Nephronophthisis-associated ciliopathies

Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, represents the most frequent genetic cause of end-stage kidney disease in the first three decades of life. Contrary to polycystic kidney disease, NPHP shows normal or diminished kidney size, cysts are concentrated at the corticomedullary junction, and tubulointerstitial fibrosis is dominant. NPHP can be associated with retinitis pigmentosa (Senior-L?ken syndrome), liver fibrosis, and cerebellar vermis aplasia (Joubert syndrome) in approximately 10% of patients. Positional cloning of six novel genes (NPHP1 through 6) as mutated in NPHP and functional characterization of their encoded proteins have contributed to the concept of "ciliopathies." It has helped advance a new unifying theory of cystic kidney diseases. This theory states that the products of all genes that are mutated in cystic kidney diseases in humans, mice, or zebrafish are expressed in primary cilia or centrosomes of renal epithelial cells. Primary cilia are sensory organelles that connect mechanosensory, visual, osmotic, and other stimuli to mechanisms of cell-cycle control and epithelial cell polarity. The ciliary theory explains the multiple organ involvement in NPHP regarding retinitis pigmentosa, liver fibrosis, ataxia, situs inversus, and mental retardation. Mutations in NPHP genes cause defects in signaling mechanisms, including the noncanonical Wnt signaling pathway. The "ciliopathy" NPHP thereby is caused by defects in tissue differentiation and maintenance as a result of impaired processing of extracellular cues. Nephrocystins, the proteins that are encoded by NPHP genes, are highly conserved in evolution. Positional cloning of additional causative genes of NPHP will elucidate further signaling mechanisms that are involved, thereby establishing therapeutic approaches using animal models in mouse, zebrafish, and Caenorhabditis elegans.     

Ghrelin down-regulates proinflammatory cytokines in sepsis through activation of the vagus nerve

OBJECTIVE: To test the hypothesis that administration of ghrelin attenuates inflammatory responses in sepsis through vagal nerve stimulation. SUMMARY BACKGROUND DATA: Ghrelin has been demonstrated to possess multiple functions, including stimulation of the vagus nerve. Our recent study has shown that plasma levels of ghrelin were significantly reduced in sepsis; and ghrelin administration improved organ perfusion and function. However, it remained unknown whether ghrelin also decreases proinflammatory cytokines in sepsis and, if so, whether the down-regulatory effect of ghrelin is mediated by activation of the vagus nerve. METHODS: Male rats were subjected to sepsis by cecal ligation and puncture (CLP). At 5 hours after CLP, a bolus intravenous injection of 2 nmol ghrelin was followed by a continuous infusion of 12 nmol ghrelin via a primed 200-microL Alzet mini-pump for 15 hours. At 20 hours after CLP, plasma and peritoneal fluid levels of TNF-alpha and IL-6 were determined. The direct effect of ghrelin on cytokine production was studied using cultured normal rat Kupffer cells or peritoneal macrophages stimulated by lipopolysaccharide (LPS). In additional animals, vagotomy or sham vagotomy was performed in sham and septic animals immediately prior to ghrelin administration and cytokine levels were then measured. RESULTS: Ghrelin significantly reduced TNF-alpha and IL-6 levels in sepsis. In contrast, ghrelin did not inhibit TNF-alpha and IL-6 release from LPS-stimulated Kupffer cells or peritoneal macrophages. However, vagotomy, but not sham vagotomy, prevented ghrelin's down-regulatory effect on TNF-alpha and IL-6 production. CONCLUSIONS: Ghrelin down-regulates proinflammatory cytokines in sepsis through activation of the vagus nerve. Pharmacologic stimulation of the vagus nerve may offer a novel approach of anti-sepsis therapy.     

育精阴对雄性豚鼠免疫性不育的实验研究

目的　研究中药育精阴治疗免疫性不育的作用及其机理。方法　运用主动免疫法造成豚鼠实验性变态反应性睾丸炎 (EAO)模型 ,观察睾丸生精细胞和附睾尾部精子质量的变化。运用不同剂量育精阴灌胃 ,观察育精阴对生精上皮和附睾尾部精子质量的作用。结果　发现实验性变态反应性睾丸炎造成睾丸生精细胞退行性病变 ,附睾精子质量下降。育精阴可减轻和修复实验性变态反应对睾丸附睾的损伤 ,提高附睾精子质量。结论　育精阴对实验性变态反应性睾丸炎造成的免疫损伤有修复作用     

微创技术在腹腔镜胆囊切除术后黄疸诊治中的应用

目的：探讨微创技术在腹腔镜胆囊切除术（LC）后黄疸的诊断与治疗中的作用。方法：在微创观念指导下，对LC术后出现黄疸的患者运用内镜逆行胰胆管造影（ERCP）和内镜括约肌切开（EST）等微创技术进行诊断与治疗。结果：我院1998年8月至2001年5月间共行3160例LC手术，术后出现黄疸者5例，均先接受B超、ERCP检查，提示胆总管结石与胆总管末端狭窄，3例EST取石一次成功，1例首次EST取石失败后予保守治疗5天后再行ERCP与碎石治疗成功，1例因结石较多较大行开腹胆总管探查术。结论：对LC术后黄疸，在B超等检查排除明显胆道损伤和胆漏后，胆总管结石应首先考虑。ERCP可进一步明确诊断，EST取石或碎石这一微创技术治疗胆道细小结石伴有胆总管末端炎性狭窄引起的梗阻效果良好。     

Association of renal injury with nitric oxide deficiency in aged SHR: prevention by hypertension control with AT1 blockade

BACKGROUND: Aged spontaneously hypertensive rats (SHR) develop end-stage renal disease resembling that of uncontrolled essential hypertension in humans. Nitric oxide (NO) and angiotensin II (Ang II) play an important role in the regulation of blood pressure and the growth of vascular smooth muscle and renal mesangial cells. The relationship between renal NO system, Ang II activity and renal injury in aged SHR is not fully understood. METHODS: The 8-week-old SHR were randomized into losartan-treated (30 mg/kg/day for 55 weeks) and vehicle treated groups. The age-matched Wistar-Kyoto rats (WKY) served as controls. Renal histology and tissue expressions of endothelial and inducible NO synthases (eNOS and iNOS) and nitrotyrosine were examined at 63-weeks of age. RESULTS: Compared to the WKY group, untreated SHR showed severe hypertension, proteinuria, renal insufficiency, a twofold decrease in renal tissue eNOS and iNOS expressions and massive nitrotyrosine accumulation. This was associated with severe glomerulosclerosis, tubular atrophy and interstitial fibrosis. Losartan therapy normalized blood pressure, prevented proteinuria and renal insufficiency, abrogated the fall in renal eNOS and iNOS protein contents, mitigated renal nitrotyrosine accumulation, and prevented the histological abnormalities found in the untreated SHR. CONCLUSIONS: Aged SHR exhibit severe renal lesions with acquired NO deficiency that are prevented by hypertension control with AT1 blockade. These findings point to the possible role of NO deficiency in the pathogenesis of renal lesions in aged SHR.     

程序化流程腹腔镜胰十二指肠切除术的初步探讨

目的评价程序化流程设计进行腹腔镜胰十二指肠切除术(laparoscopic pancreaticoduodenectomy, LPD)的安全性和有效性。 方法选取2016年1月至2017年12月期间在中山大学孙逸仙纪念医院接受LPD且所有临床资料均完整的100例患者的病例资料,包括按照程序化流程进行手术的试验组50例、非程序化流程进行手术的对照组50例,分析两组患者围手术期的各项指标。 结果试验组与对照组患者的术前资料对比,无明显差异(P> 0.05)。相对于对照组,试验组手术时间明显缩短[(256.4 ± 50.64)min vs (298.5±87.23)min]、出血量明显减少[(84.5 ± 32.82)ml vs ( 218.9 ± 88.73)ml](P<0.05);术后并发生症发生率、术后住院时间等比较,未见明显统计学差异(P> 0.05)。 结论经过精准的手术前评估,程序化流程LPD技术可行,并能明显缩短手术时间,近期治疗效果良好。     

从肌耻骨孔区域的膜解剖平面来改进3D塑形补片

经腹腔镜腹膜前间隙腹股沟疝修补术因其创伤小、恢复快、术后麻木疼痛少,已成为当前主流术式。然而资料统计显示腹腔镜疝修补术没有使并发症和复发得到彻底消除。通过分析腹膜前间隙肌耻骨孔区域的膜解剖平面结构,得出当前3D塑形补片可能存在的缺陷,并尝试提出改进补片设计的方案。     

脱细胞基质生物补片与聚丙烯补片在腹股沟嵌顿疝治疗中应用效果的前瞻性随机对照研究

目的探讨脱细胞基质生物补片与聚丙烯补片在腹股沟嵌顿疝治疗中的临床效果及安全性。 方法采用前瞻性随机分组研究2013年5月至2015年5月,四川省人民医院60例腹股沟嵌顿疝患者作为研究对象。试验组采用脱细胞基质生物补片修补,对照组采用聚丙烯补片修补。对比分析2组患者手术时间、术后住院时间2组患者的复发率、手术切口感染、慢性疼痛、异物感等发生率情况。 结果试验组与对照组在一般资料、手术时间、术后住院时间方面比较,差异均无统计学意义（P>0.05）。术后随访3年,2组患者复发率、切口感染率、慢性疼痛发生率比较,差异均无统计学意义（P>0.05）。对照组患者术后异物感发生率高于研究组,对照组的血清肿发生率低于试验组,差异均有统计学意义（P<0.05）。 结论脱细胞基质生物补片治疗腹股沟嵌顿疝可降低术后异物感发生率,但不会增加复发率,具有一定的临床应用价值。     

The Effects of Laparoscopic Sleeve Gastrectomy on Obesity-Related Hypertriglyceridemia-Induced Acute Pancreatitis

Background

Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is a significant clinical problem and is characterized by high recurrence rate compared with non-HTG-AP. The objective of this study was to investigate the effects of laparoscopic sleeve gastrectomy (LSG) on obesity-related HTG-AP.

Methods

Twenty-nine patients with obesity-related HTG-AP were admitted to our hospital and treated with the conventional therapy or LSG surgery according to the wishes of patients. Clinical data and the recurrence rate of AP were collected at baseline and at four different time points (3, 6, 9, and 12 months) after the treatments for all patients.

Results

Of the 29 patients, 28 patients (19 patients with conventional therapy and 9 patients with LSG surgery) completed the 12-month follow-up. Clinical data and the severity scores of AP were comparable at baseline when the patients were admitted to the intensive care unit. The LSG group experienced a large weight loss (percent total weight loss, 26.87?±?1.44%; percent excess weight loss, 79.56?±?1.37%) and triglyceride reduction (from 15.77?±?1.02 to 1.36?±?0.09 mmol/L), and no recurrence was observed at 12 months after the surgery. In the conventional treatment group, however, body weight was not changed although triglyceride was significantly decreased (from 17.34?±?1.29 to 8.25?±?1.12 mmol/L), and more importantly, 47.4% of the patients had at least one recurrence of AP in 12 months after the treatment.

Conclusions

LSG might be an effective way to cure obesity-related HTG-induced AP since it prevents the recurrence of this disease. Further randomized studies will be needed to standardize this way of treatment.

     

髌骨爪结合克氏针张力带治疗髌骨下极粉碎性骨折

目的探讨髌骨爪结合克氏针张力带治疗髌骨下极粉碎性骨折的临床疗效。 方法回顾分析中国人民解放军第184医院骨科2008年08月至2014年10月收治髌骨下极粉碎性骨折53例,排除髌骨体骨折病例。给予单纯克氏针张力带治疗(克氏针组)28例,克氏针张力带结合髌骨爪治疗(髌骨爪结合组)25例。记录克氏针组及髌骨爪组的愈合时间、术后并发症及其末次随访的膝关节功能比较,统计学方法采用SPSS 13.0统计软件进行数据分析,骨折愈合时间采用独立样本t检验,两组的术后并发症及其末次随访的膝关节功能采用χ²检验, 结果53例均获得随访,随访时间平均(12.5±2.9)个月,髌骨爪结合组愈合时间(9.7±0.9)周早于克氏针组愈合时间(10.3±0.9)周,组间的差异有统计学意义(t ＝ 2.393,P <0.05),根据美国纽约特种外科医院(HSS)评分标准进行评价,克氏针组优10例,良9例,可7例,差2例,优良率67.9%;髌骨爪结合组优13例,良10例,可1例,差1例,优良率92%;两组差异有显著性意义(χ²＝ 4.681 ,P <0.05),克氏针组中1例术后出现创伤性关节炎。3例出现内固定松动,4例关节僵硬,髌骨爪结合组中1例术后创伤性关节炎,未出现内固定松动,两组并发症发生率差异有显著性意义(χ²＝ 4.045 ,P <0.05)。 结论采用髌骨爪结合克氏针张力带治疗髌骨下极粉碎性骨折可以早期膝关节功能锻炼,避免关节僵硬,疗效满意。