BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

BACKGROUNDOcclusal splints have been the preferred modalities in the management of myofascial temporomandibular disorders (TMDs), but now controversy exists in reporting whether they are successful for TMDs treatments. The aim of this study was to give objective evidence to the assessment of treatment effect of occlusal splints for myofascial TMDs patients by clinical assessments and surface electromyography (sEMG) measurements of masseter muscles (MM).

METHODSThirty-six patients (12 males and 24 females) aged 16 - 57 (38 ± 11) years participated in the study. All participants diagnosed with myofascial TMD were randomized into two groups (18 of each). Patients in the first group (A) were treated with occlusal splints for 1 month, while patients in the second group (B) were treated with placebo (non-occluding palatal) splints. Clinical assessments were performed at the beginning of the study and 1 month after treatment. sEMG measurements for MM were performed at mandibular postural position (MPP) and maximum intercuspal contacted position (ICP) 1 month after the treatment. The root mean square (RMS) and the median frequency (MF) as linear indices of sEMG data were used to demonstrate muscle activity and muscle fatigue. Data were analyzed by ANOVA and post hoc SNK test. The differences were considered significant at P < 0.05.

RESULTSIt was found that 89% of group A either completely recovered (39%) or clinically improved (50%), while only 22% of group B had a spontaneous improvement. sEMG analysis showed that at MPP, the mean of RMS value of MM in group A was lower than that of group B, which shows statistical differences (P < 0.01). At ICP, the RMS value of MM in group A was higher than that of group B, which shows statistical differences (P < 0.01). At MPP, MF value of MM in group A was higher than that of group B (P < 0.05). At ICP, MF value of MM was lower than that of group B (P < 0.01).

CONCLUSIONSOcclusal splint could eliminate or improve the signs and symptoms of TMD patients with myofascial pain. sEMG analysis indicates that the wearing of occlusal splints may reduce the degree of fatigue of the masticatory muscles. The splint therapy outcome has a correlation with the electromyographic changes in the masticatory muscles.

Adolescent ; Adult ; Double-Blind Method ; Electromyography ; Female ; Humans ; Male ; Middle Aged ; Myofascial Pain Syndromes ; physiopathology ; therapy ; Splints

BACKGROUNDThe hygiene hypothesis has been proposed to explain the pathogenesis of asthma. Allergen exposure was shown to inhibit asthma in an animal model. But the optimal timing of allergen exposure remains unclear. This study aims to explore the time effcct of allergen exposure and the possible mechanisms.

METHODSNeonate Wistar rats were randomly divided into asthma group, control group and day 1, day 3, day 7, and day 14 groups. The day 1, day 3, day 7 and day 14 groups were injected with ovalbumin (OVA) subcutaneously on days 1, 3, 7 and 14 after birth, respectively. Six weeks later, all groups, except the control group, were sensitized and stimulated with OVA to make the asthma model. We observed the pulmonary pathologic changes, detected the regulatory T cells, and CD28 expression level in thymus and spleen by flow cytometry.

RESULTSThe asthmatic inflammation in the day 1, day 3 and day 7 groups, but not the day 14 group, was alleviated. The asthma group and day 14 group had lower proportions of regulatory T cells in the thymus compared with the control group, day 1, day 3, and day 7 groups. There was no significant difference in the CD28 expression levels on the regulatory and conventional T cells among groups. But the control group and the day 1, day 3, and day 7 groups had relatively higher proportions of CD28 positive regulatory T cells in the thymus than the day 14 group and the asthma group.

CONCLUSIONSThere is a "time-window" for early allergen exposure. The impairment of regulatory T cells may promote the development of asthma. Allergen exposure in the "time-window" can make the thymus produce normal quantity of regulatory cells. The CD28 signal on regulatory T cells may participate in the production of regulatory T cells.

Allergens ; immunology ; Animals ; Asthma ; etiology ; CD28 Antigens ; analysis ; physiology ; Disease Models, Animal ; Female ; Ovalbumin ; immunology ; Rats ; Rats, Wistar ; Signal Transduction

BACKGROUNDCyanotic congenital heart defects with decreased pulmonary blood flow due to lung ischemia, hypoxia, and others lead to infant morbidity and mortality more than acyanotic heart disease does. Despite the great effort of medical research, their genetic link and underlying microRNAs molecular mechanisms remain obscure. In this study, we aimed to investigate microRNAs regulation during cyanotic defects in lung of immature piglets.

METHODSCyanotic piglet model was induced by main pulmonary artery-left atrium shunt with distal pulmonary artery banding. Four weeks later, hemodynamic parameters confirmed the development of cyanotic defects and pulmonary lobe RNA was extracted from all animals. We studied the repertoire of porcine lung microRNAs by Solexa deep sequencing technology and quantified highly expressed microRNAs by microarray hybridization. Furthermore, we quantitated selected microRNAs from cyanotic and control piglets by quantitative RT-PCR.

RESULTSAfter surgical procedure 4 weeks later, the cyanotic model produced lower arterial oxygen tension, arterial oxygen saturation, and higher arterial carbon dioxide tension, hematocrit and hemoglobin concentration than controls (all P < 0.05). In 1273 miRNAs expressed in the immature piglets lungs, 2 most abundant microRNAs (miR-370 and miR-320) demonstrated significant difference between cyanotic and control group (all P < 0.05).

CONCLUSIONOur results extended lung microRNA profile in immature piglets and suggested that miR-370 and miR-320 are significantly up-regulated in cyanotic lung tissues.

Animals ; Chronic Disease ; Cyanosis ; genetics ; physiopathology ; Gene Expression Profiling ; Heart Atria ; surgery ; MicroRNAs ; analysis ; physiology ; Pulmonary Artery ; surgery ; Pulmonary Circulation ; Real-Time Polymerase Chain Reaction ; Swine ; Swine, Miniature

BACKGROUNDPulmonary embolism (PE) is a common and often fatal disease. Early after pulmonary thromboembolism, inflammation and associated intimal hyperplasia occur within the pulmonary arteries, similar to what is observed with chronic thromboembolic pulmonary hypertension. This study tested the hypothesis that thrombolytic and anticoagulant agents would have anti-inflammatory effects or inhibit intimal hyperplasia of involved pulmonary arteries.

METHODSSeventy-two male New Zealand white rabbits were randomly divided into two groups (54 rabbits in the PE group and 18 in the sham group). Experimental PE was induced in 54 rabbits by femoral vein injection of autologous blood clots and confirmed with pulmonary angiography, and other 18 rabbits underwent sham operations. Fifty-four rabbits in the PE group were randomly divided into three groups: a control group (treated with normal saline), a low-molecular- weight heparin (LMWH) group (treated with LMWH), and a urokinase (UK) group (treated with UK). Arterial blood gas was analyzed at 2, 7, and 28 days (n = 6 per time point by random group division), then lung tissues were removed and were analyzed for pro-inflammatory cytokines and chemokines, and were stained for intimal hyperplasia.

RESULTSThe overall survival of rabbits undergoing PE was 100%. PE distribution detected on digital signal angiography (DSA) and histopathology was shown in 67% of rabbits (36/54) in the bilateral low lobar pulmonary arteries (PAs). The results showed that alveolar-arterial partial pressure of oxygen (PO2) difference (PA-aO2) significantly increased and PO2 decreased in the control group compared with the sham group. Compared with controls, the UK group had a decreased level of PA-aO2 on day 2 (P < 0.05), however, there was no significant difference in the LMWH group. Compared with controls, the LMWH group had a decreased level of monocyte chemoattractant protein-1 (MCP-1) in affected tissue and serum samples on days 7 and 28 (P < 0.05), and the UK group had decreased levels on days 2 and 7 (P < 0.05). Compared with sham group, all PE groups had an increased level of interleukin-13 (IL-13) and transforming growth factor-β (TGF-β) in unaffected lung tissue samples at days 2 and 7. IL-13 in affected lung tissue in the LMWH group was decreased at all time points compared with controls (P < 0.05). However, TGF-β in affected lung tissue of the LMWH and UK groups increased at day 28. There was less intimal hyperplasia in involved pulmonary arteries at days 7 and 28 in the LMWH group compared with controls; there was no statistical difference in the UK group compared with controls.

CONCLUSIONSUK treatment can rapidly improve the V/Q mismatch in PE and appears a short-term anti-inflammatory benefit. However, LMWH maybe inhibit the later local inflammatory reaction and reduce intimal hyperplasia.

Animals ; Chemokines ; analysis ; Cytokines ; analysis ; Heparin, Low-Molecular-Weight ; therapeutic use ; Male ; Oxygen ; blood ; Pulmonary Artery ; drug effects ; pathology ; Pulmonary Embolism ; drug therapy ; immunology ; Rabbits ; Urokinase-Type Plasminogen Activator ; therapeutic use

BACKGROUNDRecent studies have shown that T helper type-2 (Th2) cells can induce the apoptosis of CD4+CD25+ Treg cells or resist the immunosuppressive effect of Treg cells. We hypothesize that an imbalance of Th2/Treg is present in patients with allergic asthma.

METHODSTwenty-two patients with mild asthma, 17 patients with moderate to severe asthma, and 20 healthy donors were enrolled. All patients were allergic to house dust mites. The proportion of peripheral blood CD4+CD25+ Treg cells and Th2 cells were determined by flow cytometry. The concentration of interleukin (IL)-10, transforming growth factor (TGF)-β and IL-4 in plasma was determined by enzyme linked immunosorbent assay. In these subjects, peripheral blood mononuclear cells from 17 mild asthmatic patients, 13 moderate to severe asthmatic patients and 14 healthy donors were acquired and expression of forkhead box P3 (Foxp3) and GATA-3 mRNA was detected by reverse-transcriptase polymerase chain reaction.

RESULTSCompared with healthy donors and patients with mild asthma, the percent of CD4+CD25+ Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma. There were no significant differences in Foxp3 mRNA expression among three groups, but a downward trend seen among patients with asthma. However, the percent of Th2 cells, IL-4 levels and expression of GATA-3 mRNA was markedly higher in patients with mild and moderate to severe asthma than in the control group. The ratio of Th2/Treg and their cytokines was increased in allergic asthma, especially for moderate to severe asthma. The ratio of GATA-3/Foxp3 mRNA was also increased in allergic asthma. In patients with moderate to severe asthma, the percentage of peripheral blood Treg cells was negatively correlated to the percentage of Th2 cells and IL-4 levels.

CONCLUSIONSThe decline of CD4+CD25+ Treg cells in patients with moderate to severe asthma may play an important role in progress of the disease. Furthermore, the deficiency of CD4+CD25+ Treg cells was associated with the over-expression of Th2 response.

Asthma ; etiology ; immunology ; Cytokines ; blood ; Forkhead Transcription Factors ; genetics ; GATA3 Transcription Factor ; genetics ; Humans ; RNA, Messenger ; analysis ; T-Lymphocytes, Regulatory ; immunology ; Th2 Cells ; immunology

BACKGROUNDAngiogenesis is an essential step for tumor development and metastasis. The cell adhesion molecule avβ3 integrin plays an important role in angiogenesis and is a specific marker of tumor angiogenesis. A novel avβ3 integrin- targeted magnetic resonance (MR) imaging contrast agent utilizing Arg-Gly-Asp (RGD) and ultrasmall superparamagnetic iron oxide particles (USPIO) (referred to as RGD-USPIO) was designed and its uptake by endothelial cells was assessed both in vitro and in vivo to evaluate the angiogenic profile of lung cancer.

METHODSUSPIO were coated with -NH3+ and conjugated with RGD peptides. Prussian blue staining was performed to evaluate the specific uptake of RGD-USPIO by human umbilical vein endothelial cells (HUVECs). Targeted uptake and subcellular localization of RGD-USPIO in HUVECs were confirmed by transmission electron microscopy (TEM). The ability of RGD-USPIO to noninvasively assess avβ3 integrin positive vessels in lung adenocarcinoma A549 tumor xenografts was evaluated with a 4.7T MR scanner. Immunohistochemistry was used to detect avβ3 integrin expression and vessel distribution in A549 tumor xenografts.

RESULTSHUVECs internalized RGD-USPIO significantly more than plain USPIO. The uptake of RGD-USPIO by HUVECs could be competitively inhibited by addition of free RGD. A significant decrease in T2 signal intensity (SI) was observed at the periphery of A549 tumor xenografts at 30 minutes (P < 0.05) and 2 hours (P < 0.01) after RGD-USPIO was injected via the tail vein. Angiogenic blood vessels were mainly distributed in the periphery of tumor xenografts with positive avβ3 integrin expression.

CONCLUSIONSRGD-USPIO could specifically label avβ3 integrin and be taken up by HUVECs. This molecular MR imaging contrast agent can specifically evaluate the angiogenic profile of lung cancer using a 4.7T MR scanner.

Animals ; Cells, Cultured ; Dextrans ; therapeutic use ; Humans ; Integrin alphaVbeta3 ; analysis ; Lung Neoplasms ; blood supply ; drug therapy ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; therapeutic use ; Mice ; Mice, Inbred BALB C ; Neovascularization, Pathologic ; prevention & control ; Oligopeptides ; therapeutic use

BACKGROUNDGeftinib is widely used in the treatment of advanced non-small cell lung cancer (NSCLC). However, only a small number of reports have described initial failure sites in patients treated with gefitinib. The aim of this study was to investigate survival, recurrence sites, and treatment after recurrence in these patients.

METHODSA retrospective review was conducted of all patients with stage III/IV NSCLC treated with gefitinib in Peking Union Medical College Hospital from October 2002 to September 2011. Patient characteristics, initial failure sites, associated clinical factors, and subsequent therapy were included in the analysis of prognostic factors.

RESULTSA total of 316 patients were identified The median progress free survival (PFS) and overall survival (OS) times were 238 days and 468 days, respectively. The median survival time after progression was 145 days. The sites of initial failure were lung (62.34%), bone (17.72%), central nerve system (CNS, 16.14%), liver (9.49%), and others (7.19%). Patients with single-site progression or multi-site progression were 81.01% and 18.99%, respectively. Progression-free survival time was associated with lung and bone failure. Additionally, the median survival time after progression was lower in patients with multi-site progression and liver progression. Other initial failure sites displayed no relationship with survival, including CNS failure. Subsequent therapy may affect survival after progression. In patients receiving continuous epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy, chemotherapy, radiotherapy, and re- treatment with EGFR-TKIs, survival time after progression was prolonged compared with the best supportive care.

CONCLUSIONSOur data suggest that patients receiving gefitinib should be closely monitored regarding lung metastasis during follow-up. Liver metastases and multi-site progression were poor prognostic factors. After failure with gefitinib, patients may benefit from radiotherapy, chemotherapy, continuous EGFR-TKI therapy and re-treatment with EGFR-TKIs.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; mortality ; Disease Progression ; Female ; Humans ; Lung Neoplasms ; drug therapy ; mortality ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Protein Kinase Inhibitors ; therapeutic use ; Quinazolines ; therapeutic use ; Retrospective Studies

BACKGROUNDEvidence has demonstrated that the distal lung, which includes airways of < 2 mm in diameter and lung parenchyma, constitutes an important component of asthma pathology. Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators and bronchoconstrictors involved in the asthmatic process. Guidelines recommend the leukotriene-modifying agents for asthma treatment. We hypothesized that a leukotriene receptor antagonist with an inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) combination would improve small airways function in moderate-to- severe asthmatics evaluated by physiological tests and high-resolution computed tomography (HRCT) analysis. This study was performed at a tertiary university hospital in Beijing.

METHODSThis was a randomized, double-blind, parallel study performed in 38 patients with moderate-to-severe asthma treated with salmeterol/futicasone (SFC) plus montelukast (SFC+M) or SFC plus placebo over 24 weeks. Small airway function was assessed by physiological studies and HRCT image analysis.

RESULTSMontelukast significantly improved air trapping as expressed by the residual volume (RV)/total lung capacity (TLC). Over 24 weeks of treatment, RV/TLC was improved by (15.41 ± 6.67)% in patients receiving SFC+M while RV/TLC was decreased by (8.57 ± 10.26)% in patients receiving SFC alone, the difference between the two groups was significant (P = 0.02). There was a trend towards a significant difference in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) in the SFC+M group compared to that in the SFC group ((17.87 ± 8.17)% vs. (12.28 ± 9.20)%, P = 0.056). There was no significant change in percentage wall area (WA%) after 24 weeks of add-on treatment with montelukast. Patients receiving SFC+M showed significant improvement in the ratio of CT-determined values at full expiration to those at full inspiration (E/I ratio) (0.894 ± 0.005 vs. 0.871 ± 0.003, P = 0.002).

CONCLUSIONWe have shown, using lung function tests and HRCT image technique, that add-on therapy with montelukast improves distal lung function reflected by air trapping, but not airway wall thickness in moderate-to-severe asthma.

Acetates ; therapeutic use ; Adult ; Airway Remodeling ; drug effects ; Anti-Asthmatic Agents ; therapeutic use ; Asthma ; drug therapy ; physiopathology ; Double-Blind Method ; Female ; Forced Expiratory Volume ; drug effects ; Humans ; Leukotriene Antagonists ; therapeutic use ; Male ; Middle Aged ; Pilot Projects ; Quinolines ; therapeutic use ; Total Lung Capacity ; drug effects

BACKGROUNDThe 2009 pandemic H1N1 (pH1N1) influenza showed that relatively young adults accounted for the highest rates of hospital admission and death. In preparation for pH1N1, the aim of the study is to identify factors associated with the mortality of patients with 2009 pH1N1 infection, especially for young patients without chronic medical conditions.

METHODSRetrospective observational study of 2151 severe or critical adult cases (≥ 14 years old) admitted to a hospital with pH1N1 influenza from September 1, 2009 to December 31, 2009 from 426 hospitals of 27 Chinese provinces. A confirmed case was a person whose pH1N1 virus infection was verified by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). Severe and critical cases were defined according to the H1N1 2009 Clinical guidelines (Third Edition, 2009) released by the Ministry of Health of China.

RESULTSAmong the 2151 patients, the mean age was 34.0 years. Two hundred and ninty-three (13.6%) died during hospital stay. One thousand four hundred and forty-two patients (67.0%) had no comorbidities and 189 (13.1%) of them died. Pregnancy (OR 8.03), pneumonia (OR 8.91), dyspnea (OR 3.95), central nervous system (CNS) symptom (OR 1.55), higher APACHE (Acute Physiology and Chronic Health Evaluation) II score (OR 1.06), Alanine aminotransferase (ALT) (OR 1.002), and the lactate dehydrogenase (LDH) level (OR 1.001) were independent risk factors for death among adults without chronic medical conditions. Higher APACHE II score (OR 1.08) and age (OR 1.06) were independent risk factors for death among adults with respiratory diseases. A multivariate analysis showed an association between mortality and CNS symptoms (OR 2.66), higher APACHE II score (OR 1.03), ALT (OR 1.006), and LDH level (OR 1.002) in patients with cardiovascular diseases. Dyspnea (OR 11.32) was an independent risk factor for patient death in patients with diabetes mellitus.

CONCLUSIONClinical knowledge of identified prognostic factors for mortality may aid in the management of adult influenza infection.

APACHE ; Adult ; Female ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; mortality ; Male ; Middle Aged ; Pandemics ; Retrospective Studies ; Risk Factors ; Time Factors