miR-n282对肝癌细胞侵袭、迁移能力的影响

目的 探究miR-4282对肝癌细胞侵袭、迁移能力的影响及作用机制.方法 qRT-PCR方法检测miR-4282转染至SMMC-7721细胞后表达量的变化.Transwell实验和细胞划痕实验检测细胞的迁移、侵袭.双荧光素酶检测miR-4282的互作基因,Westernblot和qRT-PCR方法验证基因及蛋白.结果 ...     

K-115增强自噬调控TGF-β1诱导的人Tenon囊成纤维细胞活化

目的:研究K-115对人Tenon囊成纤维细胞(HTFs)增殖和迁移的影响,并探讨其相关作用机制,为青光眼术后抗瘢痕治疗提供新思路。方法:选取2018-09/2019-09于河北省人民医院行青光眼手术患者的Tenon囊组织,采用组织块法进行HTFs原代培养,应用转化生长因子-β1(TGF-β1)诱导HTFs模拟青光眼滤过性手术后的细胞活化模型,并采用K-115处理细胞。将细胞分为4组：对照组采用溶剂二甲基亚砜(DMSO)处理;TGF-β1组采用10μg/L TGF-β1处理24h; TGF-β1+5 K-115组采用5μmol/L K-115预处理2h后加入10μg/L TGF-β1处理24h; TGF-β1+10 K-115组采用10μmol/L K-115预处理2h后加入10μg/L TGF-β1处理24h。通过细胞增殖实验观察细胞的增殖能力;划痕试验检测细胞的迁移能力;透射电子显微镜观察细胞内自噬小体的形成;Hoechst 33342/PI染色观察细胞凋亡情况。结果:细胞增殖实验结果提示K-115可以抑制TGF-β1诱导的HTFs增殖;划痕试验提示K-115可以抑制TGF-β1诱...     

奥氮平致呃逆1例

本文目的是通过报道1例奥氮平致呃逆,以引起临床医生对此不良反应的关注.1例47岁的男性癫痫性精神障碍患者,既往无重大躯体疾病史及呃逆病史,在接受丙戊酸钠缓释片及卡马西平治疗基础上,加用奥氮平10 mg/d,4天后出现持续性呃逆,停用奥氮平2天后,呃逆消失.再次应用奥氮平7天后又出现持续性呃逆,停用奥氮平2天后,呃逆又消...     

Catalytic N-methyl amidation of carboxylic acids under cooperative conditions

Amide is a fundamental group that is present in molecular structures of all domains of organic chemistry and the construction of this motif with high atom economy is the focus of the current research. Specifically, N-methyl amides are valuable building blocks in natural products and pharmaceutical science. Due to the volatile nature of methyl amine, the generation of N-methyl amides using simple acids with high atom economy is rare. Herein, we disclose an atom economic protocol to prepare this valuable motif under DABCO/Fe₃O₄ cooperative catalysis. This protocol is operationally simple and compatible with a range of aliphatic and (hetero)aromatic acids with very good yields (60–99%). Moreover, the Fe₃O₄ can be easily recovered and high efficiency is maintained for up to ten cycles.

The generation of N-methyl amides using simple acids with high atom economy is rare owning to the volatile nature of methyl amine. Herein, an atom economic protocol was disclosed to prepare this valuable motif under DABCO/Fe₃O₄ cooperative catalysis.

Amide is a fundamental group that is present in molecular structures of all domains of organic chemistry.¹ It is widely distributed in natural products, synthetic drugs and functional polymers, and is also the key chemical connection in proteins.² It has been shown that amide bond formation alone accounts for 65% of all preliminary screening reactions in the pharmaceutical industry.³ This means the generation of amide bonds with high atom efficiency is of high practical importance. And not surprisingly, ‘amide formation avoiding poor atom economy reagents’ was voted as the top challenge for organic chemistry by the ACS Green Chemistry Institute in 2007.³From synthetic point of view, the ideal way to produce amide bonds would be the direct coupling of readily available carboxylic acids and amines, but this process is thermodynamically unfavourable due to the formation of the corresponding carboxylate-ammonium salt,⁴ therefore, stoichiometric amount of coupling reagents, such as DCC, DIC, EDCI, HATU, HBTU, HCTU, SOCl₂, BOP, acid chloride etc, are generally required to sidestep thermal conditions for amide bond formation.⁵ These reagents are highly successful, but the process generally suffers from poor atom economy and side products removal issue especially in the large-scale applications.⁵ To overcome these drawbacks, “nonclassical” amide bonds formation routes were investigated.⁶ In these processes, the catalyst takes the role of a coupling reagent in generating an active ester suitable for amidation in a waste-free manner. However, these processes have not been applied in the preparation of N-methyl amides, probably because the methyl amine was delivered in its hydrochloride salt, alcoholic or aqueous form due to its volatile nature.On a different note, N-methyl amides are extensively presented in numerous natural products and pharmaceutical molecules, as shown in Fig. 1,⁷ and the methylation of amides is a promising way to improve the pharmacological property of molecules.⁸ However, the synthesis of N-methyl amides compounds relies heavily on non-catalytic approaches.^5,9 Catalytic approaches were also investigated by Hisaeda,¹⁰ Kundu,¹¹ Li,¹² Guo,¹³ Yu,¹⁴ Maruoka,¹⁵ Wang,¹⁶ Chen,¹⁷ Lamaty¹⁸ and their co-workers starting from nitriles, primiary amides, aldoximes, aldehydes, lignin, carbamoylsilane and alcohols. Until recently, Thakur,¹⁹ Marce,²⁰ Sadeghzadeh²¹ and their co-workers developed elegant N-methyl amidation approach starting from carboxylic acids under nano-MgO, diatomite Earth@IL/ZrCl₄ and Mg(NO₃)₂·6H₂O catalysis respectively, while limitations like poor substrate scope or sophisticated tailored catalyst still persist. Mindful of all the above issues, developing an N-methyl amidation process of simple carboxylic acids, which is still of great challenge in synthesis, and establishing a broad (hetero)aryl scope with high atom economy from commercial available reagents and catalysts were critical considerations in this study. Moreover, the significance of N-methyl amides combined with our interests in the development of green synthetic approaches motivated us to explore the direct coupling of the carboxylic acids and isothiocyanates. To the best of our knowledge, this is the first successful work using isothiocyanatomethane to prepare N-methyl amides.Open in a separate windowFig. 1Marketed drugs bearing N-methyl amide group.Our initial investigation begins with phenylacetic acid and isothiocyanatomethane as model substrate for condition optimization. Using acetonitrile as solvent, only trace amount of product was detected under catalyst free or p-toluenesulfonic acid (PTSA) catalysis conditions (

Analysis of circRNA‐mRNA expression profiles and functional enrichment in diabetes mellitus based on high throughput sequencing

To study the pathogenesis of diabetes mellitus (DM) and identify new biomarkers, high‐throughput RNA sequencing provides a technical means to explore the regulatory network of MD gene expression. To better elucidate the genetic basis of DM, we analysed the circRNA and mRNA expression profiles in serum samples from diabetic patients. The circRNAs and mRNAs with abnormal expression in the DM group and non‐diabetic group (NDM) were classified by RNA sequencing and differential expression analysis. The circRNA‐miRNA‐mRNA regulatory network reveals the mechanism by which competitive endogenous RNAs (ceRNAs) regulate gene expression. The biological functions and interactions of circRNA and mRNA were analysed by gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Differential expression analysis showed that 441 circRNAs (366 up‐regulated, 75 down‐regulated) and 683 mRNAs (354 up‐regulated, 329 down‐regulated) were significantly differentially expressed in the DM group compared with the NDM group. Screening of the differential genes at the nodes of the interaction network showed that a single circRNA could interact with multiple miRNAs and then jointly regulate more mRNAs. In addition, the expressions of circRNA CNOT6 and AXIN1 as well as mRNA STAT3, MYD88, and B2M were associated with the progression of diabetes. Enrichment pathway analysis indicated that differentially expressed circRNA and mRNA may participate in Nod‐like receptor signalling pathway, insulin signalling pathway, sphinolipid metabolism pathway, and ribosome pathway, and play a role in the pathogenesis of diabetes. This study provides a theoretical basis for elucidating the molecular mechanism of DM occurrence and development at circRNA and mRNA levels.     

Rituximab for the treatment of refractory anti-glomerular basement membrane disease

BackgroundAnti-glomerular basement membrane (anti-GBM) disease is a rare but severe autoantibody-mediated immune disorder. The typical clinical presentation includes rapidly progressive glomerulonephritis and often concurrent pulmonary hemorrhage. The present study is aimed to investigate the therapeutic effects of rituximab either used alone or with other immunosuppressants.MethodsEight patients diagnosed with anti-GBM disease and treated with rituximab from 2014 to 2020 were retrospectively reviewed.ResultsEight patients included 5 males and 3 females with a median age of 58.5 years. They all presented severe kidney injuries and 1 patient had lung hemorrhage. At diagnosis, the median of serum creatinine was 246 µmol/L (ranging from 91 to 850 µmol/L), with 3 patients requiring dialysis. All of them received corticosteroids and plasmapheresis. Rituximab was given as either standard four weekly doses or one pulse ranging from 100 to 600 mg. After a median follow-up of 34.5 months, kidney function was partially recovered or stabilized in 5/8 (62.5%) patients, free of dialysis. Anti-GBM antibodies remained undetected in all patients during follow-up. No severe adverse effect associated with rituximab was observed.ConclusionRituximab may be an alternative therapy in the treatment of patient with severe or refractory anti-GBM disease.     

肌激动器在安氏Ⅱ类错(牙合)治疗中的应用

目的 肌激动器矫正器在安氏Ⅱ类错[牙合]患者治疗中的应用特点。方法 20名10～11岁的以下凳后缩为主的安氏Ⅱ类错[牙合]患者应用肌激动器进行矫治。男9名,女11名。每位患者治疗前拍摄头颅侧位、曲面断层及手腕骨X线片。对肌激动器治疗前后及固定矫活器治疗后的头颅侧位X光片进行18个项目的测量,并对治疗前后测量结果进行配对t检验。结果SNA、ANB、OJ、U1／SN、UL-ELine、LL-ELine等在治疗后减小,差异有显著性;SNB、Li／MP、U1／PP、U6／PP、L1／MP、L6／MP、鼻唇角及额唇角增大,差异有显著性。下颌升支、下颌体以及下颌综合长度均有增长,差异有显著性。下领平面角在正畸治疗后无显著变化。结论 肌激动器在生长发育期的Ⅱ类患者的治疗中可以减小覆盖、覆皓、改善[牙合]关系并有效的改善患者下颌后缩的面型。对于存在拥挤的Ⅱ类患者,肌激动器度二期治疗时的拔牙治疗也可以达到良好的治疗效果。     

热环境对机体功能影响的机制及防护研究进展

热环境增加高温作业人员发生热损伤的风险,充分认识热环境对高温作业人员机体的影响和危害,对提高高温作业人员防暑意识、减少作业时的职业性热损伤具有重要意义.笔者主要从热环境的定义、热环境对人体主要功能系统影响的机制、热应激的影响因素及防护研究进展进行综述,为高温作业人员对热致疾病的认识及防护提供参考.     

音乐疗法联合右美托咪定对LC患者炎症的影响

目的：探讨音乐疗法联合右美托咪定对腹腔镜胆囊切除术(LC)患者炎症的影响。方法：选择2020年10月～2021年4月本院因胆囊良性疾病全身麻醉下择期行LC手术患者60例,随机分为两组,每组30例：对照组给予右美托咪定治疗;试验组给予音乐疗法+右美托咪定治疗。记录两组术中情况和生命体征;采用视觉模拟评分法(VAS)评估患者术后疼痛程度;用ELISA法测定血浆中TNF-α、IL-8、IL-10的浓度。结果：两组患者的ASA分级、性别、年龄、体重指数、麻醉时长、手术时长、输液量、出血量比较差异均无统计学意义。试验组在出手术室时以及术后8h、24h、48h的VSA评分与对照组同时间点相比较均明显降低。接受音乐疗法后,试验组的MAP、HR与对照组同时间点相比较均明显降低;试验组TNF-α、IL-8的浓度与对照组同时间点相比较均明显降低;试验组IL-10的浓度与对照组同时间点相比较明显升高。结论：音乐疗法联合右美托咪定可以更好的缓解LC患者术后疼痛,降低炎症反应。     

多节段布鲁菌性脊柱炎与脊柱结核MRI特征分析

目的 探讨多节段布鲁菌性脊柱炎(BS)及脊柱结核(ST)在MRI中的不同影像特点,从而提高早期诊断及鉴别诊断水平.方法 回顾性分析33例由临床或病理确诊为多节段BS患者、30例多节段ST患者,根据两者MRI表现,分析其发生部位、椎体形态、周围组织情况及伴随征象.结果 多节段BS患者的椎体形态、椎间盘受累、后凸畸形、死骨...