[Clinical analysis of 4 acute ischemic stroke children treated with endovascular thrombectomy].

Objective: To assess the feasibility of endovascular thrombectomy (EVT) for the treatment of acute ischemic stroke (AIS) in children. Methods: Clinical data and follow-up information of 4 AIS children who received EVT in the Department of Intervention & Hemangioma at the Children's Hospital of the Capital Institute of Pediatrics from December 2020 to June 2021 were collected retrospectively. The vascular recanalization after EVT was assessed by the modified thrombolysis in cerebral infarction (mTICI) score. Efficacy outcomes were assessed with initial and postprocedural Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score, and the modified Rankin scale (mRS) score at 3 and 6 months after treatment. Safety assessments included perioperative complications and intracranial hemorrhage post-treatment. Results: A total of 5 EVT treatment were performed on 4 children with AIS, of whom 3 were male. The age of onset was 4.6, 13.8, 7.8, 8.0, 8.9 years, respectively. The time from symptom onset to initiation of EVT was 19.0, 25.0, 22.0, 4.0, 16.5 hours, respectively and all patients achieved successful recanalization of the vessel after EVT (mTICI≥2b). The PedNIHSS score was 39, 14, 25, 39, 24 before treatment and decreased to 8, 1, 12, 39, 5 at discharge. All the procedures were performed with no perioperative complications. Only 1 patient with congenital heart disease had a recurrent AIS with malignant brain oedema and brain hernia. Although the occluded vessels were successfully recanalized,the symptoms were not improved and this patient died after treatment abandonment. The other 3 patients achieved good recovery at 6 months postoperatively. The mRS score of 3 patients was 3, 1, 2 at 3 months after EVT and decreased to 2, 1, 1 at 6 months. Conclusion: EVT treatment may be feasible and safe for pediatric AIS due to large vessel occlusion even when the treatment was initiated 6 hours post stroke, but children with heart disease may have a dismal prognosis.

Chondroitin Sulfate Enhances Proliferation and Migration via Inducing ß-Catenin and Intracellular ROS as Well as Suppressing Metalloproteinases through Akt/NF-κB Pathway Inhibition in Human Chondrocytes.

BACKGROUND: Chondroitin sulfate (CS) is found in humans' cartilage, bone, cornea, skin, and arterial wall. It consists of the foundation substance in the extracellular matrix (ECM) of connective tissue. The oral supplement form of CS is clinically used in treating osteoarthritis (OA). METHODS: Cell migration was observed by the transwell assay. The EMT, Akt/IKK/IκB pathways, TIMPs, collagen and MMPs in cell lysate were determined by Western blotting. The expression of MMP activity was determined by gelatin zymography. The production of reactive oxygen species (ROS) was determined by using a fluorescence spectrophotometer. RESULTS: In the current report, we demonstrated that CS can increase the cell proliferation and migration of chon-001 chondrocytes. Treatment with CS induced the epithelial-mesenchymal transition and increased the expression of type II collagen and TIMP-1/TIMP2 and inhibited the expressions and activities of metalloproteinase-9 (MMP-9) and metalloproteinase-2 (MMP-2). The phosphorylation of Akt, IκB kinase (IKK), IκB and p65 was decreased by CS. CS treatment resulted in ß-catenin production and XAV939, a ß-catenin inhibitor, and inhibited the cell proliferation by CS treatment. In addition, also significantly induced intracellular ROS generation. Treatment with antioxidant propyl gallate blocked cell migration induced by CS. CONCLUSION: We demonstrated that CS induced cell proliferation and migration of chondrocytes by inducing ß-catenin and enhancing ROS production. Moreover, our studies demonstrated that CS can increase the activity of chondrocytes and help patients with osteoarthritis to restore cartilage function.

Protein kinase C signalling involved in prothoracicotropic hormone-stimulated prothoracic glands in the silkworm, Bombyx mori.

In the present study, the participation of protein kinase C (PKC) signalling in prothoracicotropic hormone (PTTH)-stimulated ecdysteroidogenesis in Bombyx prothoracic glands (PGs) is demonstrated and characterized. PTTH stimulated phosphorylation of a 37-kDa protein in Bombyx PGs both in vitro and in vivo, as recognized by a PKC substrate antibody. Treatment with either A23187 or thapsigargin also stimulated this 37-kDa protein phosphorylation. PTTH-stimulated phosphorylation of the 37-kDa protein was markedly attenuated in the absence of Ca2+ . The phospholipase C (PLC) inhibitor, U73122, greatly inhibited PTTH-stimulated phosphorylation of this protein, indicating the involvement of Ca2+ and PLC. A mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor (U0126), a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) and a chemical activator of adenosine 5'-monophosphate-activated protein kinase (AMPK) (5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside) did not affect PTTH-stimulated phosphorylation of the 37-kDa protein, implying that ERK and PI3K/AMPK are not the upstream signalling pathways for PKC-dependent protein phosphorylation. The mitochondrial oxidative phosphorylation inhibitors (the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone and diphenylene iodonium) inhibited PTTH-stimulated phosphorylation of the 37-kDa protein, indicating its redox regulation. Treatment with PKC inhibitors (either calphostin C, chelerythrine C or rottlerin) reduced PTTH-stimulated phosphorylation of the 37-kDa protein. PTTH-stimulated ecdysteroidogenesis was also inhibited by treatment with rottlerin, thus further confirming participation of PKC-dependent phosphorylation in PTTH signalling. From these results, we demonstrated that redox-regulated PTTH-stimulated PKC signalling is involved in ecdysteroid secretion in Bombyx PGs.

A user-friendly objective prediction model in predicting colorectal cancer based on 234 044 Asian adults in a prospective cohort.

BACKGROUND: Prediction models of colorectal cancer (CRC) had limited application for not being user-friendly. Whether fecal immunochemical tests (FITs) can help predict CRC has been overlooked. PATIENTS AND METHODS: With 1972 CRCs identified, 234 044 adults aged ≥40 years were successively enrolled between 1994 and 2008. Prediction models were developed by questionnaire/medical screening and quantitative FIT. NNS (number needed to scope to find one cancer) is time dependent, spanning entire study period. Significant 'risk factors' were family history, body mass index, smoking, drinking, inactivity, hypertension, diabetes, carcinoembryonic antigen, and C-reactive protein. RESULTS: Positive FIT (≥20 µg/g hemoglobin/feces) had cancer risk 10-fold larger than negative FIT, and within each age group, another 10-fold difference. The C statistic of FIT (0.81) with age and sex alone was superior to the 'common risk-factors' model (0.73). NNS, stratified by age and by FIT values, demonstrated a scorecard of cancer risks, like 1/15 or 1/25, in 5 years. When FIT was negative, cancer risk was small (1/750-1/3000 annually). The larger the FIT, the sooner the appearance of CRC. For every 80-µg/g increase of FIT, there were 1.5-year earlier development of CRC incidence and 1-year earlier development of CRC mortality, respectively. Given the same FIT value, CRC events appeared in the proximal colon sooner than the distal colon. CONCLUSIONS: A simple user-friendly model based on a single FIT value to predict CRC risk was developed. When positive, NNS offered a simple quantitative value, with a better precision than most risk factors, even combined. When FIT is negative, risk is very small, but requiring a repeat every other year to rule out false negative. FIT values correlated well with CRC prognosis, with worst for proximal CRC.

[Analysis of four cases with congenital pulmonary airway malformation complicated by chronic pulmonary aspergillosis].

Objective: To investigate the clinical characteristics, treatment and prognosis of congenital pulmonary airway malformation (CPAM) complicated with chronic pulmonary aspergillosis (CPA) in children. Methods: The clinical manifestation, laboratory test, radiological feature, treatment and prognosis of 4 pediatric patients diagnosis of CPAM with CPA ascertained between March 2016 and April 2020 at the Department of No.2 Respiratory Medicine and Thoracic Surgery of Beijing Children's Hospital were retrospectively analyzed. Results: The 4 children included 2 males and 2 females, their age ranged from 9.9 to 13.6 years. Cough presented in 3 cases, hemoptysis in 2 cases, whereas in 1 case, pneumothorax was the first manifestation of the condition. Past history revealed multiple hospital admissions for pneumonia in 2 children and 1 with more than 2 episodes of wheezing. Aspergillus IgG was positive in 3 patients. Significantly elevated total IgE and fumigatus-specific IgE levels were noted in 2 children. CT demonstrated multiple cystic lesions, and fungal balls were seen in 2 children. They all underwent lobectomy and the lung tissue from the 4 children all demonstrated CPAM with Aspergillus infection. Aspergillus fumigatus was isolated from the abscess collected during operation in 1 patient. Postoperative, voriconazole was given in 3 children for 8 weeks, recurrence was observed in 2 children with characteristics of allergic bronchopulmonary aspergillosis. Voriconazole was given in one patient for 12 weeks with no recurrence. Conclusions: CPAM might be complicated with CPA,if there are hemoptysis, and fungal ball in chest CT, cautious preoperative examinations for microorganism are necessary. The necessity and duration of postoperative antifungal therapy need to be determined on individual basis.

MiR-155 affects proliferation and apoptosis of bladder cancer cells by regulating GSK-3ß/ß-catenin pathway.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-155 affects proliferation and apoptosis of bladder cancer cells by regulating GSK-3ß/ß-catenin pathway, by Z.-C. Dong, D. Zhang, X.-X. Zhang, Z.-Q. Yao, H. Wu, C.-H. Chen, J.-Q. Tian, published in Eur Rev Med Pharmacol Sci 2019; 23 (13): 5682-5690-DOI: 10.26355/eurrev_201907_18305-PMID: 31298320" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18305.

Circular RNA ZNF292 affects proliferation and apoptosis of hepatocellular carcinoma cells by regulating Wnt/ß-catenin pathway.

OBJECTIVE: The purpose of this study was to explore the function of circular ribonucleic acid (circRNA) zinc finger protein 292 (ZNF292) in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The expression of circRNA ZNF292 in Huh-7 cells was knocked down by small interfering RNAs (siRNAs), and the effect of circRNA ZNF292 knockdown on the proliferation of Huh-7 cells was analyzed by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Then, flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were adopted to analyze the impacts of circRNA ZNF292 knockdown on the cycle distribution and apoptosis of Huh-7 cells. Besides, the influences of circRNA ZNF292 knockdown on Wnt/ß-catenin signaling pathway and its downstream molecules were detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. RESULTS: Compared with those in siRNA-normal control (NC) group, the proliferation of Huh-7 cells was significantly inhibited and their cloning ability was remarkably weakened (p<0.05), the proportion of cells in S phase was decreased while that in G1 phase was increased (p<0.05), the apoptosis rate of Huh-7 cells was higher and the number of apoptosis was larger in siRNA-2# knockdown group (p<0.05). Besides, in Huh-7 cells with circRNA ZNF292 knockdown, the expressions of Axin, ß-catenin, phosphorylated signal transducer and activator of transcription 3 (p-STAT3), p-STAT5, Cyclin A and Cyclin-dependent kinase 2 (CDK2) were down-regulated, while the expressions of STAT3 and STAT5 did not change remarkably. CONCLUSIONS: Knock downing circRNA ZNF292 leads to cell cycle arrest in G1 phase, thus suppressing cell proliferation and promoting cell apoptosis. The regulatory mechanism of circRNA ZNF292 may involve the regulation of cell cycle and related genes.

[Clinical characteristics and prognostic analysis of 458 children with high-risk neuroblastoma in a single center].

Objective: To summarize the clinical characteristics of high-risk neuroblastoma (HR-NB) in a single center, analyze the prognostic factors of HR-NB. Methods: The clinical data of children with HR-NB who were treated and followed up at the hematology-oncology center of Beijing Children's Hospital from February 1, 2007 to June 30, 2018 were analyzed retrospectively. The clinical features were summarized. Kaplan-Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors. The last follow-up time was June 30, 2019. Results: A total of 458 children with HR-NB were enrolled in this study, including 265 males (57.9%) and 193 females (42.1%), the age at diagnosis was 40.0 months (4.5-148.0 months), the follow-up time was 22.0 months (0.2-138.0 months) and the time of tumor progression or recurrence was 15 months (1-72 months). The 5-year event-free survival (EFS) rate was (31.2±2.6)% and the 5-year overall survival (OS) rate was (43.9±3.2)%. The 5-year EFS rate and 5-year OS rate in 142 hematopoietic stem cell transplantation (HSCT) patients with bone marrow metastases were better than that in 196 non-transplantation cases with bone marrow metastases ((26.5±4.5)% vs. (25.1±3.6)%, χ²=13.773, P=0.001; (38.1±5.5)% vs. (35.7±4.7)%, χ²=9.235, P=0.002); 128 transplantation patients with bone metastases had higher 5-year EFS rate and 5-year OS rate than 188 non-transplantation cases with bone metastases ((28.5±5.0)% vs. (26.7±3.8)%, χ²=10.222, P=0.001; (37.1±6.0)% vs. (36.2±4.8)%, χ²=7.843, P=0.005). The 5-year EFS rate was higher in 37 HSCT patients with MYCN amplification than in 49 non-transplantation cases with MYCN amplification ((26.8±8.0) % vs. (20.5±6.4) %, χ²=5.732, P=0.017). No significant difference was found in 5-years OS rate between transplantation group with MYCN amplification and non-transplantation group with MYCN amplification ((31.4±8.6) % vs. (26.2±7.4) %, χ²=3.230, P=0.072). Univariate survival analysis showed that lactate dehydrogenase (LDH)≥1 500 U/L was associated with poor prognosis of patients with MYCN amplification (χ²=6.960, P=0.008). Multivariate Cox analysis showed bone marrow metastasis and LDH≥1 500 U/L were independent risk factors for poor prognosis of patients with non-MYCN amplification (HR=2.427, 1.618;95%CI：1.427-4.126, 1.275-2.054, P<0.05) for both comparisons. Conclusions: LDH≥1 500 U/L was the poor prognostic factor for patients with MYCN amplification. The bone marrow metastasis and LDH≥1 500 U/L were the poor prognostic factors for HR-NB patients with non-MYCN amplification. HSCT can improve the prognosis of patients with bone or bone marrow metastasis. It can also retard the time of progression or recurrence for patients with MYCN amplification.

[Epidemiological investigation on clinical characteristics of 801 inpatients with chronic wounds].

Objective: To analyze the clinical characteristics of 801 inpatients with chronic wounds. Methods: The medical records of patients with chronic wounds who were admitted to the General Hospital of Southern Theater Command of PLA (hereinafter referred to as the author's unit) from January 2013 to December 2017, including gender, occupation, wound type, age, department distribution, recovery status, recovery time, hospitalization time, hospitalization cost, treatment method, clinical outcome, and medical expenses were retrospectively analyzed. Data were statistically analyzed with chi-square test, Fisher's exact probability test, and Kruskal-Wallis H test. Results: Of 245 037 inpatients admitted to the author's unit within 5 years, 801 (3.3‰) patients with chronic wounds met the inclusion criteria. The composition ratio of chronic wound patients during the 5 years was 2.4‰ (106/44 230)-3.9‰ (191/49 342). Among chronic wound patients, there were 527 males and 274 females, with manual labor, retired, and unemployed patients accounted for a large proportion. The main type of chronic wound was unhealed wound after surgery, accounting for 28.2% (226/801), followed by diabetic wound, accounting for 22.7% (182/801) and traumatic wound, accounting for 16.5% (132/801). There was statistically significant difference in gender distribution of patients with different types of chronic wounds (χ(2)=28.236, P<0.05). The main types of wound in male patients were unhealed wound after surgery, diabetic wound, and traumatic wound, while the main types of wound in female patients were diabetic wound and unhealed wound after surgery. There was statistically significant difference in the age group distribution of patients with different types of chronic wounds (P<0.01). Patients aged 41-60 years had a high incidence of unhealed wound after surgery and traumatic wound, and patients aged 61-80 years had a high incidence of diabetic wound. Patients with chronic wounds in department of orthopedics had the highest recovery rate, followed by comprehensive department. There were statistically significant differences in hospitalization time and hospitalization cost of patients with chronic wounds admitted to different departments (χ(2)=47.390, 107.390, P<0.05). There were no statistically significant differences in cure status and cure time of patients with chronic wounds admitted to different departments (χ(2)=7.163, 15.510, P>0.05). Patients treated with surgery in combination with drug had higher recovery rates than patients given other treatment methods. There was no statistically significant difference in the cure rate of patients with different treatment methods (χ(2)=7.600, P>0.05). There were statistically significant differences in cure time, hospitalization cost, and hospitalization time of patients given different treatment methods (χ(2)=38.067, 130.520, 130.890, P<0.05). There were no statistically significant differences in hospitalization cost and hospitalization time of patients with different clinical outcomes (χ(2)=2.070, 5.790, P>0.05). The total medical cost of 801 patients with chronic wounds was about 47 million yuan, of which the total hospitalization cost per capita was 50, 725 yuan, with a minimum of 1 164 yuan and a maximum of about 1.16 million yuan per capita, and with drug and materials costs accounted for high proportions of the total cost. Conclusions: Patients with chronic wounds in the author's unit are mainly physical labor and middle-aged and elderly people, with more male patients than female patients. The main type of wound is unhealed wound after surgery, which brings serious economic burden to the patients and the society. Therefore, it is necessary to strengthen the public knowledge about chronic wounds and improve the awareness of prevention and treatment.

Insulin enhances and metformin reduces risk of colorectal carcinoma in type-2 diabetes.

BACKGROUND: Identifying colorectal cancer associated risks is important for conducting a program for the survey and prevention of colorectal cancer. AIM: To investigate the association between use of insulin or metformin with colorectal cancer (CRC) in type 2 diabetes (T2DM). DESIGN: Population-based cohort study. METHODS: Through analysis of National Health Insurance (NHI) database between 1998 and 2010 in Taiwan, we identified 66 324 T2DM patients aged ≥ 20 years and selected subjects without diabetes by 1: 1 randomly matching with the study cohort based on age, sex and index date. We followed up the participants until 31 December 2011 or when they withdrew from the NHI program. RESULTS: Compared with non-diabetic subjects, the T2DM patients exhibited an increased risk of CRC [adjusted HR (aHR) = 1.56, 95% confidence interval (CI) = 1.39-1.75], after adjustment for age, sex, urbanization level, comorbidities and examinations of colonoscopy, sigmoidoscopy, or stool occult blood test. Among the T2DM patients, insulin usage increased the risk of CRC (aHR = 1.86, 95% CI = 1.58-0-2.19) after adjustment for age, sex, urbanization level, comorbidities, metformin usage and examinations; nevertheless, metformin decreased the risk of CRC (aHR = 0.65, 95% CI = 0.54-0.77) after adjustment for age, sex, urbanization level, comorbidities, insulin usage and examinations. Compared with the non-insulin cohort, the risk of CRC tended to increase with the incremental dosage of insulin exposure. CONCLUSION: Our population-based cohort study demonstrated an association between T2DM and CRC. Among the T2DM patients, insulin use was associated with an increased risk of CRC and metformin use was associated with a decreased risk of CRC. Inability to obtain information on several potential confounding factors, such as lifestyle and dietary habits, is the major limitation of the study.

Limb salvage in antiphospholipid syndrome with repetitive arterial occlusions.

Outcomes of vascular surgery for patients with primary antiphospholipid syndrome (APS) presenting with acute limb ischaemia (ALI) are poor, with a high rate of postoperative arterial thrombosis and limb amputation. A primary antiphospholipid syndrome 42-year-old male patient presented with acute limb ischaemia. Timely endovascular thrombectomy successfully prevented irreversible tissue damage but failed to maintain this due to recurrent thrombosis. Intensive plasma exchange following repeated endovascular therapy (EVT) ameliorated this thrombotic event. Two weeks post-discharge, thrombotic arterial reocclusion led to readmission and repeated management. Following successful reperfusion, intensive immunosuppressive therapy and anticoagulant agents ensured that the patient was free from recurrent events during the next eight months. This case highlights the combination of endovascular thrombectomy and intensive plasma exchange for limb salvage in such cases.

[Clinical and genetic characteristics of focal epilepsy in children caused by GATOR1 complex gene variation].

Objective: To summarize the clinical and genetic characteristics of focal epilepsy in children caused by GATOR1 complex gene variation. Methods: The clinical data, gene variation and treatment outcome of 12 children with focal epilepsy caused by GATOR1 complex gene variation admitted to Beijing Children's Hospital Affiliated to Capital Medical University from June 2016 to October 2018 were retrospectively analyzed. Results: There were 7 males and 5 females in 12 cases. The epilepsy onset age was 5.5 (3.0, 12.0) months, and from 11 days to 16 months of age. The epileptic seizure types were all focal motor seizures, and one case combined with epileptic spasms. The frequency of seizures in all patients was more than one time per day. Seven cases had frontal lobe epilepsy and two cases had lateral temporal lobe epilepsy. One case had a family history of febrile seizures and two had a family history of suspicious epilepsy. Epileptic form discharges were observed in 9 patients during the interictal phase by electroencephalograms (EEG), and all of them were focal discharges. Eight cases had clinical seizures detected by EEG, in 4 of whom the seizures were originated in frontal region. There were no abnormalities in brain magnetic resonance imaging in 11 cases whereas 1 case had malformation of cortical development of left frontal lobe. Eight patients had DEPDC5 gene variation, one had NPRL2 gene variation, three had NPRL3 gene variation. One case had de novo variation and the other 11 had hereditary variation. There were 11 types of gene variation, including 5 nonsense variations, 3 missense variations, 2 frame shift variations and 1 in frame deletion variation. There was no clear relationship between the clinical phenotype and the genotype. During the follow-up period from 6 months to 2 years and 6 months, 6 cases had seizure control, 3 of them were controlled by oxcarbazepine. The other 6 cases had drug-refractory epilepsy, 2 of them failed with vagus nerve stimulation and ketogenic dietary therapy as well, meanwhile combined with mental retardation. Conclusions: GATOR1 complex gene variation can lead to genetic focal epilepsy, which usually has early onset with frequent seizures. Most of the patients have focal epileptic form discharges on EEG, and there is usually no structural lesion in brain imaging. Most of the patients have hereditary loss-of-function variations. Approximately half of cases are drug-resistant epilepsy.

Texture differentiation using audio signal analysis with robotic interventional instruments.

Robotic minimally invasive surgery (RMIS) has played an important role in the last decades. In traditional surgery, surgeons rely on palpation using their hands. However, during RMIS, surgeons use the visual-haptics technique to compensate the missing sense of touch. Various sensors have been widely used to retrieve this natural sense, but there are still issues like integration, costs, sterilization and the small sensing area that prevent such approaches from being applied. A new method based on acoustic emission has been recently proposed for acquiring audio information from tool-tissue interaction during minimally invasive procedures that provide user guidance feedback. In this work the concept was adapted for acquiring audio information from a RMIS grasper and a first proof of concept is presented. Interactions of the grasper with various artificial and biological texture samples were recorded and analyzed using advanced signal processing and a clear correlation between audio spectral components and the tested texture were identified.

STAT3-induced upregulation of lncRNA DUXAP8 functions as ceRNA for miR-577 to promote the migration and invasion in colorectal cancer through the regulation of RAB14.

OBJECTIVE: Previous reports have shown that long non-coding RNAs (lncRNAs) are involved in a series of biological processes and cancer in humans. Recently, lncRNA double homeobox A pseudogene 8 (DUXAP8) was frequently reported to be aberrantly expressed in multiple cancers and play a functional role. However, the exact expression, function, and mechanism of DUXAP8 in colorectal cancer (CRC) remain uncovered. PATIENTS AND METHODS: The expression levels of DUXAP8 were detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The clinical influence of DUXAP8 in HCC patients was statistically analyzed. Luciferase reporter and ChIP assays were carried out for the exploration of whether STAT3 was able to bind to the promoter of DUXAP8. Lost-of-function experiments were carried out for the determination of possible cellular function in CRC cells. The modulating associations between DUXAP8 and miR-577 and RAB14 were further studied in CRC cells. RESULTS: In this study, we first provided evidence that DUXAP8 was overexpressed in CRC and increasing expression of DUXAP8 indicates advanced clinical progression and poor survival of CRC patients. Then, transcription factor STAT3 was demonstrated to upregulate DUXAP8 in CRC cells. Functional assays via in vitro assays revealed that DUXAP8 knockdown through shRNA in HCT116 and LOVO cells inhibited cell proliferation, migration and invasion, and promoted apoptosis. Furthermore, an inverse relationship between DUXAP8 and miR-577 was found. In addition, we confirmed that DUXAP8 served as competing endogenous RNA to modulate miR-577, which can modulate RAB14, a well-studied oncogene. CONCLUSIONS: Our study revealed that the STAT3-induced up-regulation of DUXAP8 might provide a new perspective for CRC therapy.

MiR-155 affects proliferation and apoptosis of bladder cancer cells by regulating GSK-3ß/ß-catenin pathway.

OBJECTIVE: GSK-3ß negatively regulates Wnt/ß-catenin signaling pathway. The abnormal miR-155 expression is associated with bladder cancer. Bioinformatics analysis revealed a complementary binding site between miR-155 and GSK-3ß mRNA. This study investigated the role of miR-155 in the proliferation and apoptosis of bladder cancer cells. PATIENTS AND METHODS: The dual luciferase reporter gene assay validated the targeted regulation between miR-155 and GSK-3ß. Tumor tissues and adjacent tissues were collected from bladder cancer patients and the expression of miR-155 and GSK-3ß mRNA was detected by RT-PCR. Bladder cancer cell line BIU-87 cells were cultured in vitro and divided into miR-NC group and miR-155 inhibitor group. The expressions of miR-155, GSK-3ß and ß-catenin were compared, cell apoptosis was detected by flow cytometry, and cell proliferation was detected by EdU staining. RESULTS: Compared with adjacent tissues, miR-155 expression was significantly increased in bladder cancer tissues, and GSK-3ß mRNA expression was significantly decreased. There was a targeted regulatory relationship between miR-155 and GSK-3ß. Compared with SV-HUC-1 cells, miR-155 expression in bladder cancer BIU-87 and 5637 cells was significantly increased, and GSK-3ß expression was significantly decreased. Transfection of miR-155 inhibitor significantly increased GSK-3ß expression in BIU-87 and 5637 cells, decreased ß-catenin expression, increased cell apoptosis, and decreased cell proliferation. CONCLUSIONS: The increased expression of miR-155 plays a role in reducing the expression of GSK-3ß and in promoting the pathogenesis of bladder cancer. Inhibition of miR-155 can up-regulate the expression of GSK-3ß, inhibit the activity of Wnt/ß-catenin pathway, attenuate proliferation and promote apoptosis of bladder cancer cells.

[Phenotypic and genotypic characteristics of fever-induced paroxysmal weakness and encephalopathy caused by ATP1A3 pathogenic variants].

Objective: To characterize fever-induced paroxysmal weakness and encephalopathy (FIPWE) caused by ATP1A3 gene pathogenic variant. Methods: Phenotypic and genotypic characteristics of 4 FIPWE patients (3 boys and 1 girl), who were ascertained from October 2016 to March 2018 in Beijing Children's Hospital due to ATP1A3 heterozygous variants, were retrospectively analyzed. The whole exsome sequencing was used for genetic testing. Results: The onset ages of 4 patients were 2 years and 9 months, 2 years and 4 months, 8 months, 2 years and 5 months respectively. The episode ranged from 1 to 3 times, and at 3 months to 2 years and 10 months intervals. All 4 patients had symptoms of limb weakness and encephalopathy, accompanied with mild to severe ataxia or athetosis. The tendon reflex was absent in all patients, and the Babinski's sign was positive. Three patients had dysphagia and 3 patients had slurred speech. Three patients had abnormal eye movements, including strabismus and opsoclonus. None of the 4 patients exhibited visual impairment, auditory impairment or talipes cavus. The duration of acute phase ranged from 1 week to 3 months. In 3 relapsing patients, symptoms became progressively worse, with relapses occurring frequently and recovery being more difficult, and various sequelae were found after the last relapse. All patients carried heterozygous variant in ATP1A3 gene. The missense variants result in the substitution of an arginine residue at position 756. Three variants were identified, including C. 2267G > T (p. R756L) (1 case), C. 2266C > T (p. R756C) (2 cases), and C. 2267G > A (p. R756H) (1 case). Three were de novo and one inherited from his father, but the grandparents did not carry the variant. All variants were reported as pathogenic. Conclusions: FIPWE is one of new clinical phenotypes of ATP1A3 spectrum disease and most cases are sporadic. The missense variants result in the substitution of an arginine residue at position 756. This report provided insights into the phenotype-genotype association in patients with FIPWE caused by pathogenic variants of ATP1A3.

Effects of miR-221 on the apoptosis of non-small cell lung cancer cells by lncRNA HOTAIR.

OBJECTIVE: The aim of this study was to investigate the effects of miR-221 on the proliferation of non-small cell lung cancer (NSCLC) cells through long non-coding RNA (lncRNA) HOX transcript antisense RNA (HO-TAIR), and to explore the possible underlying mechanism. PATIENTS AND METHODS: Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was applied to detect the expression level of HOTAIR in 38 NSCLC patients. The correlations of HOTAIR expression with clinic-pathological features, as well as the correlation between HOTAIR expression and miR-221 expression was analyzed by RT-PCR. Furthermore, NSCLC cell lines were cultured in vitro, and the expressions of HOTAIR and miR-221 in NSCLC cells were also detected. A549 cells were transfected with miR-221 mimics, miR-221 inhibitors, HOTAIR-small interfering RNAs (siRNAs) and plasmid cytomegalovirus deoxyribonucleic acid (pcDNA)3.1-HOTAIR. The interaction between miR-221 and HOTAIR in transfected cells was analyzed via RT-PCR and Northern blotting. Ultimately, flow cytometry was adopted to analyze the effects of miR-221 on the apoptosis of NSCLC cells through HOTAIR. RESULTS: The expression of HOTAIR in tissues of clinical patients only exhibited a correlation with the stage of cancer. The expressions of HOTAIR in patients with stage I and II were remarkably lower than those with stage III and IV. Additionally, the expression of HOTAIR was negatively correlated with the expression of miR-221 (r=-0.7651, p<0.0001). Further studies revealed that there was a negatively regulatory interaction between miR-221 expression and HOTAIR expression. Apoptosis assay results manifested that miR-221 significantly promoted the apoptosis of NSCLC cells by negatively regulating HOTAIR expression. CONCLUSIONS: MiR-221 promotes the apoptosis of NSCLC cells through negative regulation of lncRNA HOTAIR, which can be used in the treatment of NSCLC.

Overexpression of lncRNA GAS5 attenuates cardiac fibrosis through regulating PTEN/MMP-2 signal pathway in mice.

OBJECTIVE: The present study aimed at investigating the effect and mechanism of lncRNA Growth Arrest-Specific 5 (GAS5) in cardiac fibrosis induced by isoproterenol (ISO) in vivo. MATERIALS AND METHODS: The C57BL/6 mice were injected subcutaneously with ISO to induce cardiac fibrosis and injected intracoronary with lentivirus pcDNA-GAS5. After 3 weeks, cardiac function was detected by echocardiography. The interstitial collagen volume was stained by Masson trichrome. The expression of GAS5 was measured by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). The expressions of phosphatase and tensin homologue (PTEN), matrix metalloprotease-2 (MMP-2), α-smooth muscle actin (α-SMA), and collagen I protein were measured by Western blot. RESULTS: Our results indicated that the expression of GAS5 was significantly down-regulated in the fibrotic myocardium. Overexpression of GAS5 after injection with pcDNA-GAS5 could attenuate cardiac fibrosis and improve cardiac function through increasing the expression of PTEN and decreasing the expression of MMP-2, α-SMA, and collagen I. CONCLUSIONS: Overexpression of GAS5 could attenuate cardiac fibrosis induced by ISO. The molecular mechanism was associated with the regulation of PTEN/MMP-2 signaling pathway.