A pilot study of genipin cross-linking effects on bullous keratopathy in rabbits

目的:评价京尼平交联治疗兔大泡性角膜病变的效果.方法:将已建立大泡性角膜病变动物模型的9只雌性新西兰白兔随机分为3组:治疗组(n=3),对照组(n=3),空白对照组(n=3).其中治疗组:刮除角膜上皮后,应用0.25%的京尼平浸泡实验眼角膜40min(24℃);对照组:刮除角膜上皮后,应用生理盐水浸泡实验眼角膜40min(24℃);空白对照组:不进行任何处理.处理后2wk内进行以下检查:裂隙灯检查、中央角膜厚度(CCT)测量、体质量和应激反应评估、组织学检查和利用原位末端转移酶标记技术(TUNEL法)检测基质层细胞凋亡.结果:与对照组和空白对照组相比,治疗组角膜水肿明显减轻、角膜上皮逐渐修复完整、角膜大泡消失、中央角膜角膜厚度显著下降(P<0.05)、体质量显著增加(P<0.05).治疗组的实验动物活动性较处理前增加,反抗行为减少,攻击性减低.治疗组角膜基质层胶原纤维排列更为紧致、规则,可见蓝色条索状交联产物.治疗组角膜基质层均偶见凋亡细胞,对照组及空白对照组未明显见凋亡细胞.结论:京尼平交联治疗可使兔大泡性角膜病变角膜水肿减轻,疼痛症状缓解,其可能的机制为京尼平交联使角膜基质层胶原纤维排列紧密,从而阻止角膜水肿和大泡的形成.     

Pharmacokinetics,biodistribution and bioavailability of isoliquiritigenin after intravenous and oral administration

Context: Isoliquiritigenin (ISL) has been shown to exhibit a variety of biological activities. However, there is little research on the pharmacokinetic behavior and tissues distribution of ISL.

Objective: Pharmacokinetics, biodistribution and bioavailability of ISL after intravenous and oral administration were determined by systematic investigation in Sprague–Dawley rats.

Materials and methods: ISL was dissolved in medicinal ethanol-Tween 80–0.9% sodium chloride saline in a volume ratio of 10:15:75. The ISL solution was injected in rats via a tail vein at a single dose of 10, 20 and 50?mg/kg and administered orally in rats at a single dose of 20, 50 and 100?mg/kg, respectively. Blood samples were collected at time intervals of 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8 and 12?h after intravenous injection. Tissues of interests in mice were collected immediately at each determined time point (0.5, 1, 2, 3 and 6?h) after cervical dislocation.

Results: The dose-normalized AUC values were 7.3, 7.6 and 8.7?μg?×?h/ml (calculated based on the dose of 10?mg/kg) for intravenous doses of 10, 20 and 50?mg/kg, respectively. The elimination half-lifes (t_1/2λ) were 4.9, 4.6 and 4.8?h at 10, 20 and 50?mg/kg intravenous doses, respectively. The F values were 29.86, 22.70, 33.62% for oral doses of 20, 50 and 100?mg/kg, respectively. Liver, heart and kidney were major distribution tissues of ISL in mice. The plasma protein binding of ISL in rats was 43.72%.

Conclusion: The work may useful for further study of the bioactive mechanism of ISL.     

丹参酮提取物物理化学质量属性相关性分析

目的：探寻丹参酮提取物化学成分的含量与物理性质之间的相关性。方法：HPLC测定50批丹参酮提取物中隐丹参酮、丹参酮IIA的含量,经典方法测定物理性质,将成分含量与物理性质进行相关性分析。结果：两变量组组内的隐丹参酮与丹参酮IIA含量,D10、D50、D90 之间,松装密度与振实密度,豪斯纳比率与压缩度指数均具有较强的相关性,休止角与均齐度、豪斯纳比率、压缩度指数具有一定的相关性,但相关性不强。两变量组的原始变量组间相关性系数最大不超过0.400,相关性不强。经过典型相关分析,3对典型变量的相关性显著,相关系数分别为0.851,0.674,0.565。结论：对于丹参酮提取物的化学、物理质量属性,原始变量组内具有较好的相关性,但组间相关性较差。相比原始变量,典型变量呈现出了较好的组间相关性,表明丹参酮提取物的物理化学属性之间具有一定的相关性。     

Plasma exchange treats severe intrahepatic cholestasis caused by dacomitinib: A case report

Rationale:Dacomitinib-induced liver injury is often manifested by mild elevations of transaminases and bilirubin, and severe intrahepatic cholestasis caused by dacomitinib for simultaneous taking orally cytochrome P450 2D6 (CYP2D6) competitive substrates has been rarely reported.Patient concerns:The patient was a 69-year-old woman with non–small cell lung cancer (NSCLC) who was prescribed oral dacomitinib for a month; she was given oral loratadine due to “allergic rhinitis” and metoprolol extended action tablets due to “tachycardia” separately for a few days during the course of dacomitinib treatment. The patient developed liver damage, increased fatigue, yellow urine, and pruritus, with significantly elevated serum levels of bilirubin and glutamyltranspetidase.Diagnosis:Intrahepatic cholestasis, drug-induced liver injury, and NSCLC.Interventions:After admission, the patient was prescribed adenosylmethionine, acetylcysteine, ursodeoxycholic acid capsule, methylprednisolone and fenofibrate for a month, with progressive elevation of liver biochemical parameters. Through drug enzyme gene assays in the liver tissue after percutaneous liver biopsy, we found both CYP2D6*10/*10 and ATP-binding cassette subfamily B member 1 GG variants (rs1045642) positive. After the poor response to the conventional medication, the patient underwent plasma exchange.Outcomes:The patient was discharged after her liver parameters improved; the parameters remained normal at several follow-up visits, and she renewed the NSCLC regimens without dacomitinib after being evaluated by oncologists.Lessons:Dacomitinib can induce severe intrahepatic cholestasis. It is considered that patients with intermediate metabolic CYP2D6 are susceptible to drug-induced liver injury caused by dacomitinib; plasma exchange may be an effective treatment.     

UBE2C promotes the progression of pancreatic cancer and glycolytic activity via EGFR stabilization-mediated PI3K-Akt pathway activation

BackgroundPancreatic cancer (PC) is among the most prevalent and deadliest endocrine tumors, yet the mechanisms governing its pathogenesis remain to be fully clarified. While ubiquitin-conjugating enzyme E2C (UBE2C) has been identified as an important oncogene in several cancers, its importance in PC has yet to be established.MethodsUBE2C expression in PC tumor samples and cell lines was examined via quantitative real-time polymerase chain reaction (qRT-PCR), while appropriate commercial kits were used to assess lactate production, ATP generation, and the uptake of glucose.ResultsUBE2C was found to be upregulated in PC patient tumors and correlated with poorer survival outcomes. In PC cell lines, the silencing of this gene suppressed the malignant activity of cells, thus supporting its identification as an oncogene in this cancer type. Mechanistically, UBE2C was found to promote enhanced matrix metalloproteinase (MMP) protein expression via activating the PI3K-Akt pathway. Moreover, it was found to bind to the epidermal growth factor receptor (EGFR), stabilizing it and driving additional PI3K-Akt pathway activation. UBE2C knockdown in PC cells impaired their uptake of glucose and their ability to produce lactate and ATP.ConclusionsIn conclusion, the results of this study support a role for UBE2C as a driver of metastatic PC progression owing to its ability to bind to EGFR and to induce signaling via the PI3K-Akt pathway.     

Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice

Aim： To investigate the effect of balsalazine treatment on intestinal mucosal permeability in dextran sulfate sodium （DSS）-induced colitis and to determine the mechanism of the balsalazine-induced changes.
Methods： Experimental colitis was induced in C57BL/6J mice by the administration of 5% DSS. Balsalazine was administered intragastrically at doses of 42, 141, and 423 mg/kg. The disease activity index （DAI） score was evaluated and colon tissue was collected for the assessment of histological changes. The amount of malondialdehyde （MDA） in the colon was determined, along with the activity of myeloperoxidase （MPO）, superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）. Mucosa from the small intestine was collected to determine the levels of tumor necrosis factor （TNF）-α and interferon （IFN）-γ. The mucosa was ultrastructurally examined with transmission electron microscopy and intestinal permeability was assayed using Evans blue.
Results： Balsalazine was found to reduce the DAI score and the histological index （HI） score, decrease the MDA content and the activity of MPO, and increase the activity of SOD and GSH-Px in colitis mice. At the same time, balsalazine ameliorated microvillus and tight junction structure, resulting in a decrease in the amount of Evans blue permeating into the intestinal wall and the levels of TNF-α and IFN-γ in colitis mice.
Conclusion： In colitis mice, the anti-colitis effect of balsalazine results in a decrease in intestinal mucosal permeability. The mechanism of this effect is partly associated with balsalazine＇s antioxidative and anti-inflammatory effects.     

外路小梁切开术治疗先天性青光眼的远期效果

目的 评价外路小梁切开术（Ｌｕｎｔｚ法）治疗先天性青光眼的远期效果。方法 随访２９例（４７只眼）行外路小梁切开术的先天性青光眼患者达５年以上。结果 应用寿命表法分析１次手术成功率：术后６、１２、１８及２４个月分别为７０．２％、６２．８％、５７．５％及５５．３％。眼压再次升高均发生在术后２年之内。１４只眼行２次小梁切开术,成功率为５０．０％,总成功率为７０．２％,成功者中具有１２只眼（３６．０％）裸     

Comparison of the effects of perineural or intravenous dexamethasone on thoracic paravertebral block in Ivor‐Lewis esophagectomy: A double‐blind randomized trial

Efforts to prolong thoracic paravertebral block (TPVB) analgesia include local anesthetic adjuvants, such as dexamethasone (Dex). Previous studies showed that both perineural (PN) and intravenous (i.v.) routes could prolong analgesia. As PN Dex is an off‐label use, anesthesiologists should be fully informed of the clinical differences, if any, on block duration. This study was designed to evaluate the two administration routes of Dex for duration of analgesia in TPVB. Ninety‐five patients scheduled for Ivor‐Lewis esophagectomy were randomized to receive TPVB (0.5% ropivacaine 15 ml), PN or i.v. Dex 8 mg. The primary end point was the duration of analgesia. The secondary end points included pain scores, analgesic consumption, adverse effects rate, and incidence of chronic pain at 3 months postoperatively. The PN‐Dex group showed better analgesic effects than the i.v.‐Dex group (p < 0.05). Similarly, the visual analogue scale scores in patients at 2, 4, 8, and 12 h postoperatively were lower in the PN‐Dex group than the i.v.‐Dex group (p < 0.05). The analgesic consumption in both the PN‐Dex and i.v.‐Dex groups was significantly lower than that in the control group (p < 0.05). Regarding the incidence of chronic pain, regardless of route, Dex decreased the incidence of chronic postsurgical pain and neuropathic pain at 3 months after surgery (p < 0.05), but there were no clinical differences between the i.v.‐Dex and PN‐Dex groups. Perineural dexamethasone improved the magnitude and duration of analgesia compared to that of the i.v.‐Dex group in TPVB in Ivor‐Lewis esophagectomy. However, there were no clinically significant differences between the two groups in the incidence of chronic pain.

Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Both perineural (PN) and intravenous (i.v.) dexamethasone (Dex) could prolong the duration of a nerve block, but the superiority of either route is still inconclusive. WHAT QUESTION DID THIS STUDY ADDRESS? The study investigated the effects of the two routes of Dex added to ropivacaine on analgesic effects of thoracic paravertebral block in patients undergoing Ivor‐Lewis esophagectomy. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? These results extend the knowledge of the superior analgesic effect of Dex for the management of perioperative pain in the setting of Ivor‐Lewis Esophagectomy. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Because PN Dex is an off‐label use, our study conformed the safety of Dex as PN adjuvants and extended its application field in clinical work.