Aromatase Inhibitors ; adverse effects ; Arthralgia ; chemically induced ; therapy ; Humans ; Integrative Medicine

Objective To determine whether ultrasound mediated microbubble destruction could increase naked human wild type p53 plasmid delivery to ovarian cancer in rats by intratumoral injection. Methods Forty rats with ovarian cancer successfully induced by chemical intoxicant were divided into four groups.The wild type p53 gene was cloned into a high expressing efficiency eukaryotic plasmid pcDNA 3.1+ and the mixture of naked human wild type p53 plasmid was carefully injected directly into the center of ovarian neoplasms with or without echo contrast agent, and it was exposed to ultrasound for twenty minutes once a week.Two months after p53 gene transfection, semiquantitative RT-PCR was used to detect wild type p53 mRNA expression and western blot was to evaluate p53 protein expression level. Results Recombinated eukaryotic expression plasmid DNA encoding pcDNA 3.1+ /p53 was successfully constructed and confirmed by sequence analyzing and endonuclease cutting. The ovarian cancer model of rat was obtained by exposure to intoxicant. Expression of human wild type p53 mRNA was significantly higher in rats transfected with wild type p53 plasmid by means of ultrasound and contrast agent than others(P

Objective To investigate the protective effect of allicin on intestinal mucosal barrier of septic rats so as to explore the possible mechanism.Methods Twenty-four male SD rats were randomly (random number) divided into sham,septic model and allicin treatment group.Septic model was established by cecal ligation and puncture (CLP) in rats.Rats in the treatment group were administered with allicin (30 mg/kg,ip)at 6 h and 12 h after modeling,while those in the model and sham groups were treated with equal amount of saline instead.Rats were sacrificed at 24 h and the serum D-lactic acid,diamine oxidase (DAO) and fluorescence isothiocyanate-dextran (FITC-Dextran,FD-40) were determined to evaluate the intestinal mucosal barrier function.The levels of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),malondialdehyde (MDA),and the activity of superoxide dismutase (SOD) in intestinal tissue were measured.Histopathological changes of intestinal mucosa injury were assessed by Hematoxylin-eosin staining.Results Compared with the sham group,levels of serum D-lactic acid,DAO and FD-40 increased significantly in the CLP group (D-lactic acid:599.4±101.1 vs.149.2±20.63 nmoL/mL,t=11.84,P＜0.01;DAO:302.1 ±64.5 vs.76.57±14.76 ng/mL,t=9.433,P＜0.01;FD-40:6664.0±1437.0vs.1446.0±205.0 ng/mL,t =9.704,P ＜0.01);intestinal morphology damage occurred in the CLP group;intestinal levels of TNF-α,IL-6 and MDA increased greatly (TNF-αt:186.35 ±20.43 vs.58.76 ±8.94 pg/mL,t=17.23,P＜0.01;IL-6:763.25±85.23vs.125.36±14.37 pg/mL,t=22.54,P＜0.01;MDA:29.36±3.27vs.7.24±0.85 nmol/mg prot,t=16.61,P＜0.01),while SOD activity reduced (35.75±6.53 vs.73.26 ±8.35 U/rmg prot,t =10.57,P ＜0.01) in the CLP group.Allicin treatment greatly inhibited the increase of D-lactic acid,DAO and FD-40 levels in rat plasma caused by CLP (D-lactic acid:330.1 ±81.77 vs.599.4±101.1 nmol/mL,t=7.086,P＜0.01;DAO:171.8±49.70vs.302.1±64.56ng/mL,t=5.45,P＜0.01;FD-40:3349.0±1167.0 vs.6664.0±1437.0 ng/mL,t=6.165,P＜0.01);intestinal morphology damage was improved in the allicin treatment group;allicin treatment greatly inhibited the intestinal levels of TNF-o,IL-6 and MDA and preserved the intestinal SOD activity compared with the CLP group (TNF-α:95.37 ±12.68 vs.186.35 ±20.43 pg/mL,t =12.29,P＜0.01;IL-6:354.27±46.27vs.763.25±85.23pg/mL,t=14.45,P＜0.01;MDA:16.27±3.14vs.29.36±3.27 nmol/mgprot,t=9.831,P＜0.01;SOD:55.35 ±6.23vs.35.75±6.53 U/mgprot,t=5.522,P ＜0.01).Conclusions Allicin could inhibit local inflammation and oxidative stress in the intestine and exerts protective effect on intestinal mucosal barrier of septic rats.

OBJECTIVE:To observe the clinical efficacy of acupoint application of antiemetic cream in the treatment of che-motherapy-induced nausea and vomiting. METHODS:90 cases of non-small cell lung cancer(NSCLC)(stage Ⅱ to Ⅲ)treated by chemotherapy(taxol+cisplatin)were randomly divided into antiemetic cream group,Weifuan group and control group,with 30 cas-es in each groupby drawing lots. Control group was given intravenous injection of ondansetron hydrochloride 8 mg 30 min before chemotherapy;antiemetic cream group was additionally given acupoint application of antiemetic cream 30 min before medication on first-forth day on the basis of control group;Weifuan group was additionally given acupoint injection of metoclopramide(brand name:Weifuan) 30 min before medication on first-forth day on the basis of control group. The clinical efficacy of 3 groups were observed during and 3 days after chemotherapy. RESULTS:After chemotherapy,the total control rates of antiemetic cream group (93.33%)and Weifuan group(90.00%)were apparently higher than the control group(66.67%),with statistical significance(P<0.01 or P<0.05);The total effective rates of TCM syndrome in antiemetic cream group (90.00%) and Weifuan group(83.33%) were apparently higher than in control group(60.00%),with statistical significance(P<0.01 or P<0.05). Therapeutic efficacy of antiemetic cream group was similar to Weifuan group,without any statistical significance(P>0.05). However,8 patients had obvi-ously pain at the injection site in Weifuan group,but tolerated to the drugs basically. CONCLUSIONS:The acupoint application of antiemetic cream combined with intravenous injection of ondansetron is effective and easy to operate in the treatment of nausea and vomiting induced by chemotherapy for stage Ⅱ to Ⅲ of NSCLC without pain,scar and sequela,and easy to be accepted by patients.

Objective To evaluate the value of endoscopic profile in an adult population with typical heartburn. Methods Clinical and endoscopic data were collected from 5042 consecutive outpatients who underwent routine upper endoscopy without any alarm features between March 2006 and Feb. 2007. Results Three hundred and thirteen (6.2%) patients were diagnosed as having typical heartburn. Of these, erosive esophagitis (EE) was found in 99 (31.6%) patients, Barrett's esophagus (BE) in 10 (3. 2%) patients, peptic ulcer disease (PUD) in 21 (6. 7%) patients and carcinoma in three (0.9 %) patients (1 with esophageal carcinoma and 2 with gastric adenocarcinoma).Multivariate analysis revealed that age＞50, male, overweight and alcohol use were independent risk factors for positive endoscopy findings (P＜0.05) and EE (P＜0.05) in heartburn patients. Male and Helicobacter pylori infection were independent risk factors for PUD (P＜ 0.05). Conclusions In China, patients with typical heartburn but without alarm features, early endoscopic examination may be helpful in avoiding missing diagnosis of tumor.

Objective To investigate celecoxib self-microemulsifying drug delivery system (CXB-SMEDDS) that was developed to increase the dissolution rate and oral bioavailability of celecoxib.Methods The formulation of CXB-SMEDDS was optimized by pseudo-ternary phase diagrams analysis.The appearance, morphology, particle size distribution and in vitro drug release behavior of CXB-SMEDDS were investigated after diluted by water.The bioavailability of CXB-SMEDDS was determined by oral administration to rats compared with CXB suspension.Results An optimized formulation was selected: Medium chain triglycerides as oil phase, Tween 20 as surfactant, Transcutol HP as cosurfactant.The ratio of oil phase, surfactant and cosurfactant was 2∶9∶9.Upon mixing with water, CXB-SMEDDS formed a clear and transparent microemulsion solution with homogeneous small spherical under transmission electron microscopy.For particle size of CXB-SMEDDS was found to be (57.6±14.2) nm.The in vitro dissolution test indicated a significant improvement in release characteristics of CXB.The AUC of CXB-SMEDDS and CXB suspension were (5.54±0.94) and (3.32±0.59) mg·L-1·h, respectively.The relative bioavailability was 166.9%.Conclusion The SMEDDS can significantly increase celecoxib dissolution in vitro and bioavailability in vivo.

Oligosaccharides are one of the essential physiological constituents of glycoproteins and glycolipids on mammalian cell surfaces and microbial metabolites. They have considerable potential as therapeutics but are only now slowly assuming this important role. One of the reasons for their slow development has been the considerable difficulty in synthesizing oligosaccharides on the scale necessary for their clinical evaluation. Classical chemical and enzymatic methods both have limitations in synthesizing large-scale oligosaccharides. In recent years, the rapid progress on molecular biotechnology has promoted the development of retaining glycosidases in oligosaccharides synthesis, which led to the production of a novel class of enzymatic activities termed the glycosynthases. These new enzymes are retaining glycosidase mutants in which the catalytic nucleophile has been converted to a non-nucleophilic residue,synthesizing oligosaccharides in high yields ( the highest yields reach 99%) without any hydrolysis. Furthermore thioglycoligases and thioglycosynthases have been developed subsequently in the past three years. Glycosynthases can be screened in high-throughput assay by the two-plasmid system and the yeast three-hybid system respectively. Their activity can be significantly enhanced by substituting alternative residues for nucleophile, additional random mutations and optimizing reaction conditions. Their regioselectivity can be modified through changes in receptors.

Arachidonic acid is an essential fatty acid in human nutrition and a biogenetic precursor of the biologically active prostaglandins and leukotrienes. ?~5 desaturase catalyzes the ?~5 dehydrogenation of di-homo-?-linolenic acid to form arachidonic acid in biosynthetic pathway of arachidonic acid. Using real time PCR technology,the transcriptional expression levels of gene encoding ?5 desaturase in three Mortierella alpina strains M10,M6 and M23,and in different growth phase of high arachidonic acid yielding strain M6,were determined. Results showed that there was a distinct corelationship between mRNA transcript level of ?~5 desaturase gene and biosynthesis of arachidonic acid. Results indicated that ?~5 desaturase plays an important role in arachidonic acid biosynthesis.

Objective To investigate the effects of antihypertension and reversing left ventricular hypertro- phy by carvedilol or bisoprolol in patients with mild to moderate essential hypertension.Methods 40 cases of mild to moderate essential hypertension patients were selected for this random single-blind,paralleling controlled clinical study.Results Patients were randomized to take 12.5～25mg carvedilol tablet orlce daily or bisoprolol 2.5～5mg once daily if DBP was still in the range of 12.0～14.6kPa(90～110mmHg)after 2 weeks' placebo baseline. Carvedilol group included 20 cases,bisoprolol group included 20 cases,and the course was 24 weeks.Blood pressure and heart rate were measured and symptoms and signs were recorded.At the end of placebo and in 24 weeks heart ultrasound,blood routine,serum glucose,blood lipid,hepatic function and renal function were examined.SBP,DBP and heart rate of patients in two groups decreased obviously.There were significant differences between the two groups.Ventricular hypertrophy of carvedilol group improved than that in pretherapy.There were significant differ- ences between the two groups.Conclusion Carvedilol was well-tolerated with less side effects such as mild headache,tiredness,dizziness,slightly elevating of serum glucose.Carvedilol could well treat the mild moderate essen- tial hypertension effectively and safely by 12.5～25mg once daily.

Objective To investigate the expression of integrin β3 and osteopontin(OPN) in eutopic and ectopic endometrium of adenomyosis. Methods From January 2007 to July 2008, the endometrium specimens were collected from 43 patients with adenomyosis undergoing hysterectomy in Peking University First Hospital. Eutopic endometrium were 11 in proliferative phase and 32 in secretory phase (18 cases in mid-secretory phase) were collected. Ectopic endometriums were also collected. In the mean time, it was chosen 41 cases with pure subserous uterine myoma or cervical intraepithelial neoplasia (CIN) Ⅱ-Ⅲ treated by hysterectomy as controls including 12 endometrium in proliferative phase and 29 endometrium in secretory phase (19 cases in mid-secretory phase). The expression of Integrin β3 subunit and OPN in the endometrium were assessed by immunohistochemical staining and quantitative real-time polymerase chain reaction. Results (1)Immunohistochemical staining showed that positive staining of integrin β3 and OPN were present predominantly in eutopic and ectopic endometrial glandular epithelium. There was significant different protein expression of integrin β3 and OPN, which were 1.6±0.8 and 1.7±0.7 in eutopic endometrium,1.7±0.7 and 1.8±0.9 in ectopic endometrium,2.1±0.9 and 2.0±0.9 in control endometrium (P<0.05). The protein expression of integrin β3 and OPN in eutopic endometrium of adenomyosis in the proliferative phase(0.8±0.4 and 0.7±0.3) were remarkably lower than those of the secretory phase(1.8±0.8 and 1.9±0.8,P<0.01). The protein expression of integrin β3 and OPN in the endometrium of controls in the proliferative phase(1.0±0.4 and 1.0±0.4) were significantly lower than those of the secretory phase(2.5±0.7 and 2.5±0.7)(P=0.000). In the mid-secretory phase, the protein expression of integrin β3(2.0±0.9) and OPN (2.1±0.8)in eutopic endometrium of adenomyosis were significantly lower than that of control endometrium(2.7±0.5 and 2.7±0.7)(P<0.01). (2)The mRNA expression level of integrin β and OPN in eutopic and ectopic endometrium were assessed by quantitative real-time PCR(result was shown by median index). It was observed that integrin β3 mRNA and OPN mRNA were significantly lower in the eutopic endometrium of adenomyosis (4.69 and 4.23), when compared with ectopic endometrium(7.96 and 14.84)and controls (13.47 and 17.40) (P<0.05). Eutopic endometrium had higher mRNA expression of integrin β and OPN mRNA in the secretory phase (5.54 and 11.40) than that in the proliferative phase(2.69 and 3.30) (P<0.01).The mRNA expression level of integrin β and OPN of control endometrium in the proliferative phase (3.12 and 4.75)were significantly lower than that in the secretory phase(19.94 and 21.00, P=0.000). The mRNA expression of integrin β and OPN were 10.10 and 14.34 in the mid-secretory phase, which were significantly lower than 21.50 and 24.18 in control endometrium(P<0.05). Conclusions High expression of integrin β3 and OPN in ectopic endometrium of adenomyosis may cause endometriotic lesions; abnormal expression of integrin β3 and OPN in the endometrium of adenomyosis during the implantation window may contribute to infertility in some patients.