Phosphorylation of Ribosomal Protein S6 Mediates Mammalian Target of Rapamycin Complex 1–Induced Parathyroid Cell Proliferation in Secondary Hyperparathyroidism

Secondary hyperparathyroidism is characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation. However, the molecular pathways mediating the increased parathyroid cell proliferation remain undefined. Here, we found that the mTOR pathway was activated in the parathyroid of rats with secondary hyperparathyroidism induced by either chronic hypocalcemia or uremia, which was measured by increased phosphorylation of ribosomal protein S6 (rpS6), a downstream target of the mTOR pathway. This activation correlated with increased parathyroid cell proliferation. Inhibition of mTOR complex 1 by rapamycin decreased or prevented parathyroid cell proliferation in secondary hyperparathyroidism rats and in vitro in uremic rat parathyroid glands in organ culture. Knockin rpS6^p−/− mice, in which rpS6 cannot be phosphorylated because of substitution of all five phosphorylatable serines with alanines, had impaired PTH secretion after experimental uremia- or folic acid–induced AKI. Uremic rpS6^p−/− mice had no increase in parathyroid cell proliferation compared with a marked increase in uremic wild–type mice. These results underscore the importance of mTOR activation and rpS6 phosphorylation for the pathogenesis of secondary hyperparathyroidism and indicate that mTORC1 is a significant regulator of parathyroid cell proliferation through rpS6.     

Perioperative renal protection

AKI is the term to describe an abrupt reduction in kidney function and it replaces all previous terms such as ARF. The new definition for AKI needs to be validated by future research. Further development of biomarkers of AKI may aid in the early diagnosis and treatment of the syndrome. Mortality due to perioperative AKI often exceeds 50% and small changes in SCr correlate to significant increases in mortality. Preoperative risk factors for the development of AKI include a past history of renal dysfunction, elevated SCr, decreased cardiac performance, and cardiac and vascular surgery. Perioperative renal protection should focus on maintenance of euvolemia, preservation of adequate renal perfusion, and avoidance of any nephrotoxins. Intraoperative fluid management should be titrated to hemodynamic parameters and UO while avoiding excess fluid administration. The ideal fluid to administer is unknown as crystalloids and colloids each have their own advantages and disadvantages. Renal perfusion should be maintained by keeping MAP >65 mmHg and research may identify new techniques to monitor and individualize therapy to maintain renal perfusion. Recent data suggest that fenoldopam may alter outcome in patients with AKI.     

输尿管镜在婴儿肾结石合并急性肾后性肾功能衰竭手术治疗中的应用

目的 探讨输尿管镜在婴儿肾结石合并急性肾后性肾功能衰竭手术中的临床应用.方法双肾结石合并急性肾后性肾功能衰竭患儿13例.男11例,女2例.年龄5～12个月,平均9个月.其中双肾结石并肾积水5例,一侧肾结石合并对侧输尿管结石嵌顿3例,双侧输尿管结石嵌顿3例,双肾结石合并肾积水伴尿道结石2例.无尿1～3 d者11例,少尿5～10 d者2例.实验室检查血BUN及SCr均高于正常,高尿酸血症8例,高血钾症9例.13例尿pH均<6.5,平均5.5.KUB检查均未见阳性结石.B超检查13例均有不同程度肾积水,9例肾积水直径>2.5 cm.CT检查结石直径0.5～1.5 cm.均未行透析治疗.13例均行输尿管镜下溶石、碎石、置入双J管内引流术治疗. 结果 13例患儿术后24 h内出现多尿,出现多尿期平均时间为术后12 h,多尿期持续24～72 h,24 h尿量约800～2500 ml,术后48～96 h尿量逐渐恢复正常.术后1～5 d BUN及SCr均恢复正常,8例高尿酸血症患儿术后1～7 d血尿酸恢复正常,9例高钾血症患儿术后1～3 d血钾恢复正常.13例患儿留置双J管2～4周,复查B超,结石排净11例、结石变小2例. 结论 对肾结石合并急性肾后性肾功能衰竭要儿应用输尿管镜下腔内手术治疗,采用溶石、碎石,置入双J管内引流,可立即解除上尿路梗阻,恢复排尿,改善肾功能.具有安全有效、损伤小的优点.可作为婴儿肾结石合并急性肾后性肾功能衰竭手术解除梗阻的首选方法.     

肾盂内灌注碱性药物溶石治疗三聚氰胺所致婴儿双肾结石

目的 探讨经输尿管导管或肾造瘘管肾盂内直接灌注碱性药物溶石治疗三聚氰胺所致婴儿双肾结石的有效性和安全性. 方法双肾结石合并急性肾后性肾功能衰竭婴儿15例.年龄5～12个月,平均9个月.结石直径0.4～1.5 cm,平均0.8 cm.15例患儿均长期食用受三聚氰胺污染的奶粉,经影像学和实验室检查诊断为急性肾后性肾功能衰竭.13例经尿道输尿管镜下通过输尿管导管行肾盂内碱性药物灌洗,20 m1 5%NaHCO3于10 min内缓慢冲洗,然后置入双J管.2例经皮肾穿刺留置肾造瘘管,术后间歇碱性药物灌洗,100 ml 1.4%NaHCO3于4～6 h内持续低压滴注,1次/d,持续2周. 结果 15例患儿均成功实施碱性药物肾盂内灌洗溶石治疗.术后2～5 d尿量恢复正常,2～3 d SCr、BUN恢复正常.13例术中经输尿管导管直接肾盂内灌注5%NaHCO3者,术中均观察到大量混浊液体自输尿管口喷涌而出.术后2周复查CT,结石消失13例,结石直径缩d~>50%者2例. 结论 经输尿管导管或肾造瘘管进行肾盂内直接碱性药物化学溶石治疗三聚氰胺所致婴儿肾结石安全、有效.     

烧伤脓毒症发病机制与防治对策

Sepsis and septic shock as a result of an invasire infection are challenging problems in extensively burned patients, and frequently end in multiple organ dysfunction syndrome (MODS).It is of great significance to further elucidate the pathogenetic mechanisms, and to seek novel intervention strategies to prevent and treat sepsis/MODS secondary to severe bums. A more complete understanding of the pathogenetic mechanisms of postburn sepsis would certainly elicit a number of potential therapeutic strategies for it. It is our belief that compre hensive clinical measures for management of severe sepsis should include rapid, adequate fluid resuscitation for bum shock, early feeding, effective control of infection, early escharectomy, and reinforcement of organ support. Once bum wound sepsis occurs, prompt removal of infected necrotic tissue is the key procedure to ensure a successful result. Further study is necessary to determine the precise mechanisms of these protective effects and the clinical advantages for postburn sepsis using evidence-based methodology system.     

术前漱口预防全麻术后呼吸道感染的临床研究

目的探讨全麻插管患者术后呼吸道感染的预防方法。方法将 2 4 0例普外科行全麻插管手术患者随机分为对照组和观察组 ,各 12 0例。观察组术前 2d开始用漱口液在三餐前后及睡前漱口 ,7次 /d ;术后第 1天用漱口液行口腔护理 ;对照组术前不予漱口液漱口 ,术后第 1天常规用生理盐水棉球行口腔护理。两组于漱口前及术后第 1天分别行咽拭子培养。结果对照组与观察组术后咽试子培养结果比较 ,差异有显著性意义 (均P <0 .0 5 )。呼吸道感染、咳嗽咳痰发生率及其症状持续时间 ,观察组明显低于对照组 (均P <0 .0 1)。结论全麻患者术前采用漱口液漱口 ,可起到局部抑菌杀菌的作用 ,减少呼吸道感染的机会。     

急性胰腺炎肺损伤发病机制的研究进展

肺损伤是急性胰腺炎常见而严重的并发症之一，研究其发病机制有着重要的临床意义。本文复习相关文献，从胰酶、中性粒细胞、巨噬细胞、细胞因子以及肝脏Kupffer细胞几方面讨论引起急性胰腺炎合并肺损伤的发病机制，从而指导我们从病因的角度来防治急性胰腺炎合并肺损伤的发生发展。     

体外受精失败MII期人卵母细胞的免疫荧光研究

目的探讨体外受精中MII期人卵母细胞受精失败的原因。方法收集体外受精后24～48h仍未受精的MII期卵母细胞,进行免疫荧光染色和碘化丙啶(PI)复染,在荧光显微镜下对其失败原因进行分类。结果卵母细胞内未见精子的在常规体外受精(IVF)周期有55.8%,显著多于卵胞浆内单精子注射(ICSI)周期中的9.7%(P<0.01);卵母细胞活化失败两者分别为14.9%和58.1%,有显著性差异(P<0.01);原核形成和(或)迁移缺陷的在两者分别为25.3%和32.3%(P>0.05);其他异常两者分别为3.9%和0.0%。结论IVF中MII期卵母细胞的受精失败主要是缺乏精子的穿透,ICSI周期中的主要原因是卵母细胞活化不完全。     

肝脏体外灌流中直接灌流与间接灌流效果的比较研究

目的在体外肝脏灌流（ECLP）实施技术研究中，对直接灌流和间接灌流孰优孰劣一直存在争议。本实验拟就临床应用对这两种方法进行评价。方法实验动物供体均为普通健康长白猪，体重在20～30kg，雌雄不拘。一组受体是普通健康长白猪，标准与供体相同；另一组受体是普通健康狗，体重在20～30kg，雌雄不拘。随机分为2组，直接灌流受体为肝衰猪，间接灌流受体为肝衰狗：A组（直接灌流组，n=5）体外肝脏与受体间直接进行血液交换；B组（间接灌流组，72-4）体外肝脏用猪血液进行ECLP循环，受体血液自循环，两个循环间的血液通过中空纤维管进行物质交换。A、B两组进行ECLP灌流时间均为4h，肝衰时间为8h，8h后处死。观察体外肝脏和受体一般情况，体外肝脏的胆汁生成量、耗氧率等，受体的血氨、肝脏酶谱和血凝情况等指标。结果A、B两组在体外肝脏的胆汁生成量、耗氧率和受体方面均没有明显的差异（P〉0．05）。结论虽然直接灌注和间接灌注两者在体外肝脏的存活和灌注效果方面没有明显的差异，但考虑到间接灌注在异种灌注中具有伦理学压力较小的诸多优点，而临床应用又以异种灌注为主，故临床应用时仍推荐应用间接灌注。