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1.
Ital J Pediatr ; 46(1): 155, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066803

RESUMO

BACKGROUND: The aim of this study was to quantify the impact of coronavirus disease 2019 (COVID-19) on pediatric operations, and establish preoperative, intraoperative, and postoperative protocols to improve the pediatric operations. METHODS: We here compare the number of patients who underwent surgery in Chongqing Medical University Affiliated Children's Hospital during the pandemic (January 23-March 11), after the pandemic (March 12-April 30), after our measures were put in place (May 1-May 21), and the equivalent period in 2019. RESULT: During the COVID-19 pandemic, 62.68% fewer patients underwent surgery than during the homologous period of time 1 year earlier (P < 0.01). After the COVID-19 pandemic, the number of orchidopexy cases increased significantly from 175.14 to 504.57 per week (P < 0.01). The large number of patients that accrued in our hospital may have increased the risk of COVID-19 transmission. In response, hospitals and clinics have made protocols and reorganized healthcare facilities (e.g., performing nucleic acid tests (NAT), adding adequate personal protective equipment (PPE)) from May 1, 2020. After the measures were implemented, the number of operations performed remained stable and comparable to the pre-pandemic period. COVID-19 RNA detection was performed in 5104 cases and there were no new confirmed cases in our hospital. CONCLUSION: This outbreak of COVID-19 has affected not only individuals with COVID-19 but also patients seeking surgical operations. Understanding the present situation helps clinicians provide a high level of treatment to all children.

2.
J Am Soc Nephrol ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046531

RESUMO

BACKGROUND: Mutations in PKD1 and PKD2, which encode the transmembrane proteins polycystin-1 and polycystin-2, respectively, cause autosomal dominant polycystic kidney disease (ADPKD). Polycystins are expressed in the primary cilium, and disrupting cilia structure significantly slows ADPKD progression following inactivation of polycystins. The cellular mechanisms of polycystin- and cilia-dependent cyst progression in ADPKD remain incompletely understood. METHODS: Unbiased transcriptional profiling in an adult-onset Pkd2 mouse model before cysts formed revealed significant differentially expressed genes (DEGs) in Pkd2 single-knockout kidneys, which were used to identify candidate pathways dysregulated in kidneys destined to form cysts. In vivo studies validated the role of the candidate pathway in the progression of ADPKD. Wild-type and Pkd2/Ift88 double-knockout mice that are protected from cyst growth served as controls. RESULTS: The RNASeq data identified cell proliferation as the most dysregulated pathway, with 15 of 241 DEGs related to cell cycle functions. Cdk1 appeared as a central component in this analysis. Cdk1 expression was similarly dysregulated in Pkd1 models of ADPKD, and conditional inactivation of Cdk1 with Pkd1 markedly improved the cystic phenotype and kidney function compared with inactivation of Pkd1 alone. The Pkd1/Cdk1 double knockout blocked cyst cell proliferation that otherwise accompanied Pkd1 inactivation alone. CONCLUSIONS: Dysregulation of Cdk1 is an early driver of cyst cell proliferation in ADPKD due to Pkd1 inactivation. Selective targeting of cyst cell proliferation is an effective means of slowing ADPKD progression caused by inactivation of Pkd1.

3.
Sci Rep ; 10(1): 16563, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024145

RESUMO

Deep brain stimulation (DBS) has been tentatively explored to promote motor recovery after stroke. Stroke could transiently activate endogenous self-repair processes, including neurogenesis in the subventricular zone (SVZ). In this regard, it is of considerable clinical interest to study whether DBS of the lateral cerebellar nucleus (LCN) could promote neurogenesis in the SVZ for functional recovery after stroke. In the present study, rats were trained on the pasta matrix reaching task and the ladder rung walking task before surgery. And then an electrode was implanted in the LCN following cortical ischemia induced by endothelin-1 injection. After 1 week of recovery, LCN DBS coupled with motor training for two weeks promoted motor function recovery, and reduced the infarct volumes post-ischemia. LCN DBS augmented poststroke neurogenetic responses, characterized by proliferation of neural progenitor cells (NPCs) and neuroblasts in the SVZ and subsequent differentiation into neurons in the ischemic penumbra at 21 days poststroke. DBS with the same stimulus parameters at 1 month after ischemia could also increase nascent neuroblasts in the SVZ and newly matured neurons in the perilesional cortex at 42 days poststroke. These results suggest that LCN DBS promotes endogenous neurogenesis for neurorestoration after cortical ischemia.

4.
J Clin Oncol ; : JCO2000979, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026937

RESUMO

PURPOSE: Randomized trials established the superiority of ibrutinib-based therapy over chemoimmunotherapy in chronic lymphocytic leukemia. Durability of progression-free survival (PFS) with ibrutinib can vary by patient subgroup. Clinical tools for prognostication and risk-stratification are needed. PATIENTS AND METHODS: Patients treated with ibrutinib in phase II and III trials provided the discovery data set and were subdivided into discovery and internal validation cohorts. An external validation cohort included 84 patients enrolled in our investigator-initiated phase II trial. Univariable analysis of 18 pretreatment parameters was performed using PFS and overall survival (OS) end-points. Multivariable analysis and machine-learning algorithms identified four factors for a prognostic model that was validated in internal and external cohorts. RESULTS: Factors independently associated with inferior PFS and OS were as follows: TP53 aberration, prior treatment, ß-2 microglobulin ≥ 5 mg/L, and lactate dehydrogenase > 250 U/L. Each of these four factors contributed one point to a prognostic model that stratified patients into three risk groups: three to four points, high risk; two points, intermediate risk; zero to one point, low risk. The 3-year PFS rates for all 804 patients combined were 47%, 74%, and 87% for the high-, the intermediate-, and the low-risk group, respectively (P < .0001). The 3-year OS rates were 63%, 83%, and 93%, respectively (P < .0001). The model remained significant when applied to treatment-naïve and relapsed/refractory cohorts individually. For 84 patients in the external cohort, BTK and PLCG2 mutations were tested cross-sectionally and at progression. The cumulative incidences of mutations were strongly correlated with the model. In the external cohort, Richter's transformation occurred in 17% of the high-risk group, and in no patient in the low-risk group. CONCLUSION: Patients at increased risk of ibrutinib failure can be identified at treatment initiation and considered for clinical trials.

5.
Cancer Med ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016643

RESUMO

BACKGROUND: AUF1 is one of the AU-rich binding proteins, which promotes rapid ARE-mRNA degradation. Recently, it has been reported that AUF1 is involved in regulating the antioxidant system because of its capacity to bind specifically to RNA containing oxidized bases and degrade oxidized RNA. Many antioxidant proteins have been reported to be overexpressed in colorectal cancer (CRC), however, the role of AUF1 in the progression of CRC has not been explored. METHODS: The expression level of AUF1 protein in human CRC cell lines and CRC tissues was detected by western blotting and immunohistochemistry (IHC. The effects of AUF1 knockdown on CRC cell proliferation, migration, invasion and changes in the signaling pathways were evaluated using a cell counting kit-8 (CCK-8), Transwell assays and western blotting. Subcutaneous xenograft tumor model was employed to further substantiate the role of AUF1 in CRC. RESULTS: AUF1 protein was upregulated in CRC tissues and CRC cells, and high expression of AUF1 was significantly associated with advanced AJCC stage (P = .001), lymph node metastasis (P = .007), distant metastasis (P = .038) and differentiation (P = .009) of CRC specimens. CRC patients with the high expression of AUF1 had an extremely poor prognosis. The knockdown of AUF1 suppressed CRC cell line proliferation, migration and invasion, inhibited CRC cells tumorigenesis and growth in nude mice, and reduced phosphorylated-ERK1/2 and phosphorylated AKT in CRC cells. CONCLUSION: Our findings demonstrate that AUF1 is probably involved in the progression of CRC via the activation of the ERK1/2 and AKT pathways. AU-rich RNA-binding factor 1 could be used as a novel prognostic biomarker and a potential therapeutic target for CRC.

6.
Int J Neurosci ; : 1-11, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32900248

RESUMO

PURPOSE: Sevoflurane is a widely used anesthetics, however, it has been reported that sevoflurane has neurotoxic effects. Studies have shown that miR-221-3p can ameliorate neuron damage. This study was to investigate whether miR-221-3p could reduce the neurotoxic effect of sevoflurane on nerve cells. MATERIALS AND METHODS: The rat hippocampal neuron cells were treated with sevoflurane or cultured normally. And we constructed neuron cells that overexpressed or low expression of miR-221-3p in the presence or absence of sevoflurane. The cells were transfected with CDKN1B or siCDKN1B, and co-transfected with miR-221-3p mimic and CDKN1B or miR-221-3p inhibitor and siCDKN1B. Cell viability and apoptosis were detected by CCK-8 and flow cytometer. Target gene of miR-221-3p were predicted by TargetScan and luciferase reporter assay. The expressions of related genes were detected by western blotting and quantitative real-time polymerase chain reaction. RESULTS: Sevoflurane decreased miR-221-3p level and increased CDKN1B level, inhibited cell viability and promoted apoptosis. Overexpress of miR-221-3p decreased CDKN1B level, up-regulated cell viability and inhibited apoptosis, and reversed the effects of sevoflurane on cell viability and apoptosis, while the effects low expression of miR-221-3p was contrary. CDKN1B was the target gene of miR-221-3p, which inhibited cell viability and promoted apoptosis, and reversed the effects of miR-221-3p mimic, whereas siCDKN1B did the opposite effects. CONCLUSIONS: Sevoflurane can cause nerve cell injury, and miR-221-3p may promote cell activity and inhibit apoptosis by inhibiting CDKN1B expression, thereby ameliorating cell injury induced by sevoflurane.

7.
Pediatr Int ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32969567

RESUMO

BACKGROUND: Thiopurine methyltransferase (TPMT) polymorphism is one of the causes for the toxicity of thiopurines, but rarely seen in Asian populations. Rather, nucleoside diphosphate-linked X-component motif 15 (NUDT15) gene is frequently linked to mercaptopurine (MP) intolerance and myelotoxicity in children with acute lymphoblastic leukemia (ALL) in East Asians, however little is known about the NUDT15 polymorphism in healthy children, especially in ethnic minorities of China. METHODS: Totally 162 cases of healthy children with Bai nationality were enrolled for NUDT15 genotyping. RESULTS: Three coding variants were identified in the NUDT15 gene including rs186364861, rs746071566 and rs116855232. Notably, the rs746071566 and rs116855232 in NUDT15 showed much higher frequencies in healthy children with Bai nationality compared with healthy East Asian populations, suggesting a concentrated distribution of these variants in the Bai ethnic group. CONCLUSION: This finding reveals the genetic polymorphism of NUDT15 in children with Chinese Bai nationality, providing a biological genetic background for the individualized therapy of thiopurines for children with Bai nationality in China.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32985859

RESUMO

Considering the extraordinary properties of graphene nanosheets, graphene-based materials from a molecular level to a macroscopic level as paper-like graphene films have recently grown for promising applications in many fields. However, there is still a major challenge in the design of the interface between adjacent graphene nanosheets so as to achieve high strength, high toughness, and high conductivity. Herein, we construct the high-performance graphene-based papers by using graphene as the matrix, carbon nanotubes (CNTs) as the reinforcement, and a long-chain molecule (1-pyrenylbutyric acid-linear diamine-1-pyrenylbutyric acid, PBA-diamine-PBA) as the bridging agent. The multiple π-π interactions between the fused rings, graphene nanosheets, and CNTs are generated among the aromatic rings of PBA, rGO, and CNTs, which significantly improve the mechanical properties and electrical properties of the cross-linked composite papers (abbreviated to CLP-X, where X is the carbon chain length). Furthermore, the linear diamines with different lengths of carbon chain affect the properties of papers after cross-linking. Especially, the as-obtained graphene-based paper (CLP-6) shows a high tensile strength (625.2 MPa), high toughness (28.5 MJ/m3), and high electrical conductivity (233.4 S/cm) as well as high solvent stability, which maintains the premium stability in different solvents. The improvement of strengthening and toughening mainly comes from the effective stress transfer and the reduction of slipping distance between rGO and CNTs during the stretching, with the help of multiple π-π cross-linking by in situ Raman analysis and simulation calculations. In addition, the high electrical conductivity leads to an excellent electromagnetic interference shielding capability (44,502 dB·cm2/g). The distinguished electric heating performance with rapid response to temperature changes is also recognized. Therefore, the proposed interface design is demonstrated as an effective way for developing a graphene-based paper with superior properties.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32941125

RESUMO

Two novel Gram-stain-positive bacteria, designated as SCSIO 52909T and SCSIO 52915T, were isolated from a deep-sea sediment sample collected at about 3448 m water depth of the South China Sea. Phenotypic, chemotaxonomic and genomic characteristics were investigated. These strains were aerobic and tested positive for catalase activity, oxidase activity and nitrate reduction. Optimal growth occurred at 28 °C, pH 7 and 3% salinity over 14 days cultivation. Its peptidoglycan structure was type A3α (l-Lys-l-Ala) and the only menaquinone was MK-8. Both strains possessed diphosphatidylglycerol, phosphatidylglycerol, an unidentified phosphoglycolipid, an unidentified glycolipid and an unidentified phospholipid. Their major fatty acids differed, but both contained iso-branched components of C16 : 0 12-methyl. Genome sequencing revealed two large genomes of 4.58 Mbp with G+C content of 67.0 mol% in SCSIO 52909T and of 4.42 Mbp with G+C content of 69.1 % in SCSIO 52915T. The two novel strains encoded genes for metabolism that are absent in most other Rubrobacter species, and possessed many more gene copy numbers of alkaline phosphatase and thioredoxin reductase. Results of gANI and 16S rRNA gene analyses suggested that the two strains represent two new species, with 74.9, 95.0 % pairwise similarity between each other, and less than 74.3 and 93.5 % to other recognized Rubrobacter species, respectively. In the phylogenetic analysis, strains SCSIO 52909T and SCSIO 52915T were separately clustered together and formed a well-separated phylogenetic branch distinct from the other known species in the genus Rubrobacter. Based on the data presented here, these two strains should be recognized as two new species in the genus Rubrobacter, for which the names Rubrobacter tropicus sp. nov., with the type strain SCSIO 52909T (=KCTC 49412T=CGMCC 1.13853T), and Rubrobacter marinus sp. nov., with the type strain SCSIO 52915T (=KCTC 49411T=CGMCC 1.13852T), are proposed.

10.
J Am Coll Cardiol ; 76(13): 1507-1516, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32972526

RESUMO

BACKGROUND: Incident cardiovascular disease (CVD) increases with increasing low-density lipoprotein cholesterol (LDL-C) concentration and exposure duration. Area under the LDL-C versus age curve is a possible risk parameter. Data-based demonstration of this metric is unavailable and whether the time course of area accumulation modulates risk is unknown. OBJECTIVES: Using CARDIA (Coronary Artery Risk Development in Young Adults) study data, we assessed the relationship of area under LDL-C versus age curve to incident CVD event risk and modulation of risk by time course of area accumulation-whether risk increase for the same area increment is different at different ages. METHODS: This prospective study included 4,958 asymptomatic adults age 18 to 30 years enrolled from 1985 to 1986. The outcome was a composite of nonfatal coronary heart disease, stroke, transient ischemic attack, heart failure hospitalization, cardiac revascularization, peripheral arterial disease intervention, or cardiovascular death. RESULTS: During a median 16-year follow-up after age 40 years, 275 participants had an incident CVD event. After adjustment for sex, race, and traditional risk factors, both area under LDL-C versus age curve and time course of area accumulation (slope of LDL-C curve) were significantly associated with CVD event risk (hazard ratio: 1.053; p < 0.0001 per 100 mg/dl × years; hazard ratio: 0.797 per mg/dl/year; p = 0.045, respectively). CONCLUSIONS: Incident CVD event risk depends on cumulative prior exposure to LDL-C and, independently, time course of area accumulation. The same area accumulated at a younger age, compared with older age, resulted in a greater risk increase, emphasizing the importance of optimal LDL-C control starting early in life.

11.
Langmuir ; 36(38): 11316-11323, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32907333

RESUMO

Tryptophan as an aromatic amino acid with a hydrophobic indole group plays important roles in stabilizing protein structures and enhancing molecular bindings in nature, but was rarely used in the molecular design of self-assembling peptides or gelators. Therefore, we prepared a series of short peptides from Trp amino acids and examined the potential roles of Trp residues for regulating peptide self-assembly and gelation. The introduced Trp amino acids not only diversify the molecular structures of peptide gelators, but also promote aromatic and hydrogen-bonding interactions for supramolecular self-assembling and gelation, which generates self-assembled nanostructures with twisted helical morphologies and supramolecular hydrogels with low minimal gelation concentrations. More importantly, the self-assembling peptides with Trp residues displayed strong preference for interacting with the lipidic membranes of bacteria, which resulted in bacterial flocculation and the death of E. coli and S. aureus.

12.
Mult Scler Relat Disord ; 46: 102484, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32932167

RESUMO

OBJECTIVE: This study aimed to perform a meta-analysis of the efficacy and safety of azathioprine (AZA) for neuromyelitis optica spectrum disorders (NMOSD), considering the potential predictive factors related to patient response to AZA in this disease. METHODS: We performed a systematic online query in PubMed, EMBASE, The Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, WANFANG DATA, and CQVIP DATA. The available studies on the use of AZA in NMOSD patients were included. RESULTS: We analyzed a total of 21 studies including 1016 patients. Results demonstrated that AZA significantly decreased annual relapse rate (ARR) by 1.164 (95% confidence intervals (CI), -1.396 to -0.932; p < 0.001). Subgroup analysis showed that AZA significantly decreased ARR in both low-dose group (effect size (ES): -1.545) and moderate-dose group (ES: -2.026). AZA therapy also resulted in a significant reduction of 1.117 (95% CI: -1.668 to -0.566; p < 0.001) in expanded disability status scale (EDSS) score. AZA did not affect EDSS score in the low-dose subgroup (ES: -0.535; p = 0.209) or the moderate-dose subgroup (ES: -0.709; p = 0.064). During AZA therapy, 47% of patients did not experience any relapses (95% CI, 39% to 54%). In addition, 13% of patients developed leukopenia, 11% had elevated liver enzyme levels, 8% experienced nausea or vomiting, 5% developed pancytopenia and 6% died during follow-up. CONCLUSION: AZA is effective in reducing relapse and improving patients' neurological function. However, liver function monitoring and routine blood monitoring remain necessary. Within the safe upper limit, a higher dose of AZA may be associated with a better efficacy for NMOSD.

13.
Breast Cancer Res Treat ; 184(1): 237-248, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32757134

RESUMO

PURPOSE: This study aimed to investigate whether genetic polymorphisms in TGFB1 contribute to breast cancer (BC) susceptibility, and explore the mechanism of action. METHODS: A total of 7 tagging SNPs (tSNPs) were genotyped in 1161 BC cases and 1337 age-matched controls among Chinese Han population. Bioinformatics analysis was used to predict functional SNP closely linked to tSNPs. Luciferase gene reporter assay was performed to determine the effect of genetic variants on promoter activity. DNA pull-down assay and mass spectrometry were used to identify the differentially binding proteins to genetic variants. RESULTS: Genotyping analysis showed that rs1800469 (C>T) in the 5' regulatory region of TGFB1 was associated with reduced BC risk. Bioinformatics analysis predicted that rs11466313 (-2389_-2391 Del/AGG) in the 5' regulatory region of TGFB1, was closely linked to tSNP rs1800469 and could be functional. The genotyping of rs11466313 by PCR-SSCP showed that rs11466313 also conferred decreased BC risk. Luciferase assays demonstrated that rs11466313 minor allele reduced over ninefold of promoter activity compared with its major allele (p < 0.001). DNA pull-down assay and mass spectrometry revealed that rs11466313 minor allele lost the binding ability with FAM98B and HSP90B. Knocking down FAM98B but not HSP90B, the enhanced promoter activity driven by TGFB1 rs11466313 major allele was attenuated. CONCLUSIONS: This study elucidates the impact of functional polymorphism rs11466313 in the regulatory region of TGFB1 on breast cancer susceptibility and gene expression, and could be helpful for future research to determine the value of this TGFB1 variant in the clinical setting.

14.
Bioresour Technol ; 317: 124030, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32862102

RESUMO

This study investigates the kinetics, attachment, biofilm development and anammox bacteria enrichment of a novel detached anammox biofilm inoculation method on non-modified virgin MBBR carriers and pre-seeded denitrifying carriers. The study compares these results to the more common use of attached anammox carriers for anammox MBBR inoculation. The anammox bacteria specific attachment-growth rates for virgin carriers inoculated with detached anammox biofilm mass were 38.1% greater for the first 25 days, leading to approximately 30% less time required to achieve complete biofilm coverage than those measured in attached biofilm carrier inoculated systems during the attachment and early biofilm growth stages. The biofilm thickness increase rate was also 52.3% higher for virgin carriers with detached biofilm inoculum. Further, inoculation using pre-seeded denitrifying carriers compared to virgin carriers demonstrated a 13.8% preferential increase in anammox bacteria specific attachment-growth rate and a corresponding 47.2% higher NH4+-N removal rate at the time of biofilm maturation.


Assuntos
Biofilmes , Reatores Biológicos , Anaerobiose , Nitrogênio , Oxirredução , Plâncton , Esgotos
16.
Chem Biol Interact ; 330: 109228, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32827518

RESUMO

This study aimed at exploring the potential mechanism of decreased in vivo exposure of the antiplatelet agent, ticagrelor and its active metabolite, AR-C124910XX, mediated by tea polyphenols, which was first revealed by our previous study, as well as predicting the in vivo drug-drug interaction (DDI) potential utilizing an in vitro to in vivo extrapolation (IVIVE) approach. The bidirectional transport and uptake kinetics of ticagrelor were determined using Caco-2 cells. Inhibition potency of major components of tea polyphenols, epigallocatechin gallate (EGCG) and epigallocatechin (EGC) were obtained from Caco-2 cells, human intestinal and hepatic microsomes (HIMs and HLMs) in vitro. A mean efflux ratio of 2.28 ± 0.38 and active uptake behavior of ticagrelor were observed in Caco-2 cell studies. Further investigation showed that the IC50 values of EGCG and EGC on the uptake of ticagrelor were 42.0 ± 5.1 µM (95% CI 31.9-54.8 µM) and 161 ± 13 µM (95% CI 136-191 µM), respectively. EGCG and EGC also displayed moderate to weak reversible inhibition on the formation of AR-C124910XX and the inactive metabolite, AR-C133913XX in HIMs and HLMs, while no clinically significant time-dependent inhibition was observed for either compound. IVIVE indicated a significant inhibition effect of EGCG on the uptake process of ticagrelor, while no potential DDI risk was found based on microsomal data. A 45% decrease in ticagrelor in vivo exposure was mechanistically predicted by incorporating intestinal and hepatic metabolism as well as intestinal absorption. This dual inhibition of tea polyphenols on ticagrelor revealed the underlying potential of transporter-enzyme interplay, in which the altered uptake process was more critical.

17.
Seizure ; 81: 222-227, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32862118

RESUMO

OBJECT: Epilepsy patients may still have seizures after surgery, and there have been few studies on the response to antiepileptic drugs (AEDs) after surgery failure. The purpose of this study was to analyze the response to AEDs after unsuccessful epilepsy surgery. METHODS: Patients who underwent unsuccessful epilepsy surgery between January 1999 and January 2019 were evaluated. Patient demographics, etiology, factors related to surgery and AED use patterns were assessed. RESULTS: After excluding the 5 patients who were lost to follow-up and the 2 patients who died, the records of 103 consecutive patients were analyzed. Ninety patients (87.4 %) had seizure recurrence within one year after surgery, 2 (1.9 %) patients had recurrence from one year to two years after surgery, and 11 (10.7 %) patients had recurrence two or more years after surgery (2-10 years). After surgery failure, the patients tried at least 2 kinds of AEDs with different mechanisms for more than 2 years. The average total number of AEDs used was 5.97, the average number of AEDs used before surgery was 3.21, and the average number of AEDs used after surgery was 4.02. After retreatment with AEDs, 10 patients (9.7 %) were seizure-free, 18 patients' (17.5 %) seizures were alleviated, and 75 patients (72.8 %) had seizures as they did prior to the adjustments. The number of AEDs used before and after surgery and the total number of AEDs were not significantly different among the seizure free group, alleviated seizure group and no change group. There were no significant differences in seizure onset age, surgery age, etiology, time between seizure onset and surgery, magnetic resonance imaging, seizure type, localization and lateralization of the surgery site among the three groups. CONCLUSIONS: The results showed that a small percentage of patients (27.2 %) who undergo unsuccessful epilepsy surgery benefit from AED adjustments; however, the vast majority of patients (72.8 %) do not benefit from AED adjustments.

18.
Onco Targets Ther ; 13: 7045-7056, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801740

RESUMO

Background: LncRNA EMX2OS (EMX2 opposite strand/antisense RNA) is notably downregulated in prostate cancer (PCa) tissues and may be regarded as a potential molecular biomarker for diagnosis and prognosis. However, its exact role in regulating the development of PCa is obscure. Methods: The EMX2OS expression was assessed in PCa tissues, paracancer tissues, PCa cells and normal prostate epithelial cells by qPCR. Gain- and loss-of-function experiments were performed to investigate the role of EMX2OS and FUS in cGMP-PKG (cyclic guanosine monophosphate-dependent protein kinase)-mediated proliferation, invasion, and migration in human PCa cell lines DU145 and PC3. Then, the interaction of transcription factor 12 (TCF12) with EMX2OS promoter was confirmed by using the dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. RNA binding protein immunoprecipitation and RNA pull-down assays were used to verify the interaction between EMX2OS and FUS protein. Finally, the role of EMX2OS and FUS in tumor growth in vivo was validated in a xenograft nude mouse model. Results: TCF12 and EMX2OS were both downregulated in PCa tissues and cells, and they negatively regulated cell proliferation, migration and invasion, and activated cGMP-PKG pathway in DU145 and PC3 cells. TCF12 was a transcription factor of EMX2OS. TCF12 and EMX2OS overexpression both down-regulated cell proliferation, migration and invasion, and activated cGMP-PKG pathway in DU145 and PC3 cells. Furthermore, EMX2OS directly bound with FUS protein and had a synergy effect with FUS protein on cGMP-PKG-mediated cell functions, which could be suppressed by (D)-DT-2 (a cGMP-PKG inhibitor). In addition, the overexpression of FUS or EMX2OS individually markedly decreased the volume and weight of tumors in vivo, and co-overexpression of them further inhibited tumor growth. Conclusion: EMX2OS, transcriptionally regulated by TCF12, played a synergy role with FUS protein in regulating the proliferation, migration and invasion of PCa cells by activating the cGMP-PKG pathway.

19.
Oncogene ; 39(35): 5795-5810, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32724162

RESUMO

Our previous research demonstrated that extracellular adenosine 5'-triphosphate (ATP) could promote breast cancer cell invasion. However, the impact of extracellular ATP on chemoresistance and the mechanisms behind ATP pro-invasion and pro-chemoresistance remain unclear. Here we aimed to determine the molecules or signaling pathways involved. cDNA microarray was performed to identify the differentially expressed genes before and after ATP treatment. As a result, Sex-determining region Y-box 9 (SOX9) was up-regulated after ATP treatment in breast cancer cells. In vitro invasion and migration assays demonstrated that knocking down SOX9 attenuated ATP-driven invasive capability. Mass spectrometry and co-IP revealed that SOX9 interacted with Janus kinase 1 (JAK1). Afterward, IL-6-JAK1-STAT3 signaling was demonstrated to promote SOX9 expression and invasion following ATP treatment. Notably, ATP-IL-6-SOX9 signaling was shown to stimulate chemoresistance in breast cancer cells. ChIP assays identified some potential SOX9 target genes, among which carcinoembryonic antigen-related cell adhesion molecule 5/6 (CEACAM5/6) was demonstrated to mediate ATP pro-invasive function, while ATP-binding cassette subfamily B member 1 (ABCB1) and ATP-binding cassette subfamily G member 2 (ABCG2) mediated ATP-driven chemoresistance. In addition, SOX9-knockdown and apyrase (an ATP hydrolase)-treated MDA-MB-231 cells illustrated decreased tumor growth and enhanced drug sensitivity in nude mice. In vitro spheroid formation assays also proved the significance of ATP-SOX9 in mediating chemoresistance. Moreover, molecules involved in ATP-SOX9 signaling were up-regulated in human breast carcinoma specimens and were associated with poor prognosis. Altogether, SOX9 signaling is vital in ATP-driven invasion and chemoresistance, which may serve as a potential target for breast cancer therapies.

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