Chemoradiotherapy combined with surgical resection is the standard treatment for locally advanced rectal cancer, but not all the patients respond to neoadjuvant treatment. Transforming acidic ...coiled-coil protein-3 (TACC3) is frequently aberrantly expressed in rectal cancer tissue. In this study, we investigated whether TACC3 could serve as a biomarker predictive of the efficacy of chemoradiotherapy. In all, 152 rectal cancer patients with tumor tissue collected at biopsy and set aside before treatment were enrolled in this study. All patients received chemoradiotherapy and surgical resection. Immunohistochemically detected tumoral TACC3 expression significantly decreased sensitivity to chemoradiotherapy risk ratio (RR) = 2.236, 95% confidence interval (CI): 1.447-3.456;
0.001 and thus the pathological complete response rate (
0.001). TACC3 knockdown using specific siRNA enhanced radiotherapy-induced decreases in proliferation and colony formation by HCT116 and SW480 cells and increased the incidence of radiotherapy-induced apoptosis. Cox multivariate analysis showed that TACC3 was a significant prognostic factor for overall survival (
0.017) and disease-free survival (
0.020). These findings suggest TACC3 expression may be predictive of chemoradiotherapy sensitivity and prognosis in locally advanced rectal cancer.
Adjuvant chemotherapy (ACT) is usually used to reduce the risk of disease relapse and improve survival for stage II/III colorectal cancer (CRC). However, only a subset of patients could benefit from ...ACT. Thus, there is an urgent need to identify improved biomarkers to predict survival and stratify patients to refine the selection of ACT. We used high-throughput proteomics to analyze tumor and adjacent normal tissues of stage II/III CRC patients with /without relapse to identify potential markers for predicting prognosis and benefit from ACT. The machine learning approach was applied to identify relapse-specific markers. Then the artificial intelligence (AI)-assisted multiplex IHC was performed to validate the prognostic value of the relapse-specific markers and construct a proteomic-derived classifier for stage II/III CRC using 3 markers, including FHL3, GGA1, TGFBI. The proteomics profiling-derived signature for stage II/III CRC (PS) not only shows good accuracy to classify patients into high and low risk of relapse and mortality in all three cohorts, but also works independently of clinicopathologic features. ACT was associated with improved disease-free survival (DFS) and overall survival (OS) in stage II (pN0) patients with high PS and pN2 patients with high PS. This study demonstrated the clinical significance of proteomic features, which serve as a valuable source for potential biomarkers. The PS classifier provides prognostic value for identifying patients at high risk of relapse and mortality and optimizes individualized treatment strategy by detecting patients who may benefit from ACT for survival.
Nearly 20% patients with stage II A colon cancer will develop recurrent disease post-operatively. The present study aims to develop a scoring system based on Artificial Neural Network (ANN) model for ...predicting 10-year survival outcome. The clinical and molecular data of 117 stage II A colon cancer patients from Sun Yat-sen University Cancer Center were used for training set and test set; poor pathological grading (score 49), reduced expression of TGFBR2 (score 33), over-expression of TGF-β (score 45), MAPK (score 32), pin1 (score 100), β-catenin in tumor tissue (score 50) and reduced expression of TGF-β in normal mucosa (score 22) were selected as the prognostic risk predictors. According to the developed scoring system, the patients were divided into 3 subgroups, which were supposed with higher, moderate and lower risk levels. As a result, for the 3 subgroups, the 10-year overall survival (OS) rates were 16.7%, 62.9% and 100% (P < 0.001); and the 10-year disease free survival (DFS) rates were 16.7%, 61.8% and 98.8% (P < 0.001) respectively. It showed that this scoring system for stage II A colon cancer could help to predict long-term survival and screen out high-risk individuals for more vigorous treatment.
Research indicates that cancer-triggered inflammation plays a pivotal role in carcinogenesis. Here, we aimed to evaluate the correlation of lymphocyte-to-monocyte ratio (LMR) before neoadjuvant ...chemoradiotherapy (CRT) with clinical outcomes in patients with locally advanced rectal cancer (LARC). We retrospectively enrolled 317 consecutive patients with LARC between 2004 and 2013. The optimal cutoff values of LMR were determined using receiver operating curve analysis. Overall survival (OS) and disease-free survival related to the LMR were analyzed using the log-rank test and multivariate Cox regression methods. We found that a low LMR (≤4.91) was prominently correlated with worse prognostic features and a shorter 3-year survival rate of LARC. Moreover, multivariate Cox analysis revealed that elevated LMR was an independent factor for better OS (hazard ratio 0.538, 95% confidence interval 0.292-0.991,
=0.047). In addition, univariate logistic regression analysis showed that the LMR was not associated with tumor pathologic regression. In conclusion, LMR is identified as a valuable prognostic marker for predicting the OS of LARC patients receiving CRT.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Neoadjuvant chemoradiotherapy (neoCRT) is a standard treatment for locally advanced rectal cancer (LARC); however, resistance to chemoradiotherapy is one of the main obstacles to improving treatment ...outcomes. The goal of this study was to identify factors involved in the radioresistance of colorectal cancer and to clarify the underlying mechanisms.
A genome-wide RNAi screen was used to search for candidate radioresistance genes. After
knockdown or overexpression, colorectal cancer cells exposed to X-rays both
and in a mouse model were assayed for DNA damage, cytotoxicity, and apoptosis. Moreover, the regulatory effects and mechanisms of RFC4 in DNA repair were investigated
. Finally, the relationships between
expression and clinical parameters and outcomes were investigated in 145 patients with LARC receiving neoCRT.
,
,
,
,
, and
were identified as potential candidate radioresistance genes. RFC4 protected colorectal cancer cells from X-ray-induced DNA damage and apoptosis
and
. Mechanistically, RFC4 promoted nonhomologous end joining (NHEJ)-mediated DNA repair by interacting with Ku70/Ku80 but did not affect homologous recombination-mediated repair. Higher
expression in cancer tissue was associated with weaker tumor regression and poorer prognosis in patients with LARC treated with neoCRT, which likely resulted from the effect of RFC4 on radioresistance, not chemoresistance.
RFC4 was identified as a radioresistance factor that promotes NHEJ-mediated DNA repair in colorectal cancer cells. In addition, the expression level of
predicted radiotherapy responsiveness and the outcome of neoadjuvant radiotherapy in patients with LARC.
The strong corrosion behavior at the Al current collector restricts the application range of LiTFSI, despite its high stability against water and thermal. The adding LiODFB into LiTFSI-based ...electrolytes as a co-salt can successfully suppress the Al corrosion. However, the mechanism of the synergistic effect and electrochemical performance at high temperatures remains unclear. In this work, electrochemical tests and physical characterization of mixed lithium salts in different proportions were carried out at a high temperature of 45 °C, and it was concluded that LiODFB0.2-LiTFSI0.8-based electrolyte had the best electrochemical performance at 45 °C. The capacity retention rate of the battery after 200 cycles is 95%, that's due to the good film-forming property of LiODFB and the high thermal stability of LiTFSI. This work provides a universal electrolyte design strategy for designing stable and safe high-temperature electrolytes for the LiCoO2 cathode.
•A dual-salts of LiTFSI and LiODFB has been used in LiCoO2-based batteries at high-temperature.•LiTFSI-LiODFB-based electrolyte shows good anti-corrosion performance to Al foil.•LiCoO2|Li cells using LiTFSIeLiODFB-based electrolyte show good cycling stability and rate performance at high-temperature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
The positive predictive value (PPV) of high risk factor questionnaire (HRFQ) plus fecal immunochemical test (FIT) as preliminary screening strategy for colorectal-related neoplasia is ...relatively low. We aim to explore independent factors associated with PPVs of HRFQ combined FIT for selecting high risk individuals for colonoscopy.
Methods
A total of 6971 residents were enrolled in a community-based screening program. Participants who had positive results of HRFQ and/or FIT and subsequently received colonoscopy were involved. The associations of socio-demographic factors, lifestyle behaviors, and high risk factors of colorectal cancer with PPVs of HRFQ, FIT, and their combination were evaluated by multivariable logistic regression models.
Results
Among 572 involved cases, 249 (43.5%) colorectal neoplasms were detected by colonoscopy, including 71 advanced adenoma (12.4%) and 9 colorectal cancer (CRC) (1.6%). The PPVs of preliminary screening were 43.5% for total colorectal neoplasms, 14.0% for advanced neoplasm, and 1.6% for CRC. Adding positive HRFQ to FIT could improve the PPV from 3.5 to 8.0% for detecting CRC. Preliminarily screened positive individuals who were males adjusted odds ratio (AOR): 1.95, 95% CI 1.31, 2.90;
p
< 0.001, elders (> 60 years) (AOR: 1.70, 95% CI 1.17, 2.46;
p
= 0.005), or ex-/current smokers (AOR: 3.04, 95% CI 1.31, 7.09;
p
= 0.10) had higher odds of PPVs of detecting colorectal neoplasms.
Conclusions
Combining HRFQ and FIT could largely improve PPVs for screening advanced neoplasm and CRC. Gender and age-specific FIT cut-off values as well as initiating ages for CRC screening might be recommended to improve the accuracy and effectiveness of current screening algorithm.
Rheumatoid Arthritis (RA) is a systemic autoimmune disease leading to joint destruction. The prevention of bone and cartilage destruction has received increased attention in recent years.
To evaluate ...the current evidences regarding the bone-protecting efficacy of Chinese medicine or the combination of Chinese medicine and Western medicine for RA.
We comprehensively searched PubMed, Embase, the Cochrane Library (www.thecochranelibrary.com), the China National Knowledge Infrastructure (CNKI), the Database for Chinese Technical Periodicals (VIP), and SinoMed. We then performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) assessing the two therapy methods.
Sixteen studies including 1,171 patients were included in the final analysis. The results showed that Chinese medicine could significantly improve the bone mineral density (BMD) (mean difference MD = 0.05 /g·cm
, 95% CI 0.03, 0.08,
< 0.00001), and decrease the serum matrix metalloproteinase 3 (MMP-3) (SMD = -2.84, 95% CI -4.22, -1.47,
< 0.0001).
Chinese medicine may provide an efficiently alternative choice for the treatment of RA in terms of the bone-protecting efficiency. Given the inherent limitations of the included studies, future well-designed RCTs are required to confirm and update the findings of this analysis.
•The soluble product of LiDFOB hinder salt decomposition.•EQCM and in situ EIS analysis revealed three stages of diffusion of soluble products.•The standing process improved the quality of the SEI ...membrane significantly.
The challenge of improving low-temperature performance in lithium-ion batteries (LIBs) is attributed to the formation of an unstable solid electrolyte interphase (SEI) film. Lithium difluoro(oxalate)borate (LiODFB) has demonstrated potential in enhancing capacity retention and reducing impedance at low temperatures by establishing a high ion conductivity and stable SEI layer. Previous research indicates that the BOF2− anion, a soluble product of film formation additive of LiODFB hinder salt decomposition by aggregating on the electrode surface. This study presents a strategy to intensify the film formation process of LiODFB additives by introducing an optimal standing time during intermittent discharge processes. Three specific stages of soluble product diffusion are discussed. Diffusion starts from the outer layer of adsorption composed of soluble substances, gradually extends to the inner layer of adsorption, and finally establishes a new connection with the electrode. A brief standing time proves insufficient for inner adsorption layer diffusion, while excessively extended standing time fails to accelerate LiODFB decomposition. A standing time of 2300 s is selected to promote a stable SEI layer. This strategy elevates the capacity retention rate of cells at –20 °C from 66.59 % to 84.44 %. The study offers a method to address battery performance degradation in low-temperature conditions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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