Development of a prognostic nomogram for esophageal squamous cell carcinoma patients received radiotherapy based on clinical risk factors.

Purpose: The goal of the study was to create a nomogram based on clinical risk factors to forecast the rate of locoregional recurrence-free survival (LRFS) in patients with esophageal squamous cell carcinoma (ESCC) who underwent radiotherapy (RT). Methods: In this study, 574 ESCC patients were selected as participants. Following radiotherapy, subjects were divided into training and validation groups at a 7:3 ratio. The nomogram was established in the training group using Cox regression. Performance validation was conducted in the validation group, assessing predictability through the C-index and AUC curve, calibration via the Hosmer-Lemeshow (H-L) test, and evaluating clinical applicability using decision curve analysis (DCA). Results: T stage, N stage, gross tumor volume (GTV) dose, location, maximal wall thickness (MWT) after RT, node size (NS) after RT, Δ computer tomography (CT) value, and chemotherapy were found to be independent risk factors that impacted LRFS by multivariate cox analysis, and the findings could be utilized to create a nomogram and forecast LRFS. the area under the receiver operating characteristic (AUC) curve and C-index show that for training and validation groups, the prediction result of LRFS using nomogram was more accurate than that of TNM. The LRFS in both groups was consistent with the nomogram according to the H-L test. The DCA curve demonstrated that the nomogram had a good prediction effect both in the groups for training and validation. The nomogram was used to assign ESCC patients to three risk levels: low, medium, or high. There were substantial variations in LRFS between risk categories in both the training and validation groups (p<0.001, p=0.003). Conclusions: For ESCC patients who received radiotherapy, the nomogram based on clinical risk factors could reliably predict the LRFS.

Integrated network pharmacology and experimental verification to reveal the role of Shezhi Huangling Decoction against glioma by inactivating PI3K/Akt-HIF1A axis.

Shezhi Huangling Decoction (SHD) has been proven clinically effective in regulating metabolic and immune homeostasis in the treatment of glioma. The investigation aimed to deconstruct the active constituents and mechanisms of SHD. Effects of SHD on malignant characteristics of HS683 and KNS89 cells have been investigated by CCK-8, clone formation, flow cytometry, and Transwell assays. A mouse xenograft model was established to assess the effect of SHD or SHD + temozolomide (TMZ) in vivo. A total of 461 constituents were found from SHD in UPLC/Q-TOF-MS/MS analysis. Functional enrichment analysis showed that pathway in cancer, proteoglycans in cancer, regulation of epithelial cell proliferation, inflammation/immune, gliogenesis, brain development, cell adhesion, and autophagy could participate in the treatment of SHD. Additionally, 9 hub genes (AKT1, TP53, CTNNB1, STAT3, EGFR, VEGFA, PIK3CA, ERBB2, and HIF1A) were identified as hub genes. Moreover, we found that SHD may greatly reduce the migration and accelerate apoptosis of HS683 and KNS89 cells. Additionally, SHD coordinates TMZ to restrict tumor growth were found in the mice. Our results suggest that the malignant behaviors of glioma cells are suppressed by SHD and the mechanism may be closing on the inhibition of the PI3K/Akt-HIF1A axis. SHD may serve as a synergistic therapeutic choice for TMZ to suppress glioblastoma growth.

Preparation of PMMA-Based Temperature/pH Responsive Nanoparticles Encapsulating 5-Fluorouracil and Methotrexate In Situ by One-Pot Dispersion Photopolymerization.

In order to achieve long-term and controllable release of anti-tumor drugs at specific sites, temperature/pH responsive nanoparticles encapsulating 5-fluorouracil and methotrexate in situ are prepared through dispersion photopolymerization under green LED irradiation. The physicochemical properties of nanoparticles are characterized by scanning electron microscopy, Fourier transform infrared, dynamic light scattering, thermogravimetric/differential scanning calorimetry, and X-ray diffraction. In vitro drug release at different temperatures and pH values is examined to ascertain the release pattern of two drugs, which can be well described by Korsmeyer-Peppas kinetic model. The cytotoxicity evaluation illustrates that the tumor cells could be more effectively killed by the drug-loaded nanoparticles, and the improved therapeutic effect is attributed to the controllable and sustainable drug release as well as the enhanced cellular uptake. The blood safety and good biocompatibility of nanoparticles are further confirmed by hemolysis assay, indicating the prepared nanoparticles are potential candidates for effective tumor treatment.

Single-Cell Sequencing Reveals the Expression of Immune-Related Genes in Macrophages of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is characterized by macrophage infiltration, which requires further investigation. This study aims to identify immune-related genes (IRGs) in macrophage and explore their potential as therapeutic targets. This study analyzed isolated glomerular cells from three diabetic mice and three control mice. A total of 59 glomeruli from normal kidney samples and 66 from DKD samples were acquired from four kidney transcriptomic profiling datasets. Bioinformatics analysis was conducted using both single-cell RNA (scRNA) and bulk RNA sequencing data to investigate inflammatory responses in DKD. Additionally, the "AUCell" function was used to investigate statistically different gene sets. The significance of each interaction pair was determined by assigning a probability using "CellChat." The study also analyzed the biological diagnostic importance of immune hub genes for DKD and validated the expression of these immune genes in mice models. The top 2000 highly variable genes (HVGs) were identified after data normalization. Subsequently, a total of eight clusters were identified. It is worth mentioning that macrophages showed the highest percentage increase among all cell types in the DKD group. Furthermore, the present study observed significant differences in gene sets related to inflammatory responses and complement pathways. The study also identified several receptor-ligand pairs and co-stimulatory interactions between endothelial cells and macrophages. Notably, SYK, ITGB2, FCER1G, and VAV1 were identified as immunological markers of DKD with promising predictive ability. This study identified distinct cell clusters and four marker genes. SYK, ITGB2, FCER1G, and VAV1 may be important roles. Consequently, the present study extends our understanding regarding IRGs in DKD and provides a foundation for future investigations into the underlying mechanisms.

Association between circadian physical activity patterns and cancer incidence through regulation of inflammation: A UK biobank study.

BACKGROUND: Physical activity (PA) has been linked with cancer incidence. However, the effects and mechanisms underpinning circadian PA trajectories on cancer remain elusive. This study aimed to explore the optimal PA patterns in reducing cancer incidence and the associated potential mediators. METHODS: Between 2006 and 2010, 502,400 participants were recruited from the UK Biobank. Out of these, 102,323 participants wore accelerometers, which allowed for collecting acceleration data continuously over 7 days. After excluding participants with previous cancer history, 96,687 participants were included in K-means cluster analysis to identify PA trajectories. The association between PA and cancer incidence was assessed using Cox regression analysis. Additionally, we investigated the mediating role of inflammation. RESULTS: A total of 5995 cancer cases were recorded during a median follow-up of 7.1 years. Four distinct PA trajectories (persistent low, single peak, double peak, and vigorous) were identified. The ideal PA patterns reduced the risk of 7 out of 17 site-specific cancers, with the lowest hazard ratios and 95% confidence intervals of cancer for bladder (0.59, 0.40-0.86), breast (0.73, 0.60-0.89), kidney (0.45, 0.26-0.78), lung (0.59, 0.41-0.84), myeloma (0.49, 0.27-0.88), and oral & pharynx (0.51, 0.26-0.98) in the vigorous pattern and for colorectal (0.71, 0.54-0.93) in the double peak pattern. Moreover, the mediating effects of inflammation were significant. CONCLUSION: Optimal PA trajectories reduced cancer incidence, especially in double peak and vigorous patterns. The protective effect was associated with both intensity and circadian rhythm. Crucially, this protection was mediated by inflammation regulation.

An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer.

BACKGROUND: Sacituzumab govitecan (SG) is an antibody-drug conjugate that targets the human trophoblast cell-surface antigen 2 to deliver SN-38 to cancer cells. In this study, we assessed the efficacy and safety of SG in patients with relapsed or refractory metastatic triple-negative breast cancer (RM-TNBC). METHODS: For this integrated analysis, from inception to January 2, 2023, we searched PubMed, Web of Science, Embase, and Cochrane library databases for prospective studies that evaluated SC in RM-TNBC patients. Primary endpoints were survival outcomes and responses. Secondary endpoints were all grade and grade ≥ 3 toxicities. RESULTS: Six hundred potentially relevant records were screened. Our analysis included 3 trials (412 patients). Median overall survival was 12.9 months (95% confidence interval [CI], 11.5-14.4), progression-free survival was 5.7 months (5% CI, 5.1-6.3), and duration of objective response was 7.4 months (5% CI, 5.8-9.0). The objective response rate was 34%, and the disease control rate was 71%. Key grade ≥ 3 toxicities (in over 10% of the patients) included neutropenia (46%), leukopenia (12%), febrile neutropenia (11%), diarrhea (11%), and anemia (10%). Four treatment-related deaths were reported. CONCLUSION: SG was associated with effectiveness in patients with RM-TNBC. Myelosuppression and diarrhea were the primary treatment-related adverse events.

Supervised breast cancer prediction using integrated dimensionality reduction convolutional neural network.

OBJECTIVES: Breast cancer is a major health problem with high mortality rates. Early detection of breast cancer will promote treatment. A technology that determines whether a tumor is benign desirable. This article introduces a new method in which deep learning is used to classify breast cancer. METHODS: A new computer-aided detection (CAD) system is presented to classify benign and malignant masses in breast tumor cell samples. In the CAD system, (1) for the pathological data of unbalanced tumors, the training results are biased towards the side with the larger number of samples. This paper uses a Conditional Deep Convolution Generative Adversarial Network (CDCGAN) method to generate small samples by orientation data set to solve the imbalance problem of collected data. (2) For the high-dimensional data redundancy problem, this paper proposes an integrated dimension reduction convolutional neural network (IDRCNN) model, which solves the high-dimensional data dimension reduction problem of breast cancer and extracts effective features. The subsequent classifier found that by using the IDRCNN model proposed in this paper, the accuracy of the model was improved. RESULTS: Experimental results show that IDRCNN combined with the model of CDCGAN model has superior classification performance than existing methods, as revealed by sensitivity, area under the curve (AUC), ROC curve and accuracy, recall, sensitivity, specificity, precision,PPV,NPV and f-values analysis. CONCLUSION: This paper proposes a Conditional Deep Convolution Generative Adversarial Network (CDCGAN) which can solve the imbalance problem of manually collected data by directionally generating small sample data sets. And an integrated dimension reduction convolutional neural network (IDRCNN) model, which solves the high-dimensional data dimension reduction problem of breast cancer and extracts effective features.

PLAG1 g.8795C>T Mutation Regulates Early Body Weight in Hu Sheep by Weakening miR-139 Binding.

Sheep birth and weaning weights indicate their growth and survival. Thus, identifying molecular genetic markers for early body weight is important in sheep breeding. Pleomorphic adenoma gene 1 (PLAG1) is important for regulating birth weight and body length in mammals; however, its relationship with sheep body weight remains unknown. Here, the 3'-untranslated region (3'-UTR) of the Hu sheep PLAG1 gene was cloned, single nucleotide polymorphisms (SNPs) were screened, genotype-early body weight relationships were analyzed, and the possible molecular mechanism was explored. PLAG1 3'-UTR sequences with five forms of base sequences plus poly(A) tails were detected in Hu sheep and the g.8795C>T mutation was identified. Luciferase reporter assay indicated that the g.8795C>T mutation influenced PLAG1 post-transcriptional activity. miRBase prediction showed that the g.8795C>T mutation was located in the miR-139 seed sequence binding region, and miR-139 overexpression significantly decreased both PLAG1-CC and PLAG1-TT activities. Moreover, the luciferase activity of PLAG1-CC was significantly lower than that of the PLAG1-TT, but miR-139 inhibition substantially increased both PLAG1-CC and PLAG1-TT luciferase activities, suggesting that PLAG1 is the target gene of miR-139. Thus, the g.8795C>T mutation upregulates PLAG1 expression by weakening its binding with miR-139, promoting PLAG1 expression, and increasing Hu sheep birth and weaning weights.

Diprenylated flavonoids from licorice induce death of SW480 colorectal cancer cells by promoting autophagy: Activities of lupalbigenin and 6,8-diprenylgenistein.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is a well-known herbal medicine, and we previously found that several licorice prenylated flavonoids could cause death of SW480 colorectal cancer cells by promoting autophagy. Given many kinds of prenylated flavonoids in licorice, the activities of other compounds deserve further investigation. In addition, the contribution of isoprenyl groups on the autophagy promotion activities has not been clarified. AIM OF THE STUDY: This study aimed to investigate whether lupalbigenin (LPB) and 6,8-diprenylgenistein (DPG), two licorice diprenylated flavonoids, could induce autophagic cell death of SW480 cells, and clarify the contribution of isoprenyl groups. MATERIALS AND METHODS: Cytotoxic activities of LPB and DPG were tested by using an MTT method, and apoptosis induction effects were evaluated by PI-Annexin V staining-based flow cytometry and protein levels of caspase-3 and PARP-1. Autophagy promotion effects of LPB and DPG were assessed by protein levels of LC3, p62, Akt and mTOR as well as number of autophagosomes in cells, and autophagy inhibitor chloroquine (CQ) was involved to identify the role of autophagy on LPB or DPG-caused death of SW480 cells. In addition, two groups of structurally similar diprenylated, mono-prenylated and free flavonoids were obtained from licorice, which were used to investigate the contribution of isoprenyl groups on their autophagy promotion activities. RESULTS: Both LPB and DPG significantly induced apoptosis of SW480 cells with strong cytotoxic activities, and meanwhile, they also promoted autophagy probably through the Akt/mTOR signaling pathway. Further studies indicated that LPB and DPG could induce autophagic cell death of SW480 cells. Moreover, isoprenyl groups contributed mainly to the cytotoxic and autophagy promotion activities of licorice prenylated flavonoids. CONCLUSION: This study reported for the first time that licorice diprenylated flavonoids LPB and DPG induced death of SW480 cells by promoting autophagy, which was mainly attributed to the isoprenyl groups. The results provided theoretical basis for researches on anti-colorectal cancer drugs and their structural modification.

Cervical Carcinoma: Evaluation Using Diffusion MRI With a Fractional Order Calculus Model and its Correlation With Histopathologic Findings.

Objective: The objective of the study is to investigate the feasibility of using the fractional order calculus (FROC) model to reflect tumor subtypes and histological grades of cervical carcinoma. Methods: Sixty patients with untreated cervical carcinoma underwent multi-b-value diffusion-weighted imaging (DWI) at 3.0T magnetic resonance imaging (MRI). The mono-exponential and the FROC models were fitted. The differences in the histological subtypes and grades were evaluated by the Mann-Whitney U test. Receiver operating characteristic (ROC) analyses were performed to assess the diagnostic performance and to determine the best predictor for both univariate analysis and multivariate analysis. Differences between ROC curves were tested using the Hanley and McNeil test, while the sensitivity, specificity, and accuracy were compared using the McNemar test. P-value <0.05 was considered as significant difference. The Bonferroni corrections were applied to reduce problems associated with multiple comparisons. Results: Only the parameter ß, derived from the FROC model could differentiate cervical carcinoma subtypes (P = 0.03) and the squamous cell carcinoma (SCC) lesions exhibited significantly lower ß than that in the adenocarcinoma (ACA) lesions. All the individual parameters, namely, ADC, ß, D, and µ derived from the FROC model, could differentiate low-grade cervical carcinomas from high-grade ones (P = 0.022, 0.009, 0.004, and 0.015, respectively). The combination of all the FROC parameters showed the best overall performance, providing the highest sensitivity (81.2%) and AUC (0.829). Conclusion: The parameters derived from the FROC model were able to differentiate the subtypes and grades of cervical carcinoma.

Ras guanine nucleotide-releasing protein-4 promotes renal inflammatory injury in type 2 diabetes mellitus.

INTRODUCTION: Ras guanine nucleotide-releasing protein-4 (RasGRP4) is an activator of Ras protein, which plays significant roles in both the inflammatory response and immune activation. This study determined the role of RasGRP4 in diabetic kidney disease (DKD) progression. METHODS: CRISPR/Cas9 technology was used to establish RasGRP4 knockout (KO) mice. Diabetes was induced by a high-fat diet combined with five consecutive daily intraperitoneal injections of streptozotocin (60 mg/kg) in C57BL/6J wild-type (WT) mice and RasGRP4 KO mice. Hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining were used to observe the histology of pathological injury. Immunohistochemical staining was used to analyze inflammatory cell infiltration. Quantitative PCR and Western blotting were used to detect the expression of inflammatory mediators and the activation of signaling pathways in renal tissues. In vitro cell co-culture experiments were performed to explore the interactions between peripheral blood mononuclear cells (PBMCs) and glomerular endothelial cells (GEnCs). RESULTS: RasGRP4 KO mice developed less severe diabetic kidney injury compared to WT mice, exhibiting lower proteinuria, reduced CD3+ T lymphocyte and F4/80+ macrophage infiltration, less inflammatory mediator expression including interleukin 6, tumor necrosis alpha, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, and lower expression levels of critical signal transduction molecules in the NLR family pyrin domain-containing 3 inflammasome and mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) signaling pathways in the diabetic kidney. In vitro experiments showed that the adhesion function of PBMCs of RasGRP4 KO mice was reduced compared to that of WT mice. Moreover, the expression of adhesion molecules and critical signal transduction molecules in the NLRP3 inflammasome and MAPK/NF-κB signaling pathways in GEnCs was stimulated by the supernatant of PBMCs, which were derived from RasGRP4 KO mice treated with high glucose and were also significantly reduced compared to those derived from WT mice. CONCLUSION: RasGRP4 promotes the inflammatory injury mediated by PBMCs in diabetes, probably by regulating the interaction between PBMCs and GEnCs and further activating the NLRP3 inflammasome and MAPK/NF-κB signaling pathways.

Discovery and Characterization of Intercondylar Transphyseal Complexes and their Oncological Significance in Transphyseal Extension of Pediatric Osteosarcoma.

OBJECTIVE: To explore whether there exist undiscovered transphyseal vasculature-canal compound structures in immature femurs and tibias, and reveal their potential oncological impact. METHODS: This investigation was divided into a morphological study and a clinical study. In the morphological part, a new-identified anatomic structure was investigated by using radiographical, anatomical, and histological methodologies. Twenty-eight 1-mm-slice thickness magnetic resonance images of pediatric knees were generated and 10 pediatric knees were dissected to verify the existence and universality, observe the radiographic and anatomic characteristics, and determined the located region of this structure. Hematoxylin-eosin staining, immunofluorescence, and angiography procedures were performed to illustrate its histological feature, molecular identification, and vascular origination, respectively. In the clinical part, 38 pediatric osteosarcoma patients were enrolled from January 2014 to December 2020. A descriptive clinical study including 13 typical participants was conducted to investigate the oncological significance of this new-identified structure. Meanwhile, the discrepancy in transphyseal osteosarcoma extension between different physeal regions was evaluated in a cross-sectional study. RESULTS: In the morphological study, we discovered a new-found vasculature-canal compound structure, intercondylar transphyseal complex (ITC), which originated from the middle genicular vessels, traversed the whole epiphysis, and breached the intact open physis in the immature proximal tibia or distal femur. The components of ITC included the juxta-articular, epiphyseal, and transphyseal segments of vessels, the canals that traverse the entire epiphysis and physis and enclosed the vessels, vascular foramina on articular facet and foramina-covered synovium. Depending on the location, ITCs can be divided into three types: femoral ITC, anterior tibial ITC, and posterior tibial ITC. Clinically, the ITC may facilitate intercondylar transphyseal sarcomatous dissemination without damaging the adjacent physeal cartilage. Compared to bilateral condylar physes, more osteosarcomas transgressed the open growth plates through intercondylar regions in which ITC was located (P = 0.022). CONCLUSION: As the "gap" on intact open physis, ITC, which is a new-identified compound structure in intercondylar regions of immature femur or tibia, may promote intercondylar transphyseal tumor extension. Moreover, the identification and characterization of ITC subvert some traditional comprehensions about physis and may provide novel perspectives for pediatric osteosarcomas.

Retraction: Analysis of risk factors and countermeasures of sepsis-associated encephalopathy.

The paper entitled "Analysis of risk factors and countermeasures of sepsis-associated encephalopathy" by YU et al., which was published online on October 15, 2021, has been withdrawn by the Publisher upon request by the authors. Their recent studies found that some data used in this paper could not be replicated in their latest studies and, as a result, they now have doubts about the accuracy of the published results.

circAMOTL1L Suppresses Renal Cell Carcinoma Growth by Modulating the miR-92a-2-5p/KLLN Pathway.

Accumulating evidence indicates that the dysregulation of circular RNAs (circRNAs) contributes to tumor progression; however, the regulatory functions of circRNAs in renal cell carcinoma (RCC) remain largely unknown. In this study, the function and underlying mechanism of circAMOTL1L in RCC progression were explored. qRT-PCR showed the downregulation of circAMOTL1L in RCC tissues and cell lines. The decrease in circAMOTL1L expression correlated with the tumor stage, metastasis, and poor prognosis in patients with RCC. Functional experiments revealed that circAMOTL1L inhibited cell proliferation and increased apoptosis in RCC cells. Subcutaneous implantation with circAMOTL1L-overexpressing cells in nude mice decreased the growth ability of the xenograft tumors. Mechanistically, circAMOTL1L served as a sponge for miR-92a-2-5p in upregulating KLLN (killin, p53-regulated DNA replication inhibitor) expression validated by bioinformatics analysis, oligo pull-down, and luciferase assays. Further, reinforcing the circAMOTL1L-miR-92a-2-5p-KLLN axis greatly reduced the growth of RCC in vivo. Conclusively, our findings demonstrate that circAMOTL1L has an antioncogenic role in RCC growth by modulating the miR-92a-2-5p-KLLN pathway. Thus, targeting the novel circAMOTL1L-miR-92a-2-5p-KLLN regulatory axis might provide a therapeutic strategy for RCC.

Clinical characteristics of magnetic foreign body misingestion in children.

Magnetic foreign body misingestion (MFBM) is now occurring more frequently. It may cause remarkable mortality and morbidity in children. A retrospective analysis of the clinical data of children admitted to Xiamen Children's Hospital between March 2017 and July 2020 due to accidental MFBM. A total of 14 children who had MFBM were collected, the proportion between urban and rural areas was 8:6, and the ratio of male to female was 6:1. The age ranged from 1.2 to 8.9 years (median 4.6 years). The number of magnetic foreign bodies ingested by mistake is 1 to 17 (average 6.5). Magnetic foreign objects are divided into magnets (3 cases) + magnetic beads (11 cases). About 40% (5/14) of this patient series showed no available misingestion history. Management includes: 4 cases of open surgery (including 1 case of laparoscopic transfer to operation), 3 cases of laparoscopic surgery, 2 cases of gastroscopy, 5 cases of conservative treatment of foreign bodies discharged through the anus. Of the 7 surgical cases, 6 cases presented with intestinal obstruction and intestinal perforation (at least 1 intestinal perforation and at most 5). Abdominal sonography has limitations in the detection of magnetic foreign bodies in the digestive tract. The proportion of laparoscopic surgery in the 7 surgical cases is nearly half. All surgical cases recovered smoothly after treatment. Our experience shows that MFBM is a big issue for the small children! The early symptoms of MFBM are often atypical especially among young children and MFBM may lead to severe adverse events. We proposed a management strategy for MFBM in children. We advise pediatricians/emergency physicians, parents/children's guardians and society should raise the collaborated alertness of MFBM. Global awareness of risk prevention of magnetic material accidental ingestion cannot be overemphasized.

Increased ADAM12 Expression Predicts Poor Prognosis in Cervical Cancer Patients before General Anesthesia.

BACKGROUND: The current study aims to investigate the expression and diagnostic value of ADAM12 in patients with cervical cancer before general anesthesia. METHODS: Seventy-eight cases of cervical cancer patients were included in the present study. RT-PCR and western blot were used to detect the expression of ADAM12 in cervical cancer tissues and adjacent tissues. Meanwhile, the expression of secretory ADAM12 in serum of cervical cancer patients and healthy people was detected by ELISA. The relationship between ADAM12 expression and prognosis of cervical cancer patients was analyzed. ROC analysis was carried out to explore the diagnostic value of ADAM12. RESULTS: Our data showed that the expression of ADAM12 mRNA and protein in cervical cancer tissues was significantly up-regulated compared with the adjacent tissues. ELISA assay showed that the content of ADAM12 in serum of cervical cancer patients was significantly higher than that of healthy people. Furthermore, ADAM12 expression was closely related to tumor invasion, TNM stage, lymph node metastasis and tumor differentiation. Kaplan-Meier survival analysis showed that the overall survival rate of patients with high ADAM12 was significantly lower than that of patients with low ADAM12 expression. The AUC of ADAM12, CEA, CA125, and SCC for cervical cancer was 0.893, 0.510, 0.769 and 0.550, respectively, while the highest value of AUC was 0.946 by the combination of the four indexes. CONCLUSIONS: In summary, increased expression of ADAM12 in cervical cancer patients can be used as an independent prognostic marker.

Role of MicroRNA, LncRNA, and Exosomes in the Progression of Osteoarthritis: A Review of Recent Literature.

Osteoarthritis (OA) is a common clinical degenerative disease characterized by the destruction of articular cartilage, which has an increasing impact on people's lives and social economy. The pathogenesis of OA is complex and unclear, and there is no effective way to block its progress. The study of the pathogenesis of OA is the prerequisite for the early diagnosis and effective treatment of OA. To define the pathogenesis of OA, this review considers the pathological mechanism of OA that involves microRNA, lncRNA, and exosomes. More and more evidence shows that microRNA, lncRNA, and exosomes are closely related to OA. MicroRNA inhibits the target gene by binding to the 3'- untranslated region of the targets. LncRNA usually competes with microRNA to regulate the expression level of downstream genes, while exosomes, as a carrier of intercellular information transfer, transmit the biological information of mother cells to target cells, and the effect of exosomes secreted by different cells on OA are different. In this review, we emphasized that different microRNA, lncRNA, and exosomes have different regulatory effects on chondrocyte proliferation and apoptosis, extracellular matrix degradation and inflammation. Besides, we classified and analyzed these molecules according to their effects on the progress of OA. Based on the analysis of the reported literature, this review reveals some pathogenesis of OA, and emphasizes that microRNA, lncRNA, and exosomes have great potential to assist early diagnosis and effective treatment of OA.

Fruit and vegetable intake and liver cancer risk: a meta-analysis of prospective cohort studies.

The associations of vegetable and fruit intake with liver cancer risk have been inconsistent based on epidemiological studies. The present study aimed to quantitatively evaluate these associations with prospective cohort studies. A systematic literature search was performed with PubMed and Scopus databases up to June 2019. Multivariate-adjusted relative risks (RRs) with a corresponding 95% confidence interval (CI) for the highest versus lowest category were pooled by using a random-effects model. Pre-specified subgroup and univariate meta-regression analyses were performed to identify the sources of heterogeneity. Dose-response analysis was conducted by using the variance weighted least squares regression model. Nine independent prospective cohort studies with 1703 liver cancer events and 1 326 176 participants were included for data synthesis. The summary estimates showed that higher vegetable intake was associated with a 39% (95%CI: 0.50, 0.75) reduction in liver cancer risk, with no significant between-study heterogeneity (P = 0.057). Dose-response analysis indicated that the risk of liver cancer was reduced by 4% (95%CI: 0.97, 0.95; P for trend <0.001) with a 100 gram per day increment of vegetable intake. Subgroup analysis showed that higher intakes of vegetables were associated with a 50% (95%CI: 0.35, 0.72) reduction of liver cancer risk in males, but not in females. However, a non-significant association was found between fruit intake and liver cancer risk. The present study provides strong evidence that higher intakes of vegetables would have beneficial effects on the prevention of liver cancer, especially for males.

Core needle biopsy as an alternative to whole section in IHC4 score assessment for breast cancer prognostication.

AIMS: IHC4 score, based on expression of four routine markers (oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker, Ki67), is a recently developed, cost-effective prognostic tool in breast cancer. Possibly, the score may be useful also in advanced diseases where only core needle biopsy (CNB) is available and neoadjuvant therapy. However, its studies on CNB are scant. This study examined whether IHC4 score assessment on CNB is comparable to that from whole section (WS). METHODS: Immunohistochemical (IHC) analysis was performed for ER, PR, HER2 and Ki67 on 108 paired CNB and WS to evaluate IHC4 score (with follow-up range 1-230 months and 5 relapse/death). Concordance between the two was examined. Factors that affected the concordance were analysed. Additionally, IHC4 score was compared with Nottingham Prognostic Index (NPI). RESULTS: There was moderate concordance between IHC4 score on CNB and WS (all cases: κ=0.699, p<0.001; ER+ cases: κ=0.595, p<0.001). Among the IHC4 components, concordance for HER2 was the poorest (κ=0.178, p<0.001 in all cases; ER+ cases: κ=0.082, p<0.097). Significant factors affecting concordance between CNB and WS included number of cores, total core length and percentage of tumour cells in cores (p≤0.030), indicating the importance of sufficient sampling. Interestingly, the concordance was also affected by patients' age (p=0.039). There was poor agreement between IHC4 score and NPI (κ≤0.160). CONCLUSION: Our results suggested that IHC4 score can be used on adequately sampled CNB. Its poor agreement with NPI highlights the independence of the two factors.

Reduced expression of Nrdp1 predicts a poor prognosis in human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive form of liver cancer with particularly poor survival rates for patients. Targeted molecular therapies are lacking, and current treatment is generally limited to surgical resection or liver transplantation. Overexpression and aberrant signaling of the ErbB family of receptors has been implicated in HCC, but the mechanisms underlying ErbB overexpression are unclear. In this study, we investigated the potential role of neuregulin receptor degradation protein-1 (Nrdp1), a regulator of ErbB3 protein stability, in HCC progression. METHODS: We compared the expression of Nrdp1 in various HCC cell lines and in 8 pairs of tumor and peritumor tissue samples using Western blot analysis. Changes in the degree of proliferation were determined before and after small interfering RNA (siRNA)-induced knockdown of Nrdp1 using a cell counting Kit-8 (ccK-8) assay and cell-cycle analysis. The correlation between Nrdp1 expression and prognosis was determined in specimens of 89 HCC patients. RESULTS: Nrdp1 expression is significantly reduced in HCC tissues compared with adjacent healthy tissues. Higher Nrdp1 expression corresponds to lower maximal tumor size (χ2, P<0.05), lower histological grade (χ2, P<0.05), and higher survival rates by Kaplan-Meier estimate (P<0.05). Higher Nrdp1 expression also corresponds to reduced expression of Ki-67, a marker of cell proliferation (Spearman, r2=0.734; P<0.05). Nrdp1 accumulates in serum-starved HepG2 cancer cells and progressively decreases in expression after re-feeding. Furthermore, depletion of Nrdp1 in healthy L02 cells by siRNA results in enhanced cell proliferation and a greater proportion of cells in S phase. CONCLUSIONS: Our findings suggest an inhibitory role for Nrdp1 in HCC tumorigenesis, and we propose that Nrdp1 may serve as a prognostic biomarker for HCC and as a potential therapeutic target for the treatment of HCC.