Allergen detection and logistic multifactor analysis of allergic rhinitis.

OBJECTIVE: This study aims to investigate the allergens in children with allergic rhinitis (AR) and AR-related influencing factors. PATIENTS AND METHODS: The clinical data of 230 children with AR admitted to our hospital from June 2020 to June 2021 were retrospectively analyzed and included in the observation group. The clinical data of 230 healthy children during the same time period were included as the control group. All children had been tested for allergens using serum allergens, and the clinical data were collected by telephone questionnaires. Univariate and multivariate logistic regression were used to analyze the risk factors affecting AR. RESULTS: A total of 230 children with AR was included in this study, and some of them had two or more allergens. The proportion of house dust mite was the highest among the inhaled allergens, about 75.22%. Shrimp accounted for the highest proportion of food allergens, about 40.87%. Compared with the control group, the proportion of floating population, home heating, allergy history, asthma and other general information in the observation group was higher. At the same time, the proportion of environmental factors such as second-hand smoke, number of residents (≤ 3), daily ventilation and cleaning (no), domestic animals, domestic plants, decoration within 2 years, and living environment (rural) in the observation group was higher. In addition, the proportion of family factors such as delivery mode (cesarean section), family history of allergic rhinitis, parents' education level (middle school and above) in the observation group was higher (p < 0.05). Univariate logistic regression analysis showed that allergic history, asthma, second-hand smoke, floating population, number of residents, domestic animals, decoration within 2 years, delivery mode, and family history of allergic rhinitis were the risk factors affecting the incidence of AR in children (p < 0.05), and daily window ventilation and cleaning were the protective factors (p < 0.05). The multivariate logistic regression analysis showed that asthma, second-hand smoke, floating population, decoration within 2 years, family history of allergic rhinitis and domestic animals were independent risk factors for the occurrence of AR (p < 0.05), and daily ventilation and cleaning were protective factors for the occurrence of AR in children (p < 0.05). CONCLUSIONS: The proportion of house dust mite in inhalation allergens and shrimp in food allergens were the highest in AR children. The incidence of AR was closely related to asthma, second-hand smoke, floating population, decoration within 2 years, family history of AR and domestic animals, etc. Targeted measures could effectively prevent the occurrence and recurrence of AR. At the same time, daily ventilation and cleaning were the protective factors which could reduce the incidence and occurrence of AR in children.

Inhibition of microRNA-543 alleviates sepsis-induced acute kidney injury via targeting Bcl-2.

OBJECTIVE: Sepsis has a high morbidity and mortality and is prone to cause acute kidney injury (AKI). Here, we aimed to demonstrate the function and molecular mechanism of microRNA-543 (miR-543) in septic AKI. MATERIALS AND METHODS: MiR-543 inhibitor or NC was transfected into LPS-treated HK-2 cells to observe lipopolysaccharide (LPS)-induced inflammation and apoptosis. The detection of inflammation and apoptosis of HK-2 cells relies on Western blot, quantitative Reverse-Transcription Polymerase Chain Reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: MiR-543 expression was increased in LPS-treated HK-2 cells. By transfecting miR-543 inhibitor into HK-2 cells, miR-543 expression was dramatically reduced. The downregulation of miR-543 remarkably inhibited the inflammation and apoptosis, which was manifested by the reduction of inflammatory cytokines (TNF-α, IL-6, IL-1ß), the reversal of apoptosis-related proteins expression (Bcl-1, Bax), the increase of cell viability and the decrease of the proportion of apoptotic cells. The result of Luciferase activity assay demonstrated that miR-543 directly targets Bcl-2. CONCLUSIONS: MiR-543 expression was increased in LPS-treated HK-2 cells, and silencing miR-543 could inhibit LPS-induced inflammation and apoptosis in HK-2 cells via targeting Bcl-2.

Hypomethylating agents for elderly patients with acute myeloid leukemia: a PRISMA systematic review and meta-analysis.

OBJECTIVE: Abnormal DNA methylation plays a critical role in acute myeloid leukemia (AML) pathogenesis and hypomethylating agents (HMAs) such as decitabine (5-aza-29-deoxycytidine) and azacitidine (5-azacytidine) are considered efficacious for treating AML. This study aimed to identify if HMAs have therapeutic advantages compared with conventional care regimens (CCR) or placebo in elderly AML patients. MATERIALS AND METHODS: We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to November July 15, 2020. Randomized controlled trials that compared the efficacy and adverse events associated with HMAs, CCR, or placebo were searched. RevMan 5.3 software was used to calculate the hazard ratio (HR) and risk ratio (RR) with a 95% confidence interval (CI). RESULTS: Seven trials with a total of 1966 participants were included. Meta-analyses showed that the overall survival of HMAs was better than that of CCR [HR=0.76, 95% CI (0.69-0.85), (p<0.01)], and the complete remission rate of elderly AML patients was increased by HMAs compared with CCR [RR=1.46, 95%CI (1.08-1.99), p=0.01)]. HMA treatment showed higher incidence of neutropenia [RR=1.30 (95%CI 1.07-1.59, p=0.008)], thrombocytopenia [RR=1.14 (95%CI 1.01-1.59, p=0.04)], and pneumonia [RR=1.37 (95%CI 1.06-1.76, p=0.02)] compared with CCR. CONCLUSIONS: Although HMAs cause a higher incidence of adverse events such as neutropenia, thrombocytopenia, and pneumonia, demethylation drugs are well-tolerated and effective for treating AML in the elderly.

Clinicopathological and prognostic value of long noncoding RNA SNHG7 in cancer patients: a meta-analysis.

OBJECTIVE: Recent studies have provided evidence that long noncoding RNA SNHG7 is highly expressed and associated with poor clinical outcomes in cancer patients. The meta-analysis is aimed to evaluate the prognostic value of SNHG7 across various cancers. MATERIALS AND METHODS: Eligible studies about prognosis and clinicopathological features of SNHG7 expression in all kinds of tumors were collected by searching the databases of PubMed, Web of Science, Embase, Cochrane Library from inception through August 13, 2020. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) from eligible studies were extracted and pooled to investigate the association between SNHG7 and survival or clinicopathology by STATA 16.0 software. RESULTS: A total of 13 studies enrolling 1029 cancer patients met the inclusion criteria in this meta-analysis. Based on the results, over-expressed SNHG7 was associated with deeper tumor invasion (OR: 2.76; 95% CI: 1.98-3.86; p: 0.000), earlier lymphatic metastasis (OR: 4.22; 95% CI: 3.04-5.86; p: 0.000), more advanced tumor stage (OR: 3.49; 95% CI: 2.45-4.98; p: 0.000) and poor histologic grade (OR: 2.23; 95% CI: 1.33-3.74; p: 0.002), but not with sex, age, tumor size and distant metastasis. As for prognosis, patients with high expression of SNHG7 were more likely to have shorter overall survival (OS) (HR: 1.64; 95% CI: 1.38-1.94; p: 0.000) and disease-free survival (DFS) (HR: 1.37; 95% CI: 1.09-1.71; p: 0.006). CONCLUSIONS: SNHG7 may serve as a novel biomarker in terms of predicting prognosis and clinicopathological characters in various human cancers.

Exosomes transferring long non-coding RNA FAL1 to regulate ovarian cancer metastasis through the PTEN/AKT signaling pathway.

The article "Exosomes transferring long non-coding RNA FAL1 to regulate ovarian cancer metastasis through the PTEN/AKT signaling pathway, by Q. Zhang, T.-Y. Len, S.-X. Zhang, Q.-H. Zhao, L.-H. Yang, published in Eur Rev Med Pharmacol Sci 2020; 24 (1): 43-54-DOI: 10.26355/eurrev_202001_19894-PMID: 31957817" has been withdrawn from the authors stating that "after the manuscript has been accepted, we are ready to continue to study the exosomes and their mechanism of action. Before the research, we read the latest guideline of exosomes research, MISEV2018. This guideline first suggests that extracellular vesicles should be used to refer to these cell-derived noncellular membrane structures, while exosomes are only applicable to those vesicles released from intracellular sources to extracellular cells by special means. Secondly, the guidelines suggest that when performing key functional verification experiments with extracellular vesicles, methods such as density gradient centrifugation should be used to purify the vesicles. Thirdly, strict negative control should be set up in the functional study of cells, such as cell-conditioned medium treated with extracellular vesicle production inhibitor (GW4869), so as to exclude the false positive of other non-extracellular vesicle components in functional analysis. In our published manuscripts, we called extracellular vesicles as exosomes, and used exosomes separation kit with low purity to separate the exosomes. No appropriate negative control is used in the functional analysis. Most importantly, the conclusion we made in our study is "SKOV3-secreted exosomes inhibited the PTEN/AKT signaling pathway by transferring lncRNA FAL1, thus inhibiting OC cell metastasis in vitro and in vivo". However, the study did not confirm whether lncRNA FAL1 was encapsulated by extracellular vesicles and transferred to OC cells or induced by extracellular vesicles to upregulate its expression in OC cells. Based on the above reasons, we believe that our understanding of extracellular vesicles is not deep enough, which leads to the inaccuracy and over-interpretation of the experimental results. In order to avoid the readers' misunderstanding of extracellular vesicles and ensure the preciseness of scientific research, all of our authors decided to withdraw this article. We will conduct our research again according to MISEV2018, interpret the experimental results and write articles again, and will submit to ERMPS in the near future". The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19894.

Neuroprotective effect of CTRP3 overexpression against sevoflurane anesthesia-induced cognitive dysfunction in aged rats through activating AMPK/SIRT1 and PI3K/AKT signaling pathways.

OBJECTIVE: To investigate the effects of C1q/tumor necrosis factor-related protein-3 (CTRP3) on postoperative cognitive dysfunction (POCD) and elucidate the potential regulatory mechanism in sevoflurane anesthesia-induced aged rats. MATERIALS AND METHODS: A sevoflurane anesthesia-induced POCD aged rat model was established and hematoxylin and eosin (H&E) staining was used to detect pathological changes of hippocampal neurons. Morris water maze task test was performed to determine the learning and memory ability of rats. Immunofluorescence, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot were used to detect CTRP3 expression. Enzyme-linked immunosorbent assay (ELISA) or qRT-PCR assays were used to evaluate the changes of markers of brain damage and inflammatory cytokines. Terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay was used to assess the apoptosis of nerve cells in hippocampus. Western blot assay were used to measure the expression levels of apoptosis-related protein, and AMP-activated protein kinase (AMPK)/SIRT1 and PI3K/AKT pathway. RESULTS: Sevoflurane exposure led to brain injury, cognitive dysfunction in aged rats and decreased the expression of CTRP3. Overexpression of CTRP3 could suppress nerve cell apoptosis, inhibit neuronal inflammation, reduce brain tissue damage and improve cognitive dysfunction of aged rats after sevoflurane anesthesia. Further studies showed that CTRP3 may play a role in POCD by regulating AMPK/SIRT1 and PI3K/AKT signaling pathways. CONCLUSIONS: CTRP3 may effectively protect against sevoflurane-induced cognitive dysfunction and served as a potential predictive indicator and therapy target for POCD.

Exosomes transferring long non-coding RNA FAL1 to regulate ovarian cancer metastasis through the PTEN/AKT signaling pathway.

OBJECTIVE: Tumor-derived exosomes have been repeatedly studied as tumor antigens, suppressing T-cell signaling molecules and promoting apoptosis in ovarian cancer (OC). Long non-coding RNAs (lncRNAs) have been recognized as major regulators in tumorigenesis, including OC. For this study, we try to find out the mechanism of exosomes and lncRNA FAL1 in OC. MATERIALS AND METHODS: After the extraction and identification of exosomes, the internalization of exosomes was observed. Invasion and migration experiments were conducted to investigate the effect of SKOV3 cells-secreted exosomes on OC tumorigenesis and metastasis. Furthermore, the in vivo findings were verified via xenograft tumors in nude mice. FAL1 was knocked out on exosomes. OC cells treated with exosomes were co-cultured with lncRNA FAL1 or/and PTEN to measure cell invasion and migration. RESULTS: SKOV3-secreted exosomes were absorbed and internalized by OC cells. After exosome treatment, the migration and invasion of OC cells were enhanced, tumors in nude mice were larger and heavier, metastasis was increased, and lncRNA FAL1 expression was increased. When lncRNA FAL1 was knocked out, the promoting effects of SKOV3 cells-secreted exosomes on OC cell metastasis were weakened, along with increased PTEN level and decreased AKT phosphorylation level. In HO-8910PM cells treated with siRNA-FAL1 exosomes and siRNA-PTEN, cell invasion and migration, and AKT phosphorylation were restored. CONCLUSIONS: SKOV3-secreted exosomes inhibited the PTEN/AKT signaling pathway by transferring lncRNA FAL1, thus inhibiting OC cell metastasis in vitro and in vivo.

MiR-9 accelerates epithelial-mesenchymal transition of ovarian cancer cells via inhibiting e-cadherin.

OBJECTIVE: To investigate the influence of micro-ribonucleic acid (miR)-9 on epithelial-mesenchymal transition (EMT) of ovarian cancer cells by targeted inhibition on E-cadherin (CDH1). PATIENTS AND METHODS: The human ovarian cancer cells were cultured and miR-9 was repressed by inhibitors and overexpressed by miRNA mimics. The expression of EMT-related proteins was measured via Western blotting (WB). The action target of miR-9 was determined through the dual-luciferase reporter gene assay. The changes in protein levels were detected using WB. RESULTS: The expression of miR-9 was markedly up-regulated in ovarian cancer tissues, that is, the expression level of serum miR-9 in ovarian cancer patients was higher than that in control group. After the inhibition of miR-9, the expression level of epithelial indicator CDH1 was increased, while that of interstitial indicator Vimentin was decreased. MiR-9 contained a complementary site in the 3'-untranslated region (UTR) of CDH1 messenger RNA (mRNA) and the mRNA and protein expressions of CDH1 in the cells were down-regulated obviously by miR-9 overexpression. CONCLUSIONS: MiR-9 promotes the EMT of ovarian cancer cells through the targeted inhibition on CDH1.

Long-term shunt patency and overall survival of transjugular intrahepatic portosystemic shunt placement using covered stents with bare stents versus covered stents alone.

AIM: To investigate the long-term shunt patency and overall survival of transjugular intrahepatic portosystemic shunt (TIPS) placement using covered stents with or without bare stents over a follow-up period up to 7 years. MATERIALS AND METHODS: A total of 154 patients undergoing TIPS placement were enrolled and analysed retrospectively. They were divided into two groups: those undergoing TIPS placement using covered with bare stents (group A, n=42) and those without bare stents (group B, n=112). RESULTS: The cumulative 5-year primary patency rate was significantly lower in group A than in group B (group A: 0% versus group B: 66.7%; p<0.001). The cumulative 5-year overall survival rates were comparable between the two groups (group A: 76% versus group B: 58.7%; p=0.214). The baseline portal vein thrombosis (hazard ratio [HR]:4.610; 95% confidence interval [CI]:2.691-7.897; p=0.000), portal pressure decrement (HR: 0.911; 95% CI: 0.845-0.982; p=0.015), and group (HR: 0.419; 95% CI: 0.239-0.736; p=0.002) were independent predictors for shunt dysfunction, while hepatocellular carcinoma (HR: 6.615; 95% CI: 2.863-15.283; p=0.000) and ascites (HR: 2.166; 95% CI: 1.298-3.615; p=0.003) were independent predictors for mortality. CONCLUSIONS: Although TIPS placement using covered with bare stents led to lowered long-term shunt patency than using covered stents alone, the overall survival rates were similar.

E2F2 induces MCM4, CCNE2 and WHSC1 upregulation in ovarian cancer and predicts poor overall survival.

OBJECTIVE: To explore the genes co-upregulated with E2F2 in ovarian cancer and their association with survival outcomes in ovarian cancer patients. MATERIALS AND METHODS: The raw data of GDS3592 was downloaded from GEO datasets for reanalysis. The overlapping subset between the top 150 upregulated genes in ovarian cancer epithelial cells (CEPIs) and the E2F2 positively correlated genes (Pearson's r≥0.5) in ovarian cancer cohort in TCGA was identified. The association between E2F2, MCM4, CCNE2 and WHSC1 and overall survival (OS) and recurrence-free survival (RFS) in ovarian cancer patients were assessed using Kaplan-Meier plotter. RESULTS: E2F2 is a significantly upregulated transcription factor in CEPIs. MCM4, CCNE2, and WHSC1 are co-upregulated with E2F2 among the 308 ovarian cancer samples (Pearson's r=0.5159, 0.3963 and 0.4941 respectively). Enforced E2F2 expression significantly enhanced MCM4, CCNE2 and WHSC1 transcription in SKOV3 and A2780 cells. High E2F2 and CCNE2 expression are associated with worse OS (high E2F2, HR: 1.48, 95%CI: 1.17-1.85, p<0.01; high CCNE2, HR: 1.36, 95%CI: 1.15-1.6, p<0.01). High MCM expression might be associated with worse RFS at the margin of significance (HR: 1.18, 95%CI: 1.00-1.39, p=0.055). CONCLUSIONS: MCM4, CCNE2, and WHSC1 are co-upregulated with E2F2 in ovarian cancer. Enforced E2F2 expression significantly increased MCM4, CCNE2, and WHSC1 expression in ovarian cancer cells. High E2F2 and CCNE2 expression are associated with worse OS among ovarian cancer patients.

Meta-analysis of osteoporosis: fracture risks, medication and treatment.

Osteoporosis is a brittle bone disease that can cause fractures mostly in older men and women. Meta-analysis is the statistical method which is applied in the frame work for the assessment of results obtained from various research studies conducted in several years. A meta-analysis of osteoporotic fracture risk with medication non-adherence has been described to assess the bone fracture risk among patients non-adherent versus adherent to therapy for osteoporosis by many researchers. Osteoporosis therapy reduces the risk of fracture in clinical trials, and real-world adherence to therapy which is suboptimal and can reduce the effectiveness of intervention. The methods of Medline, Embase, and CINAHL were literature searched for these observational studies from year 1998 to 2009, and up to 2015. The results of meta-analysis of osteoporosis research on fractures of postmenopausal women and men are presented. The use of bisphosphonate therapy for osteoporosis has been described with other drugs. The authors, design, studies (women %), years (data), follow-up (wks), fractures (types), and compliance or persistence results from years 2004 to 2009 from are shown in a brief table. The meta-analysis studies have been reviewed from other researchers on osteoporosis and fractures, medications and treatments.

Comprehensive analysis of phenotypes and genetics in 21 Chinese families with haemophilia B: characterization of five novel mutations.

Molecular characterization of haemophilia B (HB) at the factor IX gene (F9) is essential to establish diagnosis, confirm genotype-phenotype correlations and to advise in genetic counselling. This study aimed to identify the causative mutations in 21 Chinese families with HB and to analyse the association of these mutations with clinical phenotype. Phenotypic analyses were performed using one-stage assay for factor IX (FIX) activity (FIX: C) and enzyme-linked immunosorbent assay for FIX antigen (FIX: Ag). Direct sequencing of the F9 gene was carried out. For those suspected to have a large deletion, multiplex ligation-dependent probe amplification (MLPA) was performed. Predicting the causal impact of new changes was studied by bioinformatics approaches. We also assessed the effect of the F9 mutations on the FIX protein structure and function. Causative mutations were detected in all study patients. There were 14 point mutations, three small deletions, one large deletion and one small in-frame duplication that together comprised a total of 19 unique variants, of which five were novel. The structural and functional defects of novel missense and in-frame deletion/duplication mutations were demonstrated by bioinformatics approaches. The 12 missense mutations include five purely quantitative mutations, five predominantly qualitative abnormalities and two combined defects. Our data confirmed the genetic heterogeneity of the F9 mutations. Quantitative missense mutations were found to be in different regions of precursor FIX compared with qualitative and combined ones.

Different impact of two mutations of a novel compound heterozygous protein C deficiency with late onset thrombosis.

We investigated the alteration of coagulation state in a protein C (PC) deficiency pedigree and the impact of the PC gene mutations. The pedigree of a proband with cerebral hemorrhagic infarction had sixteen members with four generations. The plasma levels of PC activity (PC:A), protein S activity (PS:A), factor V:C and factor VIII:C, and routine coagulation tests were measured. Nine exons of the PC gene (PROC) were sequenced. Plasma PC:A and PC antigen (PC:Ag) of the proband were 26 and 18%, respectively, which was significantly lower than normal ranges. Two heterozygous missense mutations of PC in the proband were identified, T>G at site 6128 (exon 7) and G>C at site 8478 (exon 9) resulting in F139V and D255H, respectively. The family members with F139V (N = 4) or D255H (N = 4) had lower levels of PC:A and PC:Ag than members with wild-type PROC (N = 6). D255H mutation caused a more significant decrease in the levels of PC:A, PC:Ag and factor V:C as compared to F139V mutation (P < 0.05). Two independent mutations, F139V and D255H, of PROC reduce PC function. Compound heterozygous condition of the two mutations can cause synergistic PC deficiency, but resulting in later onset of cerebral thrombosis.

Quercetin protects oligodendrocyte precursor cells from oxygen/glucose deprivation injury in vitro via the activation of the PI3K/Akt signaling pathway.

The aim of this study was to investigate the protection of quercetin (QUE) on oligodendrocyte precursor cells (OPCs) from oxygen/glucose deprivation (OGD)-induced injury in vitro and explore whether the PI3K/Akt signaling pathway contributed to the protection provided by quercetin. The OGD condition was induced by including 2mM sodium dithionite (Na(2)S(2)O(4)) in glucose-free DMEM medium. The concentration of QUE in this study ranged from 3µM to 81µM. OPCs were identified by immunocytochemical staining. Cell viability was analyzed using the water soluble tetrazolium salt-8 (WST-8) and lactate dehydrogenase assay (LDH). The morphological changes of the nucleus were measured using Hoechst 33258 nuclear staining, and the ratio of apoptotic cells was determined by FITC annexin V- and propidium iodide (PI) flow cytometry assay kit. In addition, the levels of pro-apoptotic proteins such as cleaved-caspase-3 and Bax and the anti-apoptotic proteins p-Akt and Bcl-2 were quantified using western blotting. The results showed that the OPC cell survival rate was significantly increased by incubation in conditioned medium supplemented with QUE as measured by the WST-8 assay, while the LDH release rate was significantly decreased as analyzed by the LDH assay. Furthermore, apoptosis assay showed that the apoptosis ratio of OPCs was also dramatically reduced by QUE. Western blotting showed that the expression levels of Bax and cleaved-caspase-3 proteins were down-regulated, while Bcl-2 and p-Akt were up-regulated. Further study showed that the increase in p-Akt by QUE was reduced by the PI3K inhibitor LY294002. These results indicated that QUE effectively protected OPCs from OGD-induced injury and that the mechanism might be related to the activation of the PI3K/Akt signaling pathway.

First principles simulation of a ceramic /Metal interface with misfit

The relaxed atomic structure of a model ceramic/metal interface, 222MgO/Cu, is simulated, including lattice constant mismatch, using first principles local-density functional theory plane wave pseudopotential methods. The 399-atom computational unit cell contains 36 O and 49 Cu atoms per layer in accordance with the 7/6 ratio of MgO to Cu lattice constants. The atomic layers on both sides of the interface warp to optimize the local bonding. The interface adhesive energy is calculated. The interface electronic structure is found to vary appreciably with the local environment.