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1.
China Pharmacy ; (12): 1655-1660, 2019.
Article in Chinese | WPRIM | ID: wpr-817116

ABSTRACT

OBJECTIVE: To establish content determination method of Triptolide-glycyrrhetic acid compound microemulsion, optimize the formula and investigate its physicochemical properties and release rate in vitro. METHODS: The content of Triptolide- glycyrrhetic acid compound microemulsion was determined by UPLC. The determination was performed on ACQUITY UPLC BEH C18 column with mobile phase consisted of 0.1% formic acid aqueous solution-acetonitrile (gradient elution) at the flow rate of 0.4 mL/min. The column temperature was 40 ℃. The detection wavelength was set at 218 nm, and sample size was 5 μL. Pseudo-ternary phase diagrams were drawn by water titration method. Using oil phase, surfactants and co-surfactants as index, the formula was optimized, and in intro release characteristics was investigated by in vitro release test. RESULTS: The linear range of triptolide and glycyrrhetinic acid were 1-40 μg/mL(r=0.999 7) and 10-400 μg/mL(r=0.999 8), respectively. The limits of quantitation were 0.5 and 0.8 μg/mL; the limits of detection were 0.1 and 0.2 μg/mL. RSDs of precision, stability and reproducibility tests were all less than 2%. Average recoveries were 100.32%-101.15% (RSD=0.36%, n=6), 99.78%-101.42% (RSD=0.59%,n=6). The optimal formula included that medium chain triglyceride as oil phase, polyethylene glycol hydroxy stearate as surfactants, ethanol as co-surfactants, water as water phase, the proportion of them was 8 ∶  28 ∶ 14 ∶ 50. The obtained microemulsion was O/W type, being transparent and clear, with average diameter, average polydispersity index and average viscosity of (62.38±3.44) nm, 0.096±0.001 and (26.84±1.10) mPa·S. Within 24 h, cumulative release rates of triptolide and glycyrrhetinic acid in obtained microemulsion were 99.8% and 99.7% (in PBS pH 2.0), 99.3% and 99.4% (in PBS pH 7.4), 98.9% and 98.4% (in PBS pH 9.0), respectively. Triptolide and glycyrrhetinic acid released faster in the single microemulsion than in the compound microemulsion. CONCLUSIONS: Established content determination method is simple and stable. The optimized formula is stable and feasible. Obtained iriptolide-glycyrrhetinic acid compound microemulsion show better sustained-release effect than sigle microemulsion.

2.
Acta Pharmaceutica Sinica ; (12): 845-851, 2018.
Article in Chinese | WPRIM | ID: wpr-779944

ABSTRACT

With the worldwide spread of multi-drug resistant (MDR) bacteria, bacterial resistance has become a major issue affecting human health. Although traditional methods for obtaining antibiotics by screening bacterial strains have found the most available antibiotics for us, this method has resulted in fewer and fewer antibiotics in the past few decades and is increasingly difficult to find the new structure of the compound entity. At present, there are few drugs that can fight super-resistant bacteria in the clinic or even research. therefore, the development and application of new technologies to address the issue of bacterial resistance is imminent. Since the first bacterial genome was sequenced more than 20 years ago, a large number of bacterial genomic sequence information can provide clues for the discovery of new antibiotics. In this review, we briefly outline the available data sources and highlight the use of genomic mining and metagenomics in discovery of new antibiotics.

3.
Chinese Journal of Tissue Engineering Research ; (53): 902-907, 2018.
Article in Chinese | WPRIM | ID: wpr-698473

ABSTRACT

BACKGROUND:A new-type nano-bionic anti-adhesion hernia mesh was developed in our previous research.OBJECTIVE:To investigate the mechanical properties and cytocompatibility of the new-type nano-bionic anti-adhesion hernia mesh.METHODS:The tensile strength of the compound hernia mesh was detected using a textile detector.Mouse fibroblasts (L929) were cultured with the compound hernia mesh,and cell structures on the mesh surface were observed under electron microscope at 1,3,5 days after culture.In addition,L929 cells were co-cultured with compound hernia mesh,polypropylene patch,and polyester patch,respectively.Cells cultured alone were used as negative controls.After 1,3,5 days of culture,MTS array was used to detect cell proliferation and evaluate cytotoxicity;after 3 days of culture,western blot was used to detect the content of type Ⅰ and Ⅲ collagens.RESULTS AND CONCLUSION:The average tensile strength of the compound hernia mesh was 31.2 N The number of fibroblasts on the nanofibrous layer of the compound hernia mesh increased as long as cultured.The cells spread along the nanofibers and pseudopodia extended from the cells formed polygon and fusiform structures,with a good cross-linking with the mesh.A complete cell layer covered all pores of the nanofibers at 5 days.The cytotoxicity of the nanofibrous layer of the compound hernia mesh was graded 0,and the cytotoxicity was graded 1 of polypropylene and polyester patches.All the three kinds of patches fulfilled the implantation requirements,and the compound hernia mesh had better biological properties.No significant differences were found among groups in the contents of type Ⅰ and Ⅲ collagens at 3 days of culture.To conclude,the new-type nano-bionic anti-adhesion hernia mesh has good mechanical properties and cytocompatibility.

4.
Chinese Medical Journal ; (24): 717-721, 2017.
Article in English | WPRIM | ID: wpr-266921

ABSTRACT

<p><b>BACKGROUND</b>Dendritic cells are professional antigen-presenting cells found in an immature state in epithelia and interstitial space, where they capture antigens such as pathogens or damaged tissue. Matrix metallopeptidase 13 (MMP-13), a member of the collagenase subfamily, is involved in many different cellular processes and is expressed in murine bone marrow-derived dendritic cells (DCs). The function of MMP-13 in DCs is not well understood. Here, we investigated the effect of MMP-13 on DC maturation, apoptosis, and phagocytosis.</p><p><b>METHODS</b>Bone marrow-derived dendritic cells were obtained from C57BL/6 mice. One short-interfering RNA specific for MMP-13 was used to transfect DCs. MMP-13-silenced DCs and control DCs were prepared, and apoptosis was measured using real-time polymerase chain reaction and Western blotting. MMP-13-silenced DCs and control DCs were analyzed for surface expression of CD80 and CD86 and phagocytosis capability using flow cytometry.</p><p><b>RESULTS</b>Compared to the control DCs, MMP-13-silenced DCs increased expression of anti-apoptosis-related genes, BAG1 (control group vs. MMP-13-silenced group: 4.08 ± 0.60 vs. 6.11 ± 0.87, P = 0.008), BCL-2 (control group vs. MMP-13-silenced group: 7.54 ± 0.76 vs. 9.54 ± 1.29, P = 0.036), and TP73 (control group vs. MMP-13-silenced group: 4.33 ± 0.29 vs. 5.60 ± 0.32, P = 0.001) and decreased apoptosis-related genes, CASP1 (control group vs. MMP-13-silenced group: 3.79 ± 0.67 vs. 2.54 ± 0.39, P = 0.019), LTBR (control group vs. MMP-13-silenced group: 9.23 ± 1.25 vs. 6.24 ± 1.15, P = 0.012), and CASP4 (control group vs. MMP-13-silenced group: 2.07 ± 0.56 vs. 0.35 ± 0.35, P = 0.002). Protein levels confirmed the same expression pattern. MMP-13-silenced groups decreased expression of CD86 on DCs; however, there was no statistical difference in CD80 surface expression. Furthermore, MMP-13-silenced groups exhibited weaker phagocytosis capability.</p><p><b>CONCLUSION</b>These results indicate that MMP-13 inhibition dampens DC maturation, apoptosis, and phagocytosis.</p>


Subject(s)
Animals , Female , Mice , Apoptosis , Physiology , Bone Marrow Cells , Cell Biology , Dendritic Cells , Cell Biology , Metabolism , Lipopolysaccharides , Pharmacology , Matrix Metalloproteinase 13 , Metabolism , Physiology , Mice, Inbred C57BL , RNA, Small Interfering
5.
Chinese Medical Journal ; (24): 2069-2075, 2017.
Article in English | WPRIM | ID: wpr-338797

ABSTRACT

<p><b>BACKGROUND</b>It remains controversial whether patients with Stage II colorectal cancer would benefit from adjuvant chemotherapy after radical resection. The aim of this study was to establish two mathematical models to identify the suitable patients for adjuvant chemotherapy.</p><p><b>METHODS</b>The current study comprised of two steps. In the first step, 353 patients with Stage II colorectal cancer who underwent surgical procedures at the Third Affiliated Hospital of Sun Yat-sen University between June 2006 and December 2015 were entered and followed up for 6-120 months. Their clinical data were collected and enrolled into the database. We established two mathematical models by univariate and multivariate Cox regression analysis to identify the target patients; in the second step, 230 patients under the same standard between January 2012 and December 2016 were entered and followed up for 3-62 months to verify the two models' validation.</p><p><b>RESULTS</b>In the first step, totally 340 surgical patients with Stage II colorectal cancer were finally enrolled in this study. Statistical analysis showed that tumor differentiation (TD) (P < 0.001), lymphovascular invasion (LVI) (P < 0.001), uncertain or positive margins (UPM) (P < 0.001), and fewer lymph nodes (LNs) (<12) retrieved (P < 0.001) were correlated with the overall survival (OS) and disease free survival (DFS). We obtained two models: (1) OS risk score = 1.116 × TD + 2.202 × LVI + 3.676 × UPM + 1.438 × LN - 0.493; (2) DFS risk score = 0.789 × TD + 2.074 × LVI + 3.183 × UPM + 1.329 × LN - 0.432. According to the models and cutoff points [(0.07, 1.33) and (-0.04, 1.30), respectively], patients can be divided into three groups: low-risk, moderate-risk, and high-risk. Moreover, the high-risk group patients could benefit from adjuvant chemotherapy. In the second step, totally 221 patients were finally used to verify the models' validation. The results proved that the models were accurate and feasible (P< 0.05).</p><p><b>CONCLUSIONS</b>According to the predictive models, patients with Stage II colorectal cancer in the high-risk group are strongly recommended for adjuvant chemotherapy, thus facilitating the individualized and precise treatment.</p>

6.
China Pharmacist ; (12): 1058-1061, 2017.
Article in Chinese | WPRIM | ID: wpr-619663

ABSTRACT

Objective: To investigate the association between the genetic polymorphism of ABCB1 C3435T and plasma concentration and adverse reactions of high-dose methotrexate(HD-MTX) chemotherapy in children with acute lymphoblastic leukemia(ALL).Methods: A total of 70 peripheral blood samples were obtained from the children with acute lymphoblastic leukemia for extracting genome DNA.The genetic polymorphism of ABCB1 C3435T locus was examined by using PCR technology and direct sequencing;enzyme-amplified immunoassay (EMIT) was employed to determine the plasma concentration of MTX in 48 h;the clinical data of patients were collected during the HD-MTX chemotherapy, the adverse reactions were statistically analyzed.The association between ABCB1 C3435T genotypes and MTX plasma concentration and adverse reactions were investigated.Results: Genetic polymorphism existed at the SNP of ABCB1 C3435T.At the SNP of ABCB1 C3435T, the percentage of CC, CT and TT genotype in the children with ALL was 31.43%, 47.14% and 21.43%, respectively.The order of C/D ratio of MTX from low to high was CC, CT and TT genotypes, there was a significant association between the gene polymorphism and the C/D ratio of MTX (P<0.05);the order of incidence of oral mucosa damage from low to high was CC, CT and TT genotypes, there was a significant association between the gene polymorphism and oral mucosa damage (P<0.05);the order of incidence of hepatotoxicity from low to high were CC, CT and TT genotypes, the gene polymorphism and hepatotoxicity had a significant association (P<0.05).Conclusion: ABCB1 C3435T genetic polymorphism and C/D ratio of MTX, gastrointestinal side effects and hepatotoxicity after HD-MTX chemotherapy in the children with ALL exhibit significant association.

7.
Herald of Medicine ; (12): 461-464,465, 2016.
Article in Chinese | WPRIM | ID: wpr-603405

ABSTRACT

Objective To investigate the association of genetic polymorphisms of ATIC and GSTP1 with plasma concentrations and adverse reactions of high-dose methotrexate( HD-MTX)in children with acute lymphoblastic leukemia (ALL). Methods A total of 70 peripheral blood samples were obtained from ALL children for extraction of genome DNA.The gene polymorphisms of ATIC T26293C and GSTP1 A313G locus were examined by using PCR and direct sequencing.Enzyme multiplied immunoassay technique(EMIT)was employed to determine the plasma concentration of MTX in 48 h.Clinical data of patients were collected during HD-MTX chemotherapy,and the adverse reactions were statistically analyzed.The associations of ATIC and GSTP1 genotypes with MTX plasma concentration and adverse reactions were investigated. Results There were genetic polymorphisms at the SNP of ATIC T26293C and GSTP1 A313G.At the SNP of ATIC T26293C,the percentages of TT, CT and CC genotypes in ALL children were 4.35%,39.13% and 56.52%,respectively,and the frequencies of T and C alleles were 23.91% and 76.09%.At the SNP of GSTP1 A313G,the percentages of AA,GA and GG genotype were 68.57%,28.57%and 2.86%,respectively,in ALL children. The frequencies of A and G alleles were 82. 86% and 17. 14%,respectively. No statistically significant difference was found in the ratio of blood MTX concentration to MTX dose at 48 h between children with different genotypes(P>0.05).In the GSTP1 A313G site,genotypes that induced the gastrointestinal reactions in the order from low to high were AA,GA,GG,and there was a significant association between gene polymorphism and gastrointestinal side effects(P<0.05).In the GSTP1 A313G site,genotypes that induced myelosuppression in the order of low to high were GG,AA, GA,and a significant association was noted between gene polymorphism and myelosuppression(P<0.05). Conclusion There are significant associations between GSTP1 A313G polymorphism and gastrointestinal side effects or myelosuppression after HD-MTX chemotherapy in ALL children.

8.
Chinese Journal of Biochemical Pharmaceutics ; (6): 20-23,28, 2016.
Article in Chinese | WPRIM | ID: wpr-603393

ABSTRACT

In the era of outbreaking of antibiotic resistance, the discovery of new antibacterial drugs is emergent.Antimicrobial peptides are important components of the natural defenses of most living organisms against invading pathogens.The unique antibacterial mechanism, direct bactericidal effect, relatively slow of resistance acquirement, and can used alone or combined with antibiotics, make antimicrobial peptides be attractive potential antibacterial drugs.In this paper, we review the physicochemical property of antibacterial peptides, action mechanism and design of antimicrobial peptides, and give a brief introduction of several promising antimicrobial peptides.

9.
Pakistan Journal of Medical Sciences. 2015; 31 (3): 572-575
in English | IMEMR | ID: emr-192065

ABSTRACT

Objective: To compare the therapeutic effects of laparotomy and laparoscopic surgery on patients with gastric cancer. Methods: Sixty-six patients with gastric cancer who were treated in our hospital from January 2012 to December 2013 were selected and divided into a control group and an observation group by the random number method [n=33]. The control group was treated by traditional laparotomy, and the observation group was treated by laparoscopic surgery. CD4 /CD8 ratios and IgG expressions in the patients were detected on preoperative and postoperative fourth days. Intraoperative blood loss, surgical time, time of anal gas evacuation and time of postoperative independent ambulation of the two groups were observed. Results: The intraoperative blood loss, surgical time, time of anal gas evacuation, time of postoperative independent ambulation, time of urinary catheter indwelling and average hospitalization stay length of the observation group were significantly different from those of the control group [P<0.05]. The postoperative rates of fever and complications in the observation group were significantly lower than those of the control group, and the two groups had significantly different CD4 /CD8 ratios and IgG levels on the postoperative 4th day [P<0.05]. Conclusion: Compared with traditional laparotomy, laparoscopic surgery can well treat patients with gastric cancer minimally invasively. Meanwhile, their postoperative recovery was facilitated due to slightly affected humoral immunity and cellular immune function

10.
Chinese Journal of Integrated Traditional and Western Medicine ; (12): 1297-1301, 2014.
Article in Chinese | WPRIM | ID: wpr-313034

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect and potential mechanism of Modified Cangfu Daotan Decoction (MCDD) on endometrial receptivity in infertility patients with polycystic ovarian syndrome (PCOS).</p><p><b>METHODS</b>Totally 298 women having normal ovulation who underwent artificial insemination were recruited as the control group, and they received no drug therapy. Another 355 infertility patients with PCOS who received ovarian stimulation therapy were recruited as the treatment group. Then they were further assigned to the treatment group I (195 cases) and the treatment group II (160 cases) according to random digit table. Patients in the treatment group I received clomiphene (CC) + human menopause gonadotropin (HMG) +human chorionic gonadotropin (HCG), while those in the treatment group II received CC + HMG + HCG and additionally took modified MCDD. The therapeutic course for all was three menstrual cycles. The pregnancy ratio, the endometrial thickness, and spiral artery pulsatility index (PI), resistance index (RI), and homeostasis model assessment-insulin resistance (HOMA-IR) were measured. Furthermore, the uncoupling protein 2 (UCP2) level was tested by Western blot.</p><p><b>RESULTS</b>Compared with the control group, the endometrial thickness decreased and PI and RI increased in the treatment group I (all P < 0.05). Compared with the treatment group I , the endometrial thickness increased and PI and RI decreased in the treatment group II (all P < 0.05). Compared with before treatment, HOMA-IR levels were significantly decreased in the treatment group II after treatment (P < 0.05). Compared with the control group before treatment, the HOMA-IR level increased in the treatment group I and the treatment group II before treatment (P < 0.05). Compared with the control group after treatment, the HOMA-IR level increased in the treatment group I (P < 0.05). But there was no statistical difference in the post-treatment HOMA-IR level between the control group and the treatment group II (P < 0.05). Compared with the control group, the post-treatment UCP2 level was increased in the treatment group II (P < 0.05). After one year follow-up, the pregnancy rate was 16.1% (48/298) in the control group, 23.1% (37/160) in the treatment group I, and 33.8% (66/195) in the treatment group II. Compared with the control group, the pregnancy rate was significantly increased in the treatment group II (P < 0.05).</p><p><b>CONCLUSION</b>MCDD was found to be capable of increasing the pregnancy rate of infertility patients with PCOS, which might be associated with improving endometrial blood flow and insulin resistance, increasing the UCP2 expression, and finally improving the endometrial receptivity.</p>


Subject(s)
Female , Humans , Pregnancy , Chorionic Gonadotropin , Clomiphene , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Gonadotropins , Infertility , Infertility, Female , Insulin Resistance , Ovulation , Ovulation Induction , Methods , Polycystic Ovary Syndrome , Drug Therapy , Pregnancy Rate
11.
Herald of Medicine ; (12): 1288-1290, 2014.
Article in Chinese | WPRIM | ID: wpr-454592

ABSTRACT

Objective In vitro detection of anti-proliferative effects of P161 combined with cisplatin ( DDP) on multiple cancer cells. Methods Growth inhibition rates of HepG2, HT29, IE8, Panc-1 and MA-782 treated by different concentrations of DDP,P161 and P161 combined with DDP were determined by MTT assay. Results DDP and P161 dose-dependently inhibited proliferation of multiple tumor cells. A synergistic effect was found in DDP combined with P161 and there was a significant difference in the effect between DDP combined with P161 and DDP alone (P<0. 05). DDP dose could be decreased to reach the same inhibitory effect. In the same concentration gradient of DDP combined with P161,the inhibition rate of Panc-1 was low and that of MA-782 was high. Conclusion P161 can increase the sensitivity of tumor cells to DDP. The combination of P161 and DDP can reduce the effective therapeutic concentration of DDP.

12.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 912-916, 2013.
Article in English | WPRIM | ID: wpr-251371

ABSTRACT

A rapid and highly selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of megestrol in human plasma was described using medrysone as internal standard (IS). Blood samples were collected from 20 healthy volunteers after oral administration of 160 mg megestrol acetate dispersible tablets. The analytes were extracted by liquid-liquid extraction procedure and separated on a hanbon lichrospher column with the mobile phase of methanol and water containing 0.1% formic acid and 20 mmol/L ammonium acetate (5:1, v/v). Positive ion electrospray ionization with multiple reaction-monitoring mode (MRM) was employed by monitoring the transitions m/z 385.5-325.4 and m/z 387.5-327.4 for megestrol and medrysone, respectively. Under the isocratic separation conditions, the chromatographic run time was approximately 2.54 min for megestrol and 2.59 min for medrysone. The calibration curve range was from 0.5 to 200.0 ng/mL. The inter-batch and intra-batch precision and accuracy were less than 5.2% relative standard deviation (RSD) and 6.4% relative error (RE). The proposed method was successfully applied in the bioequivalence study of megestrol acetate dispersible tablets.


Subject(s)
Humans , Calibration , Gas Chromatography-Mass Spectrometry , Methods , Reference Standards , Megestrol , Blood , Chemistry , Pharmacokinetics , Therapeutic Equivalency
13.
Chinese Journal of Cardiology ; (12): 315-319, 2013.
Article in Chinese | WPRIM | ID: wpr-291979

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the inhibitory effect and related mechanism of bradykinin on mechanical stress induced myocardial hypertrophy.</p><p><b>METHODS</b>Neonatal rat cardiomyocytes were isolated and cultured in silicon plates. All cardiomyocytes were randomly divided into three groups: control group, mechanical stretch group (mechanical stretch of silicon plates to 120% for 30 min) and mechanical stretch plus bradykinin group (1×10(-8) mol/L for 24 h before stretch). The protein synthesis and surface area of cardiomyocytes were detected by [(3)H] leucine incorporation and immunofluorescence of α-MHC, respectively. mRNA expression of atrial natriuretic peptide (ANP) and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) was detected by real time-PCR, the phosphorylation of calcineurin (CaN), the expression of Angiotensin II receptor 1 (AT1R) and angiotensin converting enzyme (ACE)by Western blot.</p><p><b>RESULTS</b>The surface area of cardiomyocytes of mechanical stretch group [(973 ± 103) µm(2)] was significantly enlarged than in control group [(312 ± 29) µm(2)] and this effect could be partly attenuated by bradykinin [(603 ± 74) µm(2), all P < 0.05]. Mechanical stretch also significantly increased the protein synthesis, up-regulated the expression of ANP and decreased the expression of SERCA2, and these effects could be partly reversed by pretreatment with bradykinin. Moreover, bradykinin partly abolished the mechanical stretch-induced increases in CaN phosphorylation, up-regulation of AT1R but preserved the expression of ACE.</p><p><b>CONCLUSIONS</b>Bradykinin significantly attenuates mechanical stretch-induced myocardial hypertrophy through inhibition of Ca(2+)/CaN pathway.</p>


Subject(s)
Animals , Rats , Bradykinin , Pharmacology , Calcineurin , Metabolism , Calcium , Metabolism , Cell Enlargement , Cells, Cultured , Myocytes, Cardiac , Metabolism , Pathology , Stress, Mechanical
14.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 912-6, 2013.
Article in English | WPRIM | ID: wpr-636389

ABSTRACT

A rapid and highly selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of megestrol in human plasma was described using medrysone as internal standard (IS). Blood samples were collected from 20 healthy volunteers after oral administration of 160 mg megestrol acetate dispersible tablets. The analytes were extracted by liquid-liquid extraction procedure and separated on a hanbon lichrospher column with the mobile phase of methanol and water containing 0.1% formic acid and 20 mmol/L ammonium acetate (5:1, v/v). Positive ion electrospray ionization with multiple reaction-monitoring mode (MRM) was employed by monitoring the transitions m/z 385.5-325.4 and m/z 387.5-327.4 for megestrol and medrysone, respectively. Under the isocratic separation conditions, the chromatographic run time was approximately 2.54 min for megestrol and 2.59 min for medrysone. The calibration curve range was from 0.5 to 200.0 ng/mL. The inter-batch and intra-batch precision and accuracy were less than 5.2% relative standard deviation (RSD) and 6.4% relative error (RE). The proposed method was successfully applied in the bioequivalence study of megestrol acetate dispersible tablets.

15.
IJPR-Iranian Journal of Pharmaceutical Research. 2012; 11 (3): 807-830
in English | IMEMR | ID: emr-160869

ABSTRACT

The inhibitors of p53-HDM2 interaction are attractive molecules for the treatment of wild-type p53 tumors. In order to search more potent HDM2 inhibitors, docking operation with CDOCKER protocol in Discovery Studio 2.1 [DS2.1] and multidimensional hybrid quantitative structure-activity relationship [QSAR] studies through the physiochemical properties obtained from DS2.1 and E-Dragon 1.0 as descriptors, have been performed on 59 1, 4-benzodiazepine-2, 5-diones which have p53-HDM2 interaction inhibitory activities. The docking results indicate that n-n interaction between the imidazole group in HIS96 and the aryl ring at 4-N of l, 4-benzodiazepine-2, 5-dione may be one of the key factors for the combination of ligands with HDM2. Two QSAR models were obtained using genetic function approximation [GFA] and genetic partial least squares [G/PLS] based on the descriptors obtained from DS2.1 and E-dragon 1.0, respectively. The best model can explain 85.5% of the variance [R[2][cv] while it could predict 81.7% of the variance [R[2]CV] With this model, the bioactivities of some new compounds were predicted

16.
Chinese Journal of Gastrointestinal Surgery ; (12): 615-617, 2012.
Article in Chinese | WPRIM | ID: wpr-321565

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the feasibility, safety and short-term outcomes of laparoscopy-assisted distal gastrectomy for advanced gastric cancer.</p><p><b>METHODS</b>From January 2007 to June 2008, 135 patients with advanced gastric cancer in the lower or middle stomach were operated, of whom 66 underwent laparoscopy-assisted distal gastrectomy(LADG) with D2 dissection of lymph nodes and 69 received conventional open D2 distal gastrectomy(ODG). Clinical data were recorded and compared between the two groups.</p><p><b>RESULTS</b>There were no significant differences in age, gender, and TNM staging between LADG and ODG(all P>0.05). All the patients in the LADG group underwent gastrectomy and lymph nodes dissection successfully without conversion to open surgery and no operative deaths occurred. The operative time was significantly longer for the LADG group than for the ODG group[(266.1±55.1) min vs. (223.8±26.8) min)]. The patients in the laparoscopic surgery group had less blood loss[(131.9±88.7) ml vs.(342.3±178.7) ml], earlier recovery of bowel activity[(3.18±1.22) d vs.(4.50±1.59) d], and shorter hospitalization time[(9.20±3.39) d vs. (11.35±4.61) d]. No significant differences were found in the total number of retrieved lymph nodes(25.81±12.53 vs. 27.47±10.28). The morbidity of complications was comparable between two groups(6.1% vs. 15.94%). No mortality and recurrence were observed during a follow-up period of 1-19 months.</p><p><b>CONCLUSIONS</b>LADG with D2 lymph node dissection is a safe and feasible procedure with adequate lymphadenectomy for advanced gastric cancer.</p>


Subject(s)
Female , Humans , Male , Middle Aged , Gastrectomy , Methods , Laparoscopy , Laparotomy , Retrospective Studies , Stomach Neoplasms , General Surgery , Treatment Outcome
17.
Chinese Journal of Gastrointestinal Surgery ; (12): 149-151, 2012.
Article in Chinese | WPRIM | ID: wpr-290833

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the safety and feasibility of laparoscopy-assisted combined radical resection for synchronous rectal and gastric cancer in elderly patients.</p><p><b>METHODS</b>Clinical data of two elderly patients undergoing laparoscopy-assisted combined radical resection for synchronous rectal and gastric cancer were analyzed retrospectively.</p><p><b>RESULTS</b>The two cases were 78 and 75 years old respectively. Both were complicated with many medical conditions. One case suffered from stage II cancer in the gastric body and stage IB rectal cancer, and the other suffered from stage IIIA gastric cancer and stage IB rectal cancer. Both cases had received laparoscopy-assisted combined radical resection for synchronous rectal and gastric cancer, with 5 cm of incision. The operative time was 260 and 255 min and the intraoperative bleeding was 60 and 80 ml respectively. No complication occurred intraoperatively. Time to resume oral intake was 4 and 5 days and length of postoperative hospital stay was 13 and 14 days respectively. No postoperative complication occurred. The patients were followed up for 13 and 12 months and no postoperative recurrence or metastasis was noticed.</p><p><b>CONCLUSION</b>Laparoscopy-assisted combined radical resection for elderly synchronous rectal and gastric cancer is safe and feasible when performed by surgeons with plentiful experience in laparoscopic technology, and associated with less injury and faster recovery.</p>


Subject(s)
Aged , Female , Humans , Laparoscopy , Methods , Rectal Neoplasms , General Surgery , Retrospective Studies , Stomach Neoplasms , General Surgery , Treatment Outcome
18.
Journal of Southern Medical University ; (12): 1034-1038, 2011.
Article in Chinese | WPRIM | ID: wpr-235203

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the short-term outcomes of patients receiving orthopedic surgery with posterior pedicle screw fixation for degenerative lumbar scoliosis.</p><p><b>METHODS</b>Between March, 2006 and August, 2009, 36 patients with degenerative lumbar scoliosis (19 males and 17 females) underwent procedures of decompression, bone implantation and pedicle screw fixation. Fifteen patients were also treated by PLIF and 21 cases received posterior-lateral fusion. The JOA scores, Oswestry disability index (ODI), and Cobb angle were recorded before and after the operation, and the surgical complications were also observed.</p><p><b>RESULTS</b>The JOA scores increased significantly by 83.3% after the operation (P<0.05). The procedures resulted in significantly lowered ODI from (67.1∓11.4)% before the operation to (32.1∓10.8)% after the operation (P<0.01). A significant improvement of the coronal Cobb's angle was achieved after the operation (26.7° preoperatively vs 12.3° postoperatively, P<0.01), and the lordosis angle was improved from 10.7° to 36.6° after the operation (P<0.01). All the patients were followed up for 12 to 50 months (mean 38 months), and no implant loosening, displacement or fragmentation, or pseudarthrosis was found at the final follow-up.</p><p><b>CONCLUSION</b>Posterior pedicle screw fixation shows good short-term therapeutic effect in treatment of degenerative lumbar scoliosis. Individualized surgical plans and adequate preoperative evaluation are keys to successful operations.</p>


Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Bone Screws , Decompression, Surgical , Methods , Lumbar Vertebrae , Pathology , Orthopedic Procedures , Methods , Scoliosis , Pathology , General Surgery , Treatment Outcome
19.
Chinese Journal of Surgery ; (12): 134-137, 2010.
Article in Chinese | WPRIM | ID: wpr-254842

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the expression and its significance of retinoic acid receptor-beta (RAR-beta) in colorectal cancer.</p><p><b>METHODS</b>RAR-beta was detected by immunohistochemistry methods and carcino-embryonic antigen (CEA) was tested by chemiluminescence immunoassay methods in normal tissues, paracancerous tissues and colorectal cancer tissues of 60 patients with colorectal cancer treated from January 2006 to January 2007. Above-mentioned data, together with the clinicopathological data of these 60 patients, were analyzed to figure out the expression and its significance of RAR-beta in colorectal cancer.</p><p><b>RESULTS</b>The expression rate of RAR-beta in tumor tissues (48%) was significantly lower than those in both normal tissues (87%) and paracancerous tissues (87%) (P < 0.05). And its expression was also significant lower in patients with lymph node metastasis (32%) and patients with advanced cancer (TNM stage III and IV) (29%) than in those without lymph nodes metastasis (60%) and those with early stage cancer (stage I and II) (69%). There was no significant differences among well, mildly and poorly differentiated cancer tissues. The CEA level rose in 20 patients, and its rising rate was remarkably higher in patients with lymph node metastasis (48%) and in patients with advanced cancer (52%) than those without lymph node metastasis (23%) and in early stage(14%).</p><p><b>CONCLUSIONS</b>The expression of RAR-beta decreases significantly in cancer tissues in patients with colorectal cancer, which may be related to the carcinogenesis of colorectal cancer; and its decreasing degree is correlated negatively with the lymph node metastasis and advanced clinicopathological stage. The expression level of RAR-beta may be a new prognostic indication of patients with colorectal cancer.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Colorectal Neoplasms , Metabolism , Pathology , Receptors, Retinoic Acid , Metabolism
20.
Chinese Journal of Gastrointestinal Surgery ; (12): 77-81, 2009.
Article in Chinese | WPRIM | ID: wpr-326552

ABSTRACT

<p><b>OBJECTIVE</b>To study the difference of gene expression profile among colorectal cancer tissue, pericancerous mucosa and normal mucosa, and to screen associated novel genes in colorectal carcinogenesis by DNA microarray.</p><p><b>METHODS</b>cDNA chip containing approximate 8000 genes was used to detect differentially expressed genes in colorectal cancer tissues, pericancerous mucosa and normal mucosa, and to screen associated novel genes in colorectal carcinogenesis by DNA microarray.</p><p><b>RESULTS</b>As compared with normal mucosa, 769 genes differentially expressed in cancerous tissue were identified, which included 363 up-regulated and 406 down-regulated genes. In pericancerous mucosa 3 cm away from cancerous tissues, 155 genes differentially expressed were identified, of whom 52 genes were up-regulated and 103 were down-regulated. In pericancerous mucosa 5 cm away from cancerous tissues, 230 genes differentially expressed were identified, of whom 46 genes were up-regulated and 184 genes were down-regulated. The genes expressed differentially were associated with several functional types. According to the primary results, the differentially expressed genes with prominent functions included tumor-related genes, genes regulating cell proliferation and apoptosis, transcriptional control genes, and construction and degradation of extracellular matrix-associated genes. The cancerous mucosa was obviously different from the normal mucosa(about 20%, 769/3944). The differences between the normal mucosa and pericancerous mucosa were relatively small (3.9%,5.8%).</p><p><b>CONCLUSIONS</b>Different tissues have their own biological property. Several genes play roles in the development of colorectal carcinogenesis. Genes in adjacent non-cancerous tissues are also expressed differentially, leading to a malignant change.</p>


Subject(s)
Humans , Colorectal Neoplasms , Genetics , Pathology , DNA, Complementary , Genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Oligonucleotide Array Sequence Analysis , Methods
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