Objective To evaluate the clinical efficacy and safety of Xuebijing injection in treatment of sepsis and multiple organ dysfunction syndrome ( MODS ). Methods A prospective multicenter clinical study was conducted. The patients with sepsis, severe sepsis, or MODS admitted to Department of Emergency and Critical Care Medicine of 70 hospitals across the country during 2006 to 2008 were enrolled. All of the patients received the basis treatment of conventional therapy, plus Xuebijing injection of 50-100 mL, 2-3 times a day for 5-7 days, and the dose might be increased in serious cases. The vital signs, 24-hour urine output, Glasgow coma score ( GCS ), white blood cell count ( WBC ), platelet count ( PLT ), Marshall score, gastrointestinal function score, syndrome of traditional Chinese medicine ( TCM ), blood lactate ( Lac ), blood glucose, serum creatinine ( SCr ), and total bilirubin ( TBil ) were observed before treatment, 1, 3, and 5 days after treatment, and at the end of the treatment. The results of above mentioned parameters after the treatment were compared with that before treatment in each patient. At the same time, the occurrence and the degree of adverse reactions were recorded to evaluate the safety of Xuebijing injection. Results A total of 2 574 patients were enrolled, and in 2 509 cases the treatment was completed in, with a drop of 65 cases. 704 cases were diagnosed to have sepsis, 768 with severe sepsis, and 1 037 with MODS. According to TCM, in 1 951 cases syndrome of stasis-toxin in the interior, and in 558 syndrome of excessive exuberance of heat-toxic in the interior were diagnosed. After the treatment of Xuebijing injection combined with conventional therapy, the temperature, heart rate, respiration rate, blood pressure, WBC, PLT, GCS, 24-hour urine output, blood glucose, Lac, SCr, TBil, Marshall score, gastrointestinal function score, as well as the symptoms, signs and TCM tongue condition and pulse condition, and TCM scores were significantly improved in all patients as well as the patients with sepsis, severe sepsis, or MODS ( P < 0.05 or P < 0.01 ). The effective rate of all patients and the patients with sepsis, severe sepsis, or MODS was 89.20%( 2 238/2 509 ), 92.76%( 653/704 ), 91.54%( 703/768 ), 85.05%( 882/1 037 ), respectively, and the 28-day survival rate was 93.90%( 2 356/2 509 ), 98.01%( 690/704 ), 96.35%( 740/768 ), 89.30%( 926/1 037 ), respectively. In 3 patients with MODS adverse events ( 0.12%) occurred, including 2 cases of stress ulcer and 1 case of Adams-Stokes syndrome. After clinical evaluation, the adverse events were found to be unrelated with the study medication, and Xuebijing injection was continued till the end of treatment. Conclusion Xuebijing injection combined with conventional therapy may effectively ameliorate systemic inflammatory response, protect organ function, alleviate the symptoms, improve organ functions, and elevate the clinical cure rate. Adverse events occur occasionally. Xuebijing injection is found to be safe.

Objective :To study influence of amlodipine combined valsartan on autonomic nervous function and serum level of Rho‐associated protein kinase 1 (ROCK1) in hypertensive patients with renal injury .Methods :A total of 94 hypertensive patients with renal injury treated in our hospital were selected ,randomly and equally divided into amlo‐dipine group and combined treatment group (received amlodipine combined valsartan ) ,both groups were treated for one month .Serum ROCK1 level and autonomic nervous function indexes before and after treatment ,therapeutic effect and incidence of adverse reactions were analyzed and compared between two groups .Results :After treat‐ment ,total effective rate of combined treatment group was significantly higher than that of amlodipine group (95. 74% vs.82.97%,P＝0. 045).Compared with before treatment ,after treatment ,there were significant reduc‐tions in serum ROCK1 level [amlodipine group : (3. 25 ± 0.32 ) ng／ml vs.(1.24 ± 0. 45 ) ng／ml ,combined treat‐ment group :(3. 34 ± 0. 35) ng／ml vs.(0.22 ± 0.15 ) ng／ml] ,24hSBP standard deviation (24hSSD) ,24h DBP SD (24hDSD) ,daytime SBP SD (dSSD) ,nighttime SBP SD (nSSD) and nDSD in two groups ( P＝0.001 all) ,and a‐bove indexes of combined treatment group were significantly lower than those of amlodipine group , P＜ 0. 01 all. Compared with amlodipine group after treatment ,there were significant reductions in incidence rates of lower limb edema (27. 66% vs.10.63%) ,nausea and vomiting (27. 66% vs.8.51%) and dizziness and weakness (23. 40% vs. 8.51%) in combined treatment group ,P＜0. 05 all.Conclusion :Amlodipine combined valsartan possesses significant therapeutic effect on hypertensive patients with renal injury .It can significantly reduce serum ROCK1 level and im‐prove autonomic nervous function and prognosis in these patients .

Objective:To produce rhBMP-4 with bioactivity in E.coli. Methods: The full-length human BMP-4 gene was mutated by PCR without changes in amino acid sequence, then the synthesized gene was cloned into plasmid pET-3c, transducted into BL21(DE)plysS, and induced by adding IPTG to a final concentration of 1.0 mmol/L. The protein product was purified using ion-exchange chromatography method and then renaturated, bioactivity was checked by C2C12 differentiation in vitro and mouse ectopic bone formation in vivo. Results: A 438 bp gene fragment encoding mature peptide of hBMP-4 was cloned , the protein product was mostly in the form of inclusion body, after renaturation, the engineering protein shows better bioactivity. Conclusion:The mutant strategy can enhance the expression of bioactive rhBMP-4 in E.coli expression system.

Traditional Chinese ancient prescriptions have been used for treatment of liver cancer for a long history and the scientific and rational compatibility is a great wealth for modern research and development (R&D) of new drugs. The research and development of new drugs are often accompanied with a large investment, a long cycle and a high risk, especially for the anti-tumor drugs R&D which are facing more risks and lower successful rate. In this research, the regularity of compatibility of drugs was analyzed from 124 anti-hepatoma ancient prescriptions by computer program. The results can offer help to the R&D of anti-hepatoma new drugs and reduce the risk of drug screening. In addition, we surveyed 22 companies in this field from six provinces such as Beijing, Shanghai, Tianjin and so on and obtained 240 risk assessment questionaires. Then we used qualitative analysis method to interpret the greatest impacts for the risks in the process of R&D, production and sales of anti-hepatoma new drugs. The study provides a basis for anti-liver cancer drugs R&D researchers, who can take effective measures to reduce the R&D risks and improve successful rate.
Carcinoma, Hepatocellular ; drug therapy ; history ; China ; Drug Discovery ; history ; Drug Incompatibility ; Drug Prescriptions ; history ; Drugs, Chinese Herbal ; history ; therapeutic use ; History, Ancient ; Humans ; Liver Neoplasms ; drug therapy ; history ; Research ; history

Objective To investigate the expression of glucagon-like peptide-1 receptor (GLP-1R) of skeletal muscle cells and the changes of skeletal muscle microstructure of diabetic rats, and to explore the relationship between the expressions of GLP-1R and insulin resistance in skeletal muscle. Methods Male Wistar rats were divided into two groups, normal glucose tolerance ( NT, n =25 ) , diabetes group ( DM group, n=30), the methods of creating diabetes model were used high-sugar high-fat diet and low-dose in-traperitoneal injection of streptozotocin. Immunohistochemical methods was used to detect the expression of GLP-1R in the muscle cells. The number of GLP-1R positive cells in the muscle of two groups was observed and compared. The relationship was analyzed between the homeostasis model assessment insulin resistance (HOMA-IR) and the number of GLP-1R positive cells. Results ⑴Compared to the NT group, the num-ber of GLP-1R positive cells in muscle of DM group was decreased (P<0. 05); ⑵ Compared to the NT group, HOMA-IR was increased in DM group (P<0. 05);⑶ Pearson correlation analysis showed that the percentage of GLP-1R positive cells expressed in rat skeletal muscle was negatively correlated with HOMA-IR (r= -0. 538, P<0. 01). Conclusions The expression of GLP-1R positive cells was decreased in the skeletal muscle of diabetic rats, insulin resistance increased. Therefore, the expression of GLP-1R on skele-tal muscle cells may promote the development of insulin resistance and diabetes mellitus.

It has been established in the recent several decades that adult stem cells play a crucial role in tissue renewal and regeneration. Adult stem cells locate in certain organs can differentiate into functional entities such as macrophages and bone cells. Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are two of the most important populations of adult stem cells. The application of these stem cells offers a new insight in treating various pathological conditions, through replenishing cells of specific functions by turning on or off the differentiating program within quiescent stem cell niches. Apart from that, they are also capable to travel through the circulation, migrate to injury sites and differentiate to enhance regeneration process. Recently, Chinese medicine (CM) has shown to be potential candidates to activate adult stem cells for tissue regeneration. This review summarizes our own, as well as others' findings concerning the use of Chinese herbal medicine in the regulation processes of adult stem cells differentiation and their movement in tissue repair and rejuvenation. A number of Chinese herbs are used as therapeutic agents and presumably preventive agents on metabolic disorders. In our opinion, the activation of adult stem cells self-regeneration not only provides a novel way to repair tissue damage, but also reduces the use of targeted drug that adversely altering the normal metabolism of human subjects.
Cell Differentiation ; Herbal Medicine ; Humans ; Medicine, Chinese Traditional ; Regeneration ; Stem Cells ; cytology ; drug effects ; Tissue Engineering

In the present study, an ultra performance liquid chromatography coupled with time-of-fight mass spectrometry (UPLC-TOF/MS) based chemical profiling approach was used to evaluate chemical constitution between co-decoction and mixed decoction of ginseng and Radix Aconiti Praeparata. Two different kinds of decoctions, namely co-decoction of ginseng and Radix Aconiti Praeparata: water extract of mixed two herbs, and mixed decoction of ginseng and Radix Aconiti Praeparata: mixed water extract of each individual herbs, were prepared. Batches of these two kinds of decoction samples were subjected to UPLC-TOF/MS analysis. The datasets of t(R) m/z pairs, ion intensities and sample codes were processed with supervised partial least squared discriminant analysis (OPLS-DA) to holistically compare the difference between these two decoction samples. Significant difference between the two decoction samples was showed in the results of positive ion mode. The contents of hypaconitine and deoxyaconitine decreased, while that of benzoylmesaconine, benzoylhypaconine and dehydrated benzoylmesaconine increased in the samples of co-decoction of ginseng and Radix Aconiti Praeparata. The content of diester-diterpenoid alkaloids decreased, while that of monoester-diterpenoid alkaloids increased, which is probably the basis of toxicity-attenuated action when combined ginseng with Radix Aconiti Praeparata.
Aconitine ; analogs & derivatives ; analysis ; Aconitum ; chemistry ; Alkaloids ; analysis ; Chromatography, High Pressure Liquid ; methods ; Drug Combinations ; Drugs, Chinese Herbal ; chemistry ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods

BACKGROUNDTo explore the effect of human osteopontin (hOPN) on the proliferation, transmigration and expression of matrix metallproteinase-2 (MMP-2) and matrix metallproteinase-9 (MMP-9) in osteosarcoma (OS) cells in vitro.

METHODSThe prokaryotic-expression vector of hOPN was produced. hOPN was then subcloned into E. coli BL21 (DE3) cells and purified with ProBond trade mark Columns. The proliferation, cell cycle and the expression of cyclin A in OS cells were investigated by using MTT assay, flow cytometry and Western blot respectively. The transmigration of OS cells was checked by using transwell cell culture chamber. The micro-pore-filter-membrane system was used to study the chemiotaxis of hOPN to OS cells. The levels of total protein were examined according to Coomassie Brilliant Blue manuals. The expression of MMP-2 and MMP-9 were evaluated by detecting the volume of degradation of gelatin on SDS-PAGE gel.

RESULTSThe prokaryotic-expression vector of hOPN and purified hOPN protein were achieved hOPN promoted OS cells proliferation in a dose-dependent manner, and stimulated cyclin A expression in OS cells to accelerate cell division cycle. hOPN facilitated the trans-membrane migration of OS cells. hOPN also enhanced the secretion of MMP-2 and MMP-9 in OS cells.

CONCLUSIONhOPN could stimulate cyclin A expression in OS cells. hOPN has chemiotaxis to OS cells and increases their transmigration. hOPN enhances the secretion of MMP-2 and MMP-9 in OS cells.

Bone Neoplasms ; pathology ; Cell Cycle ; drug effects ; Cell Division ; drug effects ; Cell Line, Tumor ; Cell Movement ; drug effects ; Humans ; Matrix Metalloproteinase 2 ; secretion ; Matrix Metalloproteinase 9 ; secretion ; Osteopontin ; Osteosarcoma ; pathology ; Sialoglycoproteins ; pharmacology

OBJECTIVETo investigate the transformation of microhardness and microstructures of human dental fluorosis after demineralization and remineralization in vitro.

METHODSForty human dental fluorosis enamel blocks were demineralized by acid-etching gel, then subjected to 1.0% casein phosphopeptides stabilized calcium phosphate (CPP-CP) for remineralization. Surface enamel microhardness was measured on the enamel blocks before and after demineralization and after remineralization. The enamel specimens was observed by stereomicroscope and scanning electron microscope, then sectioned (100 microm) and examined by transmission light microscope and polarized light microscope.

RESULTSBefore demineralization, the average knoop hardness value of the fluorosed teeth was (241.53 +/- 21.31) kHV. After demineralization, obvious decrease of the surface hardness of the enamel was observed, the mean value was (175.76 +/- 24.99) kHV (P < 0.05), the percent of the surface microhardness demineralization (% SMHD) was (27.23 +/- 1 4.79)%, and major demineralization was under the surface of the enamel, which was similar to the early natural enamel caries. After remineralization, obvious increase of the surface hardness of the enamel was observed, the mean value was (210.17 +/- 21.48) kHV (P < 0.05), the percent of the surface microhardness remineralization (% SMHR) was (52.32 +/- 4.23)%, major remineralization was under the surface of the enamel.

CONCLUSIONRemineralization could be used to prevent and cure the early natural enamel caries of fluorosed dental teeth.

Calcium Phosphates ; Cariostatic Agents ; Caseins ; Dental Caries ; Dental Enamel ; Hardness ; Humans ; In Vitro Techniques ; Tooth Demineralization ; Tooth Remineralization

Objective To explore the value of Multi-detector CT in spinal cord angiography. Methods Ten patients with initial MR and clinical findings suggestive of spinal cord vessel disease were performed CT spinal cord angiography.Among these,7 patients were performed DSA later within 1 week, and 4 patients were therapy by operation.CT protocol:Toshiba Aquilion 64 slice CT scanner,0.5 mm thickness,0.5/r,120 kV,350 mA,choose aortic arch level as inspection position,and use"surestart" technique with CT threshold 180 HU.Contrast medium was Iohexol(370 mg I/ml),with injection velocity of 6 ml/s.The total volume was 80 ml.The CT spinal cord angiography images were analyzed according to disease model,disease range,feeding artery,fistula,draining veins,and were compared with DSA and operation results.Results All CT spinal cord angiography images displayed spinal vessel malformation. Among these,3 patients were inner-medullary arteriovenous malformation;2 patients were peri-medullary arteriovenous fistula;5 patients were spinal dural arteriovenous fistula.All cases showed disease range,and draining veins clearly,one patient had two vessels that were false positive,and all the other cases showed feeding arteries clearly,which were confirmed by DSA.Conclusion There are great values for CT spinal angiography in diagnosing spinal vessel disease,it can be a screening exam before DSA.