人工智能辅助技术在进展期胃癌原发灶不同区域HER-2评估及判断预后中的应用

背景与目的：胃癌中人类表皮生长因子受体2 (HER-2)表达存在较高的异质性,全面地评估患者的HER-2状态有利于发现抗HER-2治疗的潜在受益者。人工智能（AI）辅助显微镜可以通过大量读片以综合判断HER-2的状态,并减少人为评估的视觉误差。本研究旨在探讨AI辅助显微镜在胃癌原发灶多区域HER-2评估中的实用性和可行性。方法：对264例进展期胃癌患者术后标本同一区域HER-2免疫组化染色切片,分别使用普通光学显微镜视觉评估、AI辅助显微镜两种方法进行评估,评价AI辅助显微镜在胃癌HER-2评估中的准确性;并使用AI辅助显微镜对上述胃癌患者原发灶的其他区域的HER-2表达进行评估,将两个区域HER-2评分较高者作为最终判读结果,并进一步分析HER-2过表达与进展期胃癌患者临床病理特征及术后生存的关系。结果：视觉评估、AI辅助显微镜与金标准三者之间HER-2评分总体差异无统计学意义（P>0.05）,但AI辅助显微镜相较视觉评估与金标准具有更高的一致性（κ=0.86 vs.κ=0.81,P<0.05）。使用AI辅助显微镜对胃癌原发灶两个不同区域的HER-2评估结果显示,两个区域...     

The Incapacity of the Surgeon to Identify NASH in Bariatric Surgery Makes Biopsy Mandatory

Background  

Nonalcoholic steatohepatitis (NASH) is a morbid condition highly related to obesity. It is unclear if the macroscopic liver appearance correlates with the histopathologic findings. The goal of this prospective study was to determine the relationship between the intraoperative liver appearance and the histopathologic diagnosis of NASH in morbidly obese subjects undergoing bariatric surgery. We also aimed to determine variables that could predict NASH preoperatively.     

Adoptive Transfer of Ex Vivo HO-1 Modified Bone Marrow�Cderived Macrophages Prevents Liver Ischemia and Reperfusion Injury

Macrophages play a critical role in the pathophysiology of liver ischemia and reperfusion (IR) injury (IRI). However, macrophages that overexpress antioxidant heme oxygenase-1 (HO-1) may exert profound anti-inflammatory functions. This study explores the cytoprotective effects and mechanisms of ex vivo modified HO-1-expressing bone marrow–derived macrophages (BMDMs) in well-defined mouse model of liver warm ischemia followed by reperfusion. Adoptive transfer of Ad-HO-1-transduced macrophages prevented IR-induced hepatocellular damage, as evidenced by depressed serum glutamic-oxaloacetic transaminase (sGOT) levels and preserved liver histology (Suzuki scores), compared to Ad-β-gal controls. This beneficial effect was reversed following concomitant treatment with HO-1 siRNA. Ad-HO-1-transfected macrophages significantly decreased local neutrophil accumulation, TNF-α/IL-1β, IFN-γ/E-selectin, and IP-10/MCP-1 expression, caspase-3 activity, and the frequency of apoptotic cells, as compared with controls. Unlike in controls, Ad-HO-1-transfected macrophages markedly increased hepatic expression of antiapoptotic Bcl-2/Bcl-xl and depressed caspase-3 activity. These results establish the precedent for a novel investigative tool and provide the rationale for a clinically attractive new strategy in which native macrophages can be transfected ex vivo with cytoprotective HO-1 and then infused, if needed, to prospective recipients exposed to hepatic IR–mediated local inflammation, such as during liver transplantation, resection, or trauma.     

Cardiopulmonary reflex is attenuated in iron overload conscious rats

Increased iron intake can lead to iron accumulation in serum and tissues. Its has been described that serum and tissue iron overload increase reactive oxygen species (ROS) levels and reduce the effectiveness of the cardiovascular neural mechanisms involved in the maintenance of the arterial blood pressure whithin a narrow range of variation, therefore, iron overload may disrupt cardiovascular homeostasis contributing to physiopathological status development. In the present study we evaluated whether iron accumulated in serum or tissue of awake animals affect the cardiovascular homeostasis through changes in the cardiopulmonary reflex (CPR). We observed that the CPR is reduced in both serum and tissue iron overloaded groups, but no changes were found in the left ventricular pressure measurements, suggesting that iron-related effects are restrict to the CPR neural pathways. We also observed that the serum overloaded group presented lower basal heart rate levels, suggesting an increased parasympathetic efferent activity directed to the heart in this group. Taken together, our data suggest an important role for the iron-generated ROS to the cardiovascular homeostasis, especially regarding the CPR in awake animals.     

单眼视网膜静脉阻塞患者对侧眼黄斑区血流密度和中心凹无血管区面积观察

目的:观察单眼视网膜静脉阻塞(RVO)患者对侧眼黄斑区血流密度和黄斑中心凹无血管区(FAZ)面积。方法:回顾性病例对照研究。2018年5~11月在长沙爱尔眼科医院临床确诊为单眼RVO的78例患者78只对侧眼纳入研究。其中,男性44例,女性34例;平均年龄(53.17±10.12)岁。视网膜中央静脉阻塞(CRVO)42例(CRVO组),视网膜分支静脉阻塞(BRVO)36例(BRVO组)。选取年龄和性别与RVO患者相匹配的33名正常健康者42只眼作为对照组。其中,男性17例22只眼,女性16例20只眼;平均年龄(53.48±10.84)岁。3组受检眼均行OCT血管成像检查,以仪器自带软件自动识别以黄斑中心凹为中心的直径6 mm区域及FAZ,自动测量黄斑区浅层和深层血流密度及FAZ面积。对比分析3组受检眼黄斑区浅层、深层血流密度和FAZ面积。结果:与对照组比较,CRVO组(t=-4.26、-4.93)、BRVO组(t=-4.79、-4.74)受检眼黄斑区浅层及深层血流密度均降低,差异均有统计学意义(P<0.05)。CRVO组、BRVO组受检眼黄斑区浅层及深层血流密度降低幅度分别为4.13%、5.51%及3.50%、4.58%,深层血流密度的降低幅度较浅层更大。CRVO组受检眼FAZ面积较对照组减小,差异有统计学意义(t=-3.43,P<0.05)。BRVO组与对照组受检眼FAZ面积比较,差异无统计学意义(t=-0.10,P>0.05)。结论:单眼RVO患者对侧眼黄斑区血流密度较正常健康眼降低,黄斑区深层血流密度的降低幅度较浅层更大。与正常健康眼比较,单眼CRVO患者对侧眼FAZ面积减小,单眼BRVO患者对侧眼FAZ面积无明显变化。     

Does the Subtalar Joint Compensate for Ankle Malalignment in End-stage Ankle Arthritis?

BackgroundPatients with ankle arthritis often present with concomitant hindfoot deformity, which may involve the tibiotalar and subtalar joints. However, the possible compensatory mechanisms of these two mechanically linked joints are not well known.Questions/purposesIn this study we sought to (1) compare ankle and hindfoot alignment of our study cohort with end-stage ankle arthritis with that of a control group; (2) explore the frequency of compensated malalignment between the tibiotalar and subtalar joints in our study cohort; and (3) assess the intraobserver and interobserver reliability of classification methods of hindfoot alignment used in this study.MethodsBetween March 2006 and September 2013, we performed 419 ankle arthrodesis and ankle replacements (380 patients). In this study, we evaluated radiographs for 233 (56%) ankles (226 patients) which met the following inclusion criteria: (1) no prior subtalar arthrodesis; (2) no previously failed total ankle replacement or ankle arthrodesis; (3) with complete conventional radiographs (all three ankle views were required: mortise, lateral, and hindfoot alignment view). Ankle and hindfoot alignment was assessed by measurement of the medial distal tibial angle, tibial talar surface angle, talar tilting angle, tibiocalcaneal axis angle, and moment arm of calcaneus. The obtained values were compared with those observed in the control group of 60 ankles from 60 people. Only those without obvious degenerative changes of the tibiotalar and subtalar joints and without previous surgeries of the ankle or hindfoot were included in the control group. Demographic data for the patients with arthritis and the control group were comparable (sex, p = 0.321; age, p = 0.087). The frequency of compensated malalignment between the tibiotalar and subtalar joints, defined as tibiocalcaneal angle or moment arm of the calcaneus being greater or smaller than the same 95% CI statistical cutoffs from the control group, was tallied. All ankle radiographs were independently measured by two observers to determine the interobserver reliability. One of the observers evaluated all images twice to determine the intraobserver reliability.ResultsThere were differences in medial distal tibial surface angle (86.6° ± 7.3° [95% CI, 66.3°–123.7°) versus 89.1° ± 2.9° [95% CI, 83.0°–96.3°], p < 0.001), tibiotalar surface angle (84.9° ± 14.4° [95% CI, 45.3°–122.7°] versus 89.1° ± 2.9° [95% CI, 83.0°–96.3°], p < 0.001), talar tilting angle (−1.7° ± 12.5° [95% CI, −41.3°–30.3°) versus 0.0° ± 0.0° [95% CI, 0.0°–0.0°], p = 0.003), and tibiocalcaneal axis angle (−7.2° ± 13.1° [95% CI, −57°–33°) versus −2.7° ± 5.2° [95% CI, −13.3°–9.0°], p < 0.001) between patients with ankle arthritis and the control group. Using the classification system based on the tibiocalcaneal angle, there were 62 (53%) and 22 (39%) compensated ankles in the varus and valgus groups, respectively. Using the classification system based on the moment arm of the calcaneus, there were 68 (58%) and 20 (35%) compensated ankles in the varus and valgus groups, respectively. For all conditions or methods of measurement, patients with no or mild degenerative change of the subtalar joint have a greater likelihood of compensating coronal plane deformity of the ankle with arthritis (p < 0.001–p = 0.032). The interobserver and intraobserver reliability for all radiographic measurements was good to excellent (the correlation coefficients range from 0.820 to 0.943).ConclusionsSubstantial ankle malalignment, mostly varus deformity, is common in ankles with end-stage osteoarthritis. The subtalar joint often compensates for the malaligned ankle in static weightbearing.

Level of Evidence

Level III, diagnostic study.     

Effect of the nonsteroidal anti-inflammatory drug indomethacin on proliferation and apoptosis of colon carcinoma cells

Purpose: Nonsteroidal anti-inflammatory drugs lower the incidence of and mortality from colon cancer. In this paper, we present the effect of indomethacin on growth inhibition and alterations in the expression of several genes involved in cell cycle and apoptosis in CaCo-2 colon adenocarcinoma cells. Methods: We used the MTT test to evaluate the effect of indomethacin on the proliferation rate of colon cancer and normal fibroblast cells in vitro. The expression of c-myc oncoprotein and p53 and p27 suppressor proteins was examined using the immunocytochemical method. Results: We have shown that indomethacin reduces the proliferation rate of CaCo-2 colon cancer cells (up to 60% at the concentration of 4 × 10⁻⁴ M), alters their morphology, and induces cell death by apoptosis. The most pronounced inhibitory effect was observed at the concentration of 6 × 10⁻⁴ M where the growth was completely suppressed. However, the growth of normal fibroblasts (Hef 522) was much less inhibited (about 30% of inhibition at the concentration of 6 × 10⁻⁴ M). Indomethacin reduces the proliferation rate and induces apoptosis in CaCo-2 colon cancer cells through enhanced expression of c-myc, p53, and p27 proteins. Conclusions: This is the first report about p27-increased expression in colon carcinoma cells induced by indomethacin treatment. Increased expression of p27 represents a new mechanism of apoptosis in cells treated with NSAIDs (indomethacin). This effect probably contributes to the anti-proliferative effect on colon cancer cells in vitro. Received: 27 April 2000 / Accepted: 7 August 2000