PDPN/CCL2/STAT3 feedback loop alter CAF heterogeneity to promote angiogenesis in colorectal cancer.

Colorectal cancer (CRC) is one of the common clinical malignancies and the fourth leading cause of cancer-related death in the world. The tumor microenvironment (TME) plays a crucial role in promoting tumor angiogenesis, and cancer-associated fibroblasts (CAFs) are one of the key components of the tumor microenvironment. However, due to the high heterogeneity of CAFs, elucidating the molecular mechanism of CAF-mediated tumor angiogenesis remained elusive. In our study, we found that there is pro-angiogenic functional heterogeneity of CAFs in colorectal cancer and we clarified that Podoplanin (PDPN) can specifically label CAF subpopulations with pro-angiogenic functions. We also revealed that PDPN + CAF could maintain CAF heterogeneity by forming a PDPN/CCL2/STAT3 feedback loop through autocrine CCL2, while activate STAT3 signaling pathway in endothelial cells to promote angiogenesis through paracrine CCL2. We demonstrated WP1066 could inhibit colorectal cancer angiogenesis by blocking both the PDPN/CCL2/STAT3 feedback loop in CAFs and the STAT3 signaling pathway in endothelial cells. Altogether, our study suggests that STAT3 could be a potential therapeutic target for blocking angiogenesis in colorectal cancer. We provide theoretical basis and new therapeutic strategies for the clinical treatment of colorectal cancer.

Risk factor analysis and risk prediction study of obesity in steelworkers: model development based on an occupational health examination cohort dataset.

BACKGROUND: Obesity is increasingly recognized as a grave public health concern globally. It is associated with prevalent diseases including coronary heart disease, fatty liver, type 2 diabetes, and dyslipidemia. Prior research has identified demographic, socioeconomic, lifestyle, and genetic factors as contributors to obesity. Nevertheless, the influence of occupational risk factors on obesity among workers remains under-explored. Investigating risk factors specific to steelworkers is crucial for early detection, prediction, and effective intervention, thereby safeguarding their health. METHODS: This research utilized a cohort study examining health impacts on workers in an iron and steel company in Hebei Province, China. The study involved 5469 participants. By univariate analysis, multifactor analysis, and review of relevant literature, predictor variables were found. Three predictive models-XG Boost, Support Vector Machine (SVM), and Random Forest (RF)-were employed. RESULTS: Univariate analysis and cox proportional hazard regression modeling identified age, gender, smoking and drinking habits, dietary score, physical activity, shift work, exposure to high temperatures, occupational stress, and carbon monoxide exposure as key factors in the development of obesity in steelworkers. Test results indicated accuracies of 0.819, 0.868, and 0.872 for XG Boost, SVM, and RF respectively. Precision rates were 0.571, 0.696, and 0.765, while recall rates were 0.333, 0.592, and 0.481. The models achieved AUCs of 0.849, 0.908, and 0.912, with Brier scores of 0.128, 0.105, and 0.104, log losses of 0.409, 0.349, and 0.345, and calibration-in-the-large of 0.058, 0.054, and 0.051, respectively. Among these, the Random Forest model demonstrated superior performance. CONCLUSIONS: The research indicates that obesity in steelworkers results from a combination of occupational and lifestyle factors. Of the models tested, the Random Forest model exhibited superior predictive ability, highlighting its significant practical application.

Phase estimation of a Mach-Zehnder interferometer via the Laguerre excitation squeezed state.

Quantum metrology has an important role in the fields of quantum optics and quantum information processing. Here we introduce a kind of non-Gaussian state, Laguerre excitation squeezed state as inputs of traditional Mach-Zehnder interferometer to examine phase estimation in realistic case. We consider the effects of both internal and external losses on phase estimation by using quantum Fisher information and parity detection. It is shown that the external loss presents a bigger effect than the internal one. The phase sensitivity and the quantum Fisher information can be improved by increasing the photon number and even surpass the ideal phase sensitivity by two-mode squeezed vacuum in a certain region of phase shift for realistic case. Our results can find significant practical applications in quantum metrology.

Analysis of factors affecting nonalcoholic fatty liver disease in Chinese steel workers and risk assessment studies.

BACKGROUND: The global incidence of nonalcoholic fatty liver disease (NAFLD) is rapidly escalating, positioning it as a principal public health challenge with significant implications for population well-being. Given its status as a cornerstone of China's economic structure, the steel industry employs a substantial workforce, consequently bringing associated health issues under increasing scrutiny. Establishing a risk assessment model for NAFLD within steelworkers aids in disease risk stratification among this demographic, thereby facilitating early intervention measures to protect the health of this significant populace. METHODS: Use of cross-sectional studies. A total of 3328 steelworkers who underwent occupational health evaluations between January and September 2017 were included in this study. Hepatic steatosis was uniformly diagnosed via abdominal ultrasound. Influential factors were pinpointed using chi-square (χ2) tests and unconditional logistic regression analysis, with model inclusion variables identified by pertinent literature. Assessment models encompassing logistic regression, random forest, and XGBoost were constructed, and their effectiveness was juxtaposed in terms of accuracy, area under the curve (AUC), and F1 score. Subsequently, a scoring system for NAFLD risk was established, premised on the optimal model. RESULTS: The findings indicated that sex, overweight, obesity, hyperuricemia, dyslipidemia, occupational dust exposure, and ALT serve as risk factors for NAFLD in steelworkers, with corresponding odds ratios (OR, 95% confidence interval (CI)) of 0.672 (0.487-0.928), 4.971 (3.981-6.207), 16.887 (12.99-21.953), 2.124 (1.77-2.548), 2.315 (1.63-3.288), 1.254 (1.014-1.551), and 3.629 (2.705-4.869), respectively. The sensitivity of the three models was reported as 0.607, 0.680 and 0.564, respectively, while the precision was 0.708, 0.643, and 0.701, respectively. The AUC measurements were 0.839, 0.839, and 0.832, and the Brier scores were 0.150, 0.153, and 0.155, respectively. The F1 score results were 0.654, 0.661, and 0.625, with log loss measures at 0.460, 0.661, and 0.564, respectively. R2 values were reported as 0.789, 0.771, and 0.778, respectively. Performance was comparable across all three models, with no significant differences observed. The NAFLD risk score system exhibited exceptional risk detection capabilities with an established cutoff value of 86. CONCLUSIONS: The study identified sex, BMI, dyslipidemia, hyperuricemia, occupational dust exposure, and ALT as significant risk factors for NAFLD among steelworkers. The traditional logistic regression model proved equally effective as the random forest and XGBoost models in assessing NAFLD risk. The optimal cutoff value for risk assessment was determined to be 86. This study provides clinicians with a visually accessible risk stratification approach to gauge the propensity for NAFLD in steelworkers, thereby aiding early identification and intervention among those at risk.

A nested case-control study of the effects of dust exposure, smoking on COPD in coal workers.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) represents a prevalent ailment, progressively surging within the ranks of coal mine laborers. The current study endeavors to elucidate the effects of dust exposure and smoking on COPD incidence amongst coal mine workers, while concurrently devising preventive strategies for this affliction. METHOD: A nested case-control study was conducted encompassing 1,416 participants aged ≥ 18 years, spanning the duration from (2017-2018) until 2020. A meticulous matching process yielded a cohort of 708 COPD patients, each paired with a control subject, forming a harmonious 1:1 ratio. Multiple logistic regression analysis was employed to scrutinize the associations between smoking, dust exposure with COPD among coal workers. RESULTS: The COPD prevalence within the cohort of coal workers under investigation amounted to 22.66%, with an accompanying incidence density of 0.09/person-year. Following meticulous adjustment for confounding variables, it was discerned that cumulative dust exposure within the range of 47.19 ~ (OR: 1.90, 95% CI: 1.05, 3.44), 101.27 ~ (OR: 1.99, 95% CI: 1.17, 3.39), as well as smoking indices of 72 ~ (OR: 1.85, 95% CI: 1.19, 2.88), 145 ~ (OR: 1.74, 95% CI: 1.17, 2.61), 310 ~ (OR: 1.85, 95% CI: 1.23, 2.77) engender an escalated vulnerability to COPD among coal workers. Furthermore, interaction analysis discerned an absence of both multiplicative and additive interactions between dust exposure, smoking, and COPD occurrence amidst coal workers. CONCLUSION: Dust exposure and smoking were unequivocally identified as precipitating risk factors for COPD incidence within the population of coal workers, albeit devoid of any discernible interaction between these two causal agents.

Repurposing of steel rolling sludge: Solvent-free preparation of α-Fe2O3 nanoparticles and its application for As(III/V)-containing wastewater treatment.

Steel rolling sludge (SRS) is the by-product of metallurgical industry with abundant iron content, which needs to be utilized for producing high value-added products. Herein, cost-effective and highly adsorbent α-Fe2O3 nanoparticles were prepared from SRS via a novel solvent-free method and applied to treat As(III/V)-containing wastewater. The structure of the prepared nanoparticles was observed to be spherical with a small crystal size (12.58 nm) and high specific surface area (145.03 m2/g). The nucleation mechanism of α-Fe2O3 nanoparticles and the effect of crystal water were investigated. More importantly, compared with the traditional methods of preparation cost and yield, this study was found to have excellent economic benefits. The adsorption results indicated that the adsorbent could effectively remove arsenic over a wide pH range, and the optimal performance of nano adsorbent for As(III) and As(V) removal was observed at pH 4.0-9.0 and 2.0-4.0, respectively. The adsorption process was consistent with pseudo-second-order kinetic and Langmuir isothermal model. The maximum adsorption capacity (qm) of adsorbent for As(III) and As(V) was 75.67 mg/g and 56.07 mg/g, respectively. Furthermore, α-Fe2O3 nanoparticles exhibited great stability, and qm remained at 64.43 mg/g and 42.39 mg/g after five cycles. Particularly, the As(III) was removed by forming inner-sphere complexes with the adsorbent, and it partially oxidized to As(V) during this process. In contrast, the As(V) was removed by electrostatic adsorption and reaction with -OH on the adsorbent surface. Overall, resource utilization of SRS and the treatment of As(III)/(V)-containing wastewater in this study are in line with the current developments in the environmental and waste-to-value research.

Co-utilization of iron ore tailings and coal fly ash for porous ceramsite preparation: Optimization, mechanism, and assessment.

Maximizing the utilization of industrial by-products, such as iron ore tailings (IOTs) and coal fly ash (CFA), is crucial toward sustainable development. This study provides a meticulous insight into the optimization, mechanism, and assessment of the co-utilization of IOTs and CFA for the preparation of porous ceramsite. Micro-CT results revealed that the prepared ceramsite exhibited an exceptional porosity, peaking at 56.98%, with a wide range of pore diameters (3.55-959.10 µm) under optimal conditions (IOTs content at 76%, preheating at 550 °C for 15 min, and sintering at 1177 °C for 14 min), while maintaining good mechanical properties (water adsorption of 1.28%, comprehensive strength of 8.75 MPa, apparent density of 1.37 g/cm3, and bulk density of 0.62 g/cm3). The primary parameters affecting the porosity were identified and ranked as follows: sintering temperature > IOTs content > sintering time. The formation and growth of pores could be attributed to the equilibrium relationship between the liquid-phase surface tension and the gas expansion force, accompanied by pore wall thinning and pore merging. Notably, the prepared ceramsite is both ecologically feasible and economically rewarding, boasting a profit margin of 9.47 $/ton. The comprehensive life cycle assessment (LCA) conducted further highlights the potential of its large-scale implementation for promoting sustainable development. This study provides an innovative strategy for the co-utilization of IOTs and CFA, with advantages such as cost-effectiveness, ecological feasibility and scalability of production.

Wnt/ß-Catenin signaling pathway in hepatocellular carcinoma: pathogenic role and therapeutic target.

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and one of the leading causes of cancer-related deaths worldwide. The Wnt/ß-Catenin signaling pathway is a highly conserved pathway involved in several biological processes, including the improper regulation that leads to the tumorigenesis and progression of cancer. New studies have found that abnormal activation of the Wnt/ß-Catenin signaling pathway is a major cause of HCC tumorigenesis, progression, and resistance to therapy. New perspectives and approaches to treating HCC will arise from understanding this pathway. This article offers a thorough analysis of the Wnt/ß-Catenin signaling pathway's function and its therapeutic implications in HCC.

Overexpression of LSD1 in hepatocellular carcinoma: a latent target for the diagnosis and therapy of hepatoma.

The aim of this study was to investigate the expression of LSD1 in human hepatocellular carcinoma (HCC) cell lines and HCC samples. In this study, we examined LSD1 expression in 60 paired liver cancer tissues and adjacent noncancerous tissues by Western blot. In addition, we analyzed LSD1 expression in 198 HCC samples by immunohistochemistry. The relationship between LSD1 expression and clinicopathological features was investigated. The HCC cell line SMMC-7721 was transfected with LSD1 siRNA expressing plasmids. We subsequently examined in vitro cell growth using the MTT assay and anchorage-independent growth through a soft-agar colony-formation assay. In addition, the expression levels of Bcl-2 and c-Myc were also examined. Immunohistochemistry and Western blotting consistently confirmed LSD1 overexpression in HCC tissues compared with adjacent non-neoplastic tissues (P < 0.01). Additionally, immunostaining showed more LSD1-positive cells in the higher tumor stage (T3-4) and tumor grade (G3) than in the lower tumor stage (T1-2, P < 0.001) and tumor grade (G1-2, P < 0.001). Knockdown of LSD1 expression in HCC cells led to decreased cell proliferation. The expression of Bcl-2 and c-Myc were down-regulated after transfection of LSD1 siRNA into HCC cell line SMMC-7721. In conclusion, because LSD1 was overexpressed in HCC and has an important role in the development of HCC, LSD1 could be a latent target in the diagnosis and therapy of HCC.

Expression of UbcH10 in pancreatic ductal adenocarcinoma and its correlation with prognosis.

The aim of this current study was to investigate the clinicopathologic features and prognostic significance of UbcH10 in pancreatic ductal adenocarcinoma (PDA). Real-time quantitative RT-PCR was employed to examine UbcH10 expression in 20 pairs of PDA and adjacent non-cancerous tissues. In addition, UbcH10 expression was analyzed by immunohistochemistry in 94 clinicopathologically characterized PDA cases. The correlation of UbcH10 expression with patients' survival rate was assessed by Kaplan-Meier and Cox regression. Our results showed that the expression levels of UbcH10 mRNA and protein in PDA tissues were both significantly higher than those in non-cancerous tissues. Simultaneously, high expression of UbcH10 was significantly correlated with the clinical stage (p<0.001), degree of histological differentiation (p<0.001), and lymph node metastasis (p=0.001). Moreover, high expression of UbcH10 was significantly associated with poor overall survival in PDA patients. In conclusion, UbcH10 might play a positive role in tumor development and could serve as an independent predictor of poor prognosis for PDA.

Association of Chinese Visceral Adiposity Index and Carotid Atherosclerosis in Steelworkers: A Cross-Sectional Study.

The Chinese Visceral Adiposity Index (CVAI) is an indicator of visceral adiposity dysfunction used to evaluate the metabolic health of the Chinese population. Steelworkers are more likely to be obese due to their exposure to special occupational factors, and have a higher prevalence of carotid atherosclerosis (CAS). This study aimed to analyze the special relationship between CVAI and CAS among steelworkers. A total of 4075 subjects from a northern steel company were involved in the cross-sectional study. Four logistic regression models were developed to analyze the correlation between CVAI and CAS. In addition, the restricted cubic spline was applied to fit the dose-response association between CVAI and CAS risk. In the study, the prevalence of CAS was approximately 25.94%. After adjustment for potential confounders, we observed a positive correlation between CVAI and CAS risk. Compared to the first CVAI quartile, the effect value odds ratio (OR) and 95% CI in the second, third, and fourth CVAI quartile were 1.523 (1.159-2.000), 2.708 (2.076-3.533), and 4.101 (3.131-5.372), respectively. Additionally, this positive correlation was stable in all subgroups except for female. Furthermore, we also found a non-linear relationship between CVAI and CAS risk (p nonlinear < 0.05). Notably, CVAI could increase the risk of CAS when higher than 106. In conclusion, our study showed that CVAI might be a reliable indicator to identify high-risk populations of CAS among steelworkers.

Risk Prediction for the Development of Hyperuricemia: Model Development Using an Occupational Health Examination Dataset.

OBJECTIVE: Hyperuricemia has become the second most common metabolic disease in China after diabetes, and the disease burden is not optimistic. METHODS: We used the method of retrospective cohort studies, a baseline survey completed from January to September 2017, and a follow-up survey completed from March to September 2019. A group of 2992 steelworkers was used as the study population. Three models of Logistic regression, CNN, and XG Boost were established to predict HUA incidence in steelworkers, respectively. The predictive effects of the three models were evaluated in terms of discrimination, calibration, and clinical applicability. RESULTS: The training set results show that the accuracy of the Logistic regression, CNN, and XG Boost models was 84.4, 86.8, and 86.6, sensitivity was 68.4, 72.3, and 81.5, specificity was 82.0, 85.7, and 86.8, the area under the ROC curve was 0.734, 0.724, and 0.806, and Brier score was 0.121, 0.194, and 0.095, respectively. The XG Boost model effect evaluation index was better than the other two models, and similar results were obtained in the validation set. In terms of clinical applicability, the XG Boost model had higher clinical applicability than the Logistic regression and CNN models. CONCLUSION: The prediction effect of the XG Boost model was better than the CNN and Logistic regression models and was suitable for the prediction of HUA onset risk in steelworkers.

Development and Internal Validation of Risk Assessment Models for Chronic Obstructive Pulmonary Disease in Coal Workers.

Coal workers are more likely to develop chronic obstructive pulmonary disease due to exposure to occupational hazards such as dust. In this study, a risk scoring system is constructed according to the optimal model to provide feasible suggestions for the prevention of chronic obstructive pulmonary disease in coal workers. Using 3955 coal workers who participated in occupational health check-ups at Gequan mine and Dongpang mine of Hebei Jizhong Energy from July 2018 to August 2018 as the study subjects, random forest, logistic regression, and convolutional neural network models are established, and model performance is evaluated to select the optimal model, and finally a risk scoring system is constructed according to the optimal model to achieve model visualization. The training set results show that the logistic, random forest, and CNN models have sensitivities of 78.55%, 86.89%, and 77.18%; specificities of 85.23%, 92.32%, and 87.61%; accuracies of 81.21%, 85.40%, and 83.02%; Brier scores of 0.14, 0.10, and 0.14; and AUCs of 0.76, 0.88, and 0.78, respectively, and similar results are obtained for the test set and validation set, with the random forest model outperforming the other two models. The risk scoring system constructed according to the importance ranking of random forest predictor variables has an AUC of 0.842; the evaluation results of the risk scoring system shows that its accuracy rate is 83.7% and the AUC is 0.827, and the established risk scoring system has good discriminatory ability. The random forest model outperforms the CNN and logistic regression models. The chronic obstructive pulmonary disease risk scoring system constructed based on the random forest model has good discriminatory power.

Defunctioning stoma in low anterior resection for rectal cancer: a meta- analysis of five recent studies.

BACKGROUND/AIMS: The necessity of a defunctioning stoma in low anterior resection with total mesorectal excision for rectal cancer remains controversial. This meta-analysis evaluates the advantages of prophylactic stomas in patients undergoing low anterior resection and assesses postoperative outcomes of patients with or without a defunctioning stoma. METHODOLOGY: Studies and relevant literatures regarding the formation of defunctioning stomas after low anterior resection were searched through PubMed and Embase. The rates of anastomotic leakage and re-operation related to leakage with or without defunctioning stoma were pooled and compared using a meta-analysis. The risk ratios were calculated with 95% confidence intervals to evaluate the influence of defunctioning stomas. RESULTS: Five recent studies including 878 patients in total were included in this meta-analysis. These studies demonstrated that defunctioning stomas significantly reduced the rate of postoperative anastomotic leakage and reoperation after low anterior resection, the pooled risk ratio was 0.34 (95% CI=0.22-0.53, p<0.00001) and 0.27 (95% CI=0.16-0.48, p<0.00001), respectively. CONCLUSIONS: Defunctioning stomas can be useful to minimize the rate of anastomotic leakage and re-operation related to leakage. Furthermore, anorectal function was not affected. However, the influence of a defunctioning stoma on long-term mortality and the quality of life in patients treated for rectal cancer is inconclusive.

Investigation of scale inhibition effect and mechanism of S-HGMF in the clean recirculating cooling water system.

The formation of scales in a recirculating water system is a common problem in industrial water treatment; it seriously affects the production in various industries and pollutes the environment. Although conventional scale inhibition methods are effective, they are expensive and harm the environment. Herein, an advanced method is proposed to solve the scaling issue in recirculating cooling water systems using the superconducting high-gradient magnetic field (S-HGMF) treatment. The scale inhibition performance could be improved by changing the magnetic flux density, operation time, and flow rate. The results showed that S-HGMF could increase the number of hydrogen bonds in the recirculating cooling water, enhance molecular interaction, increase the thickness of the ion hydration shell, reduce the nucleation rate, stabilize the water quality, improve the solubility of scale-forming ions, and inhibit scale formation. The scale inhibition performance reached 8.10%. Interestingly, S-HGMF had a memory effect in that it could maintain the scale inhibition effect for some period after treatment completion. Moreover, S-HGMF changed the crystal structure of the scale and promoted the transformation of the scale to a metastable phase. Ultimately, calcite was transformed to aragonite to reduce the precipitation of hard scale (calcite), achieving the purpose of scale inhibition. As a physical method, the application of S-HGMF to inhibit scaling has great potential for industrial applications.

Chlorate induced false reduction in chemical oxygen demand (COD) based on standard dichromate method: Countermeasure and mechanism.

Deliberate addition of mildly oxidative chlorate (ClO3-), so-called "chemical oxygen demand (COD) remover", into wastewater in China or electrochemical production of ClO3- from Cl- induces the false COD reduction, which would bring about false appearance of effluents meeting the COD discharge standards. In this study, an easy sulfite-based reduction method was developed for the first time to remove ClO3- from the water samples before COD determination to eliminate this interference of ClO3-. In this reaction system, keeping the reaction temperature of sulfite reducing ClO3- at 60 °C was crucial for fast ClO3- removal rate, fixed molar [sulfite]ini/[chlorate]ini ratio value and the synchronous exhaustion of sulfite and ClO3-, which were of great significance for the real application of this improved COD determination method. The ClO3- interference on COD determination could be successfully eliminated after 20 min reduction of ClO3- by sulfite at pHini 4.0∼6.0 with the molar [sulfite]ini/[chlorate]ini ratio value in the range of 5∼6 when concentration of ClO3- was below 5 mM. Despite of the involvement of SO4·- in the sulfite reducing ClO3- system, the degradation of organic matters by SO4·- could be greatly impeded due to the lessened dissolved oxygen for SO4·- production at high reaction temperature and the scavenging of SO4·- by sulfite. In this reaction system, ClO2, ClO2- and ClO- were also generated and could be further reduced by sulfite stoichiometrically via oxygen transfer process with Cl- as the final product. In general, this study pioneered an effective, fast and convenient method for COD determination of the ClO3--laden wastewaters and evaluating the real electrochemical wastewater treatment performance in terms of COD removal.

Efficacy evaluation of nilotinib treatment in different genomic subtypes of gastrointestinal stromal tumors: A meta-analysis and systematic review.

Nilotinib has been used as a third-line drug for gastrointestinal stromal tumors (GISTs) after a failure of sunitinib. In this study, we aimed to evaluate the efficacy of nilotinib in different genomic subtypes of GISTs. We searched the English articles through EMBASE, Cochrane Library and PubMed Database regarding to the use of nilotinib on GISTs, which published up to February 15, 2019. Inclusion criteria were: GISTs patients received nilotinib in a clinical trial and had detailed genetic subtype records (such as KIT exon 9, KIT exon 11, or PDGFRA mutations, or wild-type). The clinical benefit rate was used to assess the efficacy of nilotinib. A total of 3 studies involving 218 GISTs were included in this meta-analysis. The overall OR (KIT group vs WT group) was 3.26 (95% CI: 1.14-9.28; P = 0.027, Pheterogeneity = 0.613). The overall OR in KIT exon 11 group vs WT group was 5.30 (95% CI: 1.79-15.68; P = 0.003, Pheterogeneity = 0.409). The overall OR in KIT exon 9 group vs WT group was 0.13 (95% CI: 0.02-0.86; P = 0.035, Pheterogeneity = 0.229). The overall OR in KIT exon 11 group vs exon 9 group was 9.96 (95% CI: 0.39-254.66; P < 0.0001, Pheterogeneity = 0.024). Different genotypes of GISTs showed different responses to nilotinib, and KIT exon 11-mutant GISTs mostly benefited from nilotinib, followed by KIT exon 9-mutant or WT one.

Proximal Gastrectomy versus Total Gastrectomy for Siewert Type II Adenocarcinoma of the Esophagogastric Junction: A Comprehensive Analysis of Data from the SEER Registry.

BACKGROUND: To determine the ideal surgical approach (total gastrectomy (TG) vs. proximal gastrectomy (PG)) for Siewert type II adenocarcinoma of the esophagogastric junction (AEG), we searched and analyzed the Surveillance, Epidemiology, and End Results (SEER) data. METHODS: Patients with Siewert type II AEG treated by TG or PG were identified from the 2004-2014 SEER dataset. We obtained the patients' overall survival (OS) and cancer-specific survival (CSS) and stratified the patients by surgical approach. We performed a propensity score 1 : 1 matching (PSM) analysis and a univariate and multivariate Cox proportional hazards model. RESULTS: A total of 2,217 patients with 6th AJCC stage IA-IIIB Siewert type II AEG was examined: 1,584 patients (71.4%) underwent PG, and 633 patients (28.6%) underwent TG. The follow-up time was 1-131 months. OS favored total gastrectomy before the PSM analysis (χ 2 = 3.952, p = 0.047), but after this analysis, there was no significant difference between TG and PG (χ 2 = 2.227, p = 0.136). The univariate and multivariate analyses identified age as an independent factor, and an X-tail analysis revealed 70 years as a cut-off point. The patients aged ≥ 70 years obtained a significant long-term OS benefit from PG compared to TG (χ 2 = 8.245, p = 0.004), and those aged < 70 years showed no difference between TG and PG (χ 2 = 0.167, p = 0.682). CONCLUSIONS: PG showed an equivalent survival benefit to TG in both the early and locally advanced stages of Siewert type II AEG. For elderly patients, PG is strongly recommended because of its clearer OS benefit compared to TG.

Epigenetic silencing of SALL2 confers tamoxifen resistance in breast cancer.

Resistance to tamoxifen is a clinically major challenge in breast cancer treatment. Although downregulation of estrogen receptor-alpha (ERα) is the dominant mechanism of tamoxifen resistance, the reason for ERα decrease during tamoxifen therapy remains elusive. Herein, we reported that Spalt-like transcription factor 2 (SALL2) expression was significantly reduced during tamoxifen therapy through transcription profiling analysis of 9 paired primary pre-tamoxifen-treated and relapsed tamoxifen-resistant breast cancer tissues. SALL2 transcriptionally upregulated ESR1 and PTEN through directly binding to the DNA promoters. By contrast, silencing SALL2 induced downregulation of ERα and PTEN and activated the Akt/mTOR signaling, resulting in estrogen-independent growth and tamoxifen resistance in ERα-positive breast cancer. Furthermore, hypermethylation of SALL2 promoter was found in tamoxifen-resistant breast cancer. Importantly, in vivo experiments showed that DNA methyltransferase inhibitor-mediated SALL2 restoration resensitized tamoxifen-resistant breast cancer to tamoxifen therapy. These findings shed light on the mechanism of SALL2 in regulation of ER and represent a potential clinical signature that can be used to categorize breast cancer patients who may benefit from co-therapy with tamoxifen and DNMT inhibitor.