[Role of NLRP3 inflammasome in heart failure and traditional Chinese medicine intervention: a review].

Heart failure is characterized by high incidence and mortality rates, and the search for effective treatment strategies for heart failure and the improvement of clinical outcomes have always been important research directions. Imbalanced inflammation has been proven to be one of the critical pathological factors in heart failure, positively correlated with adverse events such as impaired cardiac function and myocardial fibrosis. In recent years, studies have confirmed that the activation of the NOD-like receptor thermal protein domain-associated protein 3(NLRP3) inflammasome plays a common regulatory role in the inflammation imbalance induced by various factors in heart failure. Moreover, certain traditional Chinese medicine(TCM) and active components can significantly inhibit the activation of the NLRP3 inflammasome, thereby improving heart failure. This article first overviewed the basic information about the NLRP3 inflammasome, summarized the regulatory mechanisms of the NLRP3 inflammasome in heart failure induced by various factors, introduced recent research progress on TCM and active components that inhibited the NLRP3 inflammasome to improve heart failure, aiming to provide references for innovative drug research in the field of integrated Chinese and western medicine for the prevention and treatment of heart failure.

[Effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction].

Jiming Powder is a traditional ancient prescription with good therapeutic effect in the treatment of heart failure, but its mechanism lacks further exploration. In this study, a mouse model of coronary artery ligation was used to evaluate the effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction. The study constructed a mouse model of heart failure after myocardial infarction using the method of left anterior descending coronary artery ligation. The efficacy of Jiming Powder was evaluated from multiple angles, including ultrasound imaging, hematoxylin-eosin(HE) staining, Masson staining, Sirius Red staining, and serum myocardial enzyme spectrum detection. Western blot analysis was performed to detect key proteins involved in ventricular remodeling, including transforming growth factor-ß1(TGF-ß1), α-smooth muscle actin(α-SMA), wingless-type MMTV integration site family member 3a(Wnt3a), ß-catenin, matrix metallopeptidase 2(MMP2), matrix metallopeptidase 3(MMP3), TIMP metallopeptidase inhibitor 1(TIMP1), and TIMP metallopeptidase inhibitor 2(TIMP2). The results showed that compared with the model group, the high and low-dose Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVID;s) and diastole(LVID;d), increased the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improved cardiac function in mice after myocardial infarction, and effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactic dehydrogenase(LDH), thus protecting ischemic myocardium. HE staining showed that Jiming Powder could attenuate myocardial inflammatory cell infiltration after myocardial infarction. Masson and Sirius Red staining demonstrated that Jiming Powder effectively inhibited myocardial fibrosis, reduced the collagen Ⅰ/Ⅲ ratio in myocardial tissues, and improved collagen remodeling after myocardial infarction. Western blot results showed that Jiming Powder reduced the expression of TGF-ß1, α-SMA, Wnt3a, and ß-catenin, decreased the levels of MMP2, MMP3, and TIMP2, and increased the level of TIMP1, suggesting its role in inhibiting cardiac fibroblast transformation, reducing extracellular matrix metabolism in myocardial cells, and lowering collagen Ⅰ and α-SMA content, thus exerting an anti-myocardial fibrosis effect after myocardial infarction. This study revealed the role of Jiming Powder in improving ventricular remodeling and treating myocardial infarction, laying the foundation for further research on the pharmacological effect of Jiming Powder.

[Mechanism of Jiming Powder in ameliorating heart failure with preserved ejection fraction based on metabolomics].

In this study, untargeted metabolomics was conducted using the liquid chromatography-tandem mass spectrometry(LC-MS/MS) technique to analyze the potential biomarkers in the plasma of mice with heart failure with preserved ejection fraction(HFpEF) induced by a high-fat diet(HFD) and nitric oxide synthase inhibitor(Nω-nitro-L-arginine methyl ester hydrochloride, L-NAME) and explore the pharmacological effects and mechanism of Jiming Powder in improving HFpEF. Male C57BL/6N mice aged eight weeks were randomly assigned to a control group, a model group, an empagliflozin(10 mg·kg~(-1)·d~(-1)) group, and high-and low-dose Jiming Powder(14.3 and 7.15 g·kg~(-1)·d~(-1)) groups. Mice in the control group were fed on a low-fat diet, and mice in the model group and groups with drug intervention were fed on a high-fat diet. All mice had free access to water, with water in the model group and Jiming Powder groups being supplemented with L-NAME(0.5 g·L~(-1)). Drugs were administered on the first day of modeling, and 15 weeks later, blood pressure and cardiac function of the mice in each group were measured. Heart tissues were collected for hematoxylin-eosin(HE) staining to observe pathological changes and Masson's staining to observe myocardial collagen deposition. Untargeted metabolomics analysis was performed on the plasma collected from mice in each group, and metabolic pathway analysis was conducted using MetaboAnalyst 5.0. The results showed that the blood pressure was significantly lower and the myocardial concentric hypertrophy and left ventricular diastolic dysfunction were significantly improved in both the high-dose and low-dose Jiming Powder groups as compared with those in the model group. HE and Masson staining showed that both high-dose and low-dose Jiming Powder significantly alleviated myocardial fibrosis. In the metabolomics experiment, 23 potential biomarkers were identified and eight strongly correlated metabolic pathways were enriched, including linoleic acid metabolism, histidine metabolism, alpha-linolenic acid metabolism, glycerophospholipid metabolism, purine metabolism, porphyrin and chlorophyll metabolism, arachidonic acid metabolism, and pyrimidine metabolism. The study confirmed the pharmacological effects of Jiming Powder in lowering blood pressure and ameliorating HFpEF and revealed the mechanism of Jiming Powder using the metabolomics technique, providing experimental evidence for the clinical application of Jiming Powder in treating HFpEF and a new perspective for advancing and developing TCM therapy for HFpEF.

Integrating network pharmacology and experimental evidence to decipher the cardioprotective mechanism of Yiqihuoxue decoction in rats after myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: "Qi deficiency and blood stasis" syndrome is one of the most common syndromes treated with Traditional Chinese Medicine among ischemic heart disease (IHD) patients in clinic. As a Chinese herbal formula with the function of tonifying Qi and activating blood, Yiqihuoxue Decoction (YQHX) has been frequently proven to be effective in the clinical treatment of IHD. AIM OF THE STUDY: The cardioprotective mechanisms of YQHX in treating ischemic heart disease were investigated, with emphasis on the key targets and pathways. MATERIALS AND METHODS: In the present study, the potential targets of compounds identified in YQHX were predicted using PharmMapper, Symmap, and STITCH databases, and a "herb-compound-target" network was constructed using Cytoscape. Subsequently, the GO and KEGG functional enrichment analyses were analyzed using the DAVID database. Furthermore, a protein-protein interaction network was constructed using STRING to obtain the key target information. Besides, we used a myocardial ischemia rat model to investigate the cardioprotective effects of YQHX. Transmission electron microscopy and Western blotting were used to observe apoptotic bodies and confirm protein expressions of key candidate targets, respectively. RESULTS: Network pharmacology showed that a total of 141 potential targets were obtained from these databases. The functional analysis results revealed that the targets of YQHX were largely associated with apoptosis, and the PI3K-AKT and MAPK pathways might represent key functional pathways. The hub genes of network include ALB, TP53, AKT1, TNF, VEGFA, EGFR, MAPK1, CASP3, JUN, FN1, MMP9, and MAPK8. In vivo, YQHX significantly improved cardiac function and suppressed apoptosis in ischemic rat myocardium. Furthermore, YQHX could significantly upregulate Nrf2 and HO-1 expression, and inhibit JNK phosphorylation. CONCLUSIONS: Based on network pharmacology and experimental evidence, this study proves that the cardioprotective effects and mechanisms of YQHX depend on multi-component, multi-target, and multi-pathway. In particular, YQHX exerts anti-apoptotic effects potentially by regulating the Nrf2/HO-1 and JNK-MAPK pathways.

Trans- and cis-acting effects of Firre on epigenetic features of the inactive X chromosome.

Firre encodes a lncRNA involved in nuclear organization. Here, we show that Firre RNA expressed from the active X chromosome maintains histone H3K27me3 enrichment on the inactive X chromosome (Xi) in somatic cells. This trans-acting effect involves SUZ12, reflecting interactions between Firre RNA and components of the Polycomb repressive complexes. Without Firre RNA, H3K27me3 decreases on the Xi and the Xi-perinucleolar location is disrupted, possibly due to decreased CTCF binding on the Xi. We also observe widespread gene dysregulation, but not on the Xi. These effects are measurably rescued by ectopic expression of mouse or human Firre/FIRRE transgenes, supporting conserved trans-acting roles. We also find that the compact 3D structure of the Xi partly depends on the Firre locus and its RNA. In common lymphoid progenitors and T-cells Firre exerts a cis-acting effect on maintenance of H3K27me3 in a 26 Mb region around the locus, demonstrating cell type-specific trans- and cis-acting roles of this lncRNA.

Protective effect of Yi-Qi-Huo-Xue Decoction against ischemic heart disease by regulating cardiac lipid metabolism.

Yi-Qi-Huo-Xue Decoction (YQHX) is the recombination of Dang-Gui-Bu-Xue Decoction (DBD), which is one of the well-known traditional Chinese Medicine (TCM) prescription, and has long been shown to have significant protective effects against myocardial ischemic injury. In previous studies, we found that YQHX could regulate lipid and glucose metabolism, promote angiogenesis, attenuate inflammatory response, and ameliorate left ventricular function in myocardial ischemia rat models. However, the underlying mechanism of how YQHX involves in lipid metabolism remains unclear so far. In this study, the underlying mechanism of YQHX in lipid metabolism disorders was elucidated in a myocardial ischemia rat model and a hypoxia-induced H9c2 cell injury model. YQHX (8.2 g·kg-1) and positive-control drug trimetazidine (10 mg·kg-1) were administered daily on the second day after left anterior descending (LAD) operation. At 7 days and 28 days after surgery, changes of cardiac morphology, structure, and function were evaluated by H&E staining and echocardiography, respectively. The plasma lipid levels and mitochondrial ATP content were also evaluated. Western blot and RT-PCR were used to determine the protein and mRNA expressions of AMPK, PGC-1α, CPT-1α, and PPARα. YQHX improved cardiac function and ameliorated lipid metabolism disorders. Furthermore, YQHX increased the expression of p-AMPK, PGC-1α, and CPT-1α without changing PPARα in ischemic rat myocardium. In vitro, YQHX activated the protein and mRNA expression of PGC-1α, CPT-1α, and PPARα in hypoxia-induced H9c2 cells injury, whereas AMPK inhibitor Compound c blocked the effects of YQHX. Taken together, the results suggest that YQHX reduces lipid metabolism disorders in myocardial ischemia via the AMPK-dependent signaling pathway.

Protective effect of Yi-Qi-Huo-Xue Decoction against ischemic heart disease by regulating cardiac lipid metabolism / 中国天然药物

Yi-Qi-Huo-Xue Decoction (YQHX) is the recombination of Dang-Gui-Bu-Xue Decoction (DBD), which is one of the well-known traditional Chinese Medicine (TCM) prescription, and has long been shown to have significant protective effects against myocardial ischemic injury. In previous studies, we found that YQHX could regulate lipid and glucose metabolism, promote angiogenesis, attenuate inflammatory response, and ameliorate left ventricular function in myocardial ischemia rat models. However, the underlying mechanism of how YQHX involves in lipid metabolism remains unclear so far. In this study, the underlying mechanism of YQHX in lipid metabolism disorders was elucidated in a myocardial ischemia rat model and a hypoxia-induced H9c2 cell injury model. YQHX (8.2 g·kg) and positive-control drug trimetazidine (10 mg·kg) were administered daily on the second day after left anterior descending (LAD) operation. At 7 days and 28 days after surgery, changes of cardiac morphology, structure, and function were evaluated by H&E staining and echocardiography, respectively. The plasma lipid levels and mitochondrial ATP content were also evaluated. Western blot and RT-PCR were used to determine the protein and mRNA expressions of AMPK, PGC-1α, CPT-1α, and PPARα. YQHX improved cardiac function and ameliorated lipid metabolism disorders. Furthermore, YQHX increased the expression of p-AMPK, PGC-1α, and CPT-1α without changing PPARα in ischemic rat myocardium. In vitro, YQHX activated the protein and mRNA expression of PGC-1α, CPT-1α, and PPARα in hypoxia-induced H9c2 cells injury, whereas AMPK inhibitor Compound c blocked the effects of YQHX. Taken together, the results suggest that YQHX reduces lipid metabolism disorders in myocardial ischemia via the AMPK-dependent signaling pathway.

Potentially fatal electrolyte imbalance caused by severe hydrofluoric acid burns combined with inhalation injury: A case report.

BACKGROUND: Hydrofluoric acid (HF) is one of the most common causes of chemical burns. HF burns can cause wounds that deepen and progress aggressively. As a result, HF burns are often severe even if they involve a small area of the skin. Published cases of HF burns have mostly reported small HF burn areas. Few cases of HF inhalation injury have been reported to date. CASE SUMMARY: A 24-year-old man suffered from extensive hydrofluoric acid burns covering 60% of the total body surface area (TBSA), including deep second degree burns on 47% and third degree burns on 13% of the TBSA, after he fell into a pickling pool containing 15% HF. Comprehensive treatments were carried out after the patient was admitted. Ventricular fibrillation occurred 9 times within the first 2 h, and the lowest serum Ca2+ concentration was 0.192 mmol/L. A dose of calcium gluconate (37 g) was intravenously supplied during the first 24 h, and the total amount of calcium gluconate supplementation was 343 g. Extracorporeal membrane oxygenation (ECMO) was applied for 8 d to handle the acute respiratory distress syndrome (ARDS) induced by the HF inhalation injury. The patient was discharged after 99 d of comprehensive treatment, including skin grafting. CONCLUSION: Extensive HF burns combined with an inhalation injury led to a potentially fatal electrolyte imbalance and ARDS. Adequate and timely calcium supplementation and ECMO application were the keys to successful treatment of the patient.

Observation on the efficacy of motherwort injection in the treatment of abnormal uterine bleeding-ovulatory dysfunction / 中国实用妇科与产科杂志

OBJECTIVE: To observe the clinical efficacy of motherwort injection in the treatment of abnormal uterine bleeding-ovulatory dysfunction(AUB-O),and provide data support for broadening the clinical application range of motherwort injection.METHODS: A multicenter,randomized,prospective study was used.The patients who were diagnosed with AUB-O in Hospital of Chengdu University of Traditional Chinese Medicine in 2018 were randomly divided into the control group and the experimental group according to random numbers.There were 75 cases in the experimental group,7 cases were lost,and 68 cases were the final cases;another 75 cases were in the control group,4 cases were lost,and there were 71 cases in the end.In the control group,only the tranexamic acid was given.On the basis of this,the experimental group was given intramuscular injection of motherwort injection 2 mL/time,b.i.d.,for 3 consecutive days.The clinical TCM symptom scores,blood loss,blood routine,coagulation function,endometrial thickness and effective rate were compared between the two groups.All data were statistically analyzed using IBM SPSS 21.0.RESULTS: After treatment,the total effective rate of the experimental group was 97.06%,which was significantly better than that(84.51%)of the control group(P0.05),but on the 2nd day and the 3rd day after treatment,the difference was statistically different(P<0.05),and the cumulative amount of bleeding after 3 days of treatment was statistically different(P<0.05).The endometrial thickness of the experimental group was lower than that of the control group(P<0.01).CONCLUSION: Motherwort injection combined with basic therapy is effective in the treatment of AUB-O.

1-Methoxycarbony-β-carboline from Picrasma quassioides exerts anti-angiogenic properties in HUVECs in vitro and zebrafish embryos in vivo / 中国天然药物

Angiogenesis is a crucial process in the development of inflammatory diseases, including cancer, psoriasis and rheumatoid arthritis. Recently, several alkaloids from Picrasma quassioides had been screened for angiogenic activity in the zebrafish model, and the results indicated that 1-methoxycarbony-β-carboline (MCC) could effectively inhibit blood vessel formation. In this study, we further confirmed that MCC can inhibit, in a concentration-dependent manner, the viability, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, as well as the regenerative vascular outgrowth of zebrafish caudal fin in vivo. In the zebrafish xenograft assay, MCC inhibited the growth of tumor masses and the metastatic transplanted DU145 tumor cells. The proteome profile array of the MCC-treated HUVECs showed that MCC could down-regulate several angiogenesis-related self-secreted proteins, including ANG, EGF, bFGF, GRO, IGF-1, PLG and MMP-1. In addition, the expression of two key membrane receptor proteins in angiogenesis, TIE-2 and uPAR, were also down-regulated after MCC treatment. Taken together, these results shed light on the potential therapeutic application of MCC as a potent natural angiogenesis inhibitor via multiple molecular targets.

1-Methoxycarbony-β-carboline from Picrasma quassioides exerts anti-angiogenic properties in HUVECs in vitro and zebrafish embryos in vivo / 中国天然药物

Angiogenesis is a crucial process in the development of inflammatory diseases, including cancer, psoriasis and rheumatoid arthritis. Recently, several alkaloids from Picrasma quassioides had been screened for angiogenic activity in the zebrafish model, and the results indicated that 1-methoxycarbony-β-carboline (MCC) could effectively inhibit blood vessel formation. In this study, we further confirmed that MCC can inhibit, in a concentration-dependent manner, the viability, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, as well as the regenerative vascular outgrowth of zebrafish caudal fin in vivo. In the zebrafish xenograft assay, MCC inhibited the growth of tumor masses and the metastatic transplanted DU145 tumor cells. The proteome profile array of the MCC-treated HUVECs showed that MCC could down-regulate several angiogenesis-related self-secreted proteins, including ANG, EGF, bFGF, GRO, IGF-1, PLG and MMP-1. In addition, the expression of two key membrane receptor proteins in angiogenesis, TIE-2 and uPAR, were also down-regulated after MCC treatment. Taken together, these results shed light on the potential therapeutic application of MCC as a potent natural angiogenesis inhibitor via multiple molecular targets.

Effect of systemic low-level light therapy on early systemic inflammatory response of severe burn rats / 第二军医大学学报

Objective To explore the effect of systemic low-level light therapy (LLLT) on early inflammatory response of severe burn rats.Methods Fifty SD rats were randomly divided into control group,burned model group,single short-term LLLT group,single long-term LLLT group and the repeated short-term LLLT group,with 10 rats in each group.After burning the rats in the single short-term LLLT group,the single long-term LLLT group and the repeated short-term LLLT group were treated by low-intensity LED irradiation (640 nm) for 5 min once a day,15 min once a day and 5 min three times a day,respectively.The levels of tumor necrosis factor α (TNF-α),interleukin (IL)-1β and IL-6 and the leukocyte count in caudal vein were determined at 1 day before modeling,immediately after modeling and on the 1st,3rd,7th and 14th day after modeling;and the wound area was measured on the 3rd,7th and 14th day after modeling.The wound healing rate was calculated.Results Compared with the control group,the serum TNF-α levels in the burned model and single short-term LLLT groups were significantly increased on the 1st day after modeling (P＜0.05),and the serum TNF-α levels in the single long-term LLLT group on the Pt day and the repeated short-term LLIT group on the 7th day were significantly increased (P＜0.05);the serum IL-1β levels were significantly decreased on the 1st day after modeling in all groups (P＜0.05),and then gradually recovered with the varied recovery rates;the serum IL-6 levels in the burned model and the repeated short-term LLLT groups were significantly increased on the 1st day after modeling (P＜0.05),then decreased;and the decrease of the burned model group was greater than that of the repeated short-term LLLT group.While the serum IL-6 level was increased on the 3rd day in the single short-term LLLT group,then decreased;and the level was significantly increased in the single long-term LLLT group (P＜0.05).Leukocyte counts of the burned model and the single long-term LLLT groups were significantly increased on the 1st day after modeling (P＜0.05),and it had no significant change in the other groups.The wound healing rate in the single short-term LLLT group,the single long-term LLLT group and the repeated short-term LLLT group was significantly higherthan that in the burned model group (P＜0.05).Conclusion Systemic LLLT use can reduce the serum levels of TNF-α,IL-1β and IL-6 and leukocyte count in caudal vein of the severe burning rats and promote wound healing,with the effects varied with different irradiation modes.

Effects of Ginseng Fruit Saponins on Serotonin System in Sprague-Dawley Rats with Myocardial Infarction, Depression, and Myocardial Infarction Complicated with Depression / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Our previous studies have demonstrated that the levels of 5-hydroxytryptamine (5-HT) and 5-HT 2A receptor (5-HT2AR) in serum and platelet were associated with depression and myocardial infarction (MI), and pretreatment with ginseng fruit saponins (GFS) before MI and depression had an effect on the 5-HT system. In this study, the effects of GFS on the 5-HT system in the Sprague-Dawley (SD) rats with MI, depression, and MI + depression were evaluated.</p><p><b>METHODS</b>A total of eighty SD rats were allocated to four groups: MI, depression, MI + depression, and control groups (n = 20 in each group). Each group included two subgroups (n = 10 in each subgroup): Saline treatment subgroup and GFS treatment subgroup. The levels of 5-HT, 5-HT2AR, and serotonin transporter (SERT) were quantified in serum, platelet lysate, and brain tissue through the enzyme-linked immunosorbent assay method, respectively.</p><p><b>RESULTS</b>Compared with those in the saline treatment subgroups, the levels of 5-HT in serum and platelet lysate statistically significantly increased in the GFS treatment subgroups of MI, depression, and MI + depression groups (serum: all P = 0.000; platelet lysate: P = 0.002, 0.000, 0.000, respectively). However, the 5-HT levels in brain homogenate significantly decreased in the GFS treatment subgroups compared with those in the saline treatment subgroups in MI and depression groups (P = 0.025 and 0.044 respectively), and no significant difference was observed between saline and GFS treatment subgroups in MI + depression group (P = 0.663). Compared with that in GFS treatment subgroup of control group, the 5-HT2AR levels in the platelet lysate significantly decreased in GFS treatment subgroups of MI, depression, and MI + depression groups (all P = 0.000). Compared to those in the saline treatment subgroups, the serum SERT levels significantly decreased in the GFS treatment subgroups in MI, depression, and MI + depression groups (P = 0.009, 0.038, and P = 0.001, respectively), while the SERT levels of platelet lysate significantly decreased in GFS treatment subgroup of MI group (P = 0.000), significantly increased in GFS treatment subgroup of depression group (P = 0.019), and slightly changed in GFS treatment subgroup of MI + depression group (P = 0.219). No significant changes for SERT levels in brain homogenate could be found between the saline and GFS treatment subgroups in MI, depression, and MI + depression groups (P = 0.421, 0.076 and P = 0.642).</p><p><b>CONCLUSIONS</b>This study indicated that GFS might inhibit the reuptake of 5-HT from serum to platelet according to decreased 5-HT2AR in platelet and SERT in serum and platelet. The change of 5-HT in serum after GFS treatment was inconsistent with that in the brain. It seemed that GFS could not pass through the blood-brain barrier to affect the central serotonergic system.</p>

Ethanol-extracted propolis enhances BBN-initiated urinary bladder carcinogenesis via non-mutagenic mechanisms in rats.

Ethanol-extracted propolis (EEP) is used for medical, dietetic and cosmetic purposes. In this study, the effects of EEP on urinary bladder carcinogenesis, its underlying mechanism and in vivo genotoxicity were investigated. In experiment 1, rats were treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 2 or 4 weeks followed by dietary administration of 0.125, 0.25, 0.5 or 1% EEP for 4 or 32 weeks, respectively. At week 6, the mRNA levels of top2a, cyclin D1 and survivin were significantly elevated in the 0.5 and 1% EEP groups. At week 36, the incidence and multiplicity of urothelial carcinomas and total tumors were markedly elevated in all EEP groups. In experiment 2, rats were fed basal diet or the 1% EEP diet for 13 weeks without carcinogen initiation. Increases in urinary precipitate, cell proliferation and incidence of simple hyperplasia were observed in the 1% EEP group. In experiment 3, dietary administration of 2.5% EEP to gpt delta rats for 13 weeks did not induce any obvious mutagenicity in the urinary bladder urothelium. Taken together, EEP enhanced BBN-initiated rat urinary bladder carcinogenesis in a non-genotoxic manner through increasing formation of urinary precipitate, enhancing cell proliferation and inhibiting apoptosis during the early stages of carcinogenesis.

Effects of rosuvastatin correlated with the down-regulation of CYP4A1 in spontaneously hypertensive rats.

The effects of long-term rosuvastatin treatment on the regulation of cytochrome P450 (CYP) 4A1 expression and vascular homeostasis of spontaneously hypertensive rat (SHR) are still unknown. In this study SHRs were randomly divided into three groups (n=10 per group): SHR group, H-Rv group (rosuvastatin 2.5 mg·kg(-1)·d(-1)), L-Rv group (rosuvastatin 0.5 mg·kg(-1)·d(-1)), and 10 male Wistar-Kyoto (WKY) rats in the control group (WKY group). All rats were treated with rosuvastatin for 12 weeks. The systolic blood pressure (SBP), left ventricle weight index (LVWI) and plasma lipids were measured during or after treatment. The expression of CYP4A1 mRNA and protein in different tissues was detected by real-time PCR and Western blot. In the heart, kidney and aorta, the CYP4A1 expressions were down-regulated at both mRNA and protein levels in rosuvastatin-treated groups compared with the untreated SHR group (P<0.05 or P<0.01), and high-dose rosuvastatin exerted a stronger down-regulatory effect. The increasing trend of blood pressure was markedly blunted in the rosuvastatin-treated groups versus the untreated SHR group, and a stronger effect was observed in high-dose group (P<0.05 and P<0.01 at different time points). LVWI, an indicator of ventricle hypertrophy, was improved in the high-dose group compared with the untreated SHR group (P<0.05). The plasma concentrations of TC, TG and LDL-C in three SHR groups (high-dose, low-dose and untreated group) were all significantly lower than those of WKY group (P<0.05 or P<0.01), which seemed unrelated to the treatment of rosuvastatin. These findings suggested that hypertension in SHRs was possibly associated with CYP4A1 overexpression, and the effects of rosuvastatin on blood pressure and ventricle hypertrophy were potentially correlated with CYP4A1 and its metabolite other than lipid profiles. Multiple mechanisms are likely involved in the beneficial effects of statins with respect to the regulation of CYP4A1.

Combination of acupressure and magnetic sticker improved the quality of life in patients with advanced gastroenteric tumor: a clinical observation / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the clinical effect of combination of acupressure and magnetic sticker on the quality of life (QOL) including appetite, defecation, and sleep in patients with advanced gastroenteric tumor.</p><p><b>METHODS</b>Totally 147 patients with advanced gastroenteric tumor were assigned to 4 groups according to different treatment methods, i.e., the supportive treatment group (A, 20 cases), the acupressure treatment group (B, 41 cases), the magnetic sticker treatment group (C, 40 cases), and a combination of acupressure and magnetic sticker treatment group (D, 46 cases). They were respectively treated with different methods, supportive treatment for group A, acupressure for group B, magnetic sticker for group C, and a combination of acupressure and magnetic sticker for group D. The scores of food intake, defecation frequency, sleep time, Karnofsky, and QOL were compared before treatment and at day 14 after treatment.</p><p><b>RESULTS</b>After treatment, the scores of food intake, defecation frequency, and sleep time were obviously improved in B, C and D groups (P < 0.01). There was statistical difference between group D and group A (P < 0.01). In addition, in comparison with A group, both Karnofsky score and QOL score increased in B, C and D groups (P < 0.01).</p><p><b>CONCLUSION</b>The assisted therapy of the combination of acupressure and magnetic sticker could ameliorate QOL such as the digestive functions and sleep in patients with advanced gastroenteric tumor.</p>

Impacts of electroacupuncture on ubiquitin-proteasome system in rats with Parkinson's disease / 中国针灸

<p><b>OBJECTIVE</b>To explore action mechanism of electroacupuncture (EA) on treatment and prevention of Parkinson's disease (PD).</p><p><b>METHODS</b>Fifty clean-grade SD rats were randomly divided into a normal group, a control group, a model group, a pretreatment group and a treatment group, ten rats in each one. The PD model was established by subcutaneous injection of rotenone in neck-back skin (2 mg/kg, dissolved in sun-flower oil, 2 mg/mL in density). The equal-volume sun-flower oil that didn't include rotenone was applied in the control group at the same area as the model group. EA was applied in the treatment group at "Fengfu" (GV 16) and "Taichong" (LR 3) with interrupted wave, 2 Hz in frequency, 1 mA in density, for 20 min. The treatment was given once day for conti-nuous 28 days. Rats in the pretreatment group received the same EA as the treatment group for 7 days, and then put into model establishment. After the model establishment, the rats received no treatment and were sacrificed after 28 days. No EA was given in the normal group, model group and control group. The ethology changes were observed and scored. The expression of Parkin, ubiquitin C terminal hydrolase-L1 (UCH-L1) and ubiquitin activating enzyme-1 (UBE1) in substantia nigra was tested by Western-blot method. The positive cell numbers of alpha-synuclein, ubiquitin (UB) and tyrosine hydroxylase (TH) in substantia nigra was tested by immunohistochemical method.</p><p><b>RESULTS</b>There were abnormal ethology manifestation such as yellow and coarse hair, arched back, weaken behavior of resisting arrest and slow movement, which was more relieved in the treatment group and pretreatment group. Compared with normal group and control group, the expression of Parkin, UCH-L1, UBE1, UB, TH in the model group was obviously decreased while alpha-synuclein was obviously increased (all P<0.01). After EA or pretreatment, the expression of Parkin, UCH-L1, UBE1, UB, TH in the treatment group and pretreatment group was higher than that in the model group while expression of alpha-synuclein in the treatment group and pretreatment group was lower than that in the model group (all P<0.01).</p><p><b>CONCLUSION</b>EA or pretreatment could not only have protective effect for rats with PD, but also increase function of ubiquitin-proteasome system, indicating action mechanism of EA on treatment and prevention of PD may be related with ubiquitin-proteasome system.</p>

Effects of electro-acupuncture on learning, memory and the morphology of hippocampal nerve tissue after cerebral ischemia in rats / 中华物理医学与康复杂志

Objective To observe the effects of electro-acupuncture ( EA ) on learning, memory and the morphology of hippocampal neural tissues in rats with a model of chronic cerebral ischemia.Methods One hundred and twenty male Sprague-Dawley rats were used. Chronic cerebral ischemia models were successfully established in 104 of them, and those rats were randomly divided into an EA group and a model group with 52 rats each. These were further subdivided into 1,2, 4 and 6 week subgroups with 13 rats in each. The EA group was given EA. The changes in spatial learning and memory ability were observed using a Morris water maze. The morphological changes in hippocampal nerve tissue were observed by HE staining.Results The escape latency in the EA group was significantly different from the model group at the 2nd, 4th and 6th week. The nerve cells in the dentate gyrus were more tightly and consistently lined-up and had rich layers, and the structures in the EA group were better than in the model group.Conclusions EA can improve spatial learning and memory and promote the repair of injury after cerebral ischemia.

Study on the functions of peripheral dendritic cells in chronic hepatitis B virus infection patients of Gan-depression Pi-deficiency syndrome and Gan-Dan damp-heat syndrome under different immune states / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the functions of peripheral dendritic cells (DCs) in chronic hepatitis B virus (HBV) infection patients of Gan-depression Pi-deficiency syndrome (GPS) and Gan-Dan damp-heat syndrome (GDS) under different immune states, thus to study the features of the immune expressions of the two syndromes in chronic HBV infection, providing objective evidence for Chinese medicine syndrome typing.</p><p><b>METHODS</b>The 40 chronic HBV patients were randomly assigned to two groups according to the immune state. Of them, there were 20 chronic HBV patients (under the condition of immune clearance; consisting of 10 patients of GPS and 10 of GDS) and 20 chronic HBV carriers (under the condition of immune tolerance; consisting of 10 patients of GPS and 10 of GDS). Besides, 10 healthy graduate volunteers of Hunan University of Traditional Chinese Medicine were recruited as the healthy control group. Their peripheral blood mononuclear cells (PBMCs) were cultured in vitro. The exterior morphological features and ultrastructure were observed by inverted microscope and electron microscope. The expressions of HLA-DR, CD80, CD86, and CDIa of the DCs surface were detected. The secretory levels of IL-12 in the supernate of DCs were detected by ELISA reagent kit. The proliferation capacities of allogeneic mixed lymphocyte were detected using MTT. The function features of DCs in the chronic HBV patients of two syndrome types under different immune states were compared, thus analyzing the difference of each index between the two syndrome types.</p><p><b>RESULTS</b>Compared with the healthy control group, the expression rates of CD86, CD80, and HLA-DR decreased in the HBV carriers group (of the two syndrome types), showing statistical difference (P < 0.05). The expression rate of CD80 decreased in the HBV group (of the two syndrome types), showing statistical difference (P < 0.05). The expression rates of CD86 and HLA-DR were lower in the GPS group than in the GDS group. The expression rate of CD80 was lower in the GPS group than in the GDS group, showing statistical difference (P < 0.05). The proliferation capacities of IL-12 and T lymphocytes were lower in the HBV patients group than in the healthy control group (P < 0.05). The proliferation capacities of IL-12 and T lymphocytes were lower in the GPS group than in the GDS group, showing statistical difference (P < 0.05).</p><p><b>CONCLUSIONS</b>The functions of peripheral DCs in chronic HBV infection of patients of the GPS and the GDS under different immune states were different. The phenotype and function tests of DCs provided objective evidence for Chinese syndrome typing of chronic hepatitis B, thus reflecting the features of immune expressions of the two syndrome types and the immunology connotation.</p>

Effect of bushen antai recipe and its various compositions on endometrial sexual hormones and receptors in mice with blastocyst implantation dysfunction / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To compare the effects and mechanisms of Bushen Antai Recipe (BAR) and its different compositions, Bushen Recipe (BSR, the Shen-nourishing part) and Huoxue Recipe (HXR, the blood-activating part) on the endometrial receptivity in mice with blastocyst implantation dysfunction (BID).</p><p><b>METHODS</b>Model mice of BID induced by indomethacin were treated respectively with BAR, BSR and HXR from the first day of pregnancy, and killed on day 5 or 6. Samples of their serum and uterine were collected for detecting serum estradiol (E2), progesterone (P) contents using radioimmunoassay; and endometrial expression levels of their receptors, ER and PR, using immunohistochemistry.</p><p><b>RESULTS</b>Serum levels of E2 and P, and endometrial expression of ER and PR increased significantly on day 6 in mice after treated by BAR, but in those treated by BSR and HXR, the improvements were significantly lesser.</p><p><b>CONCLUSION</b>BAR, by combined application of both Shen-nourishing and blood-activating methods, could impact E2, P, ER and PR to improve the endometrial receptivity to a higher extent in BID mice so as to promote embryo implantation.</p>