OBJECTIVETo explore the proliferation inhibition and apoptosis effects of polysaccharides extracts from Hedyotis diffusa (PEHD) on multiple myeloma (MM) cell line RPMI 8226 cells in vitro, so as to provide experimental theory for the clinical application in the treatment of MM.

METHODSMTT assay was used to examine the effects of PEHD on cell growth. The apoptotic cells were analyzed by flow cytometry with AnnexinⅤ/PI staining. Hoechst staining was used to observe the morphological changes of RPMI 8226 cell apoptosis. The expression levels of caspase-3,-8,-9, PARP, nucleoprotein NF-κB protein and other channel protein were assayed by Western blotting method.

RESULTSThe growth of RPMI 8226 cells were suppressed after treatment with PEHD, the highest inhibition rate reached to 92.3%, the results in the doses from 1 to 4 mg/ml showed a dose-and-time-dependent manner. The proportion of apoptotic cells in 1, 2 and 3 mg/ml PEHD treatment groups for 24 h were 22.52%, 62.31% and 69.94%, respectively, and significantly higher than that of control 8.93%. After treated with PEHD, apoptotic body appeared in RPMI 8226 cells nucleus and the number of apoptotic body increased in a dose-dependent manner. With the increasing of PEHD concentration, the expression of caspase-8,-9,-3 and PARP protein increased. The expression of Mcl-1, Bcl-xl, Bid and Bim protein decreased gradually, but the expression of Bax, Bak and Bad protein increased, and the expression of p-AKT protein (60 kDa) and NF-κB obviously decreased.

CONCLUSIONPEHD could inhibited the growth of RPMI 8226 cells and displayed a dose-and-time-dependent manner, its mechanism may involve cell apoptosis induction, which was associated with the activation of caspase-8, caspase-9, and caspase-3 protein and the down-regulation of p-AKT and NF-κB protein expression.

Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Hedyotis ; chemistry ; Humans ; Multiple Myeloma ; metabolism ; pathology ; NF-kappa B ; metabolism ; Polysaccharides ; pharmacology ; Proto-Oncogene Proteins c-akt ; metabolism

AIM:To investigate whether Yiqi-Wenyang-Huoxue-Huatan formula ( YWHHF) attenuats brain injury induced by hypoxia-hypercapnia pulmonary hypertension ( HHPH) in the rats by inhibiting excessive endoplasmic re-ticulum stress response .METHODS:Healthy SPF male SD rats ( n=50 ) were randomly divided into 5 groups: control group, hypoxia-hypercapnia group, low-dose YWHHF group, middle-dose YWHHF group and high-dose YWHHF group. The rats in control group lived in normal environment , while the rats in other 4 groups were raised for 4 weeks in oxygen tank with low oxygen concentration and high CO 2 concentration .YWHHF was perfused in the rats of low-, middle-and high-dose groups at 0.15, 0.3 and 0.6 g/kg daily, respectively.The rats in hypoxia-hypercapnia group were given isomet-ric distilled water.The surgery was performed on the rats after 4 weeks, and the brain and lung tissues were quickly collect-ed to detect brain water content and observe the morphological changes after mean pulmonary artery pressure recording and heart perfusion .The caspase-3 activity and the apoptotic index of the brain cells were determined .The expression of c-Jun N-terminal kinase (JNK), caspase-12, C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) at protein and mRNA levels in brain tissues was detected by Western blot and RT-PCR.RESULTS:Compared with con-trol group, mean pulmonary artery pressure, brain water content, brain apoptotic index, caspase-3 activity, and the protein and mRNA levels of JNK, caspase-12, CHOP and GRP78 in the rest 4 groups were increased , and the brain and lung tis-sues had obvious damage under light microscope .Compared with hypoxia-hypercapnia group , mean pulmonary artery pres-sure, brain water content , brain apoptotic index , caspase-3 activity, and the protein and mRNA expression of JNK , caspase-12, CHOP and GRP78 in low-, middle-and high-dose YWHHF groups were decreased , and the pathological dam-age of the brain and lung tissues was obviously reduced under light microscope .These changes in middle-dose YWHHF group were the most significant .CONCLUSION:YWHHF effectively relieves the brain injury induced by HHPH in rats , which may be associated with inhibiting excessive endoplasmic reticulum stress response .

AIM:To investigate the relationship between transforming growth factor-β(TGF-β)/Smads signa-ling pathway and pulmonary arterial endothelial-mesenchymal transition(EndoMT)in hypoxia-hypercapnia pulmonary hy-pertension(HHPH)process and the regulatory effect of Yiqi-Wenyang-Huoxue-Huatan formula(YWHHF).METHODS:Healthy male SD rats were randomly divided into 5 groups:normal control(N)group,hypoxia-hypercapnia(HH)group, high-dose YWHHF(YH)group,middle-dose YWHHF(YM)group and low-dose YWHHF(YL)group.The rats in N group was housed in normoxic environment,and the rats in the other 4 groups were housed in hypoxia-hypercapnia environ-ment(9%~11%O2and 5%~6%CO2)for 4 weeks,8 h/d,6 d/week.The excess water vapor was absorbed by anhy-drous CaCl2,and CO2was absorbed by sodium hydroxide.The rats in YWHHF groups were put into the oxygen chamber before the same volume of YWHHF at different concentrations were given(200 g/L for YH group,100 g/L for YM group and 50 g/L for YL group).The average pulmonary artery pressure and the average carotid artery pressure were measured during the operation.After operation,the right ventricular free wall and left ventricle plus interventricular septum were col -lected for determining the right ventricular hypertrophy index.Moreover,the morphological changes of the lung tissues were observed under light microscope.The mRNA and protein levels of α-smooth muscle actin(α-SMA),CD31,TGF-β1 and Smad2/3,and the protein level of p-Smad2/3 were detected by RT-PCR and Western blot.RESULTS:Compared with N group,the pulmonary artery mean pressure,the mRNA and protein expression of α-SMA,TGF-β1 and Smad2/3,and the protein level of p-Smad2/3 were increased, the levels of CD31 were decreased(P<0.05), and the lung tissue damage was observed in the other 4 groups.Compared with HH group,the pulmonary artery mean pressure,the mRNA and protein expression of α-SMA,TGF-β1 and Smad2/3,and the protein level of p-Smad2/3 were decreased, while the mRNA and protein levels of CD31 were increased.Moreover,the lung tissue damage was reduced in YH,YM and YL groups.CON-CLUSION:TGF-β/Smads pathway may be involved in the process of EndoMT under hypoxia and hypercapnia condition, and YWHHF may reduce EndoMT by inhibiting the expression of TGF-β/Smads pathway-related molecules.

Chronic primary immune thrombocytopenia (CITP) is the most common acquired autoimmune disease that seriously threaten the physical and mental health of patients. Compared with Western medicine treatment, the intervention and treatment of Chinese medicine (CM) has shown certain therapeutic advantages. This paper reviewed the new pathogenesis progress on T cell immune abnormality in CITP, and CM studies on interferes effects of cellular immune regulation of CITP in recent years. Qi deficiency failing to control blood and internal obstruction of blood stasis are the two common types of CM syndromes in CITP patients, the corresponding treatments include invigorating Pi (Spleen), supplementing qi, activating blood, as well as tonifying qi and activating yang, regulating Gan (Liver) to invigorate Pi. The authors also mentioned the problems in the research field of CM for CTIP treatment, and put forward new ideas for the research in the future.

OBJECTIVETo investigate the potential effect of pure total flavonoids from Citrus paradisi Macfad peel (PTFC) on the proliferation of human myeloid leukemia cells Kasumi-1, HL-60 and K562, and the underlying mechanisms.

METHODSPTFC was extracted from Citrus paradisi Macfad peel and was identified by high performance liquid chromatography. The effect of PTFC on the proliferation and apoptosis of leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescent microscopy and flow cytometry, respectively. The effect of PTFC on the expression levels of apoptosis-related regulators was determined by Western blot assay.

RESULTSTreatment with PTFC inhibited leukemia cell proliferation in a dose- and time-dependent manner and triggered Kasumi-1 cell apoptosis. Treatment with PTFC significantly increased the levels of activated poly adenosine diphosphate-ribosepolymerase and caspase-3/-9, but reduced the levels of Mcl-1 expression in Kasumi-1 cells. However, PTFC did not obviously induce HL-60 cell apoptosis.

CONCLUSIONPTFC inhibited leukemia cell proliferation and induced their apoptosis by modulating apoptosisrelated regulator expression in leukemia cells in vitro.

Graft-versus-host disease (GVHD) is the most common complication after allogeneic hematopoietic stem cell transplantation, and also an important factor affecting the survival and quality of life in patients after transplantation. Currently, immunosuppressive therapy is commonly used for GVHD, but the curative effect is not ideal. How to effectively prevent and treat GVHD is one of the difficulties to be solved urgently in the field of transplantation. In this paper, we summarize the latest progress in pathogenesis, prevention and treatment of GVHD with Chinese medicine (CM). We hope it will provide ideas and methods for exploring the mechanism and establishing a new comprehensive therapy for GVHD with CM.
Allografts ; Graft vs Host Disease ; drug therapy ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Medicine, Chinese Traditional ; Quality of Life

OBJECTIVE: To investigate the potential efficacy of panaxadiol saponins component (PDS-C) in the treatment of aplastic anemia (AA) model mice. METHODS: Totally 70 mice were divided into 7 groups as follows: normal, model, low-, medium-, high-dose PDS-C (20, 40, 80 mg/kg, namely L-, M-, H-PDS-C), cyclosporine (40 mg/kg), and andriol (25 mg/kg) groups, respectively. An immune-mediated AA mouse model was established in BALB/c mice by exposing to 5.0 Gy total body irradiation at 1.0 Gy/min, and injecting with lymphocytes from DBA mice. On day 4 after establishment of AA model, all drugs were intragastrically administered daily for 15 days, respectively, while the mice in the normal and model groups were administered with saline solution. After treatment, the peripheral blood counts, bone marrow pathological examination, colony forming assay of bone marrow culture, T lymphocyte subpopulation analysis, as well as T-bet, GATA-3 and FoxP3 proteins were detected by flow cytometry and Western blot. RESULTS: The peripheral blood of white blood cell (WBC), platelet, neutrophil counts and hemoglobin (Hb) concentration were significantly decreased in the model group compared with the normal group (all P<0.01). In response to 3 dose PDS-C treatment, the WBC, platelet, neutrophil counts were significantly increased at a dose-dependent manner compared with the model group (all P<0.01). The myelosuppression status of AA was significantly reduced in M-, H-PDS-C groups, and hematopoietic cell quantity of bone marrow was more abundant than the model group. The colony numbers of myeloid, erythroid and megakaryocytic progenitor cells in the model group were less than those of the normal mice in bone marrow culture, while, PDS-C therapy enhanced proliferation of hematopoietic progenitor cells by significantly increasing colony numbers (all P<0.01). Furthermore, PDS-C therapy increased peripheral blood CD3 and CD3CD4 cells and reduced CD3CD8 cells (P<0.05 or P<0.01). Meanwhile, PDS-C treatment at medium- and high doses groups also increased CD4CD25FoxP3 cells, downregulated T-bet protein expression, and upregulated GATA-3 and FoxP3 protein expressions in spleen cells (P<0.05). CONCLUSION PDS-C possesses dual activities, promoting proliferation hematopoietic progenitor cells and modulating T lymphocyte immune functions in the treatment of AA model mice.

OBJECTIVE: To explore the clinical effect and adverse reactions of Strychnos nux-vomica in bortezomib-induced peripheral neuropathy (BIPN) of patients with multiple myeloma (MM). METHODS: A total of 19 MM patients with BIPN were enrolled and Nux Vomica Capsule (NVC, 0.4 g, thrice daily) were orally administrated for 30 days. Comparative analysis on parameters between pre- and post-therapy, including peripheral neuropathy (PN) grade, neurotoxicity score, Chinese medicine (CM) syndrome score, total neuropathy score (TNS), coagulation function, and serum nerve growth factor (NGF) levels were conducted. The adverse events were monitored. RESULTS: In BIPN of MM patients who received NVC, PN grade was lowered, neurotoxicity score was obviously decreased (P⩽0.01), and both CM syndrome score and TNS were remarkably decreased (P<0.01). After the therapy, activated partial thromboplastin time was prolonged (P<0.01) and fibrinogen was declined (P<0.05), showing improvement in the hypercoagulable state of patients. No significant difference of NGF recovery degrees was detected between pre- and post-therapy (P>0.05). No evident adverse reactions were observed during the course of treatment. CONCLUSION Strychnos nux-vomica L. has significantly effect with a good safety in treatment of BIPN in MM patients.

OBJECTIVETo investigate the current status of smoking and passive smoking among Chinese females to provide evidence for related strategy development.

METHODSData from 32 720 women aged 45-65 years old who participated in the 2008 to 2010 Chinese Multi-center Women Breast Cancer Screening Project, were used to analyze the prevalence rates of smoking/heavy smoking, daily smoking, smoking cessation, successful smoking cessation, passive smoking, etc.

RESULTSA total of 913 females, accounted for 2.8% of all the women in the study, had reported the history of smoking. There were significant differences seen regarding the prevalence rates of smoking in different regions (Beijing, 2.8%; Tianjin, 5.9%; Nanchang, 1.7%; Feicheng, 0.9%; Shenyang, 1.8%). The prevalence rates of current smoking, daily smoking, and heavy smoking were 1.8%, 1.0% and 0.2%, respectively. The prevalence rates of smoking and current smoking increased with age but not the prevalence rates of daily smoking and heavy smoking. Among the smokers, the median initiation age of smoking, the median daily cigarette per day, and median year of smoking were 30 years old, 10 cigarette, and 16 years, respectively. And the prevalence rates of smoking cessation and successful smoking cessation were 19.1% and 8.2%. The prevalence rate of passive smoking was 45.7% (12 730/27 874). After combing the number of smokers and the number of passive smokers, the total exposure rate to tobacco was 41.8% (13 670/32 720).

CONCLUSIONThere was a relatively low level of smoking among Chinese females, so as the rate of smoking cessation. However, passive smoking presented a relatively high level among Chinese females.

Aged ; China ; epidemiology ; Female ; Humans ; Middle Aged ; Prevalence ; Smoking ; epidemiology ; Tobacco Smoke Pollution ; statistics & numerical data