cancer cells presents a novel and potentially effective strategy. In this study, we introduced FexMoyS nanoparticles (NPs), which act as sequential bioreactors to manipulate the TME. FexMoyS NPs were synthesized using thermal decomposition and modified with polyethylene glycol (PEG). Their morphology, chemical composition, and photothermal properties were characterized. The capability to produce ROS and deplete GSH was evaluated. Effects on CRC cells, including cell viability, apoptosis, and glycolysis, were tested through various in vitro assays. In vivo efficacy was determined using CRC-bearing mouse models and patient-derived xenograft (PDX) models. The impact on the MAPK signaling pathway and tumor metabolism was also examined. The FexMoyS NPs showed efficient catalytic activity, leading to increased ROS production and GSH depletion, inducing ferroptosis, and suppressing glycolysis in CRC cells. In vivo, the NPs significantly inhibited tumor growth, particularly when combined with NIR light therapy, indicating a synergistic effect of photothermal therapy and chemodynamic therapy. Biosafety assessments revealed no significant toxicity in treated mice. RNA sequencing suggested that the NPs impact metabolism and potentially immune processes within CRC cells. FexMoyS NPs present a promising multifaceted approach for CRC treatment, effectively targeting tumor cells while maintaining biosafety. The nanoparticles exhibit potential for clinical translation, offering a new avenue for cancer therapy.


Assuntos
Neoplasias Colorretais , Ferroptose , Glicólise , Polietilenoglicóis , Espécies Reativas de Oxigênio , Animais , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Humanos , Camundongos , Polietilenoglicóis/química , Ferroptose/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Linhagem Celular Tumoral , Microambiente Tumoral/efeitos dos fármacos , Nanopartículas/química , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C , Camundongos Nus , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Glutationa/metabolismo
3.
Aging Clin Exp Res ; 36(1): 56, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441718

RESUMO

BACKGROUND AND AIMS: Acute myocardial infarction (AMI) is one of the most prevalent illnesses endangering the elderly's health. The predictive nutritional index (PNI) has been shown in several studies to be a good predictor of nutritional prognosis. In this study, we explored the correlation between PNI during hospitalization and the outcome of elderly AMI patients. METHODS: Elderly AMI patients in the Cardiac Intensive Care Unit of Huadong Hospital from September 2017 to April 2020 were recruited for analysis. The clinical and laboratory examination data of subjects were retrieved. All enrolled patients were monitored following discharge. The primary clinical endpoints encompass major adverse cardiovascular events (MACEs) and Composite endpoint (MACEs and all-cause mortality). Survival analyses were conducted via the Kaplan-Meier and the log-rank analyses, and the Cox, proportional hazards model, was employed for hazard rate (HR) calculation. RESULTS: 307 subjects were recruited for analysis. The optimal PNI threshold is 40.923. Based on the Kaplan-Meier analysis, the elevated PNI group experienced better prognosis (P < 0.001). Cox analysis demonstrated that the PNI group was a stand-alone predictor for elderly AMI patient prognosis (HR = 1.674, 95% CI 1.076-2.604, P = 0.022). Subgroup analysis showed that the HR of the PNI group was the highest in the ST-segment elevation myocardial infarction (STEMI) subgroup (HR = 3.345, 95% CI 1.889-5.923, P = 0.05), but no discernible difference was observed in the non-ST-segment elevation myocardial infarction (NSTEMI) subgroup. CONCLUSION: Based on our analyses, the PNI during hospitalization can accurately predict the prognosis of elderly STEMI patients but not that of elderly NSTEMI patients.


Assuntos
Infarto do Miocárdio , Infarto do Miocárdio sem Supradesnível do Segmento ST , Infarto do Miocárdio com Supradesnível do Segmento ST , Idoso , Humanos , Avaliação Nutricional , Prognóstico , Estudos Retrospectivos , Infarto do Miocárdio/diagnóstico , Hospitalização
4.
BMJ Open ; 14(1): e080210, 2024 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267247

RESUMO

INTRODUCTION: In recent years, the incidence of thyroid cancer has increased manyfold and young adults, who have a greater financial burden and occupational stress, comprise a large number. Previous studies have shown mixed results, even distinct results, on suicide rates among thyroid cancer survivors. As the overdiagnosis and overtreatment of thyroid cancer has gradually become a topical issue, the study aims to summarise the risk of suicide among patients with thyroid cancer to provide robust evidence of the effects of thyroid cancer on suicide. METHODS AND ANALYSIS: A total of six databases (MEDLINE, Embase, Web of Science Core Collection, PsycINFO, CINAHL and Google Scholar) will be searched according to MeSH, subheadings, and free words, and the planned search date is 31 Jnauary 2024. The search strategy had three parts, such as suicide, cancer and epidemiological studies, moreover, we will collect the detailed suicide information by reviewers' extraction. Standard mortality ratio (SMR) was used as the outcome measure, when SMRs were not available, the risk ratio, HR and detailed number of suicides were extracted to calculate the SMRs. ETHICS AND DISSEMINATION: The Institutional Review Board of Peking University People's Hospital provided ethical approval exemption and approved the data collection and subsequent analyses in accordance with the Declaration of Helsinki as revised in 2013. PROSPERO REGISTRATION NUMBER: CRD42023445542.


Assuntos
Suicídio , Neoplasias da Glândula Tireoide , Adulto Jovem , Humanos , Revisões Sistemáticas como Assunto , Metanálise como Assunto , Neoplasias da Glândula Tireoide/epidemiologia
5.
J Glob Health ; 14: 05001, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38214889

RESUMO

Background: Several large-scale observational studies have found deep vein thrombosis (DVT) to be related with coronavirus disease 2019 (COVID-19). However, whether there is a clear causal connection between the two is unknown. Methods: Our primary analytical method was the inverse variance-weighted (IVW) approach, complemented by the Mendelian randomisation-Egger (MR-Egger) and weighted median methods. We also used MR-Egger to examine the presence of pleiotropy and the Mendelian randomisation pleiotropy residual sum and outlier (MR-PRESSO) approach to analyse for heterogeneity in the data. Results: We did not observe a direct causal relationship between COVID-19 susceptibility (odds ratio (OR) = 1.023; 95% confidence interval (CI) = 0.828-1.264, standard error (SE) = 0.108, P = 0.833), hospitalisation (OR = 1.030; 95% CI = 0.943-1.125, SE = 0.374, P = 0.720), severity (OR = 0.994; 95% CI = 0.923-1.071, SE = 0.038, P = 0.877), and DVT. The results of the reverse Mendelian randomisation (MR) for DVT and COVID-19 susceptibility exhibited heterogeneity and horizontal pleiotropy. Even after removing outliers, we detected no direct causal relationship between the two (OR = 1.015; 95% CI = 0.954-1.080, SE = 0.032, P = 0.630). Similarly, we found no direct causal relationship between DVT and COVID-19 hospitalisation (OR = 0.999; 95% CI = 0.907-1.102, SE = 0.050, P = 0.999) or severity (OR = 1.014; 95% CI = 0.893-1.153, SE = 0.065, P = 0.826). Conclusions: In this MR study, we identified no direct causal impact in a European population between DVT and the COVID-19 susceptibility, severity, or hospitalisation.


Assuntos
COVID-19 , Trombose Venosa , Humanos , Hospitalização , Trombose Venosa/epidemiologia , Trombose Venosa/genética , Análise da Randomização Mendeliana
6.
Int Immunopharmacol ; 126: 111276, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38016348

RESUMO

This study reported on the intratumor genomic and immunological heterogeneity of different tumor lesions from a single patient with multiple primary colorectal cancer (MPCC). The goal of this study was to explore the molecular and microenvironment characteristics of tumor lesions from different primary sites in a patient with MPCC. A total of three tumor lesions located in the hepatic flexure of the transverse colon, sigmoid colon, and rectum were collected from a 72-year-old male patient with MPCC. All three tumor samples were examined by using whole-exome sequencing (WES) and single-cell RNA sequencing (scRNA-seq). The transcriptome data of The Cancer Genome Atlas (TCGA) colon cancer (COAD) dataset were explored to characterize the biological impacts of certain immune cells. Only three nonsynonymous mutations were shared by all of the tumor lesions, whereas a number of single nucleotide variant (SNV) and copy number variation (CNV) mutations were shared by tumor samples from the sigmoid colon and rectum. Transcriptomic analysis showed that tumor lesions derived from the transverse colon had decreased levels of RTK, ERK, and AKT pathway activity, thus suggesting lower oncogenic properties in the transverse lesion compared to the other two samples. Further immune landscape evaluation by using single-cell transcriptomic analysis displayed significant intratumor heterogeneity in MPCC. Specifically, more abundant mucosal-associated invariant T (MAIT) cell infiltration was found in transverse colon tumor lesions. Afterwards, we found that higher MAIT cell infiltration may correlate with a better prognosis of patients with colon cancer (immunohistochemical status was MSI-L/pMMR) by using a publicly available TCGA dataset.


Assuntos
Neoplasias do Colo , Neoplasias Primárias Múltiplas , Masculino , Humanos , Idoso , Transcriptoma , Variações do Número de Cópias de DNA , Perfilação da Expressão Gênica , Neoplasias Primárias Múltiplas/patologia , Genômica , Microambiente Tumoral/genética
7.
Nutrition ; 117: 112214, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37837772

RESUMO

OBJECTIVES: The aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio, an indicator for liver fibrosis, could be easily detected in clinical practice. The aim of this study was to examine the association between the AST/ALT ratio and skeletal muscle mass among Chinese community adult residents. METHODS: We enrolled 2644 participants, age ≥18 y, undergoing bioelectrical impedance analysis and liver function test. Univariate and multivariate logistic regression models were used to analyze the effect of the AST/ALT ratio on the presence of low muscle mass (LMM). Multiple linear regression analysis was used to assess the factors associated with the skeletal muscle mass index (SMI) and to construct a formula to calculate the SMI. RESULTS: When the AST/ALT ratio was regarded as a categorical variable, AST/ALT quartiles 9-2.19) kept independent effects on the presence of LMM status. When it was regarded as a continuous variable, each unit of the AST/ALT ratio was significantly associated with a 49% (P < 0.01) augment of the prevalence of LMM. By multiple general linear regression analysis, the formula was constructed with an adjusted R2 of 0.72: SMI (kg/m2) = -0.14 AST/ALT ratio + 1.35 sex (male: 1; female: 0) + 0.72 overweight status (yes: 1; no: 0) - 0.14 age (≤65: 0; >65: 1) + 6.26. CONCLUSION: In general, the high AST/ALT ratio was an independent adverse indicator of the presence of LMM.


Assuntos
População do Leste Asiático , Músculo Esquelético , Adulto , Humanos , Masculino , Feminino , Alanina Transaminase , Aspartato Aminotransferases , Testes de Função Hepática
8.
iScience ; 26(11): 108131, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37867958

RESUMO

Transforming growth factor ß1 (TGFß1) has been identified as a major pathogenic factor underlying the development of chronic kidney disease (CKD). This study investigated the role of miR-92b-3p in the progression of renal fibrosis in unilateral ureteral occlusion (UUO) and unilateral ischemia-reperfusion injury (uIRI) mouse models, as well as explored its underlying mechanisms in human proximal tubular epithelial (HK2) cells. We found that renal fibrosis increased in UUO mice after miR-92b knockout, while it reduced in miR-92b overexpressing mice. MiR-92b knockout aggravated renal fibrosis in uIRI mice. RNA-sequencing analysis, the luciferase reporter assay, qPCR analysis, and western blotting confirmed that miR-92b-3p directly targeted TGF-ß receptor 1, thereby ameliorating renal fibrosis by suppressing the TGF-ß signaling pathway. Furthermore, we found that TGF-ß suppressed miR-92b transcription through Snail family transcriptional repressors 1 and 2. Our results suggest that miR-92b-3p may serve as a novel therapeutic for mitigating fibrosis in CKD.

10.
Eur J Surg Oncol ; 49(12): 107079, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37826966

RESUMO

BACKGROUND: Due to the increasing recognition of gastrointestinal stromal tumor (GIST), novel insights have appeared in both preclinical and clinical research and begun to reshape the field. This study aims to map the research landscape through bibliometric analysis and provide a brief overview for the future of the GIST field. METHODS: We searched the Web of Science Core Collection without publication data restrictions for GISTs and performed a bibliometric analysis with CiteSpace and VOSviewer software. RESULTS: In sum, 5,911 of 13,776 records were included, and these studies were published in 948 journals and written by 24,965 authors from 4,633 institutions in 100 countries. Referring to published reviews and bibliometric analysis, we classified the future trends in four groups. In epidemiological study, precise incidence and clinicopathological features in different regions and races might become potential hotspots. Novel therapy, such as drugs, modified strategies, radioligand therapy, was persistent hotspots in GIST fields, and ctDNA-guided diagnosis, monitoring, and treatment might meet future clinical needs. The debate over serosa surgery vs. mucosa surgery will remain active for a long time in GIST surgery, and function reserve surgery, biology-based surgery will play an important role in future. Moreover, rare GIST type, like NF-1-associated GIST, Carney triads and SDH mutant GIST, need more studies in pathogenesis and genetic mutation to provide appropriate treatment for this orphan GIST patients. CONCLUSIONS: Potential hotspots in future GIST trends might involve epidemiology, agents, resection therapy and rare type GIST, moreover, researchers could pay more attention in these four fields.


Assuntos
Tumores do Estroma Gastrointestinal , Humanos , Tumores do Estroma Gastrointestinal/epidemiologia , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/terapia , Bibliometria , Mutação
11.
Zhongguo Gu Shang ; 36(9): 901-4, 2023 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-37735086

RESUMO

There are inconsistencies in treatment outcomes, measurement instruments, and criteria for assessing clinical effectiveness in studies related to distal radius fractures (DRF), resulting in potential biases and failing to provide high-quality clinical evidence. To address these challenges, international researchers have reached a consensus on developing the core outcome indicator set for distal radius fractures(COS-DRF). However, it's important to note that the existing COS-DRF framework could not reflect the unique characteristics of Traditional Chinese Medicine (TCM) treatment. Currently, there are no established standards for treatment outcomes and measurement instruments specific to TCM clinical research, nor has a COS-DRF been established for TCM clinical studies in China. In light of these gaps, our research team aims to construct a core set of treatment outcomes for TCM clinical research on distal radius fractures. This involves compiling a comprehensive list of treatment outcomes and measurement instruments, initially derived from a thorough literature review and expert consensus, which will then undergo further refinement and updates based on real-world clinical experiences, incorporating feedback from 2 to 3 rounds of expert consensus or Delphi questionnaire surveys. Our goal is to establish a COS-DRF or CMS-DRF that aligns with the principles and practices of TCM, and provide high-quality evidence for clinical practice.


Assuntos
Fixação de Fratura , Medicina Tradicional Chinesa , Fraturas do Punho , Humanos , China , Consenso , População do Leste Asiático , Avaliação de Resultados em Cuidados de Saúde , Fraturas do Punho/terapia , Literatura de Revisão como Assunto , Fixação de Fratura/métodos , Fixação de Fratura/normas
12.
Nano Lett ; 23(15): 7037-7045, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37463459

RESUMO

The chemical mechanism (CM) of surface-enhanced Raman scattering (SERS) has been recognized as a decent approach to mildly amplify Raman scattering. However, the insufficient charge transfer (CT) between the SERS substrate and molecules always results in unsatisfying Raman enhancement, exerting a substantial restriction for CM-based SERS. In principle, CT is dominated by the coupling between the energy levels of a semiconductor-molecule system and the laser wavelength, whereas precise tuning of the energy levels is intrinsically difficult. Herein, two-dimensional transition-metal dichalcogenide alloys, whose energy levels can be precisely and continuously tuned over a wide range by simply adjusting their compositions, are investigated. The alloys enable on-demand construction of the CT resonance channels to cater to the requirements of a specific target molecule in SERS. The SERS signals are highly reproducible, and a clear view of the SERS dependences on the energy levels is revealed for different CT resonance terms.

13.
BMC Gastroenterol ; 23(1): 192, 2023 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-37270504

RESUMO

BACKGROUND: The clinicopathological features, surgical outcomes, and long-term survival of patients with young-onset colon cancer (≤ 40 years old) remain controversial. METHODS: The clinicopathologic and follow-up data of patients aged < 40 years with colon cancer between January 2014 and January 2022 were reviewed. The primary objectives were clinical features and surgical outcomes. Long-term survival was investigated as a secondary objective. RESULTS: Seventy patients were included in the study, and no significant rising trend (Z=0, P=1) of these patients was observed over the 8-year study period. Stage IV disease was accompanied by more ulcerative or infiltrating type (84.2% vs. 52.9%, P=0.017) and lymphovascular or perineural invasion (64.7% vs. 25.5%, P=0.003) than stage I-III disease. After a median follow-up time of 41 months (range 8-99 months), the 1-, 3-, and 5-year estimated overall survival (OS) rates were 92.6%, 79.5%, and 76.4%, respectively. The 1-, 3-, and 5-year progression-free survival (PFS) rates were 79.6%, 71.7%, and 71.7%, respectively. Multivariate Cox regression showed that M+ stage (hazard ratio [HR], 3.942; 95% confidence interval [CI], 1.176-13.220, P=0.026) was the only independent risk factor affecting OS. Meanwhile, tumor deposits (HR, 4.807; 95% CI, 1.942-15.488, P=0.009), poor differentiation (HR, 2.925; 95% CI, 1.012-8.454, P=0.047), and M+ stage (HR, 3.540; 95% CI, 1.118-11.202, P=0.032) independently affected PFS. CONCLUSIONS: The differences in the clinical features, surgical outcomes, and long-term survival between young adults and elderly colon cancer patients need further investigation.


Assuntos
Neoplasias do Colo , Idoso , Humanos , Adulto Jovem , Adulto , Prognóstico , Estudos Retrospectivos , Modelos de Riscos Proporcionais , Resultado do Tratamento , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Estadiamento de Neoplasias
14.
Pol Arch Intern Med ; 133(11)2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-37154798

RESUMO

INTRODUCTION: Gastroesophageal reflux disease (GERD) is a highly prevalent gastrointestinal disorder that causes diverse esophageal and extraesophageal symptoms. Many clinical practice guidelines (CPGs) have been issued around the world to provide practical evidence regarding GERD management. However, some of the recommendations discussed in various CPGs are inconsistent across individual documents. OBJECTIVES: We aimed to summarize the evidence from CPGs on GERD and assess the consistency of the recommendations. PATIENTS AND METHODS: In this scoping review, we identified current CPGs on the clinical management of GERD, which were comprehensively searched for in electronic databases and on relevant scientific websites. The recommendations were extracted using the population­intervention­comparison framework and were subsequently categorized into tables. RESULTS: Ultimately, 24 CPGs were identified. They included 86 recommendations, which were classified into 5 categories: definition, epidemiology, diagnosis, treatment, and complications. Among the identified recommendations, 68 were proposed in at least 2 CPGs, and they were assessed for the consistency of direction and strength. Overall, 32.4% of the recommendations (22/68) were consistent in direction and strength, whereas 60.3% (41/68) were consistent in direction but inconsistent in strength. Moreover, 7.4% (5/68) were inconsistent in direction. These referred to the relationship between GERD and tobacco consumption, Helicobacter pylori infection, diagnostic utility of the 2­week proton pump inhibitor test, cessation of special food, and antireflux surgery for GERD with extraesophageal symptoms. CONCLUSIONS: Most CPG recommendations regarding GERD were consistent in direction, except for 5 discrepancies, for which further well­designed, large­scale research is required to explain the inconsistency.


Assuntos
Refluxo Gastroesofágico , Infecções por Helicobacter , Helicobacter pylori , Humanos , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/terapia , Refluxo Gastroesofágico/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/complicações , Inibidores da Bomba de Prótons , Guias de Prática Clínica como Assunto
15.
Genome Med ; 15(1): 4, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694225

RESUMO

BACKGROUND: The genetic architectures of colorectal cancer are distinct across different populations. To date, the majority of polygenic risk scores (PRSs) are derived from European (EUR) populations, which limits their accurate extrapolation to other populations. Here, we aimed to generate a PRS by incorporating East Asian (EAS) and EUR ancestry groups and validate its utility for colorectal cancer risk assessment among different populations. METHODS: A large-scale colorectal cancer genome-wide association study (GWAS), harboring 35,145 cases and 288,934 controls from EAS and EUR populations, was used for the EAS-EUR GWAS meta-analysis and the construction of candidate EAS-EUR PRSs via different approaches. The performance of each PRS was then validated in external GWAS datasets of EAS (727 cases and 1452 controls) and EUR (1289 cases and 1284 controls) ancestries, respectively. The optimal PRS was further tested using the UK Biobank longitudinal cohort of 355,543 individuals and ultimately applied to stratify individual risk attached by healthy lifestyle. RESULTS: In the meta-analysis across EAS and EUR populations, we identified 48 independent variants beyond genome-wide significance (P < 5 × 10-8) at previously reported loci. Among 26 candidate EAS-EUR PRSs, the PRS-CSx approach-derived PRS (defined as PRSCSx) that harbored genome-wide variants achieved the optimal discriminatory ability in both validation datasets, as well as better performance in the EAS population compared to the PRS derived from known variants. Using the UK Biobank cohort, we further validated a significant dose-response effect of PRSCSx on incident colorectal cancer, in which the risk was 2.11- and 3.88-fold higher in individuals with intermediate and high PRSCSx than in the low score subgroup (Ptrend = 8.15 × 10-53). Notably, the detrimental effect of being at a high genetic risk could be largely attenuated by adherence to a favorable lifestyle, with a 0.53% reduction in 5-year absolute risk. CONCLUSIONS: In summary, we systemically constructed an EAS-EUR PRS to effectively stratify colorectal cancer risk, which highlighted its clinical implication among diverse ancestries. Importantly, these findings also supported that a healthy lifestyle could reduce the genetic impact on incident colorectal cancer.


Assuntos
Neoplasias Colorretais , Estudo de Associação Genômica Ampla , Humanos , População do Leste Asiático , Predisposição Genética para Doença , Fatores de Risco , Medição de Risco , Estilo de Vida , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética
16.
Bioact Mater ; 22: 225-238, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36254273

RESUMO

Staplers have been widely used in the clinical treatment of gastrointestinal reconstruction. However, the current titanium (Ti) staple will remain in the human body permanently, resulting in some adverse effects. In this study, we developed a type of biodegradable staple for colonic anastomosis using 0.3 mm diameter magnesium (Mg) alloy wires. The wire surface was modified by micro-arc oxidation treatment (MAO) and then coated with poly-l-lactic acid (PLLA) to achieve a moderate degradation rate matching the tissue healing process. The results of tensile tests on isolated porcine colon tissue anastomosed by Mg and Ti staples showed that the anastomotic property of Mg staples was almost equal to that of Ti staples. The in vitro degradation tests indicated the dual-layer coating effectively enhanced the corrosion resistance and maintained the tensile force of the coated staple stable after 14-day immersion in the simulated colonic fluid (SCF). Furthermore, 24 beagle dogs were employed to conduct a comparison experiment using Mg-based and clinical Ti staples for 90-day implantation by ent-to-side anastomosis of the colon. The integrated structure of Mg-based staples was observed after 7 days and completely degraded after 90 days. All animals did not have anastomotic leakage and stenosis, and 12 dogs with Mg-based staples fully recovered after 90 days without differences in visceral ion levels and other side effects. The favorable performance makes this Mg-based anastomotic staple an ideal candidate for colon reconstruction.

18.
Front Surg ; 9: 968585, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338632

RESUMO

Background: Colonic gastrointestinal stromal tumor (cGIST) and rectal gastrointestinal stromal tumor (rGIST) are two rare subtypes of gastrointestinal stromal tumor (GIST). The view that colonic and rectal carcinoma are different is generally accepted; however, whether there is a difference between cGIST and rGIST is still unknown. Here, we aimed to provide evidence for future clinical management and research by comparing the differences between the two types of GIST in the above-mentioned aspects. Methods: Patients were enrolled from three medical centers in China and published literature was collected following the inclusion and exclusion criteria. Propensity score matching was used to eliminate differences between cohorts. Results: Between cGIST and rGIST patients, significant differences were observed in age, tumor size, mitotic index, NIH risk category, growth pattern, and symptoms. Adjuvant therapy is used in a high proportion of cGIST patients, and neoadjuvant therapy is used in a high proportion of rGIST patients. Although local resection is the main surgical method in both cohorts, the proportion is higher in cGIST patients. The overall survival of rGIST patients was better than that of the cGIST patients before propensity score matching (PSM). Interestingly, no significant differences in prognosis were observed after PSM. Conclusions: Although there were significant differences between cGIST and rGIST patients in baseline characteristics, clinicopathological features, treatment choice, and overall survival rate before PSM, no significant differences in long-term survival were observed between the two groups after PSM. In our study, there may be no differences in the tumor entity between cGIST and rGIST.

19.
Front Genet ; 13: 922055, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246625

RESUMO

Background: Recently, the role of pyroptosis in cancer has attracted people's attention, but its function in colon cancer remains unclear. This study aimed to construct a pyroptosis-related model that can effectively predict the prognosis of patients with colon cancer and explore the potential functions of pyroptosis-related genes. Methods: We identified 40 differentially expressed PRGs between colon cancer and normal colon tissues. The model was established using the least absolute shrinkage and selection operator (LASSO) Cox regression method, and the patients were divided into high- and low-risk groups. Finally, we verified its biological function in vitro based on three PRGs and demonstrated discrepant expression of PRGs within colon cancer and non-tumor tissues at the protein level with immunohistochemistry. Results: A pyroptosis-related prognosis model was constructed, which divided 446 patients with colon cancer into high- and low-risk groups. Kaplan-Meier analysis results showed that the survival of patients with colon cancer in the high-risk group was worse than that in the low-risk group. Finally, we also confirmed that this score is an independent prognostic factor for colon cancer progression. Conclusion: In summary, the model established by three PRGs was a reliable indicator for predicting prognosis, suggesting that pyroptosis might be a noteworthy therapeutic target in CC.

20.
Front Bioeng Biotechnol ; 10: 1001994, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36177184

RESUMO

Colorectal cancer (CRC) is one of the most common cancers of the digestive tract, and patients with advanced-stage cancer have poor survival despite the use of multidrug conventional chemotherapy regimens. Intra-tumor heterogeneity of cancerous cells is the main obstacle in the way to effective cancer treatments. Therefore, we are looking for novel approaches to eliminate just cancer cells including nanoparticles (NPs). PPy@Fe3O4 NPs were successfully synthesized through a portable method. The characterization of transmission electron microscopy (TEM), Fourier-Transformed infrared spectrometer, and X-ray powder diffraction have further proved successful preparation of PPy@Fe3O4 NPs. NIR irradiation was used to test the photothermal properties of NPs and an infrared camera was used to record their temperature. The direct effects of PPy@Fe3O4 NPs on colorectal cancer cell DLD1 were assessed using CCK8, plate clone, transwell, flow cytometry, and western blotting in CRC cell. The effect of PPy@Fe3O4 NPs on neoplasm growth in nude mice was evaluated in vivo. This study demonstrated that PPy@ Fe3O4 NPs significantly inhibit the growth, migration, and invasion and promote ferroptosis to the untreated controls in colorectal cancer cells. Mechanical exploration revealed that PPy@Fe3O4 NPs inhibit the multiplication, migration, and invasion of CRC cells in vitro by modulating the NF-κB signaling pathway. Importantly, Ferroptosis inhibitors Fer-1 can reverse the changes in metastasis-associated proteins caused by NPs treatment. Collectively, our observations revealed that PPy@Fe3O4 NPs were blockers of tumor progression and metastasis in CRC. This study brought new insights into bioactive NPs, with application potential in curing CRC or other human disorders.

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