BACKGROUND & AIMS: :Twelve days after their common bile ducts had been ligated rats were icteric and their hepatic lymph nodes and lymph ducts were two or three times their normal size. Cannulation of the hepatic lymph ducts of these rats yielded bile-stained lymph which flowed at nine times its normal rate. As the lymph flowed, so the concentration of bilirubin in the blood declined; after 5 days the rats were no longer jaundiced, and by day 11 there were normal amounts of bilirubin in the blood. In another series it proved possible on seven occasions to insert the free end of the hepatic lymph cannula into the duodenum at the time that the bile was obstructed. Five of these animals showed no increase in serum bilirubin and remained in good condition until the experiments were terminated up to 61 days later. It seems that the effects of biliary obstruction can be mitigated by shunting the hepatic lymph into the intestine.

背景与目标： 结扎总胆管12天后，大鼠黄疸，肝淋巴结和淋巴结是正常大小的两到三倍。这些大鼠的肝淋巴管插管产生胆汁染色的淋巴，其流动速率是正常速率的9倍。随着淋巴的流动，血液中胆红素的浓度下降; 5天后，大鼠不再黄疸，到第11天，血液中的胆红素含量正常。在另一个系列中，有七次证明可以在胆汁阻塞时将肝淋巴插管的自由端插入十二指肠。其中五只动物的血清胆红素没有增加，并且保持良好状态，直到实验在61天后终止。似乎可以通过将肝淋巴分流到肠道来减轻胆道阻塞的影响。

BACKGROUND & AIMS: PURPOSE OF REVIEW:Obstruction of the outlet secondary to a recurrent bladder neck contracture postprostatectomy or cystectomy presents a reconstructive challenge combined with the goal of restoring normal lower urinary tract function. The majority of bladder neck contractures are responsive to urethral dilation or cold knife direct visual internal urethrotomy. Urethral stents and anastomotic urethroplasty have been used with increasing frequency to regain urethral continuity. In the postcystectomy patient, obstruction due to stricture must be differentiated from dysfunctional voiding - unfavorable pouch voiding mechanics, insufficient pouch pressure generation or failure of external sphincter relaxation. RECENT FINDINGS:Aggressive electrocautery resection with urethral stent placement and anastomotic urethroplasty are viable options for achieving patency after bladder neck obstruction. For those desirous of achieving a continent endpoint, artificial urinary sphincter should be planned as a second stage procedure after stabilization of the bladder neck. Creation of a catheterizable limb remains an option for the unreconstructable urethra. If augmentation cystoplasty is necessary due to storage pressure abnormalities, an appendicovesicostomy or reconfigured ileum segment is a reasonable method to achieve continence. SUMMARY:The incidence of recurrent obstruction due to tissue in-growth or stricture is similar between urethral stent placement and anastomotic urethroplasty, respectively. The high incontinence rate after either initial treatment should be expected and factored into the overall treatment plan.

背景与目标：

BACKGROUND & AIMS: :A new model of soft-tissue infection is used to investigate the effect of the local wound environment on the septic focus. Island pedicle flaps were raised on the buttock of 24 adult ewes and multiply inoculated with Staphylococcus aureus. Flaps with bacterial inoculation, without compromise of venous outflow, showed distal necrosis (mean +/- SEM percent of surface area, 25.8% +/- 8.6%) and developed septic foci with bacterial counts one log less than the amount injected. Flaps with inoculation and venous outflow obstruction underwent subtotal necrosis (mean percent of surface area, 73.3% +/- 11.2%) and had counts two logs higher than the nonobstructed flaps but without discrete septic foci. Flaps without inoculation, with or without venous obstruction, survived completely. Venous outflow obstruction is shown herein to potentiate tissue necrosis by raising bacterial counts in a septic focus and preventing defensive abscess formation by the host.

背景与目标： : 一种新的软组织感染模型用于研究局部伤口环境对脓毒症灶的影响。在24只成年母羊的臀部上举起岛状蒂皮瓣，并多次接种金黄色葡萄球菌。在不影响静脉流出的情况下接种细菌的皮瓣显示远端坏死 (平均表面积的/- SEM百分比，25.8%/- 8.6%)，并形成败血性病灶，细菌计数比注射量少1 log。接种和静脉流出阻塞的皮瓣发生了次全坏死 (平均表面积百分比，73.3%/- 11.2%)，其计数比未阻塞的皮瓣高两个对数，但没有离散的败血症灶。未经接种，有或没有静脉阻塞的皮瓣完全存活。本文显示静脉流出梗阻可通过增加败血症灶中的细菌计数并防止宿主形成防御性脓肿来增强组织坏死。

BACKGROUND & AIMS: :Renal fibrosis leads to end-stage renal disease, but antifibrotic drugs are difficult to develop. Chronic kidney disease often results in muscle wasting, and thereby increases morbidity and mortality. In this work, adeno-associated virus (AAV)-mediated overexpressing miR-29a was hypothesized to counteract renal fibrosis and muscle wasting through muscle-kidney crosstalk in unilateral ureteral obstruction (UUO) mice. miR-29a level was downregulated in the kidney and skeletal muscle of UUO mice. The secretion of exosome-encapsulated miR-29a increased in cultured skeletal muscle satellite cells and HEK293 renal cells after stimulation with serum from UUO mice. This result was confirmed by qPCR and microRNA deep sequencing in the serum exosomes of mice with obstructed ureters. A recombinant AAV-miR-29a was generated to overexpress miR-29a and injected into the tibialis anterior muscle of the mice 2 weeks before UUO surgery. AAV-miR-29a abrogated the UUO-induced upregulation of YY1 and myostatin in skeletal muscles. Renal fibrosis was also partially improved in the UUO mice with intramuscular AAV-miR-29a transduction. AAV-miR-29a overexpression reversed the increase in transforming growth factor β, fibronectin, alpha-smooth muscle actin, and collagen 1A1 and 4A1 levels in the kidney of UUO mice. AAV-green fluorescent protein was applied to trace the AAV route in vivo, and fluorescence was significantly visible in the injected/uninjected muscles and in the kidneys. In conclusion, intramuscular AAV-miR-29a injection attenuates muscle wasting and ameliorates renal fibrosis by downregulating several fibrotic-related proteins in UUO mice.

背景与目标： : 肾脏纤维化导致终末期肾脏疾病，但抗纤维化药物很难开发。慢性肾脏疾病通常会导致肌肉消瘦，从而增加发病率和死亡率。在这项工作中，假设腺相关病毒 (AAV) 介导的过表达miR-29a可通过单侧输尿管梗阻 (UUO) 小鼠的肌肉-肾脏串扰来抵消肾脏纤维化和肌肉萎缩。UUO小鼠肾脏和骨骼肌的miR-29a水平下调。用UUO小鼠血清刺激后，培养的骨骼肌卫星细胞和HEK293肾细胞中外泌体包裹miR-29a的分泌增加。通过qPCR和microRNA深度测序在输尿管阻塞小鼠的血清外泌体中证实了这一结果。产生重组AAV-miR-29a以过表达miR-29a，并在UUO手术前2周将其注射到小鼠的胫前肌中。AAV-miR-29a消除了UUO诱导的骨骼肌中YY1和肌肉生长抑制素的上调。肌内AAV-miR-29a转导的UUO小鼠的肾纤维化也得到部分改善。AAV-miR-29a过表达逆转了UUO小鼠肾脏中转化生长因子 β，纤连蛋白，α-平滑肌肌动蛋白以及胶原蛋白1A1和4A1水平的增加。应用AAV-绿色荧光蛋白在体内追踪AAV途径，在注射/未注射的肌肉和肾脏中显着可见荧光。总之，肌内AAV-miR-29a注射通过下调UUO小鼠的几种纤维化相关蛋白来减轻肌肉萎缩并改善肾脏纤维化。

BACKGROUND & AIMS: :In experimental small bowel obstruction an increased proportion of smooth endoplasmic reticulum and an increased number of lysosomes were seen in many liver cells. The occurrence of cytoplasmic vacuoles as well as the glycogen depletion were not pathognomonic and in the toxic pathogenesis the ultrastructural damage in the liver was only of a low degree and can be explained as a reactive (e.g. detoxication) phenomenon. The increase of plasma corticosterone content (stress reaction) differed only slightly from that of the controls, but a severe disturbance of fluid balance (increase of hematocrit and decrease of serum Na+ and C1-) and circulation failure were the more conspicuous findings, compared to toxic liver cell disturbance in the pathogenesis of small bowel obstruction.

背景与目标： : 在实验性小肠梗阻中，在许多肝细胞中观察到光滑内质网的比例增加和溶酶体数量增加。细胞质空泡的发生以及糖原的耗竭不是病理性的，在毒性发病机理中，肝脏的超微结构损伤程度较低，可以解释为反应性 (例如解毒) 现象。血浆皮质酮含量 (应激反应) 的增加与对照组仅略有不同，但更明显的是体液平衡严重紊乱 (血细胞比容增加，血清Na和C1-降低) 和循环衰竭。在小肠梗阻的发病机理中与毒性肝细胞紊乱相比。

BACKGROUND & AIMS: PROBLEM:We investigated whether deranged nitric oxide synthase (NOS) and neuropeptide Y (NPY) expression is detectable in the stenotic segments of patients with congenital ureteropelvic junction obstruction. METHODS:Using real-time reverse transcription-polymerase chain reaction (RT-PCR), we quantified mRNA amounts of NPY, neuronal (n), endothelial (e) and inducible (i) NOS in the stenotic segments of 20 patients with congenital ureteropelvic junction obstruction (aged 5.1+/-7.0 years) and of 21 unaffected controls (aged 23.5+/-24.2 years). Additionally, mRNAs of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), smooth muscle alpha-actin (Smactin), endothelial cell marker (CD31), and protein gene product 9.5 (PGP 9.5) were evaluated. Immunohistochemistry was made for NPY, nNOS, eNOS, iNOS, PGP 9.5, and CD 31. RESULTS:The mRNA of nNOS was significantly reduced in the obstructed junctions when related to the mRNAs of Smactin (P < 0.001) or GAPDH (P < 0.05), respectively. A significant reduction was also obtained for eNOS mRNA when standardized to CD31 (P < 0.05), GAPDH or Smactin mRNA (P < 0.05, and P < 0.001, respectively). NPY, PGP 9.5 and iNOS mRNAs were found in comparable quantities in both groups. In the stenotic segments, Smactin mRNA level was about twofold higher than in our control specimens, as shown by the lower CT values for the patients in real-time PCR (16.9+/-2.0 vs 17.9+/-2.6, P < 0.05). Furthermore, Smactin, nNOS, iNOS, eNOS, and NPY mRNA levels in specimens of unaffected ureteropelvic junctions were independent of age. Major differences between control and stenotic tissues were detected by immunohistochemistry: There was a dramatic reduction of innervation density as evidenced by nNOS and NPY labeling. CONCLUSION:Taken together, we found alterations in NOS gene expression and NPY innervation in tissue specimens of patients with congenital ureteropelvic junction obstruction.

背景与目标：

BACKGROUND & AIMS: :The effects of variation in speaking rate on relative nasal airflow (percent nasal flow) and on the perception of nasality were examined. In addition, the effects of gender and speech rate elicitation techniques (metronome-controlled, self-controlled) were examined. Nineteen normal speakers each produced a stimulus phrase containing nonnasal sounds. Oral and nasal airflows were measured using the Rothenberg aerodynamic system. Results indicated that percent nasal flow and perception of nasality were both greater at slow speaking rates compared to normal and fast rates. Males were perceived as more nasal than females. The metronome-controlled rates were associated with greater nasality than the self-controlled rates. Discussion focuses on physiological correlates to these findings.

背景与目标： : 检查了说话率的变化对相对鼻气流 (鼻气流百分比) 和对鼻知觉的影响。此外，还检查了性别和言语速率激发技术 (节拍器控制，自我控制) 的影响。19名普通演讲者各自产生一个包含非鼻音的刺激短语。使用Rothenberg空气动力学系统测量口腔和鼻气流。结果表明，与正常和快速速度相比，慢速说话时的鼻流量百分比和鼻感觉均更高。男性被认为比女性更鼻音。节拍器控制率比自我控制率更高。讨论的重点是与这些发现相关的生理学。

BACKGROUND & AIMS: BACKGROUND/AIMS:Few studies have compared endoscopic biliary stenting and endoscopic nasobiliary drainage for preoperative biliary drainage in patients with malignant distal biliary obstruction. We aimed to evaluate their safety and efficacy in such patients awaiting pancreaticoduodenectomy. METHODOLOGY:Seventy-six of 80 patients (40 with pancreatic cancer, 26 with distal bile duct cancer, and 14 with ampullary cancer) who underwent endoscopic preoperative biliary drainage were included, and we evaluated whether endoscopic biliary stenting or endoscopic nasobiliary drainage provided a safer and more effective drainage for patients awaiting pancreaticoduodenectomy. We also determined whether the type of cancer influenced tube dysfunction. RESULTS:No significant differences in the overall rate of catheter-related complications, the rate of tube dysfunction, or the median interval from preoperative biliary drainage to the time of tube dysfunction were observed between the two groups. Tube dysfunction was observed significantly more frequently in patients with pancreatic cancer than in those with distal bile duct or ampullary cancer. CONCLUSIONS:Both endoscopic biliary stenting and endoscopic nasobiliary drainage provided safe and effective drainage for patients awaiting pancreaticoduodenectomy. Tube dysfunction was associated with preoperative biliary drainage significantly earlier in patients with pancreatic cancer than in those with distal bile duct cancer or ampullary cancer.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Presence of microvascular obstruction (MVO) derived from cardiac magnetic resonance (CMR) imaging is among the strongest outcome predictors after ST-segment elevation myocardial infarction (STEMI). We aimed to investigate the comparative predictive values of different biomarkers for the occurrence of MVO in a large cohort of reperfused STEMI patients. METHODS:This study included 128 STEMI patients. CMR imaging was performed within the first week after infarction to assess infarct characteristics, including MVO. Admission and peak concentrations of high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase (CK), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine transaminase (ALT) were measured. RESULTS:MVO was detected in 69 patients (54%). hs-cTnT, CK, hs-CRP, LDH, AST and ALT peak concentrations showed similar prognostic value for the prediction of MVO (area under the curve (AUC) = 0.77, 0.77, 0.68, 0.79, 0.78 and 0.73, all p > 0.05), whereas the prognostic utility of NT-proBNP was weakly lower (AUC = 0.64, p < 0.05). Combination of these biomarkers did not increase predictive utility compared to hs-cTnT alone (p = 0.349). CONCLUSIONS:hs-cTnT, CK, hs-CRP, LDH, AST and ALT peak concentrations provided similar prognostic value for the prediction of MVO. The prognostic utility of NT-proBNP was lower. Combining these biomarkers could not further improve predictive utility compared to hs-cTnT alone.

背景与目标：

BACKGROUND & AIMS: :We report a case about a neonate who died of severe subaortic stenosis due to a giant vascular dilation of the left ventricular outflow tract. We emphasize the fatal result of this benign lesion and make differential diagnosis with haemangiomas and valvular blood cysts.

背景与目标： : 我们报告了一例新生儿，该新生儿因左心室流出道的巨大血管扩张而死于严重的主动脉下狭窄。我们强调这种良性病变的致命结果，并与血管瘤和瓣膜性血囊肿鉴别诊断疾病。

BACKGROUND & AIMS: :We investigated the relationship between the reversibility of airflow limitation, the concentration of nitric oxide (NO) in exhaled air, and the inflammatory cells in the sputum of patients with stable chronic obstructive pulmonary disease (COPD). We examined nine normal healthy control subjects and 20 nonatopic patients with COPD. Ten patients had no reversibility of airflow limitation (increase in FEV(1) of < 12% and < 200 ml after 200 microg of inhaled salbutamol), and 10 patients had partial reversibility of airflow limitation (increase in FEV(1) of < 12% but > 200 ml after 200 microg of inhaled salbutamol). Exhaled NO levels were higher in COPD patients with partial reversibility of airflow limitation than in those with no reversibility of airflow limitation (median 24 [interquartile range 15.3 to 32] ppb versus 8.9 [4.6 to 14.7] ppb; p < 0.01). Compared with healthy control subjects, only COPD patients with partial reversibility of airflow limitation had increased concentrations of sputum eosinophils. We conclude that, in patients with stable COPD, even a partial bronchodilator response to inhaled salbutamol is associated with increased exhaled NO and sputum eosinophilia, suggesting that these patients may have a different response to treatment than do those without reversible airflow limitation.

背景与目标： : 我们研究了稳定的慢性阻塞性肺疾病 (COPD) 患者气流受限的可逆性，呼出空气中一氧化氮 (NO) 的浓度与痰液中炎症细胞之间的关系。我们检查了9名正常健康对照受试者和20名COPD非特应性患者。10例患者没有气流限制的可逆性 (吸入沙丁胺醇200微克后FEV(1) 增加 <12% 和 <200毫升)，10例患者有气流限制的部分可逆性 (吸入沙丁胺醇200微克后FEV(1) 增加 <12% 但> 200毫升)。在具有部分气流受限可逆性的COPD患者中，呼出的NO水平高于没有气流受限可逆性的患者 (中位数24 [四分位距15.3 32] ppb与8.9 [4.6至14.7] ppb; p <0.01)。与健康对照组相比，只有气流受限部分可逆性的COPD患者痰嗜酸性粒细胞浓度升高。我们得出的结论是，在稳定期COPD患者中，即使对吸入沙丁胺醇的部分支气管扩张剂反应也与呼出气NO和痰嗜酸性粒细胞增多有关，这表明这些患者对治疗的反应可能与没有可逆气流受限的患者不同。

BACKGROUND & AIMS: OBJECTIVE:To report our experience with TURED in infertile men with EDO associated with abnormal development of the mesonephric or Wolffian duct, causing a contemporary malformation of the ipsilateral upper urinary tract. DESIGN:Retrospective clinical study. SETTING:Infertile men in an hospital environment. PATIENT(S):Seven patients affected by Zinner syndrome, from March to September 2005, were selected. INTERVENTION(S):Underwent TURED. MAIN OUTCOME MEASURE(S):Semen analysis, endocrine profile, transrectal ultrasonography and seminal vesicles aspiration, excretory urography, computerized tomography (CT), or magnetic resonance imaging (MRI). RESULT(S):Before surgery, the patients experienced a decreased intensity and force of ejaculation and a low motile sperm count. The detection of the ipsilateral upper urinary tract malformation by the patients was incidental. After surgery, all patients reported having a projectile ejaculation, an increase in the average postoperative volume, and of the total motile sperm count. CONCLUSION(S):A seminal vesicle cyst combined with ipsilateral renal agenesis, described as Zinner syndrome, is a rare urological anomaly. It is frequently asymptomatic or else characterized by infertility, symptoms of bladder irritation, or pain in the scrotum and perineum. In selected patients, TURED can improve semen quality with subsequent ability to impregnate. The upper urinary tract malformation should be treated in symptomatic cases only.

背景与目标：

BACKGROUND & AIMS: PURPOSE:Partial bladder outlet obstruction (PBOO) results in marked biochemical alterations in the bladder. In this study, we focused on comparison of thapsigargin sensitive sarco/endoplasmic reticulum Ca(2+) ATPase activity (SERCA) and Citrate Synthase after short term PBOO in young versus old rabbits. MATERIALS AND METHODS:A total of 20 young and 20 mature male rabbits were divided into 4 sub-groups of 5 rabbits each (4 obstructed and 1 sham-control rabbit). The rabbits in the groups were evaluated after 1, 3, 7, and 14 days of obstruction, respectively. The activities of SERCA and citrate synthase were examined as markers for sarcoplasmic reticular calcium storage and release and mitochondrial function, respectively. RESULTS:The SERCA activity of bladder body smooth muscle in the young animals increased at 7 and 14 days. For the old rabbits, the SERCA activity decreased significantly by 1 day and remained this level throughout the course of obstruction, and was significantly lower than young at all time periods. The citrate synthase activity in the young animals decreased over the 1-7 days, and then returned toward control level by 14 days following obstruction. In the old animals, citrate synthase activity of bladder body smooth muscle progressively decreased over the course of the study, and was significantly lower in the old than the young animals after 14 days obstructed. CONCLUSION:The urinary bladders of the young rabbits have a considerable greater ability to adapt to PBOO than do those of the old rabbits. The deterioration of mitochondrial and SR function may be important mechanisms underlying geriatric voiding dysfunction.

背景与目标：

BACKGROUND & AIMS: :Uncovering new therapeutic targets for renal fibrosis holds promise for the treatment of chronic kidney diseases. Bromodomain and extra-terminal (BET) protein inhibitors have been shown to effectively ameliorate pathological fibrotic responses. However, the pharmacological effects and underlying mechanisms of these inhibitors in renal fibrosis remain elusive. In this study, we determined that the inhibition of Brd4, a BET family member, with a selective potent chemical inhibitor, JQ1, could prevent the development of renal fibrosis and block the progression of fibrosis in rats that have undergone unilateral ureteral obstruction (UUO). Inhibiting Brd4 with either JQ1 or genetic knockdown resulted in decreased expression of fibrotic genes such as α-smooth muscle actin, collagen IV and fibronectin both in UUO-induced fibrosis and upon TGF-β1 stimulation in HK-2 cells. Brd4 inhibition also suppressed the oxidative stress induced by UUO in vivo or by TGF-β1 in HK-2 cells. Moreover, Nox4, which is constitutively active in renal cells and is involved in the generation of hydrogen peroxide, was up-regulated during UUO-mediated fibrosis and induced by TGF-β1 in HK-2 cells, and this up-regulation could be blunted by Brd4 inhibition. Consistently, Nox4-mediated ROS generation and fibrotic gene expression were attenuated upon Brd4 inhibition. Further, the transcriptional activity of Nox4 was suppressed by JQ1 or siRNA against Brd4. Additionally, Smad3 and ERK1/2 phosphorylation, which are upstream signals of Nox4 expression, were inhibited both in JQ1-administered UUO rats and Brd4-inhibited HK-2 cells. In conclusion, these results indicated that the inhibition of Brd4 might protect against renal fibrosis by blocking the TGF-β-Nox4-ROS-fibrosis axis, suggesting that Brd4 could be a promising therapeutic target.

背景与目标： : 发现肾脏纤维化的新治疗靶点有望治疗慢性肾脏疾病。溴结构域和末端外 (BET) 蛋白抑制剂已被证明可以有效改善病理性纤维化反应。然而，这些抑制剂在肾纤维化中的药理作用和潜在机制仍然难以捉摸。在这项研究中，我们确定BET家族成员Brd4与选择性强效化学抑制剂JQ1的抑制作用可以防止发生单侧输尿管梗阻 (UUO) 的大鼠肾脏纤维化的发展并阻断纤维化的进展。在UUO诱导的纤维化和TGF-β1刺激HK-2细胞中，用JQ1或基因敲除抑制Brd4导致纤维化基因如 α-平滑肌肌动蛋白，ⅳ 型胶原和纤连蛋白的表达降低。Brd4抑制也抑制了UUO在体内或TGF-β1在HK-2细胞中诱导的氧化应激。此外，Nox4在肾细胞中具有组成性活性并参与过氧化氢的产生，在UUO介导的纤维化过程中被上调，并由TGF-β1在HK-2细胞中诱导，这种上调可能被Brd4抑制抑制。一致地，Nox4-mediated ROS的产生和纤维化基因表达在Brd4抑制下减弱。此外，针对brd4的JQ1或siRNA抑制了Nox4的转录活性。此外，作为Nox4表达的上游信号的Smad3和ERK1/2磷酸化在JQ1-administered UUO大鼠和Brd4-inhibited HK-2细胞中均被抑制。总之，这些结果表明，Brd4的抑制可能通过阻断tgf-β-nox4-ros纤维化轴来预防肾脏纤维化，这表明Brd4可能是一个有希望的治疗靶标。

BACKGROUND & AIMS: -2

背景与目标： -2