年龄与成年人肾细胞癌临床分期的相关性分析

目的 探讨年龄与成年人肾细胞癌（renalcell carcinoma，RCC）临床分期的相关性。方法 回顾性分析310例病理确诊的成年RCC患者的临床资料，按年龄大小分为10岁以下组（≤40岁）、40-60岁组、60岁以上组（≥60岁），对三组患者的症状表现、病理学特点、淋巴结转移进行比较，以此了解年龄与成年人RCC临床分期的相关性。结果 40岁以下组偶发癌所占的比例明显低于10-60岁组（X^2=3．294，P=0．070），60岁以上组则显著低于40-60岁组（X^2=3．950，P=0．047）；分化不良RCC的发生率随年龄增长逐渐降低（11．6％vs．5．2％vs．2．7％），且40岁以下组与60岁以上组相比较差异有显著性意义（P=0．038）；淋巴结转移的发生率同样随年龄的增长而降低，且40岁以下组与其他两组相比较差异均有显著性意义（P〈0．05）；三组临床分期的构成比差异有显著性意义（P〈0．01）．Ⅰ期所占的比例随年龄增长逐渐降低，Ⅱ期在10岁以下组中所占的比例明显低于其他两组．而Ⅰ期＋Ⅱ期在40-60岁组中的比例则明显高于其他两组。结论 偶发癌在各年龄组的不同比例值是导致不同年龄组患者临床分期出现差异的主要因素；淋巴结转移及分化不良RCC是导致这种差异的次要因素。     

解剖型钢板治疗胫骨远端骨折

胫腓骨骨折发生率很高,约占长骨骨折的10％。胫腓骨远端骨折在胫腓骨骨折中最为常见,由于涉及干骺端的骨折,髓内钉治疗有其局限性。2002年3月～2003年7月,笔者采用解剖型钢板治疗胫骨远端骨折12例,取得了良好疗效。     

RIPK3‐Mediated Necroptosis Promotes Donor Kidney Inflammatory Injury and Reduces Allograft Survival

Kidney transplant injury occurs with ischemia and alloimmunity. Members of the receptor interacting protein kinase family (RIPK1,3) are key regulators of “necroptosis,” a newly recognized, regulated form of necrosis. Necroptosis and apoptosis death appear to be counterbalanced as caspase‐8 inhibition can divert death from apoptosis to necrosis. Inhibition of necroptosis in donor organs to limit injury has not been studied in transplant models. In this study, necroptosis was triggered in caspase inhibited tubular epithelial cells (TEC) exposed to tumor necrosis factor alpha in vitro, while RIPK1 inhibition with necrostatin‐1 or use of RIPK3^?/? TEC, prevented necroptosis. In vivo, short hairpin RNA silencing of caspase‐8 in donor B6 mouse kidneys increased necroptosis, enhanced high‐mobility group box 1 release, reduced renal function and accelerated rejection when transplanted into BALB/c recipients. Using ethidium homodimer perfusion to assess necrosis in vivo, necrosis was abrogated in RIPK3^?/? kidneys postischemia. Following transplantation, recipients receiving RIPK3^?/? kidneys had longer survival (p = 0.002) and improved renal function (p = 0.03) when compared to controls. In summary, we show for the first time that RIPK3‐mediated necroptosis in donor kidneys can promote inflammatory injury, and has a major impact on renal ischemia–reperfusion injury and transplant survival. We suggest inhibition of necroptosis in donor organs may similarly provide a major clinical benefit.

     

Analysis of differentially expressed genes in fetal skin of scarless and scar-forming periods of gestational rats

Objective: To study the differences of gene expression between earlier gestational skin and later gestational skin of rats with the aids of single primer amplification (SPA) and high-density oligonucleotide DNA array to understand the molecular mechanism of scarless healing. Methods: Total RNAs were isolated from fetal rat skin of the scarless (E15) and scar-forming (E18) periods of gestation (term =21.5 days). The RNAs from earlier gestational skin (EGS) and later gestational skin (LGS) were both reversely transcribed to cDNAs, then labeled with the incorporation of fluorescent dCTP for preparing the hybridization probes by SPA method. The mixed probes were then hybridized to the oligonucleotide DNA arrays which contained 5 705 probes representing 5 705 rat genes. After highly stringent washing, these DNA arrays were scanned for fluorescent signals to display the differentially expressed genes between the 2 groups of skin. Results: Among 5 705 rat genes, there were 53 genes (0.93%) with differentially expressed levels between EGS and LGS groups, 27 genes, including fibroblast growth factor 2 ( FGF2 ) and follistatin were up-regulated (0.47%) and 26 genes were down-regulated (0.46%) in fetal skin during scarless period versus scar-forming period. Higher expressions of FGF2 and follistatin in EGS than those in LGS were also revealed by RT-PCR method. Conclusions: High-density oligonucleotide DNA array provided a powerful tool for investigating differential gene expression in earlier and later gestational fetal skins. This technology validates that the mechanism of fetal scarless healing is very complicate and the change of many gene expressions is associated with fetal scarless healing.     

“黑皮”，绝对劣品后遗症

为了变美而使用化妆品，不曾想却伤害了自己的肌肤。本刊记者提醒爱美女孩应引以为戒！[编者按]     

The targeting of phosphoinositide-3 kinase attenuates pulmonary metastatic tumor growth following laparotomy

OBJECTIVE: We aimed to characterize a potential role for phosphatidylinositol 3-kinase (PI3k) in leading to accelerated postoperative metastatic tumor growth. BACKGROUND: PI3k enhances tumor cell survival in part by phosphorylating Akt and reducing apoptosis. Postoperatively, apoptosis is reduced within local recurrences and distant metastases. This reduction is associated with the phenomenon of accelerated postoperative tumor growth. METHODS: Balb/c mice underwent a tail vein injection of 1x10 metastatic murine mammary adenocarcinoma 4T1 cells. Animals were divided into the following treatment groups (n=10/group): group A, controls; group B, DMSO intraperitoneally (IP) daily from days 14 to 21; group C, IP LY294002 daily from days 14 to 21; group D, laparotomy only; group E, laparotomy followed by IP DMSO for 7 days; and group F, laparotomy followed by LY294002 IP for 7 days. All laparotomies were performed on day 14. Animals were killed at day 28. Metastatic tumor burden was assessed using the lung/body weight ratio and a histologic metastatic index. Mitotic counts and apoptotic indices were established using a combination of hematoxylin and eosin histology and TUNEL immunohistochemistry. A parallel survival study was performed, and PI3k activity was assessed using western blots for phospho-Akt. RESULTS: Laparotomy was associated with increased systemic tumor burden (P=0.001). Postoperatively, LY294002 significantly attenuated metastatic tumor growth (P<0.001). Effective PI3k inhibition was confirmed by demonstrating a reduced Akt phosphorylation. Moreover, PI3k inhibition led to reduced proliferation, increased apoptosis (P<0.001), and enhanced postoperative survival (P<0.001). CONCLUSIONS: Targeting PI3k with postoperative LY294002 significantly attenuates the acceleration in postoperative metastatic tumor growth seen following laparotomy.     

Reconstruction of thumb loss complicated by skin defects in the thumb-index web space by combined transplantation of free tissues

OBJECTIVE: To introduce a new technique of 1-stage reconstruction for thumb loss complicated by thumb-index web space contracture and to report its clinical effectiveness. METHODS: From November 1994 to September 2004 there were 11 patients with thumb loss and contracture in the thumb-index web space who had a combined transplantation of free tissues to reconstruct the missing thumb and to rebuild the web space. The reconstructive procedure used the second toe and the anterolateral thigh flap in 5 patients, the second toe and the scapular flap in 2, the big toe wraparound flap and the anterolateral thigh flap in 3, and the big toe wrapround flap and the scapular flap in 1. The 2 independent free tissues were connected together by a vascular combination to form an assembly with 1 common vascular pedicle, which then was anastomosed to the selected vessels in the recipient hand. In this vascular series the dorsalis pedis artery and the greater saphenous vein served as the common vascular pedicle of the flap transfers and the radial artery and the cephalic vein provided the recipient vessels. The outcomes of the reconstructions were evaluated using the Michigan Hand Outcomes Questionnaire. RESULTS: The flaps survived completely in all patients except 1. In this patient a small area in the distal part of the transplanted anterolateral thigh flap became necrotic but healed after dressing changes without the need for further surgical intervention. A mean follow-up period of 3.6 years showed a mean increase of 4.3 cm in the width of the thumb-index web space and a considerable improvement in overall hand function was noted on the Michigan Hand Outcomes Questionnaire with effect sizes of greater than 3 (large effect) in all domains. CONCLUSIONS: Combined transplantation of the second toe or the big toe wraparound flap and a free skin flap is suitable to reconstruct a missing thumb and repair the associated skin defect in the adjacent thumb-index web space. We found good functional recovery and an acceptable appearance in this series of patients.Type of study/level of evidence: Therapeutic, Level IV. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.     

The molecular and clinical impact of hepatocyte growth factor, its receptor, activators, and inhibitors in wound healing

Wound healing involves a number of cellular and molecular events, many of which are controlled by soluble growth factors. In the process of healing, hepatocyte growth factor, a cytokine known to act as mitogen, motogen, and morphogen, has been postulated to play multiple roles during several stages of this complex biological process. Produced primarily by stromal fibroblasts, hepatocyte growth factor regulates angiogenesis, vascular permeability, cell migration, matrix deposition and degradation, and other biological processes. The current article discusses recent progress in understanding the multiple roles played by this growth factor in tissue repair.     

Influence of CYP3A5 gene polymorphisms of donor rather than recipient to tacrolimus individual dose requirement in liver transplantation

BACKGROUND: Tacrolimus is a widely used immunosuppressant in organ transplantation, but it is characterized by a narrow therapeutic index and high interindividual variations of its pharmacokinetics. Tacrolimus is a substrate for CYP3A. It has been conjectured that CYP3A5 polymorphism is associated with tacrolimus pharmacokinetic variations. The objective of this study was to evaluate the contribution of polymorphisms of the donor and recipient CYP3A5 gene on tacrolimus disposition in liver transplantation. METHODS: Fifty-three liver transplant recipients treated with tacrolimus were enrolled in this study. Tacrolimus dosage and blood trough concentration were investigated at 1 week, 2 weeks, and 1 month after transplantation. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was applied to determine the genotype of CYP3A5 gene. RESULTS: The concentration/dose (C/D) ratios in patients with *1/*1(*1/*3) genotype donor were significantly lower than in patients with *3/*3 genotype donor at 2 weeks (P = 0.036) and 1 month (P = 0.021), but not at 1 week posttransplantation. Combination analysis showed that such significance still existed between CYP3A5 expressor group and nonexpressor group for both donor and recipient genotype. Also differences of C/D ratio between CYP3A5 expressor and nonexpressor donors in nonexpressor recipients were larger than those between recipients in nonexpressor donors. CONCLUSION: The large interindividual variation of tacrolimus dose requirement is influenced by the metabolic activity of CYP3A5. Polymorphisms of the donor CYP3A5 gene seem to contribute more to such variation than the recipient. A larger population and further studies are needed to explore the exact mechanisms for tacrolimus pharmacokinetics.     

Nerve conduit filled with GDNF gene-modified Schwann cells enhances regeneration of the peripheral nerve

A recombinant retrovirus vector containing the glial cell line-derived neurotrophic factor (GDNF) gene was constructed and transfected into Schwann cells (SCs) to investigate the possibility of GDNF transfection and functional expression of transfected SCs, including GDNF secretion and its mRNA expression. We found that transfection of the GDNF gene into SCs led to significantly enhanced expression of GDNF mRNA. The rate of GDNF secretion by GDNF-SCs was also increased. Functionally, more surviving motoneurons were seen when they were cocultured in GDNF-SC-conditioned medium than when they were in normal SC-conditioned medium. When bridging a rat sciatic nerve defect with a conduit filled with GDNF-transfected SCs, nerve regeneration was better than that of the control. In conclusion, transfection of SCs with the GDNF gene could enhance SC function. Application of genetically modified SCs could be a better way to promote nerve regeneration.