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1.
Gut ; 73(7): 1169-1182, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38395437

RESUMO

OBJECTIVE: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), mostly characterised by HBV integrations, is prevalent worldwide. Previous HBV studies mainly focused on a few hotspot integrations. However, the oncogenic role of the other HBV integrations remains unclear. This study aimed to elucidate HBV integration-induced tumourigenesis further. DESIGN: Here, we illuminated the genomic structures encompassing HBV integrations in 124 HCCs across ages using whole genome sequencing and Nanopore long reads. We classified a repertoire of integration patterns featured by complex genomic rearrangement. We also conducted a clustered regularly interspaced short palindromic repeat (CRISPR)-based gain-of-function genetic screen in mouse hepatocytes. We individually activated each candidate gene in the mouse model to uncover HBV integration-mediated oncogenic aberration that elicits tumourigenesis in mice. RESULTS: These HBV-mediated rearrangements are significantly enriched in a bridge-fusion-bridge pattern and interchromosomal translocations, and frequently led to a wide range of aberrations including driver copy number variations in chr 4q, 5p (TERT), 6q, 8p, 16q, 9p (CDKN2A/B), 17p (TP53) and 13q (RB1), and particularly, ultra-early amplifications in chr8q. Integrated HBV frequently contains complex structures correlated with the translocation distance. Paired breakpoints within each integration event usually exhibit different microhomology, likely mediated by different DNA repair mechanisms. HBV-mediated rearrangements significantly correlated with young age, higher HBV DNA level and TP53 mutations but were less prevalent in the patients subjected to prior antiviral therapies. Finally, we recapitulated the TONSL and TMEM65 amplification in chr8q led by HBV integration using CRISPR/Cas9 editing and demonstrated their tumourigenic potentials. CONCLUSION: HBV integrations extensively reshape genomic structures and promote hepatocarcinogenesis (graphical abstract), which may occur early in a patient's life.


Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B , Neoplasias Hepáticas , Integração Viral , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/patologia , Vírus da Hepatite B/genética , Humanos , Integração Viral/genética , Animais , Camundongos , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Sequenciamento Completo do Genoma , Variações do Número de Cópias de DNA , Idoso
2.
Anal Chem ; 96(24): 9944-9952, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38843071

RESUMO

Label-free photoelectrochemical sensors have the advantages of high sensitivity and a simple electrode structure. However, its performance is greatly limited due to the photoactive materials' weak photoactivity and poor stability. Herein, a robust homogeneous photoelectrochemical (PEC) aptasensor has been constructed for atrazine (ATZ) based on photoetching (PE) surface oxygen vacancies (Ov)-enriched Bismuth vanadate (BiVO4) (PE-BVO). The surface of the Ov improves the carrier separation ability of BiVO4, thus providing a superior signal substrate for the sensor. A thiol molecular layer self-assembled on PE-BVO acts as a blocker, while 2D graphene acts as a signal-on probe after release from the aptamer-graphene complex. The fabricated sensor has a wide linear detection range of 0.5 pM to 10.0 nM and a low detection limit of 0.34 pM (S/N = 3) for ATZ. In addition, it can efficiently work in a wide pH range (3-13) and high ionic strength (∼6 M Na+), which provides promising opportunities for detecting environmental pollutants under complex conditions.

3.
Breast Cancer Res Treat ; 204(1): 89-105, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38066250

RESUMO

PURPOSE: To investigate potential differences in pathological complete response (pCR) rates and overall survival (OS) between HER2-low and HER2-zero patients with early-stage hormone receptor (HR)-positive and triple-negative breast cancer (TNBC), in the neoadjuvant chemotherapy setting. METHODS: We identified early-stage invasive HER2-negative BC patients who received neoadjuvant chemotherapy diagnosed between 2010 and 2018 in the National Cancer Database. HER2-low was defined by immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization, and HER2-zero by IHC0. All the methods were applied separately in the HR-positive and TNBC cohorts. Logistic regression was used to estimate the association of HER2 status with pCR (i.e. ypT0/Tis and ypN0). Kaplan-Meier method and Cox proportional hazards model were applied to estimate the association of HER2 status with OS. Inverse probability weighting and/or multivariable regression were applied to all analyses. RESULTS: For HR-positive patients, 70.9% (n = 17,934) were HER2-low, whereas 51.1% (n = 10,238) of TNBC patients were HER2-low. For both HR-positive and TNBC cohorts, HER2-low status was significantly associated with lower pCR rates [HR-positive: 5.0% vs. 6.7%; weighted odds ratio (OR) = 0.81 (95% CI: 0.72-0.91), p < 0.001; TNBC: 21.6% vs. 24.4%; weighted OR = 0.91 (95% CI: 0.85-0.98), p = 0.007] and improved OS [HR-positive: weighted hazard ratio = 0.85 (95% CI: 0.79-0.91), p < 0.001; TNBC: weighted hazard ratio = 0.91 (95% CI: 0.86-0.96), p < 0.001]. HER2-low status was associated with favorable OS among patients not achieving pCR [HR-positive: adjusted hazard ratio = 0.83 (95% CI: 0.77-0.89), p < 0.001; TNBC: adjusted hazard ratio = 0.88 (95% CI 0.83-0.94), p < 0.001], while no significant difference in OS was observed in patients who achieved pCR [HR-positive: adjusted hazard ratio = 1.00 (95% CI: 0.61-1.63), p > 0.99; TNBC: adjusted hazard ratio = 1.11 (95% CI: 0.85-1.45), p = 0.44]. CONCLUSION: In both early-stage HR-positive and TNBC patients, HER2-low status was associated with lower pCR rates. HER2-zero status might be considered an adverse prognostic factor for OS in patients not achieving pCR.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Terapia Neoadjuvante/efeitos adversos , Modelos de Riscos Proporcionais , Receptor ErbB-2/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico
4.
BMC Cancer ; 24(1): 115, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263067

RESUMO

AIMS: Selective lateral pelvic lymph node (LPN) dissection (LPND) following neoadjuvant chemoradiotherapy (nCRT) for rectal cancer is widely recognized. This study aimed to determine the effects of nCRT before LPND on local control and prognosis of rectal cancer patients. MATERIALS AND METHODS: Data were retrieved from a prospective database for rectal cancer patients with clinical LPN metastasis receiving total mesorectal excision and LPND at three institutions between January 2012 and December 2019. Selection bias was minimized using propensity score matching (PSM) and short-term and clinical outcomes were compared. RESULTS: Patients (n = 213) were enrolled and grouped as either nCRT (n = 97) or non-nCRT (n = 116). PSM was used to identify 83 matched pairs. In the matched cohort, nCRT patients had a longer operation duration (310.6 vs. 265.0 min, P = 0.001), lower pathological LPN metastasis rate (32.5% vs. 48.2%, P = 0.040), and fewer harvested lymph nodes (22 vs. 25, P = 0.018) compared to the non-nCRT group. However, after PSM, the two groups had similar estimated overall 3-year survival (79.5% vs. 80.7%, P = 0.922), 3-year disease-free survival (66.1% vs. 65.5, P = 0.820), and 3-year local recurrence-free survival (88.6% vs. 89.7%, P = 0.927). Distant metastasis was the predominant recurrence pattern in the overall (45/58, 77.6%) and matched (33/44, 75.0%) cohorts. CONCLUSIONS: LPND without nCRT is effective and sufficient in preventing local recurrence in patients with LPN metastases. Future prospective randomized controlled studies are warranted to confirm these findings. Since systemic metastasis is the predominant recurrence pattern in patients with LPN metastasis post-LPND, improved perioperative systemic chemotherapy is needed to prevent micrometastasis.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Metástase Linfática , Excisão de Linfonodo , Linfonodos , Prognóstico , China
5.
HPB (Oxford) ; 26(1): 125-136, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37806829

RESUMO

BACKGROUND: Despite recommendations for primary tumor resection (PTR) with or without liver resection (LR) in the patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and isolated liver metastases, there are conflicting data for their impact on overall survival (OS). METHODS: 2320 patients with GEP-NETs and isolated liver metastases were identified from NCDB. Multiple imputations were used to accommodate missing data, and inverse probability of treatment weighting (IPTW) was conducted to minimize bias. RESULTS: Patients with PTR had a greater OS than those without PTR (3-year rate of 88.6% vs. 69.9%, P < 0.001), which was preserved in the adjusted analysis (IPTW-adjusted HR = 0.387, 95% CI: 0.264-0.567; P < 0.001). Patients with LR had a greater OS than those without LR (3-year rate 87.7% vs. 75.2%, P = 0.003), which was also preserved in adjusted analysis (IPTW-adjusted HR = 0.450, 95% CI: 0.229-0.885; P = 0.021). Patients undergoing both PTR and LR had the greatest survival advantage than those with other surgical interventions (P < 0.001). CONCLUSIONS: Either PTR or LR is associated with improved survival for GEP-NET patients with isolated liver metastases. However, there remains significant selection bias in the current study, and caution should be exercised when selecting patients for resection.


Assuntos
Neoplasias Hepáticas , Metastasectomia , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Metastasectomia/efeitos adversos , Neoplasias Hepáticas/patologia , Neoplasias Pancreáticas/patologia
6.
Anal Chem ; 95(43): 15975-15984, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37812773

RESUMO

Developing a dual-photoelectrode fuel cell based self-powered sensor (DPFC-SPS) with an ideal signal output capability and high sensitivity performance for the detection of environmental pollutant atrazine (ATZ) has an important value. In this work, the in situ molecularly imprinting functionalized p-type organic semiconductor polyterthiophene (MI-pTTh) is used as a photocathode to construct a DPFC-SPS toward the typical environmental pollutant ATZ for the first time. Due to its excellent photoactivity, higher stability, and superior oxygen reduction reaction activity, pTTh serves as the photocathode material for constructing a self-powered sensing platform with a stable signal output and high photoelectric activity. Based on the sensitive light-triggered large self-bias of the DPFC-SPS, the open circuit potential (EOCV) of the device reaches 1.21 V and the maximum power density (Pmax) reaches 121.5 µW·cm-2, which is much higher than most reported PFC-SPSs. Simultaneously, in situ molecularly imprinted (MI) functionization of pTTh can further endow it with specific recognition ability, helping the constructed SPS achieve high sensitivity, selectivity, and effective recognition of the important environmental pollutants ATZ in complex systems. It exhibits a broad linear relationship from 0.002 to 100 nM and a low detection limit (estimated by S/N > 3) of 0.21 pM toward ATZ. The mechanism of the binding kinetics of the MI-pTTh with the target ATZ is further studied via in situ infrared spectroscopy. This work provides theoretical guidance for sensing strategies using dual-photoelectrode devices and offers a rational device design for cost-effective electricity generation from renewable resources.

7.
BMC Cancer ; 23(1): 1268, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129822

RESUMO

PURPOSE: Previous randomized studies have shown a survival benefit of using regorafenib but a high rate of adverse events in unresectable colorectal cancer patients. To reduce these adverse events and improve the tolerability, we examined the appropriate dose of regorafenib based on body weight. METHODS: We used a nationwide claims database in Japan and examined the efficacy and safety of regorafenib for patients with metastatic colorectal cancer between groups divided by body weight (60 kg) and median average dose (120 mg) between 2013 and 2018. We also assessed overall survival (OS) and adverse events between these groups. RESULTS: We identified 2530 Japanese patients (heavy weight/high dose: 513, light weight/low dose: 921, heavy weight/low dose: 452, and light weight/high dose: 644). There was no significant difference in the adverse events and OS after inverse probability treatment weighting (IPTW) adjustment between heavy weight/high dose group and light weight/low dose group (hazard ratio, HR=0.97). Among the light-weight patients, higher average dose was associated with shorter OS (IPTW adjusted HR=1.21, 95% CI 1.05 - 1.39, Table 3) while among the heavy-weight patients, there was no significant difference in OS between high and low dose groups (IPTW adjusted HR=1.14, 95% CI 0.95 - 1.37). CONCLUSION: The findings suggest that a low dose of regorafenib for light-weight patients may be as safe and effective as high doses for heavy-weight patients. Further studies should be conducted to identify an appropriate dose based on each patient's physique and condition.


Assuntos
Neoplasias Colorretais , Piridinas , Humanos , Estudos Retrospectivos , Piridinas/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Neoplasias Colorretais/patologia , Peso Corporal
8.
J Surg Oncol ; 127(6): 945-955, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36807890

RESUMO

BACKGROUND: The role of primary tumor resection (PTR) in the survival of gastrointestinal neuroendocrine carcinoma (GI-NEC) patients with liver metastases only remains poorly defined. Therefore, we investigated the impact of PTR on the survival of GI-NEC patients with nonresected liver metastases. METHODS: GI-NEC patients with a liver-confined metastatic disease diagnosed between 2016 and 2018 were identified in the National Cancer Database. Multiple imputations by chained equations were used to account for missing data, and the inverse probability of treatment weighting (IPTW) method was used to eliminate selection bias. Overall survival (OS) was compared by adjusted Kaplan-Meier curves and log-rank test with IPTW. RESULTS: A total of 767 GI-NEC patients with nonresected liver metastases were identified. Among all patients, 177 (23.1%) received PTR and had a significantly favorable OS before (median: 43.6 months [interquartile range, IQR, 10.3-64.4] vs. 8.8 months [IQR, 2.1-23.1], p < 0.001 in log-rank test) and after (median: 25.7 months [IQR, 10.0-64.4] vs. 9.3 months [IQR, 2.2-26.4], p < 0.001 in IPTW-adjusted log-rank test) the IPTW adjustment. Additionally, this survival advantage persisted in an adjusted Cox model (IPTW adjusted hazard ratio = 0.431, 95% confidence interval: 0.332-0.560; p < 0.001). The improved survival persisted in subgroups stratified by primary tumor site, tumor grade, and N stage, even in the complete cohort (excluding patients with missing data). CONCLUSIONS: PTR led to improved survival for GI-NEC patients with nonresected liver metastases regardless of primary tumor site, tumor grade, and N stage. However, the decision for PTR should be made on an individualized basis following multidisciplinary evaluation.


Assuntos
Carcinoma Neuroendócrino , Neoplasias Gastrointestinais , Neoplasias Hepáticas , Humanos , Neoplasias Gastrointestinais/patologia , Neoplasias Hepáticas/cirurgia , Modelos de Riscos Proporcionais , Estimativa de Kaplan-Meier , Estudos Retrospectivos
9.
BMC Surg ; 23(1): 131, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37194000

RESUMO

BACKGROUND: To explore the clinical prognostic utility of the preoperative cholesterol-to-lymphocyte ratio (CLR) in outcomes for colorectal cancer liver metastasis (CRLM) patients receiving simultaneous resection of the primary lesion and liver metastases. METHODS: A total of 444 CRLM patients receiving simultaneous resections were enrolled. The optimal cut-off value for CLR was determined using the highest Youden's index. Patients were divided into the CLR < 3.06 group and the CLR≥3.06 group. Propensity score matching analysis (PSM) and the inverse probability of treatment weighting (IPTW) method were conducted to eliminate bias between the two groups. The outcomes included short-term outcomes and long-term outcomes. Kaplan-Meier curves and log-rank tests were used to analyse progression-free survival (PFS) and overall survival (OS). RESULTS: In the short-term outcome analysis, after 1:1 PSM, 137 patients were distributed to the CLR < 3.06 group and CLR≥3.06 group. No significant difference was noted between the two groups (P > 0.1). Compared with patients with CLR < 3.06, patients with CLR≥3.06 had comparable operation times (320.0 [272.5-421.0] vs. 360.0 [292.5-434.5], P = 0.088), blood loss (200.0 [100.0-400.0] vs. 200.0 [150.0-450.0], P = 0.831), postoperative complication rates (50.4% vs. 46.7%, P = 0.546) and postoperative ICU rates (5.8% vs. 11.7%, P = 0.087). In the long-term outcome analysis, Kaplan-Meier analysis showed that compared with patients with CLR < 3.06, patients with CLR≥3.06 had worse PFS (P = 0.005, median: 10.2 months vs. 13.0 months) and OS (P = 0.002, median: 41.0 months vs. 70.9 months). IPTW-adjusted Kaplan-Meier analysis showed that the CLR≥3.06 group had worse PFS (P = 0.027) and OS (P = 0.010) than the CLR < 3.06 group. In the IPTW-adjusted Cox proportional hazards regression analysis, CLR≥3.06 was an independent factor for PFS (HR = 1.376, 95% CI 1.097-1.726, P = 0.006) and OS (HR = 1.723, 95% CI 1.218-2.439, P = 0.002). IPTW-adjusted Cox proportional hazards regression analysis including postoperative complications, operation time, intraoperative blood loss, intraoperative blood transfusion and postoperative chemotherapy revealed that CLR≥3.06 was an independent factor for PFS (HR = 1.617, 95% CI 1.252-2.090, P < 0.001) and OS (HR = 1.823, 95% CI 1.258-2.643, P = 0.002). CONCLUSIONS: The preoperative CLR level predicts unfavourable outcomes in CRLM patients receiving simultaneous resection of the primary lesion and liver metastases and should be taken into consideration when developing treatment and monitoring strategies.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Estudos Retrospectivos , Neoplasias Colorretais/patologia , Hepatectomia/métodos , Prognóstico , Linfócitos/patologia , Complicações Pós-Operatórias/etiologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário
10.
HPB (Oxford) ; 25(10): 1255-1267, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37414710

RESUMO

BACKGROUND: Literature is lacking on the impact of advancements in minimally invasive surgery (MIS) on outcomes for patients with gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs). Herein, we compared perioperative and oncologic outcomes among patients with GEP-NECs undergoing open, laparoscopic, and robotic resection. METHODS: Patients with GEP-NECs diagnosed 2010-2019 were identified from the National Cancer Database (NCDB). We used the inverse probability of treatment weighting method to account for selection bias. Patients were stratified by surgical approach; and pairwise comparisons were conducted by analyzing short- and long-term outcomes. RESULTS: Receipt of MIS increased from 34.2% in 2010 to 67.5 % in 2019. Altogether, 6560 patients met study criteria: 3444 (52.5%) underwent open resection, 2783 (42.4%) underwent laparoscopic resection and 333 (5.1%) underwent robotic resection. Compared with open resection, laparoscopic or robotic resection were associated with shorter post-operative length of stay, reduced 30-day and 90-day post-operative mortality, and prolonged overall survival (OS). Compared with laparoscopic resection, robotic resection was associated with reduced 90-day post-operative mortality, however, there was no significant difference in OS. CONCLUSION: This NCDB analysis demonstrates that MIS approaches for treating GEP-NECs have become more common, with improved perioperative mortality, shorter post-operative length of stay and favorable OS, compared with open resection.

11.
BMC Cancer ; 22(1): 921, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36008803

RESUMO

BACKGROUND: The prognostic values of preoperative aspartate aminotransferase (AST), monocyte-to-lymphocyte ratio (MLR), AST·MLR index (AMLRI) and operation injury condition in patients with colorectal cancer liver metastases (CRLM) remains unclear. This retrospective study assessed the relationship between these markers, progression-free survival (PFS), and overall survival (OS) in CRLM patients undergoing resection. METHODS: AMLRI was defined as AST × MLR. Operation injury condition was defined according to operation time and blood loss. Cox regression analyses were used to identify risk factors and to develop nomograms. C-indexes, time-dependent receiver operating characteristic (time-ROC) curves and calibration curves were used to assess the models. RESULTS: A total of 379 patients were enrolled. The optimal cut-off value of the AMLRI was 3.33. In the multivariable analysis, AMLRI > 3.33 (hazard ratio [HR] = 2.162, p = 0.002) and serious operation injury condition (HR = 1.539, p = 0.012) were predictive for unfavourable OS, and AMLRI > 3.33 (HR = 1.462, p = 0.021) was predictive for unfavourable PFS. The nomograms were superior to Fong's Clinical Risk Score (CRS) according to the C-indexes (PFS: 0.682 vs. 0.600; OS: 0.730 vs. 0.586) and time-ROCs. CONCLUSIONS: Preoperative AMLRI and operation injury condition are easily accessible predictors for prognosis. The nomograms performed better than CRS for the prediction of recurrence and survival.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Neoplasias Hepáticas/patologia , Linfócitos/patologia , Monócitos/patologia , Prognóstico , Estudos Retrospectivos
12.
HPB (Oxford) ; 24(3): 342-352, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34400051

RESUMO

BACKGROUND: This study aimed to investigate the work status of clinicians in China and their management strategy alteration for patients with hepatocellular carcinoma (HCC) during the COVID-19 pandemic. METHODS: A nationwide online questionnaire survey was conducted in 42 class-A tertiary hospitals across China. Experienced clinicians of HCC-related specialties responded with their work status and management suggestions for HCC patients during the pandemic. RESULTS: 716 doctors responded effectively with a response rate of 60.1%, and 664 were included in the final analysis. Overall, 51.4% (341/664) of clinicians reported more than a 60% reduction of the regular workload and surgeons declared the highest proportion of workload reduction. 92.5% (614/664) of the respondents have been using online medical consultation to substitute for the "face-to-face" visits. Adaptive adjustment for the treatment strategy for HCC was made, including the recommendations of noninvasive and minimally invasive treatments such as transcatheter arterial chemoembolization for early and intermediate stage. Targeted therapy has been the mainstay for advanced stage and also as a bridge therapy for resectable HCC. DISCUSSION: During the COVID-19 pandemic, online medical consultation is recommended to avoid social contact. Targeted therapy as a bridge therapy is recommended for resectable HCC considering the possibility of delayed surgery.


Assuntos
COVID-19 , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Pandemias , SARS-CoV-2 , Inquéritos e Questionários
13.
BMC Surg ; 21(1): 105, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648470

RESUMO

BACKGROUND: Recent studies suggest red blood cell distribution width (RDW) was a prognostic factor in various types of cancer patients, although the results are controversial. The objective of this study was to investigate the significance of RDW in patients with intrahepatic cholangiocarcinoma (ICC) after radical resection. METHOD: The relationship between the preoperative serum RDW value and clinic pathological characteristics was analyzed in 157 ICC patients between January 2012 and June 2018 who underwent curative resection. X-tile software was used to determine 40.2 fl, 12.6% as the optimal cut-off value for RDW-SD and RDW-CV respectively. 153 patients were classified into the low RDW-SD (≤ 40.2, n = 53) group and the high RDW-SD (> 40.2, n = 104) group, low RDW-CV (≤ 12.6, n = 94) group and the high RDW-CV (> 12.6, n = 63). Based on the RDW-SD combined with RDW-CV (SCC), classified into SCC = 0, 1 and 2 group. Kaplan-Meier survival analysis and Cox proportional hazard models were used to examine the effect of RDW on survival. RESULTS: Kaplan-Meier curve analysis showed that Patients with RDW-SD > 40.2 were significantly associated with better OS (P = 0.004, median OS: 68.0 months versus 17.0 months). Patients with RDW-CV > 12.6 were significantly associated with better OS (p = 0.030, median OS: not reach versus 22.0 months). Compared with a SCC = 0 or SCC = 1, SCC = 2 was significantly associated with better OS (p < 0.001, median OS: not reach versus 33.0 months versus 16, respectively). In the multivariate analysis, RDW-SD > 40.2 fl (HR = 0.446, 95% CI: 0.262-0.760, p = 0.003), RDW-CV > 12.6% (HR = 0.425, 95%CI: 0.230-0.783, p = 0.006), SCC = 2 (HR = 0.270, 95%CI: 0.133-0.549, p < 0.001) were associated with favorable OS. The multivariate analysis showed RDW-SD, RDW-CV and SCC level were not independent prognostic factors for DFS. CONCLUSIONS: Preoperative low levels of RDW are associated with poor survival in ICC after curative resection. This provides a new way for predicting the prognosis of ICC patients and more targeted intervention measures.


Assuntos
Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Índices de Eritrócitos , Humanos , Prognóstico , Análise de Sobrevida
15.
Talanta ; 277: 126409, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38897014

RESUMO

Atrazine (ATZ) is a widely used herbicide that can cause serious harm to organisms and ecosystems. An immobilization-free photoelectrochemical (PEC) aptasensor has been herein developed for ATZ based on aptamer molecular gate functionalized mesoporous SiO2@MB controlled release system. Compared with traditional immobilization-based sensors, immobilization-free sensors (IFSs) avoid the modification of the recognition element on the electrode surface. Mesoporous SiO2 with large surface area and good biocompatibility can be used as nanocontainers to stably encapsulate the signal shuttle molecule methylene blue (MB). The bifunctional aptamer (APT) is used not only as the recognition element for ATZ but also as the signal switch to block or release MB. In the presence of ATZ, the specific recognition between ATZ and APT will cause the detachment of APT from the surface of SiO2, thus the molecular gate will open and release MB. Due to pH modulation, the positively charged MB can reach the surface of the negatively charged Ti(III) self-doped TiO2 NTs (Ti(III)-TiO2 NTs) electrode to act as an electron donor, which increases the photocurrent. The immobilization-free aptasensor has shown ultrasensitive detection of ATZ with a wide linear range from 1.0 pM to 100.0 nM and a low detection limit of 0.1 pM. In addition, the sensor has excellent selectivity, stability and anti-interference ability, and has been used in real water sample analysis successfully. This strategy has provided a new idea for the design of advanced immobilization-free PEC sensors for environmental pollutant detection.

16.
ACS Appl Mater Interfaces ; 16(13): 16820-16829, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38527957

RESUMO

Silicon is expected to be used as a high theoretical capacity anode material in lithium-ion batteries with high energy densities. However, the huge volume change incurred when silicon de-embeds lithium ions, leading to destruction of the electrode structure and a rapid reduction in battery capacity. Although binders play a key role in maintaining the stability of the electrode structure, commonly used binders cannot withstand the large volume expansion of the silicon. To alleviate this problem, we propose a PGC cross-linking reconfiguration binder based on poly(acrylic acid) (PAA), gelatin (GN), and ß-cyclodextrin (ß-CD). Within PGC, PAA supports the main chain and provides a large number of carboxyl groups (-COOH), GN provides rich carboxyl and amide groups that can form a cross-linking network with PAA, and ß-CD offers rich hydroxyl groups and a cone-shaped hollow ring structure that can alleviate stress accumulation in the polymer chain by forming a new dynamic cross-linking coordination conformation during stretching. In the half cell, the silicon negative prepared by the PGC binder exhibited a high specific capacity and capacity maintenance ratio, and the specific capacity of the silicon negative electrode prepared by the PGC binder is still 1809 mAh g-1 and the capacity maintenance ratio is 73.76% following 200 cycles at 2 A g-1 current density, indicating that PGC sufficiently maintains the silicon negative structure during the battery cycle. The PGC binder has a simple preparation method and good capacity retention ability, making it a potential reference for the further development of silicon negative electrodes.

17.
J Endocr Soc ; 8(2): bvad168, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38205165

RESUMO

Objective: G1 and G2 colorectal neuroendocrine neoplasms (NENs) are a group of rare and indolent diseases. We aimed to delineate their genetic characteristics and explore their metastatic mechanisms. Methods: We used next-generation sequencing technology for targeted sequencing for 54 patients with G1 and G2 colorectal NENs. We delineated their genetic features and compared the genetic characteristics between metastatic NENs and nonmetastatic NENs. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was utilized to explore their abnormal pathways and study their potential metastatic mechanisms. Results: We collected 23 metastatic NENs and 31 nonmetastatic NENs. In the whole cohort, the common mutated genes were NCOR2, BRD4, MDC1, ARID1A, AXIN2, etc. The common copy number variations (CNVs) included amplification of HIST1H3D, amplification of HIST1H3E, and loss of PTEN. The KEGG enrichment analysis revealed that PI3K-Akt, MAPK, and Rap1 were the major abnormal pathways. There were significantly different genetic features between metastatic NENs and nonmetastatic NENs. The metastatic NENs shared only 47 (22.5%) mutated genes and 6 (13.3%) CNVs with nonmetastatic NENs. NCOR2, BRD4, CDKN1B, CYP3A5, and EIF1AX were the commonly mutated genes in metastatic NENs, while NCOR2, MDC1, AXIN2, PIK3C2G, and PTPRT were the commonly mutated genes in nonmetastatic NENs. Metastatic NENs presented a significantly higher proportion of abnormal pathways of cell senescence (56.5% vs 25.8%, P = .022) and lysine degradation (43.5% vs 16.1%, P = .027) than nonmetastatic NENs. Conclusion: G1 and G2 colorectal NENs are a group of heterogeneous diseases that might obtain an increased invasive ability through aberrant cell senescence and lysine degradation pathways.

18.
Cancer Lett ; 593: 216967, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38768679

RESUMO

BACKGROUND: To predict clinical important outcomes for colorectal liver metastases (CRLM) patients receiving colorectal resection with simultaneous liver resection by integrating demographic, clinical, laboratory, and genetic data. METHODS: Random forest (RF) models were developed to predict postoperative complications and major complications (binary outcomes), as well as progression-free survival (PFS) and overall survival (OS) (time-to-event outcomes) of the CRLM patients based on data from two hospitals. The models were validated on an external dataset from an independent hospital. The clinical utility of the models was assessed via decision curve analyses (DCA). RESULTS: There were 1067 patients included in survival prediction analyses and 1070 patients included in postoperative complication prediction analyses. The RF models provided an assessment of the model contributions of features for outcomes and suggested KRAS, BRAF, and MMR status were salient for the PFS or OS predictions. RF model of PFS showed that the Brier scores at 1-, 3-, and 5-year PFS were 0.213, 0.202 and 0.188; and the AUCs of 1-, 3- and 5-year PFS were 0.702, 0.720 and 0.743. RF model of OS revealed that Brier scores of 1-,3-, and 5-year OS were 0.040, 0.183 and 0.211; and the AUCs of 1-, 3- and 5-year OS were 0.737, 0.706 and 0.719. RF model for postoperative complication resulted in an AUC of 0.716 and a Brier score of 0.196. DCA curves clearly demonstrated that the RF models for these outcomes exhibited a superior net benefit across a wide range of threshold probabilities, signifying their favorable clinical utility. The RF models consistently exhibited robust performance in both internal cross-validation and external validation. The individualized risk profile predicted by the models closely aligned with the actual survival outcomes observed for the patients. A web-based tool (https://kanli.shinyapps.io/CRLMRF/) was provided to demonstrate the practical use of the prediction models for new patients in the clinical setting. CONCLUSION: The predictive models and a web-based tool for personalized prediction demonstrated a moderate predictive performance and favorable clinical utilities on several key clinical outcomes of CRLM patients receiving simultaneous resection, which could facilitate the clinical decision-making and inform future interventions for CRLM patients.


Assuntos
Neoplasias Colorretais , Hepatectomia , Neoplasias Hepáticas , Aprendizado de Máquina , Complicações Pós-Operatórias , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Masculino , Feminino , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/genética , Pessoa de Meia-Idade , Hepatectomia/métodos , Idoso , Medicina de Precisão , Intervalo Livre de Progressão , Adulto
19.
Cancer Lett ; 588: 216778, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38458593

RESUMO

This study aims to investigate applicable robust biomarkers that can improve prognostic predictions for colorectal liver metastasis (CRLM) patients receiving simultaneous resection. A total of 1323 CRLM patients from multiple centres were included. The preoperative aspartate aminotransferase to platelet ratio index (APRI) level from blood of patients were obtained. Patients were stratified into a high APRI group and a low APRI group, and comparisons were conducted by analyzing progression-free survival (PFS), overall survival (OS) and postoperative early recurrence. Tumour samples of CRLM were collected to perform single-cell RNA sequencing and multiplex immunohistochemistry/immunofluorescence (mIHC/IF) to investigate the association of APRI levels and the tumour microenvironment of CRLM. Compared with APRI <0.33, PFS disadvantage (IPTW-adjusted HR = 1.240, P = 0.015) and OS disadvantage (IPTW- adjusted HR = 1.507, P = 0.002) of APRI ≥0.33 were preserved in the IPTW-adjusted Cox hazards regression analyses. An APRI ≥0.25 was associated with a significantly increased risk of postoperative early recurrence after adjustment (IPTW-adjusted OR = 1.486, P = 0.001). The external validation showed consistent results with the training cohort. In the high APRI group, the single-cell RNA sequencing results revealed a heightened malignancy of epithelial cells, the enrichment of inflammatory-like cancer-associated fibroblasts and SPP1+ macrophages associated with activation of malignant cells and fibrotic microenvironment, and a more suppressed-function T cells; mIHC/IF showed that PD1+ CD4+ T cells, FOXP3+ CD4+ T cells, PD1+ CD8+ T cells, FOXP3+ CD8+ T cells, SPP1+ macrophages and iCAFs were significantly increased in the intratumoral region and peritumoral region. This study contributed valuable evidence regarding preoperative APRI for predicting prognoses among CRLM patients receiving simultaneous resection and provided underlying clues supporting the association between APRI and clinical outcomes by single-cell sequencing bioinformatics analysis and mIHC/IF.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Linfócitos T CD8-Positivos/patologia , Microambiente Tumoral , Hepatectomia/efeitos adversos , Contagem de Plaquetas , Neoplasias Hepáticas/patologia , Prognóstico , Neoplasias Colorretais/patologia , Aspartato Aminotransferases , Fatores de Transcrição Forkhead , Estudos Retrospectivos
20.
J Gastrointest Oncol ; 14(3): 1279-1292, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37435225

RESUMO

Background: Simultaneous resections have been increasingly performed for colorectal liver metastasis patients. However, studies explored risk stratification for these patients are scarce. Among which, a clear definition of early recurrence remains controversial and models for predicting early recurrence in these patients are lacking. Methods: Colorectal liver metastasis patients who developed recurrence followed by simultaneous resection were enrolled. Early recurrence was determined by the minimum P value method, and patients were divided into an early recurrence group and late recurrence group. Standard clinical data were collected from each patient including demographics features, preoperative laboratory tests and postoperative regular follow-up results. All the data were accessed by clinicians and recorded accordingly. The nomogram for early recurrence was constructed in the training cohort and validated externally in the test cohort. Results: The optimal value of early recurrence by the minimum P value method was 13 months. A total of 323 patients were included in the training cohort, of which 241 (74.6%) experienced early recurrence. Seventy-one patients were included in the test cohort, of which 49 (69.0%) experienced early recurrence. Significantly worse post-recurrence survival (median 27.0 vs. 52.8 months, P=0.00083) and overall survival (median 33.8 vs. 70.9 months, P<0.0001) were observed in patients with early recurrence in the training cohort. Positive lymph node metastases (P=0.003), tumour burden scores ≥4.09 (P=0.001), preoperative neutrophil-to-lymphocyte ratios ≥1.44 (P=0.006), preoperative blood urea nitrogen levels ≥3.55 µmol/L (P=0.017) and postoperative complications (P=0.042) were independently associated with early recurrence, and all these predictors were included in the nomogram. The nomogram for predicting early recurrence had a receiver operating characteristic curve of 0.720 in the training cohort and a receiver operating characteristic curve of 0.740 in the test cohort. The Hosmer-Lemeshow test and calibration curves showed acceptable model calibration in the training set (P=0.7612) and in the test set (P=0.8671). The decision curve analysis results for the training cohort and test cohort also indicated that the nomogram showed good clinical applicability. Conclusions: Our findings provide clinicians with new insights into accurate risk stratification for colorectal liver metastasis patients receiving simultaneous resection and contributing to the management of patients.

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