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<p><b>OBJECTIVE</b>To synthesize compounds based on imidazo-fused heterocycles and evaluate their anti-tumor activity against breast cancer.</p><p><b>METHODS</b>The compounds 1a-1e, 2a and 2b were synthesized by aerobic copper-catalyzed halocyclization of methyl N-heteroaromatics with aliphatic amines; 3a and 3b were generated by sonogashira reaction and Suzuki reaction, respectively; the compounds 4a-4c were obtained by Buchwald-Hartwig reaction of the corresponding amines and 1e. The effects of these compounds against breast cancer cells and their nephrotoxicity were determined using MTT assay. Annexin VFITC/PI apoptosis detection kit was used to assess the apoptosis-inducing effects of these compounds in breast cancer cells. With normal saline as the control, the safety and anti-tumor activity of the compound 2a (daily dose of 10 mg/kg for 14 days) was tested in a mouse model bearing human breast cancer xenografts.</p><p><b>RESULTS</b>The compounds 2a, 4a, 4b and 4c all showed obvious anti-tumor activities. Among these compounds, 2a showed the most potent anti-tumor effect against breast cancer cells with an IC of 9.77 ± 2.32 μmol/L, similar to that of cisplatin (IC=8.96 ± 2.35 μmol/L); 2a also showed a slightly lower nephrotoxicity than cisplatin, and their CC was 10.79±0.87 μmol/L and 8.45±0.68 μmol/L, respectively. 2a obviously promoted apoptosis of breast cancer cells and caused a moderate suppression of the breast cancer growth in the tumor-bearing mouse models without producing serious adverse effects.</p><p><b>CONCLUSIONS</b>Four compounds synthesized based on imidazo-fused heterocycles have anti-tumor activities against breast cancer. The compound 2a is capable of dose-dependently promoting apoptosis of breast cancer cells and has a good safety and a moderate efficacy for suppressing tumor growth in mouse models bearing human breast cancer xenografts.</p>
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<p><b>OBJECTIVE</b>To observe the clinical efficacy of auricular point sticking on prevention and treatment of gastrointestinal complications after gynecological laparoscopic operation of general anesthesia, and to explore whether it is achieved by regulating the secretion of plasma motilin (MTL).</p><p><b>METHODS</b>Sixty patients who received selective gynecological laparoscopy under general anesthesia were randomly assigned into an observation group and a control group, 30 patients in each one. The patients in the observation group were treated with auricular point sticking at each morning and night, 30 min before anesthesia, revival after surgery and 24 h after surgery. The adhesive fabric with vaccaria seeds was pressed at shenmen (TF), wei (CO), benmen (CO), jiaogan (AH) and pizhixia (AT) for 3 to 5 min until the sensation of sourness, distension and numb appeared. The treatment was given for one week. The patients in the control group were treated only with similar adhesive fabric at auricular points at identical time points; each auricular point was pressed for 3 to 5 min. The anus exhaust time, defecating time and borborygmus were recorded; the level of plasma MTL was tested 30 min before anesthesia, 24 h after o-peration and 48 h after operation; the occurrence of nausea and vomiting from the end of operation to the end of treatment were also recorded.</p><p><b>RESULTS</b>Compared with the control group, the occurrence of nausea after operation was reduced in the observation group (<0.05), and the anus exhaust time and defecating time were shortened (both<0.05), and the recovery of borborygmus was improved (<0.05). The levels of MTL 24 h and 48 h after surgery were higher than those before operation in the two groups (all<0.05); The levels of MTL 24 h and 48 h after surgery in the observation group were significantly lower than those in the control group (both<0.05).</p><p><b>CONCLUSIONS</b>The assist of auricular point sticking could reduce the occurrence of nausea-vomiting and accelerate the recovery of gastrointestinal function in gynecological laparoscopic operation under general anesthesia, which is likely to be related with the inhibition on excess secretion of MTL.</p>
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Objective To evaluate the effect of ORM1 genetic polymorphism on the time-course of muscle relaxation induced by rocuronium.Methods Seventy American Society of Anesthesiologists physical status [or Ⅱ patients,aged 25-55 yr,scheduled for elective gynecological laparoscopic surgery,with body mass index of 20-25 kg/m2,were enrolled in this study.Anesthesia was induced with iv midazolam and fentanyl and target-controlled infusion of propofol.After the patients lost consciousness,neuromuscular block was assessed with TOF Watch-SX using single stimulation of the ulnar nerve.When the maximal twitch depression was achieved,tracheal intubation was facilitated with rocuronium 0.6 mg/kg.The patients were mechanically ventilated.End-tidal carbon dioxide partial pressure was maintained at 35-45 mmHg.The onset time,nonresponse time,clinical duration,75％ recovery time and recovery index of rocuronium were recorded.Peripheral venous blood samples were collected before surgery for determination of concentrations of plasma alpha1 acid glycoprotein,C-reactive protein (by enzyme-linked immunosorbent assay)and albumin (by biochemical method).ORM1 genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism.The patients were divided into 3 groups according to the ORM1 genotypes:wild homozygote (ORM1*F1/*F1) group (AA group),mutation heterozygote (ORM1'F1/*S)group (AG group) and mutation homozygote (ORM1*S/*S) group (GG group).Results There were 40 cases in group AA,25 cases in group AG,and 5 cases in group GG.There were no significant differences in plasma alphal acid glycoprotein,albumin and C-reactive protein concentrations between the three groups (P＞0.05).Compared with group AA,the clinical duration,75％ recovery time and recovery index of rocuronium were significantly prolonged (P＜0.05),and no significant change was found in the onset time and nonresponse time in AG and GG groups (P＞0.05).Conclusion ORM1 genetic polymorphism is one of the genetic factors which affect the time-course of muscle relaxation induced by rocuronium.
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ObjectiveTo investigate the effect of SalB on bone marrow-derived mesenchymal stem cells (BMSCs) apoptosis induced by hypoxia and serum deprivation (hypoxia/SD) in the vitro. Methods BMSCs were cultured in the vitro and randomly divided into control group, hypoxia/SD group and SalB group.SalB group was composed by four groups and were pretreated by complete medium with 0.1、 1、 10、 100 mg/L SalB for 1 hour. And after that they were washed with phosphate buffer for 2 times, added by IMDM with 0.1、1、 10、 100 mg/L SalB and cultured with hypoxia/SD group together in the same condition of hypoxia/SD for 6hours. The control group was cultured for 6 hours in the condition of aerobic and enough serum. Apoptosis was detected by Hoechst33342 staining with inverted phase contrast, fluorescence microscope and Annexin V/PI dual-color flow cytometry. Results Significant apoptosis of BMSCs was induced by hypoxia/SD in the vitro.The early apoptosis of BMSCs induced by hypoxia/SD was significantly decreased by SalB of 0.1、 1、 10 mg/L(P＜0.05) . Conclusion0.1、 1、 10 mg/L SalB can decrease the early apoptosis of BMSCs induced by hypoxia/SD.
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Objective To observe the results of multifocal visual evoked potential (mfVEP) examination in patients with anterior ischemic optic neuropathy (AION) before and ater treatment,and to probe its clinical significance.Methods A total of 90 patients (90 eyes) with AION were examined by mfVEP;the second-order reaction of mfVEP was analyzed.The reaction was divided into upper and lower hemi-field of visual field,or 1 / 4 quadrant visual field (superior nasal,inferior nasal,superior temporal,and inferior temporal).The sum of waves of each response was analyzed and the results in various regions were compared.The features of wave configuration was compared between the AION eyes and the contralateral eye,and between the AION eyes before and after treatment.Results The amplitude and latency of P-wave of mfVEP was 0.198±0.033 and 100.197±7.354 respectively in AION eyes before treatment,and was 0.271±0.024 and 98.567±6.794 in the contralateral eyes;the difference was significant (t=16.556,18.330;P＜0.01).The amplitude and latency of P-wave of mfVEP was 0.229±0.016 and 100.104±10.603 respectively in AION eyes after treatment,which differed much from that before the treatment (t=13.649,8.858;P＜0.01) and also from that of the contralateral eyes (t=13.649,8.858;P＜0.01).Conclusions The amplitude and latency of P-wave of mfVEP may accurately reflect the recovery of local optic nerve damage in AION eyes before and after treatment with good repeatability.AION can be used as a new method for AION diagnosis and detection of the prognosis.
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Objective To evaluation the efficacy of ketamine on the expression of adhension molecular CR3and intracellular cAMP, cGMP in neutrephils in patients associated with cardiopulmonary bypass (CPB), as well as the cardiovascular function of the CPB patients. Method Sixty patients operated on with prosthetic valve replace-rnent under CPB were randomly divided into 4 groups: placebo, ketamine 0.1 mg/kg ( ketamine Ⅰ) ,ketamine 0.5 mg/kg ( ketamine Ⅱ) ,ketamine 1 mg/kg( ketamine Ⅲ). Each group included 15 eases. Venous blood sam-pies were obtained during anesthesia induction (T1), 10 min before CPB (T2), end of CPB (T3) and 24 hoursafter operation (T4). The expression of CR3 was measured by Flow cytometry and the concentration of cAMP/cGMP by HPLC. Results Ketamine with various dosages decreased the expression of CR3 at the T3 and T4 inpatients of ketamine groups compared with patients of placebo group (P<0.05). The dosages of ketamine Ⅱgroup and ketamine Ⅲ group had more significant effect than that of ketamine Ⅰ group. The dosages of ketamineⅡ and ketamine Ⅲ group increased the intracellular cAMP at the T3 and T4 compared with ketamine Ⅰ groupand placebo (p<0.05), respectively. However,cGMP was lower in ketamine Ⅱ and ketamine Ⅲ group thanthat in ketamine Ⅰ group and placebo (P<0.05) at the T3.Morever,the mean arterial blood pressure was higherin ketamine Ⅱ and ketamine Ⅲ group at T4. Only the patients of ketamine Ⅲ group required less inotropic drugsafter operation. Conclusions Ketamine can reduce the expression of adhhension molecular CB3 and intracellularcAMP, cGMP in neutrophils from patients associated with CPB.
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Objective To observe the effect of MAC of the isoflurane at the general combined with epidural anesthesia with lidocaine and dicaine.Methods 78 cases of the cholecystectomy patients randomly double-blindly divided Ⅳ groups. General combined with epidural anesthesia were performed at the Ⅰ、Ⅱ、 Ⅲ groups. And general anesthesia were performed at the contronal group. The MAC of the isoflurane are checked with up-and-down method with electronic stimulation at left on C5 leveral. Results The MAC of the three observed groups of the general combined with epidural anaesthesia were 0.67?0.097%、0.68?0.084%、0.61?0.103 % differently. There is no siginificant difference.But the MAC of the general contronl group is 1.15?0.088%.There are siginificant difference with the three observed groups,The MAC of the isoflurane can be reduced with general combined with epidural anesthesia. Coinclousions The MAC the isoflurane can be reduced with general combined with epidural anaesthsia significantly compared with singal general anesthesia. And there are no significant different in the three observed groups.It is the pulsing action with lidocaine combined with dicaine at epidural anesthesia. The mechanism of anaesthesia with lidocaine or dicaine supposed to be the same.
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Objective To evaluate the clinical features, diagnosis, and outcome of the treatment of cytomegalovirus (CMV) retinitis, and the relationship between CMV retinitis and acquired immunodeficiency syndrome (AIDS). Methods A total of 95 eyes of 56 patients with cytomegalovirus retinitis and AIDS were studied. The fundus feature, visual acuity and CD4 + T lymphocyte counts were analyzed and the follow up periods ranged from 2 weeks to 18 months. Results Before the definitive diagnosis of CMV retinitis, the courses of AIDS were 4 to 26 months in all patients. In the initial examination, the granular form of CMV retinal lesion was noted in 55 eyes (57%) in which retinal lesion of 46 eyes was peripheral. The fulminant form of CMV retinitis of 25 eyes (26%) was found in the posterior pole and consisted of densely opaque retinal lesions with blotchy hemorrhage and vasculitis. The overlap between these two presentations was noted in 15 eyes. Papillitis was observed in 7 eyes of CMV retinitis in this series of patients. The visual acuity ranged from finger counting to 0.5. The patients with extensive CMV retinitis or CMV retinitis in the posterior pole got poorer vision. The CD4 + T lymphocyte counts of 30 patients was 0 30 (mean, 15?9/?l), and the survival time ranged from 2 weeks to 18 months (mean, 6.4?3.3 months). The vision was improved and CD4 + T lymphocyte counts was significantly higher in the group treated with ganciclovir, and progression of CMV retinitis occured and the vision decreased in the non treated group. Conclusion CMV retinitis is the most common intraocular complication in patients with AIDS. Diagnosis of CMV retinitis is based on the characteristic of necrotizing retinitis which was typically associated with retinal hemorrhage and vasculitis. Ganciclovir is effective for the treatment of CMV retinitis.