Preservation of the left colic artery and superior rectal artery in laparoscopic surgery can reduce anastomotic leakage in sigmoid colon cancer.

BACKGROUND: The aim was to study the clinical significance in the preservation of the left colic artery (LCA) and superior rectal artery (SRA) for the laparoscopic resection of sigmoid colon cancer (SCC). PATIENTS AND METHODS: A total of 316 patients with SCC were divided into two groups. Group A received D3 resection with preservation of LCA and SRA, whereas Group B ligatured artery at the root of the inferior mesenteric artery. The operation time, number of resected lymph nodes, blood loss and anastomotic leakage rate were compared. RESULTS: In Group A, the average operation time was 283.02 ± 51.48 min, the average blood loss was 111.81 ± 77.08 ml and the average lymph node dissection was 14.8 ± 7.7. There was no statistical significance in blood loss and number of resected lymph nodes between Group A and B (P > 0.05). Longer operating time were observed in Group A as compared to Group B (P < 0.05). The anastomotic leakage rate had statistical significance between these two groups (P < 0.05). CONCLUSIONS: Preservation of LCA and SRA was safe and feasible for the laparoscopic surgery of SCC, which could reduce anastomotic leakage rate.

Hsa_circ_0026416 promotes proliferation and migration in colorectal cancer via miR-346/NFIB axis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been confirmed to be key regulators of many diseases. With many scholars devoted to studying the biological function and mechanism of circRNAs, their mysterious veil is gradually being revealed. In our research, we explored a new circRNA, hsa_circ_0026416, which was identified as upregulated in CRC with the largest fold change (logFC = 3.70) of the evaluated circRNAs via analysing expression profiling data by high throughput sequencing of members of the GEO dataset (GSE77661) to explore the molecular mechanisms of CRC. METHODS: qRT-PCR and western blot analysis were utilized to assess the expression of hsa_circ_0026416, miR-346 and Nuclear Factor I/B (NFIB). CCK-8 and transwell assays were utilized to examine cell proliferation, migration and invasion in vitro, respectively. A luciferase reporter assay was used to verify the combination of hsa_circ_0026416, miR-346 and NFIB. A nude mouse xenograft model was also utilized to determine the role of hsa_circ_0026416 in CRC cell growth in vivo. RESULTS: Hsa_circ_0026416 was markedly upregulated in CRC patient tissues and plasma and was a poor prognosis in CRC patients. In addition, the area under the curve (AUC) of hsa_circ_0026416 (0.767) was greater than the AUC of CEA (0.670), CA19-9 (0.592) and CA72-4 (0.575). Functionally, hsa_circ_0026416 promotes cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, hsa_circ_0026416 may function as a ceRNA via competitively absorbing miR-346 to upregulate the expression of NFIB. CONCLUSIONS: In summary, our findings demonstrate that hsa_circ_0026416 is an oncogene in CRC. Hsa_circ_0026416 promotes the progression of CRC via the miR-346/NFIB axis and may represent a potential biomarker for diagnosis and therapy in CRC.

Post-therapy pathologic tumor volume predicts survival in gastric cancer patients who underwent neoadjuvant chemotherapy and gastrectomy.

BACKGROUND: To demonstrate that post-therapy pathological tumor volume (ypTV) should be considered as an independent prognostic factor in advanced gastric cancer (GC) patients who underwent neoadjuvant chemotherapy (NAC) and gastrectomy. METHODS: A total of 253 GC patients who received gastrectomy between January 2010 and December 2016 in our hospital were enrolled in this study. Clinicopathologic factors were evaluated using univariable and multivariable analysis. ypTV was calculated using π* (tumor diameter/2)2 *tumor invasion depth (cm3). RESULTS: Cut-point survival analysis demonstrated that the appropriate cut-offs for ypTV were 3, 6, 10, and 19 (cm3). Patients with tumor volumes of 0-3.0, 3.1-6.0, 6.1-10.0, 10.1-19.0, ≥19.1 cm3 were defined as ypTV1, 2, 3, 4a and 4b. Using multivariable analysis, the tumor volume (ypTV stage, P < 0.05), ypN stage (P < 0.05), response to NAC (P < 0.05), vascular invasion (P < 0.05) and ypTvNM staging (P < 0.05) were independent prognostic factors. Kaplan-Meier analysis demonstrated that the 8th AJCC/UICC ypTNM staging was not a significant predictor for survival (P > 0.05); however, our newly defined ypTvNM staging was a significant predictor for survival (P < 0.05). CONCLUSIONS: ypTV should be considered as an independent prognostic factor for GC patients after NAC. ypTvNM staging should be recommended to improve the accuracy of prognostic prediction for GC patients who received NAC plus gastrectomy.

Clinical risk factors for central lymph node metastasis in papillary thyroid carcinoma: a systematic review and meta-analysis.

BACKGROUND: Prophylactic central lymph node dissection (CLND) in clinically node-negative patients remains controversial, and predictive factors for central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) are not well defined. Herein, we conducted a systematic review to quantify the clinicopathologic factors predictive for CLNM in patients with PTC. METHODS: A systematic search of electronic databases (PubMed, Embase, Cochrane CENTRAL, Scopus and Wanfang Database) for studies published until July 2014 was performed. Cohort, case-control studies and randomized controlled trials that examined clinical risk factors of CLNM were included. RESULTS: Twenty-five studies (4 prospective and 21 retrospective studies) involving 7,719 patients met final inclusion criteria. From the pooled analyses, male gender (OR 1.93, 95% CI 1.40 to 2.64), tumour multifocality (OR 1.93, 95% CI 1.62 to 2.30), tumour size >0.5 cm (OR 3.48, 95% CI 2.24 to 5.41), capsular invasion (OR 1.91, 95% CI 1.36 to 2.67), extrathyroidal extension (OR 2.42, 95% CI 1.58 to 3.71), lymphovascular invasion (OR 13.29, 95% CI 5.61 to 31.48) and lateral lymph node metastasis (OR 14.33, 95% CI 5.34 to 38.50) were significantly associated with increased risk of CLNM, while age >45 years (OR 0.65, 95% CI 0.51 to 0.83) and lymphocytic thyroiditis (OR 0.70, 95% CI 0.53 to 0.92) resulted in decreased risk of CLNM. Bilaterality and tumour location were not significantly associated with CLNM development (all P > 0.05). CONCLUSIONS: Our analysis identified several clinicopathologic factors associated with CLNM. These findings may guide the necessity and extent of prophylactic CLND and ultimately improve the outcomes of patients with PTC.

A clinically applicable prediction model for the risk of in-hospital mortality in solid cancer patients admitted to intensive care units with sepsis.

PURPOSE: To develop and validate a user-friendly model to predict the risk of in-hospital mortality in solid cancer patients admitted to the ICU with sepsis. METHODS: Clinical data of critically ill patients with solid cancer and sepsis were obtained from Medical Information Mart for Intensive Care-IV database and randomly assigned to the training cohort and validation cohort. The primary outcome was in-hospital mortality. The least absolute shrinkage and selection operator (LASSO) regression and logistic regression analysis were used to feature selection and model development. The performance of the model was validated and a dynamic nomogram was developed to visualize the model. RESULTS: A total of 1584 patients were included in this study, of whom 1108 were assigned to the training cohort and 476 to the validation cohort. The LASSO regression and logistic multivariable analysis showed that nine clinical features were associated with in-hospital mortality and enrolled in the model. The area under the curve of the model was 0.809 (95% CI 0.782-0.837) in the training cohort and 0.770 (95% CI 0.722-0.819) in the validation cohort. The model exhibited satisfactory calibration curves and Brier scores in the training set and validation set were 0.149 and 0.152, respectively. The decision curve analysis and clinical impact curve of the model presented good clinical practicability in both the two cohorts. CONCLUSION: This predictive model could be used to assess the in-hospital mortality of solid cancer patients with sepsis in the ICU, and a dynamic online nomogram could facilitate the sharing of the model.

Process Optimization, Microstructure and Mechanical Properties of Wire Arc Additive Manufacturing of Aluminum Alloy by Using DP-GMAW Based on Response Surface Method.

Double-pulsed gas metal arc welding (DP-GMAW) is a high-performance welding method with low porosity and high frequency. Periodic shrinkage and expansion of the melt pool during DP-GMAW leads to unusual remelting, and the re-solidification behavior of the weld metal can significantly refine the weld structure. The advantages of DP-GMAW have been proven. In order to better apply DP-GMAW to aluminum alloy arc additive manufacturing, in this paper, the single-pass deposition layer parameters (double-pulse amplitude, double-pulse frequency and travel speed) of DP-GMAW will be optimized using the response surface method (RSM) with the width, height, and penetration of the deposition layer as the response values to find the superior process parameters applicable to the additive manufacturing of aluminum alloy DP-GMAW. The results show that the aluminum alloy components made by DP-GMAW additive are well formed. Due to the stirring of double-pulse arc and the abnormal remelting and solidification of metal, the microstructures in the middle and top areas show disordered growth. The average ultimate tensile strength of the transverse tensile specimen of the member can reach 175.2 MPa, and the elongation is 10.355%.

POU5F1 promotes the proliferation, migration, and invasion of gastric cancer cells by reducing the ubiquitination level of TRAF6.

POU5F1 plays an important role in maintaining the cancer stem cell (CSC) -like properties of gastric cancer (GC) cells. The impact of POU5F1 on the proliferation and metastasis of GC was examined, along with the potential of ATRA as a specific therapeutic agent for GC. The dysregulation of POU5F1 expression in GC tissues was analyzed using public databases and bioinformatics techniques, and the disparity in POU5F1 expression between normal gastric tissues and GC tissues was further assessed through western blot, RT-qPCR, and immunohistochemistry. The present study aimed to investigate the impact of POU5F1 on the proliferation, migration, and invasion of GC cells through both in vivo and in vitro experiments. Additionally, the effects of ATRA on the proliferation, migration, and invasion of GC cells were examined using in vivo and in vitro approaches. Our findings revealed a significant upregulation of POU5F1 in GC tissues, which was found to be associated with a poorer prognosis in patients with GC. Moreover, POU5F1 was observed to enhance the proliferation, migration, and invasion of GC cells in vitro, as well as promote subcutaneous tumor growth and lung metastasis of GC cells in vivo. The overexpression of POU5F1 mechanistically triggers the process of Epithelial-mesenchymal transition (EMT) by down-regulating E-Cadherin and up-regulating N-Cadherin and VIM. POU5F1 hinders the ubiquitination of TRAF6 through negative regulation of TRIM59, thereby facilitating the activation of the NF-κB pathway. Furthermore, the administration of ATRA effectively impedes the proliferation, migration, and invasion of GC cells by suppressing the expression of POU5F1. The upregulation of POU5F1 elicits EMT, fosters the initiation of the NF-κB signaling pathway in GC cells, and stimulates the proliferation, invasion, and metastasis of GC cells. All-trans retinoic acid (ATRA) can impede these POU5F1-induced effects, thereby potentially serving as an adjunctive therapeutic approach for GC.

Stressing State Analysis of Partially Prestressed Concrete Beams with High Strength Reinforcement Based on NSF Method.

This paper analyzes the flexural behavior of a partially prestressed steel high-strength reinforced concrete beams based on the structural stress state theory and the numerical shape function method. First, the generalized strain energy density is formed by the measured strain data of the test beam to reflect the structural stress state of the beams, and then the Mann-Kendall criterion is used to judge characteristic points of the generalized strain energy density curve. Two characteristic points, namely, post-elastic boundary load and failure load, are detected, so that the whole loading process is divided into three structural stressing state stages. Unlike the ultimate load, failure load is defined according to the general law from quantitative to qualitative change, which represents the starting point of the failure stage of the beam. Then, experimental strains and deflections, strain/stress fields interpolated by the numerical shape function method, and internal forces calculated by integration are respectively analyzed to obtain their changing characteristics and working behavior around the characteristic points, which can also verify the correction and effectiveness of the Mann-Kendall criterion. In addition, through the analysis above, it can be known that the failure loads of the test beams can be effectively improved by increasing the prestressed reinforcement ratio or concrete strength.

NSF-Based Analysis of the Structural Stressing State of Trussed Steel and a Concrete Box Girder.

This paper analyses the characteristics of the mechanical behavior of a trussed steel and concrete box beam under bending conditions based on the structural stressing state theory and the numerical shape function method. Firstly, the parametric generalized strain energy density was introduced to characterize the structural stressing state of trussed steel stud concrete box girders, and the strain energy density sum was plotted. Then the Mann-Kendall criterion was used to discriminate the leap point of the curve change and to redefine the structural failure load. By analyzing the strain and displacement, the existence of a sudden change in the structural response during the load-bearing process was again demonstrated. Afterwards, the numerical shape function method was used to extend the strain data, and further in-depth analyses of strain/stress fields and internal forces were carried out to show in detail the working characteristics of each under load. Through an in-depth analysis from different angles, the rationality of updating the failure load was verified. Finally, the effects of different structure parameters on the evolution of the structural stresses of the members were analyzed in a transversal comparison. The analysis results of the stress state of a steel-concrete truss structure reveal the working behavior characteristics of a steel-concrete truss structure from a new angle, which provides a reference for the design of a steel-concrete truss structure in the future.

Upregulation of CRABP2 by TET1-mediated DNA hydroxymethylation attenuates mitochondrial apoptosis and promotes oxaliplatin resistance in gastric cancer.

Oxaliplatin is the main chemotherapy drug for gastric cancer (GC), but quite a few patients are resistant to oxaliplatin, which contributes to the poor prognosis of GC patients. There is therefore an urgent need to identify potential targets for reversing chemotherapy resistance in GC patients. In this study, we analyzed the tumor samples of GC patients who received neoadjuvant chemotherapy based on oxaliplatin through quantitative proteomics and identified the potential chemoresistance-related protein cellular retinoic acid binding protein 2 (CRABP2). CRABP2 was significantly upregulated in the tumor tissues of chemoresistant GC patients and was closely related to prognosis. The results of cell function experiments showed that CRABP2 can promote the oxaliplatin resistance of GC cells in vitro. Coimmunoprecipitation and GST pulldown assays showed that CRAPB2 expedited the binding of BAX and PARKIN in GC cells and facilitated the ubiquitination-mediated degradation of BAX. Furthermore, both the in vitro assay and cell-derived xenograft (CDX) in vivo model verified that CRABP2 promoted oxaliplatin resistance by inhibiting BAX-dependent cell apoptosis. Further experiments proved that the abnormally high expression of CRABP2 in oxaliplatin-resistant GC cells was affected by TET1-mediated DNA hydroxymethylation. The patient-derived xenograft (PDX) model suggested that interference with CRABP2 reversed oxaliplatin resistance in GC in vivo. In conclusion, the results of our study show that CRABP2 was a key molecule in oxaliplatin resistance regulation and could be a new target for reversing the chemoresistance of GC.

Cancer stem cells in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most intractable challenges among human diseases with poor prognosis and shortness of effective therapeutic options. Cancer stem cells (CSCs), a tumor sub-population, are considered the cause of tumor growth, differentiation, metastasis and therapeutic resistance, etc. In this review, we discuss the known methods for isolation and verification of ESCC CSCs, the biomarkers of ESCC CSCs and their significance in diagnosis and prognosis. Then we review the ESCC CSC signaling pathway and therapeutic resistance. In pace with the detailed studies of ESCC CSCs increasing, treatment strategies of ESCC based on CSCs are becoming more promising.

FBXO39 predicts poor prognosis and correlates with tumor progression in cervical squamous cell carcinoma.

BACKGROUND: Cancer/testis antigen (CTA) is a class of antigen molecules mainly expressed in the germinal epithelium of testis and some tumor tissues. FBXO39, also known as F-box protein 39, is a crucial CTA molecule. F-box protein 39 (FBXO39) is overexpressed in cervical squamous cell carcinomas (CESCs), however its function in cancer development and clinical significance are still unknown. METHODS: We used paraffin-embedded tumor tissues from 124 patients and fresh-harvested and paired adjacent normal esophageal tissues from 15 CESC patients who underwent primary surgical resection in Xijing Hospital between 2015 and 2020. The expression level of FBXO39 was evaluated through immunohistochemistry, Western Blot and q-PCR. Prognostic and survival analyses were conducted using univariate/multivariate analysis and log-rank analysis with SPSS 23.0. CCK-8, wound-healing and Transwell assays were applied to demonstrate that FBXO39 promoted the proliferation, migration and invasion. Finally, we constructed a xenografts model of the C-33A cell lines to observe the effect of FBXO39 on tumorigenesis in vivo. RESULTS: Immunohistochemical results showed that FBXO39 was highly expressed in cancer tissues than in corresponding non-cancer tissues. Similarly, we proved this result at protein and mRNA level by Western-Blotting and q-PCR. Prognostic and OS analyses showed that the FBXO39 expression level was an individual prognostic factor in CESC patients. CCK-8, wound-healing and Transwell assays proved that the overexpression of FBXO39 in Si-Ha cells promoted the proliferation, migration and invasion of the cells. Knocking down FBXO39 in C-33A cells inhibited the proliferation, migration and invasion of cells. The experimental results of xenografts model in nude mice showed that the knockdown of FBXO39 in C-33A cells slowed down the growth of tumor. CONCLUSION: FBXO39 is a poor prognostic factor of cervical squamous cell carcinoma, which may provide a novel therapeutic target for CESC.

Prognostic Significance of Signet-Ring Cell Components in Patients With Gastric Carcinoma of Different Stages.

Background: Gastric carcinoma (GC), which contains signet ring cell (SRC) components are frequently observed in postoperative pathological assessment. This study aims to study the prognostic significance of SRC components in GC patients. Methods: From 2003 to 2017, surgically resected primary GC patients were retrospectively reviewed. All enrolled patients were divided into three groups according to the proportion of SRC. The overall survival (OS) and disease-free survival (DFS) of GC patients with different tumor stages were analyzed. Results: Patients with SRC or mixed-SRC were more associated with female, younger age, middle or lower third of the stomach, larger tumor, higher pN stage, and more lymphovascular invasion. For GC patients in stage I, multivariate survival analysis showed that age >60, SRC components >50%, and pT stage were independent prognostic factors for OS (all p < 0.05). The 5-year OS of patients with SRC were higher than that of patients with pure adenocarcinoma (p = 0.021). For GC patients in stage II/III, multivariate survival analysis showed that age >60, SRC proportion, surgical types, Borrmann's type, pT stage, pN stage, and lymphovascular invasion were independent prognostic factors for OS (all p < 0.05). The 5-year OS/DFS of patients with SRC were lower than that of patients with pure adenocarcinoma (p < 0.001). Conclusions: SRC seemed to be a favorable prognostic factor in GC patients in stage I. However, for GC patients in stage II/III, the SRC components were associated with poor prognosis, independent of other clinicopathological factors.

Bond Behavior of Reinforced Concrete Considering Freeze-Thaw Cycles and Corrosion of Stirrups.

In relatively cold environments, the combination of freeze-thaw and steel bar corrosion is a key factor affecting the durability of concrete. The adjustment of the stirrup ratio would change the mechanical performance of surrounding concrete, while the circumferential compressive stress can further improve the bonding performance. Hence, based on eccentrically tensioned specimens, the influence of corrosion of stirrups and freeze-thaw of concrete on bond properties is discussed in this paper. The monotonic pull-out test of reinforced concrete specimens is carried out to study the variation rules of bond strength and slip between steel bar and concrete under the coupling action of corrosion rate, freeze-thaw times and stirrup spacing. Based on the experimental data, the empirical formula for the ultimate bond strength is obtained, and a bond-slip constitutive model is established considering the stirrup spacing, stirrup corrosion rate and freeze-thaw times. Then, a refined finite element pull-out specimen model is established by ABAQUS simulation, and the numerical simulation results are compared with the real test ones, so as to make up for the deficiencies in the test and lay the foundation for further finite element analysis.

Stressing State Analysis of Reinforced Concrete Beam Strengthened by CFRP Sheet with Anchoring Device.

This paper investigates the working performance of reinforcement concrete (RC) beams strengthened by Carbon-Fiber-Reinforced Plastic (CFRP) with different anchoring under bending moment, based on the structural stressing state theory. The measured strain values of concrete and Carbon-Fiber-Reinforced Plastic (CFRP) sheet are modeled as generalized strain energy density (GSED), to characterize the RC beams' stressing state. Then the Mann-Kendall (M-K) criterion is applied to distinguish the characteristic loads of structural stressing state from the curve, updating the definition of structural failure load. In addition, for tested specimens with middle anchorage and end anchorage, the torsion applied on the anchoring device and the deformation width of anchoring device are respectively set parameters to analyze their effects on the reinforcement performance of CFRP sheet through comparing the strain distribution pattern of CFRP. Finally, in order to further explore the strain distribution of the cross-section and analyze the stressing-state characteristics of the RC beam, the numerical shape function (NSF) method is proposed to reasonably expand the limited strain data. The research results provide a new angle of view to conduct structural analysis and a reference to the improvement of reinforcement effect of CFRP.

Exosome-transmitted circCOG2 promotes colorectal cancer progression via miR-1305/TGF-ß2/SMAD3 pathway.

Circular RNAs (circRNA) are abundantly present in the exosome. Yet, the role of exosome-transmitted circRNA in colorectal cancer (CRC) remains unclear. In this study, we examined the function and mechanism of circCOG2 in CRC. We analyzed the expression of circCOG2 in CRC tissues, plasmas, and exosomes by qRT-PCR. The function of circCOG2 was evaluated by CCK-8, clone formation, transwell and wound healing assay, and using an in vivo study; while its mechanism was analyzed using a dual luciferase reporter assay, RNA pull-down assay, Western blot, and rescue experiments. We found that circCOG2 was increased in CRC tissues, plasmas, and exosomes. Upregulated circCOG2 promoted CRC proliferation, migration, and invasion through the miR-1305/TGF-ß2/SMAD3 pathway, and this effect could be transmitted from CRC cells with the high metastatic potential to CRC cells with low metastatic potential by exosomes. Our results revealed that circCOG2 is correlated with poor prognosis and may be used as a therapeutic target for CRC.

Experimental Investigation on the Static Performance of Stud Connectors in Steel-HSFRC Composite Beams.

In this research, high strength fiber reinforced concrete (HSFRC) was used to replace the normal strength concrete (NSC) in steel-concrete composite beams to improve their working performance, which might change the static performance of stud connectors. Firstly, push-out tests were conducted to investigation on the static performance of stud connectors in steel-HSFRC composite beams and compared with steel-NSC composite beams. Studs of 8 sizes, 13 mm, 16 mm, 19 mm and 22 mm in diameter and 80 mm and 120 mm in height were adopted to study the influence of stud dimension. The test phenomenon shown that the crack resistance of HSFRC was better than that of NSC, and there were some splitting cracks on NSC slabs whereas no visible cracks on HSFRC slabs when specimens failed. Next, the load-slip curves of studs were analyzed and a typical load-slip curve was proposed which was divided into four stages. In addition, the effects of test parameters were analyzed according to the characteristic points of load-slip curve. Compared with NSC slab, HSFRC slab could provide greater restraining force to the studs, which improved the shear capacity and stiffness of studs while suppressed the ductility of studs. The shear capacity, stiffness and ductility of studs would significantly increase with the increasement of stud diameter and the studs with large diameter were more suitable for steel-HSFRC composite beams. The stud height had no obvious influence on the static performance of studs. Finally, based on the test results, the empirical formulas for load-slip curve and shear capacity of stud connectors embedded in HSFRC were developed which considered the influence factors more comprehensively and had better accuracy and applicability than previous formulas.

UBQLN4 is activated by C/EBPß and exerts oncogenic effects on colorectal cancer via the Wnt/ß-catenin signaling pathway.

Ubiquilin 4 (UBQLN4) is an important member of the ubiquitin-like protein family. An increasing number of studies have shown that UBQLN4 is an important regulator of tumorigenesis. Nevertheless, the biological function and detailed mechanisms of UBQLN4 in colorectal cancer (CRC) development and progression remain unclear. Here, we identified UBQLN4 upregulation in CRC tissues and it is positively associated with CRC size, TNM stage, and lymphatic metastasis. Patients with high UBQLN4 expression had a poor prognosis. Functionally, overexpression of UBQLN4 significantly promoted CRC cell proliferation, migration, and invasion, while UBQLN4 silencing elicited the opposite effect. This result was consistent with the conclusion that UBQLN4 expression correlated positively with the CRC size and lymphatic metastasis. In vivo, UBQLN4 silencing also inhibited tumor growth. Mechanistically, using gene set enrichment analysis (GSEA) and western blot experiments, we identified that UBQLN4 activated the Wnt/ß-catenin signaling pathway to upregulate ß-catenin and c-Myc expression, thereby promoting CRC proliferation, migration and invasion. A rescue experiment further verified this conclusion. Dual luciferase reporter, real-time quantitative PCR (RT-qPCR), western blot and chromatin immunoprecipitation (ChIP) assays indicated that the transcription factor CCAAT/enhancer-binding protein beta (C/EBPß) directly bound to the UBQLN4 core promoter region and activated its transcription, upregulating ß-catenin and c-Myc expression to promote CRC progression. Thus, our findings suggest that UBQLN4 is a key oncogene in CRC and may be a promising target for the diagnosis and treatment of patients with CRC.

Poor histologic tumor response after adjuvant therapy in basal-like HER2-positive breast carcinoma.

AIMS: HER2-positive breast carcinomas are all treated with first-line anti-HER2 therapy. However, immunohistochemical and molecular profiling demonstrates significant heterogeneity among HER2-positive carcinomas. Basal-like HER2-positive breast carcinomas are poorly differentiated from pure HER2-positive breast carcinomas. MATERIALS AND METHODS: Seventy-five patients with HER2-positive, ER- and PR-negative breast carcinomas who received anti-HER2 based neoadjuvant therapy were retrospectively analyzed. Thirty-seven cases were classified as basal-like HER2-positive breast carcinoma with any positivity for CK5/6, and thirty-eight cases were classified as pure HER2-positive breast carcinoma with completely negativity for CK5/6. The clinicopathological features and tumor responses after neoadjuvant therapy and outcomes were analyzed. RESULTS: Compared to non-basal HER2-positive breast carcinoma, basal-like HER2-positive breast carcinoma showed distinctive histologic features including poor differentiation and syncytial tumor cells with pushing, invasive borders and a significantly higher proportion of apocrine metaplasia. They also demonstrated significantly higher histologic grade; 18/37 (48.6%) of basal-like carcinomas were grade 3, whereas only 5/38 (13.2%) of non-basal carcinomas were grade 3 (p = 0.001), Furthermore, basal-like HER2-positive breast carcinomas were more likely to be positive or completely negative for p53 (p = 0.009), and demonstrated a higher percentage of TP53 mutation (p = 0.17). These tumors were less responsive to anti-HER2 based neoadjuvant therapy, with Miller-Payne grades 1-3 higher than pure HER2-positive breast carcinoma (25/37 [67.6%] vs 16/38 [42.1%]), and the percentage of grade 4-5 was lower (12/37 [32.4%] vs 22/38 [57.9%]; p = 0.027). CONCLUSIONS: Basal-like HER2-positive breast carcinoma has distinctive clinicopathological features and less histologic tumor response after neoadjuvant therapy. There is urgent need to recognize basal-like HER2-positive breast carcinoma to be treated precisely.

Histological Differentiated/Undifferentiated Mixed Type Should Not Be Considered as a Non-Curative Factor of Endoscopic Resection for Patients With Early Gastric Cancer.

BACKGROUND: Histological differentiated/undifferentiated mixed-type adenocarcinomas are frequently found in patients with early gastric cancer (EGC). Yet it is unclear whether these mixed-type adenocarcinomas can be treated by endoscopic resection (ER) in EGC patients. AIMS: To evaluate the lymph node metastasis (LNM) rate and long-term outcomes in mixed-type EGC patients and assess the feasibility of ER in these patients. METHODS: Clinicopathological features, risk factors of LNM, and overall survival (OS) and progression-free survival (PFS) rates of EGC patients were analyzed according to different histological types. RESULTS: Patients with mixed-type EGC had higher LNM rates than patients with non-mixed-type EGC (11.4 vs. 6.2%, P = 0.044). In the multivariate analysis, larger tumor diameter, presence of an ulcer, submucosal invasion, histological undifferentiated type, histological mixed type, and lymphovascular invasion resulted as independent risk factors for LNM in EGC patients (all P < 0.05). The LNM rate in mixed-type patients who met the Japanese ER criteria was 3.3%, including fulfilling the absolute criteria 0%. The 5-year OS and PFS rates in mixed-type patients were 94.59 and 91.47%, respectively. There was no statistical significance in the OS (P = 0.870) and PFS (P = 0.705) between mixed-type and non-mixed-type EGC patients fulfilling the Japanese ER criteria. CONCLUSION: Histological differentiated/undifferentiated mixed type in EGC patients meeting the Japanese absolute criteria for ER are associated with low risk of LNM and favorable prognosis, and thus, it should not be considered as a non-curative factor for ER.