The objective of this paper is to discover new potent inhibitors against EphB4 for cancer therapy via computer-aided drug design strategies including building 3D-QSAR models,virtual screening and molecular doc-king means.The first step is to generate pharmacophore models based on Catalyst/HypoGen algorithm.The best model,Hypo1,has the highest Correl value (0.96),the lowest RMS value (0.89),the closest total cost (101.26) to fixed cost (89.20),and the best Δcost (89.14).Subsequently,Hypo1 was subjected to test set validation and Fischer′s randomization verification and then was used as a 3D query to screen database.In order to further nar-row the number of hits,drug-likeness screening and molecular docking techniques were applied.Finally,23 novel molecules with diverse scaffolds were selected as possible candidates against EphB4 for further studies based on predicted activity analysis,docking scores,and binding modes analysis methods.

Objective To evaluate the effect of intravitreal injection of triamcinolone for diffuse diabetic macular edema with optical coherence tomography (OCT). Methods 24 patients (25 eyes) with diffuse diabetic macular edema that failed to respond to previous treatment with of laser photocoagulation received an intravitreal injection of 4mg/0.1ml triamcinolone to each eye. The visual acuity, founds fluorescein angiography (FFA), and measurement of the macular retinal thickness with OCT were examined before and after the therapy. Mean follow-up time was 4.6 months (range 3-6 months ). Results Mean best-corrected visual acuity was improved from 0.12?0.07 to 0.30?0.16, the visual acuity improvement was statistically significant(P

OBJECTIVETo observe effects of treatment from the lung and treatment from the intestine on the level of vasoactive intestinal peptide (VIP) in the lung and intestine of ulcerative colitis (UC) rats.

METHODSThe UC rat model was established in 52 rats by using rabbit intestine mucosa tissue allergen combined TNBS-ethanol model (with the model successful rate of 78.0%). Eight rats randomly selected from 40 successfully modeled rats and 8 of 16 rats from the normal group were recruited as the model group and the normal control group before intervention (at week 0). The rest 32 successfully modeled rats were randomly divided into the model group, the Western medicine treatment group (salazosulfapyridine), the treatment from lung group (Huangqi Jiegeng Decoction), and the treatment from intestine group (Huangqi Huanglian Decoction), 8 in each group. Rats in each treatment group were administered with corresponding medication 8 times the dose of a 60 kg adult human. Another 8 normal rats were recruited as the normal group. Equal volume of pure water was given to rats in the model group and the normal group by gastrog avage, once per day. Contents of VIP in the lung tissue and the intestinal tissue were detected at week 0 and 4 after 4-week consecutive intervention. Pathomorphological changes of the lung tissue and the colon tissue were observed under light microscope.

RESULTSCompared with the normal control group at week 0, evenly distributed diffuse inflammation could be seen in the pulmonary interstitial tissue; the bronchial wall was thickened; a huge amount of infiltration surrounded bronchi and blood vessels; a large area of necrosis of intestinal mucosa and inflammatory cell infiltration could also be seen in the model group. Pathological injuries of the lung and the colon were more alleviated in each treatment group than in the model group at the same time point. Compared with the normal control group at the same time point, VIP contents in the lung tissue significantly decreased in the model group at the end of week 4 (P<0.05); VIP contents in the colon tissue significantly increased in the model group at the end of week 0 and 4 (P <0.05). Compared with the model group, VIP contents in the lung tissue significantly increased in the Western medicine treatment group and the treatment from lung group at the end of week 4 (P<0.01); VIP contents in the colon tissue significantly decreased in the treatment from lung group and the treatment from intestine group (P<0.05, P<0.01).

CONCLUSIONTreatment from the lung and treatment from the intestine showed predominant advantage in improving local inflammation of the lung and the intestinal tract, alleviating pathological injuries, promoting repair of injuries through regulating VIP contents in the lung tissue and the colon tissue.

Animals ; Colitis, Ulcerative ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Intestinal Mucosa ; metabolism ; Intestines ; Lung ; Male ; Rabbits ; Rats ; Vasoactive Intestinal Peptide

Objective To evaluate effect of en bloc resection of malignant sacral tumor involving partial sacrum and ipsilateral sacroiliac joint with reservation of contralateral sacral foramina.Methods Between February 2005 and July 2010,16 patients with malignant sacral tumor involving partial sacrum and ipsilateral sacroiliac joint underwent hemi-sacrectomy and functional reconstruction.The operation achieved en bloc resection of tumor with reservation of contralateral sacral foramina.There were 10 males and 6 females,aged from 17 to 70 years (average,37.9 years).There were 5 cases of chondrosarcoma,3 cases of Ewing's sarcoma,2 cases of malignant schwannoma,2 cases of osteosarcoma,1 case of malignant giant cell tumor of bone,1 case of lymphoma and 2 cases of metastatic tumor.Results The surgical time ranged from 4 to 11.5 hours (average,6.5 hours).The average blood loss was 3600 ml (range,1500 to 5500 ml).Five patients underwent type Ⅰ resection,while 11 patients underwent type Ⅱ resection.All patients were followed up for 21 to 59 months (average,34.4 months).Three months after operation,13 patients had difficulty with ankle plantar flexion,while sphincter function was more or less reserved in 16 patients.Four patients (25％)had wound healing complications,which was cured after debridement and drainage.Local recurrence occurred in 7 patients.There were 5 cases of local recurrence among 6 patients who had intralesional margin;4 recurrence lesions located in the sacrum and 1 in soft tissue.Eight patients (50.0％) survived without tumor,2 patients (12.5％)survived with tumor,and 6 patients (37.5％) died of tumor.Conclusion The en bloc resection of tumor involving partial sacrum and ipsilateral sacroiliac joint with reservation of contralateral sacral foramina was feasible and had better outcome compared with total sacrectomy.

AIM:To observe and compare clinical effects of coaxial 1. 8mm microincision phacoemulsification and 3. 2mm small incision phacoemulsification.
●METHODS:A total of 117 eyes of 85 patients with age-related cataract in our hospital were divided randomly into two groups:43 patients (59 eyes) in the coaxial 1. 8 mm microincision cataract surgery group ( C - MlCS ) , 42 patients (58 eyes) in the coaxial 3. 2 mm traditional small incision cataract surgery group (C-SlCS). A total of 117 eyes were received phacoemulsification with intraocular lens implantation. Uncorrected visual acuity was recorded preoperatively and postoperatively at 1, 7, 30 and 90d. The effective phacoemulsification time and average ultrasound energy were recorded in surgery. Corneal endothelial cell and corneal topography were recorded preoperatively and postoperatively at 90 d.
●RESULTS:Uncorrected visual acuity ( logMAR) was no overall statistical significance difference between C-MlCS group and C-SlCS group (P>0. 05), but was significant statistical difference in different time-point within both groups(P<0. 05). Uncorrected visual acuity in different time-point had nothing to do with corneal wound size in cataract surgery(P>0. 05). On the 1 day after surgery, uncorrected visual acuity was 0. 16±0. 11 in C-MlCS group and 0. 22±0. 18 in C-SlCS group(P<0. 05). AVE was (7. 00± 2.72)% in C-MlCS group and (6. 16±3. 16)% in C-SlCS group (P>0. 05). EPT was (3. 09±1. 61)s in C-MlCS group and (3. 20±1. 92)s in C-SlCS group (P>0. 05). At 90 d after surgery, corneal endothelial cell loss percentage was (5. 81±2. 28)% in C-MlCS group and (5. 69±2. 38)% in C-SlCS group (P>0.05), SlA was (0.35±0.11) Din C-MlCS group and (0. 61±0. 13) D in C-SlCS group (P<0. 05).
● CONCLUSION: Compared with coaxial 3. 2mm traditional small incision cataract surgery, 1. 8mm coaxial microincision cataract surgery can get earlier visual rehabilitation and significantly reduce SlA. The coaxial 1. 8mm microincision cataract surgery is safe, effective and deserves further clinical applications.

Adolescent ; Adult ; Carbon Monoxide Poisoning ; epidemiology ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Young Adult

Identification and validation of a new target is one of the most important steps for new antituberculosis (TB) drug discovery. Researches have shown that Mycobacterium tuberculosis (Mtb) encodes 20 CYP450 enzymes which play important roles in the synthesis and metabolism of lipid, cholesterol utilization, and the electron transport of respiratory chain in Mtb. With the critical roles within the organism as well as the protein structures of six Mtb CYP450 enzymes being clarified, some of them have been highlighted as potential anti-tuberculosis targets. In this paper, the phylogenetic analysis, the structural features, and the enzymatic functions of Mtb CYPs, as well as the mechanism of interactions with selective inhibitors such as azole antifungal agents for the CYPs have been reviewed and summarized. The druggability of the CYPs has also been analyzed for their further utility as targets in high throughput screening and rational design of more selective inhibitors.
Antitubercular Agents ; chemistry ; pharmacology ; Azoles ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme Inhibitors ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Drug Delivery Systems ; methods ; Drug Discovery ; Humans ; Mycobacterium tuberculosis ; drug effects ; enzymology ; genetics ; Phylogeny ; Tuberculosis ; drug therapy ; microbiology

Objective To investigate the effect of Dexamethasone on microtubule - associated protein 1 light chain 3(LC3)expression of cells and neurons in cerebral cortex of juvenile Wistar rats with sepsis. Methods Models of juvenile Wistar rats with sepsis were established through cecal ligation and puncture(CLP). Totally 60 cases of 30 -day - old juvenile male Wistar rats were randomly divided into sham - operation group(10 cases),non - treated group (25 cases)and Dexamethasone group(25 cases). Twelve hours after CLP,rats in Dexamethasone group were injected with Dexamethasone(1 mg / kg)via tail vein every other day,with a total of 3 times. The same dose of saline was used in the non - treated group. All rats were killed at the age of 40 days. Expressions of LC3 and neuronal nuclei(NeuN)of cells in cerebral cortex of rats were detected by using immunofluorescence assay,and the number of positive cells was calculated by using image analysis system software. Expressions of LC3 - Ⅰ and LC3 - Ⅱ protein were measured by a-dopting Western blot. Results Three hours after CLP,rats appeared to be curled up and showed piloerection and shi-vering and the neurobehavioral score in non - treated group was significantly lower than that in sham - operation group (t = 9. 895,P = 0. 000). Twelve of 25 rats in Dexamethasone group died in 10 days after CLP(48% ),while 8 of 25 rats in non - treated group died(32% ),and the difference was not statistically significant between the 2 groups(χ2 =1. 333,P = 0. 248). The immunofluorescence staining and image analysis showed the percentage of LC3 positive cells in non - treated group was significantly increased(0. 606 7 ± 0. 030 1 vs 0. 353 3 ± 0. 025 8,t = 15. 644,P = 0. 000;0. 606 7 ± 0. 030 1 vs 0. 270 3 ± 0. 019 4,t = 22. 450,P = 0. 000). In non - treated group,the LC3 expression of cells in the cerebral cortex of rats was up - regulated,and the LC3 - Ⅱ/ LC3 - Ⅰ ratio was significantly higher than that in sham operation group and Dexamethasone group(0. 413 3 ± 0. 022 5 vs 0. 205 0 ± 0. 015 2,t = 18. 802,P = 0. 000;0. 413 3 ± 0. 022 5 vs 0. 185 0 ± 0. 023 5,t = 17. 206,P = 0. 000). The LC3 positive neurons in the cerebral cortex of rats were less in sham operation group and Dexamethasone group. The LC3 positive neurons were more in non - treated group than that in sham operation group and Dexamethasone group(0. 580 0 ± 0. 020 0 vs 0. 298 3 ± 0. 014 7,t =27. 783;P = 0. 000;0. 580 0 ± 0. 020 0 vs 0. 261 7 ± 0. 017 2,t = 28. 614;P = 0. 000). Conclusions The LC3 expres-sion of cells in the cerebral cortex of juvenile Wistar rats with sepsis was up - regulated,LC3 - Ⅱ/ LC3 - Ⅰ ratio in-creased,and the number of LC3 positive neurons also increased,while Dexamethasone could have inhibitory effect on them.

BACKGROUND:Clinical y, bone marrow mesenchymal stem cel s combined with artificial bones for early osteonecrosis of the femoral head have a wonderful outcome.
OBJECTIVE:To review the biological properties of bone marrow mesenchymal stem cel s and to summarize the application progress of bone marrow mesenchymal stem cel s combined with different artificial bones in the treatment of early osteonecrosis of the femoral head.
METHODS:PubMed (2003-2013), FMJS (2003-2013), Wanfang (2005-2013), CNKI (2005-2013) and CBM (2005-2013) databases were retrieved by computer using the keywords of“bone marrow mesenchymal stem cel s;artificial bone;osteonecrosis of the femoral head”in Chinese and English.
RESULTS AND CONCLUSION:It wil lower the pressure of the femoral head, accelerate repair of the blood capil ary, improve the blood supply, osteoblast proliferation and differentiation, and thus delay or even prevent artificial joint replacement after osteonecrosis of the femoral head by applying bone marrow mesenchymal stem cel s combined with different artificial bones, such as corl ine hydroxyapatite, calcium hydroxylaptite, biological ceramics and calcium sulfate bones. But now, there are stil a lot of problems which need to be solved, including pathological mechanism underlying bone marrow mesenchymal stem cel s for treatment of osteonecrosis of the femoral head, obvious difference between the quantity and quality of seed cel s because of individual difference, different sites and culture techniques. So, artificial bone materials are under review, and large-sample randomized control trials are required. Its long-term outcomes also lack for fol ow-up observation, as wel as there is no a unified quantitative standard for the appropriate selection of indication, curative effect evaluation and the awareness of the operation.

Objective To evaluate the sensitivity and specificity of prenatal ultrasound for detecting fetal cleft lip and palate,and the diagnosis rate of associated congenital structural and chromosomal abnormalities.Methods Thirty one thousand two hundred and forty five singleton pregnant women accepted prenatal examination and delivered in Guangzhou Women & Children' s Medical Center from Jan.2006 to Dec.2010 were recruited in this study.All pregnant women underwent prenatal ultrasound screening during second trimester,and whose fetuses were suspected to be cleft lip and palate were suggested to accept karyotype analysis.All babies delivered received oral examination to diagnose cleft lip and palate.Results Cleft lip and palate was diagnosed in 48 cases (1.5‰,48/31 245).Among which,there were 16 cases (33.3％,16/48) of cleft lip,21 cases (43.8％,21/48) of cleft lip with cleft palate and 11 cases (22.9％,11/48) of cleft palate.Prenatal ultrasound screening suggested 18 cases of cleft lip and 14 cases were comfirmed after birth with the accuracy rate of 77.8％,3 cases were diagnosed to be cleft lip with cleft palate and one cases was misdiagnosed.Prenatal ultrasound screening suggested 18 cases of cleft lip with cleft palate in accordance with the diagnosis after birth.Thirteen cases were normal in prenatal ultrasound screening,but two were diagnosed as cleft lip and 11 were diagnosed as cleft palate after birth.The sensitivity of prenatal ultrasound screening for cleft lip and cleft lip with cleft palate was 86.5％(32/37),and the sensitivity for cleft lip and palate was 66.7％ (32/48),the false positive rate was 2.1％ (1/48).Ten cases (27.8％,10/36) of cleft lip with cleft palate were found to be complicated with other abnormalities.Nine of the 18 cases prenatally diagnosed cleft lip with cleft palate accepted karyotype analysis and 7 were abnormal.Twenty-three of 36 cases with fetal cleft lip and palate in prenatal ultrasound screening were induced.Conclusions Ultrasound screening has a high sensitivity for detection of cleft lip with or without cleft palate,but difficult to detect cleft palate.The risk of combining with chromosomal defects in cleft lip fetus is very low,but might increase once associated with cleft palate.