The impact of different doses of antithymocyte globulin conditioning on immune reconstitution upon hematopoietic stem cell transplantation

IntroductionAnti-thymocyte globulin (ATG) is used prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for graft-versus-host disease (GVHD) prophylaxis. Two different ATG doses (7.5 or 10 mg/kg) were evaluated in comparison with a group without ATG therapy.MethodsWe retrospectively analyzed 132 patients who were transplanted with HSCT without ATG (non-ATG), or who received 7.5 mg/kg ATG (ATG-7.5) or 10 mg/kg ATG (ATG-10) prior to transplantation. The immune cells (CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, CD19⁺ B cells and CD16⁺CD56⁺ NK cells) were examined in peripheral blood every three months post-HSCT for 12 months.ResultsCompared with non-ATG group, combined ATG-7.5/ATG-10 groups had significantly lower CD3⁺CD4⁺ T cells and higher CD3⁺CD8⁺ T cells at 3, 6, 9, 12 months post-HSCT; thus, displaying a lower CD4/CD8 ratio in the ATG groups compared to non-ATG group. The ratio of CD19⁺ B cells was statistically lower (at 3rd month, p = .014; at 6th month, p = .025) in combined ATG-7.5/ATG-10 groups at 3 and 6 months post-HSCT, but not at 9 and 12 months after HSCT. The ratios of CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, CD19⁺ B cells and CD16⁺CD56⁺ NK cells were similar between the ATG-7.5 and ATG-10 groups at all examined time points. The overall survival (OS), progression-free survival (PFS), relapse and acute GVHD (aGVHD) were comparable among recipients without ATG therapy and with ATG-7.5 or/and ATG-10 therapies. Multivariate analysis revealed that immune cells ratios were not independent factors affecting prognosis.ConclusionThe ATG therapy at higher and lower doses led to a delayed reconstitution of T cells and the inversion of CD4/CD8 ratio for at least one year after HSCT.     

Ferulic acid enhances insulin secretion by potentiating L-type Ca2+ channel activation

ObjectiveTo investigate the effect of ferulic acid, a natural compound, on pancreatic beta cell viability, Ca²⁺ channels, and insulin secretion.MethodsWe studied the effects of ferulic acid on rat insulinoma cell line viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay. The whole-cell patch-clamp technique and enzyme-linked immunosorbent assay were also used to examine the action of ferulic acid on Ca²⁺ channels and insulin secretion, respectively.ResultsFerulic acid did not affect cell viability during exposures up to 72 h. The electrophysiological study demonstrated that ferulic acid rapidly and concentration-dependently increased L-type Ca²⁺ channel current, shifting its activation curve in the hyperpolarizing direction with a decreased slope factor, while the voltage dependence of inactivation was not affected. On the other hand, ferulic acid have no effect on T-type Ca²⁺ channels. Furthermore, ferulic acid significantly increased insulin secretion, an effect inhibited by nifedipine and Ca²⁺-free extracellular fluid, confirming that ferulic acid-induced insulin secretion in these cells was mediated by augmenting Ca²⁺ influx through L-type Ca²⁺ channel. Our data also suggest that this may be a direct, nongenomic action.ConclusionThis is the first electrophysiological demonstration that acute ferulic acid treatment could increase L-type Ca²⁺ channel current in pancreatic β cells by enhancing its voltage dependence of activation, leading to insulin secretion.     

Toxicity assessment of environmental pollutant phenanthrene in clam Venerupis philippinarum using oxidative stress biomarkers

The objective of this study was to assess potential toxic effects of phenanthrene (PHE) on tissues of clam Venerupis philippinarum using parameters of antioxidant defenses and oxidative stress. Antioxidant biomarkers including ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), superoxide dismutase (SOD), and glutathione (GSH), as well as DNA damage and lipid peroxidation (LPO) in gills and digestive glands of V. philippinarum, were analyzed after a 1-, 3-, 6-, 10- and 15-day exposure to seawater containing PHE at concentrations of 2, 10, 50 μg/L. The results showed that the activity of most antioxidant enzymes was induced throughout the exposure period, and different trends were detected with time of exposure. The oxidative stress could be obviously caused in the gills and digestive glands under the experimental conditions. Overall, our results show that digestive glands are more sensitive to marine environmental stressors than gills, and GSH is proposed as potential useful biomarker as it showed good correlation with the target contaminant. This could provide useful information for toxic risk assessment of environmental pollutant PHE.     

Inequalities in enrollment of women and racial minorities in trials testing uric acid lowering drugs

AimsWe investigated sex and racial inequalities in clinical trials testing serum uric acid (SUA) lowering drugs and analyzed the temporal trends of participation among the pre-specified demographic groups.Data were collected from publications of clinical trials testing SUA-lowering drugs. Linear regression analysis was performed to assess the relation between drug approval year and proportion of women and minorities enrolled in clinical studies.Data synthesisThe mean percentage enrollment of women in clinical trials significantly decreased over the time (r = −0.43, P-value = 0.02). Moreover, there was a statistically significant difference in mean percentage enrollment of women among trials testing different SUA-lowering drugs, with the highest representation in rasburicase (71.1%) and the lowest representation of women in dotinurad (0.8%). Over the time, also the mean percentage enrollment of racial minorities decreased, passing from 8.7% to 2.2% in a 10-year period.Women were proportionally underrepresented compared with their share of the population with asymptomatic hyperuricemia, overall (participation-to-prevalence ratio (PPR) = 0.34), in trials testing xanthine oxiase inhibitors (PPR = 0.38) and uricosurics (PPR = 0.29), and in trials with febuxostat, allopurinol, pegloticase, halofenate/arhalofenate, verinurad, lesinurad and dotinurad. Women were proportionally underreppresented also compared with their share of the population with gout, overall (PPR = 0.69) and in trials testing XOIs (PPR = 0.69), uricosurics (PPR = 0.68), and all SUA-lowering drugs excepted for rasburicase, pegloticase and topiroxostat.ConclusionsOur analysis shows that women and racial and ethnical minorities are underrepresented in controlled clinical trials testing SUA-lowering drugs, with similar pattern across drug classes.     

RvD1 treatment during primary infection modulates memory response increasing viral load during respiratory viral reinfection

Resolvin D1 (RvD1), which is biosynthesized from essential long-chain fatty acids, is involved in anti-inflammatory activity and modulation of T cell response. Memory CD8+ T cells are important for controlling tumor growth and viral infections. Exacerbated inflammation has been described as impairing memory CD8+ T cell differentiation. This study aimed to verify the effects of RvD1 on memory CD8+ T cells in vitro and in vivo in a respiratory virus infection model. Peripheral blood mononuclear cells were treated at different time points with RvD1 and stimulated with anti-CD3/anti-CD28 antibodies. Pre-treatment with RvD1 increases the expansion of memory CD8+ T cells. The IL-12 level, a cytokine described to control memory CD8+ T cells, was reduced with RvD1 pre-treatment. When the mTOR axis was inhibited, the IL-12 levels were restored. In a respiratory virus infection model, Balb/c mice were treated with RvD1 before infection or after 7 days after infection. RvD1 treatment after infection increased the frequency of memory CD8+ T cells in the lung expressing II4, II10, and Ifng. During reinfection, RvD1-treated and RSV-infected mice present a high viral load in the lung and lower antibody response in the serum. Our results show that RvD1 modulates the expansion and phenotype of memory CD8+ T cells but contributed to a non-protective response after RSV reinfection.     

针刺结合风市穴刺络拔罐治疗足少阳经型坐骨神经痛30例

目的:探讨针刺结合风市穴刺络拔罐治疗足少阳经型坐骨神经痛的临床疗效。方法:将60例足少阳经型坐骨神经痛患者随机分两组,每组30例。刺络拔罐组运用针刺结合风市穴刺络拔罐治疗,针刺穴取患者双侧腰夹脊、肾俞、大肠俞及患侧环跳、委中、昆仑、承山;常规针刺组单纯运用针刺治疗,取穴同刺络拔罐组。两组均每日治疗1次,10次为1个疗程,刺络拔罐组风市穴刺络拔罐每周1次,治疗3个疗程后通过疼痛视觉模拟评分(VAS)、日本骨科学会下腰痛(JOA)评分评定疗效。结果:刺络拔罐组总有效率为96.7%(29/30),优于常规针刺组的90%(27/30,P<0.05);两组治疗后疼痛VAS评分、JOA评分较治疗前均有明显改善(P<0.01)。结论:针刺结合风市穴刺络拔罐治疗足少阳经型坐骨神经痛的临床疗效较好,且操作简便,无不良反应,安全性高。     

Methods for development of a core outcome set for clinical trials integrating traditional Chinese medicine and Western medicine

Clinical trial outcome reporting differs between studies integrating traditional Chinese medicine (TCM) and Western medicine, so that some clinical trials are not eligible for inclusion in a systematic review. The excluded studies are therefore less widely disseminated, and even valid studies are less likely to yield impact. This problem may be addressed by developing core outcome sets (COSs) for integrative medicine in specific healthcare areas. The first stage of development is to define the scope of the COS for integrative medicine, the second stage is to establish the need for such a COS, and the third stage is to develop a protocol and register the COS. The final stage involves three steps: (i) development of a comprehensive list of outcomes (including efficacy outcomes and safety outcomes and TCM syndromes) using systematic review, qualitative or cross-sectional research, and reviews of package inserts and medical records; (ii) merging and grouping of outcomes within domains; (iii) conducting two rounds of Delphi survey and consensus meetings with a range of stakeholders. The final COS will include a general COS and core TCM syndrome- set. Development of COSs for clinical trials of integrative medicine may help to standardize outcome reporting and reduce publication bias in the future.