VHL病一例报告并文献复习

目的 探讨von Hippel-Lindau(VHL)病的临床和影像学特点,提高对本病的认识.方法 VHL患者1例.患者男,50岁,因无痛性全程肉眼血尿伴视物模糊5个月入院.影像学及眼底镜检查诊断双肾多发性肿瘤,肾囊肿,胰腺囊肿,肝囊肿,右眼视网膜血管瘤.12年前有小脑血管母细胞瘤手术史,无家族史.结果 行左侧保留肾单位肿瘤切除术(肿瘤5枚),肿瘤最大约3.5cm×3.5 cm,病理报告肾多发性透明细胞癌.术后口服索尼替尼治疗.随访4个月,肾功能正常,右肾肿瘤缩小.结论 VHL病是一种家族性常染色体显性遗传性肿瘤病,病变表现为中枢神经系统血管母细胞瘤、内脏肿瘤和内脏多发囊肿等.全面的影像学检查是诊断和随访的重要手段.

Abstract：

Objective To investigate the clinical and imaging features of von Hippel-Lindau disease to raise awareness of the disease. Methods The clinical and imaging data of a case of VHL patient were analyzed retrospectively and discussed with relative literature review. The patient was a 50-year-old man, who was admitted with the chief complaints of painless gross hematuria and blurred vision for 5 months. Imaging data and ophthalmoscopy examination showed bilateral multiple renal tumors, renal cysts, pancreatic cysts, hepatic cysts and retinal angioma in his right eye. He suffered a surgical operation for his cerebellar hemangioblastoma 12 years ago without family history. Results The patient underwent nephron- sparing surgery (NSS) in the left kidney. Five renal tumors were removed, and the largest tumor was 3.5 cm× 3.5 cm. Postoperative oral administration of Sorafenib agents was applied. Followed up for 4 months, the renal function was normal and the right kidney tumor reduced. Pathology confirmed the diagnosis of multiple renal clear cell carcinoma. Conclusions VHL disease is a familial autosomal dominant hereditary syndrome, with the performance of hemangioblastorna in central nervous system, visceral tumors and multiple visceral cysts. Comprehensive imaging examination plays a major role in both the diagnosis and the follow-up of VHL disease.     

曲安奈德术中局部应用在降低LIDH术后早期神经根水肿反应性疼痛的对照研究

目的：通过对腰椎间盘突出症的病人术中神经根局部应用曲安奈德,对照未行该治疗组,比较评估术中应用曲安奈德对减轻术后早期神经根水肿反应性疼痛的疗效。方法：对2010年9月～2015年9月在我院腰椎间盘突出症患者185例,术中神经节给药组96 例和对照组89例。在行腰椎间盘髓核摘除术结束后缝合伤口前,实验组在神经根周围放入含有曲安奈德的明胶海绵。对照组:神经根周围放入不含任何药物的明胶海绵。对比两组发生神经根水肿反应的发生率,以及两组发生神经根水肿反应的患者术前、术后即刻、6h、12 h,1～12d腰臀部及手术侧下肢疼痛情况行 VAS 视觉评分,通过统计分析评估术中神经根局部应用曲安奈德对减少术后早期神经根水肿反应的作用。结果：两组术后神经根功能在术后即刻均获得良好的恢复,两组神经痛在水肿期均有不同程度的“反跳”,实验组“反跳”率(36.5%)明显低于对照组(57.3%),P<0.05,实验组的改善率的差别有统计学意义,且发生神经根水肿反应的两组中,实验组水肿期VAS评分明显低于对照组,具有显著性差异 (P＜0.05),而水肿前期及水肿后期,两组均可达到良好水平,且两组的VAS评分统计学无明显差别(P>0.05)。结论：腰椎间盘髓核摘除术中神经根周围放入含有曲安奈德的明胶海绵,操作简单、安全,能有效的减少腰椎间盘突出症术后早期神经根水肿反应性疼痛的发生率及减轻反应性疼痛的程度。     

放射性直肠炎的预后危险因素分析

目的探讨与放射性直肠炎预后相关的危险因素。方法对2007年8月至2010年2月期间收治的33例放射性直肠炎患者的临床疗效及生活质量进行随访以评价预后,并进一步通过回顾性分析不同预后患者临床资料的差异．寻找与预后相关的危险因素。结果33例患者的原发肿瘤包括宫颈癌22例、前列腺癌3例、卵巢癌2例、直肠癌2例、子宫内膜癌2例、宫颈癌合并卵巢癌1例、阴道癌1例。在收集到放疗资料的18例患者中,照射剂量为（61．3±12．9）Gy。接受放疗至出现放射性直肠炎症状的时间为（11．7±12．8）个月,均通过临床症状及结肠镜检查确诊。治疗方法包括药物保留灌肠11例．甲醛局部烧灼止血9例,手术治疗12例（为直肠阴道瘘、大出血、肠梗阻等严重并发症者．其中行病变肠管切除9例,单纯造瘘3例）,1例未行任何治疗。患者总的临床有效率75％,总体生活质量（63．79±20．92）分,预后良好者占75％;手术治疗的有效率为91．7％。性别为与预后相关的危险因素（P〈0．05）,而病变程度、治疗方法并非预后的危险因素（均P〉0．05）。结论性别是放射性直肠炎预后的危险因素：病变程度不同并不意味着预后不同：对出现严重并发症的患者采取手术治疗可明显改善其近期生活质量。     

RNA干扰靶向抑制磷脂酰肌醇3-激酶P85α蛋白表达对结直肠癌细胞周期和细胞凋亡的影响

目的探讨RNA干扰靶向抑制磷脂酰肌醇3-激酶（P13K）P85α蛋白表达对结直肠癌细胞周期与细胞凋亡的影响。方法设计4条shRNA干扰载体及1条阴性对照载体．分别稳定转染结直肠癌SW480细胞。采用Western blot筛选出对P13K P85α蛋白抑制效率最高的shRNA干扰片段．然后通过PI标记法和Annexin V—FITC标记法分别检测干扰后SW480细胞周期和细胞凋亡情况。结果转染shRNA／324后．SW480细胞P13K P85α蛋白降低最为显著．抑制率为90％。选择该干扰片段进行后续实验。干扰组与对照组SW480细胞的G1期细胞数量分别占（62．4±2．7）％和（51．2±3．5）％;S期细胞数量占（23．9±1．7）％和（34．1±3．4）％;氟尿嘧啶所诱导的细胞凋亡率为（11．1±3．7）％和（1．4±0．6）％;上述差异均有统计学意义（P〈0．05）。结论P13K P85α蛋白表达下降可引起结直肠癌SW480细胞周期阻滞,细胞凋亡增加：PI3K P85α可能成为结直肠癌基因治疗的新靶点。     

改良APACHE-Ⅱ评分对结直肠癌并急性肠梗阻患者术后并发症的预测价值

目的 探讨改良急性生理和慢性健康状态评价系统Ⅱ（APACHE-Ⅱ）对结直肠癌并急性肠梗阻患者术后并发症的预测价值.方法 回顾性分析92例结直肠癌并急性肠梗阻患者术后并发症情况,对传统APACHE-Ⅱ评分和改良APACHE-Ⅱ评分系统（将慢性健康指标中的严重器官功能不全或免疫损害改为梗阻时间和梗阻程度,并以此两项作为肠梗阻侵袭度）预测术后并发症的敏感度、特异度、准确性及约登指数进行比较,并通过绘制受试者工作特征曲线（ROC）来计算曲线下面积（AUC）.结果 92例患者术后有25例出现并发症（包括3例围手术期死亡病例）,并发症组APACHE-Ⅱ评分（13.72±4.24）、改良APACHE-Ⅱ评分（19.28±4.92）及肠梗阻侵袭度评分（5.56±2.20）均显著高于无并发症组（10.58±3.44、14.69±3.73和4.10±1.52,均P＜0.01）.改良APACHE-Ⅱ评分取最佳截点（20分）,其预测术后并发症的敏感度、特异度、准确性、约登指数及AUC分别为0.640、0.940、0.859、0.580和0.839,均高于传统APACHE-Ⅱ评分（以14分为最佳截点）,其上述指标分别为0.560、0.896、0.804、0.456和0.784.结论 将APACHE-Ⅱ评分系统增加肠梗阻侵袭度这一指标后,能更好地预测结直肠癌并急性肠梗阻患者的术后并发症.     

The critical role of the epidermal growth factor receptor in endochondral ossification

Loss of epidermal growth factor receptor (EGFR) activity in mice alters growth plate development, impairs endochondral ossification, and retards growth. However, the detailed mechanism by which EGFR regulates endochondral bone formation is unknown. Here, we show that administration of an EGFR-specific small-molecule inhibitor, gefitinib, into 1-month-old rats for 7 days produced profound defects in long bone growth plate cartilage characterized by epiphyseal growth plate thickening and massive accumulation of hypertrophic chondrocytes. Immunostaining demonstrated that growth plate chondrocytes express EGFR, but endothelial cells and osteoclasts show little to no expression. Gefitinib did not alter chondrocyte proliferation or differentiation and vascular invasion into the hypertrophic cartilage. However, osteoclast recruitment and differentiation at the chondro-osseous junction were attenuated owing to decreased RANKL expression in the growth plate. Moreover, gefitinib treatment inhibited the expression of matrix metalloproteinases (MMP-9, -13, and -14), increased the amount of collagen fibrils, and decreased degraded extracellular matrix products in the growth plate. In vitro, the EGFR ligand transforming growth factor α (TGF-α) strongly stimulated RANKL and MMPs expression and suppressed osteoprotegerin (OPG) expression in primary chondrocytes. In addition, a mouse model of cartilage-specific EGFR inactivation exhibited a similar phenotype of hypertrophic cartilage enlargement. Together our data demonstrate that EGFR signaling supports osteoclastogenesis at the chondro-osseous junction and promotes chondrogenic expression of MMPs in the growth plate. Therefore, we conclude that EGFR signaling plays an essential role in the remodeling of growth plate cartilage extracellular matrix into bone during endochondral ossification.     

The protective role of Smad7 in diabetic kidney disease: mechanism and therapeutic potential

OBJECTIVE

Although Smad3 has been considered as a downstream mediator of transforming growth factor-β (TGF-β) signaling in diabetes complications, the role of Smad7 in diabetes remains largely unclear. The current study tests the hypothesis that Smad7 may play a protective role and has therapeutic potential for diabetic kidney disease.

RESEARCH DESIGN AND METHODS

Protective role of Smad7 in diabetic kidney disease was examined in streptozotocin-induced diabetic mice that have Smad7 gene knockout (KO) and in diabetic rats given Smad7 gene transfer using an ultrasound-microbubble-mediated technique.

RESULTS

We found that mice deficient for Smad7 developed more severe diabetic kidney injury than wild-type mice as evidenced by a significant increase in microalbuminuria, renal fibrosis (collagen I, IV, and fibronectin), and renal inflammation (interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α], monocyte chemoattractant protein-1 [MCP-1], intracellular adhesion molecule-1 [ICAM-1], and macrophages). Further studies revealed that enhanced renal fibrosis and inflammation in Smad7 KO mice with diabetes were associated with increased activation of both TGF-β/Smad2/3 and nuclear factor-κB (NF-κB) signaling pathways. To develop a therapeutic potential for diabetic kidney disease, Smad7 gene was transferred into the kidney in diabetic rats by an ultrasound-microbubble-mediated technique. Although overexpression of renal Smad7 had no effect on levels of blood glucose, it significantly attenuated the development of microalbuminuria, TGF-β/Smad3-mediated renal fibrosis such as collagen I and IV and fibronectin accumulation and NF-κB/p65-driven renal inflammation including IL-1β, TNF-α, MCP-1, and ICAM-1 expression and macrophage infiltration in diabetic rats.

CONCLUSIONS

Smad7 plays a protective role in diabetic renal injury. Overexpression of Smad7 may represent a novel therapy for the diabetic kidney complication.Diabetic nephropathy is a major complication of diabetes (1–4). Approximately 20–40% of patients with type 1 or type 2 diabetes mellitus (DM) develop diabetic nephropathy (5,6). Diabetic nephropathy is characterized by excessive deposition of extracellular matrix (ECM) proteins in the mesangium and tubulointerstitium, thickness of basement membrane of the glomeruli, and loss of podocytes with the development of microalbuminuria and a decline of renal function (2,3,7). Both in vivo and in vitro studies have demonstrated that renal fibrosis and inflammation play an important role in the pathogenesis of diabetic kidney disease (2–4,7–10). Transforming growth factor-β (TGF-β) family is a crucial mediator in the development of diabetic nephropathy (11–15).It is now clear that after binding to its receptors, TGF-β signals through two critical downstream mediators, Smad2 and Smad3, to exert its biological activities such as ECM production. In addition, TGF-β₁ also induces an inhibitory Smad called Smad7, which negatively regulates activation of Smad2/3 by TGF-β receptor competition and degradation via the ubiquitin-proteasome degradation mechanism (16,17). Recent studies have demonstrated that overexpression of Smad7 is capable of inhibiting renal fibrosis and inflammation by blocking the activation of both TGF-β/Smad and nuclear factor-κB (NF-κB) signaling pathway (18–22). In contrast, deletion of Smad7 promotes renal fibrosis and inflammation (23), suggesting that Smad7 may be a key regulator and a therapeutic agent for renal fibrosis and inflammation (24). Although it has been reported that Smad3 is pathogenic in fibrosis including diabetic kidney disease (25,26), the role of Smad7 in diabetes complications remains unexplored, and it is unknown whether blockade of the TGF-β signaling pathway by Smad7 has therapeutic potential for diabetes complications. Thus, in the current study, we uncovered the role of Smad7 in diabetic kidney disease induced in Smad7 knockout (KO) mice and developed new therapeutic strategy for diabetic kidney complication by targeting the TGF-β/Smad pathway with ultrasound-microbubble-mediated Smad7 gene therapy.     

Comparison of effective inspired concentration of sevoflurane in preterm infants with different postconceptual ages

Objective: Screening examination for retinopathy of prematurity (ROP) is stressful and painful to the neonate. Sevoflurane has been used successfully in anesthesia for full‐term and premature neonates and has been recently used for pediatric outpatient procedures. In this study, we examined the effective inspired concentration of sevoflurane to prevent movement in response to stimulation of examination in 50% of patients (EIC50) of sevoflurane, as well as the response of sevoflurane to age in the preterm outpatients undergoing fundus examination. Methods: Preterm pediatric outpatients at different postconceptual ages (duration from the mother’s last menstrual period to the date when the examination for ROP was performed) with <44 weeks (group A) and 44–64 weeks (group B) undergoing fundus examination were included. SpO₂ and ECG were monitored in operation room. In the process of anesthetic induction, the oxygen flow rates were 3 l·min^?1, and subjects spontaneously breathed 6% sevoflurane by mask. The time to loss of movement was recorded as induction time. Six percent sevoflurane was inhaled continuously for the same duration, and then the inspired concentration of sevoflurane was adjusted to maintenance concentration. When no movement or crying was observed, the speculums were used to keep the eyelids open, and then the eye examinations were performed by the same ophthalmologist. During induction time and maintenance time, the occurrence of coughing, clenching, gross purposeful movement, breath holding or desaturation to SpO₂ < 95% was recorded. After completion of the procedure, patients were observed in the same room until spontaneous eye opening or verbalization occurred. Up and down method was used to determine subsequent maintenance concentration in each group. The initial maintenance concentration was 3%. The gradient of increase or decrease was 0.5%. If the preceding subject had not moved, the sevoflurane concentration was decreased by 0.5%; if the preceding subject had moved, the concentration was increased by 0.5%. When at least six independent alternations from no‐movement to movement were observed, test was terminated. Results: Twenty‐four pediatric outpatients completed the investigation in group A. The effective inspired concentration prevented movement in response to stimulation of examination in 50% of patients (EIC50) of sevoflurane was 2.5% in group A. Twenty‐seven patients completed the investigation and EIC50 values of sevoflurane were 3.0% in group B. The induction time in group A was significantly lower than that in group B. The gestational ages, anesthesia time, and awake time were similar in two groups. Conclusion: Anesthesia with inhaled sevoflurane by a face mask can be accomplished in preterm outpatients undergoing fundus examination without intubation and i.v. accession. The EIC50 is lower, and the induction time is shorter in smaller aged patients compared with those in older ones.     

Differential effects of advanced glycation end-products on renal tubular cell inflammation

Aim: The authors recently showed that advanced glycation end‐products (AGE) in the form of glycated albumin (GA) upregulated renal tubular expression of interleukin (IL)‐8 and soluble intercellular adhesion molecule‐1 (sICAM‐1), but not other important cytokines known to mediate diabetic nephropathy. This implies that other molecules such as the carbonyl intermediates of AGE or other modified protein lysine‐albumin may participate in diabetic tubular injury. Methods: Human proximal tubular epithelial cells (PTEC) were growth‐arrested and exposed to methylglyoxal (MG), MG‐bovine serum albumin (BSA)‐AGE, carboxymethyllysine (CML)‐BSA, AGE‐BSA or BSA with or without prior addition of rosiglitazone that was previously shown to attenuate the pro‐inflammatory effect of GA alone. Results: MG‐BSA‐AGE and AGE‐BSA upregulated tubular expression of connective tissue growth factor (CTGF), transforming growth factor (TGF)‐β, and vascular endothelial growth factor (VEGF), whereas CML‐BSA stimulated expression of IL‐6, CCL‐2, CTGF, TGF‐β and VEGF. These AGE compounds also activated nuclear factor (NF)‐κB and their effects were attenuated by pre‐incubation with anti‐RAGE antibody. MG and BSA did not affect the expression of any of these molecules. Rosiglitazone did not affect the in vitro biological effects of MG, MG‐BSA‐AGE, AGE‐BSA or CML‐BSA on PTEC. Conclusion: AGE exhibit differential inflammatory and fibrotic effects on PTEC via RAGE activation and NF‐κB signal transduction. Rosiglitazone had no effect on these responses. Further investigations on compounds that nullify the downstream effects of these AGE are warranted.     

肺癌介入治疗中体-肺分流的研究(附167例分析)

目的：了解原发性肺癌支气管动脉造影中出现的体肺分流征象及其对ＢＡＩ 疗效的影响。材料与方法：对１６７例原发性肺癌患者在介入治疗前行支气管动脉造影,注射造影剂后１ 、３ 、５ｓ 观察是否提前出现体肺分流。结果：１６７ 例中出现体肺分流者６６ 例,占３９ ．５ ％ ,体肺分流与肺癌的组织类型及肿块大小无明显关系,而与肿块的发生部位有关,中心型肺癌比周围型多。结论：体肺分流发生的形式中以支气管动脉与肺动脉者最多,分流发生的原因是因为肿瘤侵及肺动脉、奇静脉,又与瘤内新生血管相通,分流血管少不影响ＢＡＩ 疗效,多则影响疗效。