A comparison of Doppler measures of ovarian blood flow between women with and without ovarian dysfunction and correlations of Doppler indices with ovarian dysfunction markers: a meta-analysis.

Background: Doppler ultrasonography is used to study ovarian vascular characteristics. However, the outcomes are reported with a considerable variability in literature. Here we review the differences in Doppler ultrasound-measured ovarian blood flow indices between women with and without ovarian dysfunction and seeks correlations between Doppler measures and ovarian markers. Methods: A literature search was conducted in electronic databases (Google Scholar, Ovid, PubMed, Science Direct, and Springer) to identify studies that used Doppler for ovarian blood flow examination and reported Doppler measures in women with and without ovarian dysfunction and/or the correlations between wDoppler indices and markers of ovarian dysfunction. After quality assessment of included studies, a meta-analysis of weighted mean differences (WMDs) between women with and without ovarian dysfunction in vascularization index (VI), flow index (FI), vascularization flow index (VFI), pulsatility index (PI) and resistance index (RI) was performed. Correlation coefficients between Doppler indices and markers of ovarian dysfunction were pooled to achieve overall estimates. Results: A total of 27 studies [2,377 women with ovarian dysfunction and 308 controls; age 27.7 years, 95% confidence interval (CI): 26.4 to 29.1] were included. These studies were of moderate quality. The VI (WMD 9.75; P<0.0001), FI (WMD 2.73; P<0.0001), and VFI (WMD 1.29; P<0.0001) were significantly higher whereas PI (WMD -1.08; P=0.001) and RI (WMD -0.26; P<0.0001) were significantly lower in women with polycystic ovarian syndrome (PCOS) than in normal women. In women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), antral follicle count was positively correlated with VI (r=0.24; P=0.001), FI (r=0.42; P<0.0001), and VFI (r=0.25; P=0.002). In women with PCOS, testosterone had statistically non-significant correlations with VI (r=0.40; P=0.081), and VFI (r=0.39; P=0.063) and was inversely correlated with PI (r=-0.30; P<0.0001) and RI (r=-0.48; P<0.0001). In women with PCOS, luteinizing hormone (LH) was inversely correlated with PI (r=-0.26; P=0.086) and RI (r=-0.25; P=0.007). Conclusions: Doppler indices are found significantly different in women with and without ovarian dysfunction and have significant correlations with markers of ovarian dysfunction. These results support the use of Doppler ultrasound to examine ovarian dysfunction. High statistical heterogeneity observed herein should be studies in future investigations.

Effect of cognitive behavioral intervention on anxiety, depression, and quality of life in patients with epilepsy.

OBJECTIVE: This study aimed to investigate the effect of cognitive behavioral therapy (CBT) on quality of life, anxiety, and depression in patients with epilepsy. METHODS: Each study subject was randomly assigned to a CBT (n=46) or control (n=49) group (1:1 ratio), and the first group underwent an 8-week CBT treatment. Anxiety, depression, and quality of life (QOLIE-31) were assessed at both baseline and endpoint using the Self-Rating Anxiety Scale (SAS), Hamilton Depression Scale (HDMA) and quality of life in Epilepsy-31 (QOLIE-31) scales. The statistical analyses included between-and within-group comparisons of the effects of CBT on these measures and associations with demographic and clinical variables. RESULTS: No differences were found between variables at baseline (P>0.05). The repeated-measures analyses found that CBT group had greater improvement in depression score compared to the control group (P<0.05). The analysis of anxiety score showed that compared to the control group, CBT intervention had no statistical significance in the total anxiety population. However, the CBT intervention decreased anxiety in women and Combined-drug group (P<0.05). The CBT group had greater improvement in overall score, medication effect, and seizure worry score than the control group (P<0.05). Stratified analysis found total and medication effects score of CBT intervention group for the combined-drug group were higher than those of the single drug group (P<0.05). CONCLUSION: Increases in overall scores, seizure worry, cognitive functioning, and medication effect were better in the CBT group. CBT can improve anxiety, depression, and quality of life in patients with epilepsy. Women and combined-drug patients with epilepsy benefit most from CBT.

A 3-Year Clinical Evaluation of Endodontically Treated Posterior Teeth Restored with Resin Nanoceramic Computer-Aided Design/Computer-Aided Manufacture (CAD/CAM)-Fabricated Partial Crowns.

BACKGROUND We aimed to investigate the clinical effects of resin nanoceramic (RNC) computer-aided design/computer-aided manufacture (CAD/CAM) partial crowns on posterior teeth after root canal treatment over a 3-year period. MATERIAL AND METHODS A total of 132 posterior teeth restored with CAD/CAM partial crowns were placed in 128 patients. The observation group (n=66) was restored with RNC restorations, while the control group received lithium disilicate-based glass ceramic (LDGC) CAD restorations. Using Federation dentaire internationale (FDI) World Dental Federation clinical criteria, 2 calibrated evaluators examined the performance of the restorations at baseline, 6, 12, 18, 24, and 36 months. The Kaplan-Meier method and the log-rank test were adopted to analyze the survival rate. The influence of potential risk factors on the main pattern of failure was studied by univariate Cox regression analysis (alpha=0.05). RESULTS At the 3-year followup, the survival rate of the partial crowns was 83.1% in the RNC group, and 93.5% in the LDGC group (P=0.061). Failures were caused by debonding (66.7%), restoration fracture (26.6%), and tooth fracture (6.7%). No significant differences were found between the 2 materials at 36 months, except for the parameters of "surface luster" (P=0.002) and "occlusal contour and wear" (P=0.009). The RNC group was significantly more likely to debond than the LDGC group (hazard ratio=9.22 [1.17,72.74], P=0.01). CONCLUSIONS RNC CAD/CAM-fabricated partial crowns are a potential clinical alternative for endodontically treated posterior teeth, with a survival rate of 83.1% at the 3-year followup. The main pattern of failure was debonding, which might be influenced by surface pretreatment of the RNC material.

A tract-based spatial statistics study of white matter integrity in epilepsy.

OBJECTIVE: To explore the changes of cerebral white matter diffusion tensor in epilepsy. METHODS: This study was a retrospective study based on diffusion tensor imaging (DTI). Twenty-six epileptic patients and 42 normal controls matched for sex, age and handedness were enrolled in our research. Based on the method of tract-based spatial statistics (TBSS), we analyzed the changes of each relevant parameter index of DTI in white matter of the brain in all subjects, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). RESULTS: In comparison with the control group, epileptic patients had decreased FA and elevated MD, AD, and RD in the anterior thalamic radiation, corticospinal tract, forceps major, forceps minor, cingulum, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus and uncinate fasciculus (P < 0.05). CONCLUSION: Widespread white matter integrity was observed in epileptic patients, which may be the structural basis for the development of affective disorders, impaired cognition, and motor abnormalities.

Effect of electrical cardioversion on 1-year outcomes in patients with early recurrence after catheter ablation for atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) recurrence is common in the 3-month blanking-period after catheter ablation, during which electrical cardioversion (ECV) is usually performed to restore sinus rhythm. Whether ECV can affect the clinical outcome of post-ablation AF patients is inconsistent, however. We aimed to explore the 1-year effect of ECV on AF recurrence and rehospitalization in patients experienced recurrence within 3-month after AF catheter ablation. METHODS: Patients who experienced recurrence within 3-month after AF catheter ablation procedure were enrolled from the China Atrial Fibrillation Registry (China-AF). A 1:3 Propensity score matching (PSM) method was applying to adjust the confounders between patients who had been treated by ECV or not. Logistic regression models were conducted to evaluate the association of ECV with 1-year AF recurrence and rehospitalization. RESULTS: In this study, 2961 patients experienced AF recurrence within 3-month after the procedure, and 282 of them underwent successful ECV, 2155 patients did not undergo ECV. One-year AF recurrence rates were 56.4% in ECV group versus 65.4% in non-ECV group (p = .003), and were 55.9% versus 65.9%, respectively, after PSM (adjusted odds ratio [OR] 0.66; 95% confidence interval (CI): 0.49-0.88, p = .005). However, the difference of 1-year rehospitalization rates between two groups were not statistically significant before (ECV group: 23.7% vs. non-ECV group: 22.3%, p = .595) and after PSM (ECV group: 24.4% vs. non-ECV group: 21.6%, adjusted OR1.14; 95% CI 0.81-1.62, p = .451). CONCLUSIONS: Successful ECV was associated with lower rate of one-year recurrence in patients with early recurrent AF after catheter ablation.

Healthcare quality and mortality among patients hospitalized for heart failure by hospital level in Beijing, China.

AIMS: This study sought to compare healthcare quality and 30 day, 90 day, and 1 year mortality rates among patients admitted to secondary and tertiary hospitals for heart failure (HF) in Beijing. METHODS AND RESULTS: This study retrospectively enrolled patients hospitalized with a primary discharge diagnosis of HF during January 2014 to December 2015, from five tertiary and four secondary hospitals, in Beijing, China. Mortality data were extracted from Beijing Death Surveillance Database. HF healthcare quality indices were used to evaluate in-hospital care. Associations between hospital level and mortality rates were assessed using generalized linear mixed models, adjusting for patients' baseline characteristics and intra-hospital correlation. Data from 1413 patients (median [interquartile range] age = 74 [65-80] years, 52.7% female) from secondary hospitals and 1250 patients (median [interquartile range] age = 72 [61-79] years, 43.3% female) from tertiary hospitals were collected. Rates of left ventricular ejection fraction assessment (73.2% vs. 90.1%) and combined use of ß-blockers and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (30.1% vs. 49.3%) were lower in secondary hospitals than those in tertiary hospitals, respectively. Patients admitted to secondary hospitals had a higher 90 day mortality [10.8% vs. 5.0%; adjusted odds ratio (OR): 2.06; 95% confidence interval (CI): 1.10-3.84, P = 0.024 and a higher 1 year mortality rate [21.0% vs. 12.1%; adjusted OR: 1.64; 95% CI: 1.02-2.62, P = 0.039], but 30 day mortality rates were not significantly different (5.5% vs. 3.0%; adjusted OR: 1.49; 95% CI: 0.63-3.52, P = 0.368). CONCLUSIONS: Worse quality of care for patients with HF in secondary hospitals was associated with higher 90 day and 1 year mortality rates. Improving care quality in secondary hospitals is crucial to improve prognosis of patients they served.

Association between use of amiodarone for non-valvular atrial fibrillation and patient survival: from the prospective China Atrial Fibrillation Registry.

BACKGROUND: Post hoc analysis of the landmark atrial fibrillation follow-up investigation of rhythm management trial revealed that amiodarone was associated with higher risks of mortality, intensive care unit admission, and non-cardiovascular death. We aim to evaluate the association between amiodarone use and patient survival under updated medical mode and level using data from the China Atrial Fibrillation (China-AF) Registry study. METHODS: Clinical data of 8161 non-valvular atrial fibrillation (NVAF) patients who were antiarrhythmic drug (AAD)-naive before enrollment into the China-AF Registry, recruited between August 2011 and February 2017, were collected. The primary outcome was all-cause mortality. A Cox proportional hazard regression model was used to evaluate the association between amiodarone use and the outcome. We also calculated the rate of sinus rhythm maintenance at the penultimate follow-up. RESULTS: Compared with 6167 patients of non-AAD group, 689 patients of the amiodarone group were younger (mean age 65.6 vs. 68.6 years), more frequently completed high school education, had fewer comorbidities such as chronic heart failure, prior bleeding, and stroke, and were more likely to be treated in tertiary hospitals while less hospitalization. The proportion of persistent AF was much lower among users of amiodarone, who were also less likely to be taking oral anticoagulants. The patients in the amiodarone group had a statistically insignificant lower incidence of all-cause mortality (2.44 vs. 3.91 per 100 person-years) over a mean follow-up duration of 300.6 ±â€Š77.5 days. After adjusting for potential confounders, amiodarone use was not significantly associated with a lower risk of all-cause mortality (adjusted hazard ratio, 0.79; 95% confidence interval, 0.42-1.49). Sub-group analysis revealed the consistent results. The rate of sinus rhythm maintenance at the penultimate follow-up in the amiodarone group was significantly higher than in the non-AAD group. CONCLUSIONS: Our study indicated that amiodarone use was not significantly associated with a lower risk of 1-year all-cause mortality compared with a non-AAD strategy in "real-world" patients with NVAF.

Down-Regulation of CIDEA Promoted Tumor Growth and Contributed to Cisplatin Resistance by Regulating the JNK-p21/Bad Signaling Pathways in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with poor prognosis and lack of effective targeted therapies. In this study, we investigated the tumor suppressive role of the cell death inducing DFF like effector A (CIDEA) in ESCC. Firstly, public datasets and ESCC tissue microarray analysis showed that CIDEA was frequently down-regulated at both the mRNA and protein level. This was significantly associated with low differentiation and TNM stage in ESCC, and indicated poor prognosis for ESCC patients. Bisulfite genomic sequencing (BGS) and methylation-specific PCR (MSP) analysis revealed that the down-regulation of CIDEA was associated with hypermethylation of its promoter, which was also correlated with the poor prognosis in ESCC patients. In vitro and in vivo functional studies demonstrated that CIDEA decreased cell growth, foci formation, DNA replication, and tumorigenesis in nude mice. Further study revealed that, during starvation or cisplatin induced DNA damage, CIDEA facilitated the G1-phase arrest or caspase-dependent mitochondrial apoptosis through the JNK-p21/Bad pathway. Therefore, CIDEA is a novel tumor suppressor gene that plays an important role in the development and progression of ESCC, and may provide a potential therapeutic target for patients with ESCC.

Sex Differences in Presentation, Quality of Life, and Treatment in Chinese Atrial Fibrillation Patients: Insights from the China Atrial Fibrillation Registry Study.

BACKGROUND There is a growing recognition of sex-related disparities in atrial fibrillation (AF). However, limited data is available in Chinese AF patients. MATERIAL AND METHODS We compared symptoms, quality of life (QoL), and treatment of AF according to sex from the China AF Registry study. RESULTS We studied 14 723 patients with non-valvular AF, of whom 5645 patients (38.3%) were female. Women were older than men (67.5±10.6 vs. 62.2±12.2). Compared to men, women had more comorbidities and a higher proportion of CHA2DS2-VASC score ≥2. Women with AF experienced more severe or disabling symptoms than men (33.7% vs. 22.9% in age <75 group; 40.3% vs. 28.7% in age ≥75 group; both P<0.0001). After multivariate analysis, women with AF still had lower QoL (OR 0.69; 95%CI, 0.63-0.76; P<0.0001). Women tended to have lower rates of ablation and rhythm-control drug use in those aged <75 years. Oral anticoagulant use was low and had no sex difference in AF patients with a CHA2DS2-VASC score ≥2. CONCLUSIONS In Chinese AF patients, women were older and more symptomatic, and had worse QoL. Despite all these differences, women tended to receive less rhythm-control treatment in those aged <75 years. Oral anticoagulant was substantially underused in high stroke risk patients, regardless of sex.

The Association Between the Use of Antiarrhythmic Drugs in Non-Valvular Atrial Fibrillation and Patient Prognosis Using Data from the China Atrial Fibrillation (China-AF) Registry.

BACKGROUND Results of the landmark Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial comparing rhythm control and rate control strategies has led to dramatic changes in the pharmacological management of non-valvular atrial fibrillation (NVAF) patients. We sought to investigate the effect of antiarrhythmic drugs (AADs) on the clinical outcomes of NVAF patients using "real-world" data from China. MATERIAL AND METHODS We evaluated the association between AAD usage and clinical outcomes using clinical data of 8161 NVAF patients who were AAD-naive before enrollment in the China Atrial Fibrillation Registry, recruited between August 2011 and February 2017. The primary outcome was all-cause mortality. RESULTS Compared with 6167 patients who never used any AADs, 1994 patients in the AAD group had lower incidence (per 100 person-years) of all-cause mortality (1.44 versus 3.91), cardiovascular death (0.45 versus 2.31), ischemic stroke (1.36 versus 2.03), and cardiovascular hospitalization (9.83 versus 10.22) over a mean follow-up duration of 316.7±90.4 days. After adjusting for potential confounders, AAD usage was associated with a lower risk of all-cause mortality [hazard ratio (HR): 0.50, 95% confidence interval (CI): 0.31-0.81] and decreased risk of cardiovascular death (HR: 0.30, 95% CI: 0.13-0.68). Subgroup analysis revealed AAD was associated with higher risk of cardiovascular hospitalization among female patients. CONCLUSIONS AAD usage was associated with lower risk of 1-year all-cause mortality and cardiovascular death in "real-world" patients with NVAF.

Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation.

BACKGROUND/AIMS: It is known that chronic low-grade inflammation contributes to the initiation and development of both diabetes and diabetic nephropathy (DN), so we designed this study to investigate the role of P2X7R and NLRP3 inflammasome in DN pathogenesis and the antagonistic effects of artificially cultivated Ophiocordyceps sinensis (ACOS). METHODS: A rat model of DN caused by high-fat-diet feeding and low-dose streptozotocin injection and a mouse podocyte injury model induced by high-glucose (HG) stimulation were established, and the intervention effects of ACOS on them were observed. The biological parameters of serum and urine and the pathological manifestations of kidney tissue were examined. The expression of mRNA and protein of P2X7R and NLRP3 inflammasome (NLRP3, ASC, and caspase-1) and downstream effectors (IL-1ß and IL-18), as well as podocyte-associated molecules, was determined by real-time quantitative PCR and Western blot assay, respectively. RESULTS: The DN rats showed to have developed insulin resistance, elevated fasting blood glucose, increased urinary protein excretion, and serum creatinine level as well as corresponding glomerular pathological alterations including podocyte damages. ACOS significantly antagonized the above changes. The experiments in vivo and in vitro both displayed that the mRNA and protein expression of P2X7R, NLRP3, ASC, caspase1 (procaspase-1 mRNA in the gene level and active caspase-1 subunit P10 in the protein level), IL-1ß, and IL-18 was significantly upregulated and the mRNA and protein expression of podocyte-associated molecules was significantly changed (downregulation of nephrin, podocin, and WT-1 expression and upregulation of desmin expression) indicating podocyte injury in the kidney tissue of DN rats and in the HG-stressed mouse podocytes, respectively. ACOS also significantly antagonized all the above changes. CONCLUSION: Our research work suggests that P2X7R and NLRP3 inflammasome are involved in the pathogenesis of DN, and ACOS can effectively inhibit the high expression of P2X7R and the activation of NLRP3 inflammasome, which may contribute to the therapeutic effects of Ophiocordyceps sinensis.

Purinergic 2X7 Receptor is Involved in the Podocyte Damage of Obesity-Related Glomerulopathy via Activating Nucleotide-Binding and Oligomerization Domain-Like Receptor Protein 3 Inflammasome.

BACKGROUND: The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R). This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation of NLRP3 inflammasome. METHODS: A mouse model of ORG was established by high-fat diet feeding. The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079). The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3, ASC, and caspase-1, as well as the podocyte-associated molecules including nephrin, podocin, and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Western blot analysis, respectively. RESULTS: The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo, which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules. Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression of podocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro, and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079. CONCLUSIONS: P2X7R could trigger the activation of NLRP3 inflammasome, and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.

Long non-coding RNA RMST silencing protects against middle cerebral artery occlusion (MCAO)-induced ischemic stroke.

Long non-coding RNAs (lncRNAs) have emerged as major regulators in neurological diseases, and clarifying their roles in cerebral ischemic injury may provide novel targets for treating ischemic stroke. In this study, we mainly studied the role of lncRNA-RMST in middle cerebral artery occlusion (MCAO)-induced mouse brain injury. We showed that RMST expression level was significantly up-regulated in oxygen-glucose deprivation (OGD)-treated primary hippocampal neuron, MCAO-induced injured brain, and the plasma of patients with ischemic stroke. RMST silencing protected against MCAO-induced ischemic brain injury in vivo and OGD-induced primary hippocampal neuron injury in vitro. Intracerebroventricular injection of RMST shRNA significantly decreased brain RMST expression, reduced brain infarct size, and improved neurological function. Collectively, this study provides evidence that lncRNA is involved in the pathogenesis of ischemic brain injury, and suggests a promising approach of RMST inhibition in treating ischemic stroke.

Prospects of Contrast-Enhanced Ultrasonography for the Diagnosis of Peripheral Arterial Disease: A Meta-analysis.

OBJECTIVES: Contrast-enhanced ultrasonography (CEUS) is a modern diagnostic method that can also be used to study microperfusion. This study compared the time to peak intensity measured by CEUS in patients with peripheral arterial disease (PAD) and healthy control participants. METHODS: After a comprehensive literature search in multiple electronic databases and study selection, a random-effect meta-analysis was performed to compare the time to peak intensity measured by CEUS in patients with PAD and healthy controls, which followed meta-regression analyses for identification of factors affecting the outcomes. RESULTS: Fourteen studies (data for 322 patients with PAD and 314 healthy individuals) were used for the meta-analysis. The age of this sample of patients with PAD was 64.92 (95% confidence interval, 62.53, 67.31) years, and that of the healthy controls was 55.32 (51.67, 58.98) years. The times to peak intensity were 18.55 (15.62, 21.48) seconds in healthy controls, 33.40 (27.65, 39.15) seconds in patients with PAD, and 76.22 (36.23, 116.22) seconds in patients with PAD and diabetes mellitus. The difference between patients with PAD and healthy controls in the time to peak intensity was statistically significant (mean difference, 24.80 [10.16, 39.44] seconds; P < .00009). The ABI was not significantly associated with the time to peak intensity in patients with PAD. Age and sex were also not significantly associated with the time to peak intensity. CONCLUSIONS: Contrast-enhanced ultrasonography is a valuable tool for the diagnosis of PAD based on its ability to differentiate the time to peak intensity between patients with PAD and healthy individuals, but little data are yet available to assess its diagnostic ability in clinical practice.

[Diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration in paratracheal mediastinal lesions].

OBJECTIVE: To explore the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in diagnosing mediastinal lesions. METHODS: A total of 264 patients with mediastinal lesions on chest CT at Provincial Hospital Affiliated to Shandong University between January 2010 and April 2012 were retrospectively enrolled. Their cytopathological results were difficult to be assessed by conventional bronchoscopy. There were 222 cases whose lymph nodes long axis was >1.5 cm. Among them, 174 cases underwent TBNA alone (group A) and the other 48 cases EBUS-TBNA alone (group B). The remaining 42 cases whose lymph nodes long axis was <1.5 cm belonged to group C and underwent TBNA (group C1) and EBUS-TBNA (group C2) sequentially as a combined procedure. The associations of pathologic examinations, diagnostic positive rate and complications were analyzed. RESULTS: Among 174 cases in group A, 154 cases were diagnosed with a positive diagnostic rate of 88.5%. There were 135 malignant lesions while 19 cases were diagnosed with benign diseases and 5 cases had accidental vascular injury. Among 48 cases in group B, 45 cases were diagnosed with a positive diagnostic rate of 93.8%. There were 33 malignant lesions while 12 cases were diagnosed with benign diseases. Among 42 patients in group C1, 31 cases were diagnosed by TBNA with a positive diagnostic rate of 73.8%. There were 23 malignant lesions while 8 cases were diagnosed with benign diseases and 2 cases had accidental vascular injury. Among 42 patients in group C2, 39 cases were diagnosed with a positive diagnostic rate of 92.8%. There were 30 malignant lesions while 9 cases had benign diseases. No difference existed in diagnostic positive rate between groups A and B (χ(2) = 0.621, P = 0.431) while the diagnostic positive rate in group A was much higher than group C1 (χ(2) = 5.945, P = 0.015). The difference between groups B and C2 was insignificant (χ(2) = 0.065, P = 0.320) while there was significant difference between groups C1 and C2 (χ(2) = 5.486, P = 0.019). CONCLUSION: With a low complication rate, EBUS-TBNA can yield a higher diagnostic positive rate in diagnosing small mediastinal diseases than conventional TBNA.

CD39/CD73 and the imbalance of Th17 cells and regulatory T cells in allergic asthma.

In the immune system, CD4+CD25+Foxp3+ regulatory T cells (Tregs) maintain self­tolerance and Th17 cells mediate inflammatory responses. CD39 is expressed on the surface of a subset of naturally occurring human Tregs that are important in constraining pathogenic Th17 cells. Additional studies have shown that Tregs differentiate into interleukin­17 (IL­17)+Foxp3+ T cells. Our previous study indicated an imbalance of Th17 and Tregs in allergic asthma; however, the underlying mechanisms remain poorly understood. Using quantitative PCR (qPCR), CD39 and CD73 mRNA levels in CD4+ T cells were investigated. Flow cytometry was used to analyze the proportion of IL­17+Foxp3+ T cells, and CD39 and CD73 expressed by CD4+ T cells and Tregs in the peripheral blood of the subjects. The results of the present study demonstrated an increased frequency of CD4+Foxp3+IL­17+ T cells in moderate to severe asthma. A deficiency in CD39 expressed on the surface of CD4+ T cells and Tregs was observed in asthma patients. The expression of CD39 and CD73 on the surface of CD4+ T cells and Tregs was negatively correlated with the number of Th17 cells. These results indicated that the plasticity of Tregs transforming to IL­17+Foxp3+CD4+ T cells, the reduced frequency of CD39+ Tregs and less effective suppression of IL­17 production by residual CD39+ Tregs leads to an imbalance of Th17 and Tregs in asthma. Therefore, enhanced CD39 activity is hypothesized to prevent the progression of asthma.

[Characteristics of histone deacetylase 9 in peripheral blood of patients with bronchial asthma].

OBJECTIVE: To investigate the expression pattern of histone deacetylase 9 (HDAC9) in peripheral blood of asthmatics and its effect on immune cells (Th2, Th17, Tregs) involved in the pathogenesis of asthma. METHODS: Forty-seven asthmatics from Ruijin Hospital were recruited and assigned to intermittent, mild and moderate-severe groups. Lung function test and Asthma Control Questionnaire were performed to evaluate asthma control and severity. Twenty healthy donors were enrolled as controls. GATA3, IL-4, and HDAC9 mRNA expression levels were measured by SYRB Green Real-time PCR. The cytokine IL-17-mainly produced by Th17 cells and TGF-ß-mainly produced by Treg cells, were measured by ELISA. RESULTS: The GATA3 and IL-4 mRNA expression levels (28.12 ± 7.57 and 743.6 ± 312.8) were up-regulated in asthmatics as compared to the healthy controls [0.56 ± 0.22, 0.7 ± 0.8 (U = 16.00, 37.00, P < 0.01)]. The HDAC9 mRNA expression levels of intermittent, mild and moderate-severe groups were 3.20 ± 0.50, 89.6 ± 18.0, 323.0 ± 65.3, respectively, which were associated with the severity of disease (H = 11.32, P < 0.05). The level of IL-17 in asthmatic group was (83 ± 55) ng/L, which was up-regulated as compared to the healthy control [(34 ± 22) ng/L (U = 153.50, P < 0.01)]. The level of TGF-ß was decreased in the asthmatic groups as compared to the healthy control, but the difference did not reach significance. HDAC9 mRNA expression level was positively correlated with GATA3 mRNA expression level (r = 0.482, P < 0.05), and also with IL-4 mRNA expression (r = 0.432, P < 0.05) and IL-17 (r = 0.538, P < 0.05), but negatively correlated with TGF-ß (r = -0.417, P < 0.05). In patients with moderate-severe asthma, HDAC9 mRNA expression level was negatively correlated with FEV(1)% (r = -0.657, P < 0.05). CONCLUSION: HDAC9 mRNA expression was up-regulated in peripheral blood of asthmatics, which was not only associate with the Th2 master transcriptional factors GATA3, cytokine IL-4 mRNA, Th17 and Treg cell-related cytokines, but also with FEV(1)% in moderate-severe asthma.

[Sensitivity of new reagents for laboratory monitoring of low molecular weight heparin: an in vitro study].

OBJECTIVE: To explore the sensitivity of new activated clotting time (ACT) reagent for laboratory monitoring of low molecular weight heparin (LMWH). METHODS: Blood samples were collected from 30 healthy volunteers and different doses of LMWH (dalteparin) added. The dalteparin concentration of final blood samples was 0.1 - 1.8 U/ml. ACT and clot rate (CR) were measured with traditional reagent kaolin and new reagent magbar. Linear regression analysis was performed and a regression equation established between different dalteparin concentrations and their corresponding ACT and CR values. RESULTS: With rising dalteparin concentrations, the ACT values became gradually extended and the CR values were gradually reduced by both kaolin and magbar. Analysis of dose-response curves was obtained in vitro. And an excellent linear relationship was observed between the ACT and dalteparin concentrations for two reagents (P < 0.01). An exponential relationship was observed between the CR and dalteparin concentrations (P < 0.01). Differences in slope of regression curves of ACT were observed with the tested reagents (magbar 1097.6 s/U vs kaolin 59.3 s/U, P < 0.01). CONCLUSION: This in vitro study has shown that the sensitivity of new ACT test reagent (magbar) is good for laboratory monitoring of dalteparin. The new reagent magbar may be used for bedside monitoring of anticoagulant activity of LMWH.

Influence of CD14 polymorphism on CD14 expression in patients with extensive burns.

We sought to investigate the association of CD14 genotype with the risk of mortality after burn, and we also attempted to evaluate whether CD14-159 C/T polymorphism affects the kinetics and extent of CD14 expression as well as its release, and TNF-alpha expression in burned patients. The study involved 64 patients in Chinese Han population incurring burns covering more than 30% of the total body surface area. CD14 polymorphism was determined by polymerase chain reaction (PCR) and subsequent restriction fragment length polymorphism (RFLP) analysis. Meanwhile, leukocyte CD14 mRNA expression and soluble CD14 (sCD14) levels were measured during a 28-day observation period. TNF-alpha mRNA and protein levels were also determined in patients with different genotypes of CD14. On day 21 after burn, CD14 mRNA expression and sCD14 levels were significantly higher in TT homozygotes than in CC genotypes (1.33+/-0.36 microg/ml vs. 0.75+/-0.28 microg/ml and 16.1+/-4.6 microg/ml vs. 9.7+/-3.4 microg/ml, P<0.05), and these values were also higher in non-survivors than in survivors (1.32+/-0.40 microg/ml vs. 0.87+/-0.32 microg/ml and 14.8+/-4.5 microg/ml vs. 11.1+/-4.8 microg/ml, P<0.05). In addition, TNF-alpha mRNA and protein levels were significantly lower in both CC homozygotes and survivors than in TT genotypes or non-survivors during the 28-day observation period (P<0.05). However, TT genotype did not impart an increased risk for burn mortality in this small study. In conclusion, CD14-159 C/T polymorphism might be associated with the kinetics and extent of CD14 expression as well as its release, and it was also related to TNF-alpha expression. However, this study did not confirm CD14-159 C/T polymorphism was associated with the outcome of extensive burns.