Objective To investigate the effect on the differentiation of bone marrow mesenchymal stem cells (BMSC) with non-contact co-culture with mechanical stimulated ligament fibroblasts. Methods A cyclic 10% uniaxia strain at 1 Hz was applied on rat pelvic ligament fibroblasts, then were co-cultured with BMSC for 3, 6 and 12 days in non-contact condition. The protein expression of collagen Ⅰ ,Ⅲ in BMSC were detected by SP method and revealed by the mean gray value. The mRNA expressions of collagens type Ⅰ and type Ⅲ in the BMSCs were measured with real-time (RT)-PCR ,and the results were indicated by the ratio between the mRNA and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) . Results (1) Protein expression; after 3 days co-culture with pelvic ligament fibroblasts, expression of collagen Ⅰ and Ⅲ in BMSC are 82. 4 ± 3. 4 and 76. 8 ± 2. 5. When compared with 80. 2 ± 2. 6 and 74. 6 ± 1. 1 in BMSC without co-culture, there was no significant difference (P > 0. 05) . After 6 days co-culture with pelvic ligament fibroblasts, the expression of collagen Ⅰ and Ⅲ of 126. 6 ±2. 2 and 118. 6 ± 1. 4 in BMSC were significantly higher than 82. 7 ±3. 0 and 76. 2 ± 1. 3 in BMSC without co-culture (P < 0. 05). Similarly, after 12 days co-culture with pelvic ligament fibroblasts, the expression of collagen Ⅰ and Ⅲ of 135. 3 ±3. 4 and 128. 7 ± 2. 6 in BMSC were significantly higher than 86. 6 ± 1. 3 and 81. 8 ± 1.4 in BMSC without co-culture (P <0.05). (2)mRNA expression:after 3 days co-culture with pelvic ligament fibroblasts , the mRNA expression of type Ⅰ and type Ⅲ collagens in BMSC are 2. 10 ±0. 20 and 1. 20 ±0. 30. When compared with mRNA expression of 2. 01 ±0. 12 and 1. 13 ±0.21 in BMSC without co-culture, no significant difference were observed (P > 0. 05). After 6 days co-culture with pelvic ligament fibroblasts , the mRNA expressions of type Ⅰ and type Ⅲ collagens mRNA were 5. 60 ±0. 21 and 2. 61 ±0. 20, which were significantly higher than 3. 70 ±0. 33 and 1. 82 ± 0. 14 in BMSC without coculture (P < 0. 05). After 12 days co-culture with pelvic ligament fibroblasts, the mRNA expressions of type Ⅰ and type Ⅲ collagens of 5. 91 ±0.31 and 2. 92 ±0. 23 were significantly higher than 4. 04 ±0. 21 and 2. 04 ±0. 13 in BMSC without co-culture (P <0. 05). Conclusion Non-contact co-culture with mechanical stretch stimulated ligament fibroblasts, it might promote synthesis of types Ⅰ and Ⅲ collagen in rat BMSCs and induced BMSC differentiated into pelvic ligament fibroblasts.

In order to provide a scientific basis for the establishment of a Daphnes Cortex medicinal material fungus library and the screening of endophytic fungi that promote the growth of Daphnes Cortex and increase the content of daphnetin, we used Illumina high-throughput testing technology to analyze 9 Daphnes Cortex samples from Gansu and Shanxi provinces. A total of 632 766 valid sequences were obtained, including 348 OTUs, 4 phyla, 20 classes, 48 orders, 108 families, 154 genera, and 208 species. The sum of the first 3 fungal genera account for more than 65% of the total abundance, with the highest reaching 98.4%. Alternaria and Phoma are the main genuses of Daphne giraldii Nitsche, and Altemaria is the dominant genus. The endophytic fungi community of Daphnes Cortex is rich in diversity, and the order of fungal diversity in different producing areas is: Gangu County > Wutai County > Tanchang County.

Objective To investigate the effects of lipopolysaccharide (LPS) on the expressions of sodium taurocholate co-transporting polypeptide (Ntcp) and bile salt export pump (Bsep),as well as the liver function markers in the serum including total bilirubin (TBIL),total bile acids (TBA),alanine aminotransferase (ALT),aspartate aminotransferase (AST) in mice.Methods One hundred and twenty-eight C57BL/6 mice were intra-peritoneally injected with different doses of 5,10,20 or 40 mg/kg LPS (n =24),respectively.No treatment or treated with 0.9％ NaC1 in mice as controls.Serum TBIL,TBA,ALT and AST levels were measured at 24 h,48 h and 72 h after LPS injection in each group.The mRNA expressions of Ntcp and Bsep were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR).The liver histological sections were stained with haematoxylin and eosin (H&E).Results The Ntcp and Bsep mRNA expressions in mice liver were significantly lower in livers of LPS-treated mice within 24-72 h compared with control group,and the lowest level was reached at 24 h in a dose-dependent manner.And the relative expressions of Ntcp mRNA and Bsep mRNA were (0.64 ± 0.02),(0.53 ± 0.14),(0.25±0.09),(0.15±0.07)and (0.74±0.12),(0.58±0.11),(0.41±0.09),(0.27 ± ± 0.11) in livers of mice injected with LPS in the different doses of 5,10,20,40 mg/kg,respectively.In addition,serum levels of TBIL,TBA,ALT,and AST were significantly increased in mice of LPS-treated group compared with control group,particularly within 24 h after LPS treatment.Serum levels of TBIL,TBA,ALT,and AST were significantly decreased in mice of 40 mg/kg LPS-treated 72 h group compared with 24 h group presenting them with (1.29 ± 0.25) μ mol/L vs.(1.71 ± 0.22) μ moL/L,(6.97 ± 0.98) μmol/Lvs.(8.96±1.01) μmol/L,(120.17±21.08) U/L vs.(179.22±16.57) U/L,(360.34 ±35.31) U/L vs.(510.97 ± 34.70) U/L,respectively.Furthermore,histological changes in liver depend on dose and the course of LPS treatment.Cytoplasm rarefaction and inflammatory cells infiltration were detected at 24 h after treatment with 5 or 10 mg/kg LPS.Acidophilic and vacuolar degeneration,neutrophils infiltration in the hepatic sinusoid and portal area,the proliferation of bile ductulus were observed at 48 h,72 h after treatment with 5 or 10 mg/kg LPS.In the 20 or 40 mg/kg LPS treatment groups,focal necrosis,infiltration with inflammatory cells,proliferation of bile ductulus and expansion of duct were observed at 24 h,48 h and 72 h after LPS treatment.Conclusions LPS decreases the mRNA expressions of Ntcp and Bsep in a dose dependent manner in mice,contributing to mechanism of liver injury induced by endotoxin.

The rising of evidence-based medicine requires high quality for clinical research and randomized controlled trial is considered as clinical research of the most level of evidence degree and contidence activity.This article illustrates several important and instructive designs of randomized controlled trials,which can give some reference for clinical research on acupuncture.And the developing direction of future clinical research on acupuncture is discussed.

Panax notoginseng (PN) is one of the commonly used clinical medicines for cardiovascular diseases and possesses a variety of pharmacological effects. P. notoginseng saponins (PNS) are the most important bioactive components in PN. The purpose of this study was to explain the mechanism of PNS on molecular network level. 18 targets of the main medicinal ingredients of PNS were gained by virtual screening based on pharmacophores and data mining. A protein interaction network of PNS was constructed with 189 nodes and 721 interactions. By a graph theoretic clustering algorithm Molecular Complex Detection (MCODE), 14 modules were detected. Gene ontology (GO) enrichment analysis of the modules demonstrated that the roles of PNS played in cardiovascular disease related to multiple biological processes, which could represent the characteristics of traditional Chinese medicine (TCM) as a whole to regulate the disease. The results showed that the blood circulation and hemostasis efficacy of PN related with the biological processes such as positive regulation of cAMP metabolic and biosynthetic process, platelet activation and regulation of blood vessel size, regulation of T cell proliferation and differentiation and so on. Therefore, the module-based network analysis will be an effective method for better understanding TCM.
Drugs, Chinese Herbal ; chemistry ; Humans ; Panax notoginseng ; chemistry ; Protein Interaction Maps ; drug effects ; Proteins ; chemistry ; Saponins ; chemistry

Objective:To introduce a novel ridge preservation technique with micro-titanium plate avoiding the use of bone grafting materials,and evaluate the potential horizontal bone preservation effect of this new technique,applied on single maxillary central incisors after tooth extraction for future implant restoration.Methods:Nine patients (six women and three men),mean age (26.0 ±5.7)years(from 1 8 to 34 years)referred to the Department of Oral Implantology,Peking University School and Hospital of Stomotology,were selected and diagnosed with unsalvageable single middle incisor with fine general con-ditions,no signs of acute local inflammation,no ongoing or previous periodontitis,healthy neighboring teeth and intact buccal bone walls.Tooth extraction,delayed implant placement and implant-supported single crown restoration were selected as treatment plan.The teeth were extracted atraumatically with lo-cal anesthesia,followed by a reflection of a minor flap to exposed 2-3 mm of the buccal bone plate.Af-ter that,a micro-titanium plate was trimmed and bended to fit the convexity of the labial bone and fixed by two mini pins with intent to support the labial soft tissue.The flap was then repositioned over the micro titanium plate and secured with two single sutures.No bone grafting materials or releasing incisions were needed.The sockets were left to heal without any intention of primary wound closure.Cone-beam compu-ted tomographic (CBCT)scans were obtained before and four months after tooth extraction.Horizontal ridge widths were measured with CBCT software,and the preservation effects were calculated and recor-ded by the percentage of horizontal ridge alteration.Results:The nine extraction sockets were healed un-eventfully.The average socket width before extraction was (7.51 ±0.48)mm (6.92-7.82 mm).The average alveolar ridge labial-palatal width at the control point of the edentulous area was (6.81 ±0.44) mm (6.04-7.38 mm)4 months after tooth extraction,the mean percentage of ridge width preserved was 90.87%±2.91%(87.28%-95.60%).Conclusion:This novel ridge preservation method by the usage of a micro-titanium plate did not interfere with the natural socket healing process,and at the same time,largely preserved the width of alveolar ridge without any bone grafting procedures.Long term results remain to be seen.

ObjectiveTo explore the feasibility and potential benefit of olfactory ensheathing cell (OEC) intraspinal transplantation in the treatment of intractable chronic neuropathic pain after spinal cord injury (SCI).Methods17 patients, 15 male and 2 female, with intractable chronic neuropathic pain after spinal cord injury was treated by OEC implant from November, 2004 to November, 2007. The age ranged from 18 to 68 (mean 40.4) years. The etiology of cord impairment included car accidents, falls, radiation damage, machine extrusion, gun-shot, and diving. The patients suffered severe persistent pain for 6 to 309 (mean 102.2) months, and the time points when cell therapy were administrated in the patients ranged from 6 to 312 (mean 105.9 months) after their injuries. Olfactory bulbs were harvested and trypsinized down to single fetal OECs. They were cultured for 12～14 days before implant. The fetal OECs were transplanted by injection into spinal cord at opposing ends of the injury site. The degree of pain was assessed and compared before operation and long-term follow-up according to the International Association of Neurorestoratology Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS), i.e., 0 point means extreme pain, uncontrolled; 1 point, severe pain, narcotics required; 2 points, mild pain, ordinary pain killer effective; 3 points, no pain.ResultsThe follow-up and pain reevaluation were performed at 0.5 to 88 months with an average of 17.5 months after cell transplantation. The mean score of pain amelioration is 1.2 points.ConclusionThe OEC intraspinal transplantation appears to have a promising role in treatment of intractable chronic neuropathic pain after SCI.

Objective To observe the protective effects of a mixture for protecting liver and supplementing stomach (保肝益胃合剂) on rat acute liver damage induced by carbon tetrachloride (CCl_4). Methods The model of rat acute liver damage was established by injection of CCl_4 2 ml/kg into the abdominal cavity.The rat models were treated respectively by the mixture for protecting liver and supplementing stomach 30 g?kg~(-1)?d~(-1),the polyene phosphatide acid radical choline capsule [Yi Shanfu (易善复), 180 mg?kg~(-1)?d~(-1)],the glycyrrhizic acid diaminogen capsule [Gan Lixin (甘利欣),30 mg?kg~(-1)?d~(-1)] infused into the stomach.The activities of serum alanine transaminase (ALT) and aspartate transaminase (AST) were detected.In the mean time,the liver pathological changes were observed,the degree of liver cell necrosis was evaluated,and the rat mortality was noted in various groups of treatment.Results The values of ALT,AST and the score of liver cell necrosis in the group treated with the mixture for protecting liver and supplementing stomach [(1.168?1.066) kU/L,(1.845?2.212) kU/L,(0.56?0.53) score] were significantly lower than those in the model group [(4.982?3.502) kU/L,(7.030?3.616) kU/L, (1.38?0.92) scores],and all the differences being statistically significant (all P

Data of clinical trial projects involved by clinical trial institutions certified by the State Food and Drug Administration from 2002 to November 2012 were collected to summarize adverse reactions in project summary/statistical reports, analyze the rate of adverse reactions of clinical trials of new traditional Chinese medicines and relevant influencing factors, and increase the awareness of the safety of new traditional Chinese medicines. A total of 73 050 cases in 209 projects of 14 specialties were collected, including 49 689 cases in the new traditional Chinese medicine group and 271 adverse reaction cases, with an incidence rate of adverse reactions at 0.55%. The adverse reaction rate in 3 months < middle long course ≤ 6 months was the highest (1.04%), whereas that in short course ≤ half a month was the lowest (0.48%). The adverse reaction was closely related with the route of administration, 1.28% for topical > 0.63% for injection > 0.50% for oral. In the administration of only the test drug, the adverse reaction rate of patches was the highest (2.68%), whereas that of aerosols and suppositories was lowest (0). In the combined administration of the test drug and the simulation agent, the adverse reaction rate of external test patch + capsule was the highest (3.38%), whereas that of capsule + oral liquid, pills + granules, tablets + oral liquid, tablets + pills, tablet + capsule was the lowest (0). In the administration of only the test drug, the adverse reaction rate was 0.47%; In the combined administration with simulation agent (drug volume increase), the adverse reaction rate was 0.74%. Different doses caused adverse reaction different rates; The adverse reaction rate of drugs with whole-course dose between 1 100-1 200 g was the highest (3.36%), that for whole-course doses of 500-600, 900-1 000, 1 400-1 500, 1 600-1 700, 1 800-1 900 g was the lowest (0). In conclusion, the adverse reaction rate of new traditional Chinese medicines was still up to 0.55%, with the adverse reaction rate between 0.47% and 0.72% over the 11 years, without significant difference in each year. The adverse reaction rate was closely related to course of treatment, approach of administration, dosage form and medication dosage, with no significant correlation with medication dosage during the course of treatment. The adverse reaction rate increased with the rise in trial duration and drug volume. In the administration of only the test drug, the adverse reaction rates of external formulations and injections were higher than that of oral dosage forms. It is suggested to give more attention to the adverse reactions of drugs with long course of treatment and large volumes, injections and external patches in clinical trials of new traditional Chinese medicines.
Clinical Trials as Topic ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Medicine, Chinese Traditional

BACKGROUNDTo compare the efficacy and side effects between cisplatin solution and cisplatin powder combination regimens for lung cancer.

METHODSA total of 223 patients were enrolled into this study. EP protocol was given to patients with small cell lung cancer (SCLC), and NP protocol to non small cell lung cancer (NSCLC). The 223 patients were randomly divided into cisplatin solution group and cisplatin powder group, and the same drugs and dosage were used in the two groups for the same type of lung cancer.

RESULTSResponse rates of the cisplatin solution group and the cisplatin powder group were 84.8% and 82.4% for SCLC ( P > 0.05), and 31.6% and 29.9% for NSCLC ( P > 0.05), respectively. The major side effects were gastrointestinal reactions and myelosuppression. Significantly higher incidence of nausea/vomiting was found in cisplatin solution group than that in cisplatin powder group for either SCLC or NSCLC ( P < 0.05). There was a remarkable difference in cost of hospitalization between the two groups ( P < 0.05).

CONCLUSIONSCisplatin solution is as effective as cisplatin powder in the treatment of lung cancer. However, the more severe nausea/vomiting reactions and higher cost of cisplatin solution should be considered in its clinical application.