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。     

Association of paraoxonase gene polymorphisms with sperm parameters

Paraoxonase (PON) is a high-density lipoprotein-associated enzyme that prevents low-density lipoprotein oxidation. PON proteins, localized in the seminiferous tubules and in spermatozoa, have been implicated in the pathogenesis of male infertility. In the present study, we sought to explore the contribution of the PON gene variants to sperm parameters. One hundred twenty oligospermic and 170 normozoospermic men were examined during infertility investigation. DNA was extracted from spermatozoa, and the PON1(L/M) 55, PON1(Q/R) 192, and PON2(S/C) 311 polymorphisms were genotyped by polymerase chain reaction and digestion with restriction enzymes. The analysis revealed that oligospermic men presented PON1 55L/L, PON1 192Q/Q, and PON2 311S/S genotypes less frequently than normozoospermic men (P < .01, P < .01, and P < .001, respectively), whereas the PON1 55M, PON1 192R, and PON2 311C alleles were significantly increased in oligospermic men (P < .004, P < .008, and P < .008, respectively). The presence of PON1 55L allele was associated with higher sperm motility in oligospermic men (P < .001), in normozoospermic men (P < .01), and in the total study population (P < .01), and the PON1 192Q allele was associated with higher sperm motility in oligospermic men (P < .01), in normozoospermic men (P < .04) and in the total study population (P < .03). On the other hand, the PON2 311S was associated with higher sperm concentration in oligospermic men (P < .03), in normozoospermic men (P < .008), and in the total study population (P < .001). In our series, the PON1 55M and PON1 192R alleles were associated with decreased sperm motility whereas the PON2 311C allele was associated with decreased concentration, supporting the significance of PON genes in semen quality.     

Association of TNFα, TNFR1, and TNFR2 polymorphisms with sperm concentration and motility

Tumor necrosis factor α (TNFα) is a multifunctional cytokine that regulates various cellular processes related to spermatogenesis. Two types of cell receptors, TNFR1 and TNFR2, mediate TNFα activity. In the present study, we sought to explore the association of TNFα -857C→T, TNFR1 36A→G, and TNFR2 676T→G polymorphisms with sperm concentration and motility. Two hundred ninety men were examined during infertility investigation; of those, 170 men were normozoospermic and 120 were oligospermic. Polymerase chain reaction analysis revealed significant differences in genotype distribution of the TNFR1 36A→G polymorphism between normozoospermic and oligospermic men. Men with oligozoospermia presented TNFR1 36A/A genotypes less frequently than normozoospermic men (P < .001). The presence of the TNFR1 36G allele was significantly increased in oligospermic men (P < .001). Furthermore, the presence of the TNFR1 36G allele was associated with lower sperm concentration in normozoospermic men (P < .03) and in the total study population (P < .001), and with lower sperm motility in normozoospermic men (P < .007) and in the total study population (P < .001). No significant associations were found between TNFα -857C→T and TNFR2 676T→G polymorphisms and semen quality. The TNFR1 36A allele is associated with increased sperm concentration and motility in our series, supporting the significance of TNFR1 gene in semen quality.     

Polymorphisms in the CYP19 and AR Genes—Relation to Bone Mass and Longitudinal Bone Changes in Postmenopausal Women With or Without Hormone Replacement Therapy: The Danish Osteoporosis Prevention Study

Polymorphisms in the androgen receptor ( AR) gene and genes encoding enzymes involved in synthesis of sex steroids (e.g., the CYP19 gene encoding aromatase) have recently received attention in osteoporosis research. In the Danish Osteoporosis Prevention Study, recent postmenopausal women were allocated to either hormone replacement therapy (HRT) or no treatment. We genotyped 1792 women for the CYP19 (TTTA)(n) repeat [short (TTTA)(n 7)] the CYP19 C(1558)-T, and the AR (CAG)(n) repeat polymorphism [short (CAG)(n < 22), long (CAG)(n >or= 22)], and investigated associations with bone mineral density (BMD) and 5-year change in BMD. The CYP19 polymorphisms were in strong linkage disequilibrium. Perimenopausal bone mass or bone loss in untreated women was not associated with the CYP19 polymorphisms. In hormone-treated women, BMD increase in the femoral neck was highest (+0.3%/year) for long CYP19 alleles, lowest (-0.09%/year) for short alleles, and intermediate (-0.002%/year) in heterozygous women, P = 0.015. Differences were also significant in the lumbar spine, total hip, and ultradistal forearm. The C(1558)-T T-allele was associated with a more pronounced response to HRT ( P = 0.04, total hip). AR genotype was not related to BMD, but a modifying effect of sex hormone-binding globulin (SHBG) was present. In the highest SHBG quartile (SHBG > 95 nmol/1, n = 222), AR genotype was associated with baseline BMD (femoral neck: P < 0.001, total hip: P = 0.008), but without a clear gene dosage effect. We have demonstrated that polymorphisms in the CYP19 gene are associated with the magnitude of bone gain in response to HRT and that the (CAG)(n) repeat polymorphism in the AR gene is associated with bone mass in women with high levels of SHBG. These findings emphasize the complexity of the genetics of bone mass and bone loss.     

The role of estrogen receptor-α gene TA polymorphism and aromatase gene TTTA polymorphism on peak bone mass attainment in males: is there an additive negative effect of certain allele combinations?

Idiopathic osteoporosis in males is influenced predominantly by low peak bone mass as a feature under a strong genetic control. Among a number of candidate genes, α-estrogen receptor (ERα) and CYP19 genes are of particular interest due to important role of estrogen in pathophysiology of osteoporosis. In the present study we examined the association of certain allelic combinations of ERα gene thymine–adenine (TA) polymorphism and aromatase gene TTTA polymorphism on bone mineral density (BMD) in young men. The study sample consisted of 92 unrelated healthy male volunteers, aged 21–35. In each subject, lumbar spine and proximal femur BMD, parameters of bone turnover and 25-OHD level were measured. Two ERα (TA) _n alleles, allele 19 and allele 21, were found to be associated with lower BMD. The presence of allele 19 was associated with significantly lower lumbar spine (P = 0.006) and trochanter (P = 0.02) BMD while the subjects positive for allele 21 had significantly lower lumbar spine (P = 0.04), trochanter (P = 0.02) and total hip (P = 0.03) BMD. Men with CYP19 (TTTA)_7-3/ERα (TA)₁₉ allele combination had significantly lower lumbar spine BMD (P = 0.02) and those with CYP19 (TTTA)_7-3/ERα (TA)₂₁ allele combination had significantly lower BMD for all three measurements, i.e. lumbar spine (P = 0.02), femoral neck (P = 0.02) and total hip (P = 0.008). These particular combinations of high-risk alleles were associated with lower median lumbar spine, femoral neck and total hip BMD than either of the allele alone suggesting that negative effect of two risk alleles on peak bone mass add up.     

Evidence for association of sex hormone-binding globulin and androgen receptor genes with semen quality

The roles of androgen receptor AR(CAG)n gene polymorphisms and sex hormone-binding globulin SHBG(TAAAA)n gene polymorphisms on semen quality were studied. One hundred fourteen men were included in the study: 85 with normal sperm count and 29 oligospermic. The genotype analysis, on DNA extracted from spermatozoa, revealed five SHBG(TAAAA)n alleles with 6–10 repeats and 18 AR(CAG)n alleles with 12–32 repeats. The SHBG allelic distribution showed that in men with normal sperm count and motility, those with short SHBG alleles had higher sperm concentration than men with long SHBG alleles ( P  = 0.039). As concerns AR(CAG)n polymorphisms, men with short AR alleles had lower sperm motility compared to those with long AR alleles ( P  < 0.001) in both total study population and normal sperm count men. The synergistic effect analysis of the two polymorphisms revealed an association between sperm motility ( P  = 0.036), because of the effect of AR(CAG)n polymorphism on sperm motility. In conclusion, long AR alleles were found to be associated with higher sperm motility, while short SHBG alleles were associated with higher sperm concentration, supporting the significance of these genes in spermatogenesis and semen quality.     

Cytochrome P450‐2D6*4 polymorphism seminal relationship in infertile men

This study aimed to assess cytochrome (CY) P450‐2D6*4 polymorphism relationship with semen variables in infertile men. In all, 308 men were included; fertile normozoospermia (N) (n = 77), asthenozoospermia (A) (n = 70), asthenoteratozoospermia (AT) (n = 75) and oligoasthenoteratozoospermia (OAT) (n = 86). They were subjected to history taking, clinical examination, semen analysis, sperm acrosin activity, seminal malondialdehyde (MDA) and CYP450‐2D6*4 genotyping. CYP450‐2D6*4 wild‐type allele was represented in 76.5% of N, 70% of A, 66.7% of AT and 57.7% of OAT men where homozygous gene mutation was present in 5.9% of N, 20% of A, 26.6% of AT and 26.9% of OAT men, respectively. Sperm acrosin activity, sperm concentration, sperm motility, linear sperm velocity and sperm normal forms were significantly higher, and seminal MDA level was significantly lower in men with CYP450‐2D6*4 wild‐type allele compared with men with homozygous mutation. It is concluded that CYP450‐2D6*4 wild‐type allele has higher frequency where homozygous‐type allele has lower frequency in N men compared with A, AT and OAT men. Sperm acrosin activity index, sperm concentration, sperm motility, linear sperm velocity and sperm normal forms were significantly higher, and seminal MDA level was significantly lower in men with CYP450‐2D6*4 wild‐type allele compared with men with homozygous mutation.     

Evidence of a treatable endocrinopathy in infertile men

PURPOSE: We establish whether a subset of infertile men have decreased serum testosterone-to-estradiol ratios and whether this condition can be corrected with an oral aromatase inhibitor. MATERIALS AND METHODS: The serum testosterone-to-estradiol ratios of 63 men with severe male factor infertility or hypergonadotropic hypogonadism (mean follicle-stimulating hormone 21.2 +/- 1.8) were compared with those of an age matched, fertile, control reference group. Of the 63 men 43 were azoospermic with biopsy proved severe male infertility and 20 were oligospermic. The men with the lowest ratios (less than 20th percentile) were treated with 50 to 100 mg of the aromatase inhibitor testolactone orally twice daily. Testosterone-to-estradiol ratios and semen analyses were evaluated during testolactone therapy. RESULTS: Men with severe male infertility had significantly lower testosterone (328 versus 543 ng/dl, p <0.01) and higher estradiol (58.4 versus 43.5 ng/l, p = 0.01) than fertile control reference subjects, resulting in a decreased testosterone-to-estradiol ratio (x10(-1) = 6.9 +/- 0.6 versus 14.5 +/- 1.2, respectively, p <0.01). Of the 45 men treated with testolactone a correction of these abnormalities was seen and ratios (x10(-1)) increased into the normal range (5.0 +/- 0.3 to 12.7 +/- 1.2, p <0.01). Semen analyses were considered evaluable only in men with sperm in the ejaculate before aromatase inhibitor treatment. Semen analyses before and during testolactone treatment revealed significant increases in sperm concentration (16.1 to 28.9 million sperm per ml, p = 0.03) and motility (27.1% to 45.3%, p <0.01) in 12 oligospermic men. CONCLUSIONS: We identified an endocrinopathy in men with severe male factor infertility that is characterized by a decreased serum testosterone-to-estradiol ratio. This ratio can be corrected by aromatase inhibition, resulting in a significant improvement in semen parameters in oligospermic patients.     

雌激素代谢酶CYP17、CYP19单核苷多态性与乳腺癌易感性的相关性分析

目的 初步探讨雌激素代谢酶CYP17和CYP19单核苷多态性与乳腺癌易感性的相关性.方法 采用聚合酶链反应-限制性片段长度多态性及短串联重复多态性方法,检测213例乳腺癌患者和430例正常对照CYP17、CYP19单核苷多态性分布.结果 乳腺癌患者雌激素代谢酶CYP17 A2/A2基因型频率为6.7%,高于对照组的2.4%(P＜0.05),CYP17变异等位基因A2病例组的频率为16.2%,亦明显高于对照组的10.6%(P＜0.05);乳腺癌患者雌激素代谢酶CYP19(TTTA)10等位基因病例组的频率为12.4%,对照组为8.2%,差异有统计学意义(P＜0.05).结论 CYP17单核苷多态性与乳腺癌易感性相关,A2/A2基因型增加乳腺癌风险;CYP19单核苷多态性与乳腺癌易感性亦相关,CYP19(TTTA)10等位基因变异升高与乳腺癌易感性高度相关.     

Polymorphisms in the aromatase gene predict areal BMD as a result of affected cortical bone size: the GOOD study.

The association between aromatase gene polymorphisms, bone parameters, and sex steroid levels was studied in 1068 men (18.9 +/- 0.6 years of age). Several aromatase gene polymorphisms were found to be associated with serum testosterone levels and cortical bone size but not with trabecular volumetric BMD. INTRODUCTION: Both testosterone and estrogens are important for the male skeleton. Aromatase, the product of the CYP19 gene, is the key enzyme in the conversion of testosterone to estradiol. A functional aromatase enzyme has been shown to be crucial for the normal development of the male skeleton. The role of genetic polymorphisms in the aromatase gene for trabecular volumetric BMD (vBMD) and cortical bone size has not previously been studied in men. MATERIALS AND METHODS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study consists of 1068 men (18.9 +/- 0.6 years of age). The TTTA repeat polymorphism (TTTAn) and three single nucleotide polymorphisms (SNPs), including the Val80 SNP, in the CYP19 gene, were analyzed. Serum levels of testosterone and estradiol were measured. Areal BMD (aBMD) was measured by DXA, whereas cortical and trabecular vBMD and cortical bone size were measured by pQCT. RESULTS: The TTTAn and the Val80 genotypes were independent predictors of aBMD of the radius, lumbar spine, total body, and cortical bone size (cortical cross-sectional area and thickness) of both the radius and tibia. In contrast, trabecular vBMD was not associated with CYP19 polymorphisms. Homozygosity for the long allele (>9 repeats) of the TTTAn and for the G allele of the Val80 SNP was associated with the highest aBMD and testosterone levels as well as with the greatest cortical bone size. Regression analyses indicated that the association with aBMD was mediated through affected cortical bone size. CONCLUSIONS: We showed, in a large well-characterized cohort of men at the age of peak bone mass, that several common aromatase polymorphisms are associated with cortical bone size but not with trabecular vBMD. One may speculate that affected CYP19 activity, resulting in altered testosterone levels during pubertal development, might contribute to the association between CYP19 polymorphisms and cortical bone size.