circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC).

BACKGROUND: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. METHODS: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. RESULTS: The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. CONCLUSIONS: Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.

Role and Mechanism of Growth Differentiation Factor 15 in Chronic Kidney Disease.

GDF-15 is an essential member of the transforming growth factor-beta superfamily. Its functions mainly involve in tissue injury, inflammation, fibrosis, regulation of appetite and weight, development of tumor, and cardiovascular disease. GDF-15 is involved in various signaling pathways, such as MAPK pathway, PI3K/AKT pathway, STAT3 pathway, RET pathway, and SMAD pathway. In addition, several factors such as p53, ROS, and TNF-α participate the regulation of GDF-15. However, the specific mechanism of these factors regulating GDF-15 is still unclear and more research is needed to explore them. GDF-15 mainly improves the function of kidneys in CKD and plays an important role in the prediction of CKD progression and cardiovascular complications. In addition, the role of GDF-15 in the kidney may be related to the SMAD and MAPK pathways. However, the specific mechanism of these pathways remains unclear. Accordingly, more research on the specific mechanism of GDF-15 affecting kidney disease is needed in the future. In conclusion, GDF-15 may be a therapeutic target for kidney disease.

Thirst Relief Effect of 0.75% Citric Acid Spray During the Anesthesia Recovery Period: A Randomized Controlled Trial.

PURPOSE: Postoperative thirst is a common clinical issue. The discomfort caused by thirst during the perioperative period is strong and significant. Postoperative thirst is associated with emotional changes, giving rise to a series of adverse psychological and physical problems to patients. This study aimed to explore the effect of 0.75% citric acid spray on thirst relief during the anesthesia recovery period in China. DESIGN: A randomized controlled trial was conducted on subjects immediately after the removal of the endotracheal tube in a postanesthesia care unit. METHODS: A total of 112 patients with TI scores ≥3 on 0-10 numeric rating scale were randomized to the intervention group (0.75% citric acid spray group; n = 56) or control group (cool water spray; n = 56) by computerized randomization. Thirst assessment was performed before and 5 minutes after the intervention. Five minutes after the intervention, if the TI score was still ≥3 points, the spray would be added and the thirst assessment would be performed again until the TI score was <3 points. The onset time, duration time, and the number of additional sprays within 20 minutes was recorded. FINDINGS: Five minutes after the intervention, the thirst intensity score of the 0.75% citric acid spray group decreased from 5.57 ± 1.35 to 3.09 ± 1.20. The onset and duration times were 0.77 ± 0.47 min and 4.41 ± 2.59 min, respectively, and the number of spray additions in 20 min was 1.09 ± 0.92. The thirst intensity score of the cool water spray group decreased from 5.29 ± 1.52 to 3.73 ± 1.54. The onset and duration time were 0.84 ± 0.42 min and 2.77 ± 1.80 min, respectively, and the number of spray additions was 1.91 ± 1.24. No incidence of adverse events, including choking, aspiration, and allergies occurred. CONCLUSION: For thirsty patients during the anesthesia recovery period, the spray method is safe and has fewer side effects, including choking, aspiration, and allergies. Thus, 0.75% citric acid spray and cool water spray are both safe and effective; however, the 0.75% citric acid spray has a better thirst relief effect that lasts longer than the cool water spray.

Safety and efficacy of edaravone combined with alteplase for patients with acute ischemic stroke: A systematic review and meta-analysis.

Early administration of edaravone for acute ischemic stroke patients (AIS) receiving intravenous thrombolysis (IVT) has a potential neuroprotective effect. This study aimed to estimate the safety and efficacy of edaravone for AIS patients receiving IVT. We searched PubMed, Embase, Cochrane Library and Chinese Databases (CNKI database, Weipu database, and Wanfang database) for randomized controlled trials (RCT) from the inception of the database to 20 July 2020. Efficacy outcome was reduced National Institutes of Health Stroke Scale (NIHSS) score before and after treatment. Safety outcomes were intracranial hemorrhage (ICH) and mortality. Review Manager 5.3 and Stata 14.0 was used to perform the meta-analysis. A total of 1877 AIS patients from 17 studies were included, 939 (50.03%) patients received edaravone combined with alteplase treatment. Compared with alteplase alone, combined treatment reduced the NIHSS score (MD=3.95,95% CI 2.92-4.99, I² = 92%) and ICH (OR=0.44,95% CI 0.29-0.66, I² =0%) during hospitalization. There was no significant association between combined treatment and mortality during follow-up (OR=0.43,95% CI 0.13-1.42, I² =0%). Conclusions: Edaravone combined with alteplase seems to be safe and effective for AIS patients' short term outcomes.

Identification of CircRNA-miRNA-mRNA Regulatory Network in Gastrointestinal Stromal Tumor.

Circular RNA (circRNA) abnormal expression and regulation are involved in the occurrence and development of a variety of tumors. However, the role of circRNAs still remains unknown in gastrointestinal stromal tumors (GISTs). In the present study, the differential circRNA expression profile of GISTs was screened by human circRNAs chip and verified by qRT-PCR. The circRNA-miRNA-mRNA regulatory network was constructed using the cytoHubba plugin based on the Cytoscape software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore circRNA functions. Six significantly differential circRNAs were also verified in 20 pairs of GISTs and adjacent tissues by qRT-PCR. The result showed that a total of 543 differentially expressed circRNAs were identified in GISTs, of which 242 were up-regulated and 301 were down-regulated. Additionally, the circRNA-miRNA-mRNA network contained six circRNAs, 30 miRNAs, and 308 mRNAs, and the targeted mRNAs were associated with "regulation of biological process," "intracellular organelle," "protein binding," and enriched in Wnt signaling pathway. Furthermore, qRT-PCR demonstrated that hsa_circRNA_061346, hsa_circRNA_103114, and hsa_circRNA_103870 were significantly up-regulated in GISTs (n = 20), and hsa_ circRNA_405324, hsa_circRNA_406821, and hsa_circRNA_000361 were dramatically down-regulated in GISTs (n = 20). In addition, all of these circRNAs were shown to have high diagnostic values, and most of them were significantly associated with tumor size, mitotic figure, and malignant degrees in GISTs (P < 0.05). Therefore, we concluded that circRNAs were abnormally expressed in GISTs, and the circRNA-miRNA-mRNA regulatory network plays an important role in the occurrence and development of GISTs. Also, the identified six candidate circRNAs might be critical circRNAs and may present as potential diagnostic biomarkers for GISTs.

Concordance Study Between IBM Watson for Oncology and Real Clinical Practice for Cervical Cancer Patients in China: A Retrospective Analysis.

Watson for Oncology (WFO) is a artificial intelligence clinical decision-support system with evidence-based treatment options for oncologists. WFO has been gradually used in China, but limited reports on whether WFO is suitable for Chinese patients. This study aims to investigate the concordance of treatment options between WFO and real clinical practice for Cervical cancer patients retrospectively. We retrospectively enrolled 300 cases of cervical cancer patients. WFO provides treatment options for 246 supported cases. Real clinical practice were defined as concordant if treatment options were designated "recommended" or "for consideration" by WFO. Concordance of treatment option between WFO and real clinical practice was analyzed statistically. The treatment concordance between WFO and real clinical practice occurred in 72.8% (179/246) of cervical cancer cases. Logistic regression analysis showed that rural registration residences, advanced age, poor ECOG performance status, stages II-IV disease have a remarkable impact on consistency. The main reasons attributed to the 27.2% (67/246) of the discordant cases were the substitution of nedaplatin for cisplatin, reimbursement plan of bevacizumab, surgical preference, and absence of neoadjuvant/adjuvant chemotherapy and PD-1/PD-L1 antibodies recommendations. WFO recommendations were in 72.8% of concordant with real clinical practice for cervical cancer patients in China. However, several localization and individual factors limit its wider application. So, WFO could be an essential tool but it cannot currently replace oncologists. To be rapidly and fully apply to cervical cancer patients in China, accelerate localization and improvement were needed for WFO.

Safety and efficacy of early antiplatelet therapy in acute ischemic stroke patients receiving endovascular treatment: A systematic review and meta-analysis.

BACKGROUND: Endovascular treatment (ET) has been proved as safety and effective in acute ischemic stroke. However, early reocclusion is an inevitable complication following ET. There is uncertainty effect of early antiplatelet therapy on outcomes in patients with acute ischemic stroke undergoing endovascular treatment. METHODS: We searched major databases for articles published from 2011 to 2019 in the present study. Safety outcomes were any intracranial hemorrhage (ICH), symptomatic intracranial hemorrhage (sICH) and mortality. Efficacy outcomes were recanalization rate and follow-up functional outcome. Review Manager 5.3 and Stata Software Package 14.0 were used to perform the meta-analysis. RESULTS: Seven studies with a total of 1251 patients were included. A total of 451 (36.1%) patients were administrated by antiplatelet agent following ET. Meta-analysis suggested that early antiplatelet did not increase the risk for ICH (OR 1.15; 95% CI 0.56-2.37; P = 0.70), sICH (OR 1.29; 95% CI 0.79-2.09; P = 0.31) and mortality (OR 0.71; 95% CI 0.45-1.12; P = 0.14). There was no association between antiplatelet therapy and recanalization rate (OR 1.03; 95% CI 0.73-1.46; P = 0.30) or functional outcome (OR 0.97; 95% CI 0.55-1.69; P = 0.90). Sensitivity analysis indicated tirofiban did not associated with any ICH and mortality, nor improve the recanalization rate and functional outcome in patients receiving ET or mechanical thrombectomy (all p > 0.05). CONCLUSIONS: Early antiplatelet therapy may be safe in acute ischemic stroke patients, further studies are needed to confirm the efficacy.

Sex differences in clinical characteristics and 1-year outcomes of young ischemic stroke patients in East China.

BACKGROUND: Data concerning sex differences in clinical characteristics and outcomes of young ischemic stroke (IS) patients in Eastern China are scarce. Understanding sex differences in clinical characteristics and long-term outcomes of young IS patients might provide valuable evidence for designing preventative measures and therapeutic interventions. METHODS: The study included 228 acute IS patients aged up to 50 years recruited in the prospective Nanjing First Hospital Stroke Registry over a 5-year period. Univariable and multivariable logistic regression analyses were performed to determine whether there were sex differences in clinical characteristics and outcomes of young IS patients. RESULTS: Admission systolic blood pressure (130.12±24.3 vs 137.96±24.3 mmHg, P=0.005) of women was significantly lower than that of men. Logistic regression showed that young women had poorer outcomes defined as having modified Rankin Scale score of 3-6 at 12 months after the adjustment for history of prior stroke, NIHSS score, and complication of pneumonia (adjusted OR: 3.45; 95% CI: 1.43-8.32). CONCLUSION: Our study indicates that there may be significant differences in clinical characteristics between young women and men with acute IS in East China. Young women were more likely to be dead or dependent at 12 months after stroke onset. More attention should be paid to young women's IS prevention and management in East China.

T-cell lymphoma with POEMS syndrome.

Angioimmunoblastic T-cell lymphoma (AITL) is a unique subtype of peripheral T-cell lymphoma. POEMS syndrome is a rare paraneoplastic syndrome caused by an underlying plasma cell disorder (PCD). The occurrence of AITL with POEMS syndrome has rarely been reported in the literature. The current study presents the case of a 53-year-old male who presented with a rapidly proliferative lymph node on the left neck, which was identified as an AITL on biopsy. The patient also exhibited the complications of polyneuropathy, M-proteinemia, hepatosplenomegaly, left ventricular hypertrophy, endocrinopathy and skin changes, and was therefore diagnosed with POEMS syndrome. To the best of our knowledge, the present study is the first to report a case of AITL with POEMS syndrome. The findings in this case suggest that the aberrant clones of B cells can also be caused by AITL.

Enhanced photocatalytic activity of chromium(VI) reduction and EDTA oxidization by photoelectrocatalysis combining cationic exchange membrane processes.

A novel technology of photoelectrocatalysis (PEC) combining with cationic exchange membrane (CEM) was proposed for simultaneous reduction of chromium(VI) and oxidization of EDTA. The application of CEM was used to enhance the efficiency for prevention of the re-oxidation of reduced chromium with the electron-hole pairs. In this study, effects of current density, pH, TiO2 dosage, hydraulic retention time (HRT), light intensity and EDTA/Cr(VI) molar ratio were all investigated. The results showed that the optimum conversion efficiency occurred at 4mA/cm(2) with the presence of CEM. Higher conversion efficiencies were observed at lower pH due to the electrostatic attractions between positive charged TiOH2(+), and negatively charged Cr(VI) and EDTA. The optimum TiO2 loading of 1g/L was depended mainly on the acidic pH range, especially at higher HRT and irradiation intensity. In addition, higher EDTA/Cr(VI) molar ratio enhanced the reduction efficiency of Cr(VI), indicating EDTA plays the role of hole scavenger in this system. Moreover, incomplete EDTA decomposition contributes to the occurrence of intermediates, including nitrilotriacetic acid, iminodiacetic acid, glycine, oxamic acid, lyoxylic acid, oxalic acid, acetic acid and formic acid, as identified by GC/MS. Consequently, transformation pathway was determined from these analyzed byproducts and molecular orbital package analysis.