Shenqi compound formula has been widely utilized to improve aging -related diabetic nephropathy. Nevertheless, the underlying active ingredients and their molecular mechanisms of action remain doubtful. Thus, we aimed to identify the Shenqi compound formula mechanism involved in diabetic nephropathy treatment using system pharmacology. Candidate constituents and targets of Shenqi compound formula were obtained from traditional Chinese medicine systems pharmacology database. DisGeNET and GeneCards were utilized to build a diabetic nephropathy target database. A interactive network diagram of "drug -active ingredient -target" was fabricated employing Cytoscape. Employing Search Tool for Retrieval of Interacting Genes database, a protein -protein interaction network was established, protein -protein interaction relationships were analyzed, and visual analysis was implemented. Afterwards, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were implemented to identify the common targets. Finally, AutoDock Vina and PyMoL were utilized to confirm the molecular docking of key targets. Using electron microscopy, the morphological structure of MPC5 cells was observed. Western blotting was implemented to confirm the protein level in MPC5 cells. A total of 165 bioactive Shenqi formula compounds and 566 related target genes were obtained from traditional Chinese medicine systems pharmacology database. Furthermore, 521 diabetic nephropathyrelated target genes were obtained from GeneCard and DisGeNet databases. We observed that Shenqi compound formula and diabetic nephropathy share 130 common target genes, providing a molecular basis to treat diabetic nephropathy with Shenqi compound formula. Protein -protein interaction visualization analysis showed that protein kinase 1, albumin, and insulin were key target genes. The key components apigenin, glycine, and quercetin were obtained using degree values. Enrichment analysis showed that Shenqi compound formula interfered with diabetic nephropathy related signaling. Nephrotic syndrome type 2 and synaptopodin levels were markedly inferior to normal in the high glucose state, but increased after Shenqi compound formula treatment, as determined by Western blotting. Shenqi compound formula treats diabetic nephropathy using multi -component, multi -target, and multi -channel mechanisms. It was demonstrated that Shenqi compound formula has a beneficial effect on diabetes.

目的 探讨肝脏超声弹性成像技术使用机器学习构建模型用于识别 2 型糖尿病(type 2 diabetes mellitus,T2DM)患者的应用价值.方法 回顾性分析 2017 年 4 月至 2021 年 8 月于杭州西溪医院行超声弹性成像的 161 例疑似T2DM患者的临床资料,将纳入研究对象按 7∶3 比例随机分为训练组(n=111)和验证组(n=50).使用多因素Logistic回归在训练组筛选独立预测因子,基于这些独立预测因子使用机器学习方法构建预测模型,同时使用验证组数据和受试者操作特征曲线评估模型的准确性和可靠性.结果 使用随机森林算法构建的预测模型在训练组和验证组中识别T2DM患者的诊断性能分别为 90.4%和 89.8%,敏感度为 81.1%和 84.1%,特异性为 89.2%和 84.9%.在模型截断值为 0.464 时,其具有良好的临床分类效能.结论 超声弹性成像技术使用随机森林构建的预测模型可识别T2DM.

目的 观察养精种玉汤对卵巢储备功能下降(diminished ovarian reserve,DOR)模型大鼠性激素水平的影响,探讨养精种玉汤通过PI3K/AKT信号通路治疗DOR的作用与机制.方法 纳入动情周期正常的雌性SD大鼠50只,随机选取其中10只作为正常对照组(等剂量生理盐水),其余SD大鼠采用首次腹腔注射环磷酰胺50mg/kg,以每天8mg/kg的剂量连续腹腔注射14d诱导DOR模型.按随机数字表法将造模成功40只大鼠分为模型对照组(等剂量生理盐水,灌胃给予)、垂体促卵泡素阳性对照组(7.5 IU/kg,皮下注射,1次/日,连续7d)、养精种玉汤低剂量(16.5g/kg,灌胃给予,2次/日,连续7d)组和养精种玉汤高剂量(66g/kg,灌胃给予,2次/日,连续7d)组,每组10只.HE染色观察卵巢组织病理学变化,并计算各组大鼠生长卵泡数量,ELISA测定血清卵泡刺激素(follicle stimulating hormone,FSH)、黄体生成素(luteini-zing hormone,LH)、雌二醇(estradiol,E2)、抗苗勒管激素(anti-Mullerian hormone,AMH)水平,Western Blot 检测大鼠卵巢组织磷脂酰肌醇3-激酶(phosphoinositide 3-kinase,PI3K)、蛋白激酶B(protein kinase B,AKT)蛋白表达.结果 养精种玉汤高剂量组可提高模型大鼠体重、子宫与左侧卵巢的湿重、子宫系数(P＜0.05),促进生长卵泡生长发育(P＜0.05),下调FSH、LH蛋白表达(P＜0.05)、上调E2、AMH蛋白表达(P＜0.05),同时使PI3K、AKT蛋白表达升高.结论 养精种玉汤高剂量组能改善DOR大鼠卵巢储备功能,其机制与激活PI3K/AKT信号通路密切相关.

Bronchial asthma is a chronic inflammatory disease of the airways involving a variety of inflammatory cells and cellular components. To study the pathogenesis, treatment, and prognosis of this disease, a reliable animal model must be established. This article summarizes and evaluates the modeling methods for asthmatic animals and presents comprehensive comparison of the study of bronchial asthma animal models from different perspectives, hoping to provide a reference for researchers in the future.

目的 评估肝脏瞬时弹性成像技术(transient elastography,TE)对2型糖尿病(type 2 diabetes mellitus,T2DM)合并非酒精性脂肪性肝病(non–alcoholic fatty liver disease,NAFLD)的临床应用价值.方法 回顾性分析2018年4月至2021年8月在杭州市西溪医院的T2DM病例共54例,按有无合并NAFLD分为NAFLD组36例和非NAFLD组18例,基于TE检查获得肝脏脂肪衰减值(controlled attenuation parameter,CAP)及硬度值(liver stiffness measurement,LSM),比较分析两组CAP和LSM与疾病的关系.结果 CAP和谷丙转氨酶(alanine aminotransferase,ALT)是T2DM合并NAFLD发生的独立危险因素,其识别T2DM合并NAFLD的诊断效能分别为0.829和0.772,两者联合诊断效能为0.944.结论 TE技术的CAP测定是识别T2DM合并NAFLD患者的有效方法,尤其联合谷丙转氨酶具有更高的诊断效能.

Ulcerative colitis (UC) is a chronic, idiopathic inflammatory bowel disease. Its pathogenesis has not been fully revealed. Moreover, the lack of effective and safe treatment strategies is an obstacle for UC treatment currently. Animal models are essential tools in disease research. Therefore, the establishment of animal models with pathological manifestations similar to human UC is conducive to the full study of this disease. In this review, we reviewed the research progress of animal models of UC, and found that chemical induction is the most commonly used method for modeling UC. Based on the development of genomics technology, gene editing or knockout-induced spontaneous colitis is a vital direction for animal models research in the future. In addition, the indexes for evaluating the modeling results of UC animal models need to be further explored.

BACKGROUND:Chinese herbal preparations (CHPs) have been reported to be effective in the management of chronic heart failure (CHF); they are beneficial in improving cardiac function, reducing hospital stays and readmission. However, the credibility of their effectiveness evidence has not been evaluated. We aim to summarize and evaluate current effectiveness evidence of traditional Chinese medicine in the management of CHF. METHODS:We will search PubMed, Embase, the Cochrane Database of Systemic Review (CDSR), and Web of Science from inception to December 2019 for systematic reviews that assessing the effectiveness of CHPs for CHF. The search will be performed without language restriction. Experimental interventions will include any type of CHPs, and control interventions will include placebo, sham interventions, usual care, or no controls. The primary outcome will be the changes in heart function classification defined by the New York Heart Association. Secondary outcomes include left ventricular ejection fraction, Six Minute Walk Test, other efficacy outcomes, and adverse events. We will use I statistics to assess the between-study heterogeneity in each meta-analysis, Eager test to detect publication bias, and the ratio of observed versus expected number of trials with positive findings. We will summarize the evidence and classify them into convincing, highly suggestive, suggestive, or weak. RESULTS:The results of this study will be published in a peer-reviewed journal. ETHICS AND DISSEMINATION:No ethical approval and patient consent are required since this study data is based on published literature. The results of the study will be submitted to a peer-reviewed journal. PROTOCOL REGISTRATION NUMBER:PROSPERO CRD 42019139649 (https://www.crd.york.ac.uk/PROSPERO/#joinuppage).

目的 制备和优化西罗莫司(sirolimus,SRL)聚合物胶束,考察其对大鼠在体肠吸收动力学的影响.方法 以去氧胆酸修饰的壳聚糖(deoxycholic acid grafted chitosan,CS-DCA)为载体,采用溶剂蒸发法制备SRL CS-DCA胶束.以包封率、载药量、粒径和电位作为考察指标,结合星点设计-效应面法优化处方.建立大鼠在体单向肠灌流模型,并通过肠腔有效吸收系数(Peff)、吸收速率常数(Ka)和药物吸收剂量分数(fa)研究不同浓度SRL CS-DCA的肠吸收特性.结果 SRLCS-DCA最优处方:载体浓度(CS-DCA)为10 mg·mL-1,药物与载体质量比为20％,该条件下制备得到的SRL CS-DCA带正电荷(37.0±2.7)mV,粒径(182.2±5.7)nm,包封率＞90％,载药量(15.8±0.5)％.SRL CS-DCA经大鼠全肠后,反映药物肠吸收程度的评价指标Peff、Ka和fa均较SRL有显著提高(P＜0.05);不同浓度的SRL CS-DCA在大鼠全肠段的Peff、Ka、fa值无显著性差异,提示胶束在10～100 μg·mL-1吸收无浓度抑制,吸收特征为被动转运的线性动力学过程,推测其可能的吸收机制为被动扩散.结论 SRL制备成聚合物胶束后,对其在大鼠小肠的吸收具有明显的促进作用,从侧面证明SRLCS-DCA能有效改善SRL口服生物利用度.

目的 建立一种高灵敏度HPLC测定大鼠血浆中益母草碱浓度,并研究益母草碱在大鼠体内的药动学特征.方法 大鼠口服益母草碱混悬溶液(50 mg·kg-1)后,不同时间点尾静脉采血,以苯甲酰精氨酸乙酯为内标,血浆样品经酸化后乙酸乙酯萃取,采用HPLC进行测定.色谱条件:采用Diamonsil C18(250 mm×4.6 mm,5μm)为色谱柱,以乙腈-0.02 mol·L-1磷酸二氢钾缓冲溶液(pH 3.0)(22∶78)为流动相,流速1.0 mL·min-1,柱温35℃,检测波长277 nm.并利用PKS 1.0软件计算药动学参数.结果 益母草碱血浆浓度在0.05～1.5 μg·mL-1内线性关系良好(r=0.999 1).方法的定量下限(LLOQ)为0.05 μg·mL-1(RSD=12.8％,n=5);提取回收率为76.5％～82.5％;批内、批间准确度为96.9％～ 104.9％;日内、日间精密度均＜10％;质控样品经反复冻融3次及-20℃放置1个月后均较稳定.大鼠口服益母草碱后,药-时曲线符合二室开放模型,主要药动学参数为tmax=0.95 h,Cmax=0.51 μg·mL-1,t1/2=3.64 h,AUC0-t=1.56 μg·mL-1·h-1,AUC0-∞=1.78 μg·mL-1·h-1.结论 该方法准确度、灵敏度高,重复性好,可用于生物样品中益母草碱浓度的测定.

Liver fibrosis is a major pathological feature of chronic liver diseases, and effective therapies are limited at present. Asiatic acid (AA) is a triterpenoid isolated from Centella asiatica, which exhibits efficient anti-inflammatory and anti-oxidative activities. However, AA shows very low plasma levels after oral administration. In this study, AA loading PEGylated nanostructured lipid carriers (P-AA-NLCs) were prepared. P-AA-NLCs were characterized for particle size distribution, polydispersity index, entrapment efficiency, X-ray powder diffraction (XRD) pattern, differential scanning colorimeter (DSC), and transmission electron microscopy (TEM). The intestinal absorption, in vivo distribution, pharmacokinetics, and anti-fibrosis effects of P-AA-NLC were studied compared with that of AA-NLC. In situ single-pass intestinal perfusion model shows that there are significant differences in absorption between the free and NLCs formulation. The P-eff values of P-AA-NLC were significantly enhanced in all four intestinal segments compared to AA-NLC and free AA (p < .05). f(a)% and K-a showed similar trends, suggesting the PEGylated NLC can improve the gastrointestinal absorption of the drug. The pharmacokinetic studies presented that P-AA-NLC prolonged blood circulation times with a 1.5-fold higher relative bioavailability compared with AA-NLC. In vivo distribution experiments demonstrated that the fluorescence concentration in the liver was higher than that in other organs and the fluorescence intensity in the liver of DIR-P-NLC was about 1.3 times that of DIR-NLC. In addition, oral administration of P-AA-NLC can significantly attenuate CCl4-induced liver fibrosis and functional impairment in a dosage-dependent manner, including an increase in the albumin (ALB) and decrease in aspartate aminotransferase (AST) and alanine transaminase (ALT). Moreover, the MDA and HYP in liver tissue were downregulated, while the SOD activity was upregulated. In conclusion, P-AA-NLC can increase gastrointestinal absorption of AA and enhance anti-liver fibrosis effects in SD rats.

目的 制备石杉碱甲渗透泵控释微丸,并探讨其在Beagle犬内的药动学特性.方法 采用挤出滚圆法制备渗透泵含药丸芯,以乙基纤维素和PEG400用量为考察因素结合星点设计效应面法优选包衣液处方,通过流化床包衣工艺制备石杉碱甲渗透泵控释微丸.按最优处方制备3批微丸并以累积释放度与时间进行零级、一级、Higuchi方程拟合考察其释药特性.以市售的石杉碱甲普通片为参比制剂,考察自制石杉碱甲渗透泵控释微丸的体内药动学特点,并比较两制剂的生物等效性.结果 微丸最优处方为PEG400用量10.5％,乙基纤维素用量61.5％,所制备的石杉碱甲渗透泵控释微丸24 h内释药具有零级释放特征,释放动力以渗透压为主.自制石杉碱甲渗透泵控释微丸的tmax与ρmax明显低于参比制剂,其t1/2比参比制剂延长约1倍,相对生物利用度为95.8％.结论 Hup-A渗透泵控释微丸在Beagle犬中有较好的缓释效果,体内相关性良好.

目的:探究硬脂胺-异硫氰基荧光素嫁接物的最优合成工艺,并对其进行应用评价.方法:以硬脂胺和异硫氰基荧光素为原料,通过偶合反应合成得到脂质材料硬脂胺-异硫氰基荧光素嫁接物,利用薄层色谱法监测反应过程;通过核磁共振对嫁接产物进行结构确证,并以溶剂、时间、温度以及投料比为考察因素,以产率为指标,得到最优合成工艺.并将合成的硬脂胺-异硫氰基荧光素嫁接物用于标记脂质纳米粒,以结扎肠循环模型考察纳米粒在小肠的吸收分布情况对其进行应用评价.结果:当反应溶剂为无水乙醇,硬脂胺和异硫氰基荧光素的反应摩尔比为2∶1,60℃搅拌反应48 h后异硫氰基荧光素与硬脂胺反应最完全,产率较高,可达(72.0±3.9)％,并能较准确地评价其标记的纳米粒在肠绒毛吸收分布情况.结论:优化后合成处方工艺反应完全,得率高;方法操作简单,重复性好;合成的硬脂胺-异硫氰基荧光素嫁接物可用于直观评价纳米粒的体内外情况.

目的:研究益母草碱(leonurine,LE)在不同溶液中的稳定性,探讨其降解动力学特性.方法:通过经典恒温试验,采用HPLC法测定LE在不同pH溶液(pH范围2.0 ～11.0)及常用有机溶剂(甲醇、乙醇、异丙醇、乙腈)中的浓度,计算降解动力学参数.富集主要降解产物,利用核磁共振进行结构鉴定,推断其降解过程.结果:LE在酸性及中性溶液中较稳定,在碱性水溶液(pH =11.0)与甲醇中,遇热稳定性发生明显变化,降解反应速率常数k分别为1.700 4和1.395 μg· mL-1 ·h-1,t09分别为1.94与3.38h,均呈现零级动力学降解特征,主要降解产物分别为丁香酸与丁香酸甲酯.结论:LE在碱性溶液与甲醇中遇热不稳定,在制剂的制备过程中应注意温度和溶剂的选择.该研究为益母草碱制剂的开发提供了理论指导和数据支持.

目的:探讨小切口基底切开引流联合中药外敷及手法通乳治疗急性化脓性乳腺炎的效果.方法:随机选取82例急性化脓性乳腺炎患者的临床资料进行回顾性分析,按照治疗方式分为3组:A组采用传统乳腺脓肿切开引流术配合回乳,B组采用小切口乳腺脓肿基底引流联合手法排乳,C组采用小切口乳腺脓肿基底引流术联合手法排乳及中药外敷,以炎症消退时间、伤口愈合时间、病程长短、并发症作为观察指标,观察3组不同治疗方式的疗效.用SPSS17.0进行统计分析.结果:3组患者均全部治愈;切口愈合时间A组平均7.5 d,B组平均7.3 d,C组平均7.2 d;A组病程平均15.6 d,B组平均12.7 d,C组平均10.0 d;炎症消退时间:A组平均12.0 d,B组平均10.1 d,C组平均8.0 d,差异无统计学意义.结论:3组治疗方式都能达到疾病痊愈,小切口乳腺脓肿基底引流联合手法排乳及中药外敷治疗急性化脓性乳腺炎可以缩短切口愈合时间、病程、降低病人术后换药痛苦、切口美观、保留母乳喂养等优点,能使患者及婴幼儿最大程度获益.

Objective To prepare asiatic acid (AA) loaded chitosan-deoxycholic acid self-assembled micelles (AA-CS-DCA PMs) adopting chitosan-deoxycholic acid (CS-DCA) as carriers and investigate its pharmacokinetic characteristics in rats.Methods AA-CS-DCA PMs were prepared by ultrasonic dispersion method.The characteristics ofmicelles were evaluated by the distribution of particle size,Zeta potential,drug loading,encapsulation efficiency,and in vitro release.Model of bile drainage was established in conscious rats and pre-column derivatization HPLC method was used to determine the concentration of AA in bile.Moreover,the pharmacokinetics characteristics ofAA-CS-DCA PMs in vivo was evaluated by tmax,Cmax and AUC0-t.Results The particle size was (70.5 ± 9.8) nm,the Zeta potential was (38.4 ± 0.8) mV,and encapsulation efficiency and drug loading were (77.8 ± 1.2)％ and (11.7 ± 0.2)％,respectively.The in vitro release profile showed a sustained release property.In vivo study showed that Cmax of AA-CS-DCA group (26.05 ± 3.04) μg/h was 2.8 times higher than that of the control group (9.19 ± 1.12) μg/h;The tmax of AA-CS-DCA PMs group prolonged significantly (P ＜ 0.05) in biliary excretion (2 h vs 1 h) and the elimination half-life t1/2 was 1.8 times of the control group [(2.68 ± 1.71) h vs (1.49 ± 0.38 h)].In addition,the AUC0-24 h which reflected the degree of drug absorption increased by 200％ compared with the control group [(99.05 ± 12.83) μg vs (33.56 ± 8.33) μg].Conclusion The chitosan-deoxycholic acid self-assembled micelles can raise the concentration of AA and prolong the retention time in vivo,which effectively improve the oral bioavailability of AA.

A solvent diffusion method was used to prepare pegylated asiatic acid (AA) loaded nanostructured lipid carriers (p-AA-NLC), and the ligated intestinal circulation model was established to observe the absorption and distribution in small intestine. The concentration of AA in bile after oral administration of p-AA-NLC was detected by HPLC in healthy SD rats to indirectly evaluate the oral absorption promoting effect of PEG-modified namoparticles. The results showed that the penetration of p-AA-NLC was enhanced significantly and the transport capacity was increased greatly in small intestinal after PEG modification. As compared with the normal nanoparticles (AA-NLC), the Cmax of the drug excretion was increased by 76%, the time to reach the peak (tmax ) was decreased and the elimination half-life t1/2 was doubled in the rats after oral administration of p-AA-NLC, and the AUC0→t was 1.5 times of the AA-NLC group, indicating that the oral bioavailability of AA-NLC was significantly improved by hydrophilic modification of PEG.

介绍黄挺教授对甲状腺癌术后的中医辨证思路及治疗经验.黄挺教授从临床实践中发现,甲状腺癌多属虚实夹杂,在机体气阴两虚、气血不足甚或阴阳虚衰的基础上夹有气滞、痰凝、瘀毒内结.黄教授认为甲状腺癌术后辨证主要与中医阴虚火旺、气阴两虚以及痰瘀互结相关,并相应的采用滋阴清热、益气养阴、化痰行瘀等法治之,以提高中医对甲状腺癌术后中医调治的疗效.

介绍了黄挺教授对化疗后手足综合征的中医辨证思路及治疗经验.黄教授认为手足综合征的发生与中医风湿袭络、痰瘀阻络以及血虚失荣等致病因素相关,并相应地采用温经通络、祛湿散寒、益气养血、化痰行瘀等法治疗,以提高对手足综合征的治疗效果.

Objective:To investigate the appearance and diagnostic value of ultrasonic inspection on extra-peritoneum acute appendicitis. Methods:The ultrasonic appearance of twenty-one extra-peritoneum acute appendicitis patients was analyzed,and compared with surgical operation results. Results:The detection rate of ultrasonic diagnosis on extra-peritoneum acute appendicitis was 80.95%,which was close to clinical operation results.Conclusion:Facing an indefinite diagnosis on extra-peritoneum acute appendicitis,ultrasonic inspection can provide a real time and convenient differential diagnosis method.

肾穿刺活检是临床对慢性肾病分型诊断和确定治疗方案的重要手段.本研究通过对1 626例超声引导肾穿刺活检病例进行统计分析,探讨超声引导肾穿刺活检成功率及并发症的发生和安全防范措施.