[Retrospective cross-sectional survey of clinical characteristics and syndrome elements distribution at different stages of coronary heart disease].

The clinical data of coronary heart disease(CHD) patients treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine and Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to March 2023 were retrospectively collected. This study involved the descriptive analysis of demographic characteristics, clinical symptoms, and tongue and pulse features. The χ~2 test was conducted to analyze the distribution of syndrome elements and their combinations at diffe-rent stages of CHD, so as to reveal the clinical characteristics and syndrome patterns at various pathological stages of CHD. This study extracted 28 symptom entries, 10 tongue manifestation entries, and 7 pulse manifestation entries, summarized the 5 main disease locations of the heart, lung, liver, spleen, and kidney, and the 8 main disease natures of blood stasis, phlegm turbidity, Qi stagnation, heat(fire), fluid retention, Qi deficiency, Yin deficiency, and Yang deficiency and 8 combinations of disease natures. The χ~2 test showed significant differences in the distribution of syndrome elements including the lung, liver, spleen, kidney, blood stasis, heat(fire), Qi stagnation, heat syndrome, water retention, Qi deficiency, Yin deficiency, and Yang deficiency between different disease stages. Specifically, the liver, blood stasis, heat(fire), and Qi stagnation accounted for the highest proportion during unstable stage, and the lung, spleen, kidney, water retention, Qi deficiency, Yin deficiency, and Yang deficiency accounted for the highest proportion at the end stage. The distribution of Qi deficiency varied in the different time periods after percutaneous coronary intervention(PCI). As shown by the χ~2 test of the syndrome elements combination, the distribution of single disease location, multiple disease locations, single disease nature, double disease natures, multiple natures, excess syndrome, and mixture of deficiency and excess varied significantly at different stages of CHD. Specifically, single disease location, single disease nature, and excess syndrome accounted for the highest proportion during the stable stage, and double disease natures accounted for the highest proportion during the unstable stage. Multiple disease locations, multiple disease natures, and mixture of deficiency and excess accounted for the highest proportion during the end stage. In conclusion, phlegm turbidity and blood stasis were equally serious during the stable stage, and a pathological mechanism caused by blood stasis and toxin existed during the unstable stage. The overall Qi deficiency worsened after PCI, and the end stage was accompanied by the Yin and Yang damage and the aggravation of water retention. There were significant differences in the distribution of clinical characteristics and syndrome elements at different stages of CHD. The pathological process of CHD witnessed the growth and decline of deficiency and excess and the combination of phlegm turbidity and blood stasis, which constituted the basic pathogenesis.

[Efficacy and mechanism of Xuefu Zhuyu Decoction on model rats of coronary heart disease with heart blood stasis syndrome based on metabolomics].

This study investigated the effects of Xuefu Zhuyu Decoction on myocardial metabolites in a rat model of coronary heart disease with heart blood stasis syndrome and explored the therapeutic mechanism of blood circulation-promoting and blood stasis-removing therapy. SD rats were randomly divided into a sham operation group, a model group, a Xuefu Zhuyu Decoction group(14.04 g·kg~(-1)), and a trimetazidine group(5.4 mg·kg~(-1)). The sham operation group underwent thread insertion without ligation, while the other groups underwent coronary artery left anterior descending branch ligation to induce a model of coronary heart disease with heart blood stasis syndrome. Three days after modeling, drug intervention was performed, and samples were taken after 14 days of intervention. General conditions were observed, and electrocardiogram and cardiac ultrasound indices were measured. Hematoxylin-eosin(HE) staining and Masson staining were used to observe tissue pathological morphology. The enzyme linked immunosorbent assay(ELISA) was used to measure the levels of triglyceride(TG) and total cholesterol(TC) in the serum. Ultra high performance liquid chromatography-quantitative exactive-mass spectrometry(UHPLC-QE-MS) technology was used to screen differential metabolites in myocardial tissue and conduct metabolic pathway enrichment analysis. The results showed that Xuefu Zhuyu Decoction significantly improved the general condition of the model rats, reduced heart rate and ST segment elevation in the electrocardiogram, increased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), and decreased left ventricular internal diameter in diastole(LVIDd) and left ventricular internal diameter in systole(LVIDs). HE staining and Masson staining showed that Xuefu Zhuyu Decoction effectively alleviated myocardial tissue structural disorders, inflammatory cell infiltration, and collagen fiber deposition in the model rats. ELISA results showed that Xuefu Zhuyu Decoction effectively regulated serum TG and TC levels in the model rats. There were significant differences in the metabolic phenotypes of myocardial samples in each group. Fourteen differential metabolites were identified in the Xuefu Zhuyu Decoction group, involving five metabolic pathways, including arginine and proline metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, ether lipid metabolism, and alanine, aspartate, and glutamate metabolism. Xuefu Zhuyu Decoction improved cardiac function and myocardial structural damage in the rat model of coronary heart disease with heart blood stasis syndrome, and its biological mechanism involved the regulation of lipid metabolism, choline metabolism, amino acid metabolism, energy metabolism, and protein synthesis pathways.

[Syndrome differentiation and treatment of coronary heart disease combined with anxiety and depression from stages of phlegm, blood stasis, and toxic pathogen based on theory of "coexistence of diseases and depression syndromes"].

Depression syndromes(anxiety and depression), as typical psychological disorders, often coexist with and mutually influence coronary heart disease(CHD). They constitute a psycho-cardiology disease involving both the blood vessels of the heart and the spirit of the heart. Based on the theory of "coexistence of diseases and depression syndromes", it was proposed that CHD and depression syndromes coexisted independently and were causally related. The factors of depression syndromes go through the entire course of CHD and have different causal relationships at different stages, leading to a pathogenic process of "depression causing disease" or "disease causing depression". In the chronic latent period, phlegm predominates, with depression leading to the production of phlegm. Phlegm accumulation and Qi stagnation initiate a mutual damage process of psycho-cardiology, marking the onset of the disease. In the pathological development period, blood stasis becomes predominant. Depression leads to blood stasis, which further obstructs Qi circulation, accelerating disease progression. In the acute attack period, toxicity becomes crucial. Depression transforms into toxicity, damaging Qi and blood, disturbing the balance of the mind, and inducing a sudden and severe exacerbation of the disease. Based on this, the approach of treating phlegm and depression together, treating blood stasis and depression together, and treating toxicity and depression together by stages was established. Research has found that this approach can simultaneously improve organic damage and emotional disorders, and also has a regulating effect on micro-level syndrome indicators, achieving harmonization of psycho-cardiology in the treatment.

[Research advances in mechanism of lipid infiltration of coronary heart disease and simultaneous treatment of phlegm and blood stasis based on phlegm-blood stasis correlation theory].

Atherosclerosis(AS) is the key pathological basis of coronary heart disease(CHD), and lipid infiltration is a classical theory to explain the pathological mechanism of AS. The theory highlights that the occurrence and development of AS are closely related to abnormal lipid metabolism, with the essence of the pathological reaction caused by the invasion of lipids into arterial intima from plasma. Phlegm and blood stasis are physiologically homologous and subject to pathological co-existence. Phlegm-blood stasis correlation is the basic theory to explain the pathogenesis characteristics of CHD and has important guiding significance for revealing the mecha-nism of lipid infiltration of CHD. Phlegm is the pathological product of abnormal metabolism of Qi, blood, and body fluid, and a gene-ral summary of a series of abnormally expressed lipid substances. Among them, turbid phlegm invades the heart vessels, gradually accumulates, and condenses to achieve the qualitative change from "invisible pathogen" to "tangible pathogen", which corresponds to the mechanism of lipid migration and deposition in the intima of blood vessels, and is the starting factor of the disease. Blood stasis is the continuous development of phlegm, and it is a result of pathological states such as decreased blood fluidity, increased blood coagulation, and abnormal rheology. The fact that blood stasis caused by phlegm accords with the pathological process of "lipid abnormality-circulatory disturbance" and is the central link of the disease. Phlegm and blood stasis aggravate each other and lead to indissoluble cementation. The phlegm-blood stasis combination serves as common pathogen to trigger the disease, which is the inevitable outcome of the disease. Based on the phlegm-blood stasis correlation theory, the simultaneous treatment of phlegm and blood stasis is established. It is found that this therapy can simultaneously regulate blood lipid, reduce blood viscosity, and improve blood circulation, which can fundamentally cut off the biological material basis of the reciprocal transformation between phlegm and blood stasis, thus exerting a significant curative effect.

Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-ß 1/Smad Pathway Regulation.

OBJECTIVE: To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. METHODS: Salt-sensitive (Dahl/SS) rats were fed with normal diet (0.3% NaCl) and the high-salt diet (8% NaCl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats (SS-13BN) were fed with the high-salt diet (8% NaCl) as the negative control group. After modeling, the model rats were randomly divided into heart failure (HF) group, Shenmai Injection (SMI) group and pirfenidone (PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay (ELISA), hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis. RESULTS: After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were significantly reduced, and the serum NT-proBNP concentration increased significantly (all P<0.05); furthermore, the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased (P<0.05); the protein and mRNA expressions of collagen type I (Col I) were up-regulated (P<0.05), and the mRNA expressions of transforming growth factor ß 1 (TGF- ß 1), Smad2 and Smad3 were significantly up-regulated (P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly (P<0.05), and the mRNA expressions of Col I, TGF- ß 1, Smad2 and Smad3, as well as Col I protein expression, were all significantly down-regulated (all P<0.05). CONCLUSION: Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-ß 1/Smad signaling pathway.

[Animal model analysis of rheumatoid arthritis based on clinical characteristics of Chinese and Western medicine].

Rheumatoid arthritis(RA) is an autoimmune disease involving multiple joints bilaterally with symmetrical polyarthritis as the main symptom. The high disability rate of this disease seriously affects the quality of life of patients and even threatens their lives. The establishment of a good animal model is of great significance for the diagnosis and clinical prevention of RA. Based on the clinical characteristics of RA in traditional Chinese and Western medicine, the common animal models of RA were summarized, including drug-induced, gene-related, and syndrome and disease combined models. Joint swelling, pain, redness, nodules, and joint deformity are the main criteria for model evaluation, which have certain differences from the clinical diagnostic criteria of RA. From the perspective of syndrome differentiation, the animal model combining syndrome and disease only simulates the syndrome of traditional Chinese medicine and has no direct causal relationship with the formation of RA. In this paper, we analyzed the advantages and disadvantages of animal models of RA and the coincidence degree of the models with the clinical characteristics and then put forward the corresponding recommendations for the evaluation and improvement of these models, aiming to make the animal models of RA closer to the clinical symptoms and play an important role in the clinical diagnosis and treatment of RA.

The effectiveness of acupuncture at Yaotongdian (EX-UE 7) for acute lumbar sprain: A protocol for a systematic review and meta-analysis.

BACKGROUND: Acupuncture at Yaotongdian (EX-UE 7) is increasingly used in acute lumbar sprain (ALS), and many studies have published that it is effective in the treatment of ALS. However, it is controversy if acupuncture at (EX-UE 7) can provide an evidence-based clinical benefit in the ALS population. METHODS: We will go through 8 databases, and conduct a systematic review of acupuncture on (EX-UE 7) and health-related outcomes in ALS patients according to the Preferred Reporting Items for Systematic Reviews. The primary objective is to assess the impact of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on clinical outcomes relevant to ALS patients, such as effective rate, life-quality evaluation, and adverse events. Cochrane Risk Assessment Tool will be used to assess the quality of eligible studies according to the Cochrane handbook. RESULTS: The results of this systematic review will provide a synthesis of current evidence of Acupuncture at Yaotongdian (EX-UE 7) and we have a specific opportunity to determine the efficacy and safety of it. CONCLUSION: This study will explore whether or not acupuncture on (EX-UE 7) can be used as one of the non-drug therapies to prevent or treat ALS. REGISTRATION NUMBER: 10.17605/OSF.IO/29QV7 (https://osf.io/29qv7/).

The efficacy and safety of Xiangsha Liujunzi decoction in the treatment of chronic non-atrophic gastritis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Chronic non-atrophic gastritis is the most common type of chronic gastritis. Even if treated with current standard pharmacotherapy, the efficacy is not very satisfactory due to many factors. Traditional Chinese Medicine decoctions are increasingly used in the treatment of chronic gastritis, and many studies have shown that Xiangsha Liujunzi decoction is effective and safe in the treatment of chronic non-atrophic gastritis. However, it is controversy if Xiangsha Liujunzi decoction can provide an evidence-based clinical efficacy and safety in the treatment of chronic non-atrophic gastritis. METHODS: We will go through 8 databases, and conduct a systematic review of Xiangsha Liujunzi decoction and health-related outcomes in chronic non-atrophic gastritis patients according to the Preferred Reporting Items for Systematic Reviews. The primary objective is to assess the impact of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on clinical outcomes relevant to chronic non-atrophic gastritis patients, such as clinical effective rate,Helicobacter pylori eradication rate, efficacy under endoscopy, 1-year recurrent rate, and number of reported adverse events. Cochrane Risk Assessment Tool will be used to assess the quality of eligible studies according to the Cochrane handbook. RESULTS: The results of this systematic review will provide a synthesis of current evidence of Xiangsha Liujunzi decoction and we have a specific opportunity to determine the efficacy and safety of it. CONCLUSION: This study will explore whether or not Xiangsha Liujunzi decoction can be used as one of the complementary and alternative therapies in the treatment of chronic non-atrophic gastritis. REGISTRATION NUMBER: Identifier: DOI 10.17605/OSF.IO/TX27U (https://osf.io/tx27u/).

Screening Study on the Anti-Angiogenic Effects of Traditional Chinese Medicine - Part II: Wild Chrysanthemum.

Background and Aims: Part 2 of our ongoing research with anti-angiogenic effects focuses on Wild chrysanthemum; a heat-clearing and detoxicating Traditional Chinese Medicine (TCM). We screened six heat-clearing and detoxicating TCM and noticed that wild chrysanthemum has a potent anti-angiogenic effect in zebrafish. This study aims to determine the genetic mechanisms underlying the anti-angiogenic effects of wild chrysanthemum. Methods: Wild chrysanthemum was decocted, concentrated, sieved and desiccated to attain the water extract. 200µg/mL wild chrysanthemum water extract (WCWE) was diluted in 0.1% dimethyl sulfoxide (DMSO) and given to zebrafish via fish water. 48h post-fertilization (hpf) fli1a-EGFP transgenic zebrafish were used to assay angiogenesis. mRNA-seq, qRT-PCR assay and a parallel reaction monitor (PRM) were carried out to reveal the underlying mechanisms. Results: WCWE showed a significant anti-angiogenic effect in zebrafish. The results of mRNA-seq showed that there were 1119 genes up-regulated and 1332 genes down-regulated by WCWE. The bioinformatic analysis based on mRNA-seq demonstrated that the proteasome signaling pathway was significantly down-regulated. The results of the qRT-PCR assay were consistent with those of the mRNA-seq assay. The results of the PRM assay showed that nine proteins involved in proteasome signaling and the protein expression level of ctnnb2 were significantly down-regulated. The results of the KEGG pathway analysis based on PRM assay demonstrated that WCWE may have an inhibitory action on the regulatory particle of the proteasome. Conclusion: Wild chrysanthemum has a significant anti-angiogenic effect in zebrafish and it may have an inhibitory action on the regulatory particle of the proteasome. The mechanisms underlying the anti-angiogenic effects of wild chrysanthemum may be related to the down-regulation of proteasome/ß-catenin signaling in zebrafish.

Gegen huangqin huanglian decoction for children rotavirus enteritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Rotavirus infection is the main cause of severe dehydration enteritis in children under 5 years old. It gives rise to malnutrition and even death in children even though there were rotavirus vaccines. However, there is no effective anti-virus drugs for rotavirus, supporting treatments are used in the clinics. Traditional Chinese medicine (TCM) has been treating diarrhea for many years. Gegen Huangqin Huanglian Decoction (GHHD)is a classic prescription for diarrhea in TCM. With the development of clinical trials and basic studies, GHHD has been proved that a good curative effect on diarrhea. Therefore, a systematic review is necessary to improve available evidence for GHHD in therapy of children under 5 years old with rotavirus enteritis. METHODS: Different studies from various databases will be involved in this study. Only randomized controlled trials of rotavirus enteritis patients diagnosed with Guidelines for the Treatment of Acute Gastroenteritis in Outpatient Pediatrics, which released by the Washington International Children's Medical Center, Zhu Futang's Practical Pediatrics (7 th Edition), and the 2016 clinical practice guidelines for children with acute infectious diarrhea in China. We will search the literature in the databases from China Conference Paper Database, manual searching. Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, CNKI (China National Knowledge Internet), WanFang, VIP (Chongqing VIP), and CBM (China Biomedical Literature CDROM Database). The primary outcomes include the total effective rate, the time of stopping diarrhea, the level of IL-6 serum concentration, fecal microflora ratio, the conversion of fecal rotavirus antigen. The secondary outcomes include clinical efficacy and the quantitative integral of TCM symptom, recovery time of stool character, treatment period. Besides, incidence of adverse events (such as irritation and toxicity) and costs will be also considered. Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3 and Stata V.12.0. RESULTS: This study will synthesize and provide high-quality evidence based on the data of the currently published GHHD for the treatment of children rotavirus enteritis, in terms of the total effective rate, the time of stopping diarrhea, the level of IL-6 serum concentration, fecal microflora ratio, stool rotavirus antigen, clinical efficacy and the quantitative integral of TCM symptom, recovery time of stool character, treatment period, and safety. CONCLUSION: This systematic review aims to evaluated the benefits and harms of GHHD for the treatment of children rotavirus enteritis reported in randomized controlled trials, and provide more options for clinicians and patients to treat children rotavirus enteritis. REGISTRATION NUMBER: INPLASY2020100023.

"Yellow-dragon Wonderful-seed Formula" for hyperuricemia in gout patients with dampness-heat pouring downward pattern: a pilot randomized controlled trial.

BACKGROUND: In Traditional Chinese Medicine (TCM) theories, the typical clinical manifestations of gout are attributed to the "dampness-heat pouring downward." Therefore, TCM practitioners always consider prescribing the formulae which are believed to clear heat and drain dampness for the management of gout. This clinical trial aims: (1) to determine the hypouricemic effect of "Yellow-dragon Wonderful-seed Formula" (YWF) decoction in gout patients with dampness-heat pouring downward pattern and (2) to determine if gypsum could provide additional significant benefits to YWF. METHODS: A total of 72 hyperuricemic individuals with gout and dampness-heat pouring downward pattern were included with 62 of them completing the trial. Participants were randomly assigned to the YWF group, the YWF + gypsum group, or the allopurinol group. YWF and YWF + gypsum decoctions were orally administered for four weeks. Allopurinol was also orally administered for four weeks as the active control. Serum uric acid (sUA) level was the primary outcome measure. Urine urate level, scores on the SF-36 scale, erythrocyte sedimentation rate (ESR), X ray film, and C reactive protein (CRP) level were the secondary outcome measures. RESULTS: Compared with the values at week 0, YWF and YWF + gypsum did not significantly decrease the sUA level at each weekend reading. YWF, YWF + gypsum, and allopurinol decreased the urine urate levels and there were significant differences between the YWF group and the YWF + gypsum group. All the changes in the eight structures of SF-36 during the intervention period were not significantly different among the three groups and there was no significant difference in the CRP level among the three groups at each weekend reading. CONCLUSIONS: YWM, which modified on the basis of Two Wonderful Herbs Powder (2WHP), does not show significant hypouricemic effect. There is a possibility that Gypsum Fibrosum may provide additional effects to YWF in decreasing the urine urate levels but cannot add benefits to YWF in other outcome measures. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-TRC-12001933 . Registered on 10 February 2012.

iTRAQ-Based Proteomics Identification of Serum Biomarkers of Two Chronic Hepatitis B Subtypes Diagnosed by Traditional Chinese Medicine.

Background. Chronic infection with hepatitis B virus (HBV) is a leading cause of cirrhosis and hepatocellular carcinoma. By traditional Chinese medicine (TCM) pattern classification, damp heat stasis in the middle-jiao (DHSM) and liver Qi stagnation and spleen deficiency (LSSD) are two most common subtypes of CHB. Results. In this study, we employed iTRAQ proteomics technology to identify potential serum protein biomarkers in 30 LSSD-CHB and 30 DHSM-CHB patients. Of the total 842 detected proteins, 273 and 345 were differentially expressed in LSSD-CHB and DHSM-CHB patients compared to healthy controls, respectively. LSSD-CHB and DHSM-CHB shared 142 upregulated and 84 downregulated proteins, of which several proteins have been reported to be candidate biomarkers, including immunoglobulin (Ig) related proteins, complement components, apolipoproteins, heat shock proteins, insulin-like growth factor binding protein, and alpha-2-macroglobulin. In addition, we identified that proteins might be potential biomarkers to distinguish LSSD-CHB from DHSM-CHB, such as A0A0A0MS51_HUMAN (gelsolin), PON3_HUMAN, Q96K68_HUMAN, and TRPM8_HUMAN that were differentially expressed exclusively in LSSD-CHB patients and A0A087WT59_HUMAN (transthyretin), ITIH1_HUMAN, TSP1_HUMAN, CO5_HUMAN, and ALBU_HUMAN that were differentially expressed specifically in DHSM-CHB patients. Conclusion. This is the first time to report serum proteins in CHB subtype patients. Our findings provide potential biomarkers can be used for LSSD-CHB and DHSM-CHB.

Screening study on the anti-angiogenic effects of Traditional Chinese Medicine - Part I: Heat-clearing and detoxicating TCM.

ETHNOPHARMACOLOGICAL RELEVANCE: Few studies have explored the anti-angiogenic effects of TCM - even more so, as it applies to cancer treatment research. Heat-clearing and detoxicating TCM is the most frequently used category in the treatment of cancerous tumors, but lacks sufficient validation studies. AIM OF THE STUDY: The present research (in our series of studies) aims to explore the anti-angiogenic effects of TCM; so we begin with heat-clearing and detoxicating TCM. MATERIALS AND METHODS: Six typical heat-clearing and detoxicating TCM (Philippine Violet Herb, Wild Chrysanthemum, Heartleaf Houttuynia Herb, Chinese Lobelia Herb, Spreading Hedyotis Herb and Uniflower Swisscentaury Root) were decocted, concentrated, sieved and desiccated to attain the water extract. This study utilized the vascular organism research model for Fli1a-EGFP zebrafish, which were raised and maintained under standard conditions. 22h post-fertilization (hpf) embryos were distributed into 12-well plates for a treatment period of 26h. The TCM water extracts which were diluted in 0.1% dimethyl sulfoxide (DMSO), were added to each well at a concentration of 200µg/ml. The positive control was 5µg/ml PTK787 (vatalanib) and the vehicle control was 0.1% DMSO. At 48hpf larvae were tricaine anesthetized and imaged. To demonstrate if TCM shows angiogenesis defects, ten larvae were randomly chosen to conduct a quantitative assay. Quantitative real-time PCR was conducted to dissect the mechanisms involved by analyzing the contributions of signaling pathways and molecules concerning angiogenesis, with a total of ten genes examined. RESULTS: All 30 larvae treated with Wild Chrysanthemum, Uniflower Swisscentaury Root and PTK787 showed angiogenesis defects. Embryos treated with Wild Chrysanthemum and Uniflower Swisscentaury Root showed a lower number of complete intersegmental vessels (ISVs) and there was statistically significant differences between TCM and the vehicle control. Wild Chrysanthemum and Uniflower Swisscentaury Root have a higher inhibition rate and the statistical difference between TCM and the vehicle control was significant. Compared with vehicle controls, Wild Chrysanthemum could significantly modulate the relative mRNA expression of all ten genes. Whereas, Uniflower Swisscentaury Root could significantly regulate the relative mRNA expression of seven genes, it did not show a significant impact on the remaining three genes. CONCLUSIONS: The present research demonstrates that Wild Chrysanthemum and Uniflower Swisscentaury Root have anti-angiogenic effects in zebrafish and that they could regulate both proangiogenic mechanisms and negative angiogenesis regulators. Their anti-angiogenic effects result from effects on negative regulators overriding their effects on proangiogenic mechanisms. The results provide new insights into their clinical application and therapeutic potential for the management of angiogenesis-dependent diseases such as cancer.

Effect of Pingan Fang, a Traditional Chinese Medicine compound, on behavioral sensitization and conditioned place preference induced by ethanol in mice.

OBJECTIVE: To observe the effect of Pingan Fang (PG) on behavioral sensitization and conditioned place preference (CPP) induced by ethanol in mice, and to determine the intervention mechanism of PG on alcohol addiction. METHODS: A behavioral sensitization mouse model induced by ethanol was established to observe the effect of PG on the development and expression of behavioral sensitization induced by ethanol by recording the spontaneous activity of mice. The resident time of mice in a white box was measured to evaluate the effect of PG on developing CPP induced by ethanol. Concentrations of dopamine (DA), Glutamate (Glu), and ã-aminobutyric acid (GABA) in the corresponding mesolimbic region of mice were determined by enzyme-linked immunosorbent assay. RESULTS: Although PG did not alter spontaneous activity in mice, it reduced the growth of spontaneous activity stimulated by ethanol. The residence time in the white box after-ethanol-training of mice in CPP experiments was decreased. CONCLUSION: Our data suggested that PG blocked the development and expression of behavioral sensitization induced by ethanol and the development of CPP in mice. The mechanism might be related to the decreased content of DA and Glu and increased content of GABA in the mesolimbic dopamine system. This suggests that PG might be useful for the prevention and treatment of alcohol addiction.

Improved prescription of taohechengqi-tang alleviates D-galactosamine acute liver failure in rats.

AIM: To investigate the hepatoprotective effect of improved prescription of Taohechengqi-tang (IPTT) against acute liver failure (ALF) in rats. METHODS: Seventy specific pathogen free male Wistar rats were randomly divided into four groups: control group (normal rats, n = 10), ALF group (ALF model, n = 20), Stronger Neo-Minophagen C (SNMC) group (ALF model + SNMC, n = 20), and IPTT group (ALF model + IPTT, n = 20). The ALF model group was administered an intraperitoneal injection of D-galactosamine (1.4 g/kg), and the control group received normal saline intraperitoneally. The SNMC and IPTT groups were treated with SMMC (15.6 mg/kg) or IPTT (28.6 g/kg) by gavage at 24 h intervals, and the ALF and control groups were treated with normal saline. At 36 h after injection, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, and cholinesterase and prothrombin time were determined, and liver histopathological scores were observed by microscopy after hematoxylin and eosin staining. mRNA expression of high mobility group box (HMGB) 1, toll-like receptor (TLR) 4, nuclear factor kappa B (NF-κB) and caspase-3 were analyzed via fluorescence quantitative reverse transcriptase polymerase chain reaction. Proliferating cell nuclear antigen (PCNA) immunohistochemistry in liver tissue was also performed. RESULTS: D-galactosamine notably decreased the biochemical and coagulation profiles in serum. IPTT not only improved liver function and histopathology but also normalized the gene expression levels in liver tissue. Compared with the model group, in the IPTT and SNMC groups, HMGB1 mRNA/ß-actin (0.06 ± 0.03, 0.11 ± 0.04 vs 0.25 ± 0.04, P < 0.05); TLR4 mRNA/ß-actin (0.07 ± 0.02, 0.22 ± 0.08 vs 0.41 ± 0.22, P < 0.05); NF-κB mRNA/ß-actin (0.74 ± 0.41, 1.78 ± 0.64 vs 2.68 ± 1.35, P < 0.05); and caspase-3 mRNA/ß-actin levels were all significantly reduced (1.61 ± 0.45, 2.57 ± 1.04 vs 3.41 ± 0.85, P < 0.05). The gene expression levels were significantly lower in the IPTT group than in the SNMC group (P < 0.05). Compared with the model group, the PCNA expression in liver tissue was significantly enhanced in the IPTT and SNMC groups (36.34 ± 4.91, 25.57 ± 2.94 vs 17.55 ± 2.40, P < 0.05). CONCLUSION: IPTT attenuates inflammation in ALF via inhibition of HMGB1 production, which may contribute to limited liver regeneration.

Efficacy and safety of Sancai powder in patients with type 2 diabetes mellitus: a randomized controlled trial.

OBJECTIVE: To assess the efficacy and safety of Sancai powder in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with single oral metformin in a randomized controlled trial (RCT). METHODS: A total of 132 patients with T2DM were enrolled in the study, who only took metformin (500-1000 mg/day) for at least three months and with inadequate glycemic control (7.0% ≤ hemoglobin A1c ≤ 9.0% ) in the past three months. The patients stopped taking metformin with lifestyle interventions for three weeks, and 105 patients qualified for the program. They were randomly divided into the Sancai powder group and the metformin group (1500 mg/day). The follow-up period was for 12 weeks. Comparisons of several variables were analyzed. RESULTS: No significant differences were found between the two groups in hemoglobin A1c (HbA1c), fasting plasma glucose (FPG) and 2 h post-meal glucose (2hPG), although they had decreased significantly (P < 0.01). Homeostasis model assessment of beta cell function index was significantly improved in Sancai powder group (P < 0.01), and there were significant differences in the changes of homeostasis model assessment of insulin resistance and insulin sensitivity index in the two groups (P < 0.05). Sancai powder significantly reduced triglyceride level (P < 0.05), although there was no significant difference in the body weight and body mass index in the two groups. CONCLUSION: In this 12-week study, Sancai powder could significantly reduce hemoglobin A1c, FPG and 2hPG levels, improved beta-cell function and insulin resistance of the T2DM inadequately controlled with metformin.

Combination Therapy with Chinese Medicine and ACEI/ARB for the Management of Diabetic Nephropathy: The Promise in Research Fragments.

BACKGROUND: The clinical benefits of the application of renin-angiotensin system (RAS) blockade, i.e., angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), have been well established in patients with diabetic nephropathies (DN). Since the combination therapy with Chinese Medicine (CM) and conventional western medicine (CWM) is considered an effective approach to many conditions, many CM experts have investigated the combination therapy with CM and RAS blockade to look for new approaches to DN. AIM: The purpose of this article is to review the antiproteinuric and renopretective effects of combination therapy of CM and ACEI/ARBs for the management of DN. METHODS: Relevant articles were identified through PubMed and three major Chinese databases (CBM, CAJD, CSTJ) up to March 2013. FINDINGS: The results of the current literature are consistent with CM theories (e.g., tonifying and replenishing CM with blood-activating and stasis-resolving CM as major therapeutic strategies for the management of DN). 91 clinical articles on the combination therapy of CM and ACEI/ARBs were identified, but only eight randomized controlled trials were eventually included in the present review. The results were not always consistent: three articles reported that CM conferred both anti-proteinuric and reno-protective effects in addition to ACEI/ARBs; three articles reported that CM failed to provide additional reno-protective benefits; two articles reported that CM conferred neither anti-proteinuric nor renoprotective effects in addition to ACEI/ARBs. CONCLUSION: Current literature indicates that combination therapy with CM and ACEI/ARBs might have polypharmacological anti-proteinuric and reno-protective effects for the management of DN. Shortcomings concerning the interaction between CM and CWM, methodology, and study design need to be addressed in future research.

The effects of modified sini decoction on liver injury and regeneration in acute liver failure induced by D-galactosamine in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified sini decoction (MSND) is a well-known traditional Chinese medical formula that has been used to treat cardiovascular and liver diseases for many years. We investigated the effects of MSND on acute liver failure and identified the possible mechanisms of these effects. MATERIAL AND METHODS: Acute liver failure was induced by intraperitoneal injection of d-galactosamine (d-GalN) into specific pathogen-free male Wistar rats. Next, the rats were treated with Stronger Neo-Minophagen C and MSND via gavage. Biochemical parameters, histological changes in the liver, the survival of rats and the mRNA levels of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), high mobility group box 1 (HMGB1) caspase-3 and proliferating cell nuclear antigen (PCNA) were analyzed. RESULTS: MSND prolonged the survival times of the acute liver failure rats. The biochemical parameters were improved, and necrosis in the liver tissues was reduced by both Stronger Neo-Minophagen C (SNMC) and MSND, but MSND induced greater effects. The mRNA expressions of HMGB1, TLR4, NF-κB, and Caspase-3 were remarkably decreased, and the expression of PCNA was remarkably increased by SNMC and MSND, and the effects of MSND were greater. CONCLUSIONS: MSND protected the liver and increased the survival rate of acute liver failure rats. These effects were likely mediated by the inhibitions of the inflammatory reaction and apoptosis and the promotion of liver tissue regeneration.

Effect of ASF (a Compound of Traditional Chinese Medicine) on Behavioral Sensitization Induced by Ethanol and Conditioned Place Preference in Mice.

ASF composed by semen and epimedium herbal is a traditional plant compound that is widely used in the treatment of insomnia. Studies have shown that saponins and flavonoids contained in semen can significantly decrease the content of excitatory neurotransmitter Glu in mice. And the total flavone of YinYangHuo can increase the release of GABA in the anterior periventricular system of rat and increase the affinity of GABA for the receptors GABAA. It can be inferred that their synergism may have effect on the neurotransmitter that causes behavioral sensitization and conditioned place preference in experimental animals and affects their drinking behaviors, which is the starting point of this research. The present study found that ASF can inhibit development and expression of behavioral sensitization induced by ethanol and the development of CPP in mice. We demonstrate the inhibition of ASF on behavioral sensitization partly due to its effect on the mesolimbic neurotransmitter system, including decreasing level of DA and Glu and increasing the content of GABA. It suggested that the ASF may have pharmacological effects in the treatment of alcohol addiction.

Chinese medicines induce cell death: the molecular and cellular mechanisms for cancer therapy.

Chinese medicines have long history in treating cancer. With the growing scientific evidence of biomedical researches and clinical trials in cancer therapy, they are increasingly accepted as a complementary and alternative treatment. One of the mechanisms is to induce cancer cell death. Aim. To comprehensively review the publications concerning cancer cell death induced by Chinese medicines in recent years and provide insights on anticancer drug discovery from Chinese medicines. Materials and Methods. Chinese medicines (including Chinese medicinal herbs, animal parts, and minerals) were used in the study. The key words including "cancer", "cell death", "apoptosis", "autophagy," "necrosis," and "Chinese medicine" were used in retrieval of related information from PubMed and other databases. Results. The cell death induced by Chinese medicines is described as apoptotic, autophagic, or necrotic cell death and other types with an emphasis on their mechanisms of anticancer action. The relationship among different types of cell death induced by Chinese medicines is critically reviewed and discussed. Conclusions. This review summarizes that CMs treatment could induce multiple pathways leading to cancer cell death, in which apoptosis is the dominant type. To apply these preclinical researches to clinic application will be a key issue in the future.