Exploring the Dual Subjectivity of Kindergarten's Self-made Play and Teaching Aids Activities from the Perspective of Children's Play Development in China

The joint development of teachers and young children is the basis for promoting the development of high-quality preschool education in the new era,and encouraging early childhood teachers to make playthings according to local conditions is both the fine tradition of China's early childhood education and the direct orientation of China's preschool education policy.Homemade play and teaching aids are some of the methods often used in kindergartens,which skillfully combine young children's daily life objects with toys and early childhood teaching,not only enriching the collective activities of young children but also cultivating children's abilities in various aspects.Kindergarten homemade"play and teaching aids"for early childhood teachers and children have their special educational significance and value,therefore,this paper is based on the children and teachers double subject basis,discussing the homemade"play and teaching aids"for children and teachers of the double subject meanings,and puts forward the realization of the This paper discusses the double-subjective meaning of homemade teaching aids for children and teachers on the basis of the double-subjective foundation of children and teachers,and puts forward specific suggestions for realizing the double-subjectivity of kindergarten homemade teaching aids to enrich the theoretical value and practical significance of homemade teaching aids,to provide theoretical references and support for the relevant staff.

Observation on Curative Effect of Self-made Wubeizi Decoction Combined with rhaFGF in Promoting Postoperative Wound Healing in Patients with Anal Fistula

[Objectives]To explore the curative effect of Self-made Wubeizi Decoction combined with recombinant human acidic fibroblast growth factor(rhaFGF)in promoting postoperative wound healing in patients with anal fistula.[Methods]A total of 82 patients with anal fistula who underwent anal fistula resection+use of setons in Luodian Hospital during January and March of 2020 were randomly divided into observation group and control group with 41 cases in each group.The control group was given rhaFGF external application regimen,and the observation group was treated with Self-made Wubeizi Decoction on the basis of the control group.After 3 weeks of treatment,the differences in curative effects of TCM syndromes were compared between the two groups.Besides,the changes in TCM symptom scores,inflammatory mediators[interleukin-12(IL-12),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)],anorectal functions[anal resting pressure(ARP),maximal systolic pressure(MSP)and maximum tolerated volume(MTV)of the anal canal],quality of life[GQOLI-74 scores]were compared.[Results]After 3 weeks of treatment,the total effective rate of the observation group was significantly higher than that of the control group(P<0.05);the levels of TCM symptom scores,IL-12,TNF-α,IFN-γ,ARP,MSP,and MTV in both groups were significantly lower than those before treatment,and these levels in the observation group was significantly lower than that in the control group at the same time(P<0.05).The GQOLI-74 scores of both groups were significantly higher than those before treatment,and the observation group was significantly higher than the control group(P<0.05).[Conclusions]The Self-made Wubeizi Decoction combined with rhaFGF therapy has a significant effect in promoting postoperative wound healing in patients with anal fistula.It can effectively inhibit the local inflammation of patients,facilitate the recovery of anorectal function and improve the quality of life,thus has high clinical application value.

Linggui Zhugan Decoction Improves High Glucose-Induced Autophagy in Podocytes

Objective To explore the influence of Linggui Zhugan Decoction(LGZGD)on high glucose induced podocyte autophagy Methods LGZGD containing serum were prepared by intragastric administation of 4.2 g·kg^(-1)(low dose),8.4 g·kg^(-1)(medium dose),and 12.6 g·kg^(-1)(high dose)LGZGD into SD rats respectively.MPC5 and AB8/13 cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro.Podocytes,MPC5 and AB8.13,were divided into control group,high glucose group,low dose LGZGD group,medium dose LGZGD group,and high dose LGZGD group,respectively.For the three LGZGD groups,before LGZGD intervention,podocytes were treated with 60 mmol/L glucose for 3 days.After treated with LGZGD containing serum,cells were collected to analyze cell migration using Transwell assay,proliferation using CCK8,apoptosis and cell cycle using flow cytometry,,autophagosome formation using transmission electron microscopy,and expression levels of Beclin-1,Atg5,LC3II/I,and P62 proteins using western blot.Results Compared with the control group,the proliferation and migration of MPC5 and AB8.13 cells in high glucose group showed slightly decreased,whereas these parameters restored after intervention with low and medium concentrations of LGZGD,with the medium dose LGZGD having the best effect.Flow cytometry analysis showed that the medium dose LGZGD group had a lower apoptosis rate(P<0.05)and higher survival rate(P>0.05)compared to the high dose group.High glucose arrested podocytes in G1 phase,whereas LGZGD shifted podocytes from being predominant in G1 phase to increasing into G2.High dose LGZGD significanly reduced increased autophagosome formation due to high glucose in both podocytes(P<0.05).Western blot analysis showed that Beclin-1,Atg5,LC3Ⅱ/Ⅰ,and P62 expressions were increased in MPC5 cells treated with high glucose,and reversed after adminstration of low and medium doses of LGZGD(P<0.05).Conclusion LGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.

Pharmacodynamic study and mechanism of action of Linggui Zhugan Decoction in the intervention of Nonalcoholic fatty liver disease

Objective: To explore the therapeutic effect of Linggui Zhugan Decoction on nonalcoholic fatty liver disease through in vivo animal experiments, and to explore the mechanism of action of Linggui Zhugan Decoction in the intervention of nonalcoholic fatty liver disease through network pharmacology and molecular docking technology. Methods: A rat model of non- alcoholic fatty liver disease was established after 20 weeks of high-fat feeding, and the rats were divided into six groups, normal group, model group, simvastatin group (4 mg/kg), low- dose group of Linggui Zhugan Decoction (2.1 g/kg), medium-dose group of Linggui Zhugan Decoction (4.2 g/kg), and high-dose group of Linggui Zhugan Decoction (8.4 g/kg), and the liver morphological changes of HE staining and oil red O staining after the intervention of Linggui Zhugan Decoction were observed, and the microplate reader detected aspartate aminotransferase, alanine aminotransferase, Four levels of blood lipids. Network pharmacology combined with molecular docking was used to screen the potential mechanism and target of Linggui Zhugan Decoction for the intervention of non-alcoholic fatty liver disease. Results: Linggui Zhugan Decoction significantly improved the levels of alanine aminotransferase and alanine aminotransferase in model rats (P<0.05). HE staining and oil red O staining showed that Linggui Zhugan Decoction significantly reduced liver lipid deposition in rats in the model group. Linggui Zhugan Decoction could significantly reduce the quadruplical levels of blood lipids in model rats (P<0.05). Network pharmacology screened out 10 key targets and 5 key signaling pathways;The molecular docking results showed that the first 20 active ingredients all had good binding ability to the top 10 targets. Conclusion: The results show that Linggui Zhugan Decoction has the effect of regulating blood lipids and improving liver tissue lesions in non-alcoholic fatty liver disease, and preliminarily verifies the regulatory effect of Linggui Zhugan Decoction on lipid metabolism-related genes.

Process Analysis of Mobile Fermentation of Spent White Hypsizygus marmoreus Substrate with Self-made Mobile Fermentation Bag

The self-made mobile fermentation bag for spent white Hypsizygus marmoreus substrate was developed, and the relevant fermentation process was studied. The results showed that under the condition of single addition of Lactobacillus,nitrogen-free extract was degraded into lactic acid, leading to decreased pH value.On day 10, the fermentation effect reached the best with Lactobacillus abundance of 5.12×10~7/ml, lactic acid content of 0.48% and strong acid flavor. At this time, the fermentation material was moist without mildew and agglomeration, and was suitable for livestock and poultry. However, after 10 days, undesirable acids and mildew generated, a large amount of lactic acid bacteria died, and the fermentation material turned black and agglomerated, and became unsuitable for feeding livestock and poultry. Throughout the fermentation process, the pH value first decreased continuously until to 4.0, and then remained stable. During the fermentation of spent white H. marmoreus substrate, the nitrogen-free extract and crude fiber contents decreased, the crude protein content increased, while other indicators remained unchanged.

Severe skeletal bimaxillary protrusion treated with micro-implants and a self-made four-curvature torquing auxiliary: A case report

BACKGROUND Bimaxillary protrusion is a clinically common dentofacial deformity,particularly among Chinese patients.This kind of malformation can severely affect facial esthetics and,even in mild cases,is difficult to correct without surgery.Unfortunately,many patients abandon treatment because of fear of surgery.Here,we describe a case of severe skeletal bimaxillary protrusion treated with nonsurgical orthodontic treatments,highlighting an alternative treatment option.CASE SUMMARY A 31-year-old woman wished to address a severe protrusion profile(approximately 8 mm overbite)and gummy smile.Cephalometric analysis and superimposition showed a severe skeletal class II pattern with a mandibular retrusion,and proclined and protrusive mandibular incisors.Panoramic radiograph showed a missing mandibular right third molar.A diagnosis of severe bimaxillary dentoalveolar protrusion was made.Taking into account the patient’s fear of orthognathic surgery,she accepted the proposed alternative treatment using micro-implants and a self-made four-curvature torquing auxiliary.The treatment allowed for maximal en masse anterior tooth retraction,proper relocation of incisors,and alleviation of the skeletal class II pattern.Esthetically,the patient’s lip protrusion was significantly decreased as was the overjet(from 10.5 mm to 1.8 mm),and the results remained stable throughout the 2-year followup.CONCLUSION Nonsurgical treatment using micro-implants and a four-curvature torquing auxiliary may benefit severe cases of skeletal bimaxillary protrusion in adults.

Self-made wire loop snare successfully treats gastric persimmon stone under endoscopy

BACKGROUND Large gastric persimmon stones are generally resistant to standard endoscopic treatments.We applied an alternative endoscopic method using a hand-made snare for the treatment of large gastric phytobezoars.AIM To explore the clinical efficacy of a self-made wire loop snare to treat giant gastric persimmon stones.METHODS A retrospective study evaluated the clinical data of 38 patients with gastroliths admitted to Taihe Hospital in Shiyan City,Hubei Province,China,between March 2015 and October 2020.The patients were divided into observation(n=23)and control(n=15)groups.Patients in the observation group were treated with selfmade wire loop snares for lithotripsy,and patients in the control group were treated with traditional foreign body forceps,snares,injection needles,and other tools.Successful stone removal,treatment time,and hospital stay were compared.RESULTS The average operating time was significantly shorter(P<0.001)in the observation group(53.4 min)than that in the control group(172.8 min).The average hospital stay of the observation group(5.4 d)was significantly shorter(P<0.001)than that in the control group(10.3 d).Successful one-time treatment was significantly more frequent(P<0.001)in the observation group(87%)than in the control group(7%).CONCLUSION Self-made guidewire loop snares were successfully used to treat gastrolithiasis, and were significantly more effective than foreign body forceps, snares, and other traditionalmethods.

Protective Effects of Self-made Compound Taoren Danshen Decoction on Rats with Acute Liver Injury

[Objectives] To study the protective effects of self-made Compound Taoren Danshen Decoction( CTDD) on acute liver injury induced by D-galactosamine in rats,and to explore its mechanism. [Methods]An acute liver injury model was established by intraperitoneal injection of 500 mg/kg of D-galactosamine. The ALT,AST,MDA,SOD and GSH-Px in serum,as well as serum TNF-α,IL-1β and IL-6 levels were measured,and liver tissue lesions were observed under microscope. [Results] CTDD can significantly reduce ALT,AST and MDA levels,increase SOD,GSH-Px activity,and significantly reduce serum TNF-α,IL-1β and IL-6 levels,and improve liver tissue lesions.[Conclusions]CTDD has a protective effect on D-galactosamine-induced acute liver injury in rats,and its mechanism may be related to inhibition of oxidative stress and inflammatory reaction.

Observation on the Effect of Umbilical Therapy of Herbal Medicine Combined with Self-Made Dysmenorrhea Paste on Primary Dysmenorrhea

Objective:To investigate the clinical effect of self-made dysmenorrhea paste combined with umbilical therapy of herbal medicine on primary dysmenorrhea.Methods:160 patients with primary dysmenorrhea were recruited from Changle People’s Hospital.Participants were randomly divided into control group and treatment group,with 80 cases in each group.The control group were administered the dysmenorrhea paste sold on the market for 5 days during three menstruation cycles,and the treatment group was given the umbilical therapy of herbal medicine combined with self-made dysmenorrhea paste.The outcome was the intensity of menstrual pain measured by using the visual analogue scale,TCM symptom score and dysmenorrhea symptom score of patients,responder rate.The clinical outcomes were measured on each menstrual cycle at baseline,treatment course(3 cycles),and follow-up period.Results:In this study,there was no significant difference in age and severity of disease between the two groups before treatment.After treatment,VAS score,TCM symptom score and dysmenorrhea symptom score of patients in both groups decreased.The total effective rate was 90.75%in the treatment group and 81.25%in the control group.Conclusion:The treatment of primary dysmenorrhea patients with self-made dysmenorrhea paste combined with application of drugs and moxibustion naval-button method has a significant clinical effect.This method can reduce the pain of patients,improve the quality of life of patients,and homemade dysmenorrhea paste has a good taste,long shelf life,easy to carry,and is worthy of promotion and application.

Effect of self-made exhaust plaster on patients with gastrointestinal dysfunction after gynecological operation

Objective:To explore the effect of self-made exhaust patch(SMEP)on gastrointestinal dysfunction after gynecological operation.Methods:A total of 200 patients with gynecological operation in the gynecological ward of Shandong Changle People's Hospital were randomly divided into the control group(n=100)and the treatment group(n=100).The recovery time of bowel sounds,the time of first anal exhaust,the duration of abdominal distention,the duration of abdominal pain,the incidence of abdominal distention and abdominal pain and linical efficacy of SMEP were observed.Results:Compared with the control group,the recovery time of gastrointestinal function and the first anal exhaust time in the treatment group were shorter;the duration of abdominal distention and abdominal pain in the treatment group were shorter than those in the control group(P<0.05);Cure rate of abdominal distention in the treatment is 62.5%and cure rate of abdominal pain in the treatment is 60%within 72 hours after operation,which is higher than that in the control group(44.%,45.9%).Conclusion:The results showed that the self-made exhaust patch can improve the clinical symptoms of patients after gynecological abdominal surgery,and the self-made exhaust patch had a significant effect on gastrointestinal dysfunction after gynecological surgery,which was worthy of clinical promotion.

Clinical observation on TCM fumigation and washing for treatment of diabetic peripheral neuropathy by self-made water-washing footbath

the quality of life seriously,and even lead to more servere complications.On the base of the well-controlled blood glucose,improving the symptoms of both lower limbs timely will has positive significance for enhancing the life quality of patients and preventing complications of limbs.This article makes a comprehensive study on the application of self-made water-washing footbath in the treatment of DPN by Chinese medicine fumigation.From March 2018 to April 2018 in our hospital 20 cases of DPN patients were collected and they were divided into observation group(treated by self-made water-washing footbath with herbs)and control group(treated by conventional barrels),10 cases in each.The results showed that Chinese medicine fumigation on both lower limbs has clinical curative effect to improve the symptoms of arthromyodynia caused by diabetes.It provide an alternative method of external treatment for DPN patients with numbness in both lower limbs which could alleviate their suffering and improve the quality of life significantly.

加味苓桂术甘汤对阳虚水停证慢性心力衰竭患者TGF-β1、TNF-α、NT-proBNP及心室重构的影响

目的探究加味苓桂术甘汤对阳虚水停证慢性心力衰竭患者TGF-β1、TNF-α、NT-proBNP及心室重构的影响。方法将2017年12月至2020年11月六安市中医院收治的98例阳虚水停证慢性心力衰竭患者纳入本研究,随机分为两组,各49例。对照组行西医常规治疗,观察组在此基础上行加味苓桂术甘汤口服治疗,治疗6个月后检测心功能,血清肿瘤坏死因子(tumor necrosis factor,TNF)-α、转化生长因子(transforming growth factor,TGF)-β1、同型半胱氨酸(homocysteine,Hcy)、氨基末端脑钠素原(amminoterminal brain sodium minogen,NT-proBNP)水平并比较临床疗效。结果两组患者治疗后各项指标均较治疗前明显改善(P<0.05)。其中观察组患者治疗后血清TNF-α、TGF-β1、Hcy、NT-proBNP、左室舒张末期内径、左室收缩末期内径和中医证候总积分低于对照组,左室射血分数、6 min步行距离和临床疗效高于对照组(P<0.05)。结论加味苓桂术甘汤治疗阳虚水停证慢性心力衰竭可减轻患者炎症反应,预防心室重构,提高临床疗效。

基于miRNA21-5p调控TGF-β1/Smads信号通路探讨苓桂气化方抗射血分数保留心力衰竭心肌纤维化的机制

目的基于miRNA21-5p调控转化生长因子-β1(transforming growth factor beta 1,TGF-β1)/Smads信号通路探讨苓桂气化方抗射血分数保留心力衰竭(heart failure with preserved ejection fraction,HFpEF)心肌纤维化的机制。方法40只4周龄自发性高血压大鼠(spontaneously hypertensive rats,SHR)平均分为HFpEF组、沙库巴曲缬沙坦组(LCZ696,0.018 g·kg^(-1))、苓桂气化方低剂量组(LGQH-L,3.87 g·kg^(-1))和苓桂气化方高剂量组(LGQH-H,7.74 g·kg^(-1)),给予高脂、高盐及高糖饮食16周及腹腔注射链脲霉素溶液8周建立HFpEF大鼠模型。10只威斯塔京都(Wistar Kyoto,WKY)大鼠和10只SHR大鼠作为对照组,以普通饲料喂养至实验结束。造模成功后,WKY、SHR和HFpEF组给予等剂量生理盐水,其他3组按照预先规定的干预措施,每天灌胃1次,持续6周。干预结束后,行超声心动图测量左心室(left ventricle,LV)前壁厚度(LV end-diastolic anterior wall thickness,LVAWd)、LV后壁厚度(LV end-diastolic posterior wall thickness,LVPWd)、LV舒张末内径(LV end-diastolic internal diameter,LVIDd)、LV射血分数(LV ejection fraction,LVEF)、LV舒张早期二尖瓣流入峰值速度(E)、舒张晚期二尖瓣流入峰值速度(A)和LV舒张早期二尖瓣环运动速度(e'),并计算E/A和E/e';酶联免疫吸附试验检测血清心房钠尿肽(atrial natriuretic peptide,ANP)、B型利钠肽(B-type brain natriuretic peptide,BNP)及半乳糖凝集素3(Galectin-3,Gal-3);病理切片进行苏木精伊红及马松染色观察心肌肥厚及纤维化,并计算LV室壁厚度(LV wall thickness,LVWT)、胶原体积分数(collagen volume fraction,CVF)及血管周围纤维化比率(perivascular fibrosis ratio,PFR);实时定量聚合酶链反应检测LV心肌miRNA21-5p及TGF-β1/Smads信号通路相关mRNA表达;蛋白印迹检测LV心肌TGF-β1/Smads信号通路相关蛋白表达。结果与对照组比较,HFpEF组的LVAWd、LVPWd、LVIDd、E/A、E/e'、ANP、BNP、Gal-3、LVWT、CVF和PFR显著升高(P<0.05或P<0.01);LV心肌miR-NA21-5,α-SMA、CollⅠ、CollⅢ、TGF-β1、Smad2、Smad3 mRNA表达和α-SMA、CollⅠ、CollⅢ、TGF-β1、P-Smad2/3蛋白表达显著上调(P<0.05或P<0.01);Smad7 mRNA及蛋白表达显著下调(P<0.05或P<0.01)。与HFpEF组比较,苓桂气化方呈剂量依赖性减少LVAWd、LVPWd、LVIDd、E/A、E/e'、ANP、BNP、Gal-3、LVWT、CVF和PFR(P<0.05或P<0.01);下调miRNA21-5p,α-SMA、CollⅠ、CollⅢ、TGF-β1、Smad2、Smad3 mRNA表达和α-SMA、CollⅠ、GF-β1、P-Smad2/3蛋白表达(P<0.05或P<0.01);上调Smad7 mRNA及蛋白表达(P<0.05或P<0.01)。结论苓桂气化方可能通过靶向miRNA21-5p调控TGF-β1/Smads信号通路抑制心肌纤维化,从而减轻HFpEF大鼠LV重塑和舒张功能障碍,是治疗HFpEF的有效中药复方。

从“微饮”立论射血分数保留的心力衰竭早期防治思想

射血分数保留的心力衰竭(heart failure with preserved ejection fraction, HFpEF)是目前心血管领域的治疗难点,防治前线前移对于减缓或逆转HFpEF发病进程至关重要。聚焦HFpEF早期的中医防治,是发挥中医治未病优势的关键。通过梳理仲景提出的“微饮”内涵和证治,结合HFpEF早期的发病机制,提出HFpEF早期以微饮内停上焦为主要病机,临证应以苓桂术甘汤为主祛饮通阳,以期阻断饮证进一步发展,截断HFpEF发展进程。从“微饮”立论HFpEF早期防治,可以防微杜渐,具有重要的临床意义。

补中益气汤加减联合灵龟八法治疗胃癌放疗后癌性疲乏临床研究

目的:观察补中益气汤加减联合灵龟八法治疗胃癌放疗后癌性疲乏的临床疗效。方法:选择胃癌放疗后癌性疲乏患者84例,按随机数字表法分为对照组和观察组各42例。对照组给予常规对症支持治疗,观察组给予补中益气汤加减联合灵龟八法治疗。2组均治疗8周。比较2组临床疗效、中医证候评分、相关癌性疲乏量表评分、生活质量评分、营养状况及炎症因子水平,并统计恶心呕吐分级情况。结果:观察组总有效率为92.86%,高于对照组78.57%(P<0.05)。治疗后,2组纳差乏力、面色萎黄、头晕气短、肢体倦怠评分均较治疗前降低(P<0.05),且观察组各项评分低于对照组(P<0.05)。治疗后,2组简短疲劳量表(BFI-C)、临床虚弱量表(CFS)评分较治疗前降低,Karnofsky功能状态评分、日常生活活动能力(ADL)评分较治疗前升高(P<0.05);且观察组BFI-C、CFS评分低于对照组,Karnofsky功能状态评分、ADL评分高于对照组(P<0.05)。治疗后,2组血清前白蛋白、白蛋白、转铁蛋白水平较治疗前升高,血清白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平较治疗前降低(P<0.05);且观察组血清前白蛋白、白蛋白、转铁蛋白水平高于对照组,血清IL-6、IL-1β、TNF-α水平低于对照组(P<0.05)。观察组呕吐总发生率为47.62%,低于对照组73.81%(P<0.05)。结论:补中益气汤加减联合灵龟八法治疗胃癌放疗后癌性疲乏患者临床疗效显著。

苓桂剂类方方证分析与传承创新

苓桂剂类方是仲景基于水气病而设的,以茯苓、桂枝为主要配伍的一类组方。仲景经典的苓桂剂类方有7个,分别是苓桂术甘汤、苓桂枣甘汤、苓桂姜甘汤、苓桂味甘汤、五苓散、茯苓泽泻汤和防己茯苓汤。对苓桂剂的7个类方方证进行了系统梳理,从组方配伍、以方测证、方证对应、核心病机等方面进行了比较和分析,然后介绍了叶天士、刘渡舟和本研究团队对苓桂剂类方在传承中的丰富和发展。最后结合现代医学进展,总结了苓桂剂类方在临床的应用拓展与创新。传承是中医发展的基石,在传承中创新是中医赋予我们的使命,苓桂剂类方方证的传承是中医传承创新的典范。

经典名方苓桂术甘汤古籍考证与分析

苓桂术甘汤是2018年国家中医药管理局公布的《古代经典名方目录(第一批)》中收载的经典名方之一。通过收集整理古籍信息,从处方历史沿革、功能主治、药品炮制、药物剂量折算等方面,对苓桂术甘汤进行考证。经考证,苓桂术甘汤在《伤寒论》和《金匮要略》中均有记载,且药物配比及炮制方法略有差异,经典名方开发宜遵照《金匮要略》中药物剂量配比,桂枝使用《中华人民共和国药典》2020版中所规定的“桂枝”,并按其项下内容进行炮制,甘草宜用“炒甘草”。功能主治在水湿痰饮之病因的基础上有所延伸,包括阳虚水盛、痰饮咳嗽呕水等。药物剂量折算可以依据汉代一两等于13.8 g进行折算。

苓桂术甘汤干预非酒精性脂肪肝病的药效学研究及作用机制探讨

目的:通过体内动物实验探究苓桂术甘汤对非酒精性脂肪肝病的治疗效果,网络药理学及分子对接技术探究苓桂术甘汤干预非酒精性脂肪肝病的作用机制。方法:高脂喂养20周建立非酒精性脂肪肝病大鼠模型,将大鼠分为6组,正常组、模型组、辛伐他汀组(4 mg/kg)、苓桂术甘汤低剂量组(2.1 g/kg)、苓桂术甘汤中剂量组(4.2 g/kg)、苓桂术甘汤高剂量组(8.4 g/kg),观察苓桂术甘汤干预后的HE染色及油红O染色的肝脏形态学变化,酶标仪检测血清中谷草转氨酶、谷丙转氨酶、血脂四项水平。利用网络药理学结合分子对接筛选苓桂术甘汤干预非酒精性脂肪肝病潜在作用机制及靶点。结果:苓桂术甘汤可显著改善模型大鼠的谷草转氨酶、谷丙转氨酶水平(P<0.05);HE染色和油红O染色显示苓桂术甘汤显著降低模型组大鼠的肝脏脂质沉积;苓桂术甘汤可显著降低模型大鼠血脂四项水平(P<0.05);网络药理学筛选出关键靶点10个,关键信号通路5条;分子对接结果表明前20活性成分均对前十靶点有良好结合能力。结论:表明苓桂术甘汤对非酒精性脂肪肝病有调节血脂及改善肝组织病变作用,并初步验证了苓桂术甘汤对脂质代谢相关基因的调控作用。

苓桂气化方治疗射血分数保留的心力衰竭早期的临床研究

目的评价苓桂气化方对射血分数保留的心力衰竭(HFpEF)早期气化不利证见水饮内停患者运动耐量及心脏舒张功能的影响。方法采用随机数字表法将60例患者随机分为对照组和试验组各30例。对照组予西医常规治疗,试验组在此基础上予苓桂气化方颗粒,每次1袋,每日2次,口服。2组均治疗4周。比较2组治疗前后6min步行试验(6MWT)距离、堪萨斯城心肌病问卷(KCCQ)评分、中医症状积分、氨基末端脑钠肽前体(NT-proBNP)、运动负荷下左室舒张末期内径(LVEDD)、左心房内径(LAD)、室间隔厚度(IVST)、左室舒张早期充盈速度峰值(E)和心房收缩期左心室充盈速度峰值(A)。监测2组患者安全性指标。结果与本组治疗前比较,2组治疗后6MWT距离、KCCQ评分、中医症状积分及E、A值均明显改善(P<0.01),NT-proBNP、LVEDD、LAD、IVST差异无统计学意义(P>0.05)。2组治疗后比较,试验组6MWT距离、KCCQ评分、中医症状积分及E、A值均优于对照组(P<0.05,P<0.01),2组NT-proBNP、LVEDD、LAD、IVST差异均无统计学意义(P>0.05)。研究期间,2组均未发生不良反应及不良事件。结论苓桂气化方可改善HFpEF早期气化不利证见水饮内停患者的运动耐量和心脏舒张功能,抑制HFpEF早期心脏重构,延缓HFpEF发展进程。

基于NLRP3/Caspase-1/GSDMD信号通路探讨苓桂气化方改善射血分数保留心力衰竭早期舒张功能的分子机制

目的观察苓桂气化方对射血分数保留心力衰竭(heart failure with preserved ejection fraction,HFpEF)早期模型大鼠心脏舒张功能的干预效应,基于核苷酸结合寡聚化结构域样受体3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)/胱氨酸天冬氨酸特异性蛋白酶-1(cysteine-containing aspartate-specific proteases-1,Caspase-1)/消皮素D(Gasdermin D,GSDMD)通路探讨其潜在的分子作用机制。方法40只自发性高血压大鼠高盐高脂高糖饮食联合腹腔注射链脲佐菌素溶液建立HFpEF早期大鼠模型,分为HFpEF组、恩格列净组(1.8 mg/kg)、苓桂气化方低剂量组(4.96 g/kg)、苓桂气化方高剂量组(9.92 g/kg),予相应药物灌胃;正常血压组、空白组予等剂量生理盐水灌胃,连续干预9周。采用超声心动图检测大鼠左心房内径(left atrial diameter,LAD)、舒张早期二尖瓣血流速度(left ventricular early diastolic filling peak velocity,E)与舒张晚期二尖瓣血流速度(atrial systolic left ventricular filling peak velocity,A)比值、左室射血分数(left ventricular ejection fraction,LVEF);酶联免疫吸附测定法检测血清心房钠尿肽(atrial natriuretic peptide,ANP)含量;苏木精—伊红染色观察心肌组织病理变化;蛋白质印迹(Western Blot,WB)法检测NLRP3、Caspase-1、GSDMD和白介素1β(interleukin-1β,IL-1β)的表达。结果与正常血压组相比,HFpEF组LAD和E/A增加(P<0.05),LVEF无明显变化(P>0.05);血清ANP含量升高(P<0.05);病理观察显示心肌炎症浸润;WB结果示NLRP3、Caspase-1、GSDMD和IL-1β蛋白含量升高(P<0.05),表明建模成功。与HFpEF组比,恩格列净组和苓桂气化方低、高剂量组的LAD和E/A减小(P<0.05),血清ANP含量降低(P<0.05),病理观察显示心肌炎症浸润减轻,WB结果示恩格列净组NLRP3、Caspase-1、GSDMD、IL-1β蛋白含量降低(P<0.05),苓桂气化方低剂量组NLRP3、IL-1β蛋白含量降低(P<0.05),苓桂气化方高剂量组NLRP3、GSDMD、IL-1β蛋白含量降低(P<0.05),其余蛋白含量有下降趋势。结论苓桂气化方能改善HFpEF早期模型大鼠心脏舒张功能,其机制可能与调控NLRP3/Caspase-1/GSDMD信号通路、减轻心肌炎症浸润、抑制心房重构相关。