Airway Reactance Predicts Static Lung Hyperinflation in Severe Asthma

Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment. Methods: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed. Results: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤−0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio. Conclusion: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH. (AU)

Antecedentes: En el asma bronquial, la hiperinsuflación pulmonar estática (SLH) medida mediante pletismografía corporal (Pleth) se asocia a un peor pronóstico. La gravedad de la SLH podría estar asociada con la disfunción de las vías respiratorias pequeñas (SAD), que puede medirse mediante la oscilometría de impulsos (IOS). Objetivo: Este estudio pretende determinar la correlación entre el SLH y la SAD en pacientes con asma grave, y la mejora de ambos parámetros en respuesta al tratamiento. Métodos: Se analizaron los datos de los pacientes que se inscribieron en el Registro de Asma Grave de Taiwán, una cohorte observacional prospectiva. Se realizaron periódicamente mediciones de Pleth e IOS. Se determinó la relación entre los parámetros espirométricos e IOS. Se analizaron los cambios en los parámetros clínicos y funcionales en respuesta al tratamiento. Resultados: De una muestra de 107 pacientes con asma grave, 83 (77,6%) presentaban SLH, definida mediante una relación volumen residual/capacidad pulmonar total (VR/CTP) aumentada. La mayoría de los pacientes eran mujeres de edad avanzada con peor función pulmonar y SAD, en comparación con los que no tenían SLH. El SAD por aumento de la resistencia/reactancia de las vías respiratorias se correlacionó significativamente con el SLH. La reactancia de las vías respiratorias a 5 Hz (X5) ≤-0,21 [kPa/(L/s)] detectó el SLH con un área bajo la curva ROC de 0,84 (p < 0,0001, sensibilidad = 85,2% y especificidad = 83,3%). Después de 12 meses, los pacientes que recibieron tratamiento biológico adicional presentaron una reducción significativa de las exacerbaciones, del nivel de óxido nítrico exhalado, del recuento de eosinófilos en sangre, una mejora del volumen espiratorio forzado en el primer segundo, de la X5, y una tendencia a la reducción del cociente RV/TLC en comparación con los que no recibieron tratamiento biológico... (AU)

A comprehensive prognostic analysis of cause-specific mortality in patients with ovarian serous cystadenocarcinoma using a competing-risks model: a case study of the SEER database.

OBJECTIVE: This retrospective study employed a competing-risks analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database to identify precise prognostic factors associated with ovarian serous cystadenocarcinoma (OSCC) in patients. PATIENTS AND METHODS: Patients with OSCC during 2004-2015 were identified in the SEER database, and their clinicopathological, demographic, and survival data were examined. Univariate analysis using Gray's test and the cumulative incidence function was used to evaluate the prognoses of events of interest. The multivariate analysis involved several models, including the Cox proportional hazards, Fine-Gray, and cause-specific (CS) hazard function models, to estimate the hazard functions of competing risks. Hazard ratios were analyzed to identify the reliability of the prognostic factors. RESULTS: Among the 10,400 individuals diagnosed with OSCC, 5,713 died from the illness, and 1,125 died from other causes. The cumulative incidence rate of events of interest was found to be significant for ethnicity, age at diagnosis, histological grade, American Joint Committee on Cancer (AJCC) stage, chemotherapy and surgery status, tumor size, marital status, and local lymph node metastases (p<0.05). The multivariate analysis revealed that ethnicity, histological grade, surgery and chemotherapy status, age at diagnosis, AJCC stage, marital status, and distant metastases were independent prognostic factors in the Cox model (p<0.05). Finally, the Fine-Gray and CS models demonstrated that ethnicity, histological grade, surgery and chemotherapy status, age at diagnosis, AJCC stage, tumor size, marital status, and combination summary stage were all identified as independent prognostic factors (p<0.05). CONCLUSIONS: This study determined the risk factors for OSCC using a competing risk analysis model established by the SEER database. The findings can help clinicians understand OSCC better and provide more accurate medical support to affected patients.

Investigating the prognostic value of constructing disulfidptosis-related gene models for lung adenocarcinoma patients.

OBJECTIVE: Disulfidptosis is a novel mode of cell death, a programmed mode of intracellular disulfide accumulation due to solute carrier family 7 member 11 (SLC7A11)-mediated abnormalities in the cell membrane cystine transport system. Numerous studies have confirmed the prominent role played by SLC7A11 in tumors, but the involvement of SLC7A11 as an important mediator of disulfidptosis in the death process of lung adenocarcinoma cells remains unclear. MATERIALS AND METHODS: We obtained 4,107 SLC7A11-related genes and analyzed them using a total of 1,040 lung adenocarcinoma transcriptome sequencing data from The Cancer Genome Atlas (TCGA) cohort and GEO (Gene Expression Omnibus) cohort and 991 relevant clinical data. First, we screened for differential genes and identified molecular subtypes for assessing characteristic differences between lung adenocarcinoma subtypes under the influence of SLC7A11-associated genes. Then, risk score models were constructed to assess the prognosis, immune infiltration, tumor microenvironment, and drug treatment effects in lung adenocarcinoma patients. Finally, we also analyzed the distribution of cell types and expression of characteristic genes within the tumor using a single-cell database. In addition, relevant drug sensitivities were predicted. RESULTS: We screened 956 genes with significant differences and identified 2 molecular subtypes and found significant differences in their prognosis and that subtype B had a significantly better survival prognosis than subtype A. In addition, we found that pathways associated with cell proliferation division and DNA repair were enriched in the high-risk type A samples. Finally, we constructed a robust risk-scoring system, and our risk analysis revealed a general reduction of various immune cell components and tumor stromal components in the immune microenvironment of high-risk lung adenocarcinoma and a distinct immune infiltration pattern of immune cells, which was associated with a lower survival rate. CONCLUSIONS: Our comprehensive analysis of SLC7A11-related genes suggests that disulfidptosis has a potential value in the tumor microenvironment, immunity, clinical outcome, and prognosis of lung adenocarcinoma. These findings may increase our understanding of disulfidptosis as a novel cell death paradigm and provide ideas for assessing the prognosis of lung adenocarcinoma and developing new diagnostic and therapeutic strategies.

Late-Night Overeating and All-Cause and Cardiovascular Disease Mortality in Adults Aged ≥ 50: A Cohort Study.

BACKGROUND: Late-night overeating (LNOE) is closely associated with many health risk factors, but whether LNOE can increase the risk of death remains unknown. Thus, the prospective cohort study aimed to investigate the relationship between LNOE and mortality using data from the National Health and Nutrition Examination Survey. METHODS: 11,893 participants aged 50 years and older were included in the study. Dietary information was obtained through 24-h dietary recall interviews. Cox regression, subgroup, sensitivity, and restricted cubic spline analyses were used to assess the association between LNOE and mortality. RESULTS: During a median follow-up of 8.3 years, 2,498 deaths occurred. After adjusting for major confounders, compared to the non-late-night eating (NLNE) group, the LNOE group was associated with higher risks of all-cause (HR = 1.47, 95% CI = 1.06-2.04) and cardiovascular disease (CVD) mortality (HR = 2.02, 95% CI = 1.13-3.60). No significant association was found between late-night eating (LNE) and mortality. Subgroup analyses showed that the LNOE group had a greater risk of all-cause and CVD mortality in participants older than 70 years, with alcohol consumption and hypertension and demonstrated an increased risk of all-cause mortality in males and higher CVD mortality in females. CONCLUSION: The habit of LNOE was an independent risk factor for all-cause and CVD mortality in US adults aged 50 years and older, which was also influenced by age, sex, alcohol consumption, and hypertension.

The association between UGT1A1 polymorphisms and treatment toxicities of liposomal irinotecan.

BACKGROUND: Initial dose adjustment is recommended for patients with known UGT1A1∗28 homozygosity for both conventional irinotecan and liposomal irinotecan (nal-IRI). A recent population pharmacokinetic (PK) study showed that Asian patients had a lower prevalence of UGT1A1∗28 homozygosity but a significantly higher maximum blood concentration of SN-38 (SN-38 Cmax) and a higher incidence of grade ≥3 neutropenia after nal-IRI administration than Caucasian patients. The current study investigated the association of UGT1A1 polymorphisms, including the Asian prevalent UGT1A1∗6, PK and toxicities of nal-IRI-based therapy in the Asian population. PATIENTS AND METHODS: A total of 162 patients with nal-IRI-based therapy and available UGT1A1∗6 and UGT1A1∗28 genotyping were included, with 82 Asian patients from six previous phase I or II studies of nal-IRI (cohort 1) and another 80 patients with nal-IRI + 5-fluorouracil/leucovorin every 2 weeks as real-world practice in a single institute in Taiwan (cohort 2). RESULTS: The frequency of UGT1A1∗6 or UGT1A1∗28 homozygosity/compound heterozygosity was 9.3%, with UGT1A1∗6/∗6 in 2.5%, UGT1A1∗28/∗28 in 1.9% and UGT1A1∗6/∗28 in 4.9%. Among the 53 patients in cohort 1 with available PK data, all 7 patients with homozygosity/compound heterozygosity harbored UGT1A1∗6 and had a significantly higher level of median dose-normalized area under the concentration-time curve (AUC) and Cmax of SN-38 than those with single heterozygosity/wild type. Of the entire study population, the incidence of grade ≥3 neutropenia and diarrhea was significantly higher in patients with homozygosity/compound heterozygosity than in those with single heterozygosity/wild type, 73.3% versus 38.1% (P = 0.012, Fisher's exact test) and 33.3% versus 9.5% (P = 0.018, Fisher's exact test), respectively. CONCLUSION: The results suggest that the recommendation of a lower starting dose of nal-IRI for patients with UGT1A1∗28 homozygosity should be extended to include patients with UGT1A1∗6 homozygosity/compound heterozygosity.

Ingestion of Lactobacillus helveticus WHH1889 improves depressive and anxiety symptoms induced by chronic unpredictable mild stress in mice.

Emerging evidence indicates that the alterations in the gut microbiota-brain axis (GBA), which is the bilateral connection between the gut microbial communities and brain function, are involved in several mental illnesses, including depression. Certain probiotic strains have been revealed to improve depressive behaviours and the dysregulation of 5-hydroxytryptamine (5-HT) metabolism in depression. Here we evaluated the potential antidepressant effects of Lactobacillus helveticus strains using an in vitro enterochromaffin cell model (RIN14B). The L. helveticus strain WHH1889 was shown to significantly promote the level of 5-hydroxytryptamine (5-HTP, 5-HT precursor) and the gene expression of tryptophan hydroxylase 1 (Tph1), which is the key synthetase in the 5-HT biosynthesis in RIN14B cells. Ingestion of 0.2 ml WHH1889 (1´109 cfu/ml) in a chronic unpredictable mild stress (CUMS) mouse model of depression for five weeks normalised depressive and anxiety-like behaviours in the forced swim test, tail suspension test, sucrose preference test, and open field test. Meanwhile, the CUMS-induced elevated level of serum corticosterone and declined levels of hippocampal 5-HT and 5-HTP were reversed by WHH1889. Furthermore, the disturbances of the gut microbiome composition with reduced microbial diversity were also improved by WHH1889, accompanied by the increased colonic 5-HTP level and Tph1 gene expression. In summary, these findings indicate that WHH1889 exerts antidepressant-like effects on CUMS mice, which is associated with the modulations of the 5-HT/5-HTP metabolism and gut microbiome composition. Therefore, ingestion of the L. helveticus strain WHH1889 with antidepressant potentials may become an encouraging therapeutic option in the treatment of depression.

Dietary Protein Intake in Relation to the Risk of Osteoporosis in Middle-Aged and Older Individuals: A Cross-Sectional Study.

OBJECTIVES: Dietary protein intake is of great significance for the bone health of middle-aged and elderly people. This study is aimed to explore the relationships between dietary protein intake and the risk of osteoporosis in middle-aged and older individuals among US population. METHODS: Based on the National Health and Nutrition Examination Survey (NHANES), this study includes a total of 20497 participants during 2005-2008, and identify 4707 middle-aged and older people aged 45 years or above. Demographic data and relevant dietary intake information are acquired through in-home management questionnaires. The logistic regression models are established to identify the odds ratio (OR) and 95% confidence interval (CI) of OP in each quartile category of energy-adjusted dietary protein intake. The receiver operating characteristic (ROC) curve is applied to explore the optimal cut-off value of daily dietary protein intake for predicting risk of OP. RESULTS: 442 participants with OP are identified among 4707 middle-aged and older people, and the dietary protein intake of OP group is significantly lower than that of non-OP group (P<0.001). The logistic regression analysis shows that with the increase of daily dietary protein intake, the prevalence of OP in each quartile category decreases gradually (P<0.001). This trend is not altered in univariate model (P<0.001), as well as the adjustments for the covariates of age and BMI (Model 1, P<0.001), the covariates of sex (Model 2, P=0.036), the covariates of smoking, drinking alcohol, education, ratio of family income to poverty, hypertension and diabetes (Model 3, P<0.001), and the covariates of dietary intake (Model 4, P=0.008). Moreover, we also identify that the daily dietary protein intake of 61.2g is the optimal cut-off value for predicting risk of OP. CONCLUSION: In general, among US population, the lower daily dietary protein intake is positively related to the ascending risk of OP in middle-aged and older individuals.

Protective effect of dexmedetomidine on neuronal hypoxic injury through inhibition of miR-134.

OBJECTIVE: To explore the mechanism of dexmedetomidine (DEX)-mediated miR-134 inhibition in hypoxia-induced damage in PC12 cells. METHODS: Hydrogen peroxide (H2O2)-stimulated PC12 cells were divided into control, H2O2, DEX + H2O2, miR-NC/inhibitor + H2O2, and miR-NC/ mimic + DEX + H2O2 groups. Cell viability and apoptosis were assessed by the 3-(4,5-dimethylthiazol(-2-y1)-2,5-diphenytetrazolium bromide (MTT) assay and Annexin V-FITC/PI staining, while gene and protein expression levels were detected by qRT-PCR and western blotting. Reactive oxygen species (ROS) levels were tested by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining, and malondialdehyde (MDA) content was determined with a detection kit. RESULTS: DEX treatment decreased H2O2-elevated miR-134 expression. H2O2-induced PC12 cell damage was improved by DEX and miR-134 inhibitor; additionally, cell viability was increased, while cell apoptosis was reduced. In addition, both DEX and miR-134 inhibitor reduced the upregulated expression of cleaved caspase-3 and increased the downregulated expression of Bcl-2 in H2O2-induced PC12 cells. However, compared to that in the DEX + H2O2 group, cell viability in the mimic + DEX + H2O2 group was decreased, and the apoptotic rate was elevated with increased cleaved caspase-3 and decreased Bcl-2 expression. Inflammation and oxidative stress were increased in H2O2-induced PC12 cells but improved with DEX or miR-134 inhibitor treatment. However, this improvement of H2O2-induced inflammation and oxidative stress induced by DEX in PC12 cells could be reversed by the miR-134 mimic. CONCLUSION: DEX exerts protective effects to promote viability and reduce cell apoptosis, inflammation, and oxidative stress in H2O2-induced PC12 cells by inhibiting the expression of miR-134.

LncRNA PRNCR1 aggravates the malignancy of oral squamous cell carcinoma by regulating miR-326/FSCN1 axis.

OBJECTIVE: The important regulatory mechanism of lncRNA PRNCR1 has been emphasized in malignant tumors. However, the role of lncRNA PRNCR1 remains unclear in oral squamous cell carcinoma (OSCC). The purpose of this study is to reveal the role of lncRNA PRNCR1 in OSCC. PATIENTS AND METHODS: RT-qPCR was used to detect mRNA expression. The functional mechanism of lncRNA PRNCR1 in OSCC was investigated by CCK-8, transwell and Luciferase reporter assays. RESULTS: LncRNA PRNCR1 was upregulated in OSCC and promoted cell proliferation, migration and invasion. LncRNA PRNCR1 directly binds to miR-326. The mutual inhibition between the expressions of lncRNA PRNCR1 and miR-326 was identified in OSCC. In addition, miR-326 restrained cell proliferation, migration and invasion in OSCC. Further, miR-326 directly targets FSCN1. FSCN1 expression was positively regulated by lncRNA PRNCR1 in OSCC. And FSCN1 promoted the progression of OSCC and aggravated the carcinogenic effect of lncRNA PRNCR1 in OSCC. CONCLUSIONS: LncRNA PRNCR1 promotes the progression of OSCC by functioning as a miR-326 'sponge' to upregulate FSCN1 expression.

Effect of appetite-conditioned reflex stimulation on early enteral nutrition tolerance after surgery.

OBJECTIVE: This study aimed to discuss the effects of appetite-conditioned reflex stimulation on the early enteral nutrition (EEN) tolerance, complications, and postoperative hospital stay in patients who underwent surgery. METHODS: Seventy patients who underwent laparoscopic radical resection of colorectal cancer surgery in our hospital between February and December 2017 were randomly divided into a stimulated appetite group (experimental group, including visual stimulation, nasal stimulation, taste stimulation and hearing stimulation) and a control group (n = 35). Both groups received EEN. EEN tolerance, complications, and postoperative hospital stay were then compared between the groups. RESULTS: Sixty-six patients, including 34 in the experimental group and 32 in the control group, completed the relevant experiment. The experimental group had significantly lower incidence rates of nausea, vomiting, bloating, use of prokinetic drugs, and gastric tube replacement (P < 0.05), and shorter tolerable regular eating time (5.0 ± 1.0 d vs 6.4 ± 1.9 d, P < 0.05) and postoperative hospital stay (7.0 ± 2.0 d vs 8.0 ± 1.8 d, P < 0.05) than the control group. No significant difference in complication rate was detected (P > 0.05). CONCLUSION: Appetite-conditioned reflex stimulation can improve EEN tolerance, decrease the risk of complications, and shorten ordinary diet recovery time and hospital stay.

Patient and procedural risk factors for increased postoperative pain after cesarean delivery under neuraxial anesthesia: a retrospective study.

BACKGROUND: There is significant interindividual variability in pain experienced after cesarean delivery. The goal of this study was to identify risk factors for increased postoperative pain in women undergoing cesarean delivery under neuraxial anesthesia with neuraxial morphine. METHODS: A retrospective chart review was conducted (June 1, 2013 to August 25, 2015). Patients were categorized into three groups, according to the weighted area-under-the-curve (AUC) of pain scores within 48 h of surgery, as mild (weighted AUC 0-3), moderate (4-6) or severe (7-10) pain. We evaluated potential factors that could influence variability in pain, including patient demographics, comorbidities, obstetric history, and surgical details. RESULTS: A total of 1899 patients were included in the analysis. Pain was mild in 896 patients, moderate in 895, and severe in 108 patients. In the multivariable analysis, the following factors were associated with increased pain severity: history of chronic pain (OR 4.12, 95% CI 1.15 to 14.75]), current tobacco use (2.52, 1.17 to 5.44), pre-existing anxiety (1.93, 1.21 to 3.07), receipt of intra-operative intravenous ketamine or fentanyl (1.56, 1.21 to 2.01), and repeat cesarean delivery (1.54, 1.18 to 2.02). Being of non-Black race and having private health insurance were associated with lower pain severity (OR 0.44, 95% CI 0.31 to 0.62 and 0.51, 0.39 to 0.68, respectively). The overall accuracy of the model was 56%. CONCLUSIONS: Certain patient and procedural factors were associated with higher levels of reported postoperative pain. Patients with those factors may require a more targeted analgesic strategy for post-cesarean delivery pain control.

Role of visfatin in promoting proliferation and invasion of colorectal cancer cells by downregulating SDF-1/CXCR4-mediated miR-140-3p expression.

OBJECTIVE: Visfatin is significantly upregulated in colorectal cancer (CRC). However, its exact role in CRC progression and the regulatory mechanism involved in this process have not been fully illuminated. The aim of this study was to investigate the roles of visfatin in CRC progression and the potential molecular mechanism. MATERIALS AND METHODS: In vitro, two CRC cell lines (DLD-1 and SW480) were transfected with visfatin, si-visfatin, and their control vectors. Some cells were transfected with miR-140-3p mimics or miRNA negative control. Cell Counting Kit-8 and transwell invasive assays were used to detect cell proliferation and invasion ability. Luciferase reporter assays were performed to confirm whether CXC motif chemokine receptor 4 (CXCR4) directly targets miR-140-3p. Western blotting and qRT-PCR analyses were respectively conducted to evaluate the protein and mRNA levels of stromal cell-derived factor-1 (SDF-1) and CXCR4. In vivo, DLD-1 cells transfected with visfatin construct or vector control were inoculated into nude mice. After 5 weeks, the mice were sacrificed, and the tumor nodules were weighed. The expression of visfatin, SDF-1, and CXCR4 in tumor tissues was detected via immunohistochemistry analysis. RESULTS: In vitro, the transfection of visfatin promoted the proliferation and invasion of CRC cells, as well as upregulated the expression of SDF-1/CXCR4. MiR-140-3p directly targets the 3'untranslated region of CXCR4. MiR-140-3p expression was downregulated by treatment with visfatin, and miR-140-3p exerted similar effects to those of visfatin knockdown on the proliferation and invasion of CRC cells. In vivo, visfatin stimulated CRC tumor growth and downregulated miR-140-3p expression, whereas it upregulated SDF-1/CXCR4 expression. CONCLUSIONS: Visfatin promotes CRC progression by downregulating the SDF-1/CXCR4-mediated expression of miR-140-3p both in vitro and in vivo.

Balloon sizing during transcatheter aortic valve implantation : Comparison of different valve morphologies.

BACKGROUND: Although balloon sizing has been found to be useful during transcatheter aortic valve implantation (TAVI), its effectiveness in patients with bicuspid aortic valve (BiAV) remains unknown. METHODS: Patients who underwent balloon sizing were retrospectively identified. The study comprised 67 patients (61.2% with BiAV). Preprocedural hypothetical transcatheter heart valve (THV) sizing was based on multislice computed tomography (MSCT) measurements at the annulus. Changes in valve size after balloon sizing were reviewed. Postprocedural MSCT measurements and the grade of paravalvular aortic regurgitation (PAR) were compared. RESULTS: When comparing patients with a BiAV and those with a tricuspid aortic valve (TiAV), there was no significant difference (p = 0.97) in the proportion of decreased (43.9% vs. 46.2%), unchanged (51.2% vs. 50.0%), or increased (4.9% vs. 3.8%) valve sizes chosen on the basis of MSCT findings. The anticipated annular sizing ratio for patients who received a smaller valve was 7.2% (3.5-10.5%) while it was 15.7% (12.5-19.0) for the others (p < 0.01), and no significant difference in the proportion of mild (or more severe) PAR cases was found between the groups (37.9% vs. 30.6%, p = 0.53 at the 1­month follow-up). Stent frame expansion and eccentricity index were comparable between the BiAV and TiAV subgroups among patients who received a smaller THV after balloon sizing. CONCLUSION: Balloon sizing is a useful tool that is complementary to the current gold standard of MSCT for THV size selection as well as for BiAV morphology assessment.

PPARγ inhibits breast cancer progression by upregulating PTPRF expression.

OBJECTIVE: Peroxisome proliferator-activated receptor γ (PPARγ) regulates fatty acid storage and glucose metabolism. Recently, PPARγ has been reported to be involved in cancer. The present study reported a PPARγ consensus binding site (AGGTCA) in the ptprf promoter and identified a strong association between PPARγ and PTPRF expression, as well as their tumor suppressor roles in a v-Ha-Ras-induced model of breast cancer. MATERIALS AND METHODS: The prognostic potential of PPARγ was assessed with a KM analysis of raw data from 3,951 breast cancer patients. The expression of PPARγ and PTPRF in the rat breast cancer cell lines was detected by Western blot and qPCR. The impact of PPARγ on cancer cell migration, invasion, and growth was confirmed using cell migration assay, transwell cell invasion assay, tri-dimensional soft agar culture, respectively. The binding of PPARγ with the ptprf promoter was then examined using electrophoretic mobility shift assay. The inhibitory effect of PPARγ on tumor growth was then examined in mouse tumor model in vivo. RESULTS: It was identified that PPARγ expression is lost in the aggressive v-Ha-Ras-induced breast cancer cell line FE1.2 but highly expressed in less malignant FE1.3 cells. Exogenous expression of PPARγ in FE1.2 cells (FE1.2-PPARγhi) resulted in a marked inhibition of proliferation compared with that in FE1.2-Vector control group. FE1.2-PPARγhi cells also exhibited reduced migration, invasion, and colony formation abilities compared with those of the controls. The PPARγ agonist rosiglitazone also suppressed the malignant properties of FE1.2 cells. Protein tyrosine phosphatase receptor F (PTPRF), a downstream target of PPARγ, was markedly induced in FE1.2-PPARγhi cells. A PPARγ consensus binding site (AGGTCA) was identified in the ptprf promoter, and an electrophoretic mobility shift assay confirmed that PPARγ bind to this promoter. Similar to the effect of vector-mediated overexpression of PPARγ, ectopic overexpression of PTPRF in FE1.2 cells led to reduced proliferation. Furthermore, a PPARγ antagonist (GW9662) and PTP inhibitor (NSC87877) abrogated the suppressive function of PPARγ and PTPRF in FE1.2 cells, respectively. PPARγ overexpression or activation suppressed the progression and distant organ metastasis of breast cancer cells in a NOD/SCID mouse model. CONCLUSIONS: These results suggest that PPARγ inhibits tumor cell proliferation, at least in part, through direct regulation of the ptprf gene and that PPARγ is a potential target for breast cancer treatment.

Association of gout medications and risk of cataract: a population-based case-control study.

BACKGROUND: The relationship between gout medication use and cataract development is controversial. Moreover, limited clinical studies have evaluated this relationship. AIM: To assess the effects of colchicine, allopurinol and benzbromarone on the risk of cataract in patients with gout. DESIGN: Population-based nested case-control study. METHODS: We enrolled 7900 patients who had received a new diagnosis of cataract >3 years after gout diagnosis into the study group and 33 475 patients who did not receive a diagnosis of cataract into the control group by matching for age, sex and the year of gout diagnosis at a ratio of 1:1. We used World Health Organization's defined daily dose (DDD) as a measure to assess the dosage of colchicine, allopurinol and benzbromarone exposure. Logistic regression was used to estimate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of cataract. RESULTS: The risk of cataract significantly increased in patients who received colchicine at a cumulative DDD of ≥66.5 (OR = 1.17, 95% CI = 1.01-1.36, P = 0.041). In the age-stratified analysis, patients with gout aged >60 years had a higher risk of cataract (OR = 1.27, 95% CI = 1.06-1.53, P = 0.011) than did patients aged <60 years. Allopurinol and benzbromarone had no association with cataract. CONCLUSIONS: In this population-based nested case-control study, we observed that colchicine use increased the risk of cataract in patients with gout, especially in those aged >60 years who received colchicine at a cumulative DDD of >66.5.

The involvement of AQP1 in myocardial edema induced by pressure overload in mice.

OBJECTIVE: To investigate the effect of aquaporin-1 (AQP1) on heart edema induced by transverse aortic constriction (TAC) in mice, and to explore whether inhibiting the expression of AQP1 could attenuate myocardial edema and improve cardiac function. MATERIALS AND METHODS: The C57BL/6 mice were divided into four groups: (1) the sham group; 2) the sham + acetazolamide group: mice were orally gavaged with acetazolamide (20 mg/kg/day) after sham operation; (3) the TAC group: a mouse model of pressure overload induced by TAC for two weeks; (4) the TAC + acetazolamide group: mice were orally gavaged with acetazolamide (20 mg/kg/day) after TAC. Cardiac function was detected by echocardiography after 2 weeks' TAC. The ratio of heart weight to body weight (HW/BW) and myocardial water content were calculated. The mRNA and protein expressions of AQP1 were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively. RESULTS: Significant myocardial hypertrophy and dysfunction were found in TAC mice. The ratio of HW/BW, myocardial water content, and the mRNA and protein expression of AQP1 of the TAC group were markedly higher than those of the sham group. By contrast, acetazolamide administration reduced the ratio of HW/BW and myocardial water content, whereas improved cardiac dysfunction induced by TAC. Moreover, acetazolamide reduced the mRNA and protein expression of AQP1 in TAC mice. CONCLUSIONS: The expression of AQP1 was closely related to myocardial edema induced by TAC. The inhibition of AQP1 could reduce myocardial edema and improve cardiac dysfunction.

Biomarkers of inflammation - LBP and TLR- predict progression of knee osteoarthritis in the DOXY clinical trial.

OBJECTIVE: To evaluate systemic inflammatory biomarkers in symptomatic knee osteoarthritis (OA) and their association with radiographic and biochemical OA progression. METHODS: Lipopolysaccharide (LPS) binding protein (LBP), soluble Toll-like receptor 4 (sTLR4) and interleukin 6 (IL-6) were measured in plasma of 431 knee OA patients from the doxycycline (DOXY) trial at baseline and 18 months. Plasma lipopolysaccharide and lipopolysaccharide binding protein (LBP) were also measured at 12 months. As a biochemical indicator of disease activity and OA progression, urinary (u) C-telopeptide of Type II collagen (uCTX-II) was measured in samples collected at baseline and 18 months. Change over 16 months in radiographic tibiofemoral joint space width (JSW in mm) and joint space narrowing (JSN≥0.5 mm) were used to indicate radiographic OA progression. Change over 18 months for uCTX-II was used as a secondary outcome. Both univariate and multivariable regression analyses were performed to test the association between Z-score transformed biomarkers and outcomes. RESULTS: Baseline LBP and time-integrated concentration (TIC) of LBP over 12 and 18 months were associated with worsening joint space width (JSW) (parameter estimates: -0.1 to -0.07) and JSN (OR: 1.32 to 1.42) adjusting for treatment group, age, body mass index (BMI) and corresponding baseline radiographic measures. Baseline sTLR4 and TIC over 18 months were associated with change in uCTX-II over 18 months (adjusted parameter estimates: 0.0017 to 0.0020). Results were not modified by treatment with doxycycline. CONCLUSION: Plasma LBP and sTLR4 were associated with knee OA progression over 16-18 months. These results lend further support for a role of systemic low-grade inflammation in the pathogenesis of knee OA progression.

Properties of oscillatory neuronal activity in the basal ganglia and thalamus in patients with Parkinson's disease.

BACKGROUND: The cardinal features of Parkinson's disease (PD) are bradykinesia, rigidity and rest tremor. Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms. This study aims to characterize properties of oscillatory activity in the basal ganglia and motor thalamus in patients with PD. METHODS: Twenty-nine patients with PD who underwent bilateral or unilateral electrode implantation for subthalamic nucleus (STN) DBS (n = 11), unilateral pallidotomy (n = 9) and unilateral thalamotomy (n = 9) were studied. Microelectrode recordings in the STN, globus pallidus internus (GPi) and ventral oral posterior/ventral intermediate of thalamus (Vop/Vim) were performed. Electromyography of the contralateral limbs was recorded. Single unit characteristics including interspike intervals were analyzed. Spectral and coherence analyses were assessed. Mean spontaneous firing rate (MSFR) of neurons was calculated. Analysis of variance and X2 test were performed. RESULTS: Of 76 STN neurons, 39.5% were 4-6 Hz band oscillatory neurons and 28.9% were ß frequency band (ßFB) oscillatory neurons. The MSFR was 44.2 ± 7.6 Hz. Of 62 GPi neurons, 37.1% were 4-6 Hz band oscillatory neurons and 27.4% were ßFB neurons. The MSFR was 80.9 ± 9.6 Hz. Of 44 Vop neurons, 65.9% were 4-6 Hz band oscillatory neurons and 9% were ßFB neurons. The MSFR was 24.4 ± 4.2 Hz. Of 30 Vim oscillatory neurons, 70% were 4-6 Hz band oscillatory neurons and 13.3% were ßFB neurons. The MSFR was 30.3 ± 3.6 Hz. Further analysis indicated that proportion of ßFB oscillatory neurons in STN and GPi was higher than that of similar neurons in the Vop and Vim (P < 0.05). Conversely, the proportion of 4-6 Hz band oscillatory neurons and tremor related neurons in the Vim and Vop was higher than that of STN and GPi (P < 0.05). The highest MSFR was for GPi oscillatory neurons whereas the lowest MSFR was for Vop oscillatory neurons (P < 0.005). CONCLUSION: The alterations in neuronal activity in basal ganglia play a critical role in generation of parkinsonism. ß oscillatory activity is more prominent in basal ganglia than in thalamus suggesting that the activity likely results from dopaminergic depletion. While both basal ganglia and thalamus have tremor activity, the thalamus appears to play a more important role in tremor production, and basal ganglia ß oscillatory activity might be the trigger.

Aspartate aminotransferase-to-platelet ratio predicts response to transarterial chemoembolisation and prognosis in hepatocellular carcinoma patients.

AIM: To evaluate the value of the aspartate aminotransferase-to-platelet ratio index (APRI) for hepatocellular carcinoma (HCC) patients who underwent transarterial chemoembolisation (TACE). MATERIALS AND METHODS: A total of 315 patients were enrolled, who were randomly divided into the training cohort (n=158) and the validation cohort (n=157). The optimal cut-off value of the APRI was determined using the X-tile software in the training cohort, and was validated in the validation cohort. Several serum-based markers, neutrophil-to-lymphocyte (N/L) and aspartate aminotransferase-to-alanine aminotransferase (AST/ALT) ratios were included to compare with the APRI. To predict individual survival rate, independent predictors were included to build a nomogram. RESULTS: Using the X-tile, a cut-off value of the APRI as 0.40 was yielded to distinguish patients with distinct outcomes in the training cohort, but failed for the N/L and ALT/AST ratios. In the training cohort, 66 patients with high APRI had poorer survival (p<0.001) than did 92 patients with low APRI. Using the same cut-off value of APRI, 61 patients with high APRI had poorer survival (p<0.001) than did 96 patients with low APRI in the validation cohort. Furthermore, a nomogram, including the APRI, TACE cycles, tumour size, and tumour number, was built based on the training cohort, and validated well in the validation cohort (concordance index [C-index] 0.713). CONCLUSION: The APRI is a promising marker to predict treatment response and outcome for HCC patients after TACE treatment.