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Supplemental Digital Content is available in the text, Background: Although a number of technical problems and donor safety issues associated with living donor liver transplantation (LDLT) have been resolved, some initial clinical studies showed an increased risk of hepatocellular carcinoma (HCC) recurrence in LDLT. This meta-analysis was conducted to assess differences in tumor recurrence between LDLT and deceased donor liver transplantation (DDLT). Methods: After systematic retrievals of studies about LDLT and DDLT for HCC, articles were selected with a rationale of emphasizing inter-group comparability. Results from multivariate analyses were combined and discussed together with univariate analyses. In subgroup analysis, the impact of organ allocation policy was taken into consideration. Results: Seven articles were included in the meta-analysis. Overall, a salient result that emerged from the seven studies was a significant increased risk of HCC recurrence in the LDLT group than in the DDLT group (P = 0.01). The most significant increase in hazard ratio was found in studies where organs tended to be allocated to non-tumor patients. Conclusions: An increased risk for HCC recurrence in LDLT as compared with DDLT patients was found. The relatively shorter preoperative observation windows in LDLT may lead to fewer cases of HCC with invasive features being screened out, which may provide a possible explanation for the high rates of HCC recurrence.

Background Glucocorticoids have been widely used to treat patients with chronic obstructive pulmonary disease (COPD). Nevertheless, corticosteroid insensitivity is a major barrier to the effective treatment of COPD and its mechanism remains unclear. This study aimed to evaluate the effect of cathelicidin LL-37 on corticosteroid insensitivity in COPD rat model, and to explore the involved mechanisms. Methods COPD model was established by exposing male Wistar rats to cigarette smoke combined with intratracheal instillation of lipopolysaccharide (LPS). Inhaled budesonide and LL-37 were consequently applied to COPD models separately or collectively to confirm the effects on inflammatory cytokines (tumor necrosis factor [TNF]-α and transforming growth factor [TGF]-β) by enzyme-linked immunosorbent assay (ELISA) and lung tissue histopathological morphology. Expression of histone deacetylase-2 (HDAC2) and phosphorylation of Akt (p-AKT) in lung were also measured. Results Briefly, COPD model rats showed an increased basal release of inflammatory cytokines (lung TNF-α: 45.7 ± 6.1 vs. 20.1 ± 3.8 pg/mL, P < 0.01; serum TNF-α: 8.9 ± 1.2 vs. 6.7 ± 0.5 pg/mL, P= 0.01; lung TGF-β: 122.4 ± 20.8 vs. 81.9 ± 10.8 pg/mL, P < 0.01; serum TGF-β: 38.9 ± 8.5 vs. 20.6 ± 2.3 pg/mL, P < 0.01) and COPD related lung tissue histopathological changes, as well as corticosteroid resistance molecular profile characterized by an increase in phosphoinositide 3-kinase (PI3K)/Akt (0.5 ± 0.1 fold of control vs. 0.2 ± 0.1 fold of control, P= 0.04) and a decrease in HDAC2 expression and activity (expression: 13.1 ± 0.4 μmol/μg vs. 17.4 ± 1.1 μmol/μg, P < 0.01; activity: 1.1 ± 0.1 unit vs. 1.4 ± 0.1 unit, P < 0.01), compared with control group. In addition, LL-37 enhanced the anti-inflammatory effect of budesonide in an additive manner. Treatment with combination of inhaled corticosteroids (ICS) and LL-37 led to a significant increase of HDAC2 expression and activity (expression: 15.7 ± 0.4 μmol/μg vs. 14.1 ± 0.9 μmol/μg, P < 0.01; activity: 1.3 ± 0.1 unit vs. 1.0 ± 0.1 unit, P < 0.01), along with decrease of p-AKT compared to budesonide monotherapy (0.1 ± 0.0 fold of control vs. 0.3 ± 0.1 fold of control, P < 0.01). Conclusions This study suggested that LL-37 could improve the anti-inflammatory activity of budesonide in cigarette smoke and LPS-induced COPD rat model by enhancing the expression and activity of HDAC2. The mechanism of this function of LL-37 might involve the inhibition of PI3K/Akt pathway. Key words: Chronic obstructive pulmonary disease; Glucocorticoid insensitivity; Histone deacetylase-2; Phosphoinositide 3-kinase/Akt pathway

Background: Klebsiella pneumoniae (KP) is a pathogen commonly causing nosocomial infection. Carbapenem-resistant KP (CRKP) is more resistant to multiple antimicrobial drugs than carbapenem-susceptible KP (CSKP) isolates. The aim of the present study was to identify the risk factors for CRKP infection and the predictors of mortality among KP-infected adult patients. Methods: Patients with CRKP and CSKP infection were categorized as the case group and control group, respectively, and we conducted a 1:1 ratio case-control study on these groups. The CRKP isolates collected were tested for antimicrobial susceptibility and presence of KP carbapenemase (KPC) gene. Clinical data were collected to identify risk factors for CRKP infection and mortality of KP infection. Risk factors were analyzed under univariable and multivariable logistic regression model. Results: The independent risk factors for CRKP infection were admission to Intensive Care Unit (odds ratio [OR]: 15.486, 95% confidence interval [CI]: 3.175–75.541, P < 0.001); use of β-lactams and β-lactamase inhibitor combination (OR: 4.765, 95% CI: 1.508–15.055, P = 0.008); use of cephalosporins (OR: 8.033, 95% CI: 1.623–39.763, P = 0.011); fluoroquinolones (OR: 6.090, 95% CI: 1.343–27.613, P = 0.019); and indwelling of urethral catheter (OR: 6.164, 95% CI: 1.847–20.578, P = 0.003). However, older age (OR: 1.079, 95% CI: 1.005–1.158, P = 0.036), Charlson comorbidity index (OR: 4.690, 95% CI: 2.094–10.504, P = 0.000), and aminoglycoside use (OR: 670.252, 95% CI: 6.577–68,307.730, P = 0.006) were identified as independent risk factors for patient deaths with KP infection. The mortality of CRKP group was higher than that of the CSKP group. KPC gene did not play a role in the CRKP group. CRKP mortality was high. Conclusion: Implementation of infection control measures and protection of the immunefunction are crucial. Key words: Infection; Klebsiella pneumonia; Logistic Regression; Mortality; Risk Factors

Background: The outcome of pediatric deceased donor liver transplantation (LT) has not been well studied, especially pediatric deceased donor livers used in adult transplantation. This study aimed to evaluate the efficacy of LT using pediatric deceased donor livers and compare the outcomes between pediatric-to-pediatric LT and pediatric-to-adult LT. Methods: A retrospective review of LT using pediatric deceased donor livers from June 2013 to August 2016 was performed. The patients were divided into the pediatric-to-pediatric LT group and pediatric-to-adult LT group based on the ages of the recipients. The survival and incidence of early vascular complications (VCs) were observed between the two groups. We also analyzed the risk factors of early VCs in pediatric LT and the effect of donor hypernatremia on the prognosis of recipients. Results: There were 102 cases of LT using pediatric deceased donor livers in our hospital from June 2013 to August 2016, 83 pediatric-to-pediatric LT (recipients’ age ≤13 years) and 19 pediatric-to-adult LT (recipients’ age ≥19 years). The ratio of early VC was similar in the two groups (19.3% vs. 10.6%, P= 0.514). Low body weight of recipient was an independent risk factor of early VC in pediatric LT (odds ratio: 0.856, 95% confidence interval: 0.752- 0.975, P = 0.019). The 1-year cumulative survival rates of grafts and patients were 89.16% and 91.57% in pediatric-to-pediatric LT and 89.47% and 94.74% in pediatric-to-adult LT, respectively (all P< 0.05). In all cases, patients using donors with hypernatremia (serum sodium levels ≥150 mmol/L) had worse graft survival (χ2=4.330, P = 0.037). Conclusions: Pediatric-to-pediatric LT group has similar graft and patient survival rates with those of pediatric-to-adult LT group. Low body weight of recipients is an independent risk factor of early VC in pediatric LT. Patients using donors with hypernatremia have worse graft survival. Key words: Liver Transplantation; Pediatric Deceased Donors; Vascular Complications

Background: Investigate into the medical expenditures of chronic kidney disease (CKD) patients through path analysis method of three consecutive years within a Grade-A tertiary hospital in Beijing to conduct the main influencing factors in diagnosis-related groups (DRGs) grouping of the diagnosis, and reassess the present grouping process to provide information and reference on cost control for hospitals and medical management departments. Methods: Eight hundred and fifty-five inpatient cases whose first diagnosis were defined as CKD in the year 2014–2016 within the hospital were selected as the sample of the study, multiple linear regression and path analysis method were adopted in DRGs grouping process to investigate the main influencing factors of total medical expenditures and DRGs grouping process. Results: The maximum proportion of the medical costs within CKD patients was the costs on treatment, with the highest of 35.3% on the year 2014, the second was the costs on drug, which accounted for

Background: Renal cell carcinoma (RCC) is the most common type of malignant renal tumors with a growing incidence in the recent years. This study aimed to investigate the influencing factors and variation trend of hospitalization expenditures among RCC patients in a single-centered hospital in Beijing during 5 consecutive years and to find the major cost items and fluctuation tendency of inpatient medical expenditures. Methods: The information of medical expenditures among RCC patients in a Grade-A tertiary hospital during the years 2012–2016 was investigated to find the main cost items and changes affecting the medical cost structure. Gray correlation method was adopted in quantitative analysis to analyze the composition of medical expenditures, and the variation of hospitalization expense structure during the five years was studied by analyzing the degree of structural variation. Results: The cost item constitution of the hospitalization expenditures among RCC patients was relatively stable in the sample hospital during the past five years. To be specific, drug costs accounted for the largest proportion of medical expenditures each year, with the highest of 37.81% in 2012, and showed a slowly declining tendency in the coming years. The cost item with the highest correlation degree was drug costs, with the value of 1.0000; followed by the costs of surgeries, 0.8423. Furthermore, drug costs shared the largest proportion (40.95%) of structural variation, followed by the costs of surgeries (18.35%). Conclusions: Drug costs are the major influencing factors of the hospitalization expenditures among RCC patients. Thus, reasonable control on excessive drugs as well as the standardization of the diagnosis and treatment behaviors is conducive in reducing medical expenditures as well as easing patients’ economic burdens. Besides, the positive growth on surgery costs suggests that the labor value of medical staffs has been gradually recognized. Key words: Degree of Structural Variation; Health Expenditure; Renal Cell Carcinoma

Background: Portosystemic shunts, including surgical portosystemic shunts and transjugular intra-hepatic portosystemic shunt (TIPS), may have benefit over endoscopic therapy (ET) for treatment of variceal bleeding in patients with cirrhotic portal hypertension; however, whether there being a survival benefit among them remains unclear. This study was to compare the effect of three above-mentioned therapies on the short-term and long-term survival in patient with cirrhosis. Methods: Using the terms "variceal hemorrhage or variceal bleeding or variceal re-bleeding" OR "esophageal and gastric varices" OR "portal hypertension" and "liver cirrhosis," the Cochrane Central Register of Controlled Trials, PubMed, Embase, and the references of identified trials were searched for human randomized controlled trials (RCTs) published in any language with full texts or abstracts (last search June 2017). Risk ratio (RR) estimates with 95% confidence interval (CI) were calculated using random effects model by Review Manager. The quality of the included studies was evaluated using the Cochrane Collaboration’s tool for the assessment of the risk of bias. Results: Twenty-six publications comprising 28 RCTs were included in this analysis. These studies included a total of 2845 patients: 496 (4 RCTs) underwent either surgical portosystemic shunts or TIPS, 1244 (9 RCTs) underwent either surgical portosystemic shunts or ET, and 1105 (15 RCTs) underwent either TIPS or ET. There was no significant difference in overall mortality and 30-day or 6-week survival among three interventions. Compared with TIPS and ET, separately, surgical portosystemic shunts were both associated with a lower bleeding-related mortality (RR = 0.07, 95% CI = 0.01–0.32; P < 0.001; RR = 0.17, 95% CI = 0.06–0.51, P < 0.005) and rate of variceal re-bleeding (RR = 0.23, 95% CI = 0.10–0.51, P < 0.001; RR = 0.10, 95% CI = 0.04–0.24, P < 0.001), without a significant difference in the rate of postoperative hepatic encephalopathy (RR = 0.52, 95% CI = 0.25–1.00, P = 0.14; RR = 1.09, 95% CI = 0.59–2.01, P = 0.78). TIPS showed a trend toward lower variceal re-bleeding (RR = 0.46, 95% CI = 0.36–0.58, P < 0.001), but a higher incidence of hepatic encephalopathy than ET (RR = 1.78, 95% CI = 1.34–2.36, P < 0.001). Conclusions: The overall analysis revealed that there seem to be no short-term and long-term survival advantage, but surgical portosystemic shunts are with the lowest bleeding-related mortality among the three therapies. Surgical portosystemic shunts may be the most effective without an increased risk of hepatic encephalopathy and TIPS is superior to ET but at the cost of a higher incidence of hepatic encephalopathy. However, some of findings should be interpreted with caution due to the lower level of evidence and the existence of significant heterogeneity. Key words: Portosystemic shunts; Endoscopic therapy; Variceal rebleeding; Cirrhosis; Meta-analysis

Background: Klebsiella pneumoniae (KP) is a pathogen commonly causing nosocomial infection. Carbapenem-resistant KP (CRKP) is more resistant to multiple antimicrobial drugs than carbapenem-susceptible KP (CSKP) isolates. The aim of the present study was to identify the risk factors for CRKP infection and the predictors of mortality among KP-infected adult patients. Methods: Patients with CRKP and CSKP infection were categorized as the case group and control group, respectively, and we conducted a 1:1 ratio case-control study on these groups. The CRKP isolates collected were tested for antimicrobial susceptibility and presence of KP carbapenemase (KPC) gene. Clinical data were collected to identify risk factors for CRKP infection and mortality of KP infection. Risk factors were analyzed under univariable and multivariable logistic regression model. Results: The independent risk factors for CRKP infection were admission to Intensive Care Unit (odds ratio [OR]: 15.486, 95% confidence interval [CI]: 3.175–75.541, P < 0.001); use of β-lactams and β-lactamase inhibitor combination (OR: 4.765, 95% CI: 1.508–15.055, P = 0.008); use of cephalosporins (OR: 8.033, 95% CI: 1.623–39.763, P = 0.011); fluoroquinolones (OR: 6.090, 95% CI: 1.343–27.613, P = 0.019); and indwelling of urethral catheter (OR: 6.164, 95% CI: 1.847–20.578, P = 0.003). However, older age (OR: 1.079, 95% CI: 1.005–1.158, P = 0.036), Charlson comorbidity index (OR: 4.690, 95% CI: 2.094–10.504, P = 0.000), and aminoglycoside use (OR: 670.252, 95% CI: 6.577–68,307.730, P = 0.006) were identified as independent risk factors for patient deaths with KP infection. The mortality of CRKP group was higher than that of the CSKP group. KPC gene did not play a role in the CRKP group. CRKP mortality was high. Conclusion: Implementation of infection control measures and protection of the immunefunction are crucial.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique used to alter cortex excitability that has been proposed as an efficient method for treating brain hyperexcitability or hypoexcitability disorders. The aim of this study was to investigate whether high-frequency rTMS could have any beneficial effects in restless legs syndrome (RLS). Methods: Fourteen patients with RLS were given high-frequency rTMS (15 Hz, 100% motor threshold) to the leg representation motor cortex area of the frontal lobe for 14 sessions over 18 days. Patients were diagnosed according to the international criteria proposed by the International Restless Legs Syndrome Study Group in 2003. The International RLS Rating Scale (IRLS-RS), Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale were used to evaluate the severity of RLS, sleep quality, anxiety and depression, respectively. The scale scores were evaluated at four-time points (baseline, end of the 14 th session, and at 1- and 2-month posttreatment). One-way analysis of variance was used to compare scale scores at different time points. Results: There was significant improvement in the IRLS-RS (from 23.86 ± 5.88 to 11.21 ± 7.23, P < 0.05), PSQI (from 15.00 ± 4.88 to 9.29 ± 3.91, P < 0.05), and HAMA (from 17.93 ± 7.11 to 10.36 ± 7.13, P < 0.05) scale scores at the end of 14 th session, with ongoing effects lasting for at least 2 months. Conclusions: High-frequency rTMS can markedly alleviate the motor system symptoms, sleep disturbances, and anxiety in RLS patients. These results suggest that rTMS might be an option for treating RLS.

BACKGROUND Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. It is suggested that increased levels of circulating leptin may contribute to anorexia in pathologic conditions including chronic obstructive pulmonary disease (COPD). Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). This study aimed to explore the role of serum leptin in the malnutrition of COPD patients, and to observe the changes of serum leptin levels during acute exacerbation, also to investigate relationship between leptin and TNF-alpha. METHODS Seventy-two COPD patients and 34 control subjects participated in this study. Seventy-two COPD patients were divided into 3 groups: group COPD IA (patients without malnutrition during acute exacerbation, n = 25), group COPD IB (patients without malnutrition during stable disease, n = 29), group COPD II (patients with malnutrition during stable disease, n = 18). To eliminate the effect of sex differences, all patients and controls were male. Body mass index (BMI), percent ideal body weight (IBW%), triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), mid-upper arm muscle circumference (MAMC), serum leptin and TNF-alpha levels, serum prealbumin (PA), serum transferrin (TF), serum albumin (Alb), total lymphocytes count (TLC), forced expiratory volume in one second (FEV(1)), maximal inspiration pressure (MIP) and maximal expiration pressure (MEP) were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-alpha levels were measured by ELISA. The between group difference and correlation of these parameters were analyzed. RESULTS Serum leptin levels were significantly lower in group COPD II [(4.07 +/- 3.42) ng/ml] than in group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml] (P < 0.05). There was no statistically significant difference in serum leptin levels between group COPD IA [(10.82 +/- 6.40) ng/ml], group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml]. There was no statistically significant difference in serum TNF-alpha levels between group COPD II [(8.03 +/- 3.37) pg/ml], group COPD IA [(8.90 +/- 1.60) pg/ml], and group COPD IB [(7.25 +/- 2.08) pg/ml]. There was no significant correlation between leptin and TNF-alpha in any group. CONCLUSIONS Leptin was not involved in anorexia and weight loss of COPD patients. There was no statistically significant difference in serum leptin levels between COPD patients during stable stage and acute exacerbation, and there was no significant correlation between TNF-alpha and leptin during the regulation of the energy balance in COPD patients.

The emergence of heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) is increasingly challenging the methods for detection in diagnostic microbiology laboratories. However, the report of hVISA is rare in China. This study summarizes the prevalence and clinical features associated with hVISA infections at our institution and the local impact they have on clinical outcome.A total of 122 methicillin-resistant Staphylococcus aureus (MRSA) isolates which were of the causative pathogens were collected. One hundred and two patients for whom we had full information of MRSA pneumonia were included. Isolates of MRSA were collected using PCR to detect the mecA gene. Both Etest and macro Etest were performed to screen for hVISA. The Staphylococcal chromosome cassette mec (SCCmec) types were determined by multiplex PCR strategy. Logistic regression analysis was used to determine the risk factors.Among the 122 MRSA isolates collected, 25 (20.5%) strains were identified as hVISA. There were 119 (97.5%) SCCmec III isolates, two (1.6%) SCCmec II isolates, and one (0.8%) SCCmec V isolate. The 30-day mortality of MRSA-hospital acquired pneumonia (HAP) was 37.3%, and 62.5% for hVISA-HAP. Vancomycin treatment was the independent risk factor of hVISA. Factors independently associated with 30-day mortality in all patients were acute physiology and Chronic Health Evaluation (APACHE) II score20, multiple lobe lesions, and creatinine clearance rate (CCR)15 ml/min.The prevalence of hVISA is 20.5% at our institution. hVISA-HAP patients had a poor clinical outcome. Vancomycin treatment was the independent predictors for hVISA infection. Factors independently associated with 30-day mortality in all patients were APACHE II score20, multiple lobe lesions and CCR15 ml/min.

Many studies have shown the superior efficacy of budesonide (BUD)/formoterol (FORM) maintenance and reliever therapy, but still lack evidence of its efficacy in Chinese asthma patients in a relative large patient-group. We finished this research to compare BUD/FORM maintenance and reliever therapy and high-dose salmeterol (SALM)/fluticasone (FP) maintenance plus an as-needed short-acting β(2)-agonist in Chinese patients with persistent uncontrolled asthma. This was a post hoc analysis based on a 6-month, multicenter, randomized, double-blind study (NCT00242775).A total of 222 eligible asthma patients from nine centers in China were randomized to either BUD/FORM+as-needed BUD/FORM (160/4.5 µg/inhalation) (640/18 µg/d; n = 111), or SALM/FP+as-needed terbutaline (0.4 mg/inhalation) (100/1000 µg/d; n = 111). The primary endpoint was time to first severe exacerbation while secondary endpoints included various measures of pulmonary function, symptom control and quality-of-life.Time to first severe exacerbation over six months was lower with the BUD/FORM than with the SALM/FP treatment (risk ratio = 0.52, 95%CI 0.22 - 1.22), but the difference did not achieve statistical significance (P = 0.13). The cumulative number of severe exacerbations in the BUD/FORM group was lower than in the SALM/FP group (7.2% vs. 13.5%; risk ratio = 0.45, P = 0.028). BUD/FORM produced significantly better improvements in reliever use, cumulative mild exacerbations, symptom-free days (%), and morning/evening peak expiratory flow (PEF) than SALM/FP (P0.05 in all cases). The two groups achieved similar improvements in their time to first mild exacerbation, forced expiratory volume in one second (FEV(1)), asthma control questionnaire and asthma symptom scores, and percentage of nights with awakening(s). Both treatments were well tolerated.In Chinese patients with persistent asthma, BUD/FORM decreased severe and mild exacerbations, decreased reliever use, increased symptom-free days, and improved morning/evening PEF compared with SALM/FP. There were no significant differences in time to first severe exacerbation or other assessments regarding daily asthma control between BUD/FORM and SALM/FP. BUD/FORM was more effective in this Chinese sub-group than in the total cohort involved in the original study.

Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent brief episodes of chorea and dystonia induced by sudden movement. Whether the central nervous system is hyper- or hypoexcitable in PKD remains undetermined. The aim of our study was to compare the somatosensory evoked potential (SEP) recovery cycle, a marker of somatosensory system excitability, in PKD patients and controls.Twenty-four PKD patients (mean age of (20.0±5.3) years; 21 males, 3 females) and 18 control age-matched subjects (mean age of (22.0±5.0) years; 17 males, 1 female) were studied. The stimuli were delivered to the median nerve in the affected dominant arm in patients and in the dominant arm in controls. The change in SEP amplitude was measured after paired electrical stimulation at interstimulus intervals (ISIs) of 5, 20, and 40 ms. The SEPs evoked by S2 (test stimulus) were calculated by subtracting the response to S1 (the conditioning stimulus) from the response to a pair of stimuli (S1+S2), and their amplitudes were compared with those of the control response (S1) at each ISI. Analysis of variance (ANOVA) or equivalent was used for non-parametric data.In patients, the P27 amplitude after the single stimulus (S1) was significantly larger than that after the control stimulus. The (S2/S1)×100 ratio for P14 and N30 SEPs did not differ significantly between PKD patients and normal subjects at ISI of 5 ms but were significantly higher in patients at ISIs of 20 and 40 ms (P0.05).Somatosensory system disinhibition takes place in PKD. The finding of reduced suppression of different SEPs, each thought to have a different origin, suggests an abnormality of intracortical and subcortical inhibitory circuits.

Acute lung infection due to Pseudomonas aeruginosa (P. aeruginosa) is a serious problem, especially in patients with structural lung conditions or immune compromised hosts, leading to an overwhelming threat with a high risk of morbidity and mortality. As an outcome of infection, fibrosis can be linked with chronic lung diseases. But some fibrotic manifestations, such as an irreversible decrease of lung function and fibrous bands seen on chest imaging, have been found after an acute infection with P. aeruginosa. Fibrogenesis/remodeling resulting from acute lung infection by P. aeruginosa is rarely reported. This study was designed to explore the relation between fibrogenesis/remodeling and acute infection by P. aeruginosa in vitro. We used flagellin protein from P. aeruginosa, a key initiator of acute P. aeruginosa lung infection, to elucidate mechanisms by which acute lung infection with P. aeruginosa can cause fibrogenesis/remodeling.We studied the effect of flagellin from P. aeruginosa (flagellin for short) on the transforming growth factor beta 1 (TGF-β1) and interleukin-8 (IL-8) expression, and the possible involvement of the signaling pathway, tumor necrosis factor receptor-associated factor 6 (TRAF6)/mitogen activated protein kinase (MAPK) pathway. Flagellin was purified from the P. aeruginosa standard strain, PAO1. Normal bronchial epithelial cells BEAS-2B were challenged with different concentrations of flagellin, and cell viability assessment was performed by cell counting kit-8. BEAS-2B cells were incubated with flagellin with the specific MAPK inhibitors or TRAF6 siRNA. Cell lysates and the cultured supernatant were collected. The level of TGF-β1 and IL-8 were detected by enzyme-linked immunosorbant assay (ELISA). Western blotting was used to detect the protein levels of MAPK signal proteins p38, c-Jun NH(2)-terminal kinase (JNK) and extracellular regulated kinase (ERK).Expression of TGF-β1 in BEAS-2B cells was elevated by flagellin vs. control groups ((104.3 ± 20.8) vs. (44.6 ± 4.4) pg/ml (P0.01)) and was ablated by either p38 or JNK inhibitors compared with flagellin treatment ((45.1 ± 18.8) vs. (104.3 ± 20.8) pg/ml and (48.1 ± 20.8) vs. (104.3 ± 20.8) pg/ml, respectively (P0.05)). Flagellin also elevated the expression of IL-8 in BEAS-2B cells vs. the control groups ((554.9 ± 57.7) vs. (51.4 ± 22.9) pg/ml (P0.01)), and p38 MAPK inhibitors weaken the expression by flagellin ((301.1 ± 155.1) vs. (554.9 ± 57.7) pg/ml (P0.05)). Western blotting revealed that all three MAPK proteins, p38, JNK and ERK were activated by flagellin challenge in an early phase, respectively in 15 minutes (P0.01), 30 minutes (P0.01) and 15 minutes (P0.01). TRAF6 siRNA which decreased expression of TRAF6, altered the activation of JNK, p38, and ERK following flagellin treatment, but its influence on the expression of TGF-β1 and IL-8 has no statistical significance.Flagellin from P.aeruginosa PAO1 induces TGF-β1 expression in normal bronchial epithelial cells, BEAS-2B, through the MAPK signal cascade in vitro. It suggests that the fibrogenesis/remodeling process may be initiated from an early stage of acute lung infection due to P. aeruginosa.

In the chronic stage of cerebral venous sinus thrombosis (CVST), recanalization can result in disparate MR appearances. We aimed to prospectively investigate the diagnostic accuracy of magnetic resonance venography (MRV) in the evaluation of the recanalization of CVST.This study prospectively evaluated the diagnostic performance of 2-dimensional time-of-flight (2D-TOF) MRV in thirty-two consecutive patients during a three- to six-month follow-up for CVST. Both 2D-TOF MRV and digital substraction angiography (DSA) were undertaken. Diagnostic accuracy of 2D-TOF MRV in the detection of recanalized thrombus was evaluated using DSA as the reference standard.MRV and DSA were completed without complications in all 32 patients. The sensitivity, specificity, positive predictive value, and negative predictive value of 2D-TOF MRV for the detection of recanalization on a segmental basis were 91% (62/68), 93% (37/40), 95% (62/65), and 86% (37/43) respectively.2D-TOF MRV provides high sensitivity and specificity for the diagnosis of recanalized CVST segments.

Macro- and microvascular diseases are the leading cause of morbidity and mortality in diabetic patients, but their mechanisms remain unclear. Recent reports provide evidence that the levels of CD55 and CD59 are decreased in diabetic microvascular diseases. However, very little is known about the levels of CD55 and CD59, the relationship between them and carotid artery intima-media thickness, and the effects of statins on CD55 and CD59 in diabetic macrovascular diseases.The mean fluorescence intensity (MFI) of CD55 and CD59 expression on peripheral blood leucocyte subsets (lymphocytes, monocytes and neutrophils) was studied using flow cytometry, and carotid artery intima-media thickness was measured using B-mode ultrasonography in 23 healthy subjects (controls), 19 patients with type 2 diabetes (T2DM), and 43 patients with type 2 diabetes and macrovascular diseases (T2DM-M). The patients with T2DM-M were assigned to two subgroups based on whether statins were used: group with statins (n = 23) and group without statins (n = 20).Compared with the controls and T2DM, the MFI of CD55 positive neutrophils was significantly lower in T2DM-M (P = 0.049 vs controls and P = 0.033 vs T2DM); similarly, the MFI of CD59 positive monocytes was also lower in T2DM-M (P = 0.038 vs controls and P = 0.043 vs T2DM). The MFI of CD59 positive neutrophils in T2DM-M was lower than in T2DM (P = 0.032). The levels of CD55 and CD59 were negatively associated with age and blood pressure (r = -0.245 - -0.352, P = 0.041 - 0.003), but not acute-phase reactants and carotid artery intima-media thickness. The levels of CD55 and CD59 increased after treatment with statins, but the results were not significantly different (P0.05).CD55 and CD59 expressions on peripheral blood leucocytes are decreased in T2DM patients with macrovascular diseases. The results suggest that the decreased levels of complement regulatory proteins might play an important role in diabetic macrovascular diseases.

CD4(+) T cells play a crucial role in the pathogenesis of aplastic anaemia. However, the mechanisms of over-proliferation, activation, infiltration of bone marrow and damage to haematopoietic cells of CD4(+) T cells in aplastic anaemia are unclear. Therefore, we screened differentially expressed genes of bone marrow CD4(+) T cells of aplastic anaemia patients and normal donors by suppressive subtractive hybridization to investigate the pathogenesis of aplastic anaemia.The bone marrow mononuclear cells of a first visit aplastic anaemia patient and a healthy donor of the same age and sex were isolated using lymphocyte separating medium by density gradient centrifugation. With the patients as "tester" and donor as "driver", their CD4(+) T cells were separated with magnetic bead sorting and a cDNA library established by suppressive subtractive hybridization. Then 15 of the resulting subtracted cDNA clones were randomly selected for DNA sequencing and homological analysis. With semiquantitative RT-PCR, bone marrow samples from 20 patients with aplastic anaemia and 20 healthy donors assessed the expression levels of differentially expressed genes from SSH library.PCR detected 89 clones in the library containing an inserted fragment of 100 bp to 700 bp. Among 15 sequenced clones, 12 were known genes including 3 repeated genes. Compared with normal donors, there were 9/12 genes over-expressed in bone marrow CD4(+) T cells of patients with aplastic anaemia. The effects of these genes included protein synthesis, biology oxidation, signal transduction, proliferative regulation and cell migration. Not all these genes had been reported in the mechanisms of haematopoietic damage mediated by CD4(+) T cells in aplastic anaemia.Screening and cloning genes, which regulate functions of CD4(+) T cells, are helpful in elucidating the mechanisms of over proliferation, activation, infiltrating bone marrow and damaging haematopoietic cells of CD4(+) T cells in aplastic anaemia.

Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. It is suggested that increased levels of circulating leptin may contribute to anorexia in pathologic conditions including chronic obstructive pulmonary disease (COPD). Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). This study aimed to explore the role of serum leptin in the malnutrition of COPD patients, and to observe the changes of serum leptin levels during acute exacerbation, also to investigate relationship between leptin and TNF-alpha.Seventy-two COPD patients and 34 control subjects participated in this study. Seventy-two COPD patients were divided into 3 groups: group COPD IA (patients without malnutrition during acute exacerbation, n = 25), group COPD IB (patients without malnutrition during stable disease, n = 29), group COPD II (patients with malnutrition during stable disease, n = 18). To eliminate the effect of sex differences, all patients and controls were male. Body mass index (BMI), percent ideal body weight (IBW%), triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), mid-upper arm muscle circumference (MAMC), serum leptin and TNF-alpha levels, serum prealbumin (PA), serum transferrin (TF), serum albumin (Alb), total lymphocytes count (TLC), forced expiratory volume in one second (FEV(1)), maximal inspiration pressure (MIP) and maximal expiration pressure (MEP) were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-alpha levels were measured by ELISA. The between group difference and correlation of these parameters were analyzed.Serum leptin levels were significantly lower in group COPD II [(4.07 +/- 3.42) ng/ml] than in group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml] (P0.05). There was no statistically significant difference in serum leptin levels between group COPD IA [(10.82 +/- 6.40) ng/ml], group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml]. There was no statistically significant difference in serum TNF-alpha levels between group COPD II [(8.03 +/- 3.37) pg/ml], group COPD IA [(8.90 +/- 1.60) pg/ml], and group COPD IB [(7.25 +/- 2.08) pg/ml]. There was no significant correlation between leptin and TNF-alpha in any group.Leptin was not involved in anorexia and weight loss of COPD patients. There was no statistically significant difference in serum leptin levels between COPD patients during stable stage and acute exacerbation, and there was no significant correlation between TNF-alpha and leptin during the regulation of the energy balance in COPD patients.

Hematopoietic stem cells (HSCs) give rise to all blood and immune cells and are used in clinical transplantation protocols to treat a wide variety of refractory diseases, but the amplification of HSCs has been difficult to achieve in vitro. In the present study, the expansive effects of aorta-gonad-mesonephros (AGM) region derived stromal cells on HSCs were explored, attempting to improve the efficiency of HSC transplantation in clinical practice.The murine stromal cells were isolated from the AGM region of 12 days postcoitum (dpc) murine embryos and bone marrow (BM) of 6 weeks old mice, respectively. After identification with flow cytometry and immunocytochemistry, the stromal cells were co-cultured with ESCs-derived, cytokines-induced HSCs. The maintenance and expansion of ESCs-derived HSCs were evaluated by detecting the population of CD34+ and CD34+Sca-1+ cells with flow cytometry and the blast colony-forming cells (BL-CFCs), high proliferative potential colony-forming cells (HPP-CFCs) by using semi-solid medium colonial culture. Finally, the homing and hematopoietic reconstruction abilities of HSCs were evaluated using a murine model of HSC transplantation in vivo.AGM and BM-derived stromal cells were morphologically and phenotypically similar, and had the features of stromal cells. When co-cultured with AGM or BM stromal cells, more primitive progenitor cells (HPP-CFCs) could be detected in ESCs derived hematopoietic precursor cells, but BL-CFC's expansion could be detected only when co-cultured with AGM-derived stromal cells. The population of CD34+ hematopoietic stem/progenitor cells were expanded 3 times, but no significant expansion in the population of CD34+Sca-1+ cells was noted when co-cultured with BM stromal cells. While both CD34+ hematopoietic stem/progenitor cells and CD34+Sca-1+ cells were expanded 4 to 5 times respectively when co-cultured with AGM stromal cells. AGM region-derived stromal cells, like BM-derived stromal cells, could promote hematopoietic reconstruction and HSCs' homing to BM in vivo.AGM-derived stromal cells in comparison with the BM-derived stromal cells could not only support the expansion of HSCs but also maintain the self-renewal and multi-lineage differentiation more effectively. They are promising in HSC transplantation.

Corneal dystrophy is a group of inherited blinding diseases of the cornea. This study was to identify the mutations of the keratoepithelin (KE) gene for proper diagnosis of corneal dystrophy.Three families with corneal dystrophy were analysed. Thirteen individuals at risk for corneal dystrophy in family A, the proband and her son in family B, and the proband in family C were examined after their blood samples were obtained. Mutation screening of human transforming growth factor beta-induced gene (BIGH3 gene) was performed.Five individuals in family A were found by clinical evaluation to be affected with granular corneal dystrophy and carried the BIGH3 mutation W555R. However, both probands in families B and C, also diagnosed with granular corneal dystrophy, harboured the BIGH3 mutation R124H.Molecular genetic analysis can improve accurate diagnosis of corneal dystrophy.