[Analysis on the secondary attack rates of SARS-CoV-2 Omicron variant and the associated factors].

Objective: To evaluate the secondary attack rates of the SARS-CoV-2 Omicron variant and the associated factors. Methods: A total of 328 primary cases and 40 146 close contacts of the SARS-CoV-2 Omicron variant routinely detected in local areas of Jiangsu Province from February to April 2022 were selected in this study, and those with positive nucleic acid test results during 7 days of centralized isolation medical observation were defined as secondary cases. The demographic information and clinical characteristics were collected, and the secondary attack rate (SAR) and the associated factors were analyzed by using a multivariate logistic regression model. Results: A total of 1 285 secondary cases of close contacts were reported from 328 primary cases, with a SAR of 3.2% (95%CI: 3.0%-3.4%). Among the 328 primary cases, males accounted for 61.9% (203 cases), with the median age (Q1, Q3) of 38.5 (27, 51) years old. Among the 1 285 secondary cases, males accounted for 59.1% (759 cases), with the median age (Q1, Q3) of 34 (17, 52) years old. The multivariate logistic regression model showed that the higher SAR was observed in the primary male cases (OR=1.632, 95%CI: 1.418-1.877), younger than 20 years old (OR=1.766, 95%CI: 1.506-2.072),≥60 years old (OR=1.869, 95%CI: 1.476-2.365), infected with the BA.2 strain branch (OR=2.906, 95%CI: 2.388-3.537), the confirmed common cases (OR=2.572, 95%CI: 2.036-3.249), and confirmed mild cases (OR=1.717, 95%CI: 1.486-1.985). Meanwhile, the higher SAR was observed in the close contacts younger than 20 years old (OR=2.604, 95%CI: 2.250-3.015),≥60 years old (OR=1.287, 95%CI: 1.052-1.573) and exposure for co-residence (OR=27.854, 95%CI: 23.470-33.057). Conclusion: The sex and age of the primary case of the Omicron variant, the branch of the infected strain, case severity of the primary case, as well as the age and contact mode of close contacts are the associated factors of SAR.

[A conceptual framework for dynamics of cccDNA in hepatitis B virus].

The resolution of the hepatitis C issue has raised expectations for a chronic hepatitis B cure, driving the industry to expand investment in research and development efforts to strengthen functional cure strategies. These strategies have a wide variety of types, and the published research findings are heterogeneous. The theoretical analysis of these strategies is of great significance for determining prioritized research orientations as well as sensibly allocating research and development resources. However, due to a paucity of necessary conceptual models, current theoretical analysis has not been able to unify various therapeutic strategies into a proper theoretical framework. In view of the fact that the decrease in the quantity of cccDNA is an inevitable core event accompanied by the process of functional cure, this paper intends to analyze several chronic hepatitis B cure strategies using cccDNA dynamics as a framework. Furthermore, there are currently few studies on the dynamics of the cccDNA field, hoping that this article can promote recognition and research in this field.

A J-shaped relationship between the atherogenic index of plasma and new-onset myocardial infarction in hypertensive patients with obstructive sleep apnea: a cohort study.

OBJECTIVE: This study aimed to investigate the relationship between baseline atherogenic index of plasma (AIP) and new-onset myocardial infarction (MI) in hypertensive patients with obstructive sleep apnoea (OSA). PATIENTS AND METHODS: 2,281 participants were included in this analysis after strict adherence to the inclusion and exclusion criteria. Hazard ratio (HR) and 95% confidence interval (CI) were estimated using multivariable Cox regression models. A generalized additive model was employed to determine nonlinear relationships. RESULTS: In multivariate-adjusted models, there was a positive association between AIP and new-onset MI (per SD increase; HR=1.42, 95% CI: 1.22-1.65). Smoothing curve fitting revealed a J-shaped association between AIP and new-onset MI, with a turning point of approximately -0.08. The addition of AIP to a model with established risk factors improved the C-index (p=0.007), integrated discrimination improvement (p=0.007), and continuous net reclassification improvement (p=0.027) for the new-onset MI. CONCLUSIONS: A J-shaped relationship was observed between AIP and new-onset MI.

Retraction Note: LncRNA RUSC1-AS1 promotes the proliferation of breast cancer cells by epigenetic silence of KLF2 and CDKN1A.

The article "LncRNA RUSC1-AS1 promotes the proliferation of breast cancer cells by epigenetic silence of KLF2 and CDKN1A, by C.-C. Hu, Y.-W. Liang, J.-L. Hu, L.-F. Liu, J.-W. Liang, R. Wang, published in Eur Rev Med Pharmacol Sci 2019; 23 (15): 6602-6611-DOI: 10.26355/eurrev_201908_18548-PMID: 31378902" has been retracted by the authors. After publication, the article was questioned on PubPeer. Concerns were raised about Figure 2, Table I, and the reliability of the published results. The same authors stated that they want to rearrange the manuscript and provide readers with a more precise model. https://www.europeanreview.org/article/18548.

[The value of preservation of subvalvular structures in patients with mitral and aortic valve replacement surgery and its effect on left ventricular contractility].

Objective: To discuss the clinical value of preserving subvalvular structure in mitral and aortic valve replacement surgery and its effect on left ventricular contractility. Methods: A total of 97 patients who underwent mitral valve replacement surgery in the Adult Cardiac Surgery of Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital from June 2016 to December 2018 were selected as the research subjects, of whom 45 cases were preserved subvalvular structure and 52 cases were in the total resection group (intraoperative total resection of the mitral valve and subvalvular chordae tendineae). General cardiac function indexes and left ventricular function quantitative indexes were compared before and in 3 months and 6 months after the operation of the two groups; The changes of the overall longitudinal strain of the long axis of the apex and the overall circumferential strain of the short axis of the left ventricle determined by the two-dimensional speckle tracking technology were compared before and after the operation. Results: The ages of the patients in the preservation group and the total resection group were (41.8±11.3) and (43.3±10.6) years old, respectively, and the male proportions were 58.0% (26 cases) and 44.0% (23 cases), respectively, with no significant difference (all P>0.05). The aortic occlusion time and cardiopulmonary bypass time of the patients in the preservation group were (57.8±4.5) and (78.6±6.7) min, respectively, which were longer than those in the total resection group [(48.1±4.4) and (48.1±4.4) min, respectively] (all P<0.05). The left atrial pressure of the patients in the preservation group at shutdown was (8.4±1.8) mmHg (1 mmHg=0.133 kPa), which was lower than that of the total resection group (11.3±2.5) mmHg (P<0.001). There were interaction effects between groups and time in regards to the left ventricular end-diastolic diameter ( LVEDD ), left ventricular ejection fraction ( LVEF ) and Tei index, as well as the strain rate of mitral annulus and left ventricular wall of interventricular septum of the preservation group and the total resection group (all P<0.05). LVEDD and LVEF of patients in the preservation group at 3rd month after operation were (44.7±4.0) mm and (45.5±4.2) mm, and at 6th months were (56.5±4.9)% and (58.8±5.0)%, respectively, all larger than (42.7±3.6) mm and (42.7±3.6) mm, (54.5±4.6)% and (56.3±4.8)% of the total resection group. The measured value of LVESD in the preservation group at 3rd month after surgery was (32.6±3.2) mm, which was greater than that in the total resection group (31.2±3.4) mm (P<0.05). The Tei index of patients in the preservation group at 3rd and 6th months after surgery were 1.0±0.2 and 0.8±0.2, respectively, which were lower than those in the total resection group 1.2±0.3 and 0.9±0.2 (all P<0.05). Conclusion: Preserving the subvalvular structure during mitral valve replacement surgery can better improve the patient's left ventricular function and left ventricular systolic capacity.

[Immunogenicity and safety of a booster vaccination with an inactivated severe acute respiratory syndrome coronavirus 2 vaccine in adults aged 18 to 59 years].

Objective: To assess the immunogenicity and safety of a booster vaccination with an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: The phase Ⅱ trial of an inactivated SARS-CoV-2 vaccine was conducted by Jiangsu Provincial Center for Disease Control and Prevention (CDC) since October 2020. The subjects were healthy adults aged 18-59 years, excluding pregnant, and not breastfeeding women. The primary vaccination schedule groups were 0-14 d 5 µg, 0-14 d 10 µg, 0-28 d 5 µg and 0-28 d 10 µg, respectively. And 50 participants in each group, a total of 200, who have received 2-doses primary vaccination were selected in ascending order of the study number and vaccinated with a booster dose (same dosage as primary vaccination) at the 6th months after post the primary vaccination (30-day window period). Blood samples were collected before and after boosting and tested for the geometric mean titers (GMT) and seroconversion of live virus neutralizing antibody, pseudovirus neutralizing antibody and receptor-binding-domain (RBD) IgG antibody. Adverse events (AE) were collected and assessed within 28 days after boosting. Results: The ages of subjects in group 0-14 d 5 µg, 0-14 d 10 µg, 0-28 d 5 µg and 0-28 d 10 µg were (43.98±9.58), (43.46±9.34), (42.56±9.08) and (43.94±11.05) years old, respectively (P=0.877). Sex ratios were balanced among the 4 groups (P=0.331). The live virus neutralizing antibody GMT (95%CI) in group 0-14 d 5 µg, 0-14 d 10 µg, 0-28 d 5 µg and 0-28 d 10 µg increased from 4.07 (3.30-5.04), 3.75 (3.08-4.55), 8.33 (7.01-11.11) and 7.69 (6.19-9.57) before the booster vaccination to 284.84 (215.28-376.86), 233.05 (178.61-304.08), 274.81 (223.64-337.68) and 280.77 (234.59-336.04) in 28 days after the booster vaccination, respectively. The rates of live virus neutralizing antibody seroconversion were all 100% in the 4 groups. The AE incidences following booster vaccination were 18.0% (9 cases), 4.0% (2 cases), 12% (6 cases), and 12% (6 cases) in the 4 groups(P=0.182). No AE was graded as level 3 or worse. No serious AE was reported. Conclusion: One booster vaccination of an inactivated SARS-CoV-2 vaccine administered 6 months after primary vaccination showed good immunogenicity and safety.

[Construction of urban scale-free network model and its epidemiological significance in the prevention and control of COVID-19].

COVID-19 is a public health emergency currently. In this study, a scale-free network model is established based on the Spring Migration data in 2020.The cities is clustered into three different modules. The epidemic of the cities in the black module was the most serious, followed by the red and the cyan. The black module contains 9 cities in Zhejiang province and 8 cities in Guangdong province, most of them located in the southeast coastal economic belt. These cities should be the key cities for epidemic prevention and control.

[Efficacy and safety of low-intensity pulsed ultrasound at different intervals by mechanical force in treating erectile dysfunction: a preliminary study].

Objective: To study the efficacy and safety of low-intensity pulsed ultrasound (LIPUS) at different intervals by mechanical force in treating erectile dysfunction (ED). Method: Forty patients with mild to moderate ED were randomized in a 1∶1 ratio to receive 16-treatment sessions of LIPUS in group A and group B, applied 3 times per week and 2 times per week, respectively. End-point assessments were made at 8th week after treatment. Efficacy were evaluated using International Index of Erectile Function-Erectile Function domain score (IIEF-EF), Erectile Hardness Score (EHS), Self-Esteem and Relationship Questionnaire (SEAR), Sexual Encounter Profile (SEP), Global Assessment Question (GAQ), and pain were assessed by Visual Analogue Score (VAS).Treatment response was confirmed by a minimal clinically importance difference (MCID) at 8th week. Results: Compared with baseline, IIEF-EF score [(17.1±5.48 vs 23.4±3.75, P<0.05) and (18.9±4.34 vs 24.1±4.32, P<0.05)], proportion of EHS 4 [(0 vs 40%, P<0.05) and (16.7% vs 55.6%, P<0.05)], and Overall Relationship score [(50.6 vs 67.5, P<0.05) and (44.4 vs 70.1, P<0.05)] were significantly improved at 8th week in two groups, respectively. Compared with baseline, the positive responses to SEP-3 increased significantly at 8th week in two groups (50.0% vs 80.0%,P<0.05) and (44.4% vs 88.9%, P<0.05), respectively. The positive responses to GAQ-2 were 90.0% and 88.9% at 8th week in two groups, respectively. There were no significant differences in IIEF-EF, EHS, SEAR, SEP and GAQ at 8th week between two groups. There was no significant difference in treatment response using MCID between two groups at end-point (80.5% vs 77.5%). The treatment duration for full sessions were 2.5 weeks less in group A than group B. No adverse effects were reported in all cases. Conclusion: LIPUS at two different intervals is effective and safe for mild to moderate ED, and the regimen at 3 times per week can achieve quite good effect in relatively short duration,while the long-term effects is still be clarified in further study.

[Effect of omeprazole on plasma concentration and adverse reactions of capecitabine in patients with colon cancer].

Objective: To investigate the effect of omeprazole on plasma concentration, efficacy and adverse reactions of capecitabine in patients with colon cancer. Methods: Seventy-two patients with colon cancer treated with capecitabine were analysed retrospective. The patients treated with capecitabine combined with omeprazole were identified as experimental group and the capecitabine treatment alone as control group.The differences of blood concentration and the side effects of capecitabine between these two groups were compared. Results: The plasma concentration of 5-Fluorouracilum in experimental group was (126.25±50.59) µg/ml, without significant difference of (123.09±56.70) µg/ml in control group (P=0.121). The incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and hand-foot syndrome in experimental group were 13.8%, 0%, 0% and 19.4%, respectively. In control group, the incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and the hand-foot syndrome were 11.1%, 0%, 0% and 19.4%, respectively, without significant difference of experimental group (P>0.05). The incidence of acid reflux and heartburn in the control group was 72.2%, significantly higher than 44.4% of the experimental group (P<0.05). The objective response rate (ORR) and progression-free survival time (PFS) in these two groups were 30.6% and 33.3%, and 8.0 month and 8.5 month, respectively, without significant difference (P>0.05). Conclusion: The intravenous omeprazole attenuates reflux and heartburn of colon cancer patients treated with capecitabine, without affecting its plasma concentration and side effects and has no impact on the PFS of these patients.

LncRNA RUSC1-AS1 promotes the proliferation of breast cancer cells by epigenetic silence of KLF2 and CDKN1A.

OBJECTIVE: To clarify the potential function of long non-coding RNA (lncRNA) RUSC1-AS1 in regulating the progression of breast cancer (BCa) and the underlying mechanism. PATIENTS AND METHODS: RUSC1-AS1 level in BCa tissues and adjacent normal tissues was first determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between RUSC1-AS1 expression with tumor size, clinical stage and overall survival of BCa patients was analyzed. Influences of RUSC1-AS1 knockdown on viability, clonality, cell cycle and apoptosis of BCa cell lines MCF-7 and BT549 were evaluated. Target genes of RUSC1-AS1 were predicted by bioinformatics, and their interaction was further confirmed by RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and rescue experiments. RESULTS: A higher abundance of RUSC1-AS1 was identified in BCa tissues relative to controls. The expression level of RUSC1-AS1 was positively correlated to tumor size and clinical grade, but negatively correlated to the overall survival of BCa patients. The silence of RUSC1-AS1 markedly inhibited viability, clonality, cell cycle progression, and induced apoptosis of MCF-7 and BT549 cells. Finally, CDKN1A and KLF2 were found to be the target genes of RUSC1-AS1, which were tumor-suppressor genes involved in RUSC1-AS1-mediated BCa progression. CONCLUSIONS: RUSC1-AS1 is highly expressed in BCa, which promotes the progression of BCa through mediating CDKN1A and KLF2. RUSC1-AS1 may serve as a potential hallmark for BCa.

Simvastatin alleviates inflammation and oxidative stress in rats with cerebral hemorrhage through Nrf2-ARE signaling pathway.

OBJECTIVE: To investigate the regulatory effects of simvastatin on the inflammation and oxidative stress in rats with cerebral hemorrhage through the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) signaling pathway. MATERIALS AND METHODS: A total of 120 healthy male rats weighing 280-300 g and 7-8 weeks old were selected to establish the traumatic brain injury (TBI) model. Rats were divided into group A (trauma operation, n=30), group B (no treatment, n=30), group C (drug administration after trauma operation, n=30), and group D (no trauma operation, drug administration, n=30). Cerebral edema content in brain tissues was measured by calculating the dry and wet weight. Neurological dysfunction was scored using the Garcia method. Positive levels of the Toll-like receptor 4 (TLR4) and interleukin-1ß (IL-1ß) were qualitatively analyzed via immunohistochemistry. Protein levels of TLR4 and IL-1ß were quantitatively analyzed via Western blotting. Moreover, the brain injury volume and neuronal apoptosis were evaluated via Nissl staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, respectively. At 48 h after injury, activities of superoxide dismutase (SOD), reduced glutathione (GSH), and oxidized glutathione (GSSG) in brain tissues were detected, and levels of malondialdehyde (MDA) and nitric oxide (NO) were detected using the enzyme activity assay kits. Finally, relative levels of the Nrf2-ARE signaling pathway and its downstream molecules heme oxygenase-1 (HO-1) and NAD (P)H dehydrogenase, quinone 1 (NQO1) were detected via reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting. RESULTS: Compared with those in group B, cerebral edema content in brain tissues significantly increased (p<0.05), the neurological dysfunction score significantly declined (p<0.05), and protein levels of TLR4 and IL-1ß were significantly upregulated in group A (p<0.05). In group C, relative levels of TLR4 and IL-1ß were down-regulated, cerebral edema content decreased, and the neurological dysfunction score significantly increased (p<0.05). After 48 h, activities of SOD, reduced GSH and GSSG and levels of MDA and NO all increased, and levels of MDA and NO declined in group C (p<0.05). Western blotting and RT-PCR showed that simvastatin could increase the transcriptional level of Nrf2. After simvastatin intervention, expression levels of downstream molecules HO-1 and NQO1 were upregulated. CONCLUSIONS: Simvastatin alleviates TLR4-mediated inflammatory injury, promotes neurological recovery and resists oxidative stress through the Nrf2-ARE signaling pathway, thus exerting a neuroprotective effect in TBI.

Effect of miR-130a on neuronal injury in rats with intracranial hemorrhage through PTEN/PI3K/AKT signaling pathway.

OBJECTIVE: The aim of this study was to investigate the effect of micro-ribonucleic acid (miR)-130a on neuronal injury in rats with intracerebral hemorrhage (ICH) through the phosphatase and tensin homolog deleted on chromosome ten/phosphatidylinositol 3-hydroxy kinase/protein kinase B (PTEN/PI3K/AKT) signaling pathway. MATERIALS AND METHODS: A total of 30 healthy male rats were randomly divided into three groups, including the blank control group, ICH model group (ICH group) and ICH model + miR-130a treatment group (miR-130a treatment group). The differences in neurological injury, the number of apoptotic cells in brain tissues, the activity of Caspase-9 and protein expressions of PTEN/PI3K/AKT were analyzed among the three groups, respectively. RESULTS: Neurological function was normal without injury in the control group. However, the neurological injury was severe in the ICH group and mild in the miR-130a treatment group. There were statistically significant differences in neurological function in the control group relative to those of the ICH group and miR-130a treatment group (p<0.05). Meanwhile, the neurological injury was markedly milder in the miR-130a treatment group than that of the ICH group, showing a statistically significant difference (p<0.05). The number of apoptotic cells was remarkably smaller in the control group when compared with the ICH group and miR-130a treatment group. However, it was markedly larger in the ICH group than that of the miR-130a treatment group, showing significant differences (p<0.05). The activity of Caspase-9 was significantly lower in the control group than ICH group and miR-130a treatment group (p<0.05). However, it increased remarkably in the ICH group compared with that of the miR-130a treatment group (p<0.05). Moreover, the protein level of PTEN in the ICH group was significantly higher than control group and miR-130a treatment group, displaying statistically significant differences (p<0.05). However, no marked difference in the protein level of PTEN was observed between the control group and miR-130a treatment group (p>0.05). The protein levels of the phosphorylated 3-hydroxy kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) were remarkably lower in the ICH group than those of the control group and miR-130a treatment group, displaying statistically significant differences (p<0.05). However, they were remarkably higher in the miR-130a treatment group than that of the control group (p<0.05). CONCLUSIONS: MiR-130a promotes neuronal growth in brain tissues in ICH rats and alleviates neuronal injury after ICH through the PTEN/PI3K/AKT signaling pathway. Our findings suggest that miR-130a exerts important clinical significance in the treatment of ICH.

[Research progress of maternal immunization].

Maternal immunization is an immune strategy that protects both mothers and early-life infants from disease by the vaccination of pregnant women. The effect of maternal immunization is influenced by the types of vaccines, the timing of vaccination, the subtypes of antibodies induced by vaccines, and the health status of mothers themselves. Inactivated influenza vaccination during pregnancy and DPT vaccination during the third trimester of pregnancy have been widely used in the world, while Hepatitis B vaccine, pneumococcal and meningococcal vaccines also show good efficacy and safety in pregnant women. This article reviews the research progress of Maternal Immunization in order to provide a reference for Maternal Immunization planning and policymaking in China.

CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer.

BACKGROUND: Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) metastasis and chemoresistance have not been fully characterized. METHODS: CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1. RESULTS: CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/ß-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients. CONCLUSIONS: CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.

[Research progress in occlusal splint therapy for temporomandibular joint disorders].

Temporomandibular disorders (TMD) is a common clinical disease with complex etiology and diverse treatment. There are many studies on the treatment of TMD. Occlusal splint therapy is the most commonly used TMD treatment solution, but its effectiveness remains unclear. A review of the latest literature is therefore conducted to evaluate the effectiveness of splint therapy for TMD.

Low expression of miR-1231 in patients with glioma and its prognostic significance.

OBJECTIVE: MiR-1231 has been reported to be down-regulated in glioma tissues and to act as a negative regulator in glioma progression. However, the clinical significance of miR-1231 remains unclear. In this study, we aimed to further demonstrate the expression pattern and prognostic value of miR-1231 in glioma patients. PATIENTS AND METHODS: We determined the expression level of miR-1231 in 154 cases of paired glioma and adjacent non-tumor tissues by quantitative Real Time-PCR (qRT-PCR). The association between miR-1231 expression levels and clinicopathological factors was examined by the χ2 test. The Kaplan-Meier survival analysis was performed to analyze the association of miR-1231 expression with overall survival (OS) and progression-free survival (PFS) of patients. The significance of survival variables was analyzed using the Cox multivariate proportional hazards model. RESULTS: We found that the expression level of miR-1231 in human glioma tissues was significantly lower than that in the adjacent nontumorous tissues (p<0.01). The expression levels of miR-1231 in glioma tissues with high grades were significantly lower than those with low grades. Decreased miR-1231 expression was significantly associated with advanced WHO grade (p=0.001) and KPS score (p=0.023). The Kaplan-Meier analysis indicated that low miR-1231 expression had a significant impact on OS (p=0.0103) and PFS (p=0.0019). Cox proportional hazards risk analysis demonstrated that miR-1231 was an independent prognostic factor for glioma. CONCLUSIONS: Our study, for the first time, provides evidence that evaluating miR-1231 in glioma may have prognostic and predictive value in the clinical management of glioma.

Inhibition of ATG12-mediated autophagy by miR-214 enhances radiosensitivity in colorectal cancer.

Radioresistance hampers success in the treatment of patients with advanced colorectal cancer (CRC). Improving our understanding of the underlying mechanisms of radioresistance could increase patients' response to irradiation (IR). MicroRNAs are a class of small RNAs involved in tumor therapy response to radiation. Here we found that miR-214 was markedly decreased in CRC cell lines and blood of CRC patients after IR exposure. Meanwhile, autophagy was enhanced in irradiated CRC cells. Mechanically, ATG12 was predicted and identified as a direct target of miR-214 by dual luciferase assay, qPCR, and Western blot. In vitro and in vivo experiments showed that miR-214 promoted radiosensitivity by inhibiting IR-induced autophagy. Restoration of ATG12 attenuated miR-214-mediated inhibition of cell growth and survival in response to IR. Importantly, miR-214 was highly expressed in radiosensitive CRC specimens and negatively correlated with plasma level of CEA. Moreover, ATG12 and LC3 expressions were increased in radioresistant CRC specimens. Our study elucidates that miR-214 promotes radiosensitivity by inhibition of ATG12-mediated autophagy in CRC. Importantly, miR-214 is a determinant of CRC irradiation response and may serve as a potential therapeutic target in CRC treatment.

FMNL2 destabilises COMMD10 to activate NF-κB pathway in invasion and metastasis of colorectal cancer.

BACKGROUND: Diaphanous-related formins (DRFs), actin necleator, have been known to participate in the progression of cancer cells. We previously reported that FMNL2 (Formin-like2), a member of DRFs, was a positive regulator in colorectal cancer (CRC) metastasis, yet proteins and pathways required for the function of this pro-invasive DRFs remain to be identified. METHODS: The relationship between FMNL2 and COMMD10 was examined using Co-IP, GST pull-down, immunofluorescence and in vitro ubiquitination assay. The in vitro and in vivo function of COMMD10 in CRC was evaluated using CCK-8 proliferation assay, plate colony formation, cell cycle, apoptosis and animal models. The inhibition of NF-κB signalling by COMMD10 was detected using dual-luciferase reporter assay and western blotting. Co-IP, GST pull-down and nuclear protein extraction assay were performed to evaluate the effect on p65 by COMMD10. Real-time PCR and western blotting were performed to detect expressions of FMNL2, COMMD10 and p65 in paired tissues. RESULTS: FMNL2 targets COMMD10 for ubiquitin-mediated proteasome degradation in CRC cells. COMMD10 targets p65 NF-κB (nuclear factor-κB) subunit and reduces its nuclear translocation, thereby leading to the inactivation of NF-κB pathway and suppression of CRC invasion and metastasis. Inhibition of NF-κB signalling by COMMD10 is necessary for FMNL2-mediated CRC cell behaviours. Downregulation of COMMD10 predicts poor prognosis of CRC patients. The expressions of FMNL2, COMMD10 and p65 are highly linked in CRC tissues. CONCLUSIONS: These data demonstrate that the FMNL2/COMMD10/p65 axis acts as a critical regulator in the maintenance of metastatic phenotypes and is strongly associated with negative clinical outcomes.

INSR gene polymorphisms correlate with sensitivity to platinum-based chemotherapy and prognosis in patients with epithelial ovarian cancer.

This study aimed to investigate the correlation between INSR gene polymorphisms on platinum-based chemotherapy sensitivity and prognosis in epithelial ovarian cancer (EOC). A total of 339 EOC patients receiving postoperative chemotherapy were recruited for the study. Tag single-nucleotide polymorphism of INSR gene was screened from HapMap combined with available literature. Frequency distribution of genotypes and alleles in INSR gene was sequenced by ABI3100-Avant. Compared with CC+GC genotype, INSR rs2252673 GG genotype and rs3745546 CC genotype showed less platinum-based chemotherapy sensitivity in EOC patients (odds ratio (OR)=0.269, 95% confidence interval (CI)=0.159~0.456; OR=0.445, 95% CI=0.214~0.926, respectively), as well as serous EOC patients (OR=0.083, 95% CI=0.024~0.278; OR=0.235, 95%CI=0.053~1.041, respectively). The clinical characteristics including age, clinical stage, histological grade and residual lesion size were significantly related with chemosensitivity to platinum drugs and mortality in EOC patients. According to Kaplan-Meier curve, compared with CC+GC genotype, rs2252673 GG genotype showed significantly decreased survival rate in EOC patients (P<0.05). Cox regression model indicated that rs2252673, age and clinical stage were independent risk factors for the prognosis in EOC (all P<0.05). These findings indicate that INSR rs2252673 and rs3745546 polymorphisms were associated with sensitivity to platinum-based chemotherapy in EOC patients and rs2252673 polymorphism may be an independent risk factor for EOC prognosis.

Down-regulation of DAB2IP promotes colorectal cancer invasion and metastasis by translocating hnRNPK into nucleus to enhance the transcription of MMP2.

DOC-2/DAB2 interacting protein (DAB2IP) is a RasGAP protein that shows a suppressive effect on cancer progression. Our previous study showed the involvement of transcription regulation of DAB2IP in metastasis of colorectal cancer (CRC). However, the molecular mechanisms of DAB2IP in regulating the progression of CRC need to be further explored. Here, we identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) and matrix metalloproteinase 2 (MMP2) as vital downstream targets of DAB2IP in CRC cells by two-dimensional fluorescence difference gel electrophoresis and cDNA microassay, respectively. Mechanistically, down-regulation of DAB2IP increased the level of hnRNPK through MAPK/ERK signaling pathway. Subsequently, translocation of hnRNPK into nucleus enhanced the transcription activity of MMP2, and therefore promoted invasion and metastasis of CRC. Down-regulation of DAB2IP correlated negatively with hnRNPK and MMP2 expressions in CRC tissues. In conclusion, our study elucidates a novel mechanism of the DAB2IP/hnRNPK/MMP2 axis in the regulation of CRC invasion and metastasis, which may be a potential therapeutic target.