Diagnosis, Differential ; Female ; Humans ; Knee Joint ; pathology ; Middle Aged ; Sarcoma, Synovial ; pathology ; Tomography, X-Ray Computed

Aim To look for novel small-molecule inhibitors of CDK9 through structure-based virtual screening and biological activity determination.Methods Homology modeling of CDK9 was based on the 3-D structure of other cyclin-dependent kinase family members,and then virtual screening by DOCK(molecular docking)of database of small molecule was carried on.MTT method was used in inhibition of tumor cell growth in vitro,while Western blot was used for further study of molecular mechanisms.Results From the top 1000 compounds with the best DOCK energy score,27 compounds were selected for biological assay based on the diversity of chemical structure and functional group.12 of 27 selected compounds showed significantly inhibition activity on tumor cell proliferation,and only one compound in 12 with half-maximum inhibition concentration(IC50)values less than 20 ?mol?L-1 named C-21 was selected for further molecular mechanism study.The western blotting data showed C-21 compound could effectively inhibit CDK9 from phosphorylating large subunit C-terminal of RNA polymerase Ⅱ in a dose-dependent manner.Conclusions Through homology modeling,virtual screening by computer,determination of biological activity and experimental studies of molecular mechanism,a new promising lead compound targeted for CDK9 was found and confirmed.

Objective After acute craniocerebral trauma , to a certain extent , arterial blood lactate and lactate clearance rate reflect the illness severity .We aimed to investigate the prognosis value of arterial blood lactate and lactate clearance rate in patients with craniocerebral trauma . Methods 94 cases with craniocerebral trauma treated in the Department of Emergency of Nanjing General Hospital of Nanjing Military Regionfrom February 2015 to November 2015 were retrospecively analysed .GCS ( Glasgow Coma Scale ) score, arterial blood lactate , blood pressureand heart rate were measured once patients admitted to hospital and 6 hours later ,arterial blood lactate was measured again to calculated the arterial blood lac-tate clearance rate .Based on the GCS score , we divided the patients into mild group (13-15), medium group (9-12) and severe group (3-8).We also divided the patients into death group and survival group according toprognosis .We compared arterial blood lactate and lactate clearance rate betweeeneach group respectively . Results There were significant differences in arterial blood lactate (F=19.99,P<0.01) and 6h lactate clearance rate(F=6.21,P<0.01)be-tween lighter group , medium group and severe group .The initial arterial blood lactate of death group was significantly higher than sur-vival group[(4.20 ±1.36)mmol/L vs (1.58 ±0.93)mmol/L], the difference was statistically significant (t=-9.78,P<0.01). The 6 h lactate clearance rate of death group was significantly lower than survival group [(31.73 ±12.84)%vs (46.25 ±12.01)%], the difference was statistically significant (t=4.55,P<0.01). Conclusion Arterial blood lactate and 6 h lactate clearance rate can evaluate the severity and prognosisof illnessin patients with craniocerebral traumaand have important application value in clinical work .

Objective To explore the association among viral load,CD4 count and neutralizing ac-tivity of plasma from chronic HIV-1 infected former blood donors in Anhui province, China. Methods 294 chronically HIV-1 B' infected individuals from former blood donors in Anhni province were enrolled, whose plasma and peripheral blood mononuelnar cells (PBMC) were isolated. The viral load and CD4 were detec-ted, and the neutralization activity of plasma against primary virus (1597) and lab-adapted strain (SF33) was detected by Luciferase Assay System based on TZM cell line, and 50% neutralizing level was calculated by the Reed-Mueneh method. Results Neutralizing activity responding against SF33 strain was higher than 1597 (P<0.05). There was a positive correlation between neutralizing concentration of plasma against SF33 and viral load (1g) (r = 0.191, P = 0.001), but there was no correlation between neutralizing concen-tration of plasma against 1597 and viral load(lg) (r = 0.097, P = 0.096). Conchtsion In chronic HIV-1 infectious people, neutralizing level against SF33 increases with viral replication, however, there is no asso-ciation of plasma neutralizing against 1597 replication with viral load.

Objective To investigate the mechanism of hypoxia regulate osteopontin (OPN) secreting by mature dendritic cells (mDCs). Methods CD14 + cells were enriched using anti-CD14 immunomagnetic beads, for inducing to mDCs, CD14 + cells were cultured with GM-CSF and IL-4 in hypoxia or normoxiain vitro. Concentration of OPN and TGF-β1 in supernatant were detected by sandwich ELISA, OPN mRNA detected by RT-PCR. Approach regulating function of A2 R in expressing of OPN by mDCs by using NECA (surrogate of adenosine), A2R agonist (CGS21680), A2R antagonist (SCH58261) and investigate role of TGF-β1 in this process by using rhTGF-β1 and anti-TGF-β1 Ab. Results Hypoxia inreased the level of OPN and OPN mRNA in mDCs, and this effect could be reversed by A2 R antagonist. Under normoxia,both NECA and A2R agonist (CGS21680) could upregulate the level of OPN and OPN mRNA in mDCs significantly, but this positive effect could be reversed by A2 R antagonist. A2 R played a role in regulating TGF-β1, and confirmed TGF-β1 involved in regulation of OPN by using rhTGF-β1 and anti-TGF-β1 Ab. Conclusion High adenosine induce the generation of TGF-β1 through the A2R on mDCs, and then TGF-β1 raise the OPN secreting by mDCs.

OBJECTIVETo observe the clinical efficacy difference between segmentation scraping and conventional acupuncture for cervical spondylosis (CS) so as to provide effective treatment method.

METHODSEighty-five cases of cervical type of CS were randomly divided into a scraping group (44 cases) and an acupuncture group (41 cases). The segmentation scraping therapy was used in the scraping group. The scraping group was treated with focusing on scraping the head and joint part of neck and occiput in the upper cervical spine injury, and focusing on scraping the lower section of cervical and shoulder in the lower cervical spine injury, once every seven days, totally for 3 times. In the acupuncture group, Fengchi (GB 20),Wangu (TE 5), Tianzhu (BL 10),Neck-Jiaji (EX-B 2), etc. were selected,once daily,for 15 days. The visual analogue scale (VAS) was used to evaluate the immediate analgesic effect after the first treatment and the clinical efficacy was observed after the end of treatment.

RESULTSAfter the first treatment, the score of VAS was decreased significantly in the scaping group (P < 0.01), but there was no significant difference in the acupuncture group compared with those before treatment (P > 0.05); the score of VAS in the scaping group after the first treatment was lower than that in the acupuncture group (3.66 +/- 0.74 vs 5.43 +/- 0.35, P < 0.01). Compared with before treatment, the scores of VAS were decreased significantly after treatment in two groups (both P < 0.01), but without significant difference between two groups (P > 0.05); the effective rate was 95.5% (42/44) in the scaping group and 87.8% (36/41) in the acupuncture group, the curative effects were similar (P > 0.05).

CONCLUSIONBoth of scraping and acupuncture therapies have good analgesic effect for cervical spondylosis, and overall effects are similar, but the immediate analgesic effect of scraping thrapy is better than that of conventional acupuncture.

Acupuncture Points ; Acupuncture Therapy ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Neck Pain ; therapy ; Spondylosis ; therapy ; Treatment Outcome

The cupping spot is considered as one kind of skin change due to cupping treatment. With literature regarding cupping spot, the influencing factors and value of cupping spot in clinical diagnosis and treatment were analyzed, which could make a further exploration on the action mechanism of cupping treatment. The literature showed that the formation of cupping spot was related with cupping temperature, pressure, cup-retaining time, cupping area, individual difference and health condition, etc; cupping spot had the ability to assist diagnosis, prevent disease, cure disease and evaluate clinical efficacy. Previous studies on cupping spot have already made some progress, and played a positive significance on finding cupping rule and studying its mechanism. However, the research for this area is still in the primary stage, which needed deeper study to reveal scientific connotations of cupping spot.
Acupuncture Therapy ; instrumentation ; Humans ; Skin ; anatomy & histology ; blood supply

Objective: To review the application of polymeric micelles as the vehicles in transdermal delivery systems.Methods: Based on the recently published papers, the researches of preparation, penetration mechanism, drug release and application of polymeric micelles in transdermal delivery systems were classified and summarized.Results: Polymeric micelles were extensively applied as drug vehicles due to the ability of solubilization and transdermal absorption enhancement.Conclusion: Polymeric micelles can be used as promising vehicles in transdermal delivery systems, which show a good application prospect.

We revisited the "Xiao Chaihu Decoction event (XCHDE)" occurred in late 1980s in Japan and the Bupleuri Radix related adverse drug reaction (ADR) reports in China After careful review, comparison, analysis and evaluation, we think the interstitial pneumonitis, drug induced Liver injury (DILI) and other severe adverse drug envents (ADEs) including death happened in Japan is probably results from multiple factors, including combinatory use of XCHDE with interferon, Kampo usage under modern medicine theory guidance, and use of XCHD on the basis of disease diagnosis instead of traditional Chinese syndrome complex differentiation. There are less ADE case reports related to XCHD preparation in China compared to Japan, mostly manifest with hypersensitivity responses of skin and perfuse perspiration. The symptoms of Radix Bupleuri injection related ADEs mainly manifest hypersensitivity-like response, 2 cases of intravenous infusion instead of intramuscular injection developed hypokalemia and renal failure. One case died from severe hypersensitivity shock. In Chinese literatures, there is no report of the interstitial pneumonitis and DILI associated with XCHDG in Japan. So far, there is no voluntary monitoring data and large sample clinical research data available. The author elaborated the classification of "reevaluation" and clarified "re-evaluation upon events" included the reaction to the suspected safety and efficacy events. Based on the current status of the clinical research on the Radix Bupleuri preparations, the author points out that post-marketing "re-evaluation upon suspected event" is not only a necessity of continuous evaluation of the safety, efficacy of drugs, it is also a necessity for providing objective clinical research data to share with the international and domestic drug administrations in the risk-benefit evaluation. It is also the unavoidable pathway to culture and push the excellent species and famous brands of TCM to the international market, in that it enhances the pharmaceutical manufactures the ability to control enterprise risk and eliminate the negative impact on traditional Chinese medicine. With the widely used and ADR report concentrated Radix Bupleuri injection as an example, the author provide a new approach to post-marketing clinical research.
Bupleurum ; chemistry ; Drug Compounding ; Drug-Related Side Effects and Adverse Reactions ; etiology ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Product Surveillance, Postmarketing ; methods ; Safety