BTLA-expressing CD11c antigen presenting cells in patients with active tuberculosis exhibit low capacity to stimulate T cell proliferation.

Despite past extensive studies on B and T lymphocyte attenuator (BTLA)-mediated negative regulation of T cell activation, the role of BTLA in antigen presenting cells (APCs) in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here, we demonstrate that BTLA expression on CD11c APCs increased in patients with ATB. Particularly, BTLA expression in CD11c APCs was likely associated with the attenuated stimulatory capacity on T cells (especially CD8+ T cell) proliferation. BTLA-expressing CD11c APCs showed lower antigen uptake capacity, lower CD86 expression, higher HLA-DR expression, and enhanced IL-6 secretion, compared to counterpart BTLA negative CD11c APCs in healthy controls (HC). Interestingly, BTLA-expressing CD11c APCs from ATB patients displayed lower expression of HLA-DR and less IL-6 secretion, but higher expression of CD86 than those from HC volunteers. Mixed lymphocyte reaction suggests that BTLA expression is likely associated with positive rather than conventional negative regulation of CD11c APCs stimulatory capacity. This role is impaired in ATB patients manifested by low expression of HLA-DR and low production of IL-6. This previous unappreciated role for BTLA may have implications in the prevention and treatment of patients with ATB.

IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin.

Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP) dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents.

[Treatment of chronic heart failure of Xin-Shen yang deficiency, interior retention of water-fluid syndrome by external application of Zhuangshenling recipe combined with western medicine: a clinical study].

OBJECTIVE: To observe the effect of external application of Zhuangshenling Recipe (ZR) combined with Western medicine (WM) on the heart function of chronic heart failure (CHF) patients of Xin-Shen yang deficiency, interior retention of water-fluid syndrome (XSYDIRWFS). METHODS: Totally 140 CHF patients of XSYDIRWFS were randomly assigned to two groups, the treatment group and the control group, 70 in each group. All patients received WM therapy. Those in the treatment group were applied with ZR at Xinshu (BL15) and Shenshu (BL23), while those in the control group were applied with placebos at Xinshu (BL15) and Shenshu (BL23). The therapeutic course for all was 12 weeks. The integrals of TCM syndrome, grading of cardiac function, brain natriuretic polypeptide (BNP), and 6 min walking distance were observed before and after treatment. RESULTS: After twelve weeks of treatment, the effective rate of improved grading of cardiac function, the total effective rate of TCM syndrome efficacy, and the BNP level were obviously better in the treatment group (P < 0.05). There was no statistical difference in 6 min walking distance between the two groups (P > 0.05). CONCLUSION: External application of ZR combined with WM could improve the heart function of CHF patients of XSYDIRWFS.

Design of broadband polarization splitter based on partial coupling in square-lattice photonic-crystal fiber.

We propose a design for a novel broadband polarization splitter based on an asymmetric dual-core square-lattice photonic-crystal fiber. The fiber is designed such that index-matched coupling between the two cores can be achieved for one polarization state, while only a part of the energy could be coupled for the other polarization state. Numerical results demonstrate that a device length of 5.9 mm shows extinction ratios as low as -20 dB with bandwidths as great as 101 nm.

Profiling dendritic cell subsets in the patients with active pulmonary tuberculosis.

Dendritic cell (DC) plays an important role in the immune response against pulmonary tuberculosis. However, the phenotypic profile of DC subsets in peripheral blood in individuals with active pulmonary tuberculosis (APT) is still inconclusive. Here, we demonstrated that the absolute numbers of total DC (tDC), myeloid DC (mDC) and plasmacytoid DC (pDC) in individuals with APT were decreased compared to healthy controls (HCs). The decreased number of DCs, especially of pDC, seems to be a useful diagnostic marker of APT. Meanwhile, the number of DCs was associated with the prolonged/complicated TB, ATD treatment effect and lymphocyte immune reactions, as manifested that relapsed APT patients with a higher number of tDC and lower number of pDC compared to newly diagnosed patients. Interestingly, mDC from APT patients displayed high expressions of CD83 and CCR7, but pDC displayed low expressions of CD83 and CCR7. Moreover, DCs from APT patients expressed lower levels of HLA-DR and CD80, but expressed a higher level of CD86 than those from HCs. However, the antigen uptake capacity of DC subsets was not different between APT and HCs, despite the antigen uptake capacity of pDC was much lower than that of mDC in both APT patients and HCs. Our data represent a systematic profile of DC subsets in the blood of APT patients, and would represent a useful biomarker for APT.

Development and characterization of monoclonal antibody against human IL-37b.

IL-37 has been described as a natural inhibitor of immune responses. Monoclonal antibody (mAb) against human IL-37b with high affinity and specificity can serve as a molecular probe to detect IL-37 and study IL-37 functions, mechanisms and related signal pathways in inflammatory diseases. However, there are very few such mAbs against human IL-37 commercially available so far. In the current study, monoclonal antibodies against human IL-37b were developed by fusing splenocytes from immunized mouse with SP2/0 myeloma cells and polyethylene glycol. Then the antibodies were screened with prokaryotic expressed human IL-37b protein and eukaryotic expressed human IL-37b protein subsequently. Western blot and flow cytometry analysis revealed that selected mAb clons were able to recognize human IL-37 with high specificity. And more importantly, the IL-37b mAbs were fluorescently labeled and can be directly used in flow cytometry and immunohistochemistry. In conclusion, the current study developed new mAbs against human IL-37b, which are applicable in flow cytometry and immunohistochemistry.

Icariin Inhibits Pulmonary Hypertension Induced by Monocrotaline through Enhancement of NO/cGMP Signaling Pathway in Rats.

It has been reported that icariin (ICA) increased contents of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) by improving expression of endothelial nitric oxide synthase (eNOS) and inhibition of phosphodiesterase type 5 (PDE5). In addition, dysfunction of the NO/cGMP pathway may play a crucial role in the pathogenesis of pulmonary hypertension (PH). In this study, the potential protective effects of ICA on PH induced by monocrotaline (MCT, 50 mg/kg) singly subcutaneous injection were investigated and the possible mechanisms involved in NO/cGMP pathway were explored in male Sprague Dawley rats. The results showed that ICA (20, 40, and 80 mg/kg/d) treatment by intragastric administration could significantly ameliorate PH and upregulate the expression of eNOS gene and downregulate the expression of PDE5 gene in MCT-treated rats. Both ICA (40 mg/kg/d) and L-arginine (200 mg/kg/d), a precursor of NO as positive control, notably increased the contents of NO and cGMP in lung tissue homogenate, which were inversed by treatment with (N) G-nitro-L-arginine-methyl ester (L-NAME), a NOS inhibitor, and L-NAME-treatment could also inhibit the protective effects of ICA (40 mg/kg/d) on mean pulmonary artery pressure and artery remodeling and tends to inhibit right ventricle hypertrophy index. In summary, ICA is effective in protecting against MCT-induced PH in rats through enhancement of NO/cGMP signaling pathway in rats.

Elevated serum IL-35 and increased expression of IL-35-p35 or -EBI3 in CD4(+)CD25(+) T cells in patients with active tuberculosis.

Despite the recent appreciation of interleukin 35 (IL-35) function in inflammatory diseases, little is known for IL-35 response in patients with active tuberculosis (ATB). In the current study, we demonstrated that ATB patients exhibited increases in serum IL-35 and in mRNA expression of both subunits of IL-35 (p35 and EBI3) in white blood cells and peripheral blood mononuclear cells. Consistently, anti-TB drug treatment led to reduction in serum IL-35 level and p35 or EBI3 expression. TB infection was associated with expression of p35 or EBI3 protein in CD4(+) but not CD8(+) T cells. Most p35(+)CD4(+) T cells and EBI3(+)CD4(+) T cells expressed Treg-associated marker CD25. Our findings may be important in understanding immune pathogenesis of TB. IL-35 in the blood may potentially serve as a biomarker for immune status and prognosis in TB.

Tuberculosis-sensitized monocytes sustain immune response of interleukin-37.

Roles of human IL-37 in infections remain poorly characterized. Although plasma IL-37 is elevated in patients with tuberculosis (TB), IL-37 source and immune correlate in TB have not been investigated. It is also unknown whether and how TB can influence the ability of immune cells to mount innate responses of IL-37 and pre-inflammatory cytokines. Here, we demonstrated that IL-37b-producing monocytes coincided with a source of elevated plasma IL-37b in TB patients. While IL-37b production in TB was associated with prolonged/complicated TB, TB burdens and inflammatory reactions, it negatively correlated with immune responses of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α or IL-10. Interestingly, mycobacterial re-infection of monocytes from TB patients, but not healthy BCG-vaccinated controls, enhanced or sustained IL-37b production by cultured monocytes. TB-sensitized monocytes from TB patients mounted more robust immune responses of IL-37b than those of pre-inflammatory cytokines during mycobacterial re-infection in culture. Our data represent new findings in terms of IL-37b responses, immune correlates and potential mechanisms in TB patients.

BTLA associates with increased Foxp3 expression in CD4(+) T cells in dextran sulfate sodium-induced colitis.

Ulcerative colitis (UC) is an inflammatory bowel disease, and its pathogenesis involves a variety of genetic, environmental, and immunological factors such as T helper cells and their secreted cytokines. B and T lymphocyte attenuator (BTLA) is an immunoregulatory receptor that has a strong suppressive effect on T-cell function. However the role of BTLA in UC remains poorly understood. Here we demonstrated that the frequency of BTLA-expressing CD3(+) T cells, especially CD4(+) T cells, increased in blood and mucosa in mice with DSS-induced colitis. The frequency of Foxp3-expressing cells in BTLA+ CD4(+) T cell from lamina propria mononuclear cells (LPMCs) was much higher in DSS-treated mice than that in controls. Similarly, the proportion of IL-17+ cells in BTLA+ CD4(+) T cells from LPMCs in DSS-treated mice is much higher than that in controls, while no perceptible difference for the proportion of IFN-γ+ cells in BTLA+ CD4(+) T cells was noted between DSS-treated mice and controls. Treatment of mesalazine, an anti-ulcerative colitis drug, down-regulated Foxp3 and IL-17 expression in BTLA positive T cells along with attenuated severity for colitis. Our findings indicate that BTLA may be involved in the control of inflammatory responses through increasing Foxp3 expression, rather than attenuating IL-17 production, in DSS-induced colitis.

[Cited status and its correlated factors of articles published in Chinese Journal of Pediatrics from 2001 to 2010].

OBJECTIVE: The present study was designed to explore the cited status and its correlated factors of articles published in Chinese Journal of Pediatrics. METHOD: Articles published in Chinese Journal of Pediatrics from 2001 to 2010 were searched using Wanfang Medical Online database, and the relationship between cited number and column and funding status were analyzed. RESULTS: Totally 3209 articles were published by Chinese Journal of Pediatrics from 2001 to 2010. Two thousand and seventy-three articles (64.60%) were cited. The total cited number was 18 546 (mean rate: 5.78 per paper). Standard/protocol/guideline was the most often cited column (mean rate: 62.92 per paper). Featured articles including editorials (mean rate: 7.12 per paper), special articles (mean rate: 6.50 per paper) and original articles (mean rate: 7.90 per paper) had higher cited rate. Cited rate of original papers in featured articles was higher than other original articles (mean rate: 6.03 per paper). Those with academic perspectives, such as Opinion/Debate/Discussion, were well cited (mean rate: 7.09 per paper). All of original articles in Rapid Pathway were well cited (mean rate: 16.20 per paper). Mean cited number of grant-supported articles was 4.81 per paper, lower than that of all kinds of papers (mean rate: 5.78 per paper) and non-grant-supported articles (mean rate: 6.06 per paper). However, it was slightly higher than that of articles except Standard/protocol/guideline (mean rate: 4.36 per paper). CONCLUSION: Cited status varies among columns. The invited papers should be increased in number to raise commentary papers and original articles with high quality.Grant-supported or non-grant-supported papers should be reviewed based on the same standard after submission.

[Influence of journals indexed by Science Citation Index (SCI) on Chinese medical journals based on the data of published articles by Chinese authors from 2000 - 2009].

OBJECTIVE: This study was designed to investigate the influence of journals indexed by Science Citation Index (SCI) on Chinese medical journals. METHOD: Articles on medicine written by Chinese and the journals that published these articles from 2000 to 2009 were searched using Science Citation Index Expanded (SCI-E) database, and the status and variation tendency of the impact factors (IF) of these journals were analyzed. Data of articles on medicine included Chinese Scientific and Technical Paper and Citations Data (CSTPCD) from 2000 to 2008 were searched (the data of 2009 have not been released). The included articles and the time-dependent changing profile were studied. These outcomes were evaluated as the fixed base relative or link relative when compared with the data of 2000 or those of last year, respectively. Geometric mean was used when mean increase was calculated and IF distribution was described with median. RESULT: Totally 3774 articles from China were published by journals indexed by SCI-E in 2000, and the number of articles published by Chinese authors increased every year. In 2008, 16 714 articles were indexed by SCI-E, 442.87% higher than those of 2000. The increment was 161.54% higher than that of articles published in the journals indexed by CSTPCD (281.33%) during the same period. From 2000 to 2009, the geometric mean of increase in the number of published articles from China in journals indexed by SCI-E was 20.87% but it was 18.21% in CSTPCD. From 2000 to 2009, the median of IF of SCI-E indexed journals that published Chinese medical articles was 1.866, 2.073, 2.390, 2.702, 2.409, 2.496, 2.380, 2.218, 2.280 and 2.331, respectively, and they did not increase or even decreased. CONCLUSION: The number of the articles indexed by SCI-E increased year by year, much faster than that of CSTPCD. However, it does not necessarily mean the increase in impact.

Retrospective analysis of thrombolysis therapy for 64 cases of acute myocardial infarction with elevated ST segment.

OBJECTIVE: To explore the cardiac protective effect of integrative therapy in acute myocardial infarction (AMI) with elevated ST segment after reperfusion. METHODS: Sixty-four AMI patients who having received decimalization by thrombolysis were assigned to two groups by retrospective analysis, 36 patients in the treated group and 28 in the control group. Both were treated by intravenous administering of urokinase for thrombolysis, and to the treated group, intravenous dripping of Xueshuantong Injection (, XST) was added. Serum levels of myocardial associated enzymes were monitored before treatment and at various time points after thrombolysis, and the heart function parameters were detected with color echocardiography before treatment and on the 7th and 14th day of treatment. The patients were followed up for 6 months to observe the incidence of cardiac events. RESULTS: The differences between groups at the peak and peak appearing time of creatine kinase and creatine kinase isoenzyme were not significant. All the heart function parameters on the 7th and 14th day in the treated group were improved and superior to those at the corresponding time points in the control group (P<0.05, P<0.01). Incidence of some heart events in the treated group within the 6-month follow-up period was lesser than that in the control group (P<0.05). CONCLUSION: XST Injection could provide effective protection for the heart after reperfusion.