还贝止咳方对肺炎链球菌致大鼠肺热的治疗作用

目的 观察还贝止咳方对肺炎链球菌致肺热模型大鼠的胸腺、脾脏指数,炎性细胞及炎性因子的影响。方法 SD幼年大鼠随机分为对照组、模型组、头孢呋辛酯片组、小儿肺热咳喘颗粒组及还贝止咳方的低、中、高剂量组,采用鼻腔滴入肺炎链球菌的方法建立大鼠肺热模型,造模前后监测大鼠体温,评价大鼠肺热模型;采用流式细胞仪及全血分析仪检测大鼠全血中的炎性细胞;采用酶联免疫技术检测大鼠肺灌洗液（BALF）中的白细胞介素（IL-4、IL-1β、IL-6、IL-10）、肿瘤坏死因子-α（TNF-α）、血清免疫球蛋白E（IgE）水平;完整剥离大鼠脾脏和胸腺,检测脾脏指数和胸腺指数。结果 与对照组比较,模型组大鼠的体温明显升高（P<0.01）,说明造模成功。与模型组比较,还贝止咳方低、中、高剂量组大鼠体温均显著降低（P<0.05、0.01）,全血中的白细胞、嗜酸性粒细胞数目、Th/Ts比值均显著降低（P<0.05、0.01）,CD3⁺CD4⁺、CD3⁺CD8⁺细胞比例显著上升（P<0.05、0.01）;BALF中的IL-10、IL-1β、IL-6、IL-4、TNF-α的水平明显降低（P<0.05、0.01）;且对IL-1β及TNF-α的下调作用优于阳性对照药;脾脏指数明显升高（P<0.05、0.01）。结论 还贝止咳方对细菌性大鼠肺炎模型具有一定的治疗作用,主要通过调节大鼠的免疫功能,减轻炎性反应发挥作用。     

阿托伐他汀联合银杏二萜内酯葡胺注射液治疗急性脑梗死的临床研究

目的探讨应用阿托伐他汀联合银杏二萜内酯葡胺注射液治疗急性脑梗死的临床效果。方法选取2015年1月—2017年12月西宁市第一人民医院收治的急性脑梗死患者82例,随机分成对照组(41例)和治疗组(41例)。对照组静脉滴注银杏二萜内酯葡胺注射液,5 m L加入250 m L生理盐水,1次/d。治疗组在对照组基础上口服阿托伐他汀钙片,20 mg/次,1次/d。两组患者均连续治疗14 d。观察两组患者临床疗效,同时比较治疗前后两组患者总胆固醇(TC)/高密度脂蛋白胆固醇(HDL-C)、载脂蛋白(Apo)B/Apo A-l比值、国立卫生研究院卒中量表(NIHSS)评分、颈动脉超声参数及白介素(IL)-1β、IL-6、超氧化物歧化酶(SOD)和丙二醛(MDA)水平。结果治疗后,对照组和治疗组临床总有效率分别为75.6%、92.7%,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清TC/HDL-C、Apo B/Apo A-l比值和NIHSS评分均显著降低(P0.05),且治疗组上述指标显著低于对照组(P0.05)。治疗后,两组左、右两侧颈总动脉内径、RI及IMT值较治疗前均显著降低(P0.05),且治疗组颈动脉超声参数显著低于对照组(P0.05)。治疗后,两组血清IL-1β、IL-6、MDA浓度较治疗前显著降低低(P0.05),血清SOD水平显著升高(P0.05),且治疗组IL-1β、IL-6、SOD、MDA水平明显优于对照组(P0.05)。结论阿托伐他汀联合银杏二萜内酯葡胺注射液治疗急性脑梗死可有效改善患者神经功能,减轻机体炎性及氧化应激损伤,疗效确切。     

基于数据挖掘、网络药理学及临床观察探究贾跃进治疗女性失眠症用药规律及机制

目的结合数据挖掘、网络药理学、分子对接方法及临床观察,探究贾跃进临床治疗女性失眠症的用药规律及作用机制。方法首先使用古今医案云平台V2.2.3将贾跃进门诊近5年中药治疗女性失眠症的处方进行药物频次、属性统计以及关联、聚类和复杂网络分析,得出核心组方;再将核心组方运用TCMSP、GEO等数据库得到各药物有效成分的靶点与疾病靶点并取交集,利用CytoscapeV3.8.0及其插件构建疾病-药物-成分-靶点、蛋白互作网络,并进行基因本体论(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析;然后通过分析以上所得的2个网络获取其关键成分及靶点并进行分子对接;最终以核心组方为治疗组,网络药理学预测结果为主要观察指标进行临床研究验证。结果数据挖掘纳入验案221例,方剂258首,涉及中药139味;药性以平、温、微寒为多;药味以甘、辛、苦为主;药物主要归肝、脾经;通过药物关联、聚类和复杂网络分析综合得出11味药物的核心组方。网络药理学共获得核心组方有效成分65种,相关靶点490个,交集靶点142个,关键成分有β-谷甾醇和豆甾醇等,关键靶点聚类有神经递质类及细胞因子类等。GO功能富集分析结果显示,可能与代谢过程、免疫系统过程和信号过程有关;KEGG通路富集分析结果显示,可能与神经活性配体-受体相互作用、血清素能突触、多巴胺能突触等有关;分子对接较好的靶点为蛋白激酶Bα(protein kinase Bα,AKT1)、5-羟色胺受体1A(5-hydroxytryptamine receptor 1A,HTR1A)、多巴胺受体D2(dopamine receptor D2,DRD2)。临床研究显示,核心组方治疗组患者血清中褪黑素(melatonin,MT)水平显著升高,5-羟色胺(5-hydroxytryptamine,5-HT)、多巴胺(dopamine,DA)水平显著降低(P0.05)。结论贾跃进治疗女性失眠症的核心组方包括茯苓、白术、合欢皮、柴胡、香附、白芍、龙骨、当归、牡丹皮、栀子、白茅根,其主要通过多成分、多靶点调控MT、5-HT、DA而实现,对临床相关研究及对女性失眠症的治疗有一定指导意义。     

复方甘草酸苷注射液改善慢性乙型肝炎肝损伤疗效和安全性的系统评价与Meta分析

为系统评价复方甘草酸苷注射液(Compound Glycyrrhizin Injection,CGI)改善慢性乙型肝炎(chronic hepatitis B,CHB)肝损伤的有效性和安全性。该研究系统检索了PubMed、Web of Science、CBM、CNKI、Wanfang和VIP数据库,检索时限为建库至2020年2月10日。纳入CGI治疗CHB的随机对照试验(randomized controlled trial,RCT),由2名作者独立对纳入研究进行资料提取,并采用Cochrane偏倚风险评价工具对纳入研究进行方法学质量评价。应用RevMan 5.3软件进行数据统计分析。最终纳入18项双臂RCT,1915例受试者。所有纳入研究的方法学质量总体不高。对于CGI vs甘草酸二铵,CGI在提高临床总有效率上优于对照组,而在提高ALT复常率、降低ALT及AST水平上2组无统计学差异;对于CGI vs甘草酸二铵+其他一般保肝药,CGI在降低AST水平上优于对照组,而在降低ALT水平和提高临床总有效率上2组无统计学差异;对于CGI+其他常用药(包括能量合剂、谷胱甘肽、维生素及门冬氨酸钾镁等)vs甘草酸二铵+其他常用药,CGI联合其他常用药在降低ALT及AST水平、提高临床总有效率上均优于对照组,而在提高ALT复常率上2组无统计学差异;对于CGI+其他常用药vs其他常用药,CGI联合其他常用药在降低ALT及AST水平、提高临床总有效率上均优于对照组;对于CGI+维生素vs甘草酸二铵+门冬氨酸钾镁+维生素,在降低AST水平上2组无统计学差异。少数纳入研究报告了CGI单独或联合其他药物使用过程中会引起轻度不良反应。研究结果表明,CGI对改善CHB肝损伤具有一定疗效,目前证据尚不足以证明CGI会引起较严重安全性问题。未来仍需更多严格设计、足够样本量并严格实施的RCT进一步评价CGI改善CHB肝损伤的效果。     

Effect of different moxibustion interventions on hepatic histomorphology and PD-1 expression in immunosuppressed rabbits: 不同灸法干预对免疫抑制兔肝脏组织形态学及PD-1表达的影响

Objective To observe the changes in hepatic histomorphology and the differences in the expression of PD-1 after different moxibustion interventions in the immunosuppressed rabbits caused by cyclophosphamide and analyze the intervention effects of different moxibustion therapies.Methods A total of 40 big-ear white rabbits were randomized into 4 groups, i.e. a blank group, an immunosuppressed model group, a moxibustion group and a herbal-paste isolated moxibustion group, 10 rabbits in each one. In the immunosuppressed model group, the moxibustion group and the herbal-paste isolated moxibustion group, the intraperitoneal injection with cyclophosphamide was administered consecutively for 7 days, 60 mg/kg, and then, the immunosuppressed models were prepared. After the models were established successfully, in the moxibustion group and the herbal-paste isolated moxibustion group, moxibustion was administer at “Shénquè (神阙CV 8)” “Guānyuán (关元CV 4)” “Zúsānlĭ (足三里ST 36)” “Píshū (脾俞BL20)” and “Shènshū (肾俞BL23)”, once every other day, 10 times in total. In the blank group and the immunosuppressed model group, the rabbits were restricted on the rabbit platform at the same time periods, without intervention. On the second day after the end of intervention, the animals were weighed and anesthetized, and the livers were extracted. After routine HE staining, the changes of hepatic histomorphology were observed under the microscope and the morphometric analysis was conducted in each group. Besides, PD-1 expression was observed with immunohistochemical method.Result Compared with the blank group, after modeling of each animal in three groups, the body mass decreased obviously (all P < 0.01), the hepatocyte count decreased (all P < 0.01), the inflammatory cellular infiltration area was increased obviously (all P < 0.01), necrosis appeared in hepatic tissue and the positive expression of PD-1 in hepatic tissue was significantly increased (all P < 0.01). After moxibustion intervention, compared with the immunosuppressed model group, the body masses of the animals were increased obviously (P < 0.05, P < 0.01), the hepatocyte count was increased obviously (both P < 0.01), the infiltration area of inflammatory cells decreased significantly (both P < 0.01) and the expression of the PD-1 decreased in the hepatic tissue (both P < 0.05) in both the moxibustion group and the herbal-paste isolated moxibustion group. Compared with the moxibustion group, the animal body mass was higher obviously (P < 0.01), the hepatocyte count was raised apparently (P < 0.01) and the infiltration area of inflammatory cells were reduced obviously (P < 0.05) in the herbal-paste isolated moxibustion group.Conclusion The intervention with different moxibustion therapies improves the condition of body mass reduction and hepatic tissue damage of the immunosuppressed rabbits caused by cyclophosphamide. The effect of herbal-paste isolated moxibustion therapy is better than that of simple moxibustion therapy.     

对比基于PET/CT的不同方法定性诊断孤立性肺结节的效能

目的对比观察基于PET/CT的不同方法定性诊断孤立性肺结节(SPN)的效能。方法收集161接受PET/CT检查的SPN患者,比较良恶性SPN患者间临床表现、高分辨率CT(HRCT)征象及SUV max值的差异;通过二元Logistic回归构建SPN的数学诊断模型,比较诊断模型、PET/CT及HRCT的诊断效能。结果161例SPN中,经病理诊断恶性131例,良性30例。PET/CT诊断恶性SPN的灵敏度、特异度及准确率分别为98.47%(129/131)、76.67%(23/30)及94.41%(152/161),HRCT分别为59.54%(78/131)、83.33%(25/30)及63.98%(103/161)。经单因素及多因素分析后,将SUV max、年龄、钙化及气管血管集束纳入回归方程并建立模型,模型诊断恶性SPN的敏感度、特异度及准确率分别为82.44%(108/131)、86.67%(26/30)及83.23%(134/161)。ROC曲线结果显示,模型、PET/CT及HRCT诊断恶性SPN的AUC分别为0.909、0.876及0.714,PET/CT及模型的AUC均高于HRCT(P均<0.001),模型与PET/CT差异无统计学意义(P=0.468)。结论基于PET/CT的Logistic回归模型及PET/CT定性诊断SPN的效能优于HRCT,且特异度高于PET/CT。     

Comparative analysis of functional and aesthetic outcomes of retroauricular full thickness versus plantar glabrous split thickness skin grafts in pediatric palmar hand burns

BackgroundOptimal management of palmar hand burns in children is controversial. We aimed to compare function and aesthetics of retroauricular full thickness skin grafts (FTSG) to plantar glabrous split thickness skin grafts (STSG).Methods32 palmar grafts in paediatric burn patients were analysed: 19 retroauricular FTSG (group 1) and 13 thick plantar glabrous STSG (group 2). The latter were harvested at a thickness of 0.5 mm. The resulting plantar donor defects were covered with a STSG from the scalp, a sequential surgical technique we termed the “Zurich move”. Clinical examination, Cutometer and Colorimeter assessment and validated patient and observer questionnaires were used. Donor site complications and subjective complaints were recorded.ResultsColorimeter results were superior in group 2 with an erythema score of 5.73 ± 2.64 (group 1) versus 2.33 ± 1.97 (group 2, p < 0.001) and a pigmentation score of 9.82 ± 5.42 (group 1) and 1.89 ± 1.92 (group 2, p < 0.001). Observers` scar evaluation using VSS and POSAS showed significantly superior results in group 2 for almost all items. Conversely, group 1 grafts were less stiff with mean normalized tissue extension R0 of 0.80 ± 0.21 versus 0.57 ± 0.24 in group 2 grafts (p < 0.05). In both groups donor sites complications were rare.ConclusionPlantar glabrous STSG showed superior functional and aesthetic results when compared to FTSG in pediatric palmar hand burns. In addition, the “Zurich Move” is safe and provides uncomplicated donor site healing on the scalp and the foot allowing rapid restoration of full function.     

Fasudil regulates T cell responses through polarization of BV-2 cells in mice experimental autoimmune encephalomyelitis

Aim:

Fasudil, a selective Rho kinase (ROCK) inhibitor, has been shown to alleviate the severity of experimental autoimmune encephalomyelitis (EAE) via attenuating demyelination and neuroinflammation. The aim of this study was to investigate the effects of fasudil on interactions between macrophages/microglia and T cells in a mice EAE model.

Methods:

Mouse BV-2 microglia were treated with IFN-γ and fasudil. Cell viability was detected with MTT assay. BV-2 microglia polarization was analyzed using flow cytometry. Cytokines and other proteins were detected with ELISA and Western blotting, respectively. Mice were immunized with MOG_35–55 to induce EAE, and then treated with fasudil (40 mg/kg, ip) every other day from d 3 to d 27 pi. Encephalomyelitic T cells were prepared from the spleen of mice immunized with MOG_35–55 on d 9 pi.

Results:

Treatment of mouse BV-2 microglia with fasudil (15 μg/mL) induced significant phenotype polarization and functional plasticity, shifting M1 to M2 polarization. When co-cultured with the encephalomyelitic T cells, fasudil-treated BV-2 microglia significantly inhibited the proliferation of antigen-reactive T cells, and down-regulated IL-17-expressing CD4⁺ T cells and IL-17 production. Furthermore, fasudil-treated BV-2 microglia significantly up-regulated CD4⁺CD25^high and CD4⁺IL-10⁺ regulatory T cells (Tregs) and IL-10 production, suggesting that the encephalomyelitic T cells had converted to Tregs. In EAE mice, fasudil administration significantly decreased both CD11b⁺iNOS⁺ and CD11b⁺TNF-α⁺ M1 microglia, and increased CD11b⁺IL-10⁺ M2 microglia.

Conclusion:

Fasudil polarizes BV-2 microglia into M2 cells, which convert the encephalomyelitic T cells into Tregs in the mice EAE model.     

Comparative effectiveness of different acupuncture courses in functional constipation: A Bayesian network meta-analysis of clinical trials

AimThe purpose of this study was to examine the comparative effectiveness of different acupuncture courses for functional constipation (FC).BackgroundThere is a need to optimize the treatment course of acupuncture for FC to improve efficacy and save health resources.MethodsWe performed a systematic electronic search of eight databases from inception to April 2021. Randomized controlled trials comparing acupuncture treatment with sham acupuncture were included. The main outcome indicators were complete spontaneous bowel movement (CSBM), spontaneous bowel movement, Bristol Stool Form Scale (BSFS), responder rate and safety evaluation (SE).ResultsIn this network meta-analysis, 19 studies with 1753 participants and 8 different acupuncture treatments were included. Using the consistency model via Monte Carlo simulation iterations, we found that the effect of acupuncture treatment at 3/4 weeks may be better in terms of CSBM and BSFS. The results of rank probability analysis showed that 6 weeks of treatment may be better for the responder rate, and 2 weeks of treatment may be better for SE. And, subgroup analysis found that, for patients with chronic severe functional constipation (CSFC), 8 weeks of acupuncture treatment may be the best for CSBM.ConclusionsBy indirect comparison, 3/4 weeks of acupuncture treatment may be the optimal course of treatment for FC in terms of improving bowel frequency and stool shape. And for CSFC, 8 weeks of acupuncture treatment may be the best. However, there is still a lack of direct comparison and publication bias that affects the accuracy of research results.     

Acute and sub-chronic toxicity studies of the extract of Thunberg Fritillary Bulb

The aim of this study was to investigate the acute and sub-chronic toxicity of extract of Thunberg Fritillary Bulb. For the acute toxicity tests, graded doses of the extract were administered orally to mice. The animals were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were orally administered the extract at doses of 1 and 3 mg/kg body weight (BW) for 26 weeks. After 26 weeks, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD₅₀) was 52.2 mg/kg body weight in the mice. In the sub-chronic toxicity tests, a dose of 1 mg/kg body weight presented no toxicity. Above the 1 mg/kg dose, the main adverse signs observed in male rats were body or head tremor and spontaneous motor activity reduction. There were no other significant changes observed in hematology, blood biochemistry, organ weight and organ histology. The overall findings of this study indicate that the extract of Thunberg Fritillary Bulb is non-toxic up to 1 mg/kg body weight, which can be considered a safe application dose.