经肝动脉灌注平阳霉素碘油乳剂对兔正常肝脏组织的影响

目的：探讨平阳霉素碘油乳剂（PLE）经肝动脉灌注对兔正常肝脏组织的影响。方法：14只4～5个月龄日本大耳白兔，体重（2.5±0.2）kg，按注入生理盐水或PLE的量分为假手术组、实验A组（低剂量组）和实验B组（高剂量组）。各组兔均开腹穿刺肝动脉，按分组剂量注入PLE。术后1，2，4，6周取病理切片，HE染色，光镜下观察肝脏组织学改变;免疫组织化学（免疫组化）染色标记血小板衍化生长因子B链（PDGF-B），并行图象分析。结果：A组HE染色肝细胞呈一过性水样变，变性在2周时最重，至6周已明显减轻。B组HE染色2周时肝细胞明显水样变，4周时可见汇管区纤维组织增生，6周时部分肝组织出现明显假小叶结构。免疫组化染色显示，PDGF-B在肝细胞胞膜及纤维间隔中有明显表达。结论：经肝动脉灌注PLE可导致正常肝脏组织产生不同程度的肝纤维化;PDGF-B参与了肝纤维化的病理过程。     

小鼠全肝缺血再灌注时肺泡巨噬细胞TLR2的激活与肺损伤的机制

目的：探讨肺泡巨噬细胞Toll样受体2（TLR2）的激活机制及其在肝脏缺血再灌注（HIR）中肺损伤的意义。方法：用野生型小鼠C3h/Heouj和TLR4缺失小鼠C3h/Hej建立HIR动物模型。于再灌注1，6，12h后经支气管肺泡灌洗液获取肺泡巨噬细胞，采用荧光定量PCR方法检测TLR2/4mRNA的表达。同时检测支气管肺泡灌洗液中内毒素及肿瘤坏死因子（TNF）的水平，肺组织湿干重比值，肺组织髓过氧化物酶的浓度，并进行肺组织学评分。结果：C3h/Heouj组HIR缺血再灌后各时点肺泡巨噬细胞TLR2/4mRNA表达升高，TLR2mRNA表达持续升高，TLR4mRNA6h达到最高值。同时C3h/Heouj组HIR后支气管肺泡灌洗液中TNF水平明显升高，肺损伤加重，肺组织湿干重比值持续升高，肺组织髓过氧化物酶持续增加(P<0.05)。C3h/Hej组HIR后TLR2mRNA表达仅轻度升高，且支气管肺泡灌洗液中TNF水平低于C3h/Heouj组(P<0.05)，肺损伤轻于C3h/Heouj组(P<0.05)。结论：HIR可致肺泡巨噬细胞表面TLR4的激活，可上调TLR2的表达，从而可加重HIR时的肺损伤。     

原位肝移植中受体血管异常时的肝动脉重建

摘要：目的 探讨原位肝移植中动脉异位重建的方法及效果。 方法 回顾性分析我院10年来的440例肝移植中36例因受体血管异常而行异位重建的方法及术后处理措施等。 结果 36例中行供肝动脉与受体肾下腹主动脉吻合20例，与肾上腹主动脉吻合10例，与胃左动脉吻合4例，与脾动脉吻合2例。5例围手术期死亡，但吻合口通畅，31例存活3个月至4年无血管相关并发症，仅1例术后2个月因胆道缺血坏死行再次肝移植。 结论 肝移植时受体肝动脉有病变或异常改变时，应将受体肾下或肾上腹主动脉、脾动脉、胃左动脉与供肝动脉进行异位重建，可取得满意效果。     

胆囊癌GBC-SD细胞经顺铂处理后的survivin表达及意义

目的: 探讨经顺铂（DDP）处理胆囊癌细胞后survivin表达及其与肿瘤细胞耐药之间的关系。 方法:采用MTT比色法测定胆囊癌细胞对4种化疗药物的敏感性。RT-PCR检测survivin mRNA的表达。Western blot检测survivin蛋白表达的变化。结果:GBC-SD细胞对化疗药物的敏感性从高到低依次为DDP>ADM>5-FU>MMC。化学药物处理后的第1天，3组胆囊癌细胞的survivin mRNA表达水平均降低;其中0.5μg/mL DDP＋GBC-SD组下降了10%，3μg /mL DDP＋GBC-SD组下降36%，6μg /mL DDP＋GBC-SD组下降了28%。第3天，0.5μg/mL DDP组和3μg/mL DDP组GBC-SD细胞的survivin mRNA表达与第1天比较，分别上升22%和64%，但6μg/mL DDP组仍持续降低，仅为第1天的66%。0.5μg/mL DDP组和3μg/mL DDP组作用3d后的GBC-SD细胞中survivin蛋白含量分别升高了15%和12%，而6μg/mL DDP组则下降了80%。 结论:低浓度的DDP即能诱导胆囊癌细胞内survivin的表达增加，这可能是胆囊癌细胞对化疗药物产生耐药性的因素之一。     

左侧结肠癌性梗阻一期切除吻合治疗:附58例报告

摘要：为探讨左侧结肠癌并急性肠梗阻理想的处理原则和方法,回顾分析58例左侧结肠癌并发急性肠梗阻行一期切除吻合术患者的临床资料。本组均成功手术，无手术死亡，术后除7例有切口不同程度液化感染外，无吻合口漏、腹腔感染等并发症，均痊愈出院。提示：对能耐受手术切除的左侧结肠癌并发梗阻，在必要的围手术期处理前提下，一期切除吻合是可行的。避免了横结肠造口、二期手术、癌肿扩散及并发症的发生。     

骨盆骨折合并盆腔血肿的髂内动脉介入栓塞治疗

笔者采用明胶海绵或不锈钢圈栓塞双侧髂内动脉治疗骨盆骨折合并盆腔血肿7例，其中6例患者术前处于休克前期或休克期，血压低，出血明显，栓塞成功后，出血停止，血压回升，栓塞后2d血压恢复正常基础水平。提示：双侧髂内动脉栓塞对治疗骨盆骨折合并盆腔血肿效果明显，是一种有效的治疗手段。     

经外膜缓释雷公藤内酯醇抑制自体移植静脉内膜增生

目的:探讨经外膜缓释雷公藤内酯醇（triptolide）对自体移植静脉内膜增生的抑制作用。方法:健康雄性新西兰大白兔24只，建立颈外静脉-颈总动脉移植模型。随机将动物等分为3组。空白组移植血管不给任何处理， F-127多聚凝胶对照组在移植血管外膜喷洒20 %F-127多聚凝胶0.5 mL，实验组在移植血管外膜喷洒携带雷公藤内酯醇300μg的F-127多聚凝胶0.5 mL。术后2周取标本。用组织形态学方法检测血管内膜增生程度，免疫组化检测标本中bcl-2和Fas的表达，TUNEL法检测标本中血管平滑肌细胞(VSMC)凋亡的水平。结果:静脉移植2周后，与空白组和F-127对照组比较，实验组血管内膜增生明显受抑制（P<0.05），bcl-2的表达［（18.2±8.4） %］显著减少，而Fas的表达［（21.4±8.9） %］显著增加，凋亡细胞［（28.4±7.6） %］也显著增加（P<0.05）。结论:经外膜缓释雷公藤内酯醇可有效抑制移植静脉内膜增生，这一作用可能系通过促进VSMC凋亡而实现的。     

股动脉假性动脉瘤外科治疗18例分析

回顾性分析股动脉假性动脉瘤18例的临床资料。1例因介入穿刺引起的股动脉假性动脉瘤行局部压迫治疗,15例行假性动脉瘤切除术,2例行股动脉结扎术。结果示1例股动脉结扎术患者术后出现肢体坏死，行膝上截肢后康复出院，另17例痊愈出院。提示对股动脉假性动脉瘤行动脉瘤切除、股动脉端端吻合可作为首选的手术方式。     

手法张力美容切口治疗乳腺纤维瘤的体会

目的:探索一种治疗彻底、创伤少、瘢癍痕小、费用低的乳腺纤维瘤治疗方法。方法:回顾近3年来465例采用手法张力美容切口治疗乳腺纤维瘤患者的临床资料。结果:465例手术均最大限度争取行乳晕或腋窝皱褶或乳腺下方皱褶切口。切口均甲级愈合，无明显瘢痕，双乳对称，外形功能无影响，站立时切口不明显。结论:手法张力美容切口治疗乳腺纤维瘤是一种适合大部分乳腺纤维瘤患者的手术方法，具有治疗彻底、创伤少、瘢痕小、费用低。     

胆道再手术原因分析：附828例报告

目的:分析导致再次胆道手术的原因，以期减少胆道再手术率。方法:总结1990—1999年间收治的再次胆道手术患者828例的临床资料，对胆道疾病再次手术的原因进行归类分析。结果:再手术的主要原因是结石复发或残留，占65.10%;结石合并Oddi括约肌狭窄占33.82%;单纯Oddi括约肌狭窄占9.54%;胆管损伤性狭窄和胆肠吻合口狭窄占10.39%;胆道系统肿瘤占6.52%。结论:胆道再手术的主要原因仍以结石复发或残留为主，其次为Oddi括约肌狭窄;损伤性胆管狭窄等与手术有关的因素不容忽视。减少胆道再次手术的关键在于初次手术的彻底性和手术方法的合理性。     

Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status

EWSR1-CREB1 and EWSR1-ATF1 are gene fusions of which one or both have now been consistently described in 5 histopathologically and behaviorally diverse neoplasms: angiomatoid fibrous histiocytoma, conventional clear cell sarcoma (of tendons and aponeuroses), clear cell sarcoma-like tumor of the gastrointestinal tract, hyalinizing clear cell carcinoma of the salivary gland, and primary pulmonary myxoid sarcoma. Some of the tumors in this group have been described only recently, and others have been the subject of recent genetic insights contributing to their characterization. These neoplasms are all rare; yet, the increasing frequency with which EWSR1-CREB1 and EWSR1-ATF1 fusions are being described in separate entities is noteworthy. The additional molecular mechanisms by which tumors with such variable morphologic, immunohistochemical, and clinical phenotypes are generated are yet to be understood. We review the clinicopathologic and molecular features of this group of neoplasms unified by the presence of EWSR1-CREB1 and EWSR1-ATF1 genetic fusions.     

Plasma glutathione S-transferase pi 1-1 AND alpha 1-1 levels in patients with bladder cancer

PURPOSE: Transitional cell carcinomas of the human bladder and many gastrointestinal tumors often contain high amounts of the detoxification enzyme glutathione S-transferase pi (GSTP1-1). Elevated levels of GSTP1-1 have been found in serum and plasma from patients with gastrointestinal, lung or head and neck cancer. GSTP1-1 and glutathione S-transferase alpha (GSTA1-1) have been reported to be increased in 10 of 15 patients (67%) with bladder cancer. We evaluate the role of GSTP1-1 and GSTA1-1 as plasma tumor markers in 50 patients with bladder cancer before and after treatment. MATERIALS AND METHODS: Blood from patients with bladder cancer was sampled in ethylenediaminetetraacetic acid tubes. Plasma GSTA1-1 and GSTP1-1 were measured using the sensitive and specific sandwich enzyme-linked immunosorbent assay. RESULTS: Respective plasma GSTA1-1 and GSTP1-1 levels were above the upper normal reference limit in 2 (4%) and 14 (28%) of the 50 patients with bladder cancer. No significant decrease in plasma GSTA1-1 or GSTP1-1 was noted in matched pairs of plasma samples collected before and after treatment. CONCLUSIONS: In contrast to earlier reports, only a limited number of patients with bladder cancer had increased plasma GSTA1-1 or GSTP1-1, which did not decrease after tumor resection. These findings argue against the use of GSTP1-1 or GSTA1-1 as plasma markers for bladder cancer.     

Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, and GSTT1 associated with head and neck cancer

BACKGROUND: Alcohol intake and tobacco smoke, in addition to other environmental and genetic factors, have been associated with head and neck cancer. We evaluated the role of metabolic enzyme polymorphisms on the risk of head and neck cancer in a hospital-based case-control study. METHODS: CYP1A1MspI, CYP2E1PstI, GSTM1, and GSTT1polymorphisms were evaluated in 103 histologically confirmed head and neck cancer cases and 102 controls by means of polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: GSTM1null increased the risk of head and neck cancer (odds ratio [OR], 2.2; 95% confidence interval [95% CI], 1.24-3.79), oral cancer (OR, 2.8; 95% CI, 1.28-5.98), and pharyngeal cancer (OR, 2.2; 95% CI, 1.08-4.63). CYP2E1PstI polymorphism indicated a risk for oral cancer (OR, 3.6; 95% CI, 1.29-11.56). The joint effect of GSTM1 null and CYP1A1 polymorphism increased the risk of head and neck cancer (OR, 2.4; 95% CI, 1.13-5.10). CONCLUSIONS: GSTM1 null alone or associated with CYP1A1 increased the risk of head and neck cancer; the CYP2E1PstI mutated allele increased the risk for only oral cancer.     

IgA肾病患者C1GALT1C1基因的体细胞突变筛查

目的 探讨IgA肾病（IgAN）患者β1,3半乳糖转移酶的分子伴侣Cosme编码基因C1GALT1C1基因体细胞突变情况。方法 27例IgA肾病患者及19例正常健康对照作为研究对象。提取研究对象外周血基因组DNA,扩增C1GALT1C1基因的编码区,采用PCR产物直接测序的方法进行突变筛查。然后,分离其中15例IgA肾病患者及7例健康男性对照的外周血B淋巴细胞,提取DNA。对C1GALT1C1基因编码区进行扩增,PCR产物进行克隆,各挑选平均8～10个克隆进行体细胞突变筛查。结果 46例个体全血基因组DNA的PCR扩增产物测序发现,2例患者及1例健康对照存在外显子T393A变异,次等位基因频率（MAF）为6．9%[SNP数据库（dbSNP）报告为9．5%]。B淋巴细胞DNA序列分析显示,在22例个体（15例IgA肾病患者,7例健康对照）送检的总共202个克隆中,未发现新的突变和多态性位点。结论 C1GALT1C1基因编码区T393A多态位点在本研究人群中为唯一发现的多态性位点,其次等位基因频率（MAF）较既往报道略低。本研究尚未发现IgA肾病患者B淋巴细胞存在体细胞突变。     

Deficiency of TBL1XR1 causes asthenozoospermia

Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) is an evolutionarily conserved protein related to spermatozoa. To clarify its role and mechanism of action in spermatozoa, qRT-PCR was used to analyse the expression of TBL1XR1 in human spermatozoa and mouse testes. The mice were established as an animal model by injecting the mice testes with small interfering RNA against TBL1XR1 or control siRNA. Our results indicated that deficiency of TBL1XR1 in mice reduced the motility of spermatozoa and disrupted the histone-to-protamine transition. We also found the decreased expression of TBL1XR1 in the spermatozoa of human patients with asthenozoospermia (AZ) compared with that in the spermatozoa of healthy males. Moreover, we carried out chromatin immunoprecipitation analyses and found that genes downstream of TBL1XR1 were related to sperm motility. Thus, TBL1XR1 might be related to sperm motility and might function through its downstream genes. Our data highlight the role of TBL1XR1 involved in spermatozoa and provide new molecular insights into the intricate systems required for male fertility.     

COL1A1 haplotypes and hip fracture

Fragility fractures resulting from low‐trauma events such as a fall from standing height are associated with osteoporosis and are very common in older people, especially women. Three single nucleotide polymorphisms (SNPs) at the COL1A1 gene (rs1107946, rs11327935, and rs1800012) have been widely studied and previously associated with bone mineral density (BMD) and fracture. A rare haplotype (T‐delT‐T) of these three SNPs was found to be greatly overrepresented in fractured individuals compared with nonfractured controls, thus becoming a good candidate for predicting increased fracture risk. The aim of our study was to assess the association of this haplotype with fracture risk in Spanish individuals. We recruited two independent groups of ～100 patients with hip fracture (a total of 203 individuals) and compared the genotype and haplotype distributions of the three SNPs in the fractured patients with those of 397 control individuals from the BARCOS Spanish cohort. We found no association with risk of fracture at the genotype level for any of the SNPs, and no differences in the SNP frequencies between the two groups. At the haplotype level, we found no association between the T‐delT‐T haplotype and fracture. However, we observed a small but significant (p = 0.03) association with another rare haplotype, G‐insT‐T, which was slightly overrepresented in the patient group. © 2012 American Society for Bone and Mineral Research.     

Impact of CYP1A1, GSTM1, and GSTT1 polymorphisms in overall and specific prostate cancer survival

ObjectivePrognostic biomarkers that distinguish between patients with good or poor outcome can be used to guide decisions of whom to treat and how aggressively. In this sense, several groups have proposed genetic polymorphisms as potential susceptibility and prognostic biomarkers; however, their validity has not been proven. Thus, the main goal of the present work was to investigate the potential role of single and combined CYP1A1, GSTM1, and GSTT1 genotypes as modifiers of cancer survival in Chilean patients with prostate cancer.Methods and materialsA total of 260 histologically confirmed patients were recruited from a voluntary screening, and genomic DNA was obtained from their blood samples for genotyping analyses to detect the CYP1A1*2A polymorphism and GSTM1 and GSTT1 deletions. The progression of illness and mortality were estimated with a median follow-up of 8.82 years. Adjusted estimated genotype risks were evaluated by hazard ratio and 95% CI using the Cox proportional model. In addition, the Kaplan-Meier survival method and log-rank test were used to evaluate patient survival with regard to genotype.ResultsThe 9-year overall and specific survival rates were 67.6% and 36.6% in the GSTT1null group, 67.6% and 58.7% in the GSTM1non-null group, 69.0% and 51.6% in the *1A/*2A group, 63.9% and 61.5% in the *2A/*2A group vs. 76.2% and 62.3% in the GSTT1non-null group, 82.3% and 50% in the GSTM1null group, and 83.7% and 56.3% in the *1A/*1A group, respectively. The hazard ratios and the Kaplan-Meier curve results demonstrate that the GSTM1non-null, GSTT1null, and CYP1A1*2A genotypes are significantly associated with mortality. Our study has two main limitations: a relatively small sample size and a low global mortality percentage (25.4%); thus, we need to continue the follow-up to confirm these findings.ConclusionsOur results suggest that the GSTM1non-null, GSTT1null, and CYP1A1*2A genotypes may be good prognosis markers, particularly in patients with high-risk tumors.     

Polycystin-1 expression in PKD1, early-onset PKD1, and TSC2/PKD1 cystic tissue.

BACKGROUND: The mutational mechanism responsible for cyst formation in polycystic kidney disease 1 gene (PKD1) remains controversial, with data indicating a two-hit mechanism, but also evidence of polycystin-1 expression in cystic tissue. METHODS: To investigate this apparent paradox, we analyzed polycystin-1 expression in cystic renal or liver tissue from 10 patients with truncating PKD1 mutations (including one early-onset case) and 2 patients with severe disease associated with contiguous deletions of TSC2 and PKD1, using monoclonal antibodies (mAbs) to both extreme N-(7e12) and C-terminal (PKS-A) regions of the protein. Truncation of the C-terminal epitope from the putative mutant proteins in each case allowed exclusive assessment of the nontruncated protein with PKS-A. RESULTS: In adult PKD1 tissue, the majority of cysts (approximately 80%) showed polycystin-1 expression, although staining was absent in a variable but significant minority (approximately 20%), in spite of the normal expression of marker proteins. Unlike adult PKD1, however, negative cysts were rarely found in infantile PKD1 or TSC2/PKD1 deletion cases. CONCLUSIONS: If a two-hit mutational mechanism is operational, these results suggest that the majority of somatic mutations in adult PKD1 are likely to be missense changes. The low level of polycystin-1-negative cysts in the three "early-onset" cases, however, suggests that a somatic PKD1 mutation may not always be required for cyst formation.     

COL1A1 Sp1 polymorphism associates with bone density in early puberty

Optimal acquisition of bone mass in puberty is a key determinant of the lifetime risk of osteoporosis and has a strong genetic basis. We investigated the relationship between the COL1A1 Sp1 polymorphism and BMD in early puberty, and how the genotypes relate to bone size and geometry as well as bone turnover and material properties in 247 10- to 13-year-old girls. Bone properties were measured using DXA, pQCT, and ultrasound. Also, serum P1NP, OC, B-ALP, and TRACP 5b were assessed. Our results showed that girls with the TT genotype had significantly lower BMC and BMD of the total body, lumbar spine, and proximal femur, as well as BUA at the calcaneus, than those with the GT and GG genotype. They also had significantly lower B-ALP, as well as P1NP/TRACP 5b and (OC + B-ALP)/TRACP 5b, compared to the others. These findings indicate that the COL1A1 polymorphism is associated with low bone properties in early puberty and suggest a possible physiological effect on collagen metabolism and bone turnover. This information may contribute to the identification of children at risk for suboptimal acquisition of peak bone mass and may ultimately be of value in the planning of early preventive strategies for osteoporosis.