OBJECTIVE: To explore the effect of bone morphogenetic protein 4(BMP4) on the cell cycle and apoptosis of hemaropoictic stem and progenitor cells (HSPC) in conditions of 5-fluorouracil (5-FU)-inducing bone marrow suppression and stress hemogenesis, and its possible mechanism. METHODS: The C57BL transgenic mice with BMP4 overexpression were established and were enrolled in transgenic group (BMP4 group), at the same time the wild type mice matching in age, sex and body weight were selected and were enrolled in control group (WT group). The bone marrow suppression was induced by injection with 5-FU in dose of 150 mg/kg, then the nucleated cells were isolated from bone marrow. After the HSPCs were markered with C-kit/sca-1 fluorescent antibodies, the changes of cell cycle and apoptosis of HSPC were detected by Aunexin V/PI and Ki67/DAPI double staining; the cell cycle-essociated hemotopoietic regulatory factors were detected by RT-qPCR. RESULTS: Under physiologic status, there were no significant differences in cell cycle and apoptotic rate of HSPC between WT group and BMP-4 group. After the bone marrow was suppressed, the ratio of HSPC at G0 phase in BMP4 group significantly decreased(P＜0.05); the apoptosis rate of HSPC significantly increased(P＜0.05); the mRNA expression levels of hypoxia-inducing factor Hif-1α and chemotactic factor CXCL12 in stroma of BMP4 group were down-regulated significanfly(P＜0.05). CONCLUSION Under non-physiologic conditions such as stress hemogenesis or bone marrow suppression, the up-regulation of BMP4 can promote HSPC into cell cycle and apoptosis of HSPC, moreover, the BMP4 may play a regulatory role for cell cycle of HSPC through direct or indirect down-regulation of Hif-1α and CXCL-12 expressions.
Animals ; Antineoplastic Agents ; Apoptosis ; Bone Morphogenetic Protein 4 ; Cell Cycle ; Hematopoietic Stem Cells ; Mice ; Mice, Inbred C57BL

OBJECTIVE: To explore the clinical efficacy of acupuncture combined with granule for nerve-root type cervical spondylosis and its effects on serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and hemorheological indexes. METHODS: A total of 114 patients with nerve-root type cervical spondylosis were randomly divided into an observation group and a control group, 57 cases in each group. The patients in both groups were treated with traction. The patients in the control group were treated with oral administration of granule, 4 g each time, 3 times a day, while based on the treatment of control group, the patients in the observation group were treated with acupuncture at Dazhui (GV 14), Tianzhu (BL 10), Houxi (SI 3), cervical Jiaji (EX-B 2), Quchi (LI 11), Hegu (LI 4) and Waiguan (TE 5), once a day. Both groups were treated for 4 weeks. The simplified McGill pain questionnaire (MPQ), neck disability index (NDI), numbness score, levels of IL-6, TNF-α, IL-1β in serum and hemorheological indexes were observed before and after treatment, and the clinical efficacy was compared between the two groups. RESULTS: The total effective rate was 91.2% (52/57) in the observation group, which was higher than 71.9% (41/57) in the control group (<0.05). Compared before treatment, the scores of MPQ, NDI and numbness in the two groups were reduced after treatment (<0.05). After treatment, the scores of MPQ, NDI and numbness in the observation group were lower than those in the control group (<0.05). After treatment, the serum levels of IL-6, TNF-α and IL-1β in the two groups were reduced (<0.05), and those in the observation group were lower than the control group (<0.05). After treatment, the plasma viscosity, fibrinogen, low shear rate of whole blood viscosity and high shear rate of whole blood viscosity in the two groups were lower than before treatment (<0.05), and those in the observation group were lower than the control group (<0.05). CONCLUSION Acupuncture combined with granule have significant clinical efficacy for nerve-root type cervical spondylosis, which could reduce the serum levels of IL-6, TNF-α and IL-1β and improve hemorheology.
Acupuncture Therapy ; Humans ; Interleukin-1beta ; Interleukin-6 ; Spondylosis ; therapy ; Tumor Necrosis Factor-alpha

OBJECTIVETo explore the expression level of insulin-like growth facter (IGF-IR) in CD34 cells of patients with myelodysplastic syndromes(MDS).

METHODSFlow cytometry was used to detect the expression of IGF-IR in the CD34 cells of 100 MDS patients and 18 normal controls.

RESULTSThe average IGF-IR expression level in the CD34 cells of 100 MDS patients (41.0±28.1)% was statistically and significantly elevated in comparison with the corresponding level in normal controls(4.3±1.8)%,(P<0.0001). The average expression level of 22 cases in high-risk groups was very significantly increased, compared with that in 78 cases of low-risk groups[(66.5±27.8)% vs (34.5%±24.9)%](P<0.0001), and the average expression level in 23 patients with chromosome abnormality was very significantly increased in comparison with that in rest 77 patients [(56.0±30.9)% vs (36.9%±26.2)%](P<0.01).

CONCLUSIONThe over-expression of IGF-IR in CD34 cells of MDS patients suggests that the IGF-IR may involve in the origin, occurrence and progress. The average IGF-IR expression level is markedly elevated in high-risk groups and the patients who showed chromosome abnormality, this trend revealed that IGF-IR correlates with malignant clonal proliferation in MDS patients, thus providing a basis for their prognosis and outcome evaluation.

Antigens, CD34 ; Bone Marrow Cells ; Chromosome Aberrations ; Flow Cytometry ; Humans ; Myelodysplastic Syndromes ; Somatomedins

Along with the increase of clinical application, the safety of traditional Chinese medicine gained more and more attentions. In particular, the safety evaluation of Chinese medical injections has become a mandatory task should be completed by pharmaceutical companies under the supervision of China Food and Drug Administration(CFDA). Due to the weak foundation of previous studies, the safety issues of Chinese medical injections have not been fully understood, and lack of scientific and rational risk management programs. Clinical safety centralized monitoring(CSCM) is an important method for post-market safety evaluation of Chinese medicine. Due to the lack of appropriate norms and procedures, the quality of similar research is uneven, and the results vary. Combined with practical experience with experts' suggestions, we developed this expert consensus on the design and implementation of CSCM from three stages (design, implementation and report) with 20 technical points, which will provide technical support for future CSCM studies.

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.
Animals ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; HEK293 Cells ; Hepatocytes ; drug effects ; metabolism ; Humans ; Lactates ; pharmacology ; Organic Anion Transporters ; metabolism ; Rats ; Rosuvastatin Calcium ; pharmacology ; Solute Carrier Organic Anion Transporter Family Member 1b1

OBJECTIVETo investigate the expression of 17 beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) in the kidney of rats and explore the capacity of the kidney for synthesizing sex hormones.

METHODSThe expressions of 17-HSD1 and sex hormones were detected by Western blotting and radioimmunoassay in rat renal cells in primary cultured for 24 and 48 h in the presence or absence of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

RESULTSAfter cell culture for 24 h, the primary rat renal cells expressed a low level of 17β-HSD1 (0.1843±0.076), which increased to 1.6651±0.044 (P<0.01) in response to co-stimulation by FSH and LH. Low levels of estradiol, progesterone and testosterone were also detected in rat renal cells (3.30±3.78, 62.60±12.33, and 22.12±3.36, respectively), and co-stimulation of FSH and LH significantly increased their levels to 8.50±2.64, 117.80±9.79, and 45.04±4.39, respectively (P<0.05). The levels of these hormones showed no significant differences between cells cultured for 24 h and 48 h (P>0.05).

CONCLUSIONThe rat renal cells express 17β-HSD1 and are capable of stably secreting sex hormones in response to co-stimulation with FSH and LH, suggesting the capacity of the rat kidneys for synthesizing sex hormones. These findings enrich the understanding of the endocrine function of the kidney.

17-Hydroxysteroid Dehydrogenases ; metabolism ; Animals ; Cells, Cultured ; Estradiol ; biosynthesis ; Follicle Stimulating Hormone ; pharmacology ; Kidney ; enzymology ; Luteinizing Hormone ; pharmacology ; Progesterone ; biosynthesis ; Rats ; Testosterone ; biosynthesis

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharma­cokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*1a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C_max, AUC_0-t, AUC_0-∞ were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL_z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol·L^-1 Danshensu. The IC₅₀ parameters was (53.04 ± 2.43) μmol·L^-1. The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvas­tatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94) % and (63.61 ± 3.94) %, respectively, by Danshensu at 1 and 10 μmol·L^-1. While transport of rosuvastatin was reduced by (8.22 ± 2.40) % and (11.56 ± 3.04) % and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATP1B1. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.

OBJECTIVETo investigate the protective effect and mechanism of Shenqi Compound on diabetic angiopathy modeled rats.

METHODSTotally 18 SD rats were randomized into 3 groups, i.e., the normal control group, the diabetic mellitus (DM) group, and Shenqi Compound group, 6 in each group. The DM rat model was established by feeding high-fat diet (to induce hyperlipidemia) +intraperitoneal injection of small dose streptozotocin (STZ). Shenqi Compound was given to rats in the Shenqi Compound group at the daily dose of 2 g/kg. Equal volume of normal saline was given to rats in the model group and the normal control group by gastrogavage. All treatment was lasted for 12 weeks. Then 2-D and ultrasonic integrated backscatter technique were used to evaluate structural and functional changes of abdominal aorta in the progression of diabetic macroangiopathy. The fibrosis degree of the aorta vessel and myocardium capillaries were observed by using HE and Masson trichrome staining. The tension of the aortic vascular ring was determined. The transforming growth factor beta (TGF-beta) mRNA expression was detected by real time PCR (RT-PCR). The protein expression of TGF-beta, collagen I, collagen III, connective tissue growth factor (CTGF), and phosphorylation P38 MAPK were detected by Western blot.

RESULTSCompared with the normal control group, abdominal aortic systolic inner diameter, diastolic inner diameter, Peterson elastic modulus, stiffness index, and backscatter integral significantly increased; the rangeability of integral backscatter and the extension coefficient of cross section significantly decreased in the DM group (all P < 0.05). After 12 weeks aforesaid indices were obviously improved in the Shenqi Compound group (P < 0.05). Results of HE and Masson staining showed that the fibrosis degree of the aorta vessel and myocardium capillaries was obviously alleviated in rats of the Shenqi Compound group (P < 0.05). Results of the aortic vascular ring tension showed that acetylcholine induced vasodilatation and maximum diastolic percent were obviously elevated in the Shenqi Compound group (P < 0.05). Compared with the normal control group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all significantly increased in the DM group (P < 0.05). Compared with the DM group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all decreased (P < 0.05).

CONCLUSIONSShenqi Compound could effectively improve the arterial function in diabetic marcoangiopathy and microvascular dysfunction. The mechanism might be due to the down-regulating the expression of TGF-beta, and further suppressing the phosphorylation of P38 MAPK, reducing the synthesis of collagen I and collagen III, therefore, ameliorating arterial and myocardial interstitial fibrosis.

Animals ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetic Angiopathies ; prevention & control ; Drugs, Chinese Herbal ; pharmacology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

PURPOSE: The purpose of this study was to investigate the influence of chronic virus-related liver disease severity on propofol requirements. MATERIALS AND METHODS: In this study, 48 male patients with chronic hepatitis B infection were divided into three groups according to Child-Turcotte-Pugh classification of liver function (groups A, B, and C with mild, moderate and severe liver disease, respectively). After intubation, propofol concentration was adjusted by +/-0.3 microg/mL increments to maintain bispectral index in the range of 40-60. Target propofol concentrations at anesthesia initiation, pre-intubation and pre-incision were recorded. RESULTS: The initial concentration used in group C was significantly lower than that used in group A or B (p<0.05), whereas no difference was observed between groups A and B. At pre-intubation, the actual required concentration of propofol increased significantly (3.2 microg/mL) in group A (p<0.05), which lead to significant differences between the groups (p<0.05). At pre-incision, the requirements for propofol decreased significantly in both groups A and B (3.0 microg/mL and 2.7 microg/mL, respectively) compared with those at pre-intubation (p<0.05), and were significantly different for all three groups (p<0.05), with group C demonstrating the lowest requirement (2.2 microg/mL). The required concentrations of propofol at pre-incision were similar to those at induction. CONCLUSION: In this study, propofol requirements administered by target-controlled infusion to maintain similar depths of hypnosis were shown to depend on the severity of chronic virus-related liver dysfunction. In other words, patients with the most severe liver dysfunction required the least amount of propofol.
Adult ; Anesthesia ; Anesthetics, Intravenous/*administration & dosage ; Chronic Disease ; Electroencephalography ; Hepatitis B, Chronic/complications/drug therapy/*surgery ; Humans ; Liver Diseases/*complications/surgery ; Male ; Middle Aged ; Piperidines/*administration & dosage ; Propofol/*administration & dosage ; Virus Diseases/*complications/surgery

Agarwood is a precious traditional Chinese medicine with the efficacy of promoting qi circulation and relieving pain, warming middle-jiao, controlling nausea and vomiting, governing inspiration and relieving asthma, therefore it is widely applied in the clinic. Meanwhile, agarwood is also a precious spice. Aquilaria sinensis is the only source of agarwood production in China. Under natural conditions, a healthy A. sinensis tree produces no agarwood. Only if being wounded or infected with fungus can it synthetize and accumulate agarwood. It takes a decade or even several decades to produce agarwood, thus natural agarwood can not meet market demands. The essay summarizes historical records of agarwood production method and modern agarwood production method, in order to provide basis and reference for large-scale production of agarwood.
China ; Drugs, Chinese Herbal ; metabolism ; Medicine, Chinese Traditional ; methods ; trends ; Thymelaeaceae ; growth & development ; metabolism