Although the animal models of hepatic fibrosis developed by former researchers have pathological changes of hepatic fibrosis, they do not include charac- teristics of important TCM syndromes such as stagnation of qi, ...Although the animal models of hepatic fibrosis developed by former researchers have pathological changes of hepatic fibrosis, they do not include charac- teristics of important TCM syndromes such as stagnation of qi, deficiency of qi, liver depression, phlegm-dampness and blood stasis because of single-factor model- ing. Animal models of hepatic fibrosis and animal models integrated disease and syndrome were reviewed, and several new types of integrated disease and syndrome animal models constructed by multiple-factor modeling method were evaluated, under the guidance of etiological theory of TCM. This kind of hepatic fibrosis model animals has dual characteristics of disease and syndrome. It is consistent with pathological characteristics of hepatic fibrosis in western medicine when replicating the basic characteristics accorded with TCM syndrome. Thus, the pathogenesis and pathogenic process of clinical disease and syndrome formation is simulated more ac- curately, providing a new platform and pathway for studying hepatic fibrosis disease with integrated traditional Chinese and western medicine.展开更多
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 mo...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.展开更多
BACKGROUND: Central adrenergic nerve and 5-serotonergic nerve can influence central cholinergic nerve on learning and memory and make easy for study; however, ginsenoside of stem and leaf (GSL) can improve function...BACKGROUND: Central adrenergic nerve and 5-serotonergic nerve can influence central cholinergic nerve on learning and memory and make easy for study; however, ginsenoside of stem and leaf (GSL) can improve functions of central adrenergic nerve; moreover, 5-serotonergic nerve and the combination with choline can produce synergistic effect and enhance learning and memory ability so as to improve learning and memory disorder of patients with Alzheimer disease (AD). OBJECTIVE : To observe the effects of GSL combining with choline on learning and memory of AD model rats DESIGN : Randomized grouping design and controlled animal study SETIING : Department of Pharmacology, Taishan Medical College MATERIALS : The experiment was carried out in the Pharmacological Department of Medical College of Jilin University from October 1996 to January 1997. Forty healthy male Wistar rats of clean grade were randomly divided into 5 groups, including sham-injury group, model group, GSL group, choline group and combination group, with 8 rats in each group. Main medications: GSL with the volume more than 92.8% was provided by Department of Chemistry, Norman Bethune Medical College of Jilin University. Panaxatriol, the main component, was detected with thin layer scanning technique and regarded as the index of GSL quality [(55±1)%, CV= 2%, n = 5]. Choline was provided by the Third Shanghai Laboratory Factory. METHODS : 150 nmol quinolinic acid was used to damage bilateral Meynert basal nuclei of adult rats so as to establish AD models. Rats in GSL, choline and combination groups were intragastric administrated with 400 mg/kg GSL, 200 mg/kg choline (20 mL/kg), and both respectively last for 17 days starting from two days before operation. Rats in sham-injury group and model group were perfused with the same volume of distilled water once in each morning for the same days. (1) Passive avoidance step-down test: Five minutes later, rats jumped up safe platform when they were shocked with 36 V alternating current. If rats jumped down from the platform and the feet touched railings, the response was wrong. Numbers of wrong response were recorded within 3 minutes, and then the test was redone after 24 hours. (2) Morris water-maze spatial localization task: Swimming from jumping-off to platform directly was regarded as right response. Additionally, 4 successively right responses were regarded as the standard. Each rat was trained 10 times a day with 120 s per time for 3 successive days. The interval was 30 s. Three days later, numbers of right response were recorded. The training times were increased to 30 for unlearned rats. (3) Measurement of activity of choline acetylase in cerebral cortex: Rats were sacrificed at 17 days after operation to obtain cerebral cortex to measure activity of choline acetylase with radiochemistry technique. (4) Synergistic effect: It was expressed as Q value: Q value = factual incorporative effect/anticipant incorporative effect; Q ≥ 1 was regarded as synergistic effect. Anticipant incorporative effect = (EA+EB-EA·EB), EA and EB were single timing effect, respectively in GSL group and choline group. E(step-down test and Morris water maze test) = (x in model group - factual value in medicine groups)/x in model group; E (activity of choline acetylase) = (factual value in medicine groups -xin model group)/xin model group. MAIN OUTCOME MEASURES : (1) Passive avoidance step-down test and Morris water-maze spatial localization task in the study of learning and memory; (2) activity of choline acetylase. RESULTS : All 40 rats were involved in the final analysis. (1) Passive avoidance response: At learning phase on first day and retesting phase on the next day, numbers of wrong responses within 3 minutes were more in model group than sham operation group, and there was significant difference [(5.88±1.46), (2.25±0.87) times; (2.63±1.06), (0.50±0.53) times; P 〈 0.01]; numbers of wrong responses within 3 minutes were less in combination group than model group, and there was significant difference [learning phase: (1.12±0.83), (5.88±1.46) times; retesting phase: (0.38±0.74), (2.63±1.06)times, P 〈 0.01]; moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.07 and 1.59, respectively and it showed synergistic effect. Spatial localization task: Training times were more in model group than sham operation group, and there was significant difference [(2.9±2.5), (12.6±3.5) times; P 〈 0.01]. Training times were less in combination group than model group, and there was significant difference [(11.8±2.4), (27.9±2.5) times, P 〈 0.01]; moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.07 and it showed synergistic effect. (3) Activity of choline acetylase: Activity was lower in model group than sham operation group, and there was significant difference [(30.56±8.33), (61.11 ±8.33) nkat/g; P 〈 0.01]. Activity was higher in combination group than model group and there was significant difference [(50.00±8.33), (30.56±8.33) nkat/g, P 〈 0.01];moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.5 and it showed synergistic effect. CONCLUSZON: GSL in combination with choline can synergically improve the disorder of learning and memory of AD model rats. Its mechanism may be involved in enhancing the function of central cholinergic system.展开更多
Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic bac...Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic background,the application of patient-specific induced pluripotent stem cell-derived cardiomyocytes(iPSC-CMs)may help to reveal cell phenotype characteristics underlying different genetic variations.Here,to verify and compare the pathogenicity of mutations(SCN5A c.4213G>A and SCN1B c.590C>T)identified from two BrS patients,we generated two novel BrS iPS cell lines that carried missense mutations in SCN5A or SCN1B,compared their structures and electrophysiology,and evaluated the safety of quinidine in patient-specific iPSC-derived CMs.Compared to the control group,BrS-CMs showed a significant reduction in sodium current,prolonged action potential duration,and varying degrees of decreased Vmax,but no structural difference.After applying different concentrations of quinidine,drug-induced cardiotoxicity was not observed within 3-fold unbound effective therapeutic plasma concentration(ETPC).The data presented proved that iPSC-CMs with variants in SCN5A c.4213G>A or SCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events.展开更多
AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesi...AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS,which addresses the possibility that formerly established rat model of colitis could be used as an IBS model after the inflammation subsided. METHODS:Colitis was induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley rats.The extent of inflammation was assessed by histological examination and myeloperoxidase(MPO)activity assay.After subsidence of colitis,the rats were subjected to rectal distension and restraint stress,then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured, respectively. RESULTS:At 2 days post-induction of colitis,the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity.At 7 days post-induction of colitis,the histological features and MPO activity returned to normal.The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance,and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.展开更多
Pulmonary hypertension due to left heart disease(PH-LHD) is regarded as the most prevalent form of pulmonary hypertension(PH). Indeed, PH is an independent risk factor and predicts adverse prognosis for patients with ...Pulmonary hypertension due to left heart disease(PH-LHD) is regarded as the most prevalent form of pulmonary hypertension(PH). Indeed, PH is an independent risk factor and predicts adverse prognosis for patients with left heart disease(LHD). Clinically, there are no drugs or treatments that directly address PH-LHD, and treatment of LHD alone will not also ameliorate PH. To target the underlying physiopathological alterations of PH-LHD and to develop novel therapeutic approaches for this population, animal models that simulate the pathophysiology of PH-LHD are required. There are several available models for PH-LHD that have been successfully employed in rodents or large animals by artificially provoking an elevated pressure load on the left heart, which by transduction elicits an escalated pressure in pulmonary artery. In addition, metabolic derangement combined with aortic banding or vascular endothelial growth factor receptor antagonist is also currently applied to reproduce the phenotype of PH-LHD. As of today, none of the animal models exactly recapitulates the condition of patients with PH-LHD. Nevertheless, the selection of an appropriate animal model is essential in basic and translational studies of PH-LHD. Therefore, this review will summarize the characteristics of each PH-LHD animal model and discuss the advantages and limitations of the different models.展开更多
As the acceleration of aged population tendency, building models to forecast Alzheimer’s Disease (AD) is essential. In this article, we surveyed 1157 interviewees. By analyzing the results using three machine learnin...As the acceleration of aged population tendency, building models to forecast Alzheimer’s Disease (AD) is essential. In this article, we surveyed 1157 interviewees. By analyzing the results using three machine learning methods—BP neural network, SVM and random forest, we can derive the accuracy of them in forecasting AD, so that we can compare the methods in solving AD prediction. Among them, random forest is the most accurate method. Moreover, to combine the advantages of the methods, we build a new combination forecasting model based on the three machine learning models, which is proved more accurate than the models singly. At last, we give the conclusion of the connection between life style and AD, and provide several suggestions for elderly people to help them prevent AD.展开更多
The prevention and treatment of myocardial ischemia is a hot and difficult point in clinical research and animal experimental research in the cardiovascular field.The combined disease and syndrome animal model with th...The prevention and treatment of myocardial ischemia is a hot and difficult point in clinical research and animal experimental research in the cardiovascular field.The combined disease and syndrome animal model with the disease characteristics of Western medicine and guided by the theory of Chinese medicineto replicate the"syndrome"of Chinese medicine on the model animals by using experimental methods is an effective tool for the research of Chinese medicine.This article summarized the methoding methods and evaluation index of the animal model combined disease of coronary heart disease myocardial ischemia with cold blood stasis,phlegm and blood stasis,qi deficiency and blood stasis syndrome,kidney deficiency and blood stasis,and concluded the treatment of Traditional Chinese medicine.At the same time,it analyzed the main deficiencies of myocardial ischemia syndrome combined with animal models to provide reference for the establishment and research of related animal models.展开更多
Background To investigate the incidence,risk factors,and clinical prognosis of cerebral hyperperfusion syndrome(CHS)after superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-duro-art...Background To investigate the incidence,risk factors,and clinical prognosis of cerebral hyperperfusion syndrome(CHS)after superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-duro-arterio-synangiosis(STA-MCA/EDAS)in adult patients with moyamoya disease(MMD).Methods The clinical data of 160 adult patients with MMD treated by STA-MCA/EDAS from January 2016 to January 2017 were retrospectively analyzed.According to CHS diagnosis,MMD patients were divided into CHS and non-CHS group.Univariate and multivariate analysis of risk factors and Kaplan-Meier curve of stroke-free survival for CHS were performed.Results A total of 12 patients(7.5%)developed postoperative CHS,of which 4 patients(2.5%)presented with cerebral hemorrhage.Univariate and multivariate analysis showed moyamoya vessel on the surgical hemisphere(OR=3.04,95%CI=1.02-9.03,P=0.046)and left operated hemisphere(OR=5.16,95%CI=1.09-21.34,P=0.041)were independent risk factors for CHS.The other variables,such as age,gender,presentation,hypertension,diabetes,smoking,mean mRS score on admission,modified Suzuki stage and pre-infarction stage on surgical hemisphere,and bypass patency,had no association with postoperative CHS(P>0.05).At final follow-up with average 38 months,there were 18 out of 133 patients(13.5%,4.91%per person year)presented with newly developed complications.There was no significant difference between newly developed complications,mean mRS scores,and Kaplan-Meier curve of stroke-free survival in patients with and without CHS(P>0.05).Conclusion The concentration of moyamoya vessels and left operated hemisphere was independent risk factors for CHS,which could not affect the clinical prognosis if treated timely and properly.The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.展开更多
Objective: To study the treatmaient of non-small cell lung cancer, we established the HU-Prim allograft transplantation tumor model. Methods: The fresh tumor samples were transplanted in the right scapular subcutaneou...Objective: To study the treatmaient of non-small cell lung cancer, we established the HU-Prim allograft transplantation tumor model. Methods: The fresh tumor samples were transplanted in the right scapular subcutaneous layer of the severe combined immunodeficient Non-obese diabetic/severe combined immunodeficient(NOD/SCID) mice. The pathological features of the tumors were observed. Nonnecrotic tissue was inoculated subcutaneously into the right axillary. When the tumor in burdened rat grew approximately 100 mm3, according to the tumor size all the animals were divided into the following four groups, eight rats in each group: solvent control group, gefitinib group(100 mg/kg), erlotinib group(50 mg/kg), afatinib group(20 mg/kg). Aniamals were treated with drugs by intragastric(i.g.) administrated, once daily, for consecutively 14 days. Measure the tumor size 2-3 times every week. Results: Hu Prime1-NSCLC mutant sensitive xenograft model research data showed that reversible tyrosine kinase inhibitors gefitinib, erlotinib and irreversible tyrosine kinase inhibitor afatinib could effectively inhibit tumor growth in EGFR positive NSCLC allografts model. The pharmacodynamic activity of irreversible inhibitor was better than that of the reversible inhibitor. Specimens from clinical anthropogenic tumor retain characteristics of the human primary malignancy, histopathology, biological characteristics, and tumor markers, etc., which can more accurately reflect the characteristics of the tumor and the impact of interventions. Conclusion: The model is not only a good antitumor drug experimental platform, but also a new evaluation tool of individualized medication.展开更多
OBJECTIVE: To study the use of Jianjining in the treatment of myasthenia gravis (MG) patients with a deficiency of both spleen and kidney via the theory on the combination of disease with syndrome. METHODS: Sixty MG p...OBJECTIVE: To study the use of Jianjining in the treatment of myasthenia gravis (MG) patients with a deficiency of both spleen and kidney via the theory on the combination of disease with syndrome. METHODS: Sixty MG patients with a deficiency of both spleen and kidney were randomly divided into an treatment group (n=30) treated with Jianjining granules and Western Medicine (prednisone or pyridostigmine bromide) and a control group (n= 30) treated with Jianjining granules. The dosage of the three drugs was reduced over the course of treatment. After 3 and 6 months of treatment, the curative effect was evaluated with the muscle weakness severity scale (MWSS). RESULTS: The MWSS score after treatment declined significantly in both groups. The score in the treatment group was much lower than that in thecontrol group (P<0.05). The total effective rate was 63.33% (19/30) in the treatment group and 36.67% (11/30) in the control group after 3 months of treatment, and 80.00% (24/30) and 50.00% (15/30), respectively, after 6 months of treatment. The obvious and total effective rates in the treatment group were much higher than those in the control group (P<0.05). After 6 months of treatment, there were no obvious differences (P>0.05) in the obvious and effective rates between the 2 groups. However, the total effective rate in the treatment group was much higher than that in the control group (P<0.01). CONCLUSION: Using the theory on the combination of disease with syndrome, we found that the curative effect of Jianjining and Western Medicine on MG patients with deficiency of both spleen and kidney is worth further exploration.展开更多
Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 monoclonal antibody conjugated to a derivative of an antitumor antibiotic, calicheamicin. GO was approved for the treatment of relapsed acute myeloid leukemia (AML) ...Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 monoclonal antibody conjugated to a derivative of an antitumor antibiotic, calicheamicin. GO was approved for the treatment of relapsed acute myeloid leukemia (AML) in the United States (US) in 2000. However, GO was withdrawn from the US market in June 2010, because a large-scale clinical trial failed to show additive or synergistic effects with conventional chemotherapy for newly diagnosed AML. GO is currently available only in Japan. However, several large clinical studies have demonstrated beneficial effects of GO when added to chemotherapy for AML in recent years;therefore, reconsideration of GO availability is gaining attention. Therefore, the role and efficacy of GO as monotherapy or in combination therapy for de novo or relapsed AML should be positively investigated.展开更多
Psoriasis is an immune-abnormal,chronic,proliferative skin disease determined by polygenic inheritance and induced by a number of environmental factors.It causes worldwide concern because of its high-prevalence,harmfu...Psoriasis is an immune-abnormal,chronic,proliferative skin disease determined by polygenic inheritance and induced by a number of environmental factors.It causes worldwide concern because of its high-prevalence,harmful and incurable characteristics.Over the years,Chinese medicine(CM) treatment of psoriasis has accumulated a wealth of clinical experience.Disease-syndrome combination, which achieves more satisfactory clinical effect,is the basis to highlight the special CM advantages in treating psoriasis.In this paper,we review the advantages of treating psoriasis with the combination of disease and syndrome,analyze the prospects of research on treating psoriasis combining disease with syndrome.We also make a point that there are several key points for the clinical research of combination of disease and syndrome.It can be expected that carrying out clinical research on the combination of disease and syndrome will help improve the clinical efficacy of medical treatment of psoriasis,which will be the main direction of research in the future.展开更多
基金Supported by National Natural Science Foundation of China(81403189,81460628,81660705,81560690)Scientific Research Project of Higher Education in Guangxi Department of Education(YB2014182)
文摘Although the animal models of hepatic fibrosis developed by former researchers have pathological changes of hepatic fibrosis, they do not include charac- teristics of important TCM syndromes such as stagnation of qi, deficiency of qi, liver depression, phlegm-dampness and blood stasis because of single-factor model- ing. Animal models of hepatic fibrosis and animal models integrated disease and syndrome were reviewed, and several new types of integrated disease and syndrome animal models constructed by multiple-factor modeling method were evaluated, under the guidance of etiological theory of TCM. This kind of hepatic fibrosis model animals has dual characteristics of disease and syndrome. It is consistent with pathological characteristics of hepatic fibrosis in western medicine when replicating the basic characteristics accorded with TCM syndrome. Thus, the pathogenesis and pathogenic process of clinical disease and syndrome formation is simulated more ac- curately, providing a new platform and pathway for studying hepatic fibrosis disease with integrated traditional Chinese and western medicine.
基金Project of National Key Basic Research Program(973 Program)(No.2013CB531705).
文摘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.
文摘BACKGROUND: Central adrenergic nerve and 5-serotonergic nerve can influence central cholinergic nerve on learning and memory and make easy for study; however, ginsenoside of stem and leaf (GSL) can improve functions of central adrenergic nerve; moreover, 5-serotonergic nerve and the combination with choline can produce synergistic effect and enhance learning and memory ability so as to improve learning and memory disorder of patients with Alzheimer disease (AD). OBJECTIVE : To observe the effects of GSL combining with choline on learning and memory of AD model rats DESIGN : Randomized grouping design and controlled animal study SETIING : Department of Pharmacology, Taishan Medical College MATERIALS : The experiment was carried out in the Pharmacological Department of Medical College of Jilin University from October 1996 to January 1997. Forty healthy male Wistar rats of clean grade were randomly divided into 5 groups, including sham-injury group, model group, GSL group, choline group and combination group, with 8 rats in each group. Main medications: GSL with the volume more than 92.8% was provided by Department of Chemistry, Norman Bethune Medical College of Jilin University. Panaxatriol, the main component, was detected with thin layer scanning technique and regarded as the index of GSL quality [(55±1)%, CV= 2%, n = 5]. Choline was provided by the Third Shanghai Laboratory Factory. METHODS : 150 nmol quinolinic acid was used to damage bilateral Meynert basal nuclei of adult rats so as to establish AD models. Rats in GSL, choline and combination groups were intragastric administrated with 400 mg/kg GSL, 200 mg/kg choline (20 mL/kg), and both respectively last for 17 days starting from two days before operation. Rats in sham-injury group and model group were perfused with the same volume of distilled water once in each morning for the same days. (1) Passive avoidance step-down test: Five minutes later, rats jumped up safe platform when they were shocked with 36 V alternating current. If rats jumped down from the platform and the feet touched railings, the response was wrong. Numbers of wrong response were recorded within 3 minutes, and then the test was redone after 24 hours. (2) Morris water-maze spatial localization task: Swimming from jumping-off to platform directly was regarded as right response. Additionally, 4 successively right responses were regarded as the standard. Each rat was trained 10 times a day with 120 s per time for 3 successive days. The interval was 30 s. Three days later, numbers of right response were recorded. The training times were increased to 30 for unlearned rats. (3) Measurement of activity of choline acetylase in cerebral cortex: Rats were sacrificed at 17 days after operation to obtain cerebral cortex to measure activity of choline acetylase with radiochemistry technique. (4) Synergistic effect: It was expressed as Q value: Q value = factual incorporative effect/anticipant incorporative effect; Q ≥ 1 was regarded as synergistic effect. Anticipant incorporative effect = (EA+EB-EA·EB), EA and EB were single timing effect, respectively in GSL group and choline group. E(step-down test and Morris water maze test) = (x in model group - factual value in medicine groups)/x in model group; E (activity of choline acetylase) = (factual value in medicine groups -xin model group)/xin model group. MAIN OUTCOME MEASURES : (1) Passive avoidance step-down test and Morris water-maze spatial localization task in the study of learning and memory; (2) activity of choline acetylase. RESULTS : All 40 rats were involved in the final analysis. (1) Passive avoidance response: At learning phase on first day and retesting phase on the next day, numbers of wrong responses within 3 minutes were more in model group than sham operation group, and there was significant difference [(5.88±1.46), (2.25±0.87) times; (2.63±1.06), (0.50±0.53) times; P 〈 0.01]; numbers of wrong responses within 3 minutes were less in combination group than model group, and there was significant difference [learning phase: (1.12±0.83), (5.88±1.46) times; retesting phase: (0.38±0.74), (2.63±1.06)times, P 〈 0.01]; moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.07 and 1.59, respectively and it showed synergistic effect. Spatial localization task: Training times were more in model group than sham operation group, and there was significant difference [(2.9±2.5), (12.6±3.5) times; P 〈 0.01]. Training times were less in combination group than model group, and there was significant difference [(11.8±2.4), (27.9±2.5) times, P 〈 0.01]; moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.07 and it showed synergistic effect. (3) Activity of choline acetylase: Activity was lower in model group than sham operation group, and there was significant difference [(30.56±8.33), (61.11 ±8.33) nkat/g; P 〈 0.01]. Activity was higher in combination group than model group and there was significant difference [(50.00±8.33), (30.56±8.33) nkat/g, P 〈 0.01];moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.5 and it showed synergistic effect. CONCLUSZON: GSL in combination with choline can synergically improve the disorder of learning and memory of AD model rats. Its mechanism may be involved in enhancing the function of central cholinergic system.
基金supported by the Natural Science Foundation of Jiangsu Province of China(Grant No.BK20160134 to LW and BK20191071 to CC)National Natural and Science Foundation of China(Grant No.81900295 to CC)Special Foundation for Clinical Science and Technology of Jiangsu Province(Grant No.BE2017754 to HWC).
文摘Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic background,the application of patient-specific induced pluripotent stem cell-derived cardiomyocytes(iPSC-CMs)may help to reveal cell phenotype characteristics underlying different genetic variations.Here,to verify and compare the pathogenicity of mutations(SCN5A c.4213G>A and SCN1B c.590C>T)identified from two BrS patients,we generated two novel BrS iPS cell lines that carried missense mutations in SCN5A or SCN1B,compared their structures and electrophysiology,and evaluated the safety of quinidine in patient-specific iPSC-derived CMs.Compared to the control group,BrS-CMs showed a significant reduction in sodium current,prolonged action potential duration,and varying degrees of decreased Vmax,but no structural difference.After applying different concentrations of quinidine,drug-induced cardiotoxicity was not observed within 3-fold unbound effective therapeutic plasma concentration(ETPC).The data presented proved that iPSC-CMs with variants in SCN5A c.4213G>A or SCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events.
基金the Research Institute of Veterinary Science,College of Veterinary Medieine,Seoul National University
文摘AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS,which addresses the possibility that formerly established rat model of colitis could be used as an IBS model after the inflammation subsided. METHODS:Colitis was induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley rats.The extent of inflammation was assessed by histological examination and myeloperoxidase(MPO)activity assay.After subsidence of colitis,the rats were subjected to rectal distension and restraint stress,then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured, respectively. RESULTS:At 2 days post-induction of colitis,the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity.At 7 days post-induction of colitis,the histological features and MPO activity returned to normal.The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance,and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.
基金funded by the China Scholarship Council(CSC)(no.202108080221)。
文摘Pulmonary hypertension due to left heart disease(PH-LHD) is regarded as the most prevalent form of pulmonary hypertension(PH). Indeed, PH is an independent risk factor and predicts adverse prognosis for patients with left heart disease(LHD). Clinically, there are no drugs or treatments that directly address PH-LHD, and treatment of LHD alone will not also ameliorate PH. To target the underlying physiopathological alterations of PH-LHD and to develop novel therapeutic approaches for this population, animal models that simulate the pathophysiology of PH-LHD are required. There are several available models for PH-LHD that have been successfully employed in rodents or large animals by artificially provoking an elevated pressure load on the left heart, which by transduction elicits an escalated pressure in pulmonary artery. In addition, metabolic derangement combined with aortic banding or vascular endothelial growth factor receptor antagonist is also currently applied to reproduce the phenotype of PH-LHD. As of today, none of the animal models exactly recapitulates the condition of patients with PH-LHD. Nevertheless, the selection of an appropriate animal model is essential in basic and translational studies of PH-LHD. Therefore, this review will summarize the characteristics of each PH-LHD animal model and discuss the advantages and limitations of the different models.
文摘As the acceleration of aged population tendency, building models to forecast Alzheimer’s Disease (AD) is essential. In this article, we surveyed 1157 interviewees. By analyzing the results using three machine learning methods—BP neural network, SVM and random forest, we can derive the accuracy of them in forecasting AD, so that we can compare the methods in solving AD prediction. Among them, random forest is the most accurate method. Moreover, to combine the advantages of the methods, we build a new combination forecasting model based on the three machine learning models, which is proved more accurate than the models singly. At last, we give the conclusion of the connection between life style and AD, and provide several suggestions for elderly people to help them prevent AD.
基金National Natural Science Foundation of China(No.81960861)Funded by Guangxi Graduate Education Innovation Program(No.YCXJ2021035)。
文摘The prevention and treatment of myocardial ischemia is a hot and difficult point in clinical research and animal experimental research in the cardiovascular field.The combined disease and syndrome animal model with the disease characteristics of Western medicine and guided by the theory of Chinese medicineto replicate the"syndrome"of Chinese medicine on the model animals by using experimental methods is an effective tool for the research of Chinese medicine.This article summarized the methoding methods and evaluation index of the animal model combined disease of coronary heart disease myocardial ischemia with cold blood stasis,phlegm and blood stasis,qi deficiency and blood stasis syndrome,kidney deficiency and blood stasis,and concluded the treatment of Traditional Chinese medicine.At the same time,it analyzed the main deficiencies of myocardial ischemia syndrome combined with animal models to provide reference for the establishment and research of related animal models.
基金supported by the National Natural Science Foundation of China(No.81801166)the Fundamental Research Funds for the Central Universities(No.14380478).
文摘Background To investigate the incidence,risk factors,and clinical prognosis of cerebral hyperperfusion syndrome(CHS)after superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-duro-arterio-synangiosis(STA-MCA/EDAS)in adult patients with moyamoya disease(MMD).Methods The clinical data of 160 adult patients with MMD treated by STA-MCA/EDAS from January 2016 to January 2017 were retrospectively analyzed.According to CHS diagnosis,MMD patients were divided into CHS and non-CHS group.Univariate and multivariate analysis of risk factors and Kaplan-Meier curve of stroke-free survival for CHS were performed.Results A total of 12 patients(7.5%)developed postoperative CHS,of which 4 patients(2.5%)presented with cerebral hemorrhage.Univariate and multivariate analysis showed moyamoya vessel on the surgical hemisphere(OR=3.04,95%CI=1.02-9.03,P=0.046)and left operated hemisphere(OR=5.16,95%CI=1.09-21.34,P=0.041)were independent risk factors for CHS.The other variables,such as age,gender,presentation,hypertension,diabetes,smoking,mean mRS score on admission,modified Suzuki stage and pre-infarction stage on surgical hemisphere,and bypass patency,had no association with postoperative CHS(P>0.05).At final follow-up with average 38 months,there were 18 out of 133 patients(13.5%,4.91%per person year)presented with newly developed complications.There was no significant difference between newly developed complications,mean mRS scores,and Kaplan-Meier curve of stroke-free survival in patients with and without CHS(P>0.05).Conclusion The concentration of moyamoya vessels and left operated hemisphere was independent risk factors for CHS,which could not affect the clinical prognosis if treated timely and properly.The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.
基金National Natural Science Foundation of Tianjin,China(16JCYBJC27500)
文摘Objective: To study the treatmaient of non-small cell lung cancer, we established the HU-Prim allograft transplantation tumor model. Methods: The fresh tumor samples were transplanted in the right scapular subcutaneous layer of the severe combined immunodeficient Non-obese diabetic/severe combined immunodeficient(NOD/SCID) mice. The pathological features of the tumors were observed. Nonnecrotic tissue was inoculated subcutaneously into the right axillary. When the tumor in burdened rat grew approximately 100 mm3, according to the tumor size all the animals were divided into the following four groups, eight rats in each group: solvent control group, gefitinib group(100 mg/kg), erlotinib group(50 mg/kg), afatinib group(20 mg/kg). Aniamals were treated with drugs by intragastric(i.g.) administrated, once daily, for consecutively 14 days. Measure the tumor size 2-3 times every week. Results: Hu Prime1-NSCLC mutant sensitive xenograft model research data showed that reversible tyrosine kinase inhibitors gefitinib, erlotinib and irreversible tyrosine kinase inhibitor afatinib could effectively inhibit tumor growth in EGFR positive NSCLC allografts model. The pharmacodynamic activity of irreversible inhibitor was better than that of the reversible inhibitor. Specimens from clinical anthropogenic tumor retain characteristics of the human primary malignancy, histopathology, biological characteristics, and tumor markers, etc., which can more accurately reflect the characteristics of the tumor and the impact of interventions. Conclusion: The model is not only a good antitumor drug experimental platform, but also a new evaluation tool of individualized medication.
基金Supported by a Key Project in Basic Research of Shanghai Municipal Committee of Science(No.10JC1414500)a Planned Project in the TCM Fund of Scientific Research under the Shanghai Municipal Health Bureau (2010J002B)
文摘OBJECTIVE: To study the use of Jianjining in the treatment of myasthenia gravis (MG) patients with a deficiency of both spleen and kidney via the theory on the combination of disease with syndrome. METHODS: Sixty MG patients with a deficiency of both spleen and kidney were randomly divided into an treatment group (n=30) treated with Jianjining granules and Western Medicine (prednisone or pyridostigmine bromide) and a control group (n= 30) treated with Jianjining granules. The dosage of the three drugs was reduced over the course of treatment. After 3 and 6 months of treatment, the curative effect was evaluated with the muscle weakness severity scale (MWSS). RESULTS: The MWSS score after treatment declined significantly in both groups. The score in the treatment group was much lower than that in thecontrol group (P<0.05). The total effective rate was 63.33% (19/30) in the treatment group and 36.67% (11/30) in the control group after 3 months of treatment, and 80.00% (24/30) and 50.00% (15/30), respectively, after 6 months of treatment. The obvious and total effective rates in the treatment group were much higher than those in the control group (P<0.05). After 6 months of treatment, there were no obvious differences (P>0.05) in the obvious and effective rates between the 2 groups. However, the total effective rate in the treatment group was much higher than that in the control group (P<0.01). CONCLUSION: Using the theory on the combination of disease with syndrome, we found that the curative effect of Jianjining and Western Medicine on MG patients with deficiency of both spleen and kidney is worth further exploration.
文摘Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 monoclonal antibody conjugated to a derivative of an antitumor antibiotic, calicheamicin. GO was approved for the treatment of relapsed acute myeloid leukemia (AML) in the United States (US) in 2000. However, GO was withdrawn from the US market in June 2010, because a large-scale clinical trial failed to show additive or synergistic effects with conventional chemotherapy for newly diagnosed AML. GO is currently available only in Japan. However, several large clinical studies have demonstrated beneficial effects of GO when added to chemotherapy for AML in recent years;therefore, reconsideration of GO availability is gaining attention. Therefore, the role and efficacy of GO as monotherapy or in combination therapy for de novo or relapsed AML should be positively investigated.
基金Supported by the Financial Industry Technology Research and Development Program of Guangdong Province(No.201105)
文摘Psoriasis is an immune-abnormal,chronic,proliferative skin disease determined by polygenic inheritance and induced by a number of environmental factors.It causes worldwide concern because of its high-prevalence,harmful and incurable characteristics.Over the years,Chinese medicine(CM) treatment of psoriasis has accumulated a wealth of clinical experience.Disease-syndrome combination, which achieves more satisfactory clinical effect,is the basis to highlight the special CM advantages in treating psoriasis.In this paper,we review the advantages of treating psoriasis with the combination of disease and syndrome,analyze the prospects of research on treating psoriasis combining disease with syndrome.We also make a point that there are several key points for the clinical research of combination of disease and syndrome.It can be expected that carrying out clinical research on the combination of disease and syndrome will help improve the clinical efficacy of medical treatment of psoriasis,which will be the main direction of research in the future.