Evaluation of miR-429 as a novel serum biomarker for pancreatic ductal adenocarcinoma and analysis its tumor suppressor function and target genes.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer. Various microRNAs have been identified to play an important role in PDAC. The study aimed to explore the role of miR-429 in PDAC. PATIENTS AND METHODS: The expression and prognostic value of miR-429 were first analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Next, miR-429 expression was evaluated in the tissues and serum of 90 patients with PDAC. CCK8, SRB, wound healing and transwell assays were used to determine the effect of miR-429 on the proliferation, invasion, and migration of PDAC cells, respectively. Weighted gene co-expression network analysis (WGCNA), correlation analysis, TargetScan, and miRDB databases were used to screen and identify the target genes of miR-429. RESULTS: The results revealed that the expression of miR-429 was downregulated in PDAC tissues and the serum compared with those in normal tissues and the serum of healthy volunteers, respectively. The decreased expression of miR-429 was significantly associated with shorter overall survival. The overexpression of miR-429 significantly inhibited the proliferation, invasion, and migration of PDAC cells. Potential target genes of miR-429 were identified using WGCNA and bioinformatics analysis, and the results showed that cadherin 11 (CDH11), inositol polyphosphate-4-phosphatase type I (INPP4A), laminin gamma 1 (LAMC1), low density lipoprotein receptor-related protein 1 (LRP1), and quaking (QKI) were potential target genes of miR-429 in PDAC. Lower expression of CDH11 and QKI was associated with a more favorable prognosis in patients with PDAC. The overexpression of miR-429 could inhibit the expression of CDH11 and QKI. A nomogram model, involving miR-429, CDH11, and QKI, was subsequently constructed to determine their ability to accurately predict overall and disease-free survival in patients with PDAC. CONCLUSIONS: Taken together, miR-429 is involved in the development and progress of PDAC. MiR-429 could be recommended as a prognostic biomarker and therapeutic indicator in PDAC diagnosis.

Effect of topically applied silver compounds on the demineralisation of hydroxyapatite.

OBJECTIVES: This study investigates the demineralization inhibitory mechanisms of AgNO3, AgF and silver diamine fluoride (SDF) using a previously used hydroxyapatite (HAP) caries demineralization model system. METHODS: HAP discs were allocated into three groups (n = 3) and immersed in demineralization solution (buffered pH 4.0, 0.1 mol/L acetic acid) for 4 h. Each disc was treated topically with either 3.16 M AgNO3, 3.16 M AgF or 3.16 M SDF using a micro-brush. The discs were then demineralized for a further 4 h. Calcium, silver, and fluoride ion selective electrodes (ISEs) were used to monitor the changes in each ion concentration at 1 min intervals throughout. Demineralization inhibition was calculated as the percentage reduction in the rate of calcium ion loss from HAP (PRCLHAP). Characterization of similarly treated HAP powder was carried out with Magic Angle Spinning-Nuclear Magnetic Resonance RESULTS: The mean PRCLHAP for each treatment group was; AgF (72.3 + 4.8%), SDF (69.7 + 5.3%) and AgNO3 (14.9 + 2.7%). Ag3PO4 was detected in all HAP powders. CaF2 and fluorohydroxyapatite (FHA) were detected only in powders treated with either AgF or SDF. The demineralization inhibitory efficacy of topically applied AgNO3 results from the formation of a Ag3PO4 barrier. Whereas, the demineralization inhibitory efficacy of topically applied AgF, and SDF, results from the formation of a barrier composed of Ag3PO4, CaF2, and FHA. SIGNIFICANCE: In addition to their anti-microbial properties, clinical topical application of silver compounds for caries preventative treatment is due to their ability to form acid-resistant barriers composed of silver phosphate. When fluoride is present, this barrier also contains CaF2 and FHA, additionally protecting the mineral.

[Characteristics of PD-L1 expression in tumor cells and tumor microenvironment of DLBCL with MYD88 L265P mutation].

Objective: To study the effect of MYD88 L265P mutation on the expression of PD-L1 in tumor cells and tumor microenvironment in diffuse large B-cell lymphoma (DLBCL), and to provide theoretical basis for immunotherapy for patients. Methods: Multiplex ligation-dependent probe amplification (MLPA) was used to detect the frequency of MYD88 L265P mutation in 72 cases of DLBCL diagnosed by pathologists in Cancer Hospital of Chinese Academy of Medical Sciences from August 2008 to May 2010. Expression of PD-L1 in tumor cells and tumor microenvironment in all samples was evaluated using PD-L1 (22C3) and PD-L1 (SP142) with Ventana automatic immunohistochemical (IHC) platform. The relationship between MYD88 L265P mutation and the expression of PD-L1 in DLBCL tumor cells and tumor microenvironment was assessed. Results: Of the 72 cases of DLBCL, MYD88 L265P mutation was detected in 15 (20.8%) cases. Nine cases with JAK2 amplification were excluded, and the remaining 63 cases of DLBCL were divided into MYD88 L265P mutant group (n=14) and MYD88 L265P wild-type group (n=49). IHC results showed that among the 14 cases of MYD88 L265P mutant groups, PD-L1 (22C3) was positive in 7 cases (7/14) of tumor cells and PD-L1 (SP142) was positive in 4 cases (4/14) of tumor microenvironment. Among the 49 cases of MYD88 L265P wild-type group, 9 cases (18.4%) were positive for PD-L1 (22C3) in tumor cells, and 38 cases (77.6%) were positive for PD-L1(SP142) in tumor microenvironment. In addition, among the 16 cases with PD-L1(22C3) expression in tumor cells, only 2 of the 7 cases with MYD88 L265P mutation were positive for PD-L1 (SP142) in tumor microenvironment. All 9 cases with wild-type MYD88 L265P were positive for PD-L1 (SP142) in tumor microenvironment. Statistical analysis showed that the expression level of PD-L1 (22C3) in tumor cells in the MYD88 L265P mutant group was significantly higher than that in the MYD88 L265P wild-type group (P=0.017). The expression level of PD-L1 (SP142) in tumor microenvironment in the MYD88 L265P mutant group was significantly lower than that in the MYD88 L265P wild-type group (P=0.001). Conclusions: MYD88 L265P mutation may play an important role in the regulation of PD-L1 expression in DLBCL tumor cells and tumor microenvironment. Further studies will provide a theoretical basis for immunotherapy of DLBCL patients with MYD88 L265P mutation.

[Analysis of the clinical efficacy and safety of bronchial thermoplasty in the treatment of patients with severe asthma and asthma-chronic obstructive pulmonary disease overlap].

Objective: To investigate the clinical efficacy and safety analysis of bronchial thermoplasty (BT) in the treatment of severe asthma and asthma-chronic obstructive pulmonary disease overlap. Methods: The clinical data of 49 patients with asthma-COPD overlap who received BT in the University of Chinese Academy of Sciences Shenzhen Hospital from January 2016 to December 2018 and 50 patients with severe asthma who received BT in the same period were retrospectively analyzed. Patients were divided into overlap group and asthma group, and the baseline data of two groups were recorded. The pulmonary function before and after treatment (including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1 as a percentage of predicted value (FEV1% pred)), hormone consumption, asthma control test (ACT) score, asthma quality of life questionnaire (AQLQ) score, asthma control questionnaire (ACQ) score, the overlap group before and after treatment COPD assessment test (CAT) score, modified British Medical Research Council (mMRC) score and postoperative respiratory adverse events in the next 3 weeks were comparatively analyzed. Results: The general baseline characteristics of the two groups are compared. The patients in the overlap group were older than those in the asthma group, and the course of disease and smoking history were longer than those in the asthma group. The inhaled hormone dosage in asthma group was greater than those in the overlap group ((64±11) years vs (48±11) years; 10.00 (10.00, 25.00) years vs 9.00 (1.75, 20.00) years; 20.00(2.00, 40.00) years vs 0 (0, 10.00) years; 320 (320, 640) µg/d vs 960 (320, 960) µg/d) (all P<0.05). The predicted values of lung function indexes FVC, FEV1, FEV1% pred in the overlap group before treatment were all lower than those in the asthma group (1.98 (1.43, 2.43) L vs 2.54 (2.02, 3.15) L; 0.92 (0.61, 1.26) L vs 1.69(1.17, 2.16) L; (50±16) L vs (65±14) L) (all P<0.05). There were no significant differences in ACT, ACQ, and AQLQ scores between the two groups before treatment (all P>0.05). Within 3 months after treatment, except for no significant improvement in FEV1% predicted value and inhaled hormone dosage in the overlap group (all P>0.05), other indexes in both groups were improved compared with those before treatment (all P<0.05). After 1 year of treatment, all indexes of the two groups were significantly improved than those before treatment, and all indexes of the asthma group were better than those of the overlap group (all P<0.05). In terms of respiratory adverse events occurring within 3 weeks after the operation, the incidence of cough and bloody sputum in the overlap group was higher than that in the asthma group, while the incidence of sputum and short-term wheezing was lower than that in the asthma group (all P<0.05). There were no statistically significant differences in the incidence of chest tightness, chest pain, segmental atelectasis and pneumonia between the two groups (all P>0.05), and the postoperative adverse reactions could be effectively controlled in a short period of time. Conclusion: BT treatment could not only improve the lung function, clinical symptoms and quality of life of asthmatic patients, but was also effective for asthma-COPD overlap patients. However, BT treatment had more benefits for asthmatic patients without serious adverse events occurred.

[Analysis of the safety and efficacy of bronchial thermoplasty for severe asthma with the first second forced expiratory volume (FEV(1)) as a percentage of the predicted value (FEV(1)%pred)<60].

Objective: To investigate the efficacy and safety of bronchial thermoplasty (BT) in severe asthma patients with the first second forced expiratory volume (FEV(1)) as a percentage of the predicted value (FEV(1)%pred) <60%. Methods: A retrospective analysis was performed on 75 patients with asthma who were treated with BT at Shenzhen University Hospital of the Chinese Academy of Sciences from January 2016 to January 2018. The patients were divided into two groups based on the FEV(1)%pred before treatment: FEV(1)%pred <60% group (39 cases) and FEV(1)%pred ≥60% group (36 cases). Comparative analysis of glucocorticoid consumption, times of acute attack, asthma control test (ACT) score, changes in lung function, and adverse reactions at 3 weeks after treatment were performed between the two groups of patients. Results: Before BT treatment, the consumption of oral prednisone, the amount of budesonide inhaled, and the times of acute attack [M (Q(1), Q(3))] in the FEV(1)%pred <60% group were significantly greater than those in the FEV(1)%pred ≥60% group, and the ACT score was significantly lower than the FEV(1)%pred ≥60% group [10.00 (0, 20.00) vs 0(0, 3.75) mg/d, 960 (320, 960) vs 320 (320, 640) µg/d, 5(4, 8) vs 4 (4, 5) times/year, 13 (9, 15) vs 17 (13, 19) scores] (all P<0.05). Except that the oral prednisone dosage in the FEV(1)%pred<60% group was still higher 1 year after treatment [0 (0, 5.00) vs 0 (0, 0) mg/d] (P=0.009), there was no significant difference in the remaining indicators between the two groups 1 year after treatment and 2 years after treatment (all P>0.05). After 1 year and 2 years of treatment, all indicators in the two groups were better than before treatment (all P<0.05). The inhaled budesonide amount and the times of acute exacerbation in the FEV(1)%pred <60% group 2 years after treatment were less than those 1 year after treatment [320 (320, 320) vs 320 (320, 640) µg/d, 0 (0, 0) vs 0(0, 1) times/year] (all P<0.05), and there was no significant difference in the remaining indicators. In the FEV(1)%pred ≥60% group, there was no significant difference between 2 years after treatment and 1 year after treatment in the above indicators except the amount of inhaled budesonide (all P>0.05). In the FEV(1)%pred <60% group, FEV(1) and the FEV(1)%pred were significantly lower than the FEV(1)%pred ≥60% group before treatment, 1 year after treatment and 2 years after treatment [FEV(1):(1.21±0.41) vs (2.26±0.80)L, (1.84±0.73) vs (2.30±0.78)L, (1.70±0.66) vs (2.38±0.76)L; FEV(1)%pred:46.2 (38.5, 53.7)% vs 80.8(66.5, 93.6)%, 60.1 (48.2, 71.6)% vs 87.4 (68.5, 96.5)%, 58.5 (48.6, 74.8)% vs 86.6 (73.0, 97.3)%] (all P<0.05). In the FEV(1)%pred <60% group, FEV(1) and FEV(1)%pred 1 year after treatment and 2 years after treatment were all increased compared with before treatment (all P<0.05). In the FEV(1)%pred ≥60% group, there was no statistical difference in FEV(1) at each time point before and after treatment (all P>0.05), but the FEV(1)%pred at 2 years after treatment was higher than before treatment (P<0.05). There were no significant differences in adverse events between the two groups (all P>0.05). Conclusion: BT can significantly improve the lung function, reduce the times of acute attack and the dosage of glucocorticoids in severe asthma patients with FEV(1)% pred<60%, which is safe and effective.

[Relationship between serum vitamin E concentration in first trimester and the risk of developing hypertension disorders complicating pregnancy].

OBJECTIVE: To investigate the incidence of hypertension disorders complicating pregnancy (HDCP) and vitamin E (VE) nutritional status among pregnant women in Beijing, and to determine the relationship between serum VE concentration in the first trimester of pregnancy and the risk of developing HDCP. METHODS: A retrospective cohort study was performed including 22 283 cases of pregnant women who underwent singleton deliveries in Tongzhou Maternal & Child Health Hospital of Beijing from January 2016 through December 2018 and received tests of serum VE concentrations in the first trimester of pregnancy. Nonconditional Logistic regression model was used to analyze the association between serum VE concentration levels and the risk of developing HDCP. RESULTS: The total incidence of HDCP was 5.4%, with the incidence of gestational hypertension around 2.1% and the incidence of preeclampsia-eclampsia around 3.3%. The median concentration of serum VE in early pregnancy was 10.1 (8.8-11.6) mg/L, and 99.7% of the participants had normal serum VE concentrations. The incidence of gestational hypertension and that of preeclampsia-eclampsia had been annually increasing in three years; a linear-by-linear association had also been observed between the serum VE concentrations and the years of delivery. According to the results of the univariable and the multivariable Logistic regression analyses, higher risks of developing HDCP had been observed among women with higher serum VE concentrations. Compared to those with serum VE concentrations in interquartile range (P25-P75) of all the participants, the women whose serum VE concentrations above P75 were at higher risks to be attacked by HDCP (OR = 1.34, P < 0.001), gestational hypertension (OR = 1.39, P = 0.002), or preeclampsia-eclampsia (OR = 1.34, P = 0.001), as suggested by the results of the multivariable Logistic regression model analyses. In addition, the women with serum VE concentrations of 11.2 mg/L or above had a significantly higher risk of developing HDCP than those whose serum VE concentrations of P40-P60 of all the participants, and this risk grew higher as serum VE concentrations in the first trimester of pregnancy increased. CONCLUSION: Women in Beijing are at good nutritional status. From January 2016 to December 2018, the incidence of HDCP increased with serum VE concentration level, and serum VE concentration of 11.2 mg/L is an indicator of an increased risk of developing HDCP, suggesting that pregnant women should take nutritional supplements containing VE carefully.

MiR-219-5p inhibits prostate cancer cell growth and metastasis by targeting HMGA2.

OBJECTIVE: To investigate the expression of micro ribonucleic acid (miR)-219-5p in prostate cancer (PCa), its influences on the biological functions of PCa, and its mechanism. PATIENTS AND METHODS: The expression differences of miR-219-5p and high mobility group protein A2 (HMGA2) in 30 pairs of PCa tissues and para-carcinoma tissues were detected via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the difference in miR-219-5p expression in PCa cell lines and normal prostatic epithelial cells was also determined via qRT-PCR. The human PC-3 cells were divided into negative control group and miR-219-5p overexpression group. Methyl thiazolyl tetrazolium (MTT) and colony formation assays were adopted to detect the cell proliferative ability, and flow cytometry was applied to determine the cell apoptosis. The expression of apoptosis-related proteins was measured via Western blotting, and the invasive and migratory abilities of the cells were examined through wound-healing and transwell assays. Bioinformatics prediction software and luciferase reporter assay were employed to verify the targets that might be controlled by miR-219-5p. Rescue experiment was conducted to clarify whether the inhibitory effects of miR-219-5p on the growth and metastasis of PC-3 cells depend on the inhibition of HMGA2. RESULTS: It was shown in qRT-PCR results that the expression level of miR-219-5p was downregulated remarkably in PCa tissues and cell lines, but overexpressed miR-219-5p could repress the proliferation and promote the apoptosis of PC-3 cells notably. The results of wound-healing and transwell assays indicated that overexpressed miR-219-5p was able to suppress the invasion and metastasis of PC-3 cells. According to Western blotting results, overexpressed miR-219-5p could up-regulate the expressions of pro-apoptotic proteins [Bax, cleaved-caspase-3 and cleaved-poly-ADP-ribose-polymerase (PARP)] and reverse the epithelial-mesenchymal transition (EMT) of PCa cells. It was predicted via the bioinformatics software that HMGA2 gene might be a target gene of miR-219-5p. The Dual-Luciferase reporter assay confirmed that there was a direct regulatory relationship between miR-219-5p and HMGA2. The rescue experiment manifested that overexpressed HMGA2 could reverse the inhibition of miR-219-5p on the growth and metastasis of PC-3 cells. CONCLUSIONS: MiR-219-5p suppresses the growth and metastasis abilities of prostate cancer cells by directly repressing the expression of HMGA2.

[Status quo and characteristic analysis among MSM-users of the "Internet Plus-based AIDS Comprehensive Prevention Service System" in Guangzhou].

Objective: To analyze the characteristics of the "Interner Plus-based AIDS Comprehensive Prevention Service System" among MSM who frequently using the Internet in Guangzhou. Methods: An online survey was conducted among MSM who were recruited through gay-website portals between August and September, 2018 in Guangzhou, to collect information regarding the use of and attitudes on the "Interner Plus-based AIDS Comprehensive Prevention Service System" . Logistic regression was used to explore the association between the use of Internet intervention tools and related behavioral characteristics. Information on the awareness of AIDS, HIV testing, and condomless anal sex behavior were compared between the core or non-core services users. Results: A total of 777 Internet-based MSM were recruited as participants including 638 men (82.1%) as core service users. MSM were satisfied in using the the "Interner Plus-based AIDS Comprehensive Prevention Service System" while more than 80.0% of the users felt that the tools were helpful in: increasing the HIV awareness, promoting test uptake, and reducing those related risk behavior. Comparing with those who did not use the tools, the users showed higher rates in practising condomless anal intercourse (1.50-1.86 times), commercial sex with men (11.60-21.21 times), and unprotected vaginal intercourse (13.62-20.67 times), in the last 6 months. Proportions of core service users appeared as: [96.6% vs. 74.8%, aOR (95%CI): 8.80 (4.85-15.97)] on HIV testing, [56.4% vs. 22.3%, aOR (95%CI): 4.54 (2.94-7.02)] on regular HIV testing and [86.2% vs. 80.6%, aOR (95%CI): 1.75 (1.06-2.89)] on awareness of HIV knowledge respectively, which were all significantly higher than the non-core service users. Conclusions: The frequent Internet using MSM in Guangzhou claimed to have had high acceptance and satisfaction on the local Internet HIV intervention service tools. The "Internet Plus-based AIDS Comprehensive Prevention Service System" had effectively reached the high-risk subgroups of MSM, increasing the awareness on related risk and promoting testing on HIV.

[Effects of bisphenol A on the expression of N-cadherin, Vimentin and FSHR in rat Sertoli cells].

Objective: To explore the effects of BPA on the expression of N-cadherin, Vimentin and FSHR in rat Sertoli cells. Methods: Primary Sertoli cells collected from prepuberty rats (18-21 d) were cultured for 48 h, and then they were treated with 0, 30, 50, 70 µmol/L BPA respectively for 24 h. The methods of MTT, real-time quantitative PCR and Western blotting were utilized to measure the cell ability of Sertoli cells, the mRNA and protein expression levels of N-cadherin, Vimentin and FSHR respectively. Results: Compared with control, the cell abilities of Sertoli cells in 50 µmol/L BPA group and 70 µmol/L BPA group increased significantly (P<0.05) . The cell abilities of Sertoli cells decreased with the increases of exposure doses of BPA. Compared with control, the expression of N-cadherin mRNA only increased in 30 µmol/L BPA group (P<0.05) , the expression of Vimentin mRNA decreased significantly in all doses group of BPA (P<0.05) , the expression of FSHR mRNA increased in all doses group of BPA (P<0.05) . Compared with the control, the protein levels of N-cadherin increased significantly in 50 µmol/L BPA group (P<0.05) , the protein levels of Vimentin decreased significantly in all doses group of BPA (P<0.05) , the protein levels of FSHR decreased significantly in 50 µmol/L BPA group and 70 µmol/L BPA group (P<0.05) . Conclusion: The mechanism of testicular toxicity from BPA might be the alterations of N-cadherin, Vimentin and FSHR by disturbing normal spermatogenesis.

[The clinical characteristics and treatment outcomes of 386 patients with hypopharyngeal cancer].

OBJECTIVE: To investigate the clinical characteristics, surgical treatment outcomes and prognostic factors of hypopharyngeal carcinoma. METHODS: A retrospective review of the Eye & ENT Hospital of Fudan University patients' database between January 2003 and June 2013 was conducted and a total of 386 patients were enrolled in the study. Patients' clinical and oncological information was collected and survival rates were analyzed using Kaplan-Meier curves. Prognostic factors were evaluated with multivariate Cox model survival analysis. RESULTS: Among the 386 patients 95.9% were males and 4.1% were females, with an average age of (58.4±9.4) years. The primary tumor sites were pyriform sinus (76.7%), posterior hypopharyngeal wall (17.3%) and postcricoid region (6.0%). There were 31(8.0%), 83(21.5%), 175(45.3%) and 97(25.1%) patients with stage T1 to T4, respectively, 99(25.6%), 74(19.2%), 181(46.9%) and 32(8.3%) patients with stage N0 to N3, respectively , and 3 patients with distant metastasis to lung on initial diagnosis. Second primary cancers were found in 28 cases (7.3%). The 5-year overall survival (OS), disease specific survival (DSS) and disease free survival (DFS) were 45.8%, 48.1% and 46.0% respectively according to Kaplan-Meier survival curves. Multivariate Cox regression model showed significant association between 5-year overall survival rate and T stage (P<0.001), N stage (P=0.003) and second primary tumors (P=0.017). Advanced T stage and lymphovascular invasion were associated with a higher rate of recurrence (P<0.001). CONCLUSIONS: Hypopharyngeal squamous cell carcinoma has a dismal prognosis, with high rates of submucosal infiltration, cervical lymph node metastasis and distant metastasis. Treatment choices should be made according to TNM stage and overall health conditions in order to achieve ideal oncologic and functional results. Surgery with postoperative chemoradiation therapy is the main treatment for advanced-stage hypopharyngeal cancer.

Diagnostic uncertainty of herpangina and hand-foot-and-mouth disease and its impact on national enterovirus syndromic monitoring.

The community burden of enterovirus is often monitored through syndromic monitoring systems based on reported cases of enterovirus-related infection (EVI) diagnoses. The extent to which this is affected by under- and over-diagnosis has not been reported. In Taiwan, children often make more than one healthcare visit during an episode of infection. We used change of diagnosis within an episode of infection as a guide of diagnostic uncertainty in a nationally representative cohort of Taiwanese children (n = 13 284) followed from birth to the 9th birthday through electronic health records. We conducted a nested case-control analysis and estimated cross-diagnosis ratios (CDRs) as the observed proportion of acute respiratory infection (ARI) diagnoses following an EVI diagnosis in excess of background ARI burdens. With 19 357 EVI diagnoses in this cohort, the CDR within 7 days was 1·51 (95% confidence interval 1·45-1·57), confirming a significant excess of ARI diagnoses within the week following an EVI diagnosis. We used age-specific CDRs to calibrate the weekly EVI burden in children aged 3-5 years in 2008, and the difference between observed and calibrated weekly EVI burdens was small. Therefore, there was evidence suggesting a small uncertainty in EVI diagnosis, but the observed EVI burdens through syndromic monitoring were not substantially affected by the small uncertainty.

Expression of high-mobility group box protein 1 in diabetic foot atherogenesis.

The role of high mobility group box 1 (HMGB1) has been demonstrated in stroke and coronary artery disease but not in peripheral arterial occlusive disease (PAOD). The pathogenesis of HMGB1 in acute and chronic vascular injury is also not well understood. We hypothesized that HMGB1 induces inflammatory markers in diabetic PAOD patients. We studied 36 diabetic patients, including 29 patients with PAOD, who had undergone amputation for diabetic foot and 7 nondiabetic patients who had undergone amputation after traumatic injury. Expression of HMGB1 and inflammatory markers were quantified using immunohistochemical staining. Mitochondrial DNA copy number was quantified using real-time polymerase chain reaction. Compared with that in the traumatic amputation group, HMGB1 expression in vessels was significantly higher in the diabetes and diabetic PAOD groups. In all subjects, arterial stenosis grade was positively correlated with the expression levels of HMGB1, 8-hydroxyguanosine, malondialdehyde, vascular cell adhesion molecule 1, and inflammatory markers CD3, and CD68 in both the intima and the media of vessels. Furthermore, HMGB1 expression level was positively correlated with 8-hydroxyguanosine, vascular cell adhesion molecule 1, nuclear factor-kB, CD3, and CD68 expression. Within the PAOD subgroup, subjects with HMGB1 expression had higher expression of the autophagy marker LC3A/B and higher mitochondrial DNA copy number. HMGB1 may be an inflammatory mediator with roles in oxidative damage and proinflammatory and inflammatory processes in diabetic atherogenesis. Moreover, it may have dual effects by compensating for increased mitochondrial DNA copy number and increased autophagy marker expression.

Social capital: a novel platform for understanding social determinants of health in systemic lupus erythematosus.

OBJECTIVE: The objective of this paper is to introduce the concept of social capital as a unique and distinct entity from the traditional psychosocial factors of social support, depressive symptoms, and self-efficacy in systemic lupus erythematosus (SLE) patients, and to evaluate how social capital varies in an SLE sample according to demographic, clinical, and psychosocial variables. METHODS: In a cross-sectional study, SLE patients completed the Adapted Social Capital Assessment Tool (A-SCAT), which measures cognitive and structural social capital. Patients also completed measures of social support, depressive symptoms, and SLE self-efficacy. Correlations were evaluated between social capital scores and demographic, clinical, and psychosocial variables. RESULTS: We recruited 89 patients (mean age: 39 ± 15 years old, 83 (93): female; mean SLEDAI: 4; mean SLICC 1). The mean A-SCAT score was 34 ± 15 (normal: 0-71); higher scores were associated with female sex, older age, higher education, Caucasian race, and non-Medicaid insurance (p ≤ 0.03 for all); associations were attributable to structural social capital. Social capital was not associated with depressive symptoms, self-efficacy, or affectionate and interaction social support, but was associated with informational and tangible social support (r = 0.39, r = 0.26, respectively, p ≤ 0.02). There were no associations between SLEDAI and SLICC and social capital, social support, and depressive symptoms. CONCLUSIONS: Social capital is a novel construct that, like other traditional psychosocial measures, addresses aspects of SLE not reflected by markers of disease activity. Social capital, however, is distinct from traditional psychosocial measures and offers a new platform on which ideas of social connectedness can broaden our understanding of health and chronic illness.

Imatinib mesylate (Gleevec™) in the treatment of diffuse cutaneous systemic sclerosis: results of a 24-month open label, extension phase, single-centre trial.

OBJECTIVES: We aimed to assess the long-term safety and tolerability of imatinib in diffuse cutaneous systemic sclerosis (dcSSc). METHODS: In this open-label, single-arm, extension-phase clinical trial, patients continued imatinib for 24 months following 12 months of initial treatment. RESULTS: Seventeen patients were enrolled. Forty of 92 adverse events (AE) and 0/6 serious (S) AEs were possibly related to medication. The MRSS decreased from a median of 21 to 16, (p=0.002). CONCLUSIONS: This study demonstrates long-term safety and tolerability of imatinib in a substantial proportion of patients with dcSSc. This is important in evaluating the relevance of this therapy in a chronic disease such as SSc.

The PGI-KLF4 pathway regulates self-renewal of glioma stem cells residing in the mesenchymal niches in human gliomas.

Gliomas display cellular hierarchies with self-renewing tumorigenic glioma stem cells (GSCs) at the apex. The GSC niches function as a regulator of GSC maintenance, however, the exact components of GSC niches that mediate this process are still far from fully defined. Here, we showed that glioma cells with aberrant mesenchymal phenotypes constitute a mesenchymal niche for GSCs. Using patient-derived specimens, we demonstrated that the paracrine PGI signaling, initiated by mesenchymal glioma cells, induces the self-renewal and tumorigenic potentials of GSCs through induction of KLF4. Treatment of intracranial orthotopic xenografts with shPGI or shKLF4 leads to less lethal potency. Our data therefore suggest that blockade of the PGI-KLF4 pathway may provide a therapeutic strategy against GSC niches.

Surveillance of avian influenza A(H7N9) virus infection in humans and detection of the first imported human case in Taiwan, 3 April to 10 May 2013.

On 3 April 2013, suspected and confirmed cases of influenza A(H7N9) virus infection became notifiable in the primary care sector in Taiwan, and detection of the virus became part of the surveillance of severe community-acquired pneumonia. On 24 April, the first imported case, reported through both surveillance systems, was confirmed in a man returning from China by sequencing from endotracheal aspirates after two negative throat swabs. Three of 139 contacts were ill and tested influenza A(H7N9)-negative.

A comparative study of flow cytometric T cell receptor Vß repertoire and T cell receptor gene rearrangement in the diagnosis of large granular lymphocytic lymphoproliferation.

INTRODUCTION: Large granular lymphocytes (LGLs) are medium- to large-sized lymphocytes with azurophilic cytoplasmic granules. Reactive vs. neoplastic LGLs are usually morphologically indistinguishable. METHODS: We investigated 25 consecutive cases of LGL lymphoproliferation using flow cytometric T cell receptor Vß (FC-Vß) repertoire and T cell receptor gene rearrangement (TCR-GR) in detecting clonality. RESULTS: Seventeen patients (68%) were T-LGL leukemia (T-LGLL) with a male predominance, a median age of 67, and a median absolute LGL count of 2.592 × 10(9) /L. All cases were clonal using the FC-Vß analysis, and all but one (94%) was clonal by TCR-GR. Eight patients (32%) had reactive LGL lymphoproliferation. Two had EBV-associated infectious mononucleosis; one was clonal by both FC-Vß and TCR-GR; and the other was clonal only by TCR-GR. The remaining six cases were polyclonal by both assays. Patients with reactive LGL lymphoproliferation were more frequently associated with an underlying/concurrent malignancy than those with T-LGLL (4/8 cases vs. 1/17; P = 0.023, Fisher's exact test). We compared the demographic, hemogram, and clonality data between these two groups and found that the only significant difference was the lower median platelet count in the LGL lymphocytosis group (201 × 10(9) /L vs. 223 × 10(9) /L; P = 0.031; Student's t-test). A literature review including the current study showed a high sensitivity of FC-Vß analysis for T-LGLL (97.2%; 107/110 cases). CONCLUSIONS: FC-Vß analysis was slightly more sensitive than TCR-GR for the detection of clonal T cell lymphoproliferation. However, we must interpret the laboratory findings with clinical context as clonal T cell lymphoproliferation may occur in patients with viral infection.

Role of mitochondrial DNA variants and copy number in diabetic atherogenesis.

Hyperglycemia-induced reactive oxygen species production can cause diabetes and its complications, including atherosclerosis. The role of mitochondrial DNA variants and mitochondrial copy number in the pathogenesis of diabetic atherogenesis is not well understood. We examined 36 diabetic patients who had undergone amputation for diabetic foot and seven non-diabetic patients who had undergone amputation after traumatic injury. Mitochondrial DNA was extracted and used for sequencing. Single nucleotide polymorphisms (SNPs) relative to the Cambridge reference sequence were analyzed. Mitochondrial DNA copy number was quantified by real-time PCR. Twenty-one novel variants were detected in 29 diabetic patients with arterial stenosis; six of the variants were heteroplasmic, and most occurred in highly evolutionarily conserved residues. These variants were more prevalent in patients with arterial stenosis than in those without stenosis. The novel variants included four in complex I (ND1: C3477A/C, A3523A/G; ND5: C13028A/C, C13060A/C), one in complex IV (COX1: T6090A/T), and one in rRNA (12srRNA: G857G/T). Compared with non-diabetic patients, the diabetic patients had significantly less mitochondrial DNA. Furthermore, among diabetic patients with arterial stenosis, there was a significant positive correlation between mitochondrial DNA copy number and the number of total SNPs. In conclusion, we identified six novel heteroplasmic mitochondrial DNA variants among diabetic patients with arterial stenosis, and we found that diabetic atherogenesis is associated with decreased amounts of mitochondrial DNA.

Right- and left-subclavian vein port-a-cath systems: comparison of complications.

BACKGROUND: Central venous access systems are frequently used for delivery of medications; however, few studies have compared surgical and postoperative complications of right versus left access via the subclavian vein (SCV). The aim of this study was to compare the surgical and postoperative complications associated with Port-A-Cath system insertion via the right and left SCV. METHODS: The medical records of patients who received Port-A-Cath insertion via the SCV for parenteral chemotherapy between August 2004 and July 2008 were reviewed. The incidence of surgical and postoperative complications was compared between patients who received right- versus left-SCV Port-A-Cath insertion. RESULTS: A total of 1,848 patients were included in the study. Right-SCV catheterization was attempted in 1,029 (55.7%) patients and was successful in 866 (84.2%). Left-SCV catheterization was attempted in 819 (44.3%) patients and was successful in 651 (79.5%). The mean length of postoperative follow-up was 417.3 ± 401.3 and 396.7 ± 379.9 days for the right- and left-SCV groups, respectively. The incidence of SCV puncture failure was significantly lower in the right-SCV group (12.3%) compared with the left-SCV group (16.8%, p = 0.006). The incidence of catheter knotting at the ipsilateral brachiocephalic vein was also significantly lower in the right-SCV group (0.0%) compared with the left-SCV group (0.5%, p = 0.038), as was the incidence of catheter occlusion (1.0% for right SCV vs. 3.5% for left SCV, p = 0.001). CONCLUSION: These findings suggest that the right-SCV approach is superior to the left-SCV approach for Port-A-Cath insertion.