[Research progress in signaling pathways related to treatment of functional dyspepsia with traditional Chinese medicine].

Functional dyspepsia(FD) is a prevalent functional gastrointestinal disease characterized by recurrent and long-lasting symptoms that significantly impact the quality of life of patients. Currently, western medicine treatment has not made breakthrough progress and mainly relies on symptomatic therapies such as gastrointestinal motility agents, acid suppressants, antidepressants/anxiolytics, and psychotherapy. However, these treatments have limitations in terms of insufficient effectiveness and safety. Traditional Chinese medicine(TCM) possesses unique advantages in the treatment of FD. Through literature search in China and abroad, it has been found that the mechanisms of TCM in treating FD is associated with various signaling pathways, and research on these signaling pathways and molecular mechanisms has gradually become a focus. The main signaling pathways include the SCF/c-Kit signaling pathway, 5-HT signaling pathway, CRF signaling pathway, AMPK signaling pathway, TRPV1 signaling pathway, NF-κB signaling pathway, and RhoA/ROCK2/MYPT1 signaling pathway. This series of signaling pathways can promote gastrointestinal motility, alleviate anxiety, accelerate gastric emptying, reduce visceral hypersensitivity, and improve duodenal micro-inflammation in the treatment of FD. This article reviewed the research on TCM's regulation of relevant signaling pathways in the treatment of FD, offering references and support for further targeted TCM research in the treatment of FD.

Chinese Herbal Medicine for the Treatment of Adult Viral Myocarditis: An Overview of Systematic Reviews and Meta-analyses of Randomized Controlled Trials.

PURPOSE: Viral myocarditis (VMC) is a life-threatening disease that can affect all ages and genders, with middle-aged adults being particularly susceptible. Numerous systematic reviews have been conducted to investigate the efficacy and safety of Chinese herbal medicine (CHM) in treating adult viral myocarditis (AVM). The objective of this study was to conduct a comprehensive overview of systematic reviews and meta-analyses of randomized controlled trials (RCTs) regarding the efficacy and safety of CHM for AVM. METHODS: A comprehensive systematic search was conducted across 8 electronic databases from their inception to June 23, 2022, augmented by manual searches of the gray literature. Systematic reviews were independently selected and data extracted in accordance with predetermined criteria by 2 reviewers. Included systematic reviews were assessed for methodologic and reporting quality using Assessing the Methodological Quality of Systematic Reviews 2 and Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The quality of evidence relating to outcome measures was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation tool. Recalculation of effect sizes and subsequent determination of 95% CIs were conducted with either a fixed-effects or random-effects model. FINDINGS: The current overview of systematic reviews included a total of 6 systematic reviews, which reported on 67 RCTs with a participant pool of 5611 individuals. The findings of our study indicate that the combination of CHM and Western medications had positive effects on the effective rate, cure rate, ECG recovery, atrial premature contraction/premature ventricular contraction, left ventricular ejection fraction, myocardial enzymes, and improvement of clinical symptoms for AVM. The adverse drug reactions in the combination therapy group were generally less than or lighter than that in the Western medication group (relative risk = 0.79; 95% CI, 0.44-1.40; P > 0.05, I2 = 0). IMPLICATIONS: Our research results provide evidence that combining CHM with Western medicine could offer potential benefits for patients with AVM. However, the number of studies included in our review is limited and the methodologic quality of these studies is modest. Therefore, there are potential uncertainties regarding the conclusion that CHM with Western medication may benefit patients with AVM. We call for more large-scale, high-quality studies with standardized designs to further verify and support our findings. This would promote a better understanding of the efficacy and safety profile of CHM and provide reliable reference evidence for clinical practice and policy making. Moreover, future research should explore optimal drug combinations, examine therapeutic doses and durations of CHM combination therapy, and evaluate its long-term efficacy and safety.

The Synergistic Effects of Astragalus mongholicus and Salvia miltiorrhiza on Coronary Heart Disease Identified by Network Pharmacology and Experiment.

BACKGROUND AND PURPOSE: Two Chinese herbal medicines Huang Qi (HQ, Astragalus mongholicus) and Dan Shen (DS, Salvia miltiorrhiza) are often combined to treat coronary heart disease (CHD). The purpose of this study was to identify the underlying synergistic effects and mechanisms of HQ and DS against CHD. METHODS: The active components and targets of HQ and DS, CHD-related genes, and the biological progression were analysed by network pharmacology. The myocardial infarction (MI) rat model was established by ligating the left anterior descending coronary artery. Cardiac function was detected by ultrasonic electrocardiography. The MI size, fibrosis, cardiac hypertrophy, lipid metabolism, blood viscosity, and coagulation indexes were analysed by histological staining or chemical methods, respectively. RESULTS: A total of 170 shared and specific seed genes of HQ and DS against CHD were identified. The shared and specific biological processes of HQ and DS against CHD were obtained. The LVEF and LVFS values significantly increased, the myocardium infarct size and fibrosis significantly decreased, the values of lipid metabolism indexes and blood viscosity indexes significantly reduced in the HQ + DS treatment group vs HQ or DS single treatment (P < 0.05); the LVEDd, LVEDs, and the CSA values significantly reduced in HQ single and HQ + DS treatment groups vs MI group (P < 0.05); the coagulation index (APTT, PT, TT, and FIB) values decreased significantly in the DS single and HQ + DS treatment groups vs MI group (P < 0.05). CONCLUSION: In MI rats, HQ and DS exhibited synergistic effects on improving cardiac function, reducing MI size, fibrosis, regulating hyperlipidaemia, and maintaining circulatory system homeostasis; HQ had the specific advantage of alleviating cardiac remodelling; DS had the specific advantage of regulating hypercoagulability. This study revealed that HQ and DS not only exerted synergistic effects but also exhibited complementary effects on CHD.

Analysis of the Efficacy and Mechanism of Action of Xuebijing Injection on ARDS Using Meta-Analysis and Network Pharmacology.

OBJECTIVE: Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas-exchange impairment due to a severe inflammatory process known as cytokine storm. Xuebijing injection (hereinafter referred to as Xuebijing) is a patent drug that was used to treat ARDS or severe pneumonia (SP) in China. However, its efficacy and mechanism of actions remain unclear. In this study, we used meta-analysis and network pharmacology to assess these traits of Xuebijing. METHODS: We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases for randomized controlled trials (RCTs) that evaluated Xuebijing therapy for ARDS or SP. The outcomes were total mortality, intensive care unit (ICU) stay time, and TNF-α and IL-6 levels. We performed a meta-analysis using RevMan 5.3 software. The putative targets, top 10 proteins, and possible pathway of Xuebinjing on ARDS were analyzed by network pharmacology. TNF-α and IL-6 were further docked with the six main active components of Xuebinjing using AutoDock 4.2.6 and PyMol 1.5.0.3 software. RESULTS: Fifteen RCTs involving 2778 patients (13 ARDS and 2 SP) were included. Compared with the control, Xuebijing treatment significantly reduced the mortality rate (risk ratio, 0.64 (95% credible interval (CrI), 0.54-0.77)), reduced the ICU stay time (mean difference (MD), -4.51 (95% CrI, -4.97--4.06)), reduced the TNF-α ((MD), -1.23 (95% CrI, -1.38--1.08)) and IL-6 ((MD), -1.15 (95% CrI, -1.52--0.78)) levels. The 56 putative targets, top 10 proteins (MAPK1 (mitogen-activated protein kinase 1), MAPK8 (mitogen-activated protein kinase 8), RELA (transcription factor p65), NFKB1 (nuclear factor NF-kappa-B p105 subunit), JUN (transcription factor AP-1), SRC (proto-oncogene tyrosine-protein kinase), TNF (tumor necrosis factor), HRAS (GTPase HRas), IL6 (interleukin-6), and APP (amyloid-beta A4 protein)), and possible pathways (Ret tyrosine kinase, IL2-mediated signaling events, CD4+/CD8+ T cell-related TCR signaling, p75(NTR)-mediated signaling, CXCR4-mediated signaling events, LPA receptor-mediated events, IL12-mediated signaling events, FAS (CD95) signaling pathway, and immune system) of Xuebinjing's action on ARDS were obtained. The molecular docking results showed that all the six components of Xuebinjing docked with TNF-α, and two components docked with IL-6 got the binding energies lower than -5. CONCLUSION: Our results recommended Xuebijing treatment for patients with ARDS. Xuebijing has therapeutic effects on ARDS patients partly by regulating the immune cell/cytokine pathways and thus inhibiting the cytokine storm. TNF-α is the cytokine both directly and indirectly inhibited by Xuebijing, and IL-6 is the cytokine mainly indirectly inhibited by Xuebijing.

Panax Notoginseng Saponins Inhibits Ventricular Remodeling after Myocardial Infarction in Rats Through Regulating ATF3/MAP2K3/p38 MAPK and NF κ B Pathway.

OBJECTIVE: To explore whether Panax notoginseng saponins (PNS) exhibits heart protective effect in myocardial infarction (MI) rats and to identify the potential signaling pathways involved. METHODS: MI rats induced by ligating the left anterior descending (LAD) coronary artery were assigned to sham coronary artery ligation or coronary artery ligation. Totally 36 Sprague-Dawley rats were randomly divided into sham group (distilled water, n=9), MI group (distilled water, n=9), PNS group (PNS, 40 mg/kg daily, n=9) and fosinopril group (FIP, 1.2 mg/kg daily, n=9) according to a random number table. The left ventricular morphology and function were conducted by echocardiography. Histological alterations were evaluated by the stainings of HE and Masson. The serum levels of C reactive protein (CRP), tumor necrosis factor α (TNF-α), growth differentiation factor-15 (GDF-15) and the ratio of metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-9 (TIMP-1) were determined by ELISA. The levels of activating transcription factor 3 (ATF3), mitogen-activated protein kinase kinase 3 (MAP2K3), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylation of p38 MAPK (p-p38 MAPK), transforming growth factor-ß (TGF-ß1), collagen I, nuclear factor kappa B p65 (NFκB p65), phosphorylation of NFκB p65 (p-NFκB p65), and phosphorylation of inhibitory kappa Bα (p-Iκ Bα) in hearts were measured by Western blot and immunohistochemical staining, respectively. RESULTS: PNS improved cardiac function and fibrosis in MI rats (P<0.05). The serum levels of CRP, TNF-α, GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats. The expressions of TGF-ß1, collagen I, MAP2K3, p38 MAPK, p-p38 MAPK, NFκB p65, p-NFκB p65, and p-IκBα were down-regulated, while ATF3 increased with the treatment of PNS (P<0.05). CONCLUSIONS: PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2K3/p38 MAPK and NFκB signaling pathways. These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.

Platycodin D alleviates liver fibrosis and activation of hepatic stellate cells by regulating JNK/c-JUN signal pathway.

Liver fibrosis is involved in the progression of most chronic liver diseases. Even though we have made a huge progress in order to understand the pathogenesis of liver fibrosis, however, there is still a lack of productive treatments. Being a traditional Chinese medicine, Platycodin D (PD), an oleanane kind of triterpenoid saponin has been put to extensive use for treating different kinds of illnesses that include not just anti-nociceptive, but also antiviral, anti-inflammatory, and anti-cancer for thousands of years. Nonetheless, there has been no clarification made for its effects on the progression of liver fibrosis. In this manner, we carried out in vitro studies for the purpose of investigating the anti-fibrosis impact of PD. Activation of hepatic stellate cells was evaluated by means of the detection of the proliferation of HSCs and the expression of specific proteins. We discovered the fact that PD had the potential of activating HSCs. Thereafter, we detected the apoptosis and autophagy of the HSCs; as the results suggested, PD induced apoptosis and autophagy of the HSCs. It augmented the expression level of apoptotic proteins that included Bax, Cytochrome C (cyto-c), cleaved caspase3 and cleaved caspase9, in addition to the autophagy relevant proteins, for instance, LC3II, beclin1, Atg5 and Atg9. Further research was carried out for the investigation of the underlying molecular mechanism, and discovered that PD promoted the phosphorylation of JNK and c-Jun. Treating the JNK inhibitor P600125 inhibited the effect of PD, confirming the impact of PD on the regulation of JNK/c-Jun pathway. Thus, we speculated that PD alleviates liver fibrosis and activation of hepatic stellate via promoting phosphorylation of JNK and c-Jun and further altering the autophagy along with apoptosis of HSCs.

Uncovering the protective mechanism of Huoxue Anxin Recipe against coronary heart disease by network analysis and experimental validation.

Coronary heart disease (CHD) is a leading cause of death and disability worldwide. Huoxue Anxin Recipe (HAR) is a novel Chinese Herbal Medicine formula of that has been used to treat CHD for several decades. Our previous study found that HAR had anti-oxidative effects, and could promote myocardial angiogenesis and improve cardiac function following myocardial infarction (MI) in rats. However, the active compounds, potential targets, and biological processes related to HAR have not been systematically investigated. Here, network pharmacology and experimental validation were used to study the protective mechanisms of HAR against CHD. We identified 124 active components, 124 verified targets, and 111 predictive targets. A total of 1192 genes related to CHD were identified by cDNA microarray and database analysis. A total of 47 putative targets of HAR against CHD were identified, including 32 verified targets and 15 predictive targets. ClueGo enrichment analysis identified 49 biological processes involved in the anti-CHD effects of HAR. Among them, the negative regulation of blood coagulation and regulation of collagen biosynthetic process were experimentally validated. After constructing a protein-protein interaction network and clustering with MECODE and ClusterONE, 162 key proteins (from ClueGo and clustering) were used to construct an internal interaction network. Complement C3 (C3), Fibrinogen alpha (FGA), Fibrinogen gamma (FGG), interleukin-6 (IL6), and Apolipoprotein A1 (APOA1) were the top 5 hub proteins identified by cytoHubber analysis. HAR limited the concentrations of C3, FGA, FGG, and IL6 and increased APOA1 levels. The results indicated that HAR could down-regulate blood coagulation, regulate collagen biosynthesis, inhibit peroxidation and inflammation injury, and promote cholesterol efflux. HAR could be a potential source of novel and effective drugs for CHD.

Network Pharmacology-Based Prediction and Verification of the Targets and Mechanism for Panax Notoginseng Saponins against Coronary Heart Disease.

Coronary heart disease (CHD) is the worldwide leading cause for cardiovascular death. Panax notoginseng saponin (PNS), which is the main bioactive compound of panax notoginseng, has been generally accepted to exert a remarkable effect on CHD for a long time. However, to reveal the underlying treatment target and corresponding mechanism of PNS against CHD is still a substantial challenge. In this work, the targets and mechanism of PNS against CHD were successfully achieved by pharmacology-based prediction and experimental verification. 36 common targets were screened out through integrating the gene expression profile of CHD and the chemical-protein data of PNS. Then, two key nodes were further selected for verification by experiment after analyzing GO function, KEGG pathway, coexpression, and topology analysis. Results showed that PNS has protected the human umbilical vein endothelial cells from H2O2-induced oxidative stress by inhibiting early cell apoptosis via upregulating VEGFA mRNA expression. Therefore, our research has successfully pointed out one treatment target and apoptotic inhibition caused by PNS with method of integrating bioinformatics prediction and experimental verification, which has partially explained the pharmacological mechanism of PNS against CHD.

[Hyperspectral prediction model of soil nutrient content in the loess hilly-gully region, China.] / é»„åœŸä¸˜é™µæ²Ÿå£‘åŒºåœŸå£¤å »åˆ†å«é‡çš„é«˜å ‰è°±é¢„æµ‹æ¨¡åž‹.

Rapid and accurate estimation of soil nutrient content based on hyperspectral data is an optimal method for the monitoring of soil nutrient and inversion of soil physical and chemical characters. The relationship between soil nutrient content and spectral reflectance was analyzed with soil samples being collected from the loess hilly-gully region of northern Shaanxi Province. The prediction models of the content of soil organic matter, total nitrogen, total phosphorus and total potassium were constructed by the combination of three techniques, including partial least squares (PLS), multiple linear regression (MLR), and support vector machine (SVM). Then, the optimal model was selected by comparison analysis. The results showed good correlations between the content of soil nutrients and spectral reflectance in visible region (400-760 nm) and near infrared region (760-1100 nm). The maximum values of correlation coefficient located in both spectral regions. The SPA-SVM model had the best applicability and highest inversion accuracy for the contents of all soil nutrients, with simple and efficient modeling process. Our results provided a reference for applying machine learning algorithm in the construction of hyperspectral prediction model of soil nutrient content in the loess hilly-gully region.

Huoxue Anxin Recipe () promotes myocardium angiogenesis of acute myocardial infarction rats by up-regulating miR-210 and vascular endothelial growth factor.

OBJECTIVE: To investigate the microRNAs (miRNAs) expression profile of acute myocardial infarction (AMI) rats and the regulating effects of Huoxue Anxin Recipe (, HAR) on angiogenesis-related miRNAs and genes. METHODS: Forty-five Wistar rats were randomly assigned to 3 groups according to a random number table: sham, AMI, and AMI+HAR groups (15 in each group). AMI rats were established by ligation of the left descending coronary artery. HAR was intragastrically administered to rats of the AMI+HAR group for successive 21 days since modeling, meanwhile the same volume of 0.9% normal saline was administered to rats of the sham and AMI groups. Doppler echocardiography was used for noninvasive cardiac function test. Hematoxylin and eosin staining was used to observe the histopathological change. miRNAs expression profile was detected by quantitative realtime polymerase chain reaction (qRT-PCR). The mRNA and protein expressions of vascular endothelial growth factor (VEGF), and a target gene of miR-210 was further detected by qRT-PCR and Western blot, respectively. The microvessels density of myocardium was evaluated by CD31 immunostaining. RESULTS: Compared with the sham group, ejection fraction (EF) and fractional shortening (FS) values were decreased significantly in the AMI group (P<0.01), while the infarction area and the interstitial collagen deposition were increased obviously. As for the AMI+HAR group, EF and FS values were increased significantly (P<0.05 vs. AMI group), and the infarction area was reduced and the interstitial collagen deposition were alleviated significantly. Total of 23 miRNAs in the AMI group expressed differently by at least 1.5 folds compared with those in the sham group; 5 miRNAs in the AMI+HAR group expressed differently by at least 1.5 folds compared with those in the AMI group. Among them, miR-210 was low in the AMI group and high in the AMI+HAR group. The relative mRNA and protein expressions of VEGF were decreased significantly in the AMI group (P<0.05 vs. sham group), and increased significantly in the AMI+HAR group (P<0.01 vs. AMI group). CD31 expression area and optical intensity were decreased significantly in the AMI group (P<0.05 vs. sham group), and increased significantly in the AMI+HAR group (P<0.01 vs. AMI group). CONCLUSIONS: HAR could reduce the infarction area, alleviate the interstitial fibrosis and improve the cardiac function of AMI rats. Those effects could be related to promoting myocardium angiogenesis of HAR by up-regulating miR-210 and VEGF.

[MicroRNA and left ventricular hypertrophy].

MicroRNAs (miRNA) plays an important role in biological development and disease occurrence and development, and acts as a "main switch" in biology. Among patients of essential hypertension, around 1/3 would suffer left ventricular hypertrophy (LVH). Hence, essential hypertension becomes an independent risk factor for cardiovascular diseases. And miRNAs plays an important role in the occurrence and development of LVH. This paper reviewed the role of miRNA in regulating the stress signaling pathway, defined its impact on the occurrence of LVH, and further emphasized the opportunities and challenges of miRNA as a biomarker and therapeutic target.

[Study of drug intervention in diversity changes of TCRVbeta gene in AIDS patients with incomplete immune reconstitution].

OBJECTIVE: To discuss the drug intervention in diversity changes of TCRVbeta gene in AIDS patients with incomplete immune reconstitution. METHOD: PBMCs were isolated from 37 cases of AIDS patients failure to immune reconstitution before and after treatment with immune 2 and 15 cases of HIV negative healthy donors. The human gene TCRVbeta CDR3 diversity quantitative detection reagent box were used, and mapped the distribution of gene scanning and calculated different CDR3 fragme of each Vbeta family size. RESULT: Compared with the normal group, there appeared some single or oligoclonal amplification of Vbeta CDR3 region in the patients, which were improved or recovered after treatment. Among them, D value of four families (9, 11, 21, 22 ) decreased after treatment in both groups. The decrease in family 21 and 22 was significant (P < 0.05) in treatment group compared with the control group. And family 18 was decreased in treatment group and increased significantly in control group (P < 0.05). CONCLUSION: Study of the mechanism showed oligoclonal of TCRVbeta family can get recovery in some degrees after treated by Immune 2 plus HAART, suggesting that the medicine may promote T-cell receptor gene rearrangement, helping immune cells to effectively identify the virus to reduce T-cell apoptosis.

[Diversity changes of TCRVbeta gene in AIDS patients with incomplete immune reconstitution and influence of drug].

OBJECTIVE: To discuss the drug intervention in diversity changes of TCRVbeta gene in AIDS patients with incomplete immune reconstitution. METHOD: PBMCs were isolated from 37 cases of AIDS patients failure to immune reconstitution before and after treatment with Immune 2 and 15 cases of HIV negative healthy donors. The human gene TCRVbeta CDR3 diversity quantitative detection reagent box were used, and mapped the distribution of gene scanning and calculated different CDR3 fragme of each Vbeta family size. RESULT: (1) Gaussian distribution of TCRVbeta families in patients with incomplete immune reconstitution after one year of HAART, had been broken with the occurrence of the offset TCR lineage. After six months of treatment of traditional Chinese medicine combined HAART, the TCR lineage has been partially restored. (2) Evaluated by the D (distance) value calculated by a quantitative analysis software which the kit provides, there were no significant difference in D value change between the two groups, but with traditional Chinese medicine can reduce the data variability. (3) CD4+ T cell counts had a significant correlation (r = -0.772, P = 0.000) with TCRVbeta genetic diversity. CONCLUSION: Study of the mechanism showed oligoclonal of TCRVbeta family can get recovery in some degrees after treated by Immune 2 plus HAART, suggesting that the medicine may promote T-cell receptor gene rearrangement, helping immune cells to effectively identify the virus to reduce T-cell apoptosis.

Effect of Yisui Shengxue Granule () on the oxidative damage of erythrocytes from patients with hemoglobin H disease.

OBJECTIVE: To investigate the effect of Yisui Shengxue Granule (, YSSXG), a complex Chinese medicine, on the oxidative damage of erythrocytes from patients with hemoglobin H (HbH) disease. METHODS: Twenty-two patients with HbH disease and 22 healthy volunteers were observed. YSSXG was given to patients with HbH disease for 3 months. Before and after the 3-month treatment, blood parameters [hemoglobin (Hb), red blood cells (RBCs), and reticulocyte percent (Ret)] were examined; inclusion bodies in erythrocytes were observed by transmission electron microscopy (TEM); activities of antioxidant defense enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (Cat)] and erythrocyte membrane malondialdehyde (MDA) concentrations were determined. RESULTS: In patients with HbH disease, measured values of RBC and Hb obtained from the first to the third months after treatment with YSSXG were significantly higher than before treatment (P<0.01). Measured values of Ret from the second to the third months after treatment were significantly lower than before treatment (P<0.05 and P<0.01, respectively). Prior to treatment with YSSXG, TEM images of RBCs showed the presence of numerous inclusion bodies. After treatment with YSSXG, the amount and volume of inclusion bodies decreased. Treatment with YSSXG also led to a significant increase in SOD activity (P<0.01), a decrease in Cat activity (P<0.01), and no significant differences in GSHPx activity (P>0.05) or MDA concentration (P>0.05). However, compared with the healthy counterparts, SOD, GSH-Px, and Cat activities presented at high levels (P<0.01) both before and after treatment. CONCLUSIONS: YSSXG could improve the degree of hemolysis and anemia in patients with HbH disease. The mechanism may be related to its antioxidative effects, which could elevate the activity of total SOD in erythrocytes and efficiently inhibit the oxidative precipitation of ß-globin chains.

[Effects of Chinese herbal medicine Yiqi Huoxue Formula on TGF-ß/smad signal transduction pathway and connective tissue growth factor in rats with renal interstitial fibrosis].

OBJECTIVE: To observe the effects of Yiqi Huoxue Formula (YQHXF), a compound Chinese herbal medicine, on transforming growth factor-ß (TGF-ß)/smad signal transduction pathway and connective tissue growth factor (CTGF) in rats with renal interstitial fibrosis METHODS: Unilateral ureteral obstruction (UUO) rat model was established and the rats were randomly divided into 5 groups: untreated group, high-, medium-, and low-dose YQHXF groups and fosinopril sodium group. Another group with sham operation was set as control. All rats were administered with corresponding drugs for 3 weeks. After the last administration, each rat was sacrificed and weighed and the serum was separated for creatinine (Cr) and blood urea nitrogen (BUN) detection. Kidneys of the rats were taken out, and mRNA and protein expressions of TGF-ß, smad2, smad7 and CTGF were measured with real-time fluorescent quantitative reverse transcription-polymerase chain reaction and Western blotting respectively; fibrosis of the kidney tissue was observed with hematoxylin-eosin (HE) staining and Masson trichrome staining. RESULTS: Compared with sham-operation group, Cr and BUN in serum of UUO groups were increased, while high-dose YQHXF treatment decreased the UUO-induced increase of Cr and BUN levels. HE staining and Masson staining results showed that the renal tubular epithelial cells in untreated group got atrophied; lumens of renal tubules expanded; fibroplastic proliferation and inflammatory cell infiltration were observed in renal interstitium; the number of glomerulus decreased and collagen increased significantly compared with sham-operation group. In the high- and medium-dose YQHXF groups and fosinopril sodium group, the histopathological changes of inflammatory cell infiltration, fibroplastic proliferation, expansion of lumens of renal tubules was improved as compared with the untreated group. The mRNA and protein expressions of TGF-ß, smad2 and CTGF in untreated group were higher than those in sham-operation group (P<0.05), and the mRNA and protein expressions of smad7 in untreated group were lower than those in the sham-operation group (P<0.05). Compared with untreated group, high- and medium-dose of YQHXF significantly down-regulated the mRNA and protein expressions of TGF-ß, smad2 and CTGF (P<0.01, P<0.05), and up-regulated the mRNA and protein expressions of smad7 (P<0.01, P<0.05). CONCLUSIONS: The mRNA expression of CTGF in UUO rats may be regulated by TGF-ß/smad signaling transduction pathway. YQHXF might inhibit the expression of CTGF through down-regulation of TGF-ß and smad2 and up-regulation of smad7, thus inhibiting the progression of renal interstitial fibrosis.

[Effects of Xuesaitong Soft Capsule on hemodynamics and cardiocyte apoptosis of rats after myocardial infarction].

OBJECTIVE: To observe the effects of Xuesaitong Soft Capsule, a compound traditional Chinese medicine, on hemodynamics and cardiocyte apoptosis of rats after myocardial infarction (MI) in different time and areas, and to explore its mechanism in inhibiting cardiac ventricle reconstitution and muscle remodeling. METHODS: Except rats in sham-operated group, MI was induced by ligaturing the left coronary artery main stem of rats' hearts. Then, rats were divided into untreated group and Xuesaitong group. Ejection fraction (EF) and fractional shortening (FS), hemodynamics, ratio of heart weight to body weight (HW/BW ratio), and pathological changes of cardiac tissue were analyzed to assess cardiac function and myocardial hypertrophy status 48 hours and 5 weeks after MI. Cardiocyte apoptosis in different areas was detected by fluorescently labeled TdT-mediated dUTP-biotin nick end labeling (TUNEL) and DNA ladder method. RESULTS: Comparing with the untreated group, EF and FS in the Xuesaitong group were significantly increased, and the apoptosis index was significantly decreased (P<0.01); 48 hours after MI, left ventricular systolic pressure and maximum rate of left ventricular pressure rise were obviously increased, while left ventricular end-diastolic pressure (LVEDP) and heart weight to body weight ratio were decreased as compared with the untreated group (P<0.01); LVEDP in the Xuesaitong group was decreased, while maximum rate of left ventricular pressure rise and fall were increased as compared with the untreated group 5 weeks after MI (P<0.01). CONCLUSION: Xuesaitong can efficiently treat reconstitution and remodeling of cardiac ventricle of rats after myocardial infarction by improving the heart function and inhibiting the cardiocyte apoptosis.

A Contemporary Treatment Approach to Both Diabetes and Depression by Cordyceps sinensis, Rich in Vanadium.

Diabetes mellitus is accompanied by hormonal and neurochemical changes that can be associated with anxiety and depression. Both diabetes and depression negatively interact, in that depression leads to poor metabolic control and hyperglycemia exacerbates depression. We hypothesize one novel vanadium complex of vanadium-enriched Cordyceps sinensis (VECS), which is beneficial in preventing depression in diabetes, and influences the long-term course of glycemic control. Vanadium compounds have the ability to imitate the action of insulin, and this mimicry may have further favorable effects on the level of treatment satisfaction and mood. C. sinensis has an antidepressant-like activity, and attenuates the diabetes-induced increase in blood glucose concentrations. We suggest that the VECS may be a potential strategy for contemporary treatment of depression and diabetes through the co-effect of C. sinensis and vanadium. The validity of the hypothesis can most simply be tested by examining blood glucose levels, and swimming and climbing behavior in streptozotocin-induced hyperglycemic rats.

[A family survey of syndromes of traditional Chinese medicine in patients with beta-thalassemia].

OBJECTIVE: To explore the relationship between syndromes of traditional Chinese medicine (TCM) and genetic background in patients with beta-thalassemia. METHODS: TCM syndromes were surveyed in the selected 78 patients with beta-thalassemia intermedia including 120 parents. The gene mutations were detected separately. The frequency and score of TCM syndromes between the offspring and their parents in different family types were analyzed, and the differences were compared. RESULTS: The 73 families were divided into two family types by hereditary characteristics. Family type one meant that genotypes of one of the parents were normal, while the offspring genotypes were heterozygous and were exactly the same as another parent. In the 22 families of type one, the heterozygous offspring manifested 6 high-frequency symptoms and signs such as spontaneous perspiration, dry mouth and dry throat, pale or sallow complexion, tidal fever and night sweating, lassitude and pale fingernails. The heterozygous parents manifested 5 high-frequency symptoms and signs such as lassitude in loins and knees, dizziness, aversion to cold and cold limbs, tinnitus, dry mouth and dry throat. The normal parents manifested 3 high-frequency symptoms and signs such as lassitude in loins and knees, dizziness, and spontaneous perspiration. TCM syndrome score in the heterozygous offspring was higher than that in the heterozygous and normal parents, but there was no significant difference (P>0.05). Family type two meant that genotypes of both parents were heterozygous, while the offspring genotypes were heterogenic duplex heterozygotes. In the 51 families of type two, the offspring manifested 9 high-frequency symptoms and signs such as pale or sallow complexion, spontaneous perspiration, dry mouth and dry throat, pale fingernails, tidal fever and night sweating, lassitude, frequent attack of common cold, dysphoria with feverish sensation in chest, and yellow discoloration of the skin and sclera. The parents manifested 3 high-frequency symptoms and signs such as lassitude in loins and knees, dizziness, aversion to cold and cold limbs. TCM syndrome score in the offspring was significant higher than that in the parents (P<0.01). CONCLUSION: In the two family types, TCM syndrome in the offspring is of yin-blood deficiency, while the syndrome of the parents is of kidney deficiency. The differences of TCM syndromes between the offspring and the parents may have some relations to the type of mutant genes and genetically modified ingredients. This research provides scientific evidence to TCM syndrome differentiation treatment of thalassemia.

Observations on after-effect duration of kidney-nourishing and marrow-replenishing therapy on 58 cases of Mediterranean anemia.

OBJECTIVE: To observe the after-effect duration of kidney-nourishing and marrow-replenishing therapy on Mediterranean anemia. METHODS: To observe the kidney-nourishing and marrow-replenishing therapy on 58 cases of Mediterranean anemia and the influence of various relative factors on the after-effect duration. RESULTS: The after-effect duration on 58 cases varied from 3-6 months, about 4 months on average, and was not influenced by sex, clinical types, genetic types, types of Mediterranean anemia and other factors. CONCLUSION: Kidney-nourishing and marrow-replenishing therapy used to treat Mediterranean anemia can not only produce good therapeutic effect during treatment but also keep after effect lasting for about 4 months, indicating that the therapy used to treat Mediterranean anemia has good clinical after effect.

[Clinical observation of Yisui Shengxue Granule in treating 25 patients with hemoglobin H disease].

OBJECTIVE: To investigate the clinical efficacy and safety of Yisui Shengxue Granule (YSSXG), a compound traditional Chinese herbal medicine for reinforcing kidney and nourishing blood, in treating hemoglobin H (HbH) disease. METHODS: YSSXG was given orally to 25 patients with HbH disease in Guangxi Zhuang Autonomous Region (high incidence area for HbH disease in China) for 3 months as one therapeutic course, 3 times a day, 10 g YSSXG was given each time (dose of YSSXG for children should be reduced properly), and blood transfusion was not given to HbH patients during the course of treatment. The levels of hemoglobin (Hb), red blood cell (RBC), HbH and reticulocyte (Ret) were observed before and after YSSXG treatment, and side effects were observed during the course of treatment. Meanwhile, the genotype was examined, and the clinical efficacy of YSSXG in treating HbH patients with different genotype was evaluated. RESULTS: The levels of Hb, RBC and Ret were obviously increased after YSSXG treatment from the first month to the end of treatment (P<0.01). After YSSXG treatment, the levels of Hb, RBC, Ret in 12 HbH patients with gene deletion were elevated (P<0.05, P<0.01), and the levels of Hb and Ret in 13 HbH patients with gene non-deletion were increased obviously (P<0.05, P<0.01). The total response rate was 84% after 3-month treatment, and there was no statistical difference in clinical efficacy between gene deletion HbH patients and non-deletion HbH patients. No adverse effect was observed during the course of treatment. CONCLUSION: YSSXG is effective and safe for treatment of HbH disease. YSSXG can improve the levels of Hb, RBC and Ret in HbH patients, especially in gene deletion HbH patients.