Intraoperative choroidal detachment during small-gauge vitrectomy: analysis of causes,anatomic, and visual outcomes

IntroductionTo investigate the incidence and causes of intraoperative choroidal detachment (CD) during small-gauge vitrectomy, as well as the anatomic and visual outcomes.MethodsWe retrospectively reviewed the medical records of 1026 consecutive patients who underwent small-gauge vitrectomy from June 2017 to December 2018 at Zhongshan Ophthalmic Centre, Guangzhou, China. Data on the presence, location, and extent of intraoperative CD and its relationship to the infusion cannula were collected. Patient demographic characteristics and postoperative anatomic and visual outcomes were also assessed.ResultsA total of six cases were found to have intraoperative CD, including two with serous CD, three with limited haemorrhagic CD, and one with CD caused by inadvertent perfusion of gas during air/fluid exchange. Retraction of the infusion cannula and acute ocular hypotony were found to be the main causes of intraoperative CD in five out of the six cases. The best-corrected visual acuity of all cases significantly improved after the surgery.ConclusionThe incidence of intraoperative CD during small-gauge vitrectomy is low; the predominant causes are retraction of the infusion cannula and acute ocular hypotony. Immediate awareness and timely closure of the incision may contribute to a better surgical prognosis.Subject terms: Uveal diseases, Diseases     

PGC-1α与卵巢功能及相关研究进展

过氧化物酶体增殖物激活受体γ共激活因子1α(peroxisome proliferator-activated receptor gamma coactivator 1 alpha,PGC-1α)属于人体内一种重要的核转录辅助激活因子,是线粒体生成的关键调节因子,通过与核受体及转录因子的相互作用参与线粒体的生物合成、适...     

水凝胶的生物力学研究进展

水凝胶是生物医用领域的重要生物材料,也是近年来的研究热点。但人体内的细胞与组织的微环境和调控机制非常复杂,水凝胶应用于再生修复领域仍存在一些待解决的科学问题。随着生物力学的发展,越来越多的研究者发现除了关注水凝胶的材料学及生物学特性以外,其生物力学特性也是调控细胞功能、影响组织再生修复的关键因素之一。因此,本文总结了水凝胶材料的生物力学研究进展,并对未来的研究工作进行了展望。     

Circular RNAs: new biomarkers of chemoresistance in cancer

Chemotherapeutics are validated conventional treatments for patients with advanced cancer. However, with continual application of chemotherapeutics, chemoresistance, which is often predictive of poor prognosis, has gradually become a concern in recent years. Circular RNAs (circRNAs), a class of endogenous noncoding RNAs (ncRNAs) with a closed-loop structure, have been reported to be notable targets and markers for the prognosis, diagnosis, and treatment of many diseases, particularly cancer. Although dozens of studies have shown that circRNAs play major roles in drug-resistance activity in tumors, the mechanisms by which circRNAs affect chemoresistance have yet to be explored. In this review, we describe the detailed mechanisms of circRNAs and chemotherapeutics in various cancers and summarize potential therapeutic targets for drug-resistant tumors.     

Ruthenium-catalyzed asymmetric hydrogenation of aromatic and heteroaromatic ketones using cinchona alkaloid-derived NNP ligands

A series of cinchona alkaloid-based NNP ligands, including a new one, have been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various aromatic and heteroaromatic ketones were smoothly reacted, yielding valuable chiral alcohols with extremely high 99.9% ee. Moreover, a proposed reaction mechanism was discussed and verified by NMR.

A series of cinchona alkaloid-based NNP ligands including a new one has been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various ketones were smoothly reacted with up to 99.9% ee.

Since the well-known failure of using racemic thalidomide, attention has been paid to the manufacture of optically pure compounds as effective components in pharmaceuticals and agrochemicals. Asymmetric hydrogenation of ketones, especially heteroaromatic ketones, has emerged as a popular facile route to approach enantiopure secondary alcohols as essential intermediates for the construction of biologically active molecules.^1–4 Knowles et al.⁵ pioneered the production of enantioenriched chiral compounds in 1968, and Noyori and co-workers^6–8 laid the cornerstone of asymmetric hydrogenation in 1990s. Subsequently, numerous catalytic systems have been developed. Ru-BICP-chiral diamine-KOH was developed and proved to be effective for asymmetric hydrogenation of aromatic ketones by Xumu Zhang.⁹ Cheng-yi Chen reported asymmetric hydrogenation of ketone using trans-RuCl₂[(R)-xylbinap][(R)-daipen] and afforded secondary alcohol in 92–99% ee.¹⁰ Mark J. Burk and Antonio Zanotti-Gerosa disclosed Phanephos-ruthenium-diamine complexes catalyzing the asymmetric hydrogenation of aromatic and heteroaromatic ketones with high activity and excellent enantioselectivity.¹¹ Qi-Lin Zhou et al. designed and synthesized chiral spiro diphosphines as a new chiral scaffold applied in the asymmetric hydrogenation of simple ketones with extremely high activity and up to 99.5% ee.^12–15 Similarly, Kitamura and co-workers have developed a set of tridentate binan-Py-PPh₂ ligands for the asymmetric hydrogenation of ketones affording excellent results.¹⁶ Recently, chiral diphosphines and tridentate ligands based on ferrocene have been developed for the asymmetric hydrogenation of carbonyl compound with a remarkable degree of success.^17–21 Despite many ligands for asymmetric hydrogenation of ketones have been reported, expensive reagent and multistep complicated reactions were employed to synthesize most of them.^22–24 In light of increasing industrial demand, easily obtained, cheap and practical chiral ligands are still highly desirable. In addition to chiral ligands, the selection of metals was essential for asymmetric hydrogenation.^25–27 Although Mn,^28–30 Fe,^31–34 Co,^35–37 Ni^38,39 and Cu^40,41 metals were proved to be effective for asymmetric hydrogenation in recent years, Rh,^42–44 Ir^45,46 and especially Ru remained the most preferred metals. Ruthenium^47–51 was chosen owing to its superior performances in terms of low price, selectivity and activity. Takeshi Ohkuma,⁵² Hanmin Huang^53,54 and Johannes G. de Vries⁵⁵ all successfully used ruthenium catalysts for asymmetric hydrogenation of ketones. Admittedly, there is a continuing interest in the development of cheaper, simpler and more efficient catalysts for the asymmetric hydrogenation of ketones under mild conditions to access corresponding secondary alcohols. Recently, we developed new NNP chiral ligands derived from cinchona alkaloid for the asymmetric hydrogenation of various ketones in extremely excellent results using a iridium catalytic system.⁵⁶ Prompted by these encouraging results, we were interested in exploring a ruthenium-catalyzed asymmetric hydrogenation of ketones with NNP chiral ligands derived from cinchona alkaloid. Here, we showed that changing from iridium to ruthenium, with the same simple synthetic ligands, delivered a catalyst catalyzed asymmetric hydrogenation of ketones to give the industrially important chiral alcohols with up to 99.9% ee. Although the catalytic activity of ruthenium catalyst was not as high as that of the iridium catalyst, the enantioselectivity could be maintained, and even showed higher enantioselectivity in the hydrogenation of some substrates.Chiral tridentate ligand NNP (L1–L10) were synthesized and characterized as reported in our previous publication. With tridentate ligands in hand, we began to evaluate the catalytic performance in benzylidene-bis(tricyclohexylphosphine) dichlororuthenium-catalyzed asymmetric hydrogenation of acetophenone employed as a standard substrate (Fig. 2). MeOH was found to be a better one as the conversion and enantioselectivity were 99.9% and 98.2%, respectively. Bases screening showed that Ba(OH)₂ was superior to the others, giving >99.9% conversion and 98.8% ee in the present catalytic system (Fig. 1). Ligand screening revealed that the configuration of chiral centers of cinchona alkaloids of the ligand markedly affected the catalytic performance. NNP ligands derived from cinchonine and quinidine appeared to benefit both the reaction rate and enantioselectivity, while those derived from cinchonidine and quinine had the opposite effect. Further, different NNP ligands that bearing different substituents on the phenyl rings were evaluated. Similar to our previous research, ligands with electron-withdonating substituents showed better catalytic performance than those with electron-withdrawing substituents. However, it was noted that the more electron-withdonating substituents furnished lower activity but same enantioselectivity. The optimal ligand L5 derived from quinidine with one methoxy group on benzene ring provided the corresponding chiral alcohol with 99.9% conversion and 98.8% ee. Considering that L3 derived from cinchonine had similar catalytic performance to L4 derived from quinidine, new ligand L10 similar to L5 with one methoxy group on benzene ring was synthesized and applied to the asymmetric hydrogenation of template substrate. 99.6% conversion and 97.6% ee was obtained. Hence, L5 was employed as better ligand in subsequent experiments.Open in a separate windowFig. 1The effect of different bases for the asymmetric hydrogenation of acetophenone (substrate/Ru/L5 = 500/1/2, ketones: 0.429 mol L⁻¹, base: 0.15 mol L⁻¹, MeOH: 2 mL, 30 °C, 6 MPa, 2 h.).Open in a separate windowFig. 2The effect of different solvents for the asymmetric hydrogenation of acetophenone. (substrate/Ru/L5 = 1000/1/2, ketones: 0.858 mol L⁻¹, Ba(OH)₂: 0.15 mol L⁻¹, solvent: 2 mL, 30 °C, 6 MPa, 2 h.).The effect of different ligand for the asymmetric hydrogenation of acetophenone^a

静息态功能磁共振局部一致性在抑郁障碍伴失眠症状患者中的研究进展

在抑郁障碍患者中,失眠是常见的伴发症状。早期有效评估抑郁障碍患者的失眠症状是预防患者睡眠问题与抑郁障碍进一步恶化的关键。目前关于睡眠评估工具的综述仅说明了主客观评估工具的效用,极少综述指出与抑郁障碍伴失眠症状相关的评估指标,也很少围绕静息态功能磁共振成像(rs-fMRI)技术作为睡眠状况的客观评估工具进行阐述。因此,本文就用于抑郁障碍伴发失眠症状患者的rs-fMRI局部一致性进行阐述,并指出目前研究单相抑郁障碍(UDD)和双相抑郁障碍(BDD)患者之间在rs-fMRI局部一致性的区别,以期为临床上UDD与BDD患者的诊断、鉴别、治疗及相关研究提供理论基础和实用性参考。     

Cardamonin suppressed the migration,invasion, epithelial mesenchymal transition (EMT) and lung metastasis of colorectal cancer cells by down-regulating ADRB2 expression

ContextCardamonin (CDN) can suppress cell growth in colorectal cancer (CRC), a common digestive malignancy.ObjectiveWe explored the effect and mechanism of CDN on metastatic CRC.Materials and methodsTwo cell lines (HT29 and HCT116) were initially treated with CDN at different concentrations (5, 10 and 20 μmol/L) or 50 μmol/L propranolol (positive control) for 24 or 48 h. Then, the two cell lines were separately transfected with siADRB2 and ADRB2 overexpression plasmids, and further treated with 10 μmol/L CDN for 24 h. The cell viability, migration and invasion were determined by cell counting kit-8 (CCK-8), wound healing and transwell assays, respectively. The levels of ADRB2, matrix metalloprotease (MMP)-2, MMP-9, E-cadherin and N-cadherin were measured by Western blotting or/and RT-qPCR. A CRC metastasis model was established to evaluate the antimetastatic potential of CDN (25 mg/kg).ResultsADRB2 (3.2-fold change; p < 0.001) was highly expressed in CRC tissues. CDN at 10 μmol/L suppressed viability (69% and 70%), migration (33% and 66%), invasion (43% and 72%) and ADRB2 expression (2.2- and 2.84-fold change) in HT29 and HCT116 cells (p < 0.001). CDN at 10 μmol/L inhibited MMP-2, MMP-9 and N-cadherin expression but promoted E-cadherin expression in CRC cells (p < 0.001). Importantly, the effect of CDN on CRC cells was impaired by ADRB2 overexpression, but further enhanced by ADRB2 down-regulation (p < 0.01). Additionally, ADRB2 overexpression reversed the inhibitory effect of CDN on metastatic lung nodules (p < 0.05). Discussion and conclusions: CDN is a potential candidate for the treatment of metastatic CRC in clinical practice.     

结合雌激素治疗儿童造血干细胞移植后出血性膀胱炎

目的:观察结合雌激素对异基因造血干细胞移植受者术后出血性膀胱炎的临床疗效和不良反应.方法:8例异基因造血干细胞移植受者,在移植后并发出血性膀胱炎,给予结合雌激素治疗,10岁以下患儿1.25 mg/次,2次/天,口服;10岁以上患儿2.5 mg/次,2次/天,口服.在临床显效和有效后逐步减量至停药,平均疗程1～2周.结果:显效5例,有效1例,2例无效死亡,死于出血性膀胱炎和严重感染各1例;出现恶心、呕吐2例,男性乳房增大2例,停药后恢复正常.结论:结合雌激素治疗异基因造血干细胞移植术后受者出血性膀胱炎具较好疗效,不良反应轻微,可作为一种有效的辅助治疗方法.     

Influence of Indium (III) Chloride on Human Dermal Fibroblast Cell Adhesion on Tantalum/Silicon Oxide Nano-Composites

Cell adhesion is an essential biological function for division, migration, signaling and tissue development. While it has been demonstrated that this cell function can be modified by using nanometer-scale surface topographic structures, it remains unknown how contaminants such as indium (III) ion might influence this specific cell behavior. Herein, the influence of indium chloride on human dermal fibroblast (GM5565) adhesion characteristics was investigated, given the frequent contact of contaminants with skin. The morphology of the adherent cells and their mitochondrial reticulum was characterized on cell culture dishes and nanopatterned surfaces by using fluorescence confocal microscopy and scanning electron microscopy. Results showed a significant proportion of cells lost their ability to align preferentially along the line axes of the nanopattern upon exposure to 3.2 mM indium chloride, with cells aligned within 10° of the pattern line axes reduced by as much as ~70%. Concurrent with the cell adhesion behaviors, the mitochondria in cells exposed to indium chloride exhibit a punctate staining that contrasts with the normal network of elongated tubular geometry seen in control cells. Our results demonstrate that exposure to indium chloride has detrimental effects on the behavior of human fibroblasts and adversely impacts their mitochondrial morphology. This shows the importance of evaluating the biological impacts of indium compounds.     

自噬相关蛋白Atg5在BPA所致肝脏脂质沉积中的作用研究

目的:观察自噬相关蛋白Atg5是否介导双酚A(bisphenol A,BPA)所致的肝脏脂质沉积。方法:将Hep G2肝细胞分为对照组、BPA不同浓度(1、10μmol/L)干预组、阳性对照组即200μmol/L油酸(oleic acid,OA)联合400μmol/L软脂酸(Palmitic acid,PA),分别给予上述不同干预24 h。采用化学酶促-比色法定量检测细胞内甘油三酯(triglyceride,TG)含量,油红O染色观察细胞内脂滴沉积情况。Real-time PCR及Western blot、免疫荧光方法检测在不同干预情况下Hep G2细胞内Atg5的表达水平。结果:1不同浓度BPA干预后,Hep G2细胞内TG含量均有不同程度的升高,其中10μmol/L BPA组升高具有统计学意义(0.197±0.033;0.094±0.014,P=0.031);2油红O染色结果与TG定量一致。3Real-time PCR结果表明,与对照组相比10μmol/L BPA组Atg5 m RNA表达并无明显变化(0.93±0.088;1.017 5±0.062 4,t=0.811,P=0.428);Western blot结果显示与对照组相比10μmol/L BPA组其蛋白表达明显减少(0.519±0.059;1,t=0.8101,P=0.000);免疫荧光进一步检测发现,与对照组相比10μmol/L BPA组Atg5荧光小点数量明显减少。结论:自噬相关蛋白Atg5可能介导BPA所致的肝脏脂质沉积的发生。