Prognostic nomogram in patients with right-sided colon cancer after colectomy: a surveillance, epidemiology, and end results-based study.

Objective: This study aimed to develop and validate a nomogram for predicting overall survival (OS) in patients undergoing surgery for right-sided colon cancer (RCC). Methods: We collected 25,203 patients with RCC from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided them into 7:3 training and internal validation set. Utilizing the Cox proportional hazards regression model, we constructed a nomogram based on prognostic risk factors. Furthermore, for external validation, we retrospectively followed up with 228 patients from Jiaxing First Hospital and assessed and calibrated the nomogram using the C-index and calibration curves. Results: After identifying independent prognostic factors through univariate and multivariate analyses, a nomogram was developed. The c-index values of this nomogram differed as follows: 0.851 (95% CI: 0.845-0.857) in the training set, 0.860 (95% CI: 0.850-0.870) in the internal validation set, and 0.834 (95% CI: 0.780-0.888) in the external validation set, indicating the model's strong discriminative ability. Calibration curves for 1-year, 3-year, and 5-year overall survival (OS) probabilities exhibited a high level of consistency between predicted and actual survival rates. Furthermore, Decision Curve Analysis (DCA) demonstrated that the new model consistently outperformed the TNM staging system in terms of net benefit. Conclusion: We developed and validated a survival prediction model for patients with RCC. This novel nomogram outperforms the traditional TNM staging system and can guide clinical practitioners in making optimal clinical decisions.

High expression of CDKN2A is associated with poor prognosis in colorectal cancer and may guide PD-1-mediated immunotherapy.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Immunotherapy targeting the programmed death protein 1(PD-1) and its ligand (PD-L1), is a promising treatment option for many cancers, but has exhibited poor therapeutic efficacy in CRC. This study aimed to identify and validate the prognostic value of immune-related genes and PD-1-associated genes for immunotherapy treatment of CRC. METHODS: An extensive analysis of prognostic immune-related DEGs and PD-1-related genes has highlighted CDKN2A as a vital overlapping gene. To further explore its expression in CRC and its prognostic value, we conducted qRT-PCR, Western blot experiments, and consulted various databases. Subsequently, we conducted gene expression analysis, survival and prognostic analysis, enrichment analysis, immune infiltration assessment, and TIDE analysis to assess the significance of CDKN2A. RESULTS: In CRC, CDKN2A was highly expressed compared to normal tissue. It was found that CDKN2A expression was related to clinicopathological features such as inflammation and tumor stage. Furthermore, a significant correlation was identified between CDKN2A and immune infiltration, specifically involving CD4 T cells, CD8 T cells, and macrophages. The analysis of the GSEA of CRC samples with high CDKN2A expression identified enrichment of genes involved in MYC target-v2 and metabolism pathways. Furthermore, UBE2I, CDK4, CDK6, TP53, and CCND1 were found to be significantly coexpressed with CDKN2A, suggesting a potential role that these gene play in CRC and immunotherapy. CONCLUSIONS: Our study revealed that high CDKN2A expression in CRC is a potentially valuable prognostic biomarker, which may guide PD-1-mediated immunotherapy.

Case report of hepatic retiform hemangioendothelioma: A rare tumor treated with ultrasound-guided microwave ablation.

Retiform hemangioendothelioma (RH) is a type of low-grade malignant angiosarcoma. It commonly involves the skin and subcutaneous tissue of the lower extremities, but a few cases have been reported in the gut. However, hepatic RH has not been previously reported. This report presents the case of RH of the liver in a 61-year-old woman who was admitted to the hospital having presented with liver space-occupying lesions of 2 months evolution. The patient underwent an abdominal ultrasound examination, which indicated a hemangioma, but abdominal computed tomography diagnosed a liver abscess. In order to determine the nature of the lesion, an ultrasound-guided liver biopsy was performed, after which a pathological diagnosis confirmed the presence of RH in the liver. The patient underwent ultrasound-guided microwave ablation three times and has been followed up for 8 years with no tumor recurrence or metastasis. Surgical excision is still the first choice for the treatment of hepatic RH. As shown in this case, however, for patients who refuse to undergo surgery or have surgical contraindications, ultrasound-guided microwave ablation is an alternative treatment option. The report of this case expands the scope of liver tumors to a certain extent and provides a reference for clinical diagnosis and treatment.

[Mechanism of essential oil from Schizonepeta tenuifolia in treatment of depression based on network pharmacology and experimental verification].

This paper aimed to explore the antidepressant effect of the essential oil from Schizonepeta tenuifolia Briq.(EOST) on the treatment of depression and its mechanism by using a combination of network pharmacology and the mouse model of lipopolysaccharide(LPS)-induced depression. The chemical components in EOST were identified using gas chromatography-mass spectrometer(GC-MS), and 12 active components were selected as the study objects. The targets related to EOST were obtained by Traditional Chinese Medicines Systems Pharmacology(TCMSP) and SwissTargetPrediction database. The targets related to depression were screened out through GeneCards, Therapeutic Target Database(TTD), and Online Mendelian Inheritance in Man(OMIM) database. The Venny 2.1 was applied to screen out the common targets of EOST and depression. The targets were imported into Cytoscape 3.7.2 to generate "drug-active component-diease-target" network diagram. The protein-protein interaction(PPI) network was constructed using STRING 11.5 database and Cytoscape 3.7.2, and the core targets were screened out. DAVID 6.8 database was used for Gene Ontology(GO) func-tional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and subsequently the enrichment results were visualized through the bioinformatics platform. The mouse model of depression was induced by intraperitoneally injecting with LPS in mice. Before modeling, mice were administrated orally with EOST. The antidepressant effect of EOST was evalua-ted by tail suspension test(TST), forced swimming test(FST), and novelty suppressed feeding test(NSFT) after modeling. The content of interleukin(IL)-1ß was determined by enzyme-linked immunosorbent assay(ELISA), and the protein expression levels of IL-1ß and pro IL-1ß in the hippocampus were determined by Western blot. There were 12 main components and 179 targets in EOAT, of which, 116 targets were related to depression, mainly involved in neuroactive ligand-receptor interaction, calcium signaling pathway, and cyclic adenosine monophosphate(cAMP) signaling pathway. Biological processes such as synaptic signal transduction, G-protein coupled receptor signaling pathway, and chemical synaptic transmission were involved. Molecular functions such as neurotransmitter receptor activity, RNA polymerase Ⅱ transcription factor activity, and heme binding were involved. In mice experiments, the results showed that EOST at 100 mg·kg~(-1) and 50 mg·kg~(-1) significantly shortened the immobility time in TST and FST as well as the feeding latency in NSFT compared with the model group, decreased the levels of serum IL-1ß and NO, and reduced the protein expression levels of IL-1ß and pro IL-1ß in the hippocampus. In conclusion, EOST shows a good antidepressant effect in a multi-component, multi-target, and multi-pathway manner. The mechanism may be attributed to the fact that EOST can down-regulate the protein expression levels of IL-1ß and pro IL-1ß, decrease the release of inflammatory factors, and reduce neuroinflammation response.

Genetic and Functional Analyses of the Novel KLF11 Pro193Thr Variant in a Three-Generation Family with MODY7.

KLF11 regulates insulin gene expression through binding to the insulin promoter and has been reported as a causative gene for maturity-onset diabetes of the young 7 (MODY7). Here, we report a novel KLF11 variant associated with a three-generation family with early childhood-onset diabetes and explore its clinical and functional characteristics. The three-generational pedigree contains five patients affected by diabetes. The pathogenic variant identified by whole-exome sequencing was further confirmed by Sanger sequencing and pedigree verification. Luciferase reporter assays and glucose-stimulated insulin secretion were used to examine whether the KLF11 variant binds to the insulin promoter and regulate insulin secretion in vitro. The proband, his son, and his uncle exhibited hyperglycemia at ages 32, 13 and 71 years, respectively. All three patients showed characteristics of metabolic syndrome (obesity, dyslipidemia, and diabetes), but the insulin secretion of islet ß-cells was impaired. A novel heterozygous missense variant, c.577 C>A (p.Pro193Thr) of the KLF11 gene was detected in all three patients. This variant co-segregates with the diabetes phenotype, consistent with an autosomal dominant disorder. The identified KLF11 p.Pro193Thr variant drastically decreased the transcriptional activity of KLF11, as demonstrated by luciferase reporter assay. Functional analyses revealed that the KLF11 Pro193Thr variant inhibited glucose-stimulated insulin secretion. We identified a novel KLF11 Pro193Thr variant in a three generation family with MODY7. These findings shed light on the molecular mechanisms underlying the pathogenesis of MODY7 and expand the genotype and clinical spectrum of MODY7.

Recent research advances in polysaccharides from Undaria pinnatifida: Isolation, structures, bioactivities, and applications.

Undaria pinnatifida, one of the most widespread seafood consumed in China and many other nations, has been traditionally utilized as an effective therapeutically active substance for edema, phlegm elimination and diuresis, and detumescence for more than 2000 years. Numerous studies have found that polysaccharides of U. pinnatifida play an indispensable role in the nutritional and medicinal value. The water extraction and alcohol precipitation method are the most used method. More than 40 U. pinnatifida polysaccharides (UPPs) were successfully isolated and purified from U. pinnatifida, whereas only few of them were well characterized. Pharmacological studies have shown that UPPs have high-order structural features and multiple biological activities, including anti-tumor, antidiabetic, immunomodulatory, antiviral, anti-inflammatory, antioxidant, anticoagulating, antithrombosis, antihypertension, antibacterial, and renoprotection. In addition, the structural characteristics of UPPs are closely related to their biological activity. In this review, the extraction and purification methods, structural characteristics, biological activities, clinical settings, toxicities, structure-activity relationships and industrial application of UPPs are comprehensively summarized. The structural characteristics and biological activities as well as the underlying molecular mechanisms of UPPs were also outlined. Furthermore, the clinical settings and structure-activity functions of UPPs were highlighted. Some research perspectives and challenges in the study of UPPs were also proposed.

Alpinetin: A Review of Its Pharmacology and Pharmacokinetics.

Flavonoids isolated from medicinal herbs have been utilized as valuable health-care agents due to their virous biological applications. Alpinetin is a natural flavonoid that emerges in many widely used medicinal plants, and has been frequently applied in Chinese patent drugs. Accumulated evidence has demonstrated that alpinetin possesses a broad range of pharmacological activities such as antitumor, antiinflammation, hepatoprotective, cardiovascular protective, lung protective, antibacterial, antiviral, neuroprotective, and other properties through regulating multiple signaling pathways with low systemic toxicity. However, pharmacokinetic studies have documented that alpinetin may have poor oral bioavailability correlated to its extensive glucuronidation. Currently, the reported pharmacological properties and pharmacokinetics profiles of alpinetin are rare to be scientifically reviewed. In this article, we aimed to highlight the mechanisms of action of alpinetin in various diseases to strongly support its curative potentials for prospective clinical applications. We also summarized the pharmacokinetics properties and proposed some viable strategies to convey an appreciable reference for future advances of alpinetin in drug development.

Effect of Tongluozhitong Prescription-Assisted Intra-Articular Injection of Sodium Hyaluronate on VAS Score and Knee Lysholm Score in Patients with Knee Osteoarthritis.

Knee osteoarthritis (KOA) has become one of the leading causes of workforce loss in the middle-aged and elderly population and a global public health problem second only to cardiovascular disease, so we need to find more effective treatments for this disease. In this study, we selected 120 patients with KOA admitted to our hospital from June 2018 to December 2020 and divided them into treatment group 1, treatment group 2, and joint group according to the random number table method, with 40 patients in each group. Treatment group 1 was treated with Tongluozhitong prescription dip-soaking therapy, treatment 2 group was treated with intra-articular injection of sodium hyaluronate, and the joint group was treated with a combination of both modalities for 4 weeks in all three groups. Clinical efficacy, visual analogue scale (VAS), Lysholm knee score (LKS), activity of daily living score (ADL), the levels of bone metabolic markers such as cartilage oligomeric matrix protein (COMP), type II collagen degradation maker (CTX-II), and matrix metalloproteinase-3 (MMP-3), and the levels of inflammatory mediators such as interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and hypersensitive C-reactive protein (hs-CRP) were used as observations to compare and analyze the therapeutic effects of the three treatment regimens in KOA patients. The results showed that the clinical excellence rates of the joint group, treatment group 1, and treatment group 2 were 72.50%, 50.00%, and 90.00%, respectively, with statistically significant differences between any two comparisons. After treatment, VAS scores, serum COMP, CTX-II, MMP-3, IL-1ß, TNF-α, and hs-CRP levels decreased in all three groups, and the levels of each index were as follows: joint group < treatment group 1 < treatment group 2, and the difference between any two comparisons was statistically significant. The LKS score and ADL score increased in all three groups, and the levels of each index were as follows: joint group > treatment group 1 > treatment group 2, with statistically significant differences in any two groups compared. None of the patients in the three groups experienced any significant adverse effects during treatment. This suggests that the dip-soaking therapy of Tongluozhitong prescription is more advantageous than intra-articular sodium hyaluronate injection treatment in suppressing the level of serum bone metabolic markers and inflammatory mediators, reducing pathological joint damage, relieving symptoms of pain, alleviating degenerative joint symptoms, and improving knee function in KOA patients. The combination of the two in KOA patients can significantly improve the efficacy and has a good safety profile.

A Generic Nomogram Predicting the Stage of Liver Fibrosis Based on Serum Biochemical Indicators Among Chronic Hepatitis B Patients.

Introduction: Liver fibrosis staging is of great importance for reducing unnecessary injuries and prompting treatment in chronic viral hepatitis B patients. Liver biopsy is not suitable to act a screening method although it is a gold standard because of various shortcomings. This study aimed to establish a predictive nomogram as a convenient tool to effectively identify potential patients with different stages of liver fibrosis for patients with chronic hepatitis B. Methods: A nomogram for multinomial model was developed in a training set to calculate the probability for each stage of fibrosis and tested in a validation set. Fibrosis stages were subgrouped as followed: severe fibrosis/cirrhosis (F3-F4), moderate fibrosis (F2), and nil-mild fibrosis (F0-F1). The indicators were demographic characteristics and biochemical indicators of patients. Continuous indicators were divided into several groups according to the optimal candidate value generated by the decision tree. Results: This study recruited 964 HBV patients undergoing percutaneous liver biopsy. The multinomial model with 10 indicators was transformed into the final nomogram. The calibration plot showed a good agreement between nomogram-predicted and observed probability of different fibrosis stages. Areas under the receiver operating characteristics (AUROCs) for severe fibrosis/cirrhosis were 0.809 for training set and 0.879 for validation set. For moderate fibrosis, the AUROCs were 0.75 and 0.781. For nil-mild fibrosis, the AUROCs were 0.792 and 0.843. All the results above showed great predictive performance in predicting the stage of fibrosis by our nomogram. Conclusion: Our model demonstrated good discrimination and extensibility in internal and external validation. The proposed nomogram in this study resulted in great reliability and it can be widely used as a convenient and efficient way.

Luteolin combined with low-dose paclitaxel synergistically inhibits epithelial-mesenchymal transition and induces cell apoptosis on esophageal carcinoma in vitro and in vivo.

Although paclitaxel is a promising frontline chemotherapy agent for various malignancies, the clinical applications have been restricted by side effects, drug resistance, and cancer metastasis. The combination of paclitaxel and other agents could be the promising strategies against malignant tumor, which enhances the antitumor effect through synergistic effects, reduces required drug concentrations, and also suppresses tumorigenesis in multiple ways. In this study, we found that luteolin, a natural flavonoid compound, combined with low-dose paclitaxel synergistically regulated the proliferation, migration, epithelial-mesenchymal transition (EMT), and apoptosis of esophageal cancer cells in vitro, as well as synergistically inhibited tumor growth without obvious toxicity in vivo. The molecular mechanism of inhibiting cell migration and EMT processes may be related to the inhibition of SIRT1, and the mechanism of apoptosis induction is associated with the reactive oxygen species (ROS)/c-Jun N-terminal kinase (JNK) pathway-mediated activation of mitochondrial apoptotic pathway.

Sox2 controls asymmetric patterning of ameloblast lineage commitment by regulation of FGF signaling in the mouse incisor.

Mouse incisors are covered by enamel only on the labial side and the lingual side is covered by dentin without enamel. This asymmetric distribution of enamel makes it possible to be abrased on the lingual side, generating the sharp cutting edge of incisor on the labial side. The abrasion of mouse incisors is compensated by the continuous growth throughout life. Epithelium stem cells responsible for its continuous growth are reported to localize within the labial cervical loop. The transcription factor Sox2 plays important roles in the maintenance of stem cell pluripotency and organ formation. We previously found that Sox2 mainly expressed in the dental epithelium. Besides, Sox2 has been reported to be a dental epithelium stem cell marker in the incisor. However, the exact mechanism of Sox2 controlling amelogenesis is still not quite clearly elucidated. Here we report that conditional deletion of Sox2 in the dental epithelium using Shhcre caused impaired ameloblast differentiation in the labial side and induced ectopic ameloblast-like cell differentiation on the lingual side. Abnormal FGF gene expression was detected by RNAscope in situ hybridization in the mutant incisor. Collectively, we speculate that asymmetric ameloblast lineage commitment of mouse incisor might be regulated by Sox2 through FGF signaling.

Activities of daily living, life orientation, and health-related quality of life among older people in nursing homes: a national cross-sectional study in China.

PURPOSE: This study aimed to explore the current status of activities of daily living (ADLs), life orientation, and health-related quality of life (HRQoL) among older people in nursing homes and to further examine the mediating role of life orientation in the impact of ADLs on HRQoL. METHODS: A national cross-sectional study was conducted among older people aged 60 and above in nursing homes by the randomly stratified cluster sampling method. The status of ADLs, life orientation and HRQoL were measured using an ADL scale, a life orientation scale and the SF-12v2 scale, respectively. Multiple linear regression models were used to identify explanatory factors associated with ADLs, life orientation, and HRQoL. The potential mediating role of life orientation in the relationship between ADL and HRQoL was explored by mediation analysis. RESULTS: The overall prevalence of ADL disability was 52.67%, and 84.37% of older people in nursing homes had a negative life orientation. The mean scores of physical health and mental health among older people in nursing homes were 45.44 ± 6.46 and 42.67 ± 8.48, respectively. Some sociodemographic characteristics were associated with poor physical health and mental health. After adjustments were made for covariates, the life orientation score mediated 13.81% of the total effect of the ADL score on physical component score of HRQoL and mediated 45.33% of the mental component score of HRQoL. CONCLUSION: A sizeable proportion of older people had ADL disability and negative life orientation, and HRQoL was poor among older Chinese people in nursing homes. Life orientation partially mediates the relationship between ADLs and HRQoL.

Long-term clinical prognosis of human infections with avian influenza A(H7N9) viruses in China after hospitalization.

BACKGROUND: Mainland China has experienced five epidemics of human cases of avian influenza A(H7N9) virus infection since 2013. We conducted a prospective study to assess long-term clinical, pulmonary function testing, and chest computed tomography (CT) imaging findings after patients were discharged from hospital. METHODS: A(H7N9) survivors in five provinces and one municipality underwent follow-up visits from August 2013 to September 2018, at three, six, and 12 months after illness onset, and a subset was also assessed at 18 and 64 months after onset. Thirteen patients were enrolled from the first A(H7N9) epidemic in 2013, 36 from the 2013-2014 second epidemic, and 12 from the 2016-2017 fifth epidemic. At each visit, A(H7N9) survivors received a medical examination, including the mMRC (modified Medical Research Council) dyspnea scale assessment, chest auscultation, pulmonary function testing and chest CT scans. FINDINGS: The median age of 61 A(H7N9) survivors was 50 years. The cumulative rate of pulmonary dysfunction was 38·5% and 78·2% for chest CT scan abnormalities at the end of follow-up. Restrictive ventilation dysfunction was common during follow-up. Mild dyspnea was documented at three to 12-month follow-up visits. INTERPRETATION: Patients who survived severe illness from A(H7N9) virus infection had evidence of persistent lung damage and long-term pulmonary dysfunction. FUNDING: National Science Fund for Distinguished Young Scholars (grant number 81525023); Program of Shanghai Academic/Technology Research Leader (grant number 18XD1400300); National Science and Technology Major Project of China (grant numbers 2017ZX10103009-005, 2018ZX10201001-010).

Putative Digenic GJB2/MYO7A Inheritance of Hearing Loss Detected in a Patient with 48,XXYY Klinefelter Syndrome.

OBJECTIVES: Nonsyndromic hearing loss (NSHL) is the most frequent type of hereditary hearing impairment. Here, we explored the underlying genetic cause of NSHL in a three-generation family using whole-exome sequencing. The proband had concomitant NSHL and rare 48,XXYY Klinefelter syndrome. MATERIAL AND METHODS: Genomic DNA was extracted from the peripheral blood of the proband and their family members. Sanger sequencing and pedigree verification were performed on the pathogenic variants filtered by whole-exome sequencing. The function of the variants was analyzed using bioinformatics software. RESULTS: The proband was digenic heterozygous for p.V37I in the GJB2 gene and p.L347I in the MYO7A gene. The proband's mother had normal hearing and did not have any variant. The proband's father and uncle both had NSHL and were compound for the GJB2 p.V37I and MYO7A p.L347I variants, thus indicating a possible GJB2/MYO7A digenic inheritance of NSHL. 48,XXYY Klinefelter syndrome was discovered in the proband after the karyotype analysis, while his parents both had normal karyotypes. CONCLUSIONS: Our findings reported a putative GJB2/MYO7A digenic inheritance form of hearing loss, expanding the genotype and phenotype spectrum of NSHL. In addition, this is the first report of concomitant NSHL and 48,XXYY syndrome.

MiRNA Polymorphisms and Hepatocellular Carcinoma Susceptibility: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is an intractable public health threat worldwide, representing the second leading cause of cancer-related mortality, with limited early detection and therapeutic options. Recent findings have revealed that the susceptibility of HCC is closely related to microRNA (miRNA). We performed this systematic review with a network meta-analysis to investigated four single nucleotide polymorphisms (SNPs) that most regularly reported in miRNAs, exploring their involvement in HCC susceptibility and interaction with hepatitis B virus (HBV). METHODS: Databases were reviewed for related studies published up to May 2019 to identify all studies that compared genotypes of miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, and miR-499 rs3746444 with no language and date restrictions. A pairwise meta-analysis was performed to estimate pooled odds ratios and 95% confidence intervals incorporating heterogeneity to assess the relationship between four miRNA polymorphisms and HCC. To further clarify the effect of polymorphisms on HCC, a Bayesian network meta-analysis was conducted to combine the effective sizes of direct and indirect comparisons. Calculations were performed by R version 3.6.1 and STATA 14.0. All steps were performed according to PRISMA guidelines. RESULTS: A total of 20 studies were enrolled in this network meta-analysis, providing 5,337 hepatocellular carcinoma cases and 6,585 controls. All included studies had an acceptable quality. Pairwise meta-analysis demonstrated that miR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, while the other three SNPs were not found to have a significant association. In the analysis of HCC patients under different HBV infection status, only miR-196a2 revealed correlation of threefold risk. The network results showed no significant difference in the distribution of genotype frequencies except for miR-196a2, which appeared to have the highest superiority index when comparing and ranking four SNPs. CONCLUSION: MiR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, especially for HBV- related HCC, and that individuals with TC/CC were more susceptible. No significant association was found in the other three miRNA genes. MiR-196a2 could serve as the best predictor of susceptibility in HCC.

Performance of common imaging techniques vs serum biomarkers in assessing fibrosis in patients with chronic hepatitis B: A systematic review and meta-analysis.

BACKGROUND: Noninvasive biomarkers have been developed to predict hepatitis B virus (HBV) related fibrosis owing to the significant limitations of liver biopsy. Both serum biomarkers and imaging techniques have shown promising results and may improve the evaluation of liver fibrosis. However, most of the previous studies focused on the diagnostic effects of various imaging techniques on fibrosis in all chronic liver diseases. AIM: To compare the performance of common imaging methods and serum biomarkers for prediction of significant fibrosis caused only by HBV infection. METHODS: A systematic review was conducted on the records available in PubMed, EMBASE, and the Cochrane Library electronic databases until December 2018. We systematically assessed the effectiveness of two serum biomarkers and three imagine techniques in predicting significant fibrosis solely caused by HBV infection. The serum biomarkers included aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the 4 factors (FIB-4). The three imaging techniques included acoustic radiation force impulse (ARFI), FibroScan, and magnetic resonance elastography (MRE). Three parameters, the area under the summary receiver operating characteristic curve (AUSROC), the summary diagnostic odds ratio, and the summary sensitivity and specificity, were used to examine the accuracy of all tests for liver fibrosis. RESULTS: Out of 2831 articles evaluated for eligibility, 204 satisfied the predetermined inclusion criteria for this current meta-analysis. Eventually, our final data contained 81 studies. The AUSROCs of serum biomarkers of APRI and FIB-4 were both 0.75. For imaging techniques (ARFI, FibroScan, and MRE), the areas were 0.89, 0.83, and 0.97, respectively. The heterogeneities of ARFI and FibroScan were statistically significant (I 2 > 50%). The publication bias was not observed in any of the serum biomarkers or imaging methods. CONCLUSION: These five methods have attained an acceptable level of diagnostic accuracy. Imaging techniques, MRE in particular, demonstrate significant advantages in accurately predicting HBV-related significant fibrosis, while serum biomarkers are admissible methods.

Discovery of chalcone-modified estradiol analogs as antitumour agents that Inhibit tumour angiogenesis and epithelial to mesenchymal transition.

Angiogenesis plays an essential role in tumourigenesis and tumour progression, and anti-angiogenesis therapies have shown promising antitumour effects in solid tumours. 2-Methoxyestradiol (2ME2), an endogenous metabolite of estradiol, has been regarded as a potential antitumour agent mainly targeting angiogenesis. Here we synthesized a novel series of chalcones based on 2-methoxyestradiol and evaluated their potential activities against tumours. Compound 11e was demonstrated to have potent antiangiogenic activity. Further studies showed that 11e suppressed tumour growth in human breast cancer (MCF-7) xenograft models without obvious side effects. Evaluation of the mechanism revealed that 11e targeted the epithelial to mesenchymal transition (EMT) process in MCF-7 cells and inhibited HUVEC migration and then contributed to hindrance of angiogenesis. Thus, 11e may be a promising antitumour agent with excellent efficacy and low toxicity.

SIRT1 expression regulates the transformation of resistant esophageal cancer cells via the epithelial-mesenchymal transition.

Sirtuin1 (SIRT1) belongs to the mammalian sirtuin family and plays an important role in deacetylating histones and non-histones. SIRT1 is associated with tumor metastasis in several tumors. However, the effect of SIRT1 on the mechanism of metastasis in resistant esophageal cancer remains unclear. In this study, we demonstrated that increased migration and invasion in drug-resistant esophageal cancer cells (EC109/PTX, TE-1/PTX). Our experiments revealed that the selective SIRT1 inhibitor (EX527) significantly suppressed cells migrate and inhibited the occurrence of the epithelial-mesenchymal transition (EMT), thereby altering the invasiveness and metastatic potential of the esophageal cancer cell lines. In addition, we observed that the inhibition of SIRT1 could alter the expression of snail. In conclusion, these results indicate that SIRT1 may promote the transformation of tumor cells by inducing the EMT and may serve as a potential molecular target for the treatment of resistant esophageal cancer.

Selective anticancer activity of the novel steroidal dihydropyridine spirooxindoles against human esophageal EC109 cells.

A series of small-molecule compounds built on steroidal dihydropyridine spirooxindoles has been reported previously. In this study, the compound 5l showed strong anti-cancer activity, especially in the esophageal cancer. Three esophageal squamous cell lines and paclitaxel-resistant cell line were investigated. The results demonstrated that compound 5l was most efficient in the EC109 cells, induced cell apoptosis through elevation of cellular ROS levels, caused G2/M phase arrest and mitochondrial dysfunction. Further study confirmed that the mechanism of 5l in esophageal cancer treatment was related to the Bcl-2 family and caspase receptor-mediated apoptotic pathway.

Targeting the Bcl-2 family and P-glycoprotein reverses paclitaxel resistance in human esophageal carcinoma cell line.

Paclitaxel (PTX) is one of the most effective drugs used in the treatment of esophageal cancer, however, paclitaxel resistance represents a key limitation during the treatment process. In this study, we investigated the changes of Bcl-2 family members in the moderate paclitaxel-resistance of esophageal carcinoma EC109/PTX cells both in vitro and in vivo. Moreover, we evaluated the reversal effect using siRNAs and the recombinant inhibitor TW37 targeting Bcl-2, Bcl-XL and Mcl-1. Our findings show that downregulation of Bcl-2, Bcl-XL and Mcl-1 can significantly promote EC109/PTX cell apoptosis and reduce the EC109/PTX cell resistance index (RI). Furthermore, TW37 in combination with a P-gp inhibitor can synergistically reverse the paclitaxel resistance in EC109/PTX cells. These results suggest that targeting of the Bcl-2 family and P-gp is capable of reversing the resistance in EC109/PTX cells and the two-inhibitor combination may be a novel treatment strategy for resistant esophageal cancer.