Gastroprotective effects of Machilus zuihoensis Hayata bark against acidic ethanol-induced gastric ulcer in mice.

Background and aim: In traditional medicine, Machilus zuihoensis Hayata bark (MZ) is used in combination with other medicines to treat gastric cancer, gastric ulcer (GU), and liver and cardiovascular diseases. This study aims to evaluate the gastroprotective effects and possible mechanism(s) of MZ powder against acidic ethanol (AE)-induced GU and its toxicity in mice. Experimental procedure: The gastroprotective effect of MZ powder was analyzed by orally administering MZ for 14 consecutive days before AE-inducing GU. Ulcer index (UI) and protection percentage were calculated, hematoxylin and eosin staining and periodic acid-Schiff staining were performed, and gastric mucus weights were measured. The antioxidative, anti-inflammatory, and anti-apoptotic mechanisms, and possible signaling pathway(s) were studied. Results and conclusion: Pretreatment with MZ (100 and 200 mg/kg) significantly decreased 10 µL/g AE-induced mucosal hemorrhage, edema, inflammation, and UI, resulted in protection percentages of 88.9% and 93.4%, respectively. MZ pretreatment reduced AE-induced oxidative stress by decreasing malondialdehyde level and restoring superoxide dismutase activity. MZ pretreatment demonstrated anti-inflammatory effects by reducing both serum and gastric tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß levels. Furthermore, MZ pretreatment exhibited anti-apoptotic effect by decreasing Bcl-2 associated X protein/B-cell lymphoma 2 ratio. The gastroprotective mechanisms of MZ involved inactivations of nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) and mitogen activated protein kinase (MAPK) signaling pathways. Otherwise, 200 mg/kg MZ didn't induce liver or kidney toxicity. In conclusion, MZ protects AE-induced GU through mucus secreting, antioxidative, anti-inflammatory, and anti-apoptotic mechanisms, and inhibitions of NF-κB and MAPK signaling pathways.

A national, multicenter, retrospective study of Castleman disease in China implementing CDCN criteria.

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.

A novel risk model for predicting early relapse in acute myeloid leukemia patients undergoing allogeneic hematopoietic stem-cell transplantation.

Relapse remains the leading cause of death in acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem-cell transplantation (allo-HSCT), limiting the efficacy of allo-HSCT. Thus, the ability to identify high-risk patients in a manner that permits early intervention has the potential to improve survival outcomes. We retrospectively enrolled 414 younger patients (aged 14-60 years) with AML who received allo-HSCT between January 2014 and May 2020. From June 2020 to June 2021, 110 consecutive patients were included prospectively in the validation cohort. The primary outcome was early relapse (relapse within 1 year). The cumulative incidence of early relapse after allo-HSCT was 11.8%. The overall survival rate for patients who relapsed within 1-year was 4.1% at 3 years after relapse. After multivariable adjustment, statistically significant associations between primary resistance, pre-transplantation measurable residual disease, DNMT3A mutation, or white blood cell count at diagnosis and early relapse were observed. An early relapse prediction model was developed based on these factors and the model performed well. Patients deemed to have a high risk or a low risk of early relapse had early relapse rates of 26.2% and 6.8%, respectively (P < 0.001). The prediction model could be used to help identify patients at risk for early relapse and to guide personalized relapse prevention.

Design, Synthesis, Insecticidal Activities and Molecular Docking of Sulfonamide Derivatives Containing Propargyloxy or Pyridine Groups.

The discovery of new highly active molecules from natural products is a common method to create new pesticides. Celangulin V targeting Mythimna separate (M. separate) midgut V-ATPase  H subunit, has received considerable attention for its excellent insecticidal activity and unique mechanism of action. Therefore, combined with our preliminary work, thirty-seven sulfonamide derivatives bearing propargyloxy or pyridine groups were systematically synthesized to search for insecticidal candidate compounds with low cost and high efficiency on the  H subunit of V-ATPase. Bioactive results showed that compounds A2-A4 and A6-A7 exhibited a better bioactivity with median effective concentration (LC50 ) values (2.78, 3.11, 3.34, 3.54 and 2.48 mg/mL, respectively) against third-instar larvae of M. separate than Celangulin V (LC50 =18.1 mg/mL). Additionally, molecular docking experiments indicated that these molecules may act on the H subunit of V-ATPase. Based on the above results, these compounds provide new ideas for the discovery of insecticides.

Comparable outcomes in patients with B-cell acute lymphoblastic leukemia receiving haploidentical hematopoietic stem cell transplantation: Pretransplant minimal residual disease-negative complete remission following chimeric antigen receptor T-cell therapy versus chemotherapy.

Introduction: Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy followed by haploidentical hematopoietic stem cell transplantation (haplo-HSCT) markedly improves the long-term survival of patients with refractory/relapsed (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Methods: We performed a parallel comparison of transplant outcomes in 168 B-ALL patients undergoing haplo-HSCT after achieving minimal residual disease (MRD)-negative complete remission (CR) from CAR-T therapy (n = 28) or chemotherapy (n = 140) between January 2016 and August 2021. We further divided the chemotherapy group into the first CR group (chemo+CR1, n = 118) and a second or more CR group (chemo+≥CR2, n = 22). Results: With a median follow-up period of 31.0 months, the 2-year overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM), and relapse rates in the CAR-T and chemotherapy groups did not differ significantly (OS, 87.9% vs. 71.5 %; LFS, 72.0% vs. 66.8%; NRM, 3.9% vs. 13.7%; relapse, 24.1% vs. 19.4%). Multivariate analysis confirmed that ≥CR2 at transplantation following chemotherapy was an independent risk factor associated with poor OS (hazard ratio (HR) 4.22 [95% CI, 1.34-13.293], p = 0.014) and LFS (HR 2.57 [95% CI, 1.041-6.343], p = 0.041). The probabilities of OS and LFS at 2 years in the CAR-T group were comparable to those in the chemo+CR1 group but significantly higher than those in the chemo+≥CR2 group (OS, 87.9% vs. 37.8%, p = 0.007; LFS, 72.0% vs. 41.7%, p = 0.043). No significant differences in the incidences of NRM were noted among the three groups. Conclusions: Our results demonstrated that patients with R/R B-ALL receiving haplo-HSCT after CAR-T therapy achieved comparable outcomes to patients transplanted post-chemotherapy-based MRD-negative CR1, without increased risk of transplant-related mortality and toxicity.

Association between Ultraviolet B Exposure Levels and Depression in Taiwanese Adults: A Nested Case-Control Study.

Depression is a common mental disorder that affects more than 264 million people worldwide. Anxiety, diabetes, Alzheimer's disease, myocardial infarction, and cancer, among other disorders, are known to increase the risk of depression. Exposure to ultraviolet B (UVB) can cause human serotonin levels to increase. The vitamin D pathway is one mechanism through which ultraviolet light absorbed through the skin can affect mood; however, UVB exposure is known to increase the risk of cancer. In this study, we explored the effects of prolonged exposure to UVB on depression. Data were retrieved from the Taiwan National Health Insurance Research Database for 2008 to 2013. Each patient with depression was matched 1:4 with a comparison patient by sex and age (±5 years); thus, the study included 23,579 patients with depression and 94,316 healthy controls for comparison. The patients had been exposed to UVB for at least 1 year to observe the cumulative effect of UVB exposure. Based on the World Health Organization UV index, we divided the observation period data into five UV levels: low, moderate, high, very high, and extreme. A multivariate Poisson regression model was used to assess the risk of depression according to UVB exposure level, adjusting for sex, age, income, urbanization level, month, and comorbidities. The results revealed that the incidence rate ratio (IRR) for patients with depression was 0.889 for moderate levels (95% CI 0.835-0.947), 1.134 for high levels (95% CI: 1.022-1.260), 1.711 for very high levels (95% CI: 1.505-1.945), and 2.785 for extreme levels (95% CI: 2.439-3.180) when compared to low levels. Moderate levels of UVB lowered the risk of depression, while high levels of UVB gradually increased the risk. We propose that UVB at normal concentrations can effectively improve depression. However, exposure to high concentrations of UVB damage DNA results in physical diseases such as skin cancer, which increase the risk of depression.

Recycled Poly(Ethylene Terephthalate) from Waste Textiles with Improved Thermal and Rheological Properties by Chain Extension.

Annual production of textile fibers is continuing to rise and the substantial discharge of undegradable waste polyester fibers can cause serious environmental and even health problems. Thus, the recycling and reuse of recycled poly(ethylene terephthalate) from waste textiles (rPET-F) is highly desirable but still challenging. Here, five chain extenders with a different number of epoxy groups per molecules were used to blend with discarded PET fibers and improve its viscosity and quality loss in the recycling process. The molecule weight, thermal properties, rheological properties and macromolecular architecture of modified r-PET were investigated. It was found that all modified rPET-F samples show higher viscosities and better thermal properties. rPET-F modified by difunctional EXOP molecules show linear structure and improved rheological properties. rPET-F modified by polyfunctional commercial ADR and synthesized copolymers exhibit a long chain branched structure and better crystallization. This study reveals a deeper understanding of the chain extension and opens an avenue for the recycling of PET textiles.

Predicting mortality in acute ischaemic stroke treated with mechanical thrombectomy: analysis of a multicentre prospective registry.

OBJECTIVES: We aimed to determine predictors of mortality within 90 days and develop a simple score for patients with mechanical thrombectomy (MT). DESIGN: Analysis of a multicentre prospective registry. SETTING: In six participating centres, patients who had an acute ischaemic stroke (AIS) treated by MT between March 2017 and May 2018 were documented prospectively. PARTICIPANTS: 224 patients with AIS were treated by MT. RESULTS: Of 224 patients, 49 (21.9%) patients died, and 87 (38.8%) were independent. Variables associated with 90-day mortality were age, previous stroke, admission National Institutes of Health Stroke Scale (NIHSS), fasting blood glucose and occlusion site. Logistic regression identified four variables independently associated with 90-day mortality: age ≥80 years (OR 3.26, 95% CI 1.45 to 7.33), previous stroke (OR 2.33, 95% CI 1.04 to 5.21), admission NIHSS ≥18 (OR 2.37, 95% CI 1.13 to 4.99) and internal carotid artery or basilar artery occlusion (OR 2.92, 95% CI 1.34 to 6.40). Using these data, we developed predicting 90-day mortality of AIS with MT (PRACTICE) score ranging from 0 to 6 points. The receiver operator curve analysis found that PRACTICE score (area under the curve (AUC)=0.744, 95% CI 0.669 to 0.820) was numerically better than iScore (AUC=0.661, 95% CI 0.577 to 0.745) and Predicting Early Mortality of Ischemic Stroke score (AUC=0.638, 95% CI 0.551 to 0.725) for predicting 90-day mortality. CONCLUSIONS: We developed a simple score to estimate the 90-day mortality of patients who had an AIS treated with MT. But the score needs to be prospectively validated. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR-OOC-17013052).

Combination treatment of Src inhibitor Saracatinib with GMI, a Ganoderma microsporum immunomodulatory protein, induce synthetic lethality via autophagy and apoptosis in lung cancer cells.

Saracatinib is an oral Src-kinase inhibitor and has been studied in preclinical models and clinical trials of cancer therapy. GMI, a fungal immunomodulatory protein from Ganoderma microsporum, possesses antitumor capacity. The aim of this study is to evaluate the cytotoxic effect of combination treatment with saracatinib and GMI on parental and pemetrexed-resistant lung cancer cells. Cotreatment with saracatinib and GMI induced synergistic and additive cytotoxic effect in A549 and A400 cells by annexin V/propidium iodide assay and combination index. Using western blot assay, saracatinib, and GMI combined treatment synergistically induced caspase-7 activation in A549 cells. Different from A549 cells, saracatinib and GMI cotreatment markedly increased LC3B-II in A400 cells. ATG5 silencing abolished the caspase-7 activation and reduced cell death in A549 cells after cotreatment. This is the first study to provide a novel strategy of treating lung cancer with or without drug resistance via combination treatment with GMI and saracatinib.

CORM-3 Regulates Microglia Activity, Prevents Neuronal Injury, and Improves Memory Function During Radiation-induced Brain Injury.

OBJECTIVE: This study aims to explore in detail, the mechanism of the carbon monoxide releasing molecule-3 (CORM-3) in regulating the activity of microglia (MG) in the treatment of radiation brain injury (RBI). METHODS: The brain injury models of BV2 cells and Balb/C mice were established and randomly divided into three groups: the normal control group (CON), the single radiation group (RAD), and the radiation plus CORM-3 intervention group (RAD+CORM). Immunofluorescence was used to observe the effects on activation of the MG. The expressions of inflammatory factors, such as intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS), were detected by Western blot. Neuron apoptosis and regeneration in the radiation brain injury (RBI) model were detected by neuronal nuclear antigen (NeuN)+TUNEL and NeuN+BrdU double staining. A Morris water maze was used to assess the spatial learning and memory of the mice. RESULTS: Within 48 h after radiation, CORM-3 inhibited activation of the MG, blocked the phosphorylation of P38, and increased the expression of ICAM-1 and iNOS. Therefore, CORM-3 might alleviate MG-mediated neuronal apoptosis and promote neural regeneration in the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. CORM-3 could increase the swimming distance and platform-stay time of the mice in the target platform quadrant after radiation. CONCLUSION: CORM-3 could effectively improve the inflammatory response induced by activation of the MG, reduce neuronal apoptosis, promote neural regeneration, and improve the learning and memory performance of mice after radiation.

CD133 inhibition via autophagic degradation in pemetrexed-resistant lung cancer cells by GMI, a fungal immunomodulatory protein from Ganoderma microsporum.

BACKGROUND: Adaptive drug resistance is an unfavourable prognostic factor in cancer therapy. Pemetrexed-resistant lung cancer cells possess high-metastatic ability via ERK-ZEB1 pathway-activated epithelial-mesenchymal transition. GMI is a fungal immunomodulatory protein that suppresses the survival of several cancer cells. METHODS: Cell viability was analysed by MTT, clonogenic, tumour spheroid, and cancer stem cell sphere assays. Western blot assay was performed to detect the protein expression. Chemical inhibitors and ATG5 shRNA were used to inhibit autophagy. Tumour growth was investigated using xenograft mouse model. RESULTS: GMI decreased the viability with short- and long-term effects and induced autophagy but not apoptosis in A549/A400 cells. GMI downregulated the expression levels of CD133, CD44, NANOG and OCT4. GMI induces the protein degradation of CD133 via autophagy. CD133 silencing decreased the survival and proliferation of A549/A400 cells. GMI suppressed the growth and CD133 expression of A549/A400 xenograft tumour. CONCLUSIONS: This study is the first to reveal the novel function of GMI in eliciting cytotoxic effect and inhibiting CD133 expression in pemetrexed-resistant lung cancer cells via autophagy. Our finding provides evidence that CD133 is a potential target for cancer therapy.

Antifungal, anti-inflamatory and neuritogenic activity of newly-isolated compounds from Disporopsis aspersa.

A new ester (1) and a terpenoid (2) were isolated from the dried whole plant of Disporopsis aspersa (HUA) ENGL. ex DIELS for the first time and their structures were elucidated, as well as their biological activities are described. The two compounds all showed good antifungal activities, especially furanone (2) exhibited better antifungal activity against Pseudoperonospora cubensis and Phytophthora infestans with EC50 value of 22.82, 18.90 µg/mL, respectively. Compound 1 exhibited a significant promotion on the neurite outgrowth in NGF-induced PC-12 cells, and moderate inhibition on the NO production induced by lipopolysaccharide (LPS) in BV-2 microglial cells.

Effects of ABT-737 combined with irradiation treatment on uterine cervical cancer cells.

The aim of the present study was to examine the role of ABT-737, an inhibitor of B-cell lymphoma 2 (Bcl-2), in enhancing the effect of irradiation on uterine cervical cancer. Based on The Cancer Genomic Atlas (TCGA), Bcl-2 mRNA expression was associated with the Tumor-Node-Metastasis stage of cervical cancer. Therefore, it was hypothesized that Bcl-2 inhibition may decrease the progression of cervical cancer. ABT-737 was added to irradiation treatment to evaluate its effectiveness in inhibiting cancer cell progression. SiHa and CaSki cervical cancer cells were selected for in vitro assays. Patients with advanced stage III uterine cancer had slightly increased mRNA expression levels of Bcl-2 compared with patients with stage I cancer, although the difference was not significant. ABT-737 and radiation administration induced a synergistic cytotoxic effect based on the MTT assay and flow cytometry results, where an increase in apoptosis was observed. The apoptotic percentages were significantly increased in the cells treated with a combination of ABT-737 and irradiation. Loss of mitochondrial membrane potential and gain of reactive oxygen species (ROS) were detected by flow cytometry in CaSki and SiHa cells treated with ABT-737 and radiation. Additionally, the protein expression levels of the cleaved forms of poly ADP ribose polymerase and caspase-7 were increased following the combined treatment. In conclusion, ABT-737 and irradiation may induce apoptosis via loss of mitochondrial membrane potential and a ROS-dependent apoptotic pathway in CaSki and SiHa cells. The present study indicates that ABT-737 may be a potential irradiation adjuvant when treating cervical cancer.

Downregulated LRRK2 gene expression inhibits proliferation and migration while promoting the apoptosis of thyroid cancer cells by inhibiting activation of the JNK signaling pathway.

Emerging studies have indicated that leucine­rich repeat kinase 2 (LRRK2) is associated with thyroid cancer (TC). The present study investigated the effect of LRRK2 on the cell cycle and apoptosis in TC, and examined the underlying mechanisms in vitro. To screen TC­associated differentially expressed genes, gene expression microarray analysis was conducted. Retrieval of pathways associated with TC from the Kyoto Encyclopedia of Genes and Genomes database indicated that the c­Jun N­terminal kinase (JNK) signaling pathway serves an essential role in TC. SW579, IHH­4, TFC­133, TPC­1 and Nthy­ori3­1 cell lines were used to screen cell lines with the highest and lowest LRRK2 expression for subsequent experiments. The two selected cell lines were transfected with pcDNA­LRRK2, or small interfering RNA against LRRK2 or SP600125 (a JNK inhibitor). Subsequently, flow cytometry, terminal deoxynucleotidyl transferase­mediated dUTP­biotin nick end labeling, a 5­ethynyl­2'­deoxyuridine assay and a scratch test was conducted to detect the cell cycle distribution, apoptosis, proliferation and migration, respectively, in each group. The LRRK2 gene was determined to be elevated in TC based on the microarray data of the GSE3678 dataset. The SW579 cell line was identified to exhibit the highest LRRK2 expression, while IHH­4 cells exhibited the lowest LRRK2 expression. LRRK2 silencing, through inhibiting the activation of the JNK signaling pathway, increased the expression levels of genes and proteins associated with cell cycle arrest and apoptosis in TC cells, promoted cell cycle arrest and apoptosis, and inhibited cell migration and proliferation in TC cells, indicating that LRRK2 repression could exert beneficial effects through the JNK signaling pathway on TC cells. These observations demonstrate that LRRK2 silencing promotes TC cell growth inhibition, and facilitates apoptosis and cell cycle arrest. The JNK signaling pathway may serve a crucial role in mediating the anti­carcinogenic activities of downregulated LRRK2 in TC.

Simplified MIPI-B prognostic stratification method can predict the outcome well-retrospective analysis of clinical characteristics and management of newly-diagnosed mantle cell lymphoma patients from China.

Mantle cell lymphoma (MCL) is an invasive B-cell lymphoma with significant individual differences. Currently, MCL international prognostic index (MIPI) score and tumor cell proliferation index Ki-67 have been proved to be the most important prognostic factors. But the prognostic effect of these factors in Asian population is uncertain. This study aimed to analyze the disease characteristics and prognostic factors of Chinese MCL patients.A total of 83 cases of newly-diagnosed MCL patients diagnosed by the Department of Pathology of our hospital between January 1, 2011, and May 31, 2016, were enrolled. The disease characteristics, treatment effects, and outcomes of the patients were collected and analyzed.According to our analysis, MCL cases accounted for 6.2% of non-Hodgkin lymphoma (NHL) cases and mainly occurred in elderly males. But the proportion of patients at stage IV by Ann Arbor staging system and high-risk group by simplified-MIPI (s-MIPI) were significantly lower than that among European patients. Immunochemotherapy containing rituximab was significantly more effective than chemotherapy (overall response rate, [ORR]: 88.5% vs 65.2%, P = .021) and significantly prolonged patient survival (progression free survival [PFS]: 45.5 m vs 16.2 m, P = .001; overall survival [OS]: 58.3 m vs 22.8 m, P = .001). The multivariate analysis showed that the B symptoms, s-MIPI and administration of immunochemotherapy were independent prognostic factors that affected PFS and OS of the patients. s-MIPI and B symptom make up s-MIPI-B stratification method, by which patients in low-risk group of s-MIPI without B symptom were classified as low-risk, patients in high-risk group of s-MIPI and patients in low-risk group of s-MIPI with B symptom as high-risk, the rest as middle-risk. 3-year PFS of the 3 groups were 74.9%, 43.4% and 16.1%, respectively (P = .001). 3-year OS were 84.4%, 62.2%, 27.6% (P <.001).Chinese MCL was male predominance. We have a minor proportion of late-stage and high-risk patients compared to European patients. Immunochemotherapy was proved to significantly improve the prognosis of MCL patients. B symptoms, s-MIPI, and administration of rituximab independently influenced the outcome. s-MIPI-B prognostic stratification method may better predict the prognosis of Asian MCL patients. Still, further confirmation in larger populations is needed.

Significant association of long non-coding RNAs HOTAIR genetic polymorphisms with cancer recurrence and patient survival in patients with uterine cervical cancer.

Up to date, no study explores the relationship of single nucleotide polymorphisms (SNPs) of long non-coding RNAs HOTAIR (lncRNAs HOTAIR) with cancer recurrence and patient survival in uterine cervical cancer for Taiwanese women. We therefore designed this study to investigate the clinical roles of lncRNAs HOTAIR SNPs in cervical cancer. One hundred and sixteen patients with cervical invasive cancer and 96 patients with preinvasive lesions as well as 318 control women were consecutively recruited. LncRNAs HOTAIR SNPs rs920778, rs12427129, rs4759314 and rs1899663 were analyzed and their genotypic frequencies were examined by real-time polymerase chain reaction. The results indicated that there were no genotypic differences between patients with cervical neoplasia and normal controls as well as among patients with invasive and invasive cancer, and normal controls. However, genotype GG in lncRNAs HOTAIR SNP rs920778 was demonstrated to be a predictor for poorer cancer recurrence probability [p=0.001, hazard ratio (HR): 7.25, 95% CI: 2.19-23.96]. Furthermore, cervical cancer patients with genotype GG in lncRNAs HOTAIR rs920778 had worse overall survival (p =0.002, HR: 7.22, 95% CI: 2.09-24.92). No significant associations exhibited between lncRNAs HOTAIR SNP rs920778 and clinicopathological parameters. In conclusion, this studied lncRNAs HOTAIR SNPs are not associated with cervical carcinongensis. However, lncRNAs HOTAIR SNP rs920778 may be regarded as an independent predictor of cancer recurrence probability and overall survival in cervical cancer patients.

Radiological Aspect of Klippel-Trénaunay Syndrome: A Case Series With Review of Literature.

Klippel-Trénaunay syndrome (KTS) is a rare angio-osteo-hypertrophic syndrome characterized by vascular malformations, soft tissue and/or bone hypertrophy, and varicose veins. For the purpose of describing the imaging findings and elucidating the role of medical imaging in the diagnosis and assessment of patient with KTS, we have reviewed the imaging data of 14 KTS patients. The imaging features on different imaging modalities were analyzed. Unilateral lower limb involvement was evident in 71% of cases (n=10) and bilateral but asymmetric lower limb involvement in the remaining 29% of cases (n=4). The most commonly depicted imaging features were varicosities in 93% (n=13), muscle hypertrophy in 79% (n=11) and venous anomalies in 64% (n=9). Other less common imaging findings included lymphedema in 29% (n=4), arterial malformations 29% (n=4), soft tissue hemangiomas 21% (n=3), pelvic and thigh phleboliths 21% (n=3), venous aneurysms 21% (n=3), bone abnormalities 14% (n=2) and lymphadenopathy 14% (n=2). A severe unilateral lower limb deformity resulting in contractures and muscle atrophy of the whole limb was depicted in 1 case. The pathognomonic marginal vein of Servelle was identified in 2 cases. AV shunt was highly suspected in 4 cases and was confirmed by DSA in 1 case, making Klippel-Trénaunay-Weber syndrome a more apt diagnosis. Associated ipsilateral duplicated renal artery was found in 1 case. We have concluded that medical imaging is the cornerstone in the diagnosis and assessment of severity and complications, follow-up and differentiation of KTS from other similar conditions. Different imaging modalities play complementary roles in the evaluation of KTS patients.

SDC4 Gene Silencing Favors Human Papillary Thyroid Carcinoma Cell Apoptosis and Inhibits Epithelial Mesenchymal Transition via Wnt/ß-Catenin Pathway.

As the most common type of endocrine malignancy, papillary thyroid cancer (PTC) accounts for 85-90% of all thyroid cancers. In this study, we presented the hypothesis that SDC4 gene silencing could effectively attenuate epithelial mesenchymal transition (EMT), and promote cell apoptosis via the Wnt/ß-catenin signaling pathway in human PTC cells. Bioinformatics methods were employed to screen the determined differential expression levels of SDC4 in PTC and adjacent normal samples. PTC tissues and adjacent normal tissues were prepared and their respective levels of SDC4 protein positive expression, in addition to the mRNA and protein levels of SDC4, Wnt/ß-catenin signaling pathway, EMT and apoptosis related genes were all detected accordingly. Flow cytometry was applied in order to detect cell cycle entry and apoptosis. Finally, analyses of PTC migration and invasion abilities were assessed by using a Transwell assay and scratch test. In PTC tissues, activated Wnt/ß-catenin signaling pathway, increased EMT and repressed cell apoptosis were determined. Moreover, the PTC K1 and TPC-1 cell lines exhibiting the highest SDC4 expression were selected for further experiments. In vitro experiments revealed that SDC4 gene silencing could suppress cell migration, invasion and EMT, while acting to promote the apoptosis of PTC cells by inhibiting the activation of the Wnt/ß-catenin signaling pathway. Besides, si-ß-catenin was observed to inhibit the promotion of PTC cell migration and invasion caused by SDC4 overexpression. Our study revealed that SDC4 gene silencing represses EMT, and enhances cell apoptosis by suppressing the activation of the Wnt/ß-catenin signaling pathway in human PTC.

Synergistic antimetastatic effect of cotreatment with licochalcone A and sorafenib on human hepatocellular carcinoma cells through the inactivation of MKK4/JNK and uPA expression.

To improve the clinical outcome of tumor chemotherapy, more effective combination treatments against tumor metastasis and recurrence are required. Licochalcone A (LicA) is the root of Glycyrrhiza inflata and has been reported to possess anti-inflammatory, antimicrobial, and antitumor effects. Sorafenib (Sor), a multikinase inhibitor, is used to treat patients with solid tumors such as advanced hepatocellular carcinoma (HCC). However, the synergistic effects of LicA and Sor on the metastasis of human HCC cells have not been reported. We found that LicA and Sor did not have cytotoxic effects or arrest growth in human SK-Hep-1 and Huh-7 cells. In addition, treatment with LicA or Sor alone inhibited migration and invasion in human SK-Hep-1 and Huh-7 HCC cells. Furthermore, cotreatment with LicA and Sor synergistically inhibited the migration and invasion of HCC cells and significantly inhibited uPA protein expression. Notably, cotreatment of LicA and Sor synergistically and significantly downregulated MKK4-JNK expression. Through tail vein injection in nude mice, the aforementioned cotreatment synergistically suppressed SK-Hep-1 cell-mediated lung metastasis. These findings first revealed the synergistic effects of LicA and Sor cotreatment against human HCC cells, further suggesting that beneficial effects on tumor regression could be confirmed through prospective clinical trials.

Hypericin inhibits hepatitis C virus replication via deacetylation and down-regulation of heme oxygenase-1.

BACKGROUND: Hepatitis C virus (HCV) is a globally prevalent pathogen and a leading cause of death and morbidity. Traditional therapy with pegylated interferon- and ribavirin has had only limited success, with some adverse effects. Direct-acting antivirals (DAAs) are effective in suppressing HCV replication, but are expensive. PURPOSE: Hypericin has been reported to be a good antiviral agent for inhibiting HCV replication, however, little is known about its mechanisms of action. The aim of this study is to elucidate the mode of action of hypericin in Ava5 human hepatoma cell line (Huh7 derivative) harboring HCV subgenomic replicon RNA. METHODS: To determine the non-structure protein 5A (NS5A) mRNA and NS3 protein expression levels, real-time PCR and Western blot analysis were performed, respectively. To investigate how hypericin inhibits HCV replication, 5-aza-2'-deoxycytidine (5-Aza-dC) and chidamide were used for determining histone modification. Furthermore, shRNA was applied to confirm the role of heme oxygenase (HO-1) in HCV repression. RESULTS: Hypericin in experiment were tested and showed no cytotoxicity. Hypericin reduced HO-1 and NS5A in a time- and dose- dependent manner. Chidamide, but not 5-Aza-dc, restored hypericin-induced reduction in HCV NS3 expression and reversed HO-1 expression in Ava5 cells. LY294002 inhibited HCV replication via HO-1 down-regulation. Constitutive expressed p-AKT was not involved in hypericin-induced reduction in HCV replication. In addition, shHO-1 inhibited HCV replication. CONCLUSION: In conclusion, hypericin inhibits HCV replication via down-regulation of HO-1 expression and deacetylation.