[Meta-analysis of effectiveness evaluation of preventive measures for acute kidney injury in children].

Objective: To comprehensively evaluate the effectiveness of preventive measures for acute kidney injury (AKI) in children and identify the effective strategies. Methods: Databases were systematically searched including CNKI, Wanfang, VIP, China Biology Medicine National Knowledge Infrastructure, PubMed, Embase, Cochrane Library databases, and the reference lists of relevant papers for randomized controlled trials on preventing pediatric AKI up to December 2023. Literature screening was conducted based on the inclusion and exclusion criteria, followed by data extraction and quality assessment of included studies. Traditional and network meta-analyses were performed, along with trial sequential analysis (TSA). Results: A total of 21 studies involving 3 483 children were included. Traditional and network meta-analysis showed that dexmedetomidine was effective in preventing AKI in children undergoing cardiac surgery or cardiac angiography (OR=0.26, 0.27; 95%CI 0.11-0.64, 0.13-0.58). Remote ischemic preconditioning (RIPC) was effective in preventing AKI in children after cardiac surgery (OR=0.43, 0.44; 95%CI 0.24-0.79, 0.23-0.83). Traditional and network meta-analysis specific to children with sepsis or septic shock showed that balanced solution was effective in preventing pediatric AKI (OR=0.58, 0.52; 95%CI 0.42-0.79, 0.37-0.73). TSA indicated that the total sample sizes of dexmedetomidine (348 cases) and RIPC (666 cases) both reached the required information size (320 and 534 cases); additionally, the Z-curve for balanced solution (cumulative Z=3.38) crossed the TSA monitoring boundary (Z=3.29). Conclusion: Dexmedetomidine reduces the risk of AKI in children undergoing cardiac surgery or cardiac angiography, RIPC decreases the risk of AKI in children after cardiac surgery, and balanced solution lowers the risk of AKI in children with sepsis or septic shock.

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published in Eur Rev Med Pharmacol Sci 2019; 23 (15): 6602-6611-DOI: 10.26355/eurrev_201908_18548-PMID: 31378902" has been retracted by the authors.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.

[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.

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.

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.

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.

[Influence of aluminum on microRNA29 and ß-site amyloid precursor protein cleaving enzyme 1 in the brain of rats].

Objective: To investigate the influence of aluminum on microRNA29 (miR29) subtypes miR29a, miR29a*, miR29b1, miR29b2, miR29c1, and miR29c2 and ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) in the brain of rats. Methods: A total of 40 Sprague-Dawley rats were randomly divided into control group and 15, 30, and 45 µmol/kg groups according to the body weight, with 10 rats in each group. The rats were exposed to aluminum (at a dose of 0.1 ml/100 g body weight) by intraperitoneal injection for 8 weeks. The rats in control group were given 0.9% normal saline, and those in exposure groups were given aluminum-maltolate (equivalent volumesof maltolate and aluminum solution were mixed before exposure) . The cerebral cortex and hippocampus were isolated after exposure ended; Western blotting was used to measure the change in BACE1 expression, and real-time reverse transcription polymerase chain reaction was used to measure the mRNA expression of miR29 subtypes in the cerebral cortex and hippocampus. Results: Compared with the control group, the 45 µmol/kg group had a significant increase in BACE1 expression in the cerebral cortex, and the 30 and 45 µmol/kg groups had significant increases in BACE1 expression in the hippocampus (all P<0.05) . Compared with the control group, the 15, 30, and 45 µmol/kg groups had significant reductions in the mRNA expression of miR29a*, miR29b2, miR29c1, and miR29c2 in the cerebral cortex and hippocampus (all P<0.01) , and the 45 µmol/kg group had significant reductions in the mRNA expression of miR29a and miR29b1 in the cerebral cortex and hippocampus (all P<0.05) . The results of correlation analysis showed that there was no correlation between the mRNA expression of miR29a*, miR29b2, miR29c1, and miR29c2 and BACE1 expression in the cerebral cortex and hippocampus (all P>0.05) , while the mRNA expression of miR29a and miR29b1 was negatively correlated with BACE1 expression (cerebral cortex: r=-0.987 and -0.981, P<0.05; hippocampus: r=-0.992 and -0.991, P<0.05) . Conclusion: Aluminum can reduce the expression of miR29 subtypes and increase BACE1 expression in the brain, and the expression of miR29a and miR29b1 is negatively correlated with BACE1 expression.

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.

Role and timing of second-line therapies for patients with recurrent platinum-resistant ovarian epithelial cancer.

OBJECTIVE: To explore the regimens and prognoses of second-line therapies for recurrent platinum-resistant ovarian epithelial cancer (OEC). MATERIALS AND METHODS: The clinical profiles and second-line regimens were retrospectively analyzed for 65 recurrent platinum-resistant OEC patients treated at Zhejiang Provincial Tumor Hospital during January 2003 to January 2013. In conjunction with literature reviews, the second-line therapies for platinum-resistant recurrent OEC were discussed. RESULTS: Their average age was 55.2 years. The stages were I (n=4), II (n=3), III (n=45), and IV (n=13). The predominant type was serous adenocarcinoma (n=47, 72.3%). Chemotherapy was refused (n=14) and resistant (n=5 1). One case was lost to follow-up and another three withdrew early. An average of four chemotherapeutic courses were offered in 61 cases. Among them, five cases selected chemotherapy after a second operation. The average therapy-free interval (TFI) was 3.5 months. The efficacies were evaluated for 61 cases. CR (n=5) and partial remission (PR, n=22). The overall survival (OS) rate was 43.6% and average progression-free survival (PFS) was 15.44 months. CONCLUSION: The efficacy of second-line therapy for recurrent platinum-resistant OEC is rather poor and the feasibility and efficacy of second operation are to be further explored.

FBX8 is a metastasis suppressor downstream of miR-223 and targeting mTOR for degradation in colorectal carcinoma.

F-box proteins are critical components of the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligases and involved in the ubiquitin-dependent proteolytic pathway. Dysregulation of F-box protein-mediated proteolysis often leads to human malignancies. F-box only protein 8 (FBX8), a novel component of F-box proteins, is down-regulated in several tumors and closely correlates with tumor progression. However, little is known about its function, regulatory mechanisms and substrates in the progression of colorectal carcinoma (CRC). Combining microRNA (miRNA) assay, functional characterization, mechanistic studies with clinical validation, we identify FBX8 as a CRC metastasis suppressor downstream of miR-223, a metastasis promoting miRNA that is transcriptionally regulated by Myocyte enhancer factor (MEF2A). mTOR is a substrate of FBX8 for ubiquitin-mediated degradation and is required for FBX8 induced cell proliferation and invasion in CRC cells. FBX8 is down-regulated in human CRC tissues and correlates with MEF2A, miR-223 and mTOR expression levels. Notably, low FBX8 expression status in CRC tissues was a significant prognostic factor for poor overall survival of patients. These findings illustrate FBX8 as a metastasis suppressor that functions through mTOR signaling pathway and has significant prognostic power.

The FOXD3/miR-214/MED19 axis suppresses tumour growth and metastasis in human colorectal cancer.

BACKGROUND: MiR-214 is aberrantly regulated in several tumours, but its underlying mechanisms in colorectal cancer (CRC) metastasis remain largely unknown. This study aimed to demonstrate the function and potential mechanism of miR-214 in regulating invasion and metastasis of CRC. METHODS: The transcription factor and targets of miR-214 were predicted by bioinformatics and validated using ChIP and dual-luciferase reporter assay. DNA methylation status was explored using bisulphite sequencing PCR. The in vitro and in vivo function of miR-214 in CRC was evaluated using MTT, plate colony formation, Matrigel invasion and animal models. Real-time PCR or western blotting was performed to detect FOXD3, miR-214 and MED19 expressions in CRC cells and clinical specimens. RESULTS: MiR-214 was downregulated in CRC and was significantly correlated with lymphatic metastasis. Downregulation of miR-214 might due to promoter hypermethylation in CRC. FOXD3 was validated as a transcription factor of miR-214 by ChIP assay. Dual-luciferase assay identified MED19 as a target of miR-214 in CRC. In vitro and in vivo experiments showed that miR-214 mediated the inhibiting effect of FOXD3 on proliferation, invasion and metastasis by targeting MED19. Spearman's correlation analysis showed a positive correlation between FOXD3 and miR-214, and negative correlations between FOXD3 and MED19, miR-214 and MED19 in CRC cells and clinical specimens. CONCLUSIONS: FOXD3/miR-214/MED19 axis is important for the regulation of growth, invasion and metastasis of CRC. Targeting the miR-214-mediated axis might be helpful for the treatment of CRC.

Correlation of serum PCSK9 in CHD patients with the severity of coronary arterial lesions.

OBJECTIVE: The present study aims to investigate the correlation between serum level of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the severity of coronary arterial lesion in patients with coronary heart disease (CHD). PATIENTS AND METHODS: Between August 2010 and January 2015, 126 CHD patients and 70 patients with coronary arterial stenosis < 50% (controls) were included in the present study. Serum PCSK9 level was determined using ELISA. Demographic characteristics, relevant clinical data and biochemical data were collected from all patients, and their relationship with PCSK9 was analyzed to evaluate the correlation of PCSK9 expression with the severity of coronary artery disease (CAD). RESULTS: Concentrations of total cholesterol (TC) and fasting blood sugar (FBS) were significantly higher in CHD patients than in controls (p < 0.05). No significant differences were observed in gender, age, body mass index (BMI), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), family history, smoking history and history of hypertension between groups (p > 0.05). Serum PCSK9 levels in the CHD group were significantly higher than those in the control group [(96.4 ± 33.2) ng/mL vs. (81.8 ± 27.6) ng/mL, p < 0.05]. Compared with those of patients with single-vessel or double-vessel disease, PCSK9 levels were significantly elevated in patients with multi-vessel disease (p < 0.05). The Gensini score of the CHD group was significantly lower than that of the control group (11.4 ± 10.5 vs. 37.3 ± 10.3, p < 0.05). The Gensini score of patients with multi-vessel disease was significantly higher compared with patients of single-vessel  or double-vessel disease (p < 0.05). Correlation analysis revealed that PCSK9 was positively correlated with many clinical parameters, including age, BMI, TC, TG, systolic blood pressure, FBS, Gensini score and LDL-C (p < 0.05). However, PCSK9 was not correlated with either gender ratio or diastolic blood pressure (p > 0.05). CONCLUSIONS: Serum PCSK9 level is significantly elevated in CHD patients and its variation is correlated with the severity of CAD.

Effectiveness of muscle basal lamina carrying neural stem cells and olfactory ensheathing cells in spinal cord repair.

We examined the effect of muscle basal lamina (MBL) with neural stem cells (NSCs) and olfactory ensheathing cells (OECs) on spinal cord injury repair. Seventy-two Sprague-Dawley rats were subjected to spinal cord hemisection and divided into 6 groups. In blank control group (group A), the ends of the spinal cord hemisection model were flushed with physiological saline. In NSC transplantation group (B), OEC transplantation group (C), MBL with NSC transplantation group (D), MBL with OEC transplantation group (E), and MBL with NSC and OEC transplantation group (F), NSCs, OECs, MBL with NSCs, MBL with OECs, and MBL with NSCs and OECs were implanted into the ends of the hemisection model. Survival and migration of transplanted cells were detected by immunohistochemistry and immunofluorescence after 4 and 8 weeks. Hind limb function repair was evaluated by Bundle branch block score at various time points before and after surgery. MBL could promote NSC growth along its lumen and promote host cell advancement in the lumen, reducing local inflammatory responses. Using MBL with NSCs and/or OECs for spinal cord repair shows advantages over simple cell transplantation. Group F contained more nerve cells in muscle basal lamina than group E. This method is useful for forming more axons, synaptic connections, and signal transduction pathways. However, these new axons showed nerve demyelination, which may greatly limit nerve signal conduction. In group F, OECs could induce neural stem cells, axonal growth, and synaptic connection formation, but its role is limited.