Comparison Between Intraoperative Target Area Cement-Enhanced Percutaneous Vertebroplasty and Conventional Percutaneous Vertebroplasty for Osteoporotic Thoracolumbar Non-Total Vertebral Fractures.

AIM: To compare the efficacy and feasibility of target area cement-enhanced percutaneous vertebroplasty (PVP) and conventional PVP in osteoporotic thoracolumbar non-total vertebral fractures. MATERIAL AND METHODS: Retrospective analysis of one hundred and two patients treated in our hospital from March 2020 to May 2021 and divided into groups A (targeted) and B (conventional PVP). The Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), anterior vertebral height ratio, intraoperative bleeding, operative time, bone cement volume, complications, and refracture of the injured vertebra were evaluated in both groups. RESULTS: The 2 days and 1-year post-operative VAS and ODI scores improved significantly in both groups (p < 0.05). The 2 days post-operative VAS and ODI scores were better in group A (p < 0.05), and there was no significant difference in the scores between the groups at the last follow-up (p > 0.05). The anterior vertebral height ratios were significantly higher in both groups 2 days postoperatively (p < 0.05); however, there was no significant difference in the 2 days and 1-year post-operative ratios in group A (p > 0.05). The anterior vertebral height ratio reduced in group B after 1 year compared to the 2 days post-operative value (p < 0.05). There was no statistical difference in intraoperative bleeding and the operative time between the groups (p > 0.05), and the bone cement volume was lesser in group A (p < 0.05). Six patients in group A and four patients in group B demonstrated cement leakage, the difference was not statistically significant (p > 0.05). Three patients in group A and 11 patients in group B demonstrated refracture, the difference was statistically significant (p < 0.05). CONCLUSION: Target area cement-enhanced PVP can effectively relieve short-term pain and functional disability and reduce the long-term possibility of secondary collapse. Therefore, it is a technically feasible and efficacious method for the treatment of osteoporotic thoracolumbar non-total vertebral fractures.

Specialized spatially-arranged non-circular fibers enhance filtration performance of African shrimp (Atya gabonensis).

African shrimp (Atya gabonensis) inhabit clear freshwaters, where the notably low concentration of food may pose a challenge to the efficacy of filter fibers on the chela for filter-feeding. Here, we investigate how the distinctive cross-sectional characteristics and spatial arrangement of the African shrimp's non-circular fibers contribute to the enhanced filtration performance of these specialized fibers. The unilateral thickening of the wall along the long axis of the elliptical cross-section of African shrimp fibers markedly enhances the filtration performance. The staggered and twisted arrangement of the fibers optimizes the surrounding flow field, achieving a favorable balance between pressure drop and collection efficiency, consequently improving their filtration performance in collecting fine particles (diameter: 2-10µm). Moreover, the arrangement of the fibers substantially increases the effective flow-facing filtering area of the fiber bundles, thus facilitating their efficiency in collecting larger particles (diameter > 10µm). The unique fiber properties of the African shrimp offer novel insights for the design and optimization of new fiber-filtering robots, presenting a wide range of potential applications, such as marine in-situ resource extraction, medical filtration, and industrial filtration.

Biomechanical study of different bone cement distribution on osteoporotic vertebral compression Fracture-A finite element analysis.

Purpose: This study aimed to compare the biomechanical effects of different bone cement distribution methods on osteoporotic vertebral compression fractures (OVCF). Patients and methods: Raw CT data from a healthy male volunteer was used to create a finite element model of the T12-L2 vertebra using finite element software. A compression fracture was simulated in the L1 vertebra, and two forms of bone cement dispersion (integration group, IG, and separation group, SG) were also simulated. Six types of loading (flexion, extension, left/right bending, and left/right rotation) were applied to the models, and the stress distribution in the vertebra and intervertebral discs was observed. Additionally, the maximum displacement of the L1 vertebra was evaluated. Results: Bone cement injection significantly reduced stress following L1 vertebral fractures. In the L1 vertebral body, the maximum stress of SG was lower than that of IG during flexion, left/right bending, and left/right rotation. In the T12 vertebral body, compared with IG, the maximum stress of SG decreased during flexion and right rotation. In the L2 vertebral body, the maximum stress of SG was the lowest under all loading conditions. In the T12-L1 intervertebral disc, compared with IG, the maximum stress of SG decreased during flexion, extension, and left/right bending and was basically the same during left/right rotation. However, in the L1-L2 intervertebral discs, the maximum stress of SG increased during left/right rotation compared with that of IG. Furthermore, the maximum displacement of SG was smaller than that of IG in the L1 vertebral bodies under all loading conditions. Conclusions: SG can reduce the maximum stress in the vertebra and intervertebral discs, offering better biomechanical performance and improved stability than IG.

High stability in filtration apparatus of African shrimp.

The African shrimp (Atya gabonensis) uses elongated setae to filter feed, adapting to high flow velocities. The setae's stability stems from carefully designed geometric and structural parameters, notably a specialized wall and distribution principle. This study highlights the robust filtration mechanism in the shrimp and potential for developing stable structures in underwater environments.

Feasibility Analysis of the Bone Cement-Gelatine Sponge Composite Intravertebral Prefilling Technique for Reducing Bone Cement Leakage in Stage I and II Kümmell's Disease: A Prospective Randomized Controlled Trial.

OBJECTIVE: Bone cement leakage is a major complication of percutaneous vertebroplasty (PVP) while treating Kümmell's disease and it is a focus of close attention during the surgical procedure. The study aimed to investigate whether pre-injecting a composite of bone cement and gelatine sponge (the "bone cement-gelatine sponge composite") before injecting bone cement during PVP aids in lowering the leakage rate in stage I and II Kümmell's disease. METHODS: This prospective analysis evaluated 74 patients with stage I and II Kümmell's disease who underwent PVP treatment at our hospital from December 2019 to December 2021. The participants were divided randomly into groups based on whether the bone cement-gelatine sponge composite was used during the surgery. The two groups were the bone cement-gelatine sponge composite group (GS group, comprising 37 patients) and the no bone cement-gelatine sponge composite group (N-GS group, comprising 37 patients). The independent samples t-test and chi-square test were employed to compare general information, operative time, cement injection volume, intraoperative bleeding, and bone cement leakage between the two groups. Additionally, the visual analogue scale (VAS) score, Oswestry disability index (ODI), anterior vertebral height ratio (AVHR), and the kyphotic Cobb angle were compared between the two groups at the preoperative, 2 days postoperative, and 6 months postoperative stages using repeated measures analysis of variance. RESULTS: All patients were followed up for more than 6 months, with an average of (11.19 ± 2.21) months. No significant differences were observed in terms of the operative time, cement injection volume, and intraoperative bleeding between the two groups (P > 0.05). The incidence of bone cement leakage in the N-GS group (32.43%) was significantly higher than that in the GS group (5.41%), and the difference was statistically significant (P < 0.05). The VAS score and ODI of the two groups at postoperative 2 days and 6 months improved significantly (P < 0.05). The AVHR and kyphotic Cobb angle were corrected to a certain extent (P < 0.05); however, no significant difference was observed between the two groups (P > 0.05). CONCLUSION: The bone cement-gelatine sponge composite intravertebral prefilling technique can lower bone cement leakage in stage I and II Kümmell's disease and can also relieve pain and improve vertebral body height.

Correlation analysis of larger side bone cement volume/vertebral body volume ratio with adjacent vertebral compression fractures during vertebroplasty.

Objective: To investigate the correlation analysis of larger side bone cement volume/vertebral body volume ratio (LSBCV/VBV%) with adjacent vertebral compression fracture (AVCF) in percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF). Methods: A retrospective analysis of 245 OVCF patients who underwent PVP treatment from February 2017 to February 2021, including 85 males and 160 females. The age ranged from 60 to 92 years, with a mean of (70.72 ± 7.03) years. According to whether AVCF occurred after surgery, they were divided into 38 cases in the AVCF group (fracture group) and 207 cases in the no AVCF group (non-fracture group). The correlation between gender, age, bone mineral density (BMD), body mass index (BMI), thoracolumbar segment fracture, bone cement disc leakage, LSBCV, bone cement volume (BCV), VBV, LSBCV/VBV ratio (LSBCV/VBV%), and BCV/VBV% and AVCF were analyzed in both groups. Risk factors for AVCF after PVP were analyzed by multifactorial logistic regression, and then the receiver operating characteristic curves (ROC curves) were plotted to identify the critical value of LSBCV/VBV%. Results: 38 patients (15.5%) developed AVCF postoperatively. Univariate analysis showed that BMD, bone cement disc leakage, LSBCV, and LSBCV/VBV% were risk factors for AVCF after PVP (P<0.05), while gender, age, BMI, thoracolumbar segment fracture, BCV, VBV, and BCV/VBV% were not significantly different in both groups (P>0.05). Multifactorial logistic regression analysis revealed that BMD, bone cement disc leakage, and LSBCV/VBV% were independent risk factors for AVCF after PVP (P<0.05). According to the ROC curve, the LSBCV/VBV% had an area under the curve of 71.6%, a sensitivity and specificity of 89.5% and 51.7%, respectively, and a critical value of 13.82%. Conclusion: BMD, bone cement disc leakage and LSBCV/VBV% are independent risk factors for AVCF after PVP. With LSBCV/VBV at 13.82%, the incidence of AVCF significantly increased.

Analysis of optimal volume fraction percentage and influencing factors of bone cement distribution in vertebroplasty using digital techniques.

PURPOSE: To explore the optimal volume fraction percentage (VF%) and influencing factors of bone cement distribution in percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fractures (OVCF) using digital techniques. PATIENTS AND METHODS: From January 2019 to February 2021, 150 patients with 0VCF who underwent PVP surgery in our hospital were analyzed. Based on postoperative X-ray and CT, the spatial distribution score of the intravertebral cement was calculated and the patients were divided into two groups: 0-7 were divided into group A; 8-10 were divided into group B. The general data of the two groups of patients were compared, and Mimics three-dimensional reconstruction images were used to measure the cement dispersion volume (CDV), vertebral body volume (VBV), and VF%. Factors affecting bone cement distribution were included in a multifactorial logistic regression analysis to construct a receiver operating characteristic (ROC) curve, calculate a cut-off value for the extensive distribution of bone cement, and analyze the correlation between bone cement distribution scores and VF%. RESULTS: There were 60 patients in group A and 90 patients in group B. Univariate analysis showed that bone mineral density (BMD), cement leakage, CDV, and VF% were significantly lower in group A than in group B (p < 0.05). Multivariate logistic regression analysis showed that BMD and VF% were independent influencing factors on bone cement distribution. The area under the curve (AUC) of VF% was 84.7%, and the cut-off value for extensive distribution of bone cement was 28.58%, which corresponded to a sensitivity and specificity of 72.2% and 91.7%, respectively. There was a strong correlation between the cement distribution score and VF% (r = 0.895, p < 0.001). CONCLUSION: BMD and VF% were important independent influencing factors of bone cement distribution. Extensive bone cement distribution can be achieved when the VF% reaches 28.58%.

Effect of cement distribution type on clinical outcome after percutaneous vertebroplasty for osteoporotic vertebral compression fractures in the aging population.

Objective: The study aimed to investigate the effect of the type of bone cement distribution on clinical outcomes following percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fractures (OVCF) in the elderly. Methods: Retrospective analysis of 160 patients diagnosed with OVCF who underwent PVP treatment from March 2018 to December 2020. Based on the kind of postoperative bone cement distribution, bone cement was classified as types I, II, III, IV, and V. Visual Analog Scale (VAS), Oswestry Disability Index (ODI), Cobb angle, anterior vertebral height ratio, refracture rate of injured vertebrae, and incidence of adjacent vertebral fractures were compared for the five types before and after three days, and one year of operation. Results: VAS and ODI at three days and one year postoperative were significantly lower than those preoperative (P < 0.05) for all five distribution types. VAS and ODI for types I, II, and III were lower at one year postoperatively than for types IV and V (P < 0.05). There was no significant difference in Cobb angle and anterior vertebral body height ratio between preoperative and three days postoperative groups (P < 0.05); however, there were significant differences between three days and one-year postoperative and preoperative groups (P < 0.05). Following one year of surgery, the Cobb angle and the anterior vertebral height ratio of types IV and V were significantly different from those of types I, II, and III (P < 0.05), and there was a statistically significant difference between types IV and V (P < 0.05). In terms of the incidence of injured vertebral refractures and adjacent vertebral fractures, the evenly distributed types I, II, and III were significantly lower than the unevenly distributed types IV and V, and the incidence of type V was higher (P < 0.05). Conclusions: The clinical efficacy of cement distribution following PVP of types I, II, and III is better than that of types IV and V, which can better relieve pain with long-lasting efficacy and minimize the occurrence of refractures of injured vertebrae and adjacent vertebral body fractures.

X-box Binding Protein 1 is a Potential Immunotherapy Target in Ovarian Cancer.

The allure of potentially dramatic and durable responses to immunotherapy has driven the study of several immune checkpoint inhibitor (ICI) agents in ovarian cancer. However, the results of ICI therapy in ovarian cancer have been rather disappointing. It is important to understand the reasons for the poor efficacy of ICI in ovarian cancer and to look for new targets for immunotherapy. To solve this problem, ovarian cancer-associated datasets were individually collected from The Cancer Genome Atlas (TCGA)、International Cancer Genome Consortium (ICGC)、Genotype-Tissue Expression (GTEx), and comprehensively performed to expression, prognostic, pathological correlation, genomic and immunologic analyses of reported all immune checkpoints by Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Tumor and Immune System Interaction Database (TISIDB), cBio Cancer Genomics Portal (cBioPortal), and Kaplan-Meier Plotter. We concluded that those well-identified immune checkpoints might not be ideal targets for ovarian cancer immunotherapy. Intriguingly, the genomic alteration of X-box binding protein 1 (XBP1), the important mediator of chemotherapy-induced cancer immunogenic cell death, was found to be a potential coregulator of immune checkpoints in ovarian cancer. Importantly, XBP1 was detected to be highly expressed in ovarian cancer compared with normal ovarian tissue, and high XBP1 expression significantly benefits both overall survival (OS) and disease-free survival (DFS) of ovarian cancer patients. More importantly, XBP1 was further observed to be closely related to anti-tumor immunity in ovarian cancer, including multiple T-cell signatures and immunity-killing molecules. In conclusion, upregulating XBP1 rather than targeting immune checkpoints represents a potentially more efficient approach for ovarian cancer therapy.

Glycosylated Cathepsin V Serves as a Prognostic Marker in Lung Cancer.

Dysregulation of cysteine cathepsin protease activity is pivotal in tumorigenic transformation. However, the role of cathepsin protease in lung cancer remains unknown. Here, we analyzed GEO database and found that lung cancer presented high expression of cathepsin V (CTSV). We then performed immunohistochemistry assay in 73 paired lung cancer tissues and normal lung tissues and confirmed that CTSV is overexpressed in lung cancer and correlates with poor prognosis. The mass spectrometry experiment showed that the N-glycosylation locus of CTSV are N221 and N292, glycosylated CTSV (band 43 kDa) was particularly expressed in lung cancer samples and correlated with lymph node metastasis. Mechanistic studies showed that only glycosylated CTSV (43-kDa band) are secreted to extracellular matrix (ECM) and promoted the metastasis of lung cancer. Importantly, the Elisa detection in serum of 12 lung cancer patients and 12 healthy donors showed that the level of CTSV in serum distinguished lung cancer patients from healthy donors. Together, our findings reveal the clinical relevance of CTSV glycosylation and CTSV drives the metastasis of lung cancer, suggesting that the glycosylated CTSV in serum is a promising biomarker for lung cancer.

FBXO32 targets PHPT1 for ubiquitination to regulate the growth of EGFR mutant lung cancer.

BACKGROUND: Phosphohistidine phosphatase 1 (PHPT1) is an oncogene that has been reported to participate in multiple tumorigenic processes. As yet, however, the role of PHPT1 in lung cancer development remains uncharacterized. METHODS: RNA sequencing assay and 18 pairs of tumor and normal tissues from patients were analyzed to reveal the upregulation of PHPT1 in lung cancer, followed by confirming the biological function in vitro and in vivo. Next, Gene Set Enrichment Analysis, lung cancer samples, apoptosis assay, mass spectrometry experiments and western blotting were used to investigate the molecular mechanism underlying PHPT1 driven progression in epidermal growth factor receptor (EGFR)-mutant lung cancer. Finally, we performed cellular and animal experiments to explore the tumor suppressive function of F-box protein 32 (FBXO32). RESULTS: We found that PHPT1 is overexpressed in lung cancer patients and correlates with a poor overall survival. In addition, we found that the expression of PHPT1 is elevated in EGFR-mutant lung cancer cells and primary patient samples. Inhibition of PHPT1 expression in EGFR mutant lung cancer cells significantly decreased their proliferation and clonogenicity, and suppressed their in vitro tumor growth. Mechanistic studies revealed that activation of the ERK/MAPK pathway is driven by PHPT1. PHPT1 is required for maintaining drug resistance to erlotinib in EGFR mutant lung cancer cells. We found that FBXO32 acts as an E3 ubiquitin ligase for PHPT1, and that knockdown of FBXO32 leads to PHPT1 accumulation, activation of the ERK/MAPK pathway and promotion of the proliferation, clonogenicity and growth of lung cancer cells. CONCLUSIONS: Our findings indicate that PHPT1 may serve as a biomarker and therapeutic target for acquired erlotinib resistance in lung cancer patients carrying EGFR mutations.

Noninvasive Method for Predicting the Expression of Ki67 and Prognosis in Non-Small-Cell Lung Cancer Patients: Radiomics.

Purpose: In this study, we aimed to develop and validate a noninvasive method based on radiomics to evaluate the expression of Ki67 and prognosis of patients with non-small-cell lung cancer (NSCLC). Patients and Methods. A total of 120 patients with NSCLC were enrolled in this retrospective study. All patients were randomly assigned to a training dataset (n = 85) and test dataset (n = 35). According to the preprocessed F-FDG PET/CT image of each patient, a total of 384 radiomics features were extracted from the segmentation of regions of interest (ROIs). The Spearman correlation test and least absolute shrinkage and selection operator (LASSO), after normalization on the features matrix, were applied to reduce the dimensionality of the features. Furthermore, multivariable logistic regression analysis was used to propose a model for predicting Ki67. The survival curve was used to explore the prognostic significance of radiomics features. Results: A total of 62 Ki67 positive patients and 58 Ki67 negative patients formed the training set and test training dataset and test dataset. Radiomics signatures showed good performance in predicting the expression of Ki67 with AUCs of 0.86 (training dataset) and 0.85 (test dataset). Validation and calibration showed that the radiomics had a strong predictive power in patients with NSCLC survival, which was significantly close to the effect of Ki67 expression on the survival of patients with NSCLC. Conclusion: Radiomics signatures based on preoperative F-FDG PET/CT could distinguish the expression of Ki67, which also had a strong predictive performance for the survival outcome.

Percutaneous Vertebroplasty with The Polymethyl Methacrylate - Gelatin Sponge Complex in the Treatment of Patients with Osteoporotic Vertebral Compression Fractures Accompanied by Superior Endplate Injuries.

AIM: To explore the clinical efficacy of percutaneous vertebroplasty (PVP) combined with the polymethyl methacrylate - gelatin sponge (PMMA-GS) complex in the treatment of patients with osteoporotic vertebral compression fractures (OVCFs) accompanied by superior endplate injuries. MATERIAL AND METHODS: A total of 77 OVCF patients with superior endplate injuries who were treated with PVP from January 2017 to December 2020 were retrospectively analyzed. The visual analogue scale (VAS) score, Oswestry disability index (ODI), and injured vertebral height ratio at one day (1d) before surgery, three days (3d) after surgery, and one year (1y) after surgery were compared between both groups. Besides, the surgical duration, PMMA(polymethyl methacrylate)injection volume, PMMA leakage rate, and adjacent vertebral fracture rate were compared between these two groups. RESULTS: Among these patients, there were 39 individuals treated with PVP combined with the PMMA-GS complex (the observation group) and 38 individuals treated with PVP (the control group). These patients in both groups completed the surgery successfully. There were no such complications as pulmonary embolism, hemopneumothorax, rib fracture, spinal cord nerve injuries, and vital organ injuries. In these two groups, the VAS score, ODI, and injured vertebral height ratio 1d before surgery were significantly different from those 3d and 1y after surgery (P 0.05). However, there was no significant difference in these indexes between both groups (P 0.05). There was no significant difference in the surgical duration and PMMA injection volume between both groups (P 0.05). However, the PMMA leakage rate and adjacent vertebral fracture rate in the observation group were significantly lower than those in the control group (P 0.05). CONCLUSION: Compared with traditional PVP, this therapy PVP combined with PMMA-GS complex in the treatment of OVCF patients with superior endplate injuries can effectively reduce the incidence of PMMA leakage and adjacent vertebral fracture rate.

Zn2+-Depletion Enhances Lysosome Fission in Cultured Rat Embryonic Cortical Neurons Revealed by a Modified Epifluorescence Microscopic Technique.

Lysosomes are integration hubs for several signaling pathways, such as autophagy and endocytosis, and also crucial stores of ions, including Zn2+. Lysosomal dysfunction caused by changes in their morphology by fusion and fission processes can result in several pathological disorders. However, the role of Zn2+ in modulating the morphology of lysosomes is unclear. The resolution of conventional epifluorescence microscopy restricts accurate observation of morphological changes of subcellular fluorescence punctum. In this study, we used a modified epifluorescence microscopy to identify the center of a punctum from a series of z-stack images and calculate the morphological changes. We stained primary cultured rat embryonic cortical neurons with FluoZin3, a Zn2+-sensitive fluorescent dye, and Lysotracker, a lysosome-specific marker, to visualize the distribution of Zn2+-enriched vesicles and lysosomes, respectively. Our results revealed that treating neurons with N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine, a cell-permeable Zn2+ chelator, shrank Zn2+-enriched vesicles and lysosomes by up to 25% in an hour. Pretreating the neurons with YM201636, a blocker of lysosome fission, could suppress this shrinkage. These results demonstrate the usefulness of the modified epifluorescence microscopy for investigating the homeostasis of intracellular organelles and related disorders.

Fracture toughness of zirconia with a nanometer size notch fabricated using focused ion beam milling.

OBJECTIVES: Zirconia with 3 mol% yttria (3Y-TZP) has been used for dental crowns and bridges due to its excellent mechanical behavior. Performing fracture toughness testing on this nanograin material, however, can be a challenge. For reliable results, fracture toughness testing requires an extremely sharp notch in the test specimen that closely approximates a very sharp crack. This study was to investigate an alternative method to produce nanometer-sized notches, which are less than the average grain size of 3Y-TZP, during the preparation of single-edge V-notched beam specimens and report the resulting fracture toughness value. METHODS: We present a method using focused ion beam (FIB) milling to fabricate nanometer-sized notches in 3Y-TZP. The notch tip is <100 nm wide, which is smaller than the grain size, and is consistent throughout the thickness of the specimen. RESULTS: The FIB-notched specimens show a much reduced average fracture toughness of 5.64 ± 1.14 MPa√m compared to 8.90 ± 0.23 MPa√m for the specimens without FIB-notches. The FIB-milling did not appear to create any monoclinic phase prior to fracture toughness testing. Fractures originated at the FIB-notches, and the notch size can be readily identified post-mortem using a microscope. A considerable amount of tetragonal-to-monoclinic phase transformation was observed throughout the fracture surfaces. SIGNIFICANCE: FIB milling provides an alternative method to fabricate nanometer-sized notches that are smaller than the grain size of tetragonal zirconia polycrystal. The fracture toughness determined using FIB-notches was ~5.64 MPa√m, smaller than the specimens with V-notches fabricated using saw blades.

RETRACTED: Long non-coding RNA LINC00978 promotes cell proliferation and tumorigenesis via regulating microRNA-497/NTRK3 axis in gastric cancer.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editors-in-Chief. Given the comments of Dr Elisabeth Bik regarding this article "…the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy/pasted from other sources, or computer generated", the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editors-in-Chief decided to retract the article.

High Expressions of CUL4A and TP53 in Colorectal Cancer Predict Poor Survival.

BACKGROUND/AIMS: Cullin 4A (CUL4A) is vital in cell survival, development, growth and cell cycle, it plays an important role in chaperone-mediated ubiquitination and interacts with TP53 in carcinogenesis. However, the clinicopathologic significance of CUL4A expression in colorectal cancer is unknown; in particular, the prognostic value of CUL4A combined with TP53 expression has not been explored. METHODS: We analyzed the expression of CUL4A in both public database (Oncomine) and 180 cases of colorectal cancer and paired normal tissues by real-time polymerase chain reaction and western blotting. Colony formation, wound healing, migration and invasion assays and tumorigenesis in nude mice were used to explore the function of CUL4A in CRC proliferation and metastasis in vitro and in vivo. Markers of epithelial to mesenchymal transition (EMT) were evaluated by western blotting. Immunohistochemistry (IHC) was used to analyse the relationship between CUL4A expression and E-cadherin expression. RESULTS: CUL4A and TP53 protein expression was significantly higher in cancerous tissues compared to normal tissues. Significant correlation between CUL4A and TP53 expression was observed. CUL4A expression was an independent prognostic factor for overall survival (OS) and disease-free survival (DFS). Interestingly, patients with tumors that had both CUL4A overexpression and mutant TP53 protein accumulation relapsed and died within a significantly short period after surgery (P < 0.001). Multivariate analysis showed that patients with both CUL4A+ and TP53+ positive tumors had extremely poor OS and DFS. Knockdown of CUL4A by a short interfering RNA (siRNA) significantly suppressed the progression of EMT, proliferation, migration, and invasion of colon cancer cells in vitro and tumor growth in vivo. ZEB1 silencing blocked CUL4A-driven these processes. CONCLUSION: CUL4A expression correlated positively with the prognosis of colorectal cancer. Mechanistically, ZEB1 was confirmed to mediate the function of CUL4A in regulating the EMT. The assessment of both CUL4A and mutant TP53 expression will be helpful in predicting colon cancer prognosis.

Efficacy of orlistat in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

In the present meta-analysis, the efficacy and safety of orlistat in the treatment of non-alcoholic fatty liver (NAFLD) and non-alcoholic steatohepatitis (NASH) were evaluated. PubMed, Embase, the Cochrane Library, Web of Science, and Wan Fang data were searched for controlled trials of orlistat in patients with NAFLD or NASH, published before August 2017. Three randomized controlled trials and four single-arm trials were included. The involved participants with NAFLD or NASH (330 patients) were analyzed for clinical outcomes including alteration in hepatic histological variables and biomarkers of liver function. Improvements were observed in levels of alanine aminotransferase [standard mean difference (SMD)=-1.41; P=0.01], aspartate aminotransferase (SMD=-2.06; P=0.0005), γ-glutamyl transpeptidase (SMD=-1.91; P=0.05), glucose [mean difference (MD)=-0.51; P=0.01], triglycerides (MD=-0.93; P=0.01), homeostasis model assessment of insulin resistance index (MD=-1.05; P=0.04) and body mass index (MD=-1.97; P=0.02), but not in liver fibrosis score (SMD=-0.14; P=0.71). On sub-analyses of the different patient groups, no significant differences were observed in patients with NASH. Taken together, these findings demonstrate that orlistat could serve as a therapeutic drug to improve biochemical indicators of liver damage, but not as first-choice drug for the management of NAFLD or NASH; thus suggesting a novel palliative drug only for the treatment of NAFLD.

Increased survival rates in gastric cancer, with a narrowing gender gap and widening socioeconomic status gap: A period analysis from 1984 to 2013.

BACKGROUND AND AIM: Gastric cancer (GC) has the fifth highest incidence rate of all cancers and has a poor prognosis. However, no recent large-scale and long-term studies have evaluated the incidence and survival rates of individuals with GC. METHODS: In order to explore the change of GC incidence and survival rates by age, gender, race, and socioeconomic status (SES), incidence data and survival status of patients with GC between 1984 and 2013 were abstracted from the Surveillance, Epidemiology, and End Results database. Totally, 87 242 cases of GC were exported and were analyzed. RESULTS: During these three decades, the incidence of GC was 7.4, 6.8, and 5.5 per 100 000 individuals in each decade. The 1-year relative survival rates (RSRs) improved from 42.4% to 44.3% to 49.0% (P < 0.0001), with a larger increase seen in the third decade. However, the long-term survival rates remained low (from 17.8% to 20.3% to 22.9% for the 5-year RSRs, P < 0.0001; from 14.1% to 16.4% to 18.6% for the 10-year RSRs, P < 0.0001). CONCLUSION: Our analysis demonstrated the decreased incidence and increased survival rate of GC. In addition, lower SES was associated with lower survival rates. It is notable that others (primarily for Asians) had the highest incidence rate but had better outcomes than Whites and Blacks.