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BACKGROUND: Compliance with colonoscopy among elderly individuals participating in colorectal cancer (CRC) screening programs is unsatisfactory, despite a high detection rate of bowel-related diseases. In this study, our aim was to analyze the impact of risk factors on the trends of compliance and detection rates in colonoscopy among high-risk individuals aged 60-74. METHODS: A retrospective study was conducted on the high-risk individuals aged 60-74 participating in the 2021 CRC screening program in Tianjin, China. Logistic regression analyses, including both univariate and multivariate analyses, were performed to explore the impact of different risk factors on colonoscopy compliance among the high-risk individuals. Besides, the study investigated the influence of various risk factors on the detection rates of bowel-related diseases among the high-risk individuals who underwent colonoscopy. RESULTS: A total of 24,064 high-risk individuals were included, and 5478 individuals received a free colonoscopy, with an overall compliance of 22.76%. Among them, the adenoma detection rate was 55.46%. Males and individuals with a positive FIT had high compliance and detection rates for CRC, advanced adenomas (AA), advanced colorectal neoplasia (ACN), and colorectal neoplasm (CN). Individuals aged 70-74 were associated with low compliance but high CRC, ACN, and CN detection rates. Individuals who reported a history of chronic constipation, bloody mucous, and CRC in first-degree relative showed high compliance but no significantwere associated with the detection rates of CRC, AA, and CN. CONCLUSION: This study reported several risk factors associated with the screening behaviors for CRC. Patterns and trends in CRC, AA, ACN, and CN compliance and detection rates correlate with risk factors.
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Neoplasias Colorretais , Detecção Precoce de Câncer , Masculino , Idoso , Humanos , Incidência , Estudos Retrospectivos , Neoplasias Colorretais/diagnóstico , Colonoscopia , Fatores de Risco , Programas de RastreamentoRESUMO
Visualization of training effectiveness is critical to patients' confidence and eventual rehabilitation. Here, an innovative magnetoinductive pressure sensor is proposed for monitoring hand rehabilitation in stroke hemiplegic patients. It couples the giant magneto and stress-impedance effects of a square spiral amorphous wire with the giant magnetoelastic effect of a polymer magnet (NdFeB@PDMS). The addition of the magnetoelastic layer results in a sensitivity improvement of 178%, a wide sensing range (up to 1 MPa), fast response/recovery times (40 ms), and excellent mechanical robustness (over 15 000 cycles). Further integration with an LC oscillation circuit enables frequency adjustment into the MHz range resulting in a sensitivity of 6.6% kPa-1 and outstanding linearity (R2 = â 0.99717) over a stress range of up to 100 kPa. When attached to a commercial split-fingerboard, the sensor is capable of dynamically monitoring the force in each finger, providing a reading of the rehabilitation process. Unlike conventional inductive sensors, the sensor is based on an inductive force-responsive material (amorphous wire), which significantly boosts the sensitivity. The approach also demonstrates the potential of magnetoelasticity in static pressure sensing, which is highly sensitive to dynamic pressure only through electromagnetic induction. This makes it more suitable for long-term and continuous human health monitoring.
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Mãos , Humanos , Mãos/fisiologia , Pressão , Elasticidade , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Impedância Elétrica , ImãsRESUMO
PURPOSE: To evaluate the effectiveness of fecal immunochemical testing (FIT) in colorectal cancer screening. METHODS: We conducted a prospective cohort study among 5,598 participants age 40-74 years between 2012 and 2020 in Tianjin, China. Inverse probability weighting was adopted to adjust for potential imbalanced factors between groups. A Cox proportional hazards model was used to estimate the weighted associations between FIT screening and advanced colorectal neoplasia. A difference-in-difference (DID) model was adopted to compare the incidence rates of advanced colorectal neoplasia between groups. RESULTS: In DID analysis, the rate of incidence was reduced by 0.34 cases per person-years in the screening group as compared with the historical FIT screening group (rate ratio [RR], 0.08 [95% CI, 0.07 to 0.10]) and by 0.06 cases per person-years in the non-FIT screening group as compared with the historical non-FIT screening group (RR, 0.37 [95% CI, 0.29 to 0.48]; P < .001 for both comparisons), with a relative reduction of 0.28. Similar benefit effect from FIT screening was observed in sex and age subgroups. CONCLUSION: FIT screening was associated with a reduction in incidence density from advanced colorectal neoplasia.
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Colonoscopia , Neoplasias Colorretais , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Sangue Oculto , China/epidemiologiaRESUMO
BACKGROUND AND AIM: The incidence of colorectal cancer (CRC) in individuals under 50 is increasing worldwide. We conducted an analysis of colonoscopy findings in high-risk individuals under 50 in the CRC screening program in Tianjin, China, to determine the detection rate and risk factors of advanced adenomas (AA), advanced colorectal neoplasia (ACN), colorectal neoplasia (CN). METHODS: Our study investigated individuals aged 40-49 who underwent CRC screening and completed colonoscopy, 2012-2020, while the 50-54 age group served as a control. We compared the detection rates of AA, ACN, and CN among three age groups using univariate and multivariable logistic regression analyses, and investigated the risk factors associated with AA, ACN, and CN among individuals aged 40-49. RESULTS: We found a gradual increase in the detection rate of AA, ACN, and CN among individuals aged 40-54. The detection rates for AA (OR 0.58; 95% CI 0.41-0.81), ACN (OR 0.58; 95% CI 0.43-0.77), and CN (OR 0.64; 95% CI 0.56-0.74) were lower in individuals aged 40-44 compared to 45-49. The detection rates of AA (OR 1.08; 95% CI 0.87-1.34) and ACN (OR 1.12; 95% CI 0.93-1.35) in individuals aged 45-49 were comparable with 50-54. Besides, lifestyle factors, BMI, and FIT are not associated with the detection rates of AA, ACN, and CN among individuals aged 40-49. CONCLUSIONS: Our study reveals screening data in individuals under 50, indicating comparable detection rates of AA and ACN in individuals aged 45-49 and 50-54. These findings provide valuable data support for optimizing the optimal age to initiate screening.
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Colonoscopia , Neoplasias Colorretais , Humanos , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Estilo de Vida , Detecção Precoce de Câncer , Programas de RastreamentoRESUMO
The incidence of bone metastasis (BM) in colorectal cancer (CRC) patients is low and the prognosis is poor. There is no clear conclusion on the risk factors affecting the survival of CRC patients with BM. The aim of this study was to investigate the factors that may affect the prognosis of CRC patients with BM. The clinical and pathological data of CRC patients with BM were retrospectively analyzed. The overall survival after BM diagnosis was estimated using the Kaplan-Meier method and Log-rank test, and a multivariable cox regression model was used to identify the prognostic factors of overall survival. This study included 178 CRC patients with BM, of whom 151 had left-sided CRC and 27 had right-sided colon cancer. 1124 CRC patients with BM from the SEER database were included to perform a sensitivity analysis of the primary outcome. Multivariate analysis showed that the N staging, site of BM, and primary tumor sidedness (PTS) were independent prognostic factors for CRC with BM. Among them, right-sided colon cancer patients with BM had a poorer prognosis. Sensitivity analyses showed that PTS was an independent prognostic factor in CRC patients with BM. Primary tumor sidedness and N stage may be potential prognostic markers for BM of CRC. The prognosis of N0 stage CRC with BM is better, while the prognosis of right-sided colon cancer is poor.
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Neoplasias do Colo , Neoplasias Colorretais , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias Colorretais/diagnóstico , Modelos de Riscos ProporcionaisRESUMO
Transmission electron microscopy (TEM) is indispensable to reveal the cellular nanostructure of the 2:17-type Sm-Co based magnets which act as the first choice for high-temperature magnet-associated devices. However, structural deficiencies could be introduced into the TEM specimen during the ion milling process, which would provide misleading information to understand the microstructure-property relationship of such magnets. In this work, we performed a comparative investigation of the microstructure and microchemistry between two TEM specimens prepared under different ion milling conditions in a model commercial magnet Sm13Gd12Co50Cu8.5Fe13Zr3.5 (wt.%). It is found that additional low-energy ion milling will preferably damage the 1:5H cell boundaries, while having no influence on the 2:17R cell phase. The structure of cell boundary transforms from hexagonal into face-centered-cubic. In addition, the elemental distribution within the damaged cell boundaries becomes discontinuous, segregating into Sm/Gd-rich and Fe/Co/Cu-rich portions. Our study suggested that in order to reveal the true microstructure of the Sm-Co based magnets, the TEM specimen should be carefully prepared to avoid structural damage and artificial deficiencies.
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INTRODUCTION: Geriatric assessment (GA) is widely used to detect vulnerability in older patients. As this process is time-consuming, prescreening tools have been developed to identify patients at risk for frailty. We aimed to assess whether the Geriatric 8 (G8) or the Korean Cancer Study Group Geriatric Score (KG-7) shows better performance in identifying patients who are in need of full GA. MATERIALS AND METHODS: A consecutive series of patients aged ≥ 60 years with colorectal cancer were included. The sensitivity, specificity, predictive value, and 95% confidence intervals (95% CI) were calculated for the G8 and the KG-7 using the results of GA as the reference standard. ROC(Receiver Operating Characteristic) was used to evaluate the accuracy of the G8 and the KG-7. RESULTS: One hundred four patients were enrolled. A total of 40.4% of patients were frail according to GA, and 42.3% and 50.0% of patients were frail based on the G8 and the KG-7, respectively. The sensitivity and specificity of the G8 were 90.5% (95% CI: 77.4-97.3%) and 90.3% (95% CI: 80.1-96.4%), respectively. For the KG-7, the sensitivity and specificity were 83.3% (95% CI: 68.6-93.0%) and 72.6% (95% CI: 59.8-83.1%), respectively. Compared to the KG-7, the G8 had a higher predictive accuracy (AUC: (95% CI): 0.90 (0.83-0.95) vs. 0.78 (0.69-0.85); p < 0.01). By applying the G8 and the KG-7, 60 and 52 patients would not need a GA assessment, respectively. CONCLUSION: Both the G8 and the KG-7 showed a great ability to detect frailty in older patients with colorectal cancer. In this population, compared to the KG-7, the G8 had a better performance in identifying those in need of a full Geriatric Assessment.
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Neoplasias Colorretais , Fragilidade , Neoplasias , Idoso , Humanos , Fragilidade/diagnóstico , Idoso Fragilizado , Detecção Precoce de Câncer , Neoplasias/diagnóstico , Sensibilidade e Especificidade , Avaliação Geriátrica/métodos , Neoplasias Colorretais/diagnósticoRESUMO
OBJECTIVE: This study seeks to assess the efficacy of exfoliated colonocytes isolated from feces (ECIF) miR-92a as a clinical colorectal cancer diagnostic marker in a larger cohort. METHODS: Clinicopathologic data from colorectal cancer patients and health controls that underwent colonoscopy, as well as patients of other cancers diagnosed, were included. A total of 963 Chinese participants were enrolled, with 292 (27.4%) having colorectal cancer, 140 (14.5%) having other types of cancer, e.g., pancreatic, liver, oral, bile duct, esophagus, and stomach cancer, 171 (17.8%) having infection in the intestine, rectal, stomach, appendix, and gastrointestinal ulcer, and 360 (37.4%) of healthy controls. ECIF samples were gathered and miR-92a levels were detected using TaqMan probe-based miR-92a real-time quantitative PCR (RT-qPCR) kit developed by Shenzhen GeneBioHealth Co., Ltd. RESULTS: Through a series of experiments, we demonstrated that the Ep-LMB/Vi-LMB magnetic separation system is feasible, highly specific, and highly sensitive at a cutoff value of 1053 copies per 6 ng of ECIF RNA. ECIF miR-92a levels were significantly higher in colorectal cancer patients than in controls. Colorectal cancer detection sensitivity and specificity were 87.3% and 86.9% respectively. Furthermore, the performance of this miR-92a detection kit demonstrated that it is an effective tool for colorectal cancer, with a high sensitivity of 84.1%, even in early cancer stages (0, I, and II). Furthermore, tumor removal resulted in lower stool miR-92a levels (3.21±0.58 vs. 2.14±1.14, P < 0.0001, n = 65). CONCLUSION: Finally, the miR-92a RT-qPCR kit detects ECIF-increased miR-92a and could be used for colorectal cancer screening.
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BACKGROUND AND AIMS: Colonoscopy is an important colorectal cancer (CRC) screening modality; however, not all high-risk groups identified by fecal immunochemical test (FIT) and/or high-risk factor questionnaire (HRFQ) undergo colonoscopy in time. The impact of delays in colonoscopy on CRC detection among high-risk populations remains poorly understood, warranting further clarification. METHODS: A retrospective study was conducted among CRC high-risk population identified by Tianjin CRC screening program. According to the colonoscopy results after HRFQ and FIT, patients were classified into CRC, advanced adenoma, non-advanced adenoma, and normal groups. The time interval between CRC screening and colonoscopy was investigated and its relationship with colonoscopy results. Logistic regression was performed to explore the risk factors of CRC detection. RESULTS: Among the high-risk population without a history of CRC or polyps, 49,810 underwent HRFQ, FIT, and colonoscopy, and a time interval of fewer than 6 months was found for 79.56% of patients (n = 39,630). People with positive FIT were more likely to undergo colonoscopy within 6 months, and detection rates of CRC and/or advanced adenoma were positively related to time intervals. Similar results were found in people with a negative FIT but positive HRFQ. A time interval longer than 6 months was a significant predictor of CRC detection in high-risk populations. CONCLUSION: For high-risk people identified by CRC screening, especially those with a positive FIT, a time interval of 6 months was associated with an increased probability of CRC detection. Our findings emphasize that populations at high risk should undergo colonoscopy at least within 6 months.
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Adenoma , Neoplasias Colorretais , Humanos , Estudos Retrospectivos , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Fatores de Risco , Detecção Precoce de Câncer/métodos , China/epidemiologia , Adenoma/diagnóstico , Adenoma/epidemiologia , Programas de Rastreamento/métodosRESUMO
Aim: Transanal endoscopic microsurgery (TEM) is widely performed in early rectal cancer. This technique offers greater organ preservation and decreases the risk of subsequent surgery. However, postoperative local recurrence and distant metastasis remain challenges for patients with high-risk pathological factors. This single-center study reports the prognosis of early rectal cancer patients over 60 years old after TEM. Methods: The data of the patients over 60 years old who underwent local anal resection were collected retrospectively. Moreover, the 5-year follow-up data were analyzed to determine the 5-year DFS and OS. Results: 47 early rectal cancer patients over 60 years old underwent TEM. There were 27 patients with high-risk factors and 20 patients without high-risk factors. Two patients underwent radical surgery after TEM and ten patients received adjuvant treatment. Local recurrence occurred in 7 patients, of which 4 underwent salvage surgery. The 5-year progression-free survival rate was 75.6%, which was lower in the high-risk patients group (69.6%) than in the non-high-risk patients group (83.3%) (P>0.05). The 5-year OS was 90.2%, but there was no statistically significant difference between the two groups (high-risk patients 87.0%, non-high-risk patients 94.4%). Furthermore, there was no significant difference in DFS and OS between people over and under 70 years old. Conclusion: Some high-risk factor patients over 60 years old do not have inferior 5-year DFS and OS to the non-high-risk patients. TEM is an option for old patients with high surgical risks. Even if postoperative pathology revealed high-risk factors, timely surgical treatment after local recurrence would be beneficial to improve the 5-year DFS and OS.
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Multi-metallic nanoparticles have been proven to be an efficient photothermal conversion material, for which the optical absorption can be broadened through the interband transitions (IBTs), but it remains a challenge due to the strong immiscibility among the repelling combinations. Here, assisted by an extremely high evaporation temperature, ultra-fast cooling and vapor-pressure strategy, the arc-discharged plasma method was employed to synthesize ultra-mixed multi-metallic nanoparticles composed of 21 elements (FeCoNiCrYTiVCuAlNbMoTaWZnCdPbBiAgInMnSn), in which the strongly repelling combinations were uniformly distributed. Due to the reinforced lattice distortion effect and excellent IBTs, the nanoparticles can realize an average absorption of >92% in the entire solar spectrum (250 to 2500 nm). In particular, the 21-element nanoparticles achieve a considerably high solar steam efficiency of nearly 99% under one solar irradiation, with a water evaporation rate of 2.42 kg m-2 h-1, demonstrating a highly efficient photothermal conversion performance. The present approach creates a new strategy for uniformly mixing multi-metallic elements for exploring their unknown properties and various applications.
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Background: The recent uptrend in colorectal cancer (CRC) incidence in China is causing an increasingly overwhelming social burden. And its occurrence can be effectively reduced by sensitizing CRC screening for early diagnosis and treatment. However, a large number of people in China do not undergo screening due to multiple factors. To address this issue, since 2012, a CRC screening program has been initiated in Tianjin. Methods: Residents aged 40-74 years were eligible for CRC screening. The first was to complete the high-risk factor questionnaire (HRFQ) and undergo fecal immunochemical test (FIT). Then those with a positive result in any of the two screening methods were recommended for a free colonoscopy. Results: The detection rate of intestinal diseases increased with age, had a male predominance, and was higher in residents from central urban areas and those with primary school above education level. The sensitivity of predicting CRC after colonoscopy in the high-risk group was 76.02%; the specificity was 25.33%.A significant decrease in the detection rate of intestinal disease, CRC and advanced adenoma was observed from positive FIT, the high-risk group and positive HRFQ, 47.13%, 44.79%, 42.30%; 3.15%, 2.44%, 1.76%; 7.72%, 6.42%, 5.08%, in that order, while no inter-group difference was found for the detection of polyps. In addition, the different combinations of HRFQ and FIT can enroll more high-risk population than FIT or (and) HRFQ only, and thus detect more intestinal diseases (include CRC/AA/Polyp). Conclusion: The superimposition of different screening method for HRFQ and FIT is an effective strategy for the detection of CRC, AA, and Polyp, compared to HRFQ or FIT alone. However, further improvements in screening and interventions are needed to promote colonoscopy compliance.
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ThMn12 -type SmFe12 -based permanent magnets have exhibited great potential in advanced magnet motors because of their high temperature stability of magnetic properties. However, the applications could be seriously limited due to the trade-off between phase stability and intrinsic magnetic properties. In this work, an effective solution is demonstrated by constructing the core-shell structure (Sm-rich shell and Y-rich core) via a spontaneous spinodal decomposition process. The anisotropy field for the (Sm0.75 Y0.25 )(Fe0.8 Co0.2 )11.25 Ti0.75 alloy is mostly optimized to be 9.24 T at room temperature. Such an enhancement is ascribed to the pinning process of domain walls by the magnetic-hardening Sm-rich shell, which is directly observed by in situ Lorentz transmission electron microscopy and reconstructed by micromagnetic simulation. Moreover, the phase stability and saturation magnetization are simultaneously increased, which is attributed to the synergistic effect of Y, Co, and Ti substitutions. More importantly, the high µ0 Ms value of 1.52 T is comparable to the reported (Sm,Zr)Fe12 -based bulk alloys that contain a larger amount of soft α-Fe phases, indicating that this strategy is more promising toward bulk magnets. The present study provides a significant concept for the development of advanced permanent magnets and also has implications for understanding the structural origin of intrinsic magnetic configurations.
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Superhydrophobic surfaces with high adhesion provide high potential for underwater applications. Inspired by Salvinia leaf, here, we have reported a simple method for fabricating adhesive Salvinia-like micropillars via photolithography and spontaneous adsorption of organic molecules from the atmosphere. With continuous hydrocarbon adsorption on sputtered cerium dioxide (CeO2) films, the surface gradually evolved and eventually became chemically heterogeneous. Huge wetting contrast from superhydrophilic to superhydrophobic over exposure time was observed; meanwhile, the wetting mode changed from the Wenzel (W) state to Cassie-Baxter (C-B) state. As a result, hydrophobic hydrocarbons (C-C/C-H) and trapped air between adjacent pillars contributed to the high apparent contact angle (CA), while the hydrophilic domains of C-O/OâC-O and CeO2 on the top layer made the surface highly adhesive with water droplets. In comparison with traditional fluorinated superhydrophobic surfaces, CeO2-coated surfaces showed high adhesive force with water droplets and can be used as a "mechanical hand" for water droplet transport. The adsorption-induced Salvinia-like micropillars with high adhesion may find many other droplet-based applications in microfluidic fields.
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BACKGROUND: A colorectal cancer screening programme (CCSP) was implemented from 2012 to 2017 in Tianjin, China. Residents with a positive faecal immunochemical test (FIT) or positive self-reported symptom questionnaire (SRSQ) were recommended to undergo colonoscopy. The objective was to investigate the potential factors associated with nonadherence to colonoscopy among a risk-increased population. METHODS: Data were obtained from the CCSP database, and 199,522 residents with positive FIT or positive SRSQ during two screening rounds (2012-2017) were included in the analysis. Logistic regression analysis was performed to assess the association between nonadherence to colonoscopy and potential predictors. RESULTS: A total of 152,870 (76.6%) individuals did not undergo colonoscopy after positive FIT or positive SRSQ. Residents with positive SRSQ but without positive FIT were more likely not to undergo colonoscopy (negative FIT: OR, 2.35; 95% CI, 2.29-2.41, no FIT: OR, 1.27; 95% CI, 1.24-1.31). Patients without a cancer history were less likely to undergo colonoscopy even if they received risk-increased reports based on the SRSQ. CONCLUSION: In the CCSP, seventy-seven percent of the risk-increased population did not undergo colonoscopy. FIT should be recommended since positive FIT results are related to improved adherence to colonoscopy. Residents with negative FIT but positive SRSQ should be informed of the potential cancer risk to ensure adherence to colonoscopy.
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Neoplasias Colorretais , Detecção Precoce de Câncer , China , Colonoscopia , Neoplasias Colorretais/diagnóstico , Humanos , Programas de Rastreamento , Sangue Oculto , Autorrelato , Inquéritos e QuestionáriosRESUMO
We previously reported that polyploid giant cancer cells (PGCCs) exhibit cancer stem cell properties and can generate daughter cells with the epithelial-mesenchymal transition phenotype. This study investigated the role of PGCC formation in the prognostic value of neoadjuvant chemoradiation therapy (nCRT) in locally advanced rectal cancer (LARC). The morphological characteristics were observed in patients with LARC after nCRT. Colorectal cancer cell lines were treated with irradiation or chemotherapeutic drugs, and the metastasis-related proteins were detected. 304 nCRT cases and 301 paired non-nCRT cases were collected for analysis. More PGCCs and morphologic characteristics related to invasion and metastasis appeared in tumor tissue after nCRT. Irradiation or chemicals could induce the formation of PGCCs with daughter cells exhibiting strong migratory, invasive, and proliferation abilities. In patients after nCRT, pathologic complete remission, partial remission, stable disease, and progressive disease were observed in 29 (9.54%), 125 (41.12%), 138 (45.39%), and 12 (3.95%) patients, respectively. Mucinous adenocarcinomas (MCs) occurred more frequently in nCRT than in non-nCRT patients (χ 2 = 29.352, P=0.001), and the prognosis in MC patients was worse than that in non-MC patients (χ 2 = 24.617, P=0.001). The difference in survival time had statistical significance for 60 days (χ 2 = 5.357, P=0.021) and 70 days (χ 2 = 18.830, P=0.001) rest interval time. On multivariable analysis, 60 days rest interval, Duke's stage, and recurrence and/or distant metastasis remained significant predictors of survival. In conclusion, irradiation or chemicals induce the formation of PGCCs and PGCCs produce daughter cells with strong migration and invasion abilities after a long incubation period. Appropriate rest interval (incubation period) is very important for patients with LARC who will receive nCRT.
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Parthenolide (PTL) and micheliolide (MCL) are sesquiterpene lactones with similar structures, and both of them have been reported to exhibit multiple biochemical and pharmacological activities. This study aims to investigate the inhibition of these two compounds on the activity of UDP-glucuronosyltransferases (UGTs). In vitro incubation mixture for recombinant UGTs-catalyzed glucuronidation metabolism of 4-methylumbelliferone (4-MU) was utilized to investigate the inhibition potential. Inhibition kinetics (including inhibition type and parameters) were determined, and in silico docking was employed to elucidate the inhibition difference between PTL and MCL on UGT1A1. MCL showed no inhibition toward all the UGT isoforms, and PTL showed strong inhibition toward UGT1A1. The half-maximal inhibitory concentration (IC50) of PTL on the activity of UGT1A1 was determined to be 64.4 µM. Inhibition kinetics determination showed that PTL exerted noncompetitive inhibition toward UGT1A1, and the inhibition kinetic constant (Ki) was determined to be 12.1 µM. In silico docking method has been employed to show that hydrogen bonds between PTL and the activity cavity of UGT1A1 contributed to the stronger inhibition of PTL on the activity of UGT1A1 than MCL. In conclusion, PTL can more easily induce drug-drug interaction (DDI) with clinical drugs mainly undergoing UGT1A1-catalyzed glucuronidation.
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Inibidores Enzimáticos , Glucuronosiltransferase/antagonistas & inibidores , Glucuronosiltransferase/química , Sesquiterpenos de Guaiano , Sesquiterpenos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacocinética , Inibidores Enzimáticos/farmacologia , Humanos , Cinética , Sesquiterpenos/química , Sesquiterpenos/farmacocinética , Sesquiterpenos/farmacologia , Sesquiterpenos de Guaiano/química , Sesquiterpenos de Guaiano/farmacocinética , Sesquiterpenos de Guaiano/farmacologiaRESUMO
We aimed to predict colorectal cancer (CRC) based on the demographic features and clinical correlates of personal symptoms and signs from Tianjin community-based CRC screening data.A total of 891,199 residents who were aged 60 to 74 and were screened in 2012 were enrolled. The Lasso logistic regression model was used to identify the predictors for CRC. Predictive validity was assessed by the receiver operating characteristic (ROC) curve. Bootstrapping method was also performed to validate this prediction model.CRC was best predicted by a model that included age, sex, education level, occupations, diarrhea, constipation, colon mucosa and bleeding, gallbladder disease, a stressful life event, family history of CRC, and a positive fecal immunochemical test (FIT). The area under curve (AUC) for the questionnaire with a FIT was 84% (95% CI: 82%-86%), followed by 76% (95% CI: 74%-79%) for a FIT alone, and 73% (95% CI: 71%-76%) for the questionnaire alone. With 500 bootstrap replications, the estimated optimism (<0.005) shows good discrimination in validation of prediction model.A risk prediction model for CRC based on a series of symptoms and signs related to enteric diseases in combination with a FIT was developed from first round of screening. The results of the current study are useful for increasing the awareness of high-risk subjects and for individual-risk-guided invitations or strategies to achieve mass screening for CRC.
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Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Idoso , Área Sob a Curva , China , Fezes/química , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco/métodos , Inquéritos e QuestionáriosRESUMO
The therapy for the advanced colon cancer (Cca) is unsatisfactory currently. To regulate the immune effector cell function has shown a positive effect on the treatment of advanced cancers. This study tests a hypothesis that administration with curcumin converts the Cca patient-derived regulatory T cells (Treg) to T helper (Th) 1 cells. In this study, a group of patients with advanced Cca was recruited into this study. The patients were treated with curcumin. The peripheral Tregs and Th1 cells were assessed by flow cytometry. The results showed that, after the curcumin therapy, the forkhead box protein (Foxp) 3 positive Treg frequency was markedly reduced, the frequency of Th1 cells was significantly increased in Cca patients. Treating with curcumin repressed the Foxp3 gene transcription in Tregs; the Tregs were then converted into Th1 cells. The results also revealed that Foxp3 bound T-bet to prevent IFN-γ expression in CD4+ T cells, which was abolished by treating with curcumin. In conclusion, the administration of curcumin can convert Tregs to Th1 cells via repressing Foxp3 expression and enhancing IFN-γ production.