Multifaceted role of microRNAs in gastric cancer stem cells: Mechanisms and potential biomarkers.

MicroRNAs (miRNAs) have received much attention in the past decade as potential key epigenomic regulators of tumors and cancer stem cells (CSCs). The abnormal expression of miRNAs is responsible for different phenotypes of gastric cancer stem cells (GCSCs). Some specific miRNAs could be used as promising biomarkers and therapeutic targets for the identification of GCSCs. This review summarizes the coding process and biological functions of miRNAs and demonstrates their role and efficacy in gastric cancer (GC) metastasis, drug resistance, and apoptosis, especially in the regulatory mechanism of GCSCs. It shows that the overexpression of onco-miRNAs and silencing of tumor-suppressor miRNAs can play a role in promoting or inhibiting tumor metastasis, apart from the initial formation of GC. It also discusses the epigenetic regulation and potential clinical applications of miRNAs as well as the role of CSCs in the pathogenesis of GC. We believe that this review may help in designing novel therapeutic approaches for GC.

Analysis of related factors of behavioral problems in children with congenital pseudarthrosis of tibia.

OBJECTIVE: This study aimed to investigate the factors associated with behavioral problems in children with congenital pseudarthrosis of the tibia. METHODS: Random sampling is utilized to obtain a sample of 90 patients. The behavioral problems of the patients are detected by Achenbach Children's Behavior Scale. Parental emotional problems are investigated by the Self-Rating Depression Scale and Self-Rating Anxiety Scale. RESULTS: The results demonstrate that the detection rate of behavioral problems in children with congenital pseudarthrosis of the tibia is 53.3% (48/90). Among these behavioral problems, an abnormal rate is higher in the four dimensions: thinking, violation of discipline, social interaction, and aggression. The anxiety and depression scores of caregivers are statistically higher in the abnormal group than in the normal group. The results of the multivariate analysis show that the anxiety degree of the parents had a significant impact on the behavior of the children. CONCLUSIONS: Children with congenital pseudarthrosis of the tibia are facing the issues of high rates of behavioral problems. Parents of children with congenital pseudarthrosis of the tibia had higher levels of anxiety and depression than parents of normal children. The anxiety and depressive state of mind of parents or caregivers had a significant impact on the behavior of children with congenital pseudarthrosis of the tibia.

Analysis of related factors of behavioral problems in children with congenital pseudarthrosis of tibia

SUMMARY OBJECTIVE: This study aimed to investigate the factors associated with behavioral problems in children with congenital pseudarthrosis of the tibia. METHODS: Random sampling is utilized to obtain a sample of 90 patients. The behavioral problems of the patients are detected by Achenbach Children's Behavior Scale. Parental emotional problems are investigated by the Self-Rating Depression Scale and Self-Rating Anxiety Scale. RESULTS: The results demonstrate that the detection rate of behavioral problems in children with congenital pseudarthrosis of the tibia is 53.3% (48/90). Among these behavioral problems, an abnormal rate is higher in the four dimensions: thinking, violation of discipline, social interaction, and aggression. The anxiety and depression scores of caregivers are statistically higher in the abnormal group than in the normal group. The results of the multivariate analysis show that the anxiety degree of the parents had a significant impact on the behavior of the children. CONCLUSIONS: Children with congenital pseudarthrosis of the tibia are facing the issues of high rates of behavioral problems. Parents of children with congenital pseudarthrosis of the tibia had higher levels of anxiety and depression than parents of normal children. The anxiety and depressive state of mind of parents or caregivers had a significant impact on the behavior of children with congenital pseudarthrosis of the tibia.

CircPVT1 promotes the tumorigenesis and metastasis of osteosarcoma via mediation of miR-26b-5p/CCNB1 axis.

INTRODUCTION: Osteosarcoma (OS) is the most aggressive malignancy among the bone tumors in the world. Circular RNAs (circRNAs) have been reported to be participated in multiple cancers, including OS. Meanwhile, circPVT1 has been proved to be upregulated in OS. However, the mechanism by which circPVT1 mediates the tumorigenesis of OS remains to be further explored. MATERIALS AND METHODS: Protein and gene expressions in OS cells were measured by western blot and RT-qPCR, respectively. Cell growth was assessed by flow cytometry and colony formation, respectively. In addition, cell migration was assessed by wound healing, and invasion was evaluated by Transwell assay. Meanwhile, the correlation among circPVT1, miR-26b-5p and CCNB1 was explored by RNA pull-down and dual luciferase assay. Finally, in vivo model was established to explore the role of circPVT1 in OS in vivo. RESULTS: CircPVT1 and CCNB1 were significantly upregulated in OS cells, while miR-26b-5p was downregulated. Knockdown of circPVT1 notably inhibited proliferation and induced apoptosis of OS cells. CircPVT1 shRNA significantly suppressed the OS cell invasion and migration. Meanwhile, circPVT1 sponged miR-26b-5p and CCNB1 was found to be the direct target of miR-26b-5p. Furthermore, silencing of circPVT1 inhibited the growth and metastasis of OS in vivo. CONCLUSION: Silencing of circPVT1 notably suppressed the tumorigenesis and metastasis of OS via miR-26b-5p/CCNB1 axis. Therefore, circPVT1 might be used as a target for OS treatment.

Analysis of Influencing Factors of Family Resilience in Children with Congenital Tibial Pseudoarthrosis.

AIM: To investigate the status of the family resilience score of caregivers of children with congenital pseudarthrosis of the tibia (CPT) and analyse its influencing factors to provide a reference and basis for clinical formulation of a family resilience intervention programme. METHODS: A total of 379 families of children with CPT were included in this study, which used a combination questionnaire to investigate the families of children with CPT. The researchers sent a link to the questionnaire to all eligible subjects to conduct a survey on the characteristics of families of children with CPT. Single factor analysis was used to compare the total scores of family resilience. Multiple linear regression was used to determine meaningful variables for single factor analysis. RESULTS: The average family resilience score was 151.79 ± 30.79, the lowest score was 20 and the highest score was 231. The CPT usually occurred in unilateral limbs (37.63%). The payment methods of medical expenses were through a rural cooperative medical system (44.85%). The caregivers were mostly the mothers (62.80%) and caregivers were 31-40 years old (62.27%). Most caregivers were farmers (30.34%). The average monthly income of the families in the past year was 1000-5000 yuan (54.09%). There were significant differences in family resilience scores between caregivers' working conditions (P = 0.039) and average monthly incomes in the past year (P = 0.008). The working conditions of caregivers and the average monthly income of families in the past year were the main factors affecting the family resilience of caregivers of children with CPT. CONCLUSION: The caregivers' working conditions and the average monthly income of families were the influencing factors in the family resilience score.

Comparative efficacy of 10 Chinese herbal injections combined with GP regimen chemotherapy for patients with advanced NSCLC a systematic review and network meta-analysis.

Background: Numerous studies have indicated that some Chinese herbal injections (CHIs) might have a beneficial treatment effect when used in combination with chemotherapy. However, the results of these studies have been inconsistent. The aim of this network meta-analysis (NMA) was to evaluate and compare the clinical efficacy and safety of different CHIs combined with gemcitabine plus cisplatin (GP) regimen chemotherapy with that of GP regimen chemotherapy alone in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Eight databases were systematically searched to identify randomized clinical trials (RCTs) from the date of inception of the database to August 11, 2021. The primary outcome measures were the objective response rate (ORR) and adverse reactions (including nausea and vomiting, and leukopenia). The secondary outcome measures were median survival time (MST) and quality of life (QOL). The quality of the included studies was assessed using the Cochrane risk of bias tool. Standard pair-wise and Bayesian NMAs were carried out to compare the effectiveness and safety of different CHIs combined with GP regimen chemotherapy using WinBUGS 14 and Stata 15.1 software. Sensitivity analysis and Egger's test were also performed to check robust. Results: A total of 92 eligible RCTs involving 7,728 patients and 10 CHIs were included. The results showed that Kangai injection (KAI), Kanglaite injection (KLT), Aidi injection and Compound Kushen (CKSI) injection displayed obvious advantages in both efficacy and safety. Aidi+GP (79.0%) showed great advantages of ORR, and KAI+GP and KLT+GP had the lowest probability in terms of leukopenia (4.4%) and nausea and vomiting (24.2%). Besides, KLT+GP was shown to positively affect MST. According to the subgroup analyses, CHIs might have a limited effect in reducing adverse reactions, and have a similar effect in squamous cell carcinoma and adenocarcinoma. Conclusions: KAI+GP of adjuvant drugs, Aidi+GP and CKSI+GP of anticancer drugs appeared to be the advantageous treatment options for patients with advanced NSCLC, owing to its superior therapeutic performance and reduced adverse reactions. KLT+GP might prolong survival. Nevertheless, additional results from multicenter trials and high-quality studies will be pivotal in supporting our findings.

[Study on difference of effect of Huoxue drugs and Yiqi Huoxue drugs on tumor metastasis based on immune remodeling].

Tumor metastasis is an important cause of tumor treatment failure. Its molecular mechanism is closely related to tumor cells remodeling immune cells and immunosuppressive microenvironment, so as to create a suitable soil for tumor cell invasion and growth. "Huoxue Huayu" is one of the important therapeutic principles in cancer treatment, but the influence of Huoxue drugs on tumor metastasis has been controversial in clinical application. In this paper, we systematically summarized the comparative study of Huoxue drugs and Yiqi Huoxue drugs in tumor metastasis in recent years, and discussed the differences of molecular mechanisms of Huoxue drugs and Yiqi Huoxue drugs in anti-tumor metastasis from the perspective of immune remodeling, so as to provide scientific basis for clinical rational application of Huoxue drugs and Yiqi Huoxue drugs.

The characteristics and related factors of insomnia among postoperative patients with gastric cancer: a cross-sectional survey.

PURPOSE: This study aims to explore the characteristics and related factors of insomnia of patients after operation for gastric cancer. METHODS: A cross-sectional survey was carried out and finally 115 patients with insomnia after operation for gastric cancer were included. The general information, gastric cancer-related information, sleep quality, and other symptoms were investigated. RESULTS: ① The Pittsburgh sleep quality index score of most insomnia patients after gastric cancer surgery was 11-15 points, and the sleep quality rating was "poor". ② The sleep quality of patients with insomnia after surgery for gastric cancer is related to the number of chemotherapy cycles, fatigue, and depression. ③ The probability of reduced sleep quality with the number of chemotherapy cycles >6 is 3.640 times that of ≤6. The probability of reduced sleep quality during moderate to severe fatigue was 4.390 times that of patients with no or mild fatigue. CONCLUSION: Attention to related factors may be associated with improvement of sleep quality in patients with gastric cancer after surgery.

The neurofibromatosis type I gene promotes autophagy via mTORC1 signalling pathway to enhance new bone formation after fracture.

Bone fracture is one of the most common injuries. Despite the high regenerative capacity of bones, failure of healing still occurs to near 10% of the patients. Herein, we aim to investigate the modulatory role of neurofibromatosis type I gene (NF1) to osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and new bone formation after fracture in a rat model. We studied the NF1 gene expression in normal and non-union bone fracture models. Then, we evaluated how NF1 overexpression modulated osteogenic differentiation of BMSCs, autophagy activity, mTORC1 signalling and osteoclastic bone resorption by qRT-PCR, Western blot and immunostaining assays. Finally, we injected lentivirus-NF1 (Lv-NF1) to rat non-union bone fracture model and analysed the bone formation process. The NF1 gene expression was significantly down-regulated in non-union bone fracture group, indicating NF1 is critical in bone healing process. In the NF1 overexpressing BMSCs, autophagy activity and osteogenic differentiation were significantly enhanced. Meanwhile, the NF1 overexpression inhibited mTORC1 signalling and osteoclastic bone resorption. In rat non-union bone fracture model, the NF1 overexpression significantly promoted bone formation during fracture healing. In summary, we proved the NF1 gene is critical in non-union bone healing, and NF1 overexpression promoted new bone formation after fracture by enhancing autophagy and inhibiting mTORC1 signalling. Our results may provide a novel therapeutic clue of promoting bone fracture healing.

Efficacy and safety of Kanglaite injection combined with first-line platinum-based chemotherapy in patients with advanced NSCLC: a systematic review and meta-analysis of 32 RCTs.

BACKGROUND: As a Chinese medicine injections, Kanglaite injection (KLT) is a complementary or alternative therapy for first-line platinum-based chemotherapy. However, the effect that certain factors, including the dose of KLT, chemotherapy cycles, evaluation criteria, or supportive treatment, have on the efficacy of the objective response rate (ORR), median survival time (MST), and adverse reactions is still unknown. METHODS: Eight databases were systematically searched from the inception dates to December 1, 2019, using the keywords Kanglaite, chemotherapy, and non small cell lung carcinoma to identify randomized clinical trials (RCTs). Analyses were performed using Review Manager 5.3 and Stata 15.1. RESULTS: There were 32 randomized controlled trials, involving 2,577 participants, that fulfilled the inclusion criteria. Compared with first-line platinum-based chemotherapy alone, KLT combined with chemotherapy could increase the ORR [risk ratio (RR), 1.41 (95% CI: 1.28 to 1.56); absolute risk difference (ARD), 0.13 (95% CI: 0.1 to 0.17)], decrease the risk ratio of adverse reactions [nausea and vomiting: RR, 0.58 (95% CI: 0.42 to 0.81); ARD, -0.17 (95% CI: -0.26 to -0.08); leukopenia: RR, 0.61 (95% CI: 0.44 to 0.86); ARD, -0.16 (95% CI: -0.24 to -0.08)], prolong MST, and increase disease control rate and Karnofsky performance status. According to the subgroup analyses, KLT combined with cisplatin or paraplatin plus paclitaxel (TP) failed to demonstrate a significant association with the ORR. And when lacking the use of supportive treatment, this combination would not decrease the RR of both adverse reactions compared with chemotherapy alone. CONCLUSIONS: KLT plus first-line platinum-based chemotherapy, except when chemotherapy regimens were TP, increased efficacy and quality of life in patients with advanced NSCLC. We are unsure whether this combination offers a low risk of adverse reactions. Additional high-quality RCTs are warranted to assess the effects of the combined therapy further.

Comparative efficacy of Chinese herbal injections combined with GP regimen chemotherapy for patients with advanced NSCLC: A protocol for systematic review and network meta-analysis.

BACKGROUND: Many research has indicated that some Chinese herb injections (CHIs) might be beneficial in combination with chemotherapy, however, with inconsistent results. Hence, the purpose of this network meta-analysis is to evaluate different CHIs plus cisplatin and gemcitabine (GP) with GP alone in terms of clinical efficacy and safety for treating patients with advanced NSCLC. METHODS: A comprehensive systematic search of clinical randomized controlled trials (RCTs) published in the PubMed, Embase, Web of Science (ISI), Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Database and China Biological Medicine Database (CBM) databases will be conducted to identify eligible studies up to the date of May 2020. The primary outcome measures objective response rate and adverse reactions (nausea and vomiting, leukopenia). The secondary outcome measures median survival time (MST), disease control rate, and quality of life. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The network meta-analysis will be performed using WinBUGS 14 and Stata 15.1 software. RESULTS: Based on the current evidence, the potential rank of the efficacy and safety of CHIs plus GP chemotherapy for advanced NSCLC will be assessed, and a prioritization regimen will be summarized. CONCLUSION: Evidence from this systematic review could be useful for patients, clinical practitioners, and guideline-makers to select an optimum proposal of CHIs plus GP for advanced NSCLC. ETHICS AND DISSEMINATION: It is not necessary for ethical approval because it is based on published studies. The protocol will be disseminated in a peer-reviewed journal or presented at a topic-related conference. PROSPERO REGISTRATION NUMBER: CRD42020167142.

The complete mitochondrial genome of Chrysomya nigripes (Diptera: Calliphoridae).

Chrysomya nigripes (Diptera: Calliphoridae) is a blow fly species of forensic importance. Here we demonstrated the complete mitochondrial genome of this species for the first time. Phylogenetic analyses indicated that entire mitochondrial genome sequences can provide more useful information for distinguishing C. nigripes from the other species.

Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration.

Treatment of intervertebral disc degeneration (IDD) seeks to prevent senescence and death of nucleus pulposus (NP) cells. Previous studies have shown that sirt6 exerts potent anti-senescent and anti-apoptotic effects in models of age-related degenerative disease. However, it is not known whether sirt6 protects against IDD. Here, we explored whether sirt6 influenced IDD. The sirt6 level was reduced in senescent human NP cells. Sirt6 overexpression protected against apoptosis and both replicative and stress-induced premature senescence. Sirt6 also activated NP cell autophagy both in vivo and in vitro. 3-methyladenine (3-MA) and chloroquine (CQ)-mediated inhibition of autophagy partially reversed the anti-senescent and anti-apoptotic effects of sirt6, which regulated the expression of degeneration-associated proteins. In vivo, sirt6 overexpression attenuated IDD. Together, the data showed that sirt6 attenuated cell senescence, and reduced apoptosis, by triggering autophagy that ultimately ameliorated IDD. Thus, sirt6 may be a novel therapeutic target for IDD treatment.

Predictable weathering of puparial hydrocarbons of necrophagous flies for determining the postmortem interval: a field experiment using Chrysomya rufifacies.

Preadult development of necrophagous flies is commonly recognized as an accurate method for estimating the minimum postmortem interval (PMImin). However, once the PMImin exceeds the duration of preadult development, the method is less accurate. Recently, fly puparial hydrocarbons were found to significantly change with weathering time in the field, indicating their potential use for PMImin estimates. However, additional studies are required to demonstrate how the weathering varies among species. In this study, the puparia of Chrysomya rufifacies were placed in the field to experience natural weathering to characterize hydrocarbon composition change over time. We found that weathering of the puparial hydrocarbons was regular and highly predictable in the field. For most of the hydrocarbons, the abundance decreased significantly and could be modeled using a modified exponent function. In addition, the weathering rate was significantly correlated with the hydrocarbon classes. The weathering rate of 2-methyl alkanes was significantly lower than that of alkenes and internal methyl alkanes, and alkenes were higher than the other two classes. For mono-methyl alkanes, the rate was significantly and positively associated with carbon chain length and branch position. These results indicate that puparial hydrocarbon weathering is highly predictable and can be used for estimating long-term PMImin.

Relationship between postoperative complications and fibular integrity in congenital pseudarthrosis of the tibia in children.

BACKGROUND: This study aimed to investigate the relationship between postoperative complications and fibular integrity in congenital pseudarthrosis of the tibia (CPT) in children. METHODS: A retrospective study was performed in 59 patients with Crawford type IV CPT who were treated with combined surgical technique from 2007 to 2011. The patients were divided into two groups, the CPT with fibular pseudarthrosis (group A) and CPT with intact fibula groups (group B), on the basis of fibula status after the union of CPT. The incidence rates of refracture, ankle valgus, tibial valgus, and limb length discrepancy in the two groups were investigated. RESULTS: In group A, 14 (36.8%) cases had refracture, 30 (78.9%) had ankle valgus; 27 (71%) exhibited tibial valgus with an average tibial valgus of 7° (6°-20°), and 24 (63.2%) had limb length discrepancy with an average limb length of 1.26 cm (0.6-4.4 cm). In group B, 2 (9.5%) cases had refracture, 11 (52.4%) had ankle valgus, 8 (42.9%) had tibial valgus with an average tibial valgus deformity of 2.9° (6°-13°), and 13 (61.9%) had limb length discrepancy with an average limb length of 1.48 cm (0.5-5 cm). Significant difference in refracture and ankle valgus was found between groups A and B (P<0.05). CONCLUSIONS: After the union of CPT, patients with fibular pseudarthrosis showed higher incidence of refracture and ankle valgus than those with intact fibula. Attention should be paid to the presence of fibular pseudarthrosis when managing CPT.

Wrapping grafting for congenital pseudarthrosis of the tibia: A preliminary report.

OBJECTIVE: Treatment of congenital pseudarthrosis of the tibia (CPT) remains a challenge. The autogenic iliac bone graft is important consistent of treatment for CPT. The purpose of this study was to investigate the role of wrapping autogenic iliac bone graft in improvement of the curing opportunities of CPT. METHODS: We combined Ilizarov fixator with intramedullary rodding of the tibia and wrapping autogenic iliac bone graft for treatment 51 cases of CPT between 2007 and 2010. The mean age is 3.2 years at index operation, of which 31 patients (61%) were below 3 years old. According to Crawford classification, 5 tibia had type-II morphology; 3, type-III; 43, type-IV. RESULTS: In the postoperative follow-up of 3.5 months (range from 3 to 4.5 months), all cases were found that the bone graft sites of pseudarthrosis of the tibia showed a significant augmentation and spindle-shaped expansion as obvious change. All cases of this series have been followed-up, average followed-up time were 1.6 years (range from 7 to 3.1 years), of which 19 cases were more than 2 years. The average time of removed the Ilizarov ring fixator was 3.5 months (range from 3 to 4.5 months). According to Johnston Clinical evaluation system, 26 cases had grade I, 21 cases, grade II, 4 cases, grade III. Following the Ohnishi X-ray evaluation criteria, union of pseudarthrosis of the tibia were 42 cases, delayed union 5 cases, nonunion 4 cases. CONCLUSION: Autogenic iliac bone graft is able to offer the activity of osteoblasts and osteogenesis induced by bone morphogenetic protein (BMP) and glycoprotein, meanwhile enclosing bone graft could help keep cancellous bone fragments in close contact around pseudarthrosis of the tibia, allowing the formation of high concentration of glycoprotein and BMP induced by chemical factors because of established the sealing environment in location, all of which could enhance the healing of pseudarthrosis of the tibia.

Combination of intramedullary rod, wrapping bone grafting and Ilizarov's fixator for the treatment of Crawford type IV congenital pseudarthrosis of the tibia: mid-term follow up of 56 cases.

BACKGROUND: The purpose of this study was to investigate the initial union rate, refracture rate and residual deformities of congenital pseudarthrosis of the tibia (CPT), using combined surgery including pseudarthrosis resection, intramedullary rodding, autogenous iliac bone grafting and Ilizarov's fixator, with a mean 5.2 years follow-up. METHODS: We retrospectively reviewed the records and diagrams of patients with Crawford type IV congenital pseudarthrosis of the tibia between February 2007 and March 2010. Patients managed by pseudarthrosis resection, intramedullary rod of the tibia, wrapping autogenous iliac bone grafting and Ilizarov's fixator were enrolled. We evaluated the bone union rate, tibial alignment, limb length discrepancy (LLD), valgus deformity of the ankle and the frequencies of refracture during period of follow-up. RESULTS: There were 56 cases enrolled in the study, with a mean follow-up 5.2 years (range, 3 to 6.7 years). The mean age of the patients at surgery was 3.5 years (range, 1.5 to 12.4 years). Fifty (89.2 %) of the 56 patients had primary bone union at site of pseudarthrosis, while 5 obtained union after second surgery and 1 failed. The average time spent to obtain pseudarthrosis initial union was 4.5 months (range, 3.0 to 10.0 months) and mean duration of Ilizarov treatment was 4.7 months (range, 3.2 to 10.4 months). Eleven (19.6 %) patients had proximal tibial valgus with a mean angle of 9.5° (range, 5 to 24°), while 10 (17.9 %) patients had ankle valgus deformities with a mean of 12.3° (range, 6 to 21°). Sixteen (28.6 %) patients had an average 2.2 cm LLD (range, 1.5-4.2 cm). Of the 50 cases who obtained initial bone union of pseudarthrosis, 13 (26.0 %) had refracture which need cast immobilization or secondary surgery. CONCLUSIONS: This combined surgery obtained initial union rate of 89.2 % at primary surgery while the refracture rate is 26.0 %. However, residual deformities such as proximal tibial valgus, LLD and ankle valgus were also existed which should be pay more attention to and dealt with. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov under the name "The Effect of Combined Surgery in Management of Congenital Pseudarthrosis of Tibia" ( NCT02640040 ), which was released on August 31, 2015.

MiR-384 regulated IRS1 expression and suppressed cell proliferation of human hepatocellular carcinoma.

Acquired evidence indicated that microRNAs (miRNAs) played essential roles in cancer development, including hepatocellular carcinoma (HCC). Functions and mechanisms of miRNAs involved in HCC remain largely unknown. Here, we found that miR-384 was significantly downregulated in HCC cells and tissues by RT-PCR. Gain and loss of function studies revealed that miR-384 significantly suppressed HCC cell proliferation. Insulin receptor substrate 1(IRS1) was identified as a direct and functional target of miR-384. Moreover, miR-384 decreased IRS1 expression, subsequently downregulating cyclin D1 and upregulating p21 and p-Rb expression. In addition, promotion of cell proliferation caused by miR-384-in was counteracted by silencing IRS1 expression with siRNAs. Taken together, our data provided convincing evidence that miR-384 exerted suppressive effect on HCC cell proliferation through the direct inhibition of IRS1 expression, suggesting miR-384 may serve as a potential therapeutic target for HCC.

Effect of Evodiamine on CYP Enzymes in Rats by a Cocktail Method.

The aim of this study was to assess the influence of evodiamine on the activities of the drug-metabolizing enzymes cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 in rats. The activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 were measured using specific probe drugs. After pretreatment for 1 week with evodiamine or physiological saline (control group) by oral administration, probe drugs phenacetin (5.0 mg/kg; CYP1A2 activity), tolbutamide (1.0 mg/kg; CYP2C9 activity), omeprazole (10 mg/kg; CYP2C19 activity), metoprolol (20 mg/kg; CYP2D6 activity) and midazolam (10 mg/kg; CYP3A4 activity) were administered to rats by oral administration. The blood was then collected at different times for ultra-performance liquid chromatography-tandem mass spectrometry analysis. The data showed that evodiamine exhibits an inhibitory effect on CYP1A2, CYP2C9 and CYP2D6 by increasing t(1/2), Cmax and AUC(0-∞), and decreasing CL/F compared with those of the control group. However, no significant changes in CYP2C19 and CYP3A4 activities were observed. In conclusion, the results indicated that evodiamine could inhibit CYP1A2, CYP2C9 and CYP2D6, which may affect the disposition of medicines primarily dependent on these pathways. Our work may be the basis of related herb-drug interactions in the clinic.

Effect of distraction osteogenesis in patient with tibial shortening after initial union of Congenital Pseudarthrosis of the Tibia (CPT): a preliminary study.

BACKGROUND: The purpose of our retrospective study was to evaluate the preliminary result of distraction osteogenesis in patient with tibial shortening after initial union of Congenital Pseudarthrosis of the Tibia (CPT). METHODS: All the CPT cases with tibial shortening after initial union managed by proximal tibial lengthening using Ilizarov technique were identified. All the patient charts and radiograms were reviewed. RESULTS: Between March 2007 and January 2012, 11 CPT cases were included with an average follow-up of 41 months (range, 34-51 months). The mean age at surgery was 8.5 years (range, 3.9-14.5y). The average length of discrepancy was 5.6 cm (range, 2.0-8.2 cm). Eight (8) cases had radiological findings of proximal tibial dysplasia, while the other 3 cases had not. The average distraction length gained was 5.3 cm (range, 3.5-8.0 cm) with a mean elongation rate of 21.4% (range, 15-30%). The Healing Index (HI) was 63.1 d/cm (range, 47-77 d/cm). In the 8 patients with proximal tibial dysplasia, 5 cases had lateral callus, 3 had central callus, and poor bone regeneration was observed in all of them with an average HI of 67 d/cm. In the other 3 patients without proximal tibial dysplasia, concave shaped callus was identified with an average HI of 52.7 d/cm. None of the patients had re-fracture, nonunion, axis deviation or angulation of the distraction area. Ankle joint stiffness was found in 2 of the patients. No evidence of knee contracture was detected. There were 5 cases with pin-tract infection which was managed by pin-tract nurse and oral administration of antibiotics. CONCLUSIONS: We concluded that proximal tibial lengthening after initial union of CPT was effective for management of tibial shortening, however it was characterized by poor bone regeneration with different types of callus from normal, greater healing index and prolonged fixator wearing. We recommended that tibial lengthening could be considered when the limb length discrepancy (LLD) was more than 4 cm in younger children after primary union of CPT.