Rh(iii)-catalyzed synthesis of dibenzo[b,d]pyran-6-ones from aryl ketone O-acetyl oximes and quinones via C–H activation and C–C bond cleavage

A redox-neutral synthesis of dibenzo[b,d]pyran-6-ones from aryl ketone O-acetyl oximes and quinones has been realized via Rh(iii)-catalyzed cascade C–H activation annulation. A possible Rh(iii)–Rh(v)–Rh(iii) mechanism involving an unprecedented β-C elimination step was proposed.

A novel procedure for the synthesis of dibenzo[b,d]pyran-6-ones via Rh(iii)-catalyzed C–H activation and C–C bond cleavage is described.

The dibenzo[b,d]pyran-6-one is one of the most important structural motifs widely present in natural products with pharmacological relevance,¹ such as gut microbiota metabolites urolithins (1–4) that show anti-inflammatory, antiglycative and neuroprotective effects,^2–4 and the extracts of an endophytic fungus Cephalosporium acremonium IFB-E007 (5–7) that have pronounced anticancer activities.⁵ In addition, the related heterocyclic structure benzo[d]naphtho[1,2-b]pyran-6-one is found in some bactericidal and antitumor natural products including gilvocarcins^6,7 (8–10) chrysomycins^8,9 (11–13), etc. (Fig. 1). Therefore, a number of approaches to access dibenzo[b,d]pyran-6-ones have been developed via the intra- or inter-molecular biaryl formation as the key step.¹⁰ However, many of these methodologies require multi-step reactions, and the development of new efficient synthetic methods, especially those easy one-step reactions that are still of great interest.Open in a separate windowFig. 1Selected representative natural products.In the past decade, transition-metal-catalyzed C–H bond activation has proven to be a powerful tool in organic syntheses¹¹ and several methods for the synthesis of dibenzo[b,d]pyran-6-ones via C–H activation have been reported.¹² Actually, in 2015, our group reported Rh(iii)-catalyzed synthesis of dibenzo[b,d]pyran-6-ones from N-methoxybenzamides and quinones through C–H activation annulation.¹³ Interestingly, we obtained the same products using aryl ketone O-acetyl oximes as substrates to react with quinones under Rh(iii)-catalyzed conditions in this work. Rh(iii)-catalyzed C–H activation using ketoximes as substrates has been developed for synthesis of various substituted heterocycles.¹⁴ Compared to the previous reports, this reaction undergoes a novel mechanism involving an unexpected C–C bond cleavage, which is attractive. Moreover, our study demonstrated that solvent is vital to these reactions. In 2018, we reported Rh(iii)-catalyzed annulation of aryl ketone O-acetyl oximes with quinones to synthesize 6H-benzo[c]chromenes with acetone as a co-solvent.¹⁵ Herein, we described Rh(iii)-catalyzed synthesis of dibenzo[b,d]pyran-6-ones using the same substrates without acetone (Scheme 1).Open in a separate windowScheme 1Rh(iii)-catalyzed divergent C–H activation annulation with quinones.Initially, the reaction of acetophenone O-acetyl oxime 1a with benzoquinone 2a was employed to optimize the reaction conditions (

基于ICT的虚拟社区活动与教师专业发展

随着信息通讯技术（ICT）的迅猛发展,虚拟社区的概念及其研究领域应运而生,并成为教育学习的重要空间和平台。基于ICT的虚拟社区将成为教师专业发展的重要舞台,成为教师超越时间和地域限制,相互联系、相互学习、协作共进的新方式。     

Safety,tolerability, and pharmacokinetics of single and multiple topical ophthalmic administration of imatinib mesylate in healthy subjects

For the long‐term efficacy of dry eye disease treatment, relieving underlying inflammation is necessary. Imatinib mesylate is a novel ophthalmic formulation of imatinib mesylate, which is expected to alleviate inflammation by inhibiting the discoidin domain receptor 1 activity. This study aims to evaluate the safety and pharmacokinetics of imatinib mesylate in healthy subjects. A randomized, double‐blind, placebo‐controlled study was conducted. In a single ascending dose, 16 subjects received a single eye drop of imatinib mesylate 0.1%, 0.3%, or matching placebo. In the multiple ascending dose (MAD), subjects received multiple eye drops of imatinib mesylate 0.1%, 0.3%, or matching placebo once daily for 7 days. Safety and tolerability were assessed by ophthalmic examination, including the visual analog scale (VAS) to monitor the burning sensation in the eyes. A total of four treatment‐emergent adverse events (TEAEs) occurred during the study. All TEAEs were mildly severe with no serious cases. VAS results in the 0.1% MAD group exhibited highest score of two points, whereas it was less than one point in others. Insignificant difference between the imatinib mesylate and placebo groups in the VAS results was seen. After a single dose administration of imatinib mesylate 0.1%, all plasma concentrations were below the lower limit of quantification. The peak plasma concentrations of imatinib were less than 0.54 µg/L in all groups. In conclusion, a single and multiple topical ophthalmic administration of imatinib mesylate was well‐tolerated in healthy subjects. Because there was minimal systemic exposure to imatinib, the adverse effect in the body seems to be insignificant.     

脊柱术后急性深部组织感染的观察及护理

目的 分析脊柱术后急性深部组织感染的特点及危险因素,探讨脊柱术后护理方式.方法 回顾该院2010年1月-2014年1月21例脊柱术后急性深部组织感染的发现与治疗过程.结果 21例患者急性深部组织感染发现及时,其中7例患者通过调整抗生素及换药,14例患者通过积极外科治疗,预后良好.结论 脊柱术后深部组织感染护理观察的重点在于患者体温的变化,患者敷料渗出物的变化,及注意患者主诉的变化.     

不育症患者指长波动不对称性特点的分析

目的 分析宁夏汉族男性不育症患者指长波动不对称性（FA）的特点。方法 遵循体质测量法,计算384例宁夏汉族男性（不育组192例,对照组192例）各指指长FA（2FA、3FA、4FA、5FA）及复合FA（CFA）的均值,比较各均值的差异性。结果 （1）不育组和对照组各指长FA均值分布趋势均为5FA < 3FA < 4FA < 2FA。（2）不育组各指长FA均值均高于对照组,2FA及4FA差异显著（P<0.05）,且不育组2FA与体重指数（BMI）正相关（P<0.05）;不育组2FA分布在|L-R|≥0.04中的人数显著高于对照组（P<0.05）。结论 2FA可能为男性不育的早期筛查提供重要的参考信息。     

Classification of hepatic cavernous hemangioma or hepatocellular carcinoma using a convolutional neural network model

BackgroundComputed tomography (CT) is a common imaging technique for diagnosis of liver tumors. However, the intensity similarity on non-contrast CT images is small, making it difficult for radiologists to visually identify hepatic cavernous hemangioma (HCH) and hepatocellular carcinoma (HCC). Recently, convolutional neural networks (CNN) have been widely used in the study of medical image classification because more discriminative image features can be extracted than the human eye. Therefore, this study focused on developing a CNN model for identifying HCH and HCC.MethodsThis study is a retrospective study. A dataset consisting of 774 non-contrast CT images was collected from 50 patients with HCC or HCH, and the ground truth was given by three radiologists based on contrast-enhanced CT. Firstly, the non-contrast CT images dataset were randomly divided into a training set (n=559) and a test set (n=215). Then, we performed preprocessing of the non-contrast CT images using pseudo-color conversion, and the proposed CNN model developed using training set. Finally, the following indicators (accuracy, precision, recall) were used to quantitatively analyze the results.ResultsIn the test set, the proposed CNN model achieved a high classification accuracy of 84.25%, precision of 81.36%, and recall of 82.18%.ConclusionsThe CNN model for identifying HCH and HCC improves the accuracy of diagnosis on non-contrast CT images.     

Predictive model of postoperative pneumonia after neoadjuvant immunochemotherapy for esophageal cancer

BackgroundPostoperative pneumonia (PP) is the most common pulmonary complication of esophagectomy. It is of great importance to identify any high-risk factors and prevent pulmonary complications to improve the prognosis of patients with esophageal cancer undergoing esophagectomy. Thus, we established a predictive model of PP in patients with neoadjuvant immunochemotherapy for resectable esophageal squamous cell carcinoma (ESCC), and provide suggestions for the best strategy for the perioperative period of the patients.MethodWe retrospectively analyzed 78 patients who underwent esophagectomy for squamous cell carcinoma after neoadjuvant immunochemotherapy between September 2019 and August 2021.We used the “glmnet” language package in R to perform least absolute shrinkage and selection operator (LASSO) regression to screen the best predictors of PP, and nomograms predicting PP were constructed utilizing screened factors. The performance of nomograms was internally validated by calibration curves, concordance index (C-index), and the Brier score for overall performance.ResultsTwenty-six patients (33.3%) had postoperative pneumonia. After LASSO regression, the factors that were independently associated with PP were diffusing capacity of the lungs for carbon monoxide (DLCO) (P=0.0002), white blood cell (WBC) difference before vs. after neoadjuvant immunochemotherapy (P=0.0133). We constructed a prediction model, plotted the nomogram, and verified its accuracy. Its Brier score was 0.147, its calibration slope was 0.98, and its C-index was 0.85 (95% CI: 0.75–0.95). Internal validation demonstrated a good discrimination power that the actual probability corresponds closely with the predicted probability.ConclusionsOur prediction model can predict the possibility of PP in patients with neoadjuvant immunochemotherapy for resectable esophageal squamous cell carcinoma and may facilitate physicians’ efforts to reduce the incidence of postoperative pneumonia.     

人喉癌细胞端粒酶催化亚基cDNA片段的扩增与克隆

目的 :测定人喉鳞状上皮癌 hep- 2细胞的端粒酶活性水平并获得 hep- 2细胞中 h TERT c DNA片段的克隆。方法 :采用 TRAP- ELISA法测定酶活性水平 ,RT- PCR技术扩增获得目的片段。利用酶切法、PCR法和序列分析法对所获克隆进行检测。结果 :hep- 2细胞具有较高的端粒酶活性水平 ,获得含h TERT c DNA片段的克隆。结论 :利用 RT- PCR法能够从具有较高端粒酶活性水平的 hep- 2细胞中扩增获得 h TERT c DNA片段     

预见性护理模式对急性脑出血患者的影响观察

目的 探讨预见性护理模式对急性脑出血患者的影响.方法 选取北京海军总医院干部病房2010年4月～2012年11月收治的急性脑出血患者102例,随机分为研究组和对照组,每组各51例.对照组实施常规护理模式,研究组实施预见性护理模式.记录两组患者住院时间、并发症发生率及家属满意度情况.结果 ①研究组住院时间为(15.40±3.06)d,对照组为(20.15±5.13)d,差异有统计学意义(P＜0.05).②研究组肺部感染、脑部再出血、消化道出血、尿路感染及褥疮发生率均低于对照组,差异有统计学意义(P＜0.05).③研究组护理满意度为98.0％,对照组为82.4％,差异有统计学意义(P＜0.05).结论 预见性护理模式是一项科学、合理、有效的护理方案,不仅能降低脑出血患者并发症发生率,缩短住院时间,还能提高家属满意度,值得在临床上进一步推广.     

关节腔内给予地佐辛用于膝关节镜的临床观察

目的 评价关节腔内给予地佐辛对膝关节镜术后镇痛的影响。方法 选择择期行膝关节镜手术患者60例,随机分为A、B两组：A组关节腔内注射地佐辛5 mg（用生理盐水配制成10 mL）;B组关节腔内注射等量生理盐水10 mL。记录术后1、4、6、8、12和24 h患者在屈膝关节90°状态下的疼痛视觉模拟评分（VAS）,记录术毕至首次需要镇痛药时间以及术后不良反应的发生情况。结果 A组术后1,4,6,8,12 h的VAS评分分别为（2.3±0.6,2.6±0.5,3.0±0.5,2.8±0.6,2.9±0.7）明显低于B组（4.5±0.7,5.3±0.6,5.8±0.8,5.9±0.5,5.6±0.6）,差异有统计学意义（P〈0.05）,术后首次要求使用镇痛药物时间A组（265±40）min明显长于B组（62±11）min,差异有统计学意义（P〈0.01）。结论 关节腔内给予地佐辛用于膝关节镜能够提供良好的术后镇痛效果,延长术后镇痛时间。