Multi-View Random-Walk Graph Regularization Low-Rank Representation for Cancer Clustering and Differentially Expressed Gene Selection.

Cancer genome data generally consists of multiple views from different sources. These views provide different levels of information about gene activity, as well as more comprehensive cancer information. The low-rank representation (LRR) method, as a powerful subspace clustering method, has been extended and applied in cancer data research. Although the multi-view learning methods based on low rank representation have achieved good results in cancer multi-omics analysis because they fully consider the consistency and complementarity between views, these methods have some shortcomings in mining the potential local geometry of data. In view of this, this paper proposes a new method named Multi-view Random-walk Graph regularization Low-Rank Representation (MRGLRR) to comprehensively analyze multi-view genomics data. This method uses multi-view model to find the common centroid of view. By constructing a joint affinity matrix to learn the low-rank subspace representation of multiple sets of data, the hidden information of each view is fully obtained. In addition, this method introduces random walk graph regularization constraint to obtain more accurate similarity between samples. Different from the traditional graph regularization constraint, after constructing the KNN graph, we use the random walk algorithm to obtain the weight matrix. The random walk algorithm can retain more local geometric information and better learn the topological structure of the data. What's more, a feature gene selection strategy suitable for multi-view model is proposed to find more differentially expressed genes with research value. Experimental results show that our method is better than other representative methods in terms of clustering and feature gene selection for cancer multi-omics data.

Shenmai Injection Improves Energy Metabolism in Patients With Heart Failure: A Randomized Controlled Trial.

BACKGROUND: In recent years, the application of Shenmai (SM) injection, a traditional Chinese medicine (TCM), to treat heart failure (HF) has been gradually accepted in China. However, whether SM improves energy metabolism in patients with HF has not been determined due to the lack of high-quality studies. We aimed to investigate the influence of SM on energy metabolism in patients with HF. METHODS: This single-blind, controlled study randomly assigned 120 eligible patients equally into three groups receiving SM, trimetazidine (TMZ), or control in addition to standard medical treatment for HF for 7 days. The primary endpoints were changes in free fatty acids (FFAs), glucose, lactic acid (LA), pyroracemic acid (pyruvate, PA) and branched chain amino acids (BCAAs) in serum. The secondary outcomes included the New York Heart Association (NYHA) functional classification, TCM syndrome score (TCM-s), left ventricular injection fraction (LVEF), left ventricular internal diastolic diameter (LVIDd), left ventricular internal dimension systole (LVIDs), and B-type natriuretic peptide (BNP). RESULTS: After treatment for 1 week, the NYHA functional classification, TCM-s, and BNP level gradually decreased in the patients in all three groups, but these metrics were significantly increased in the patients in the SM group compared with those in the patients in the TMZ and control groups (P < 0.05). Moreover, energy metabolism was improved in the NYHA III-IV patients in the SM group compared with those in the patients in the TMZ and control groups as evidenced by changes in the serum levels of FFA, LA, PA, and BCAA. CONCLUSIONS: Integrative treatment with SM in addition to standard medical treatment for HF was associated with improved cardiac function compared to standard medical treatment alone. The benefit of SM in HF may be related to an improvement in energy metabolism, which seems to be more remarkable than that following treatment with TMZ.

[Genome survey analysis and SSR loci mining of Bupleurum falcatum].

Buplewrum falcatum is a traditional Chinese medicine,which is mainly used for the treatment of cold and liver protection. B. falcatum is dominantly cultivated in Japan as well as planted in China,Korea and other countries and regions. In order to determine the appropriate sequencing strategy,the genome survey before large-scale genome sequencing is needed. This survey can provide information about the size and complexity of the whole genome of the target species. In the present study,the next generation sequencing technology( Illumina Hiseq 2000) was used to analyze the genome size and complexity of B. falcatum. In addition,SSR loci were analyzed from the sequenced data. Primer 3 was used to design specific primers and 33 pairs of primers were randomly selected for PCR with template DNA of B. falcatum,and the PCR system and optimal annealing temperature were screened. A total of 288. 64 G genome sequence data was obtained,and the estimated genome size of B. falcatum was 2 119. 58 Mb. The measured genome data depth was138×; the rate of heterozygosity was 1. 84%; and the ratio of repeat sequence was 83. 89%. It is speculated that the genome of B. falcatum is complex. The preliminary assembly was performed with K-mer = 41,and the contig N50 was 224 bp,the total length 896. 97 Mb,the scaffold N50 313 bp,and the total length was 922. 67 Mb. A total of 91 377 SSR sequences were detected in the sequenced genome data which were distributed in 70 809 unigenes.The main type is dinucleotide repeats,with 49 680 sequences,accounting for70. 16%. Among the 33 pairs of primers randomly synthesized according to the obtained SSR sequences,21 pairs were successfully amplifying the target sequences. The results will be helpful for later large scale genome sequencing and SSR molecular markers development for germplasm identification and trait mapping.

Panax Notoginseng Saponins Attenuate Myocardial Ischemia-Reperfusion Injury Through the HIF-1α/BNIP3 Pathway of Autophagy.

BACKGROUND AND OBJECTIVE: Panax Notoginseng Saponins (PNS) is a formula of Chinese medicine commonly used for treating ischemia myocardial in China. However, its mechanism of action is yet unclear. This study investigated the effect and the mechanism of PNS on myocardial ischemia-reperfusion injury (MIRI) through the hypoxia-inducible factor 1α (HIF-1α)/bcl-2/adenovirus E1B19kDa-interacting protein3 (BNIP3) pathway of autophagy. METHODS: We constructed a rat model of myocardial injury and compared among 4 groups (n = 10, each): the sham-operated group (Sham), the ischemia-reperfusion group (IR), the PNS low-dose group, and the PNS high-dose group were pretreated with PNS (30 and 60 mg/kg, respectively). Serum creatine kinase, malonaldehyde (MDA), lactate dehydrogenase, myocardial tissue superoxide dismutase, and reactive oxygen species were detected in rats with myocardial ischemia-reperfusion after the intervention of PNS. The rat myocardial tissue was examined using hematoxylin and eosin (H&E) staining, and the mitochondria of myocardial cells were observed using transmission electron microscopy. The expressions of microtubule-associated protein light chain 3 (LC3), HIF-1α, BNIP3, Beclin-1, and autophagy-related gene-5 (Atg5) in rat myocardial tissue were detected using Western blotting. RESULTS: The results showed that PNS was significantly protected against MIRI, as evidenced by the decreasing in the concentration of serum CK, MDA, lactate dehydrogenase, and myocardial tissue superoxide dismutase, reactive oxygen species, the attenuation of myocardial tissue histopathological changes and the mitochondrial damages of myocardial cells, and the increase of mitochondria autophagosome in myocardial cells. In addition, PNS significantly increased the expression of LC3 and the ratio of LC3II/LC3I in rat myocardial tissue. Moreover, PNS significantly increased the expression of HIF-1α, BNIP3, Atg5, and Beclin-1 in rat myocardial tissue. CONCLUSIONS: The protective effect of PNS on MIRI was mainly due to its ability to enhance the mitochondrial autophagy of myocardial tissue through the HIF-1α/BNIP3 pathway.

Coriolus versicolor aqueous extract ameliorates insulin resistance with PI3K/Akt and p38 MAPK signaling pathways involved in diabetic skeletal muscle.

Patients with type 2 diabetes mellitus (T2DM) are usually with poor immunity and easier to suffer from cancer and microbial infections. Herein, we report an efficient anti-diabetic medicinal mushroom, Coriolus versicolor (CV). This study aimed to investigate the anti-diabetic and anti-insulin-resistance effects of CV aqueous extract in myoblasts (L6 cells) and skeletal muscle of T2DM rat. Our results showed that CV extract treatment significantly reduced blood glucose levels of T2DM rats, whereas CV extract increased glucose consumption in insulin resistant L6 cells. Besides, the translocation and expression of glucose transporter 4 were enhanced by CV extract, which indicated that CV extract was effective in diabetic skeletal muscle. Moreover, CV extract treatments resulted in remarkable anti-insulin-resistance effects, which was reflected by the change of gene and protein expression levels in PI3K/Akt and p38 MAPK pathways. PI3K inhibitor, LY29004, and p38 MAPK inhibitor, SB203580 confirmed it further. In conclusion, our results demonstrated that the CV extract exhibited anti-diabetic and anti-insulin-resistance effects in diabetic skeletal muscle, and the effects were mediated by PI3K/Akt and p38 MAPK pathways. These findings are remarkable when considering the use of commercially available CV by diabetic patients who also suffer from cancer or microbial infections.

Determinants of Quality of Life for Breast Cancer Patients in Shanghai, China.

PURPOSE: To evaluate the association of social support status, health insurance and clinical factors with the quality of life of Chinese women with breast cancer. METHODS: Information on demographics, clinical characteristics, and social support status was collected from 1,160 women with newly diagnosed breast cancer in Shanghai, China. The Perceived Social Support Scale was used to assess different sources of social support for breast cancer patients. The quality of life was evaluated using the Functional Assessment of Cancer Therapy-Breast Cancer that consisted of five domains: breast cancer-specific, emotional, functional, physical, and social & family well-being. Multivariate linear regression models were used to evaluate the associations of demographic variables, clinical characteristics, and social support status with the quality of life measures. RESULTS: Adequate social support from family members, friends and neighbors, and higher scores of Perceived Social Support Scale were associated with significantly improved quality of life of breast cancer patients. Higher household income, medical insurance plans with low copayment, and treatment with traditional Chinese medicine for breast cancer all were associated with higher (better) scores of quality of life measures whereas patients receiving chemotherapy had significantly lower scores of quality of life. CONCLUSION: Social support and financial aids may significantly improve the quality of life of breast cancer survivors.

Potent therapeutic effects of shouwu jiangqi decoction on polycystic ovary syndrome with insulin resistance in rats.

OBJECTIVE: To investigate the effect of Shouwu Jiangqi Decoction (SJD) on polycystic ovary syndrome (PCOS) with insulin resistance (IR) in rats and to explore the underlining molecular mechanisms. METHODS: A total of 51 female Sprague-Dawley rats were randomly divided into 6 groups: control group (n=7), model group (n=8), SJD high-dose group (n=9), SJD medium-dose group (n=9), SJD low-dose group (n=9) and DMBG group (n=9). Radioimmunoassay was used to measure serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone concentrations and qRT-PCR and western blot were used to examine the expression levels of mRNA and protein respectively of insulin receptor substrate 1 (IRS-1) and phosphatidylinositide 3-kinases (PI3K) p85α in different groups. RESULTS: FSH level significantly decreased in the model group compared with the normal control (P<0.01), and high-dose SJD and DMBG can significantly increase FSH level (P<0.01). LH level showed a mild increase without statistic significance in the model group compared with the control and different dosages of SJD had no significance effect on LH level, while DMBG can significantly decrease LH level (P<0.01). Testosterone level significantly increased in the model group compared with the control group (P<0.01), and high-dose SJD and DMBG can significantly decrease testosterone level (P<0.01). The expression of IRS-1 as well as PI3Kp85α were significantly decreased in the model group compared with the normal control group at both mRNA (P<0.001) and protein (P<0.01) level, and both high-dose SJD and DMBG can enhance IRS-1 and PI3K expression (P<0.05). CONCLUSIONS: SJD has potent therapeutic effects on PCOS with IR in rats. The therapeutic effects of SJD on IR and ovulatory dysfunction are probably achieved through correcting the defective insulin signaling transduction.

[Study on Chemical Constituents of Strychnos nux-vomica].

Objective: To isolate and identify the chemical constituents from the seeds of Strychnos nux-vomica. Methods: Chromatographic separation techniques such as silica gel chromatography,ODS chromatography and Sephadex LH-20 chromatography were used for the isolation and purification. The structures of the chemical constituents were identified on the basis of mass spectrometry,NMR spectroscopy and so on. Results: 16 compounds were isolated and their structures were identified as: α-amyrin( 1), vomicine( 2), stearic acid( 3), ß-sitosterol( 4),vanillin( 5), ethyl gallate( 6),methyl gallate( 7),novacine( 8),strychnine( 9), daucosterol( 10),brucine chloromethochloride( 11),loganic acid( 12),strychnine chloromethochloride( 13),brucine( 14),geniposide( 15) and loganin( 16). Conclusion: Compounds 3,6,7 and 15 are isolated from this genus for the first time.

[Anesthetic effect of preemptive analgesia of frequency acupoint electrical stimulation on painless-induced abortion].

OBJECTIVE: To explore the anesthetic effect of preemptive analgesia of frequency acupoint electrical stimulation on painless-induced abortion as well as its effect on anesthetics dosage. METHODS: Ninety cases of early pregnancy who selected painless-induced abortion were randomly divided into two groups, 45 cases in each group. Frequency acupoint electrical stimulation at Ciliao (BL 32) and Shenshu (BL 23), disperse-densewave, 2 Hz/100 Hz in frequency for 15 to 20 min, was applied in the group A, which was followed by intravenous anesthesia of propofol. The intravenous anesthesia of propofol was applied in the group B. The blood pressure (BP), heart rate (HR) and SpO2 before, during and after surgery, anesthetic effect and dosage, waking time and adverse events were observed in the two groups. RESULTS: The BP and HR during and after the surgery in the group A were not statistically different from those before the surgery (all P > 0.05). The BP was reduced and HR was slowed down during the surgery in the group B, which was significantly different from those before the surgery as well as those in the group A (all P < 0.05). The dosage of propofol was (114. 3-+6. 1) mg in the group A. obviously less than (193.2 +/- 8.9) mg in the group B (P < 0.05). The waking time was (5.6 +/- 1.2) min in the group A, obviously less than (10.1 +/- 3.9) min in the group B (P < 0.05). As for anesthetic effect, the incidence of Grade I in the group A was more than the group B (P < 0.05). The adverse events, including nausea, vomiting and contractions pain in the group A were evidently less than those in the group B (all P < 0.05). CONCLUSION: The preemptive analgesia of frequency acupoint electrical stimulation could significantly improve anesthetic effect of painless-induced abortion, reduce dosage of anesthetics, shorten waking time of surgery and guarantee the safety of surgery.

12-Deoxyphorbol 13-palmitate inhibit VEGF-induced angiogenesis via suppression of VEGFR-2-signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: 12-Deoxyphorbol 13-palmitate (G) is one toxic compound isolated from Euphorbia fischeriana, an Asian spice used for cancer treatment as a folk remedy. However, whether 12-deoxyphorbol 13-palmitate affects angiogenesis remains unclear. AIM OF THE STUDY: To explore the in vitro and in vivo antiangiogenic effects of 12-deoxyphorbol 13-palmitate and its underlying mechanisms. MATERIALS AND METHODS: We explored antigenic functions in human umbilical vein endothelial cells (HUVEC) by 12-deoxyphorbol 13-palmitate, including proliferation, migration and metastasis through matrigel plug assay, chorioallantoic membrane assay, in vitro migration assay, tube formation assay, motility assay. Antibody chip was applied to screen differentially expressed proteins modulated by 12-deoxyphorbol 13-palmitate, and was further confirmed by RT-PCR and western blot analysis. Tumor xenograft mice were applied to investigate whether 12-deoxyphorbol 13-palmitate could inhibit microvessel density in vivo. RESULTS: 12-Deoxyphorbol 13-palmitate inhibited vascular endothelial growth factor (VEGF)-induced angiogenic processes in vitro, such as proliferation, in vitro migration, and tube formation of HUVEC. In chorioallantoic membrane assay, 12-deoxyphorbol 13-palmitate significantly inhibited neovessel formation. Antibody chip technology demonstrated decreased expression of TIMP-1, TIMP-2, VEGF, basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMP)-2, VEGFR-2 and VEGFR-3 proteins in HUVEC after 24h. In addition, 12-deoyphorbol 13-palmitate inhibited the in vivo growth of MCF-7 cells in grafted mouse model. Immunohistochemistry staining showed decreased microvessel density (CD31) and attenuated VEGFR-2 signaling pathways by 12-deoxyphorbol 13-palmitate. CONCLUSION: 12-Deoxyphorbol 13-palmitate may be utilized to target active angiogenesis through VEGF/VEGFR2 signal pathway for cancer.

Bortezomib regulates the chemotactic characteristics of T cells through downregulation of CXCR3/CXCL9 expression and induction of apoptosis.

The chemotactic movement of T lymphocytes mediated by chemokines and their receptors plays an important role in the pathogenesis of graft-versus-host disease (GVHD) post-allogeneic hematopoietic stem cell transplantation (allo-HSCT). CCR7 and CXCR3 are two receptors associated with the development of GVHD. Bortezomib, a proteasome inhibitor, was recently found to prevent GVHD in a mouse model and to decrease the production of Th1 cytokines. Here, we report that bortezomib differentially regulates the expression of CXCR3 and CCR7 on T cells; it significantly decreases CXCR3 expression on T cells as well as its CD4(+)/CD8(+) subsets in a dose-dependent manner, while it does not significantly affect CCR7 expression on T cells and subsets. Moreover, the secretion of CXCL9 by activated T cells is also increasingly downregulated with increasing concentrations of bortezomib. Meanwhile, bortezomib inhibits T-cell chemotactic movements toward CXCL9 in a dose-dependent manner, but has no effect on CCL19-induced T-cell chemotaxis. Additionally, it was found that bortezomib treatment also prompts T-lymphocyte apoptosis through activation of caspase-3 and its downstream PARP cleavage in a dose- and time-dependent manner. These results suggest that bortezomib may act as a suppressor of GVHD by downregulating T-cell chemotatic movement toward GVHD target organs, as well as by inducing apoptosis.

Effects of Er'zhi Tiangui Granule () on sequential expressions of integrin ß 3 and its ligand osteopontin in mouse endometrium during controlled ovarian hyperstimulation.

OBJECTIVE: To investigate the effects of Er'zhi Tiangui Granule (, ETG) on sequential expressions of integrinß3 and its ligand osteopontin in the mouse endometrium during controlled ovarian hyperstimulation (COH) and implantation period. METHODS: Seventy-five Mature female Kunming mice were randomly divided into 3 groups, a normal control group, a model group, and a treatment group administrated with ETG for 10 days, 25 in each group. After mated with male mice, every 5 mice were sacrified in each group at the 0, 2nd, 4th, 6th, and 8th days to take their endometrium. In-situ hybridization was used to detect the expressions of integrinß3 and osteopontin in the endometrium. RESULTS: mRNA expressions of integrinß3 and osteopontin in the endometrium during implantation period showed similar time sequence rules in the treatment group to those in the normal control group; the peak values of them were a little lower in the treatment group than the normal control without significant differences. In the model group, integrinß3 mRNA expression was higher at the 2nd day, obviously lower at the 4th and 6th days, and insignificantly lower at the 8th day; and osteopontin expression was remarkably lower at the 4th, 6th, and 8th days, compared with the normal control and the treatment groups (P<0.05, P<0.01). CONCLUSIONS: COH might influence the sequential expressions of integrinß3 and its ligand osteopontin, bring forward the integrinß3 expression peak, impact on the cooperation of integrinß3 and osteopontin, so as to damage the endometrial receptivity. ETG could regulate the sequential expressions of integrinß3 and its ligand osteopontin to improve the mouse endometrial receptivity during COH.

Berberine alleviates ischemic arrhythmias via recovering depressed I(to) and I(Ca) currents in diabetic rats.

The present study was designed to elucidate the potential mechanism underlying that berberine suppressed ischemic arrhythmias in a rat model of diabetes mellitus (DM). Streptozotocin (STZ)-induced diabetic rats were subjected to ischemia by the occlusion of left anterior descending (LAD) coronary artery. Berberine was orally administered for 7 days before ischemic injury in diabetic rats. Whole-cell patch-clamp was performed to measure the transient outward K⁺ current (I(to)) and L-type Ca²âº current (I(Ca)). Results showed that oral administration of berberine (100 mg/kg) attenuated ischemia-induced arrhythmias in diabetic rats. Berberine significantly shortened the prolonged QTc interval from 214 ± 6ms to 189 ± 5ms in ischemic diabetic rats, and also restored the diminished I(to) and I(Ca) current densities in the same animal model rats. In conclusion, the ability of berberine to protect diabetic rats against cardiac arrhythmias makes it possible to be a prospective therapeutic agent in clinical management of cardiac disease secondary to diabetes.

Berberine elicits anti-arrhythmic effects via IK1/Kir2.1 in the rat type 2 diabetic myocardial infarction model.

The purpose of this study was to explore the anti-arrhythmic mechanisms of berberine in diabetic rats with myocardial infarction. Sixty rats were divided into four groups: (1) normal control; (2) myocardial infarction group (MI); (3) Type 2 diabetes with myocardial infarction group (T2DM+MI); and (4) Type 2 diabetic with myocardial infarction berberine-treated group (BBR). Berberine (60 mg/kg/day) was administered after coronary artery ligation in the T2DM+MI group for 14 days. Currents were measured using whole-cell patch-clamp techniques. Western blot was performed for quantification of target proteins. The study showed that arrhythmias induced by myocardial infarction were aggravated in diabetic rats. Arrhythmia scores in the MI group were significantly higher than in the control group. Interestingly, the administration of berberine at a dose of 60 mg/kg/d recovered arrhythmia scores (P > 0.05). RMP (Resting membrane potential) which could be recovered by berberine (P < 0.05), was significantly reduced in both the infarction groups. I(K1) current and current density markedly decreased in the MI and T2DM+MI groups (P < 0.05) and could be reversed by berberine (P < 0.05). The relative expression of Kir2.1 in rats in the MI and T2DM+MI group were both significantly decreased (P < 0.05); berberine recovered depressed Kir2.1 to nearly normal levels. The results suggest that the effects of berberine on I(K1)/Kir2.1 may be an important mechanism for producing anti-arrhythmic effects.

Protective effect of the daming capsule on impaired baroreflexes in STZ-induced diabetic rats with hyperlipoidemia.

BACKGROUND: The Daming capsule (DMC) is a traditional Chinese medicine used to treat hyperlipoidemia. Both clinic trials and studies on animal models have demonstrated that DMC is beneficial against diabetic symptoms. Impairment of the baroreflex can cause life-threatening arrhythmias and sudden cardiac death in patients with diabetes mellitus (DM). This study was designed to elucidate the effects of DMC on baroreflexes in streptozocin (STZ)-induced diabetic rats with hyperlipoidemia. METHODS: Wistar rats were randomly divided into three groups: untreated controls, rats pretreated STZ and high lipids (a diabetes model or DM rats), and DM rats treated with DMC. The baroreflex sensitivity was examined during intravenous injection of phenylephrine (PE) or sodium nitroprusside (SNP) and quantified by the change in heart rate over the change in mean arterial blood pressure (ΔHR/ΔMABP). Morphological remodeling of baroreceptors was analyzed by transmission electron microscopy (TEM). The mRNA levels and expression of GluR2 and a GABAA receptor subunit were measured by quantitative RT-PCR and Western blotting. RESULTS: Compared to untreated DM rats, DMC significantly elevated the ratio of ΔHR/ΔMABP by enhancing the compensatory reduction in HR (-ΔHR) in response to PE-induced hypertension (+ΔMABP) (P < 0.05). In the presence of SNP, DMC increased the ΔMABP (P < 0.05). In addition, DMC markedly shortened the duration of blood pressure changes elicited by PE or SNP in DM rats compared to the untreated DM group (P < 0.05). Electron microscopy revealed disrupted myelin sheaths, swollen ER, and lysed mitochondria in the nucleus ambiguous (NAm) DM rats. These signs of neuropathology were largely prevented by treatment with DMC for 30 days. Treatment with DMC elevated both mRNA and protein level of GluR2 in the NAm of DM rats, but had no effect on GABAA receptor expression. CONCLUSION: The Daming capsule partially reversed the parasympathetic baroreflex impairment observed in STZ-induced diabetic rats with hyperlipoidemia. Treatment with DMC also prevented the degeneration of neurons and myelinated axons in the brain stem NAm and reversed the down-regulation of GluR2 mRNA. Rescue of NAm function may contribute to the medicinal properties of DMC in diabetic rats.

[Study on climate regionalization of Artemisia annuua in Guangxi].

OBJECTIVE: To analyze the major effective factors under the climatic conditions of Guangxi which influence artemisinin content, in order to determine the best planting region. METHOD: The correlation, the gradually regression analysis with the statistical analysis system, the geography space analysis and the regionalization with GIS were used for the study. RESULT AND CONCLUSION: The temperature and the sunshine-hour were the major effective factors to artemisinin content, followed by the rainfall amount, the humidity showed less influence, and wind speed had no effect; And the climatic factors of seedling stage and the flowering season were the most influences to the artemisinin content. The artemisinin content was higher during the flowering season, in the region of temperature relatively lower and the rainfall amount smaller. The knoll and the mountainous region in northeast and southwest of Guangxi is the best suitable region for the Artemisia annua planting. The plain area in the southeast and middle of Guangxi is the not suitable region; Other areas are suitable regions for the A. annua planting.

[Observation on the therapeutic effect of acupoint application on constipation].

OBJECTIVE: To test the therapeutic effect, safety of acupoint application for treatment of constipation. METHODS: Forty-two cases were randomly divided into a treatment group of 22 cases and a control group of 20 cases. The treatment group were treated with acupoint application, with the cake made by Sanleng (Rhizoma Spargani), Ezhu (Rhizoma Zedoariae), Dahuang (Radix et Rhizoma Rhei) and Bingpian (Borneolum), which was applied at Tianshu (ST 25), Qihai (CV 6), Guanyuan (CV 4); the control group were treated with oral administration of Congrong Tongbian Oral Liquid. RESULTS: The total effective rate was 81.8% in the treatment group and 50.0% in the control group, the treatment group being better than the control group (P < 0.05); the first defecation time was (5.1 +/- 2.8) h in the treatment group and (10.1 +/- 7.3) h in the control group, with a significant difference between the two groups (P < 0.05). CONCLUSION: TCM acupoint application therapy has a definite therapeutic effect on constipation.

Inhibition of expression of vascular endothelial growth factor and its receptors in pulmonary adenocarcinoma cell by TNP-470 in combination with gemcitabine.

Angiogenesis is required for solid tumor growth and facilitates tumor progression and metastasis. The inhibition effects of O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), an angiogenesis inhibitor, and gemcitabine, a chemotherapeutic agent, on expression of growth factors were investigated using human pulmonary adenocarcinoma cell line, A549. The A549 cells were divided into four groups: control group, 10(-6) mg/ml gemcitabine treated group, 10(-4) mg/ml TNP-470 treated group and gemcitabine+TNP-470 treated group. The mRNA and protein expression of vascular endothelial growth factor (VEGF) and its receptors, FMS-like tyrosine kinase-1 (FLT-1) and kinase insert domain-containing receptor (KDR), in different groups were measured. The growth of A549 cell cultured with gemcitabine or TNP-470 was inhibited in an almost dose-dependent manner. Although gemcitabine (10(-6) mg/ml) alone and TNP-470 (10(-4) mg/ml) alone had no effect on the mRNA and protein expression of VEGF and its receptors (FLT-1, KDR) in A549 cells compared to the control (P>0.05), 10(-6) mg/ml gemcitabine in combination with 10(-4) mg/ml TNP-470 had significant effect (P<0.01). Moreover, combination of the two drugs significantly inhibited the mRNA expression of VEGF, FLT-1 and KDR compared to either drug alone (P<0.05). This study suggests that combined treatment with TNP-470 plus gemcitabine may augment the antiangiogenic and antineoplastic effects in lung cancer cells in vitro.

Comparison of low and high doses of carvedilol on restoration of cardiac function and calcium-handling proteins in rat failing heart.

1. The beta-adrenoceptor antagonist carvedilol reverses cardiac dysfunction in the failing heart. A recent study showed that beta-adrenoceptor antagonists indirectly normalize Ca(2+)-regulatory proteins. The relationship between these two phenomena and the suitable dosage of carvedilol remains unclear. 2. We investigated the change in left ventricular (LV) remodelling and function in a rat model of heart failure due to myocardial infarction (MI) with or without carvedilol (30 or 2 mg/kg per day) treatment for 6 weeks. The expression of mRNA and proteins of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLB) in cardiomyocytes was also measured. 3. There was significant LV remodelling and cardiac contractile dysfunction in MI rats. The expression of SERCA mRNA and protein were downregulated (P < 0.01), but the expression of PLB mRNA and protein were upregulated (P < 0.01) in MI rats compared with sham-operated rats. After treatment with carvedilol, LV remodelling and cardiac contractile dysfunction were clearly improved. Low-dose carvedilol was better at improving some parameters of LV remodelling and function than the high dose. Carvedilol partially restored the low expression of SERCA (P < 0.05), but had no effect on PLB expression (P > 0.05). Moreover, low-dose carvedilol induced a more significant improvement in SERCA expression than did the high dose (P < 0.05). 4. The results of the present study suggest that carvedilol is effective in improving LV remodelling and cardiac contractile dysfunction after MI. This may be related to the normalization of SERCA expression.