A comparison of the effect of alendronate and You-Gui-Wan on osteoporosis in female rats with kidney-yang deficiency

Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.

Human androgen deficiency： insights gained from androgen receptor knockout mouse models

The mechanism of androgen action is complex. Recently, significant advances have been made into our understanding of how androgens act via the androgen receptor （AR） through the use of genetically modified mouse models. A number of global and tissue-specific AR knockout （ARKO） models have been generated using the Cre-loxP system which allows tissue- and/or cell-specific deletion. These ARKO models have examined a number of sites of androgen action including the cardiovascular system, the immune and hemopoetic system, bone, muscle, adipose tissue, the prostate and the brain. This review focuses on the insights that have been gained into human androgen deficiency through the use of ARKO mouse models at each of these sites of action, and highlights the strengths and limitations of these Cre-loxP mouse models that should be considered to ensure accurate interpretation of the phenotype.

Observation of tongue picture and tongue and nailbed microcirculation before and after blood dialysis in 125 uremic patients with deficiency of kidney-yang

using a WZD—1 microcirculation microscope,we observed the tongue tipand nail-bed microcirculation of uremic patients with deficiency of kidney-yangbefore and after blood dialysis.The results showed that the pathological basis ofuremia with deficiency of kidney-yang may be microcirculation disturbance,in-crease of metabolites and water retention.The effusion from capillary loops intongue tip may be one of the pathogenetic factors of a swollen and jaggedtongue.The flow rate of blood in capillary loops in the nail-bed was apparentlyabnormal and markedly improved after blood dialysis.The weighted integral ofnail-bed microcirculation decreased from moderately abnormal (4.99±1.52) toapproximately normal (1.98±0.97) (P【0.01).Microcirculation seems to be a sensi-tive criterion for reflecting the pathologic changes of uremia with deficiency ofkidney-yang.

Establishment and evaluation of a mouse model of bronchial asthma with Yin deficiency syndrome

Objective: To establish and evaluate a mouse model of bronchial asthma with Yin deficiency syndrome. Methods: The mouse model of bronchial asthma with Yin deficiency syndrome was established by the treatment with injecting ovalbumin(OVA) two times to sensitize, inhaling OVA 14 times to stimulate, and using thyroxin through lavage during late stimulation. This model was evaluated through body weight, asthmatic behaviors, respiratory function, autonomous activity, lung pathology, and pulmonary fluid clearance. Results: OVA combined with thyroxin was an appropriate method to induce the mouse model with increased food and water intake, autonomous activity, asthmatic behaviors score, and respiratory rate, decreased body weight, tidal volume, and wet/dry ratio of lung, and changed with pathology of lung tissue. The changes of the above mentioned parameters indicated that the model was the bronchial asthma with Yin deficiency syndrome. Conclusion: The OVA combined with thyroxin is a good pattern to establish a mouse model of bronchial asthma with Yin deficiency syndrome successfully, which can highly simulate the clinical symptoms of this disease.

Rat model for study of the essence of spleen deficiency and dampness in Chinese medicine

Objective:To explore the essence of spleen deficiency and dampness in Chinese medicine by successfully constructing a rat model with this syndrome.Methods:Rat models with the syndrome of dampness and spleen deficiency were established with the use of a high-fat,low-protein diet and excessive fatigue induced by loaded swimming.A total of 25 common clinical serological markers were tested.The T test,rank test,and partial least squares regression-discriminant analysis were used to analyze the data.Results:Total protein,albumin,motilin,interferon-γ,interleukin-2,immunoglobulin A,immunoglobulin G,and complement 3 levels in the model rats were lower than those in the control group(P=0.029,P=0.032,P<0.001,P<0.001,P<0.001,P<0.001,P<0.001,P<0.001,respectively).The serum creatinine,total cholesterol,aldosterone,antidiuretic hormone,gastrin,interleukin-4,somatostatin,atrial natriuretic peptide,and vasoactive intestinal peptide levels in the model group were higher than those in the control group(P<0.001,P=0.015,P<0.001,P<0.001,P<0.001,P<0.001,P<0.001,P<0.001,P<0.001,respectively).There was no statistical difference between the two groups in aspartate transaminase,alanine aminotransferase,globulin,albumin/globulin,blood urea nitrogen,high-density lipoprotein,and low-density lipoprotein.The model animal syndrome used two important variables in analysis with partial least squares regression-discriminant analysis.At the same time,the two dimensions were difficult to distinguish for each biological index.Conclusion:Spleen deficiency is often associated with dampness.The index that represents spleen deficiency can also represent dampness.Cytokines,immunoglobulins,and gastrointestinal hormones play a major causative role in both spleen deficiency and dampness.

Novel translational rat models of dopamine transporter deficiency

Dopamine （DA） is one of the brain＇s fundamental neurotransmitters. Despite the fact that the dopaminergic synapses constitute less than 1% of all brain synapses, DA is implicated in a number of critical physiological functions and in the pathogenesis of important psychiatric diseases such as schizophrenia, attention-deficit/hyperactivity disorder （ADHD）, Parkinson＇s disease （PD） and others.

Rat Models of Fatty Liver due to Liver Depression and Spleen Deficiency

[Objectives] To establish animal models of fatty liver due to liver depression and spleen deficiency that were suitable for activity discovery of traditional Chinese medicine( TCM) compounds,efficacy evaluation,new drug research and development and correspondence between prescription and syndrome of TCM. [Methods] A syndrome score scale that was suitable for evaluating the rat models was established according to the evolvement rules of etiology and pathogenesis of TCM and the modern clinical pathological mechanism. At the same time,bifendate pills and Sanqi Zhigan pills were selected as drug counterevidence for the models. Rats in model groups were given different proportions of high-fat and low-protein fodder and different concentrations of alcohol every day,and intraperitoneally injected with porcine serum twice a week. Drug groups were given with bifendate pills and Sanqi Zhigan pills( 8. 1 mg/kg,and 2. 7 g/kg) respectively for 14 consecutive days.During the experiment,general status,weight,daily fodder intake and daily water intake of the animals were observed,and TCM syndromes were scored. After the experiment,the levels of alanine aminotransferase( ALT),aspartate aminotransferase( AST),γ-glutamine transpeptidase( γ-GT),total cholesterol( TC),triglycerides( TG),low density lipoprotein-cholesterol( LDL-C),and high density lipoprotein-cholesterol( HDL-C) in serum were detected,and the pathological changes in liver tissue were observed. [Results] Compared with the control group,body weight,daily fodder and water intake of rats increased slowly in the model group,and the levels of ALT,AST,γ-GT,TC,TG and LDL-C increased significantly,while the level of HDL-C dropped. Pathological examination showed that steatosis and fat granule were observed in hepatocytes of rats in the model group. Behavioral observation found that main symptoms and minor symptoms of rats in the model group conformed to the syndrome manifestation of liver depression and spleen deficiency,which suggested that the three model groups were established successfully. Among them,three rats died in model group 1,and one rat died in model group 2. The manifestation of all the above lesions can be alleviated by drug counterevidence. [Conclusions]The animal model of fatty liver due to liver depression and spleen deficiency shows an obviously lower mortality and shorter duration and can be used for research of correlation between prescription and syndrome and its mechanism.

Electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure

Objective: To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure.Methods: Guinea pigs model of iron deficiency anemia complicated with chronic heart failure in 10 guinea pigs of the experimental group was made by feeding a low iron diet,pure water and subcutaneous injection of isoproterenol. The control group consisting of 11 guinea pigs was given normal food, normal water and injected with normal saline. The left ventricular outflow tract model specimen was also prepared. The standard microelectrode technique was used to observe electrophysiological changes of autonomic cells in the outflow tract of left ventricular heart failure complicated with iron deficiency anemia in guinea pig model. The indicators of observation were maximal diastolic potential, action potential amplitude, 0 phase maximal depolarization velocity, 4 phase automatic depolarization velocity, repolarization 50% and 90%, and spontaneous discharge frequency.Results: Compared with the control group, 4 phase automatic depolarization velocity,spontaneous discharge frequency and 0 phase maximal depolarization velocity decreased significantly(P < 0.01) and action potential amplitude reduced(P < 0.01) in model group. Moreover, repolarization 50% and 90% increased(P < 0.01).Conclusions: There are electrophysiological abnormalities of the left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with heart failure.

Effects of Different Processed Products of Radix Codonopsis on Intestinal Flora of Rats with Spleen Deficiency

[Objectives]This study aimed to observe the effects of different processed products of Radix Codonopsis on intestinal flora in rats with spleen deficiency.[Methods]Rat models with spleen deficiency were established by bitter-cold purgation method with Radix et Rhizoma Rhei.Normal group,model group,Radix Codonopsis group,fried Radix Codonopsis group,rice-fried Radix Codonopsis group,honey-fried Radix Codonopsis group and bran-fired Radix Codonopsis group were designed.After subjecting to corresponding treatments,the changes in the quantity of intestinal microorganisms of the rats were detected.[Results]There was no significant change in the quantity of intestinal microorganisms of the rats in the normal group and model group.The rats in the rice-fried Radix Codonopsis group were administered after successful modeling,and the abundance of Bifidobacterium and Lactobacillus in the intestines of the rats increased,and the quantity of Escherichia coli and Staphylococci reduced.The rats in the Radix Codonopsis group,fried Radix Codonopsis groups,honey-fried Radix Codonopsis group and bran-fried Radix Codonopsis group were administered after successful modeling,and the abundance of Bifidobacterium and Lactobacillus in the intestines of the rats increased(the increases were smaller than those in the rice-fried Radix Codonopsis group),and the abundance of E.coli and Staphylococci reduced,close to normal levels.[Conclusions]Different processed products of Radix Codonopsis have obvious regulation effect on intestinal flora of rats with spleen deficiency,and the regulation effect of rice-fried Radix Codonopsis on rats with spleen deficiency is better than that of Radix Codonopsis,fried Radix Codonopsis,honey-fried Radix Codonopsis and bran-fried Radix Codonopsis.

Guipi decoction effects on brain somatostatin levels and receptor mRNA expression in rats with spleen deficiency

BACKGROUND： Somatostatin is abundant in the hypothalamus, cerebral cortex, limbic system, and mesencephalon. Somatostatin mRNA expression in the brain of rats with spleen deficiency is noticeably reduced, as well as attenuation of cognitive function. OBJECTIVE： To observe the interventional effect of Guipi decoction on somatostatin level and somatostatin receptor 1 （SSTRl） mRNA expression in different encephalic regions of rats with spleen deficiency, and to compare the interventional effects of Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellet. DESIGN： A randomized controlled observation. SETTING： Basic Medical College, Beijing University of Traditional Chinese Medicine. MATERIALS： Fifty adult Wistar male rats, of clean grade, weighing （160 ± 10） g, were provided by Beijing Weitong Lihua Laboratory Animal Technology Co., Ltd. The protocol was performed in accordance with ethical guidelines for the use and care of animals. Somatostatin 1 polyclonal anti-rabbit antibody and SSTRl in situ hybridization kit were provided by Department of Neuroanatomy, Shanghai Second Military Medical University of Chinese PLA. The drug for developing rat models of spleen deficiency was composed of Dahuang, Houpu and Zhishi, and prepared at 2：1：1. Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellet recipes were made according to previous studies. METHODS： This study was performed at the Basic Medical College, Beijing University of Traditional Chinese Medicine from March 2002 to March 2005. The rats were randomly divided into 5 groups, with 10 rats in each group： normal, model, Guipi decoction, Chaihu Shugan powd.er, and Tianwang Buxin pellet groups. Rat models of the latter 4 groups were developed by methods of purgation with bitter and cold nature drugs, improper diet, and overstrain. The rats received 7.5 g/kg of the drugs each morning and were fasted every other day, but were allowed free access to water at all times. The rats were forced to swim in 25 ℃ water until fatigued. Rats in the normal group were intragastrically administered the same amount of normal saline. Rats in the Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellet groups were intragastrically administered 7.5 g/kg Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellet, respectively, every afternoon. All rats were treated for 6 weeks. MAIN OUTCOME MEASURES： Somatostatin protein and SSTRI mRNA expression in the ventral nucleus of hypothalamus, hippocampal CAl region, and cortex of prefrontal lobe were determined by immunohistochemistry and in situ hybridization, respectively. RESULTS： Fifty rats were included in the final analysis. In the model group, expression of somatostatin protein and SSTRl mRNA in the ventral nucleus of hypothalamus, hippocampal CAl region, and cortex of prefrontal lobe were significantly less than in the normal group （P 〈 0.01）. Above-mentioned indices were identical in the Chaihu Shugan powder and model groups. However, expression of somatostatin protein and SSTRl mRNA were significantly higher in the Guipi decoction group compared to model group （P 〈 0.01）. In the Tianwang Buxin pellet group, SSTRl mRNA expression in rat ventral nucleus of hypothalamus and somatostatin level in rat hippocampal CAl region and cortex of prefrontal lobe, as well as ventral nucleus of hypothalamus, were significantly higher compared to model group （P 〈 0.01 ）. CONCLUSION： Somatostatin level and SSTRl mRNA expression in rats with spleen deficiency were lower than in normal rats. Guipi decoction and Tianwang Buxin pellet up-regulated somatostatin level and SSTRl mRNA expression.

Flammulina velutipes polysaccharide-iron (Ⅲ) complex used to treat iron deficiency anemia after being absorbed via GLUT2 and SGLT1 transporters

Iron deficiency anemia(IDA)is a common nutritional problem, but traditional iron supplements cause many adverse reactions. Thus, the development of a novel iron supplement might be significant for the treatment of IDA. This study aimed to study the transport mechanism of Flammulina velutipes polysaccharide-iron complex(FVP1-Fe(Ⅲ))in Caco-2 cells and the therapeutic effect on IDA rats, as well as the influence on gut microbiota in vivo. These results showed that in vitro, the uptake of FVP1-Fe(Ⅲ)was mediated by sodium-dependent glucose transporter-1(SGLT1)and facilitated glucose transporter-2(GLUT2)and GLUT2 played a dominant function. The multidrug resistance-associated protein-2(MRP-2)was involved in the efflux of FVP1-Fe(Ⅲ)across the Caco-2 cells. In vivo, FVP1-Fe(Ⅲ)had a better restorative effect on blood parameters and iron status indicators in rats with IDA as compared with FeSO_4 and exerted this effect by downregulating the expression of hepcidin. FVP1-Fe(Ⅲ)could also regulate gut microbiota dysbiosis in iron deficiency rats by returning the relative abundance of gut microbiota to the normal level. Besides, as a dietary factor, vitamin C(vit C)could enhance the therapeutic effect of FVP1-Fe(Ⅲ). These present findings showed that FVP1-Fe(Ⅲ)could be exploited as a novel iron supplement to treat IDA.

Cost effectiveness of routine duodenal biopsies in iron deficiency anemia

AIM To investigate the cost effectiveness of routine small bowel biopsies(SBBs) in patients with iron deficiency anemia(IDA) independent of their celiac disease(CD) serology test results.METHODS We used a state transition Markov model. Two strategies were compared: routine SBBs during esophagogastroduodenoscopy(EGD) in all patients with IDA regardless their celiac serology status(strategy A) vs SBBs only in IDA patients with positive serology(strategy B). The main outcomes were quality adjusted life years(QALY),average cost and the incremental cost effectiveness ratio(ICER). One way sensitivity analysis was performed on all variables and two way sensitivity analysis on selected variables were done. In order to validate the results,a Monte Carlo simulation of 100 sample trials with 10,and an acceptability curve were performed.RESULTS Strategy A of routine SBBs yielded 19.888 QALYs with a cost of $218.10 compared to 19.887 QALYs and $234.17 in strategy B. In terms of cost-effectiveness,strategy A was the dominant strategy,as long as the cost of SBBs stayed less than $67. In addition,the ICER of strategy A was preferable,providing the cost of biopsy stays under $77. Monte Carlo simulation demonstrated that strategy A yielded the same QALY but with lower costs than strategy B. CONCLUSION Our model suggests that EGD with routine SBBs is a cost-effective approach with improved QALYs in patients with IDA when the prevalence of CD is 5% or greater. SBBs should be a routine screening tool for CD among patients with IDA,regardless of their celiac antibody status.

Electrophysiological changes of Papillary Muscles in Guinea Pigs with iron deficiency anemia and heart failure

Objective:To investigate the changes of left ventricular papillary muscle action potentials in guinea pigs with iron deficiency anemia and heart failure.Methods:A total of 20 cases of iron deficiency anemia with heart failure were treated with experimental group and 10 normal guinea pigs as control group. Blood samples were collected to determine hemoglobin content, red blood cell number and whole blood iron index, and the changes of cardiac function and hemodynamics were detected by 6240 biological signal collection system to determine whether the model was successful or not, Intracellular microelectrode technique was used to determine the action potentials of the papillary muscles in the model group and the control group. the potential amplitudes (APA), overshoot values (APA), maximum depolarization rate (Vmax), 20 % of repolarization, 50 % and 90 % of repolarization (APD20, APD50 and APD90 ) and the average velocity of repolarization were measured. Compare statistical difference between the model group and the control group.Results: 14 cases of model group survived completely, compared with control group, APD50 and APD90 prolonged, and the average velocity decreased.Conclusions: the action potential repolarization duration in the guinea pig papillary muscle of iron deficiency anemia with heart failure is prolonged, and the average repolarization velocity is slow.

中医证候动物模型建立及评价方法研究

中医证候动物模型是揭示中医基础理论、促进中医药临床发展的重要载体,更是促进中医药现代化与国际化不可或缺的重要工具。目前,中医证候动物模型建立方法多样,评价标准不一。基于五脏的主要生理功能,以临床常见的心气虚证、肝郁证、脾气虚证、肺气虚证、肾阳虚证为代表,总结分析近年来最常用的中医证候动物模型的构建及评价方法,为建立更为科学客观的中医证候动物模型构建方法及评价体系提供参考。

基于组轨迹模型的全球艾滋病疾病负担变化模式研究

目的基于组轨迹模型分析全球与中国1990-2021年人类免疫缺陷病毒/获得性免疫缺陷综合征(HIV/AIDS)感染者的疾病负担现状及趋势变化情况,为我国艾滋病防控提供参考依据。方法由全球疾病负担研究(GBD 2021)数据获得1990-2021年HIV/AIDS感染者的疾病指标,利用Joinpoint模型描述全球及中国1990-2021年HIV/AIDS疾病负担变化趋势,探索潜在转折点并拟合基于疾病负担指标的单组轨迹模型。结果Joinpoint回归趋势分析显示,1990-2021年全球和中国标准化发病率呈先增长后下降趋势,全球伤残调整寿命年率(DALYs)与标准化死亡率呈先增长后下降的趋势,而中国标准化死亡率与DALYs呈现波动上升趋势。组轨迹分析结果显示,年龄标准化发病率可分为低水平上升组、中水平上升组和高水平下降组3组轨迹,年龄标准化死亡率与DALYs可分为低水平上升组、中水平上升后下降组和高水平上升后下降组3组轨迹。结论HIV/AIDS的疾病负担整体趋势在地区间存在差异。针对低水平上升组,可通过加强预防教育,增加检测机会,确保感染者得到尽早管理;针对中水平上升后下降组,可通过定期评估现行防控措施,确保资源合理配置,提高干预效果;针对高水平下降组,应推动加强基础教育,推广安全套使用,减少新发感染人数,以期降低疾病负担。

A study on the clinical prediction model of the yin deficiency type of perimenopausal syndrome

Background:The yin deficiency type of perimenopausal syndrome(PMS)as a common category of PMS based on the theory of traditional Chinese medicine(TCM)has a high prevalence with severe symptoms and long course of disease.Therefore,it is necessary to construct a prediction model to assist in diagnosis.Objective:This study aimed to investigate the independent predictors of the yin deficiency type of PMS and to develop a clinical prediction model of this disease.Methods:PMS patients who attended the Third Affiliated Hospital of Zhejiang Chinese Medical University between February 2020 and August 2023 were selected and divided chronologically into training and validation groups.Logistic regression analysis was applied in the training group to clarify the independent predictors of the yin deficiency type of PMS,and a nomogram was plotted.Internal and external validations were performed in the training and validation groups to evaluate the model’s accuracy,goodness of fit,and clinical adaptability.Results:Hot flashes and sweating(≥10 episodes/day),palpitations,emotional fluctuations,and abnormal sexual activity were independent predictors of the yin deficiency type of PMS(P>0.05).Based on the clinical prediction model constructed,the area under the receiver operating characteristic curve(AUR OC)in the training group was 0.989(95%CI 0.980–0.998),and the AUR OC in the validation group was 0.971(95%CI 0.940–0.999).This demonstrates that the model has superior prediction performance.The Hosmer-Lemeshow test was used to evaluate the model’s goodness of fit with P=0.596 for the training group and P=0.883 for the validation group,indicating a good fit.The decision curve analysis(DCA)curve and clinical impact curve(CIC)indicated good clinical adaptability.Conclusion:The model can accurately predict the occurrence of the yin deficiency type of PMS,which may help clinicians identify such patients at an early stage.

Study of establishing disease-syndrome combined with animal model for immune thrombocytopenic purpura without additional conditions

Objective:To explore the feasibility of establishing the disease-syndrome combined animal model for immune thrombocytopenic purpura(ITP)without additional conditions.Methods:Three batches of data related to the ITP model mice obtained by replication at different time were analyzed,and whether the APS-injected model mice replicated through the passive immune modeling method could simulate the pathogenesis and clinical characteristics of human ITP was evaluated according to the differentiation criteria for diseasesyndrome combined model.Results:The APS-injected replicated ITP model mice possessed the following traits:(1)Compared with the normal group,the platelet count was significantly decreased,and coagulation time was significantly increased in the model group(P<.01).(2)Compared with the normal group,the medullary thrombocytogenous megakaryocytes were significantly decreased(P<.05,.01,.001).(3)The APS-injected sites and other parts of the model mice had spontaneous hemorrhage.(4)Behavioral changing signs were observed 1 week after the modeling(i.e.low activity,delayed activity,poor appetite,skin petechia/hemorrhage and spontaneous hemorrhage at the injected sites or other parts),and were getting more and more severe.Conclusion:According to the syndrome differentiation criteria for disease-syndrome combined model of ITP,the APS-injected animal model of ITP replicated through the passive immune modeling method without additional conditions possesses the characteristics of disease-syndrome combined model.It provides an ideal tool for the development of traditional Chinese medicine pharmacology experiment.

中老年冠心病心绞痛患者中医虚证诊断模型的探索与构建

目的 构建中老年冠心病心绞痛中医虚证的诊断预测模型。方法 选取2021年1月至2022年12月南京中医药大学泰州附属医院住院的160例冠心病心绞痛中老年(50~85岁)患者的临床资料,统计年龄、性别、体重指数、吸烟、饮酒、血常规、血脂、肝肾功能、冠状动脉血管病变程度,以及高血压病、糖尿病、胃肠道疾病、慢性阻塞性肺疾病、脑血管疾病等合并症作为自变量,每位患者均给出虚实辨证,其结果作为因变量。应用单因素logistic回归筛选变量,多因素logistic回归分析建立模型,可视化模型。使用受试者操作特征曲线、校准曲线及决策曲线分析评估模型。结果 160例患者实证83例,虚证77例。多因素回归结果显示:年龄>67~85岁[OR=2.776,95%CI(1.219,6.321),P=0.015]、糖尿病[OR=2.230,95%CI(0.960,5.178),P=0.062]、Genisi评分4.50~7.50[OR=10.126,95%CI(2.574,39.843),P=0.001]、Genisi评分8.00~15.75 [OR=13.510,95%CI(3.441,53.040),P<0.001]、Genisi评分16.00~80.00[OR=53.032,95%CI(11.769,230.027),P<0.001]是冠心病心绞痛虚证的预测因子。模型方程为:Logit(虚证概率)=-4.231+1.021×年龄(>67~85岁)+0.802×患糖尿病+2.315×Gensini等级(4.50~7.50)+2.603×Gensini等级(8.00~15.75)+3.952×Gensini等级(16.00~80.00)。该模型受试者曲线下面积值为0.852(95%CI:0.795~0.910)。校准度曲线提示准确度较好,决策曲线分析表现在该预测变量在6%~85%广大风险范围内展现出较好的正向收益率。结论 本研究构建了一个中老年冠心病心绞痛虚证诊断预测模型,有较好的临床预测能力。

脾虚泄泻模型大鼠肠组织结构及分泌型免疫球蛋白A含量变化研究

为研究脾虚泄泻大鼠肠道结构和肠道分泌型免疫球蛋白A的变化,试验选取24只健康SD大鼠,雌雄各半,随机分为脾虚泄泻模型组和空白对照组,在不同阶段采用“饮食失调+苦寒泻下”的方法人工复制大鼠脾虚泄泻模型,连续14 d监测大鼠的采食量、饮水量、精神状态、粪便等临床特征变化,记录第7天和第14天时大鼠的空腹体质量,采集小肠组织进行结构观察,并测定盲肠内容物中分泌型免疫球蛋白A的含量。结果表明,与空白对照组相比,模型组大鼠在试验期间出现粪便稀溏、食欲下降、消瘦、蜷缩扎堆、精神萎靡等临床症状;与空白对照组相比,模型组大鼠的体质量显著降低(P<0.05);模型组大鼠十二指肠绒毛高度,空肠隐窝深度、绒毛高度、绒毛宽度,回肠隐窝深度和绒毛宽度均显著低于空白对照组(P<0.05);模型组大鼠十二指肠隐窝深度、绒毛宽度及回肠绒毛高度均极显著低于空白对照组(P<0.01);模型组大鼠小肠不同段的绒毛高度与隐窝深度比值均低于空白对照组,但差异不显著(P>0.05);模型组大鼠盲肠内容物中sIgA含量极显著低于空白对照组(P<0.01)。结果提示,本试验成功建立了脾虚泄泻大鼠模型,脾虚泄泻可损伤大鼠小肠黏膜结构并降低盲肠中sIgA含量。

黄精改善中年房劳肾精亏虚大鼠免疫功能紊乱的作用研究

[目的]研究黄精对中年房劳肾精亏虚模型大鼠免疫功能紊乱的调节作用。[方法]采用“中年雄鼠+雌雄同笼”方法制备中年房劳肾精亏虚大鼠模型,模拟中年男性因房劳致肾精亏虚引起的免疫功能紊乱状态。实验期间测定大鼠脾脏系数;苏木精-伊红(hematoxylin-eosin,HE)染色观察脾组织形态学变化;测定骨髓中性粒细胞和淋巴细胞占比,外周血淋巴细胞数量及其占比和中性粒细胞占比;脾淋巴细胞增殖试验检测脾脏淋巴细胞增殖能力;流式细胞术测定脾组织T淋巴细胞亚群占比;原位末端转移酶标记(terminal-deoxynucleoitidyl transferase mediated nick end labeling,TUNEL)检测脾组织细胞凋亡情况;免疫印迹检测脾组织与增殖相关蛋白磷酸化磷脂酰肌醇3-激酶(phospho-phosphatidylinositol 3-kinase,p-PI3K)、磷酸化蛋白激酶B(phospho-ptotein kinase B,p-AKT)和与凋亡相关蛋白B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)、Bcl-2相关X(Bcl-2 associated X,Bax)蛋白表达。[结结果]黄精可降低中年房劳肾精亏虚模型大鼠骨髓和外周血中性粒细胞占比,升高骨髓淋巴细胞占比,升高外周血淋巴细胞数量及其占比,降低脾组织T淋巴细胞(CD4^(+)/CD8^(+))比值,提高脾组织T淋巴细胞增殖能力,减少脾组织内的细胞凋亡,升高脾组织中与增殖相关蛋白p-PI3K和p-AKT的表达。[结论]黄精通过影响T淋巴细胞及其亚群占比,改善中年大鼠因肾精亏虚引起的免疫功能紊乱,其机制可能与调控脾组织与增殖相关蛋白PI3K/AKT的表达有关。