Elucidating the phenomenon of HESC-derived RPE: anatomy of cell genesis, expansion and retinal transplantation

Healthy Retinal Pigment Epithelium (RPE) cells are required for proper visual function and the phenomenon of RPE derivation from Human Embryonic Stem Cells (HESC) holds great potential for the treatment of retinal diseases. However, little is known about formation, expansion and expression profile of RPE-like cells derived from HESC (HESC-RPE). By studying the genesis of pigmented foci we identified OTX1/2-positive cell types as potential HESC-RPE precursors. When pigmented foci were excised from culture, HESC-RPE expanded to form extensive monolayers, with pigmented cells at the leading edge assuming a precursor role: de-pigmenting, proliferating, expressing keratin 8 and subsequently re-differentiating. As they expanded and differentiated in vitro, HESC-RPE expressed markers of both developing and mature RPE cells which included OTX1/2, Pax6, PMEL17 and at low levels, RPE65. In vitro, without signals from a developing retinal environment, HESC-RPE could produce regular, polarised monolayers with developmentally important apical and basal features. Following transplantation of HESC-RPE into the degenerating retinal environment of Royal College of Surgeons (RCS) dystrophic rats, the cells survived in the subretinal space, where they maintained low levels of RPE65 expression and remained out of the cell cycle. The HESC-RPE cells responded to the in vivo environment by downregulating Pax6, while maintaining expression of other markers. The presence of rhodopsin-positive material within grafted HESC-RPE indicates that in the future, homogenous transplants of this cell type may be capable of supporting visual function following retinal dystrophy.     

一家三代同患遗传性对称性色素异常症4例

先证者男,7岁,双手及双足部出现色素减退伴色素沉着斑7年,诊断为遗传性对称性色素异常症。家族三代14人中共有4例患该病,病程及症状相同。     

Rokitansky-Aschoff Sinuses of the Gallbladder are Associated with Black Pigment Gallstone Formation: A Scanning Electron Microscopy Study

Rokitansky-Aschoff sinuses are the result of hyperplasia and herniation of epithelial cells through the fibromuscular layer of the gallbladder wall and are usually referred to as adenomyomatosis. The role of this study is to demonstrate that Rokitansky-Aschoff sinuses of the gallbladder are a risk factor for the formation of black pigment gallstones. A total of 179 removed gallbladders, were hystologically examinated. Sixty-four of the 179 consecutive cholecystomized patients had typical adenomyomatosis. Thirty-eight of the 64 patients with adenomyomatosis had black pigment gallstones, alone ( n =22) or in association with single ( n =12) or multiple ( n =4) cholesterol gallstones in the same gallbladder. Twelve of these patients did not have the typical risk factors for black stones (hemolysis, cirrhoses, gastrectomy, etc). Gallstones were examined by infrared spectroscopy and X-ray diffractometry. In addition, in a subset of 14 patients, the gallstones and the gallbladder wall were examined by scanning electron microscopy. At least in the initial phases of formation, Rokitansky-Aschoff sinuses were found close to small intraparietal vessels and sometimes they contained black pigment microstones. After the fourth to fifth decades of life, black gallstones can be found in the Rokitansky-Aschoff sinuses and in the main gallbladder lumen. Black pigment gallstones can form in Rokitansky-Aschoff sinuses of the gallbladder in absence of the typical risk factors for bilirubin suprasaturation of bile.     

Ceftriaxone‐associated biliary pseudolithiasis in children: do we know enough?

Ceftriaxone is an antibiotic agent frequently used in paediatric hospital practice for the treatment of severe bacterial infections. The use of this agent can result in cholelithiasis and/or biliary sludge, more commonly in children than in adults. This systematic review was aimed at analysing available literature concerning ceftriaxone‐associated biliary pseudolithiasis in paediatric patients, with a special emphasis on the clinical aspects. A literature analysis was performed using Medline and Embase electronic databases (articles published in English up to December 2019), with the search terms and combinations as follows:’ceftriaxone’, ‘cholelithiasis’, ‘biliary sludge’ ‘gallstones’ ‘neonates’ ‘children’ ‘clinical aspects’ ‘management’. Several case reports, case series and prospective/retrospective studies have documented a relationship between ceftriaxone treatment and biliary pseudolithiasis in the paediatric population, even though literature data regarding neonates and infants are scarce. Ceftriaxone‐associated biliary pseudolithiasis is dose‐dependent and usually asymptomatic but, sometimes, it may present with abdominal pain, nausea and emesis. Abdominal ultrasonography should be performed when this complication is suspected. Generally, ceftriaxone‐associated cholelithiasis resolves over a variable period of time (days to months) after cessation of therapy. Therefore, a conservative approach to this condition is advocated, but a prolonged follow‐up may be necessary. A personalized assessment of factors predisposing to ceftriaxone‐associated biliary pseudolithiasis before prescribing the drug can allow to minimize the risk of developing it, with significant advantages in terms of human and economic costs.     

原发性胆囊癌与胆囊结石（附84例分析）

本文分析作者收治的８４例胆囊癌的临床特点并结合文献探讨胆囊结石的关系。目前尚无证据说明胆囊结石是胆囊癌的致癌因，但它在成癌过程中很可能起着促进作用。年龄超过５０岁、女性、合并胆囊炎或接触化学致癌物质可以认为是胆囊结石者易患胆囊癌的高危因素。在目前，早期诊断胆囊癌依然十分困难，治疗预后恶劣的情况下，对于具有高危因素者如不能确认胆囊形态正常，施行预防性胆囊切除是合理的。     

Gallstones at chronic spontaneous urticaria patients: A retrospective clinical study

Chronic spontaneous urticaria (CSU) is a chronic, inflammatory skin disease can be triggered by many factors such as inflammatory process. To assess accompanying gallstone in CSU patients and to evaluate laboratory test results. We retrospectivelyscanned the files of the 108 patients with CSU who had been diagnosed CSU in September 2017–September 2019. Accompanied gallstone cases by detecting transabdominal ultrasound (TUS) or were 11 patients. Nine patients had also had cholecystectomy history. We seperated these 20 patients as Group A than the rest. WBC count is 9.38 ± 2.37 in Group A and 8.03 ± 2.04 in Group B. Platelet count was also differ between two groups significantly (Group A = 328.70 ± 85.62 × 10³/mm³ vs. Group B = 287.12 ± 72.77 × 10³/mm³). Neutrophil count was more in Group A (5.87 ± 1.65) than Group B (4.76 ± 1.75). Gallstone history of family was significantly higher in Group A (n = 12 positive/8 negative) than Group B. These findings were significant statistically p < .05. CSU can be associated with inflammation and gallstones. It is needed to perform further investigations to detect these relations and pathways.     

Gastric outlet obstruction by a lost gallstone: Case report and literature review

IntroductionSpilled gallstones from a laparoscopic cholecystectomy can be a source of significant morbidity, most commonly causing abscesses and fistulae. Preventative measures for loss, careful removal during the initial surgery, and good documentation of any concern for remaining intraperitoneal stones needs to be performed with the initial surgery.Case reportAn 80-year-old male with a history of complicated biliary disease resulting in a cholecystectomy presented to general surgery clinic with increasing symptoms of gastric outlet obstruction. CT imaging was concerning for a malignant process despite negative biopsies. A distal gastrectomy and Billroth II reconstruction was performed and final pathology showed dense inflammation with a single calcified stone incarcerated within the gastric wall of the inflamed pylorus and no malignancy.DiscussionStones lost during laparoscopic cholecystectomy are not innocuous and preventative measures for loss, careful removal during the initial surgery, and good documentation of any concern for remaining intraperitoneal stones.ConclusionThis is the first case of gastric outlet obstruction caused by an intramural obstruction of the pylorus from a spilled gallstone during a laparoscopic cholecystectomy and subsequent inflammation. This is an etiology that must be considered in new cases of gastric outlet obstruction and can mimic malignancy.     

重组色素上皮细胞衍生因子的制备及其对脑胶质瘤血管新生的影响

目的 用大肠杆菌表达色素上皮细胞衍生因子(PEDF)，及评价其在脑胶质瘤血管新生中的作用。方法 构建pET41／PEDF表达载体，用金属亲和层析(His Tag)和阴离子交换层析纯化重组蛋白，并以管腔形成试验验证重组蛋白活性。同时，采用酶联免疫吸附试验(ELISA)测定血管内皮细胞生长因子(VEGF)与血小板反应素-1(TSP-1)的变化。结果 用基因工程手段获得终产量为3．8mg／L，可抑制内皮细胞管腔形成的PEDF蛋白；PEDF可下调VEGF(减少1．8倍)和上调TSP-1(增高5．3倍)的表达。结论 PEDF可能是抑制脑胶质瘤新生血管形成的主要因素。     

Clinical and laboratory manifestations of congenital dyserythropoietic anemia type I in young adults

OBJECTIVES: Congenital dyserythropoietic anemia (CDA) type I is a rare autosomal recessive macrocytic anemia whose natural history is not well documented. The aim of the present study was to evaluate the clinical picture of the disease in young adults. METHODS: The study sample consisted of 17 patients of mean age 11.9 +/- 5.4 yr (range 18-33 yr) and one older patient (age 44 yr), all Israeli Bedouins. The degree of anemia was evaluated as well as the extent of development of gallstones and iron overload. In each subject we determined the hemochromatosis gene mutations and the uridine dyphosphate-glucoronosyltransferase (UGT-1A) gene polymorphism associated with Gilbert's syndrome. RESULTS: The patients were found to have moderate anemia, with the women displaying lower mean hemoglobin levels than the men (8.2 +/- 0.9 g dL(-1) vs. 10 +/- 1.3 g dL(-1); P=0.0059). The majority of patients (59%) had received at least one blood transfusion, with the women having a significantly higher transfusion requirement. Although delayed puberty was noted, final height and weight were within normal limits, and eight patients had progeny. Biliary stones were found in three of 16 patients, two of whom were homozygous for UGT-1A gene polymorphism. None of the patients carried the common hemochromatosis gene mutation, although serum ferritin levels were moderately elevated (788 +/- 332 ng mL(-1)). CONCLUSIONS: CDA type I in young adults is characterized by moderate macrocytic anemia, more severe in women, and a tendency to cholelithiasis and secondary progressive iron overload. We suggest that iron overload in this patient population should be monitored and chelation therapy initiated when indicated to prevent organ damage