Differential CD26-mediated activation of the CD3 and CD2 pathways after CD6-depleted allogeneic bone marrow transplantation

Patients who have undergone allogeneic bone marrow transplantation (allo-BMT) are susceptible to a variety of opportunistic infectious complications in the months to years after engraftment. Impaired in vitro T-cell functions have been documented in these patients, and these T-cell dysfunctions contribute to the prolonged immune deficiency after allo-BMT. In the present study, we examined the expression of CD26 as well as the reconstitution of CD26-mediated T-cell costimulation via the CD3 and CD2 pathways at various times in patients aged greater than 18 years after CD6-positive, T-cell depleted allo- BMT. We found that the percentage of CD26- and CD3-positive cells, as well as the levels of expression of both antigens, was lower than in normal controls during the first 4 months after CD6-depleted allo-BMT. Subsequently, the amount of lymphocytes expressing CD3 and CD26 and the quantitative surface expression of CD3 and CD26 were not significantly different in patients and normal controls. Functional studies showed that CD26-mediated T-cell proliferation via the CD3 pathway was considerably improved and almost reached normal levels by 1 year, whereas recovery of CD26-mediated T-cell proliferation via the CD2 pathway was delayed for at least 2 years after CD6-depleted allo-BMT. As CD26 involvement in the regulation of human thymocyte activation is restricted preferentially to the CD3 pathway--unlike its involvement with both CD3 and CD2 pathways of peripheral T cells--our results suggest that the different effects of CD26-mediated costimulation via the CD3 and CD2 pathways after CD6-depleted allo-BMT may be a reflection of peripheral T-cell immaturity in those individuals, similar to that seen in mature medullary thymocytes or cord T lymphocytes.     

Fc gamma receptor II (CD32) on malignant B cells influences modulation induced by anti-CD19 monoclonal antibody

Antigenic modulation is one of many factors determining the effectiveness of monoclonal antibody (MoAb)-mediated therapy. To select the isotype of a CD19 MoAb most suitable for radioimmunotherapy of patients with B-cell malignancies, we studied the influence of MoAb isotype on modulation, after binding of the MoAb to different cell-line cells. The CD19-IgG1 MoAb was found to induce modulation of CD19 antigens on Daudi cell line cells more rapidly than did its IgG2a switch variant. We provide evidence that this difference in modulation rate is caused by the expression of Fc gamma receptor II (Fc gamma RII) on these cells. Experiments aimed at elucidating the mechanism of Fc gamma RII involvement in modulation induction by CD19-IgG1 showed that Fc gamma RII did not comodulate with CD19 MoAbs. However, cocrosslinking of CD19 and Fc gamma RII with CD19-IgG1 MoAb resulted in enhanced calcium mobilization in Daudi cells. This increased signal induction accompanies the enhanced capping and subsequent modulation of CD19 antigens. Because Fc gamma RII is expressed in varying densities on malignant B cells in all differentiation stages, our results have implications for the MoAb isotype most suitable for use in MoAb-based therapy of patients with B-cell malignancies.     

Inguinal hernia repair: Toward Asian guidelines

Groin hernias are very common, and surgical treatment is usually recommended. In fact, hernia repair is the most common surgical procedure performed worldwide. In countries such as the USA, China, and India, there may easily be over 1 million repairs every year. The need for this surgery has become an important socioeconomic problem and may affect health‐care providers, especially in aging societies. Surgical repair using mesh is recommended and widely employed in Western countries, but in many developing countries, tissue‐to‐tissue repair is still the preferred surgical procedure due to economic constraints. For these reason, the development and implementation of guidelines, consensus, or recommendations may aim to clarify issues related to best practices in inguinal hernia repair in Asia. A group of Asian experts in hernia repair gathered together to debate inguinal hernia treatments in Asia in an attempt to reach some consensus or develop recommendations on best practices in the region. The need for recommendations or guidelines was unanimously confirmed to help overcome the discrepancy in clinical practice between countries; the experts decided to focus mainly on the technical aspects of open repair, which is the most common surgery for hernia in our region. After the identification of 12 main topics for discussion (indication, age, and sex; symptomatic and asymptomatic hernia: type of hernia; type of treatment; hospital admission; preoperative care; anesthesia; surgical technique; perioperative care; postoperative care; early complications; and long‐term complications), a search of the literature was carried out according to the five levels of the Oxford Classification of Evidence and the four grades of recommendation.     

超声与X线引导穿刺行经皮肾镜取石术临床对比的Meta分析

目的：通过系统评价的方法比较在超声和X线引导穿刺行经皮肾镜治疗肾结石的临床效果。方法计算机检索PubMed、EMbase、Cochrane、CNKI等数据库,收集关于超声和X线分别引导下行经皮肾镜取石术治疗肾结石的临床对照试验。评价指标包括结石清除率、并发症率、穿刺时间、出血量和术后住院时间。所有的数据采用RevMan 5.0软件进行Meta分析。结果该研究共纳入9个研究,包括1693位患者。 Meta分析的结果显示超声与X线引导穿刺下患者的结石清除率无明显差别[OR=1.11,95%CI(0.83,1.49),P=0.47];而在并发症发生率[OR=0.43,95%CI(0.27,0.69),P=0.00]、穿刺时间[WMD=-4.54,95%CI (-0.45,-8.62),P=0.03]、出血量[WMD=-22.77,95%CI(-36.57,-8.97),P=0.00]和术后住院时间[WMD=-0.16,95%CI(-0.28,-0.03),P=0.02]方面比较,超声引导下建立通道的效果要优于X线。结论超声和X线引导下经皮肾镜治疗肾结石的结石清除率效果相当,但超声引导下所用穿刺时间少且术后并发症低。     

阿尔茨海默症患者主要照顾者悲伤与照顾负担的相关性研究

[目的]探索阿尔茨海默症患者主要照顾者悲伤与照顾负担的相关性。[方法]采用Marwit-Meuser照顾者悲伤量表(MM-CGI)和照顾负担量表(CBI),选择2018年3月至2019年3月在开封市某三级甲等医院就诊的80名阿尔茨海默症患者,对其主要照顾者的悲伤和照顾负担情况进行调查。[结果]阿尔茨海默症照顾者悲伤总分为(56.46±7.92)分,照顾负担总分为(61.99±12.92)分,两者均处于中等偏高水平。阿尔茨海默症患者主要照顾者悲伤程度与照顾负担呈正相关。[结论]医护人员应探索积极、有效的干预措施应对阿尔茨海默症患者主要照顾者的悲伤情绪及其照顾负担。     

Hypoxia-induced factor-1 alpha upregulates vascular endothelial growth factor C to promote lymphangiogenesis and angiogenesis in breast cancer patients

Hypoxia-induced factor-1 alpha （HIF-1α） affects many effector molecules and regulates tumor lymphangio- genesis and angiogenesis during hypoxia. The aim of this study was to investigate the role of HIF-1α in the regu- lation of vascular endothelial growth factor C （VEGF-C） expression and its effect on lymphangiogenesis and an- giogenesis in breast cancer. Lymphatic vessel density （LVD）, microvessel density （MVD） and the expressions of HIF-1α and VEGF-C proteins were evaluated by immunohistochemistry in 75 breast cancer samples. There was a significant correlation between HIF-1α and VEGF-C （P = 0.014, r = 0.273, Spearman＇s coefficient of correlation）. HIF-1α and VEGF-C overexpression was significantly correlated with higher LVD （P = 0.003 and P = 0.017, re- spectively）, regional lymph nodal involvement （P = 0.002 and P = 0.004, respectively） and advanced tumor, node, metastasis （TNM） classification （P = 0.001 and P = 0.01, respectively）. Higher MVD was observed in the group expressing higher levels of HIF-1α and VEGF-C （P = 0.033 and P = 0.037, respectively）. Univariate analysis showed shorter survival time in patients expressing higher levels of HIF-1α and VEGF-C. HIF-1α was also found to be an independent prognostic factor of overall survival in multivariate analysis. The results suggest that HIF-1α may affect VEGF-C expression, thus acting as a crucial regulator of lymphangiogenesis and angiogenesis in breast cancer. This study highlights promising potential of HIF- 1α as a therapeutic target against tumor lymph node me- tastasis.     

牙周膜干细胞的研究进展

牙周病是一种由菌斑微生物引起的慢性感染性疾病,可引起牙周支持组织的破坏和丧失,最终导致牙齿松动脱落。牙周病治疗的最终目标是修复和重建受损的牙周支持组织。从牙周膜中分离获取的间充质干细胞具有成体干细胞的特性及多重分化潜能,可以分化为骨组织和牙周支持组织等多种类型的组织,这对牙周组织修复再生和牙周组织工程具有重大意义,因而备受关注。本文就牙周膜干细胞、牙周膜干细胞的生物学特性、牙周膜干细胞的影响因素及其调控机制等研究进展作一综述。