Attenuation of allograft rejection by intragraft inhibition of class II transcativator in high responder rat liver transplantation

Major histocompatibility complex‐II (MHC‐II) plays an important role in graft rejection and class II transactivator (CIITA) is the key regulator for MHC‐II expression. The aim of this study was to determine the efficacy of intragraft inhibition of CIITA in attenuating liver transplant rejection. Three plasmids containing small hairpin RNA (shRNA) against rat CIITA (pCIITA‐shRNA) and one control plasmid of pHK‐shRNA were constructed. In vitro dendritic cell (DC) transfection and liver transfection via portal vein in donor rats (n = 8) by shRNA plasmids were performed to confirm the inhibitory effect of pCIITA‐shRNA on CIITA expression. It showed that expressions of CIITA and MHC‐II were significantly inhibited by pCIITA‐shRNA in both DC in vitro and liver of donor rats in vivo (p < 0.05 vs. control pHK‐shRNA treatment). pCIITA1‐shRNA was proved to be the best inhibitor among three pCIITA‐shRNAs and then used in high‐responder rat liver transplantation model (DA donors‐to‐Lewis recipients). Transplant groups (n = 16/group) include untreated recipients transplanted with donor liver graft pretreated with either saline, or pHK‐shRNA, or pCIITA1‐shRNA. Cyclosporine‐treated (10 mg/kg, im, day 0–7) recipients transplanted with unmodified liver grafts were used as no rejection control. The results showed that the recipient rats survived significantly longer in pCIITA1‐shRNA‐treated group with markedly attenuated liver graft rejection (p < 0.05 vs. saline and pHK‐shRNA‐treated groups). Furthermore, significantly decreased intragraft expressions of CIITA, MHC‐II, IL‐2, and IFN‐γ were found in pCIITA1‐shRNA‐treated group (p < 0.05 vs. saline and pHK‐shRNA‐treated groups). This study suggests that intragraft inhibition of CIITA could be a novel strategy for attenuating graft rejection in liver transplantation. © 2014 Wiley Periodicals, Inc. Microsurgery 35:52–59, 2015.     

卒中一级预防指南:美国心脏协会/美国卒中协会致医疗专业者的声明(第七部分)

本更新版指南的目的是为那些尚未患卒中或短暂性脑缺血发作的人群提供深入及时的卒中预防循证建议。循证建议涉及危险因素的控制、头颈部循环的动脉粥样硬化性疾病的介入方法,以及为预防血栓形成和血栓栓塞性卒中而进行的抗栓治疗。更为深入的建议还涉及遗传和药理学试验,以及其他特殊情况下的卒中预防,如镰状细胞病和卵圆孔未闭。     

Value of handgrip strength in predicting the mortality of hemodialysis patients

Objective To analyze the risk factors of mortality among patients treated by maintenance hemodialysis (MHD), and identify whether handgrip strength (HGS) or other nutrient markers could predict the mortality independently. Methods One hundred and eight patients receiving regular MHD in Peking Union Medical College Hospital from July to September, 2008 were involved. Baseline data including clinical data, nutrient data such as subjective global assessment, anthropometrics and biochemical measurement were collected. After being followed for 72 months, the patients' mortality and morbidity of cardiovascular event were recorded. Cox regression model was used to estimate the risk factors of mortality. Results The average age of 108 MHD patients was (57.6±13.0) years. During the 6-years following up, 35 patients died (32.4%), of whom 62.9% died of cardiovascular events. Among variables, patients’ age, residual urine volume, serum creatinine level, prealbumin level and mean leg circumference were risk factors for all-cause mortality. The patient with lower HGS bore higher risk for all-cause mortality (HR=2.842, 95%CI 1.390-5.811) and cardiovascular death (HR=2.826, 95%CI 1.150-6.947). After adjusting gender, age, history of cardiovascular disease and diabetes, body mass index (BMI), dialysis vintage, Kt/V, nPCR and prealbumin, lower handgrip strength was still an independent risk factor of all-cause mortality (HR=2.505, 95%CI 1.112-5.642). In prediction for all-cause mortality by HGS, the area under the receiver operating characteristic curve(ROC) were 0.705 and 0.682 among men and women respectively. Conclusion Lower handgrip strength can predict mortality of maintenance hemodialysis patients independently.     

单节段ProDisc-CDisc-C人工颈椎间盘置换术后旋转中心的位置变化

目的探讨单节段Pro Disc-C人工颈椎间盘置换术的临床疗效以及术后置换节段屈伸活动旋转中心(center of rotation,COR)的位置变化及其临床意义。方法回顾分析2010年6月-2012年2月收治的23例行单节段Pro Disc-C人工颈椎间盘置换术患者临床资料。男9例,女14例;年龄27~65岁,平均45岁。病程10~84个月,平均25个月。其中神经根型颈椎病15例,脊髓型颈椎病5例,混合型颈椎病3例。病变节段:C4、5 5例,C5、6 14例,C6、7 4例。采用日本骨科学会评分(JOA)及颈椎功能障碍指数(NDI)评价临床疗效;比较术前和末次随访时颈椎整体活动度、置换节段及相邻节段活动度、椎间隙高度以及置换节段屈伸活动COR位置坐标(COR-X,COR-Y)的变化;比较分析COR位置变化与术后临床疗效以及影像学指标之间的关系。结果 23例患者均顺利完成手术,其中1例术后出现声嘶,术后3个月症状消失。患者均获随访6~36个月,平均18.3个月。末次随访时假体无移位、松动、下沉及断裂。末次随访时JOA评分较术前显著增加,NDI评分较术前显著减少,差异均有统计学意义(P0.05)。与术前比较,末次随访时颈椎整体活动度,置换节段活动度,上、下相邻节段活动度以及置换节段COR-Y差异均无统计学意义(P0.05);椎间隙高度、置换节段COR-X显著增加(P0.05)。置换节段COR-X变化与术后JOA、NDI、置换节段活动度均无明显相关性(P0.05)。根据手术前后COR-X之差是否小于均值1.86 mm将患者分为两组,两组间术后置换节段活动度差异有统计学意义(P0.05),而两组间术后JOA、NDI、颈椎整体活动度、邻近节段活动度及椎间隙高度差异均无统计学意义(P0.05)。结论单节段Pro Disc-C人工颈椎间盘置换术临床疗效满意,能有效维持颈椎整体活动度、置换节段和相邻节段活动度,增加置换节段的椎间隙高度。术后置换节段矢状面COR位置较术前显著前移,且术后置换节段活动度随COR前移距离增大而减小。     

Management of nonfunctioning islet cell tumors

AIM: To more clearly define the clinical and pathological characteristics and appropriate diagnosis and treatment of nonfunctioning (NFICTs) islet cell tumors, and to review our institutional experience over the last 30 years. METHODS: The records of 43 patients confirmed to have nonfunctioning islet cell tumors of pancreas were retrospectively reviewed. Survival was estimated by the Kaplan-Meier methods and potential risk factors for survival were compared with the log-rank tests. RESULTS: The mean age was 31.63 years (range, 8 to 67 years). There were 7 men and 36 women. Twenty-eight patients had a confirmed diagnosis of nonfunctioning islet cell carcinoma (NFICC) and benign islet cell tumors were found in 15 patients. The most common symptoms in patients with NFICTs were abdominal pain (55.8%), nausea and/or vomiting (32.6%), fatigue (25.6%) and abdominal mass (23.3%). Preoperative ultrasonic and computed tomography localized the tumors in all patients. Forty-three NFICTs were distributed throughout the pancreas, with 21 located to the right of the superior mesenteric vessels, 10 in the body of the pancreas, 6 in the tail of the pancreas, and multiple tumors were found in one patient. Thirty-nine of 43 patients (91%) underwent surgical resection. Surgical treatment was curative in 30 patients (70%) and palliative in 9(21%). The resectability and curative resection rate in patients with NFICC of pancreas were 89% and 61%, respectively. The overall cumulative 5- and 10-year survival rates for patients with NFICC were 58.05% and 29.03%, respectively. Radical operation and diameter of cancer small than 10 cm were positive prognostic factors in females younger than 30 years old. Multivariate Cox regression analysis indicated that radical operation was the only independent prognostic factor, P=0.007. CONCLUSION: Nonfunctioning islet cell tumors of pancreas are found mainly in young women. The long-term results for patients undergone surgery, especially curative resection are good.     

Human intrathymic lineage commitment is marked by differential CD7 expression: identification of CD7- lympho-myeloid thymic progenitors

The identity and lineage potential of the cells that initiate thymopoiesis remain controversial. The goal of these studies was to determine, at a clonal level, the immunophenotype and differentiation pathways of the earliest progenitors in human thymus. Although the majority of human CD34(+)lin(-) thymocytes express high levels of CD7, closer analysis reveals that a continuum of CD7 expression exists, and 1% to 2% of progenitors are CD7(-). CD34(+)lin(-) thymocytes were fractionated by CD7 expression and tested for lineage potential in B-lymphoid, T-lymphoid, and myeloid-erythroid conditions. Progressive restriction in lineage potential correlated with CD7 expression, that is, the CD7(hi) fraction produced T and NK cells but lacked B and myelo-erythroid potential, the CD7(int) (CD10(+)) fraction produced B, T, and NK cells, but lacked myelo-erythroid potential. The CD7(-) fraction produced all lymphoid and myelo-erythroid lineages and expressed HSC-associated genes. However, CD34(+)lin(-)CD7(-) thymocytes also expressed early T lymphoid genes Tdt, pTalpha, and IL-7Ralpha and lacked engraftment capacity, suggesting the signals that direct lymphoid commitment and corresponding loss of HSC function are rapidly initiated on arrival of HSC in the human thymus. Thus, differential levels of CD7 identify the progressive stages of lineage commitment in human thymus, initiated from a primitive CD7(-) lympho-myeloid thymic progenitor.     

A novel method for lymphadenectomy along the left laryngeal recurrent nerve during thoracoscopic esophagectomy for esophageal carcinoma

Background

Due to limited space in the left upper mediastinum, complete dissection of lymph nodes (LN) along left recurrent laryngeal nerve (RLN) is difficult. We herein present a novel method for lymphadenectomy along the left RLN during thoracoscopic esophagectomy in the semi-prone position for esophageal carcinoma. The method, suspension the esophagus and push aside trachea, allows en bloc lymphadenectomy along the left RLN from the below aortic arch to the thoracic inlet.

Methods

Between September 2014 and September 2015, a total of 110 consecutive patients with esophageal carcinoma were treated with thoraco-laparoscopic esophagectomy with cervical anastomosis in the semi-prone position. Outcomes between those who received surgery with the novel method and conventional surgery were compared.

Results

Fifty patients underwent the novel method and sixty received conventional surgery. The operative field around the left RLN was easier to explore with the novel method. The estimated blood loss was less (23.7±8.2 vs. 34.2±10.3 g, P=0.001), and the number of harvested LNs along the left RLN was greater (6.4±3.2 vs. 4.1±2.8 min, P=0.028) in the novel method group, while the duration of lymphadenectomy along left RLN was longer in the novel method group (28.2±3.9 vs. 20.3±2.8 min, P=0.005). The rate of hoarseness in the novel and conventional groups was 10% and 16.7%, respectively. No significant difference in postoperative morbidity related to the left RLN was noted between the groups.

Conclusions

The novel method during semi-prone esophagectomy for esophageal carcinoma is associated with better surgeon ergonomics and operative exposure.     

抗血吸虫成虫表膜抗原单克隆抗体检测循环抗原及/或免疫复合物的实验研究

本文报告用单克隆抗体检测血吸虫感染兔血清中循环抗原及/或免疫复合物的实验结果.以血吸虫成虫盐水浸液抗原ACSE免疫BALB/c小鼠,取其脾脏与SP2/0骨髓瘤细胞融合获得抗成虫表膜的单克隆抗体8SE_4。此抗体经DE_(52)柱层析提纯后制成HRP-8SE_4结合物.血清样本与HRP-8SE_4作用后加入PEG(mw·6000)沉淀免疫复合物,然后加入底物OPD显色,于492nm读数,OD值即反映血循环中抗原及/或免疫复合物的量。实验结果表明5只重感染兔(接种尾蚴15O0～2000条)于感染后6wk可见OD值明显升高,达到感染前的1.9～4.5倍。5只轻感染兔接种尾蚴10～500条亦于感染6wk后OD值明显上升,至感染后8wk达高峰,此后至11wk剖杀时仍维持在较高水平.5轻感染兔检虫数为4～326条,未见虫荷与检测结果有明显相关。本实验结果提示感染兔血清中有循环表膜抗原及/或其复合物存在。至于检测该抗原能否用于考核治疗效果,有待进一步研究。