[Exploration on origin of Simiao Yong'an Decoction].

Simiao Yong'an Decoction is composed of Lonicerae Japonicae Flos, Scrophulariae Radix, Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizome, which was chosen as one of the 100 classic prescriptions in Catalogue of Ancient Classics Prescription(the first batch). Through tracing to the source, It was found that the Simiao Yong'an Decoction(but not named) originated from the Shi Shi Mi Lu, and was later cited by books such as Ancient and Modern Book Integration-Full Record of Medical Department and New Edition of Useful Prescriptions. Literature shows that this prescription was not named until first reported in the Effect of Traditional Chinese Medicine on Arterial Embolism Gangrene in 1956 by a journalist LYU Min. This article recorded that SHIJIA Baoshan, a monk from Hebei Province, used self-named "Simiao Yong'an Decoction" to treat local arterial embolic gangrene. After comparison, there was two difference between ancient books and SHIJIA Baoshan's records. Firstly, according to ancient books, the composition and dosage of Simiao Yong'an Decoction is Lonicerae Japonicae Flos 90 g, Scrophulariae Radix 90 g, Angelicae Sinensis Radix 60 g, Glycyrrhizae Radix et Rhizome 30 g", and the ratio is 3∶3∶2∶1. By SHIJIA Baoshan's record, the composition and dosage are: Lonicerae Japonicae Flos 66 g, Scrophulariae Radix 132 g, Angelicae Sinensis Radix 99 g, Glycyrrhizae Radix et Rhizome 33 g, and the ratio changed to 2∶4∶3∶1. Secondly, ancient books show that patients can be healed after taking seven or ten days of the previous prescription, however, it would take 3 or 4 months, even 7 months in SHIJIA Baoshan's records. It can be considered that the previous prescription should be used at the beginning of gangrene, while the modified Simiao Yong'an Decoction by SHIJIA Baoshan is widely used in the middle and late stages of gangrene, even the critical condition, that is the reason for longer treatment and larger dosage. Nowadays, Simiao Yong'an Decoction is not limited to the treatment of gangrene and bulla in clinic. Relevant studies have confirmed that Simiao Yong'an Decoction has the effects such as anti-inflammatory, plaque stabilization, lipid-lowering, vascular protection, improvement of hemorheology, anticoagulation, inhibition of thrombosis and fibrinolysis, etc. In the follow-up, we should carry out the analysis of the compatibility of this four medicines, and redefine the scope of its clinical application under the theory of traditional Chinese medicine.

[The Thyroid Hormone Receptor Mediated Luciferase Reporter Gene Assays Screening for EDCs].

OBJECTIVE: This study in order to use report gene assay based on the thyroid hormone receptor (TR) α/ß from human origin for screening endocrine disruptors chemicals (EDCs), evaluating the thyroid hormone activity of Bisphenol (BPA), 1-Naphthaleny methyl carbamate and 1-naphthol (1-NAP). METHODS: Using Rhesus monkey kidney cells (LLC-MK2) as transfection cell to establish the gene report assay system based on pGL-3-promega and pGL4.27 of TRα/ß through the method of transient transfection. Using T3 and T4 as positive subjects to evaluation the effectiveness of two detection systems and detect the thyroid hormone activity of BPA, 1-Naphthaleny methyl carbamate, 1-NAP. RESULTS: The TRß LLC-MK2 report gene assay based on pGL3-promega, the minimum detectable limit of T3 is 1.216×10-11 mol/L, the largest induction multiple was shown at 7.482×10-6 mol/L, the expression multiple of induced Lucifrerase was 5.98-fold that of the vehicle control, the EC50 was 3.327×10-8 mol/L; The minimum detectable limit of T4 was 1.622×10-8 mol/L, the largest induction Luc expression was 3.4-fold of vehicle control, the EC50 was 2.213×10-7 mol/L. The TRß LLC-MK2 report gene assay based on pGL4.27, the minimum detectable limit of T3 was 9.863×10-12 mol/L, the largest induction Luc expression as shown at 1.671×10-6 mol/L, resulting in 8.57-fold of vehicle control, the EC50 is 3.327×10-8 mol/L. The minimum detectable limit of T4 was 1.349×10-9 mol/L, the largest induction Luc expression was 4.6-fold of vehicle control, the EC50 is 4.074×10-7 mol/L. There was no thyroid hormone activity by using TRß report gene assay to evaluate BPA, 1-Naphthaleny methyl carbamate or 1-NAP, but 1-Naphthaleny methyl carbamate and 1-NAP have some degree receptor antagonism. CONCLUSIONS: The TRß LLC-MK2 report gene assay based on pGL3- promega and pGL4.27 show highly sensitive (pGL4.27 relatively higher), can be used to screen for EDCS and test chemical thyroid hormone activity effectively.

[Expert consensus on the design and implementation of clinical safety centralized monitoring study of Chinese medical injection].

Along with the increase of clinical application, the safety of traditional Chinese medicine gained more and more attentions. In particular, the safety evaluation of Chinese medical injections has become a mandatory task should be completed by pharmaceutical companies under the supervision of China Food and Drug Administration(CFDA). Due to the weak foundation of previous studies, the safety issues of Chinese medical injections have not been fully understood, and lack of scientific and rational risk management programs. Clinical safety centralized monitoring(CSCM) is an important method for post-market safety evaluation of Chinese medicine. Due to the lack of appropriate norms and procedures, the quality of similar research is uneven, and the results vary. Combined with practical experience with experts' suggestions, we developed this expert consensus on the design and implementation of CSCM from three stages (design, implementation and report) with 20 technical points, which will provide technical support for future CSCM studies.

[Effect of Huanglian Jiedu Decoction on Monocyte Development in apoE Gene Knockout Mice].

OBJECTIVE: To observe monocyte (Mo) development in wild type C57BL/6 mice and apoE gene knockout (apoE(-/-)) mice, and to evaluate the immuno-regulatory effect of Huanglian Jiedu Decoction (HJD) on peripheral Mo development in apoE(-/-) mice. METHODS: Four, 8, 12, and 16 weeks old female C57BL/6 mice were set up as control groups of different ages, while 4, 8, 12, and 16 weeks old female apoE(-/-) mice were set up as hyperlipidemia groups of different ages. Four-week old female C57BL/6 mice were recruited as a blank group. Four-week old female apoE(-/-) mice were randomly divided into the control group, the Western medicine group, and the Chinese medicine group by paired comparison, 5 in each group. Equivalent clinical dose was administered to mice according to body weight. Mice in the Western medicine group were administered with Atrovastatin at the daily dose of 10 mg/kg by gastrogavage, while those in the Chinese medicine group were administered with HJD at the daily dose of 5 g/kg by gastrogavage. Body weight was detected each week. After 4 weeks blood lipids levels (such as TG, TC, LDL-C, and HDL-C), and the proportions of Mo and Ly6c(hi) were detected. RESULTS: Compared with 4-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05). Levels of TC and TG, and the proportion of Ly6c(hi) subtype increased, but the proportion of Mo de- creased in 8-week-old apoE(-/-) mice (P <0. 05). Levels of TC, TG, and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05). Levels of TC, TG, LDL-C, and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with 8-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05); levels of TC and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05); levels of TC and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with C57BL/6 mice of the same age, TC and TG increased, HDL-C decreased (P < 0.01) in 4-and 8-week-old apoE(-/-) mice (P < 0.01); levels of TC, TG, LDL-C increased, and HDL-C level decreased in 12- and 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01); the proportion of Mo increased in 4-week-old apoE(-/-) mice (P < 0.05); proportions of Mo and Ly6c(hi) increased in 8-week-old apoE(-/-) mice (P < 0.05). Compared with the blank control group, levels of TC, TG, and LDL-C, proportions of Mo and Ly6c(hi) increased (P < 0.01, P < 0.05), but HDL-C level decreased (P <0. 01) in the control group after intervention. Compared with the control group, body weight gained less in the Western medicine group and the Chinese medicine group (P < 0.05); the proportion of Ly6c(hi) subtype decreased in the Chinese medicine group (P < 0.05). CONCLUSIONS: In development process blood lipids levels in apoE(-/-) mice are not only associated with age. Blood lipids levels induced growth changes in natural immune system are also correlated with age. In early stage of lipids development HJD intervention could correct this special immune disorder in apoE(-/-) mice.

[Study on Macrocosmic Diagnostic Criteria for Coronary Heart Disease with Intermingled Phlegm- Blood Stasis Syndrome].

Macrocosmic diagnostic criteria for coronary heart disease (CHD) with phlegm-damp- ness syndrome (PDS) were established after screening based on macrocosmic indices of CHD with PDS after previous literature analyses and experts consultations. The weights of macrocosmic indices of PDS were compared using analytic hierarchy process (AHP). Macrocosmic diagnostic criteria for CHD with intermingled phlegmblood stasis syndrome were studied by combining with diagnostic criteria for CHD patients with blood stasis syndrome (BSS) set by Academician CHEN Ke-ji group.

[Treating influenza patients of wind-heat affecting Fei syndrome by jinhua qinggan granule: a double-blinded randomized control trial].

OBJECTIVE: To assess the effect and safety of Jinhua Qinggan Granule (JHG) in treating influenza patients of wind-heat affecting Fei syndrome (WHAFS). METHODS: Totally 136 influenza patients of WHAFS were randomized by stratification into 3 groups, the high dose JHG group (44 cases, 10 g each time), the low dose JHG group (45 cases, 5 g JHG + 5 g placebo each time), and the placebo control group (47 cases, 10 g placebo each time). All medication was administered three times daily for 5 days. The fever disappearance time, the fever disappearance rate, efficacy of TCM syndrome, the disappearance rate of main symptoms and physical signs of flu, the negative rate of virus nucleic acid in the pharyngeal secretion, and safety indicators were assessed. RESULTS: The median fever disappearance time was 32.8 h (95% CI: 22.5-41.0 h) in the high dose JHG group, 26.0 h (95% CI: 14.5-36.5 h) in the low dose JHG group, 39.5 h (95% CI: 29.0-46.0 h) in the placebo control group. There was statistical difference in the median fever disappearance time between the low dose JHG group and the placebo control group (P = 0.011). Three days after treatment, the markedly effective rate of TCM symptoms in the low dose JHG group was 66.7%, higher than that of the placebo control group (38.3%), and its effective rate was superior to that of the high dose JHG group (P = 0.043). Five days after treatment, the recovery rate of the low dose JHG group (42.2%) was higher than that of the high dose JHG group (25.0%, P = 0.026) and that of the placebo control group (14.9%, P = 0.002). The markedly effective rate of the low dose JHG group (86.7%) was higher than that of the placebo control group (55.3%, P = 0.001). Similar effects were obtained in the low dose JHG group and the high dose JHG group, but slightly poor in partial indicators of the high dose JHG group. There was no statistical difference in adverse reaction among these three groups (P > 0.05). CONCLUSIONS: JHG was effective and safe in treating influenza patients of WHAFS. Routinely low dose was the optimal dosage of JHG.

Clinical research of acupoint application for "treatment of winter disease in summer" used to prevent and treat bronchial asthma in children.

OBJECTIVE: To preliminarily analyze key factors influencing curative effect through clinical observations of acupoint application for "treatment of winter disease in summer" used to prevent and treat bronchial asthma in children. METHODS: In an observational study and prospective cohort study, we observed children in remission of asthma at three class III grade A TCM hospitals in Liaoning, Hubei, and Chengdu. RESULTS: A total of 609 children conformed to diagnostic and inclusive standards for remission of bronchial asthma. Through follow-up visits, we observed their skin reactions and the time and chance of treatment with different therapies in the three hospitals; we also compared and analyzed different drugs, acupoints, and preparations. We found that the key Chinese drugs were Bai Jie Zi (Semen Sinapis Albae) and Yian Hu Suo (Rhizoma Corydalis); the key acupoints were Feishu (BL 13), Gaohuang (BL 43), Dingchuan (EX-B1), Tiantu (CV 22), and Shanzhong (CV 17); and the best preparation was a mixture of drugs, ginger juice, and musk. Acupoint application was practiced on the hottest days of summer and the coldest days of winter for 0.5 to 2 h with the lowest rate of asthma relapse. CONCLUSIONS: The present data analysis shows that the curative effect of acupoint application for "treatment of winter disease in summer" may be influenced by recipes of Chinese drugs, preparations, prescriptions of acupoints, chance, time, and skin reactions. A curative effect is the result of the comprehensive action of these factors.

Study on syndrome differentiation strategy of phlegm and blood stasis syndromes of coronary heart disease based on expert consultation on medical cases.

BACKGROUND: It is becoming more and more important to judge whether patients with coronary heart disease (CHD) have phlegm and blood stasis syndromes in the process of traditional Chinese medicine (TCM) diagnosis and treatment of CHD. The syndrome differentiation strategy of phlegm and blood stasis syndromes of CHD is still not standardized, and it is particularly necessary to make syndrome differentiation simpler and more accurate. METHODS: Twenty-eight medical cases that met the criteria, comprising 10 ancient medical cases and 18 modern ones, were selected from the TCM literature, which were then analyzed by 57 experts via questionnaire. Statistical analysis of the data was mainly based on frequency analysis. RESULTS: (I) The average age of the 57 experts from 20 provinces was 48.9±8.5 years; 89.5% were associate professor or above, and 75.4% of them worked at a tertiary hospital. (II) Consistency of expert consultation over medical cases: for the ancient medical cases, the diagnostic consistency rate of phlegm syndrome was 27/34 (79.4%) and additional diagnosis rate of the blood stasis syndrome was 27/57 (47.4%); for the modern medical cases, the consistency rate compared with the original diagnosis of phlegm syndrome was 54/80 (67.5%) and that of blood stasis syndrome was 73/90 (81.1%). (III) The top five experts' diagnostic basics of phlegm syndrome were oppression in the chest, slippery pulse, greasy fur, coughing of phlegm, and chest pain; the top five diagnostic basics of blood stasis syndrome were chest pain, dark tongue, oppression in chest, red tongue, and ecchymosis on tongue. (IV) In the questionnaire consultation on CHD phlegm-blood stasis syndrome cases, the diagnostic basis of "symptom or (and) tongue manifestation" accounted for 12/27 (44.4%) of the diagnostic basics of phlegm syndrome and 28/38 (73.7%) of that of blood stasis syndrome basis. CONCLUSIONS: Modern Chinese medicine experts pay much attention to the diagnosis and treatment of CHD based on TCM pathology theories of phlegm and blood stasis. To collect and detect the patients' symptoms and tongue manifestation is an important strategy of the experts for CHD phlegm and blood stasis syndrome differentiation.

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease.

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine-based approach was proposed to identify the underlying molecular modules of PSCS complicated with IHD, which could be used for interpreting the pharmacological mechanisms of well-established Chinese herbal formulas (e.g., Tao Hong Si Wu Tang, Dan Shen Yin, Hunag Lian Wen Dan Tang and Gua Lou Xie Bai Ban Xia Tang). In addition, these results delivered novel understandings of the molecular network mechanisms of IHD phenotype subtypes with PSCS complications, which would be both insightful for IHD precision medicine and the integration of disease and TCM syndrome diagnoses.

[Effect of glucocorticoid with traditional Chinese medicine in severe acute aespiratory syndrome (SARS)].

OBJECTIVE: To evaluate the effects of traditional Chinese medicine in 461 cases of severe acute respiratory syndrome(SARS) on glucocorticoid's dosage. METHOD: By using the polycentric nonrandomized concurrent controled trial and under the condition of glucocorticoid use, the patierts were divided into two groups: the integrated traditional Chinese and western mendicine(ITCWM) and simplicity western mendicine alone(WM). The observation indexes were time in hospital, pneumonia duration, mortality, glucocorticoid's gross dosage, glucocorticoid's average dosage of days and glucocorticoid use time. RESULT: In the ITCWM group, average time in hospital was shortened (P = 0.058), pneumonia duration was shortened (P = 0.057), mortality fell (P = -0.001). The median of glucocorticoid' s gross dosage was 1,277.0 mg x d(-1) in the ITCWM group, and that was 1,680.0 mg x d(-1) in the WM group (P = 0.083). The median of glucocorticoid's average dosage of days was 84.40 mg x d(-1) in the ITCWM group, and that was 115.33 mg x d(-1) in the WM group (P = 0.025). According to the analysis of 461 cases divided by stages and different ponderance, within 7 days after illness, in the ITCWM group, the glucocorticoid' s average dosage decreased. In the common type, the dosage in the ITCWM and in the WM was 146.43 mg x d(-1), and 183.64 mg x d(-1), respectively (P = 0.057), in the severe type, that was 137.71 and 177.86 mg x d(-1), respectively (P = 0.001). CONCLUSION: Compared with the group of simplicity western mendicine, in the group of integratived Chinese and western mendicine, time in hospital shorten, pneumonia duration shorten, mortality fall, simultaneity, glucocorticoid's average dosage is decreased. The use of TCM in the forepart of treatment can be capable of decreasing glucocorticoid's dosage.

Detection of herb-symptom associations from traditional chinese medicine clinical data.

Background. Traditional Chinese medicine (TCM) is an individualized medicine by observing the symptoms and signs (symptoms in brief) of patients. We aim to extract the meaningful herb-symptom relationships from large scale TCM clinical data. Methods. To investigate the correlations between symptoms and herbs held for patients, we use four clinical data sets collected from TCM outpatient clinical settings and calculate the similarities between patient pairs in terms of the herb constituents of their prescriptions and their manifesting symptoms by cosine measure. To address the large-scale multiple testing problems for the detection of herb-symptom associations and the dependence between herbs involving similar efficacies, we propose a network-based correlation analysis (NetCorrA) method to detect the herb-symptom associations. Results. The results show that there are strong positive correlations between symptom similarity and herb similarity, which indicates that herb-symptom correspondence is a clinical principle adhered to by most TCM physicians. Furthermore, the NetCorrA method obtains meaningful herb-symptom associations and performs better than the chi-square correlation method by filtering the false positive associations. Conclusions. Symptoms play significant roles for the prescriptions of herb treatment. The herb-symptom correspondence principle indicates that clinical phenotypic targets (i.e., symptoms) of herbs exist and would be valuable for further investigations.

[Analysis on acupoint prescription for acupoint sticking therapy of treating winter diseases in summer for preventing and curing chronic cough and asthma].

Based on ZhangShi YiTong written by ZHANG Lu of Qing dynasty, and the record that external application of Baijiezi (seeds of Brassica Alba) for treating asthma of cold syndrome, retrospective study is conducted to modern literature of treating winter diseases in summer with acupoint sticking therapy for preventing and treating chronic cough and asthma. Learning from thoughts and methods of evidence-based medicine, and according to subject characteristics of TCM and acupuncture, acupoints and point-selecting discipline of prescription for preventing and treating chronic cough and asthma in summer with acupoint sticking are analyzed. The results show that the top ten common acupoints used for acupoint sticking therapy of treating winter diseases in summer are Feishu (BL 13), Dingchuan (EX-B 1), Xinshu (BL 15), Geshu (BL 17), Danzhong (CV 17), Shenshu (BL 23), Gaohuang (BL 43), Dazhui (GV 14), Pishu (BL 20), Tiantu (CV 22), most of which belong to the Bladder Meridian of Foot-Taiyang, Conception Vessel and Governor Vessel or extra-meridian points. It refers that the core acupoints of acupoint sticking therapy are Feishu (BL 13), Dingchuan (EX-B 1), Xinshu (BL 15), Geshu (BL 17), Danzhong (CV 17), and adjunct points can be selected by syndrome, disease different stage, disease or symptoms.

[Comment of the criteria for assessment of therapeutic effects of acupuncture and moxibustion on spastic paralysis of apoplexy].

Acupuncture and moxibustion have obvious therapeutic effect on spastic paralysis of apoplexy, but there is no common standard for evaluation of therapeutic effects. Available standards for assessment of therapeutic effect of acupuncture and moxibustion on spastic paralysis of apoplexy are not complete. Acupuncture and moxibustion improve clinical symptoms of the patient of spastic paralysis of apoplexy to a considerable degree, a evaluation system for results of clinical symptoms of the patient can be set up, so as to perfect the criteria for evaluation of therapeutic effects of acupuncture and moxibustion on this disease.

[Effects of D-galactose combined with lesions of nucleus basalis of Meynert on hippocampal long-term potentiation and synaptic morphology].

AIM: To study the changes of synaptic plasticity in rat model with Alzheimer disease (AD). METHODS: AD rat model was conducted by D-galactose intraperitoneal injection combined with lesions of nucleus basalis of Meynert (nbM). Behavioral performance, LTP in dentate gyrus and synaptic morphology in hippocampal CA1 were observed. RESULTS: (1) Escape latencies in place test in model rats were longer than that in control rats, and swimming time and distance between the two groups in platform quadrant were significant differently (P < 0.01). (2) The numerical density (Nu) and surface density (Su) of synaptic contact zones markedly decreased (P < 0.01) in model rats. (3) Augment of population spike (PS) in perforant path-dentate gyrus of model rats after high frequency stimulation was smaller than that of the control (P < 0.05). CONCLUSION: The results suggest that the decreased synaptic plasticity in hippocampus could responsible for the impairment of spatial learning of model rats.