Over-expression of P-glycoprotein (Pgp) is associated with the development of multi-drug resistance ( MDR). Pgp has been focused on as the main target in designing chemotherapy strategy. In this article we review some of the latest advancement in designing and evaluation methods of P- glycoprotein inhibitors.

Soft tissue related complications are quite frequent in limb lengthening. Muscle fibers may proliferate or regenerate after stretching injury over 10-20% of their original length. However, the cells which are engaged in this phenomenon are not confirmed yet. We chased the S-phase cells (phase for DNA replication) in the posterior leg muscle during limb lengthening by immunohistochemical technique. We lengthened the tibiae of fifteen New Zealand white rabbits. We divided them into three groups and each group is consisted of five rabbits. In group 1, we lengthened the left tibiae by 10% of their original length, in Group 2, 20%, and in group, 3, 25%, respectively, At the end of lengthening posterior muscles of lengthened left side and of controlled right side were fixed and processed for Immunohistochemical staining which could detect the incorporation of bromodeoxyuridine(BDU). Labelling index(LI:% of positively stained S-phase nuclei) of group 1 was zero. LI of groups for more than 20% lengthening (sum of group 2 and 3) was statistically significant. In conclusion, nuclei around or within the muscle tissue are in S-phase during limb lengthening which means proliferation of the muscle fivers or of the certain cells that abut muscle fibers.
Bromodeoxyuridine ; DNA ; Extremities ; Immunohistochemistry ; Leg ; Muscles ; Rabbits ; Tibia

BACKGROUND:Vascular endothelial growth factor (VEGF) is a crucial factor for regulating bone marrow mesenchymal stem cells in microenvironment, which can promote endothelial differentiation of bone marrow mesenchymal stem cells. But there is no report about VEGF effect on regulating the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. OBJECTIVE:To investigate the regulatory role of VEGF in the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. METHODS:The bone marrow mesenchymal stem cells were isolated and cultured from mouse long bones. cellCounting Kit-8 was used to test the proliferation of bone marrow mesenchymal stem cells cultured with different concentrations of recombinant VEGF proteins. The appropriate concentration of VEGF recombinant protein was selected to test their effects on the osteogenic differentiation of bone marrow mesenchymal stem cells. The mRNA and protein levels of Osterix, Runx2, alkaline phosphatase, osteocalcin and heme oxygenase-1 in bone marrow mesenchymal stem cells under induction of VEGF were detected by molecular biology methods. RESULTS AND CONCLUSION:(1) VEGF promoted the proliferation of bone marrow mesenchymal stem cells dose-dependently, and 100μg/L was the optimum concentration. (2) VEGF promoted the expression of Osterix, Runx2, alkaline phosphatase and osteocalcin in bone marrow mesenchymal stem cells under osteogenic induction. Similar results were obtained by alizarin red staining and quantification of numbers of calcium nodules. (3) VEGF induced the expression of heme oxygenase-1 in bone marrow mesenchymal stem cells at mRNA and protein levels. These findings indicate that VEGF can induce the expression of heme oxygenase-1 i in bone marrow mesenchymal stem cells, and promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.

Objective To investigate the effect ot ionizing radiation (IR) on the expressions of HMGB1 in the radiation-sensitive and radiation-resistant human cervical cancer cells and to analysis the role of HMGB1 in the regulation of radiosensitivity.Methods Human cervical cancer cells HeLa and its radioresistant strain HeLaR cells were irradiated with different doses of X-rays.The cells were collected at different time points after irradiation.The expressions of protein and mRNA of HMGB1 were detected by Western blot and real-time quantitative PCR.Results At the protein level,the expression of HMGB1 in HeLaR cells was significantly reduced at 6-36 h after 2,5 and 10 Gy X-ray irradiation (t =3.574-9.754,P ＜0.05),and then it was recovered to the control level at 48 h after IR.On the contrary,the expression of HMGB1 in HeLa cells was significantly increased at 6,12,48 h after 2 Gy IR (t =3.945-4.864,P＜0.05),at 6,36,48hafter5 GyIR (t=-2.875-3.295,P＜0.05),and at 36,48 h after 10 Gy IR (t =-4.480,-4.517,P ＜ 0.05).At mRNA level,the trend of HMGB1 expression alteration was consistent with that of protein expression.Conclusions The changes of HMGB1 expression can be differently induced by X-rays in the human cervical cancer radiation-sensitivity cells and radiation-resistant cells.HMGB1 may be involved in the radioresistance of human cervical cancer.

OBJECTIVETo investigate the relationship between hormone sensitive lipase (HSL) gene polymorphism and aerobic endurance.

METHODSThe (CA)n repeats polymorphism genotypes in HSL intro 6 of 123 outstanding long distance runners and 127 controls of Han nationality in northern China were analyzed by PCR and Fluorescence labeled STR-genescan. Repeat polymorphisms were grouped according to segmentation point and alleles were divided into long or short chains. Chi-square test was used to analyze the frequency difference of allelic and genotypic between athlete and control groups.

RESULTS(CA) n repeats polymorphism in HSL gene was total of 9 different repeat number of alleles, which composed of 25 different genotypes. The chi-square test result showed that when compared short and long chain alleles split by 4, there was a significant difference (P <0.05) of genotype distribution in 5/10 km group compared with control. Compared the rest groups with control, there was no significant difference.

CONCLUSIONCompared short and long chain alleles split by 4, the LL genotype of (CA)n of HSL was associated with aerobic endurance and it might be a molecular marker of elite 5/10 km long distance runners.

Alleles ; China ; Ethnic Groups ; Genotype ; Humans ; Physical Endurance ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Sterol Esterase ; genetics

The purity of 4,4′-dimethoxy-5,6,5′,6′-bis (methylenedioxy)-2′-morpholine methylenebiphenyl-2-methyl formate methanesulfonate (IMH), a new drug for fatty liver treatment, was determined through differential scanning calorimetry (DSC). Analysis of two-factor non repeatability method was performed in the investigation the effects of two factors (heating rate and sample weight) on purity determination. The DSC experimental parameters were optimized as follows: heating rate was 10 ℃·min^-1, temperature range was 150-300 ℃, sample weight was 2.0-4.1 mg, and N₂ flow rate was 80 mL·min^-1. The linear correlation coefficient (r) of this DSC method was 0.999 8. The RSD value (n = 6) of precision was 0.03%. The standard value and uncertainty of the purity results of the multiple batches of IMH drugs were (99.74 ± 0.29)%, (99.91 ± 0.28)%, (99.90 ± 0.28)%, and (99.81 ± 0.28)% with inclusion factor (K) of 2 and confidence probability (P) of 0.95. The results were basically consistent with the results of the mass balance method. The DSC mehod is a simple, rapid and accurate method, and provides a new reference method for determining the purity of IMH drugs, improves the accuracy and reliability of purity determination.

Objective To determine the median effective concentration (EC50) of amitriptyline for intravenous regional anesthesia (IVRA) in rats.Methods Ninety healthy male SD rata weighing 190-240 g were randomly divided into 3 groups (n=30 each) : amitripryline group,bupivncaine group and lidocaine group.The rat's tail was divided into 3 epual parts: the proximal,middle and distal part.A 24 gauge needle was inserted into vena caudalis in the distal part.Esmarch bandage was applied around the tail from distal to proximal to expel blood from the taft and was removed after a tourniquet was applied between the proximal and middle part of the tail to occlude artery.0.5 ml of amitriptyline,bupivncaine or lidocaine was injected into the taft vein immediately after the application of the tourniquet.Ten minutes after drug administration the tourniquet was released.The ECho was determined by the up-and-down sequence method.The initial concentration of amitriptyline was 0.05%,the consecutive concentration-ratio was 1.4i4; the initial concentration of bupivacaine was 0.03%,the consecutive concoatration-ratio was 1.667 and the initial concentration of lidncaine was 0.08%,the consecutive concentrationratio was 1.250.EC50 and 95% confidence interval were calculated.Tail-flick latency (TFL) was assessed at 1 h before (baseline) and at 3 min and 2 d after drug administration.Central nervous system toxicity (seizure,convulsion,death) and local tissue damage to the tail were also recorded.Results The EC50 for IVRA was 0.111% (95% CI,0.092%-0.133%) in amitripthline group; 0.058% (95% CI,0.048%-0.078%) in bupivacaine group and 0.129% (95% CI,0.103%-0.160%) in lidocaine group respectively.The EC50 was significantly lower in bupivacaine group than in amitriptyline and lidocaine group.There was no significant difference in EC50 between amitriptyline and lidocaine group.The TFL measured at the proximal part of the tail was not significantly different between different time points in each group.The TFL measured at the middle part at 3 rain after drug adminisuation was significantly increased as compared with the baseline in all 3 groups but was not significantly different between the baseline and that measured at 2 d after drug administration.No CNS toxicity and local tissue damage were found during the experiment in all 3 groups.Conclusion Amitriptyline can produce intravenous regional anesthesia.The potency of amitriptyline is significantly lower than that of bupivncaine but is not significantly different from that of lidocaine.

Objective To discuss imaging classification of blunt traumatic thoracic aortic injury (BTTAI) and weigh guideline value of its imaging classification to surgical options.Methods BTTAI in 12 patients were divided into three types in accordance with outline of aortic injury revealed by CT imaging,i.e.,type A of normal outline of aortic blood vessel but free endothelium in aortic cavity,type B of abnormal aortic outline and contrast extravasation to aortic lumen exterior but only confining to mediastina,and type C of abnormal aortic outline and contrast leakage to thoracic cavity.Significance of BTTAI morphological classification was analyzed according to data,such as systemic injury severity score (ISS),local injury sites,surgical approaches and patients' outcome.Results Multiple injuries combined with BTTAI were observed in all patients whose aortic lesion image could be all generalized by above-mentioned classification.BTTAI image showed type A in three patients,type B in seven and type C in two.Pseudoaneurysm was confirmed as the foremost common BTTAI.There were no significant differences in ISS,hypotension morbidity,treatment methods or mortality between each type of BTTAI.Conclusions BTTAI occurs mostly in multiple injuries and thus overall injury severity assessment is not only depended on aortic lesion classification.BTTAI classification in this study reflects injury severity of vessel wall,takes account to location of lesion and adjacent relations (especially length of landing zone) and hence has accurate referential value for surgical decisions.

Objective To investigate feasibility and validity of endovascular aortic repair (EVAR) of traumatic thoracic aortic injuries (TTAI).Methods A retrospective analysis was conducted on data of 13 patients with TTAI.Pathological changes were evaluated by spinal CT angiography (CTA) preoperatively and re-evaluated by digital subtraction angiography (DSA) in EVAR.CTA was performed again to confirm therapeutic effects at postoperative 3,6,12 months and annually thereafter.Results All patients had successful EVAR.Complete or partial cover of left subclavian artery was observed in four patients.Endoleak in angiography shortly after stent delivery was noticed in three patients.However,endoleak disappeared in one patient after short stent placement for twice; endoleak was evidently decreased in one patient after balloon dilation.Follow-up was performed for another patient with slight endoleak.A total of 12 patients were followed up,which showed no complications,such as endoleak,ischemia of left upper extremity,paralysis or stent-graft migration.Conclusion EVR is safe and effective in treatment of TTAI.

Objective To explore the relationship between gastric juice pH and hospital-acquired pneumonia ( HAP) , the gastric bacterial colonization and etiology of HAP in neurologic intensive care unit patients by monitoring gastric juice pH value.Methods From October 2014 to May 2015, consecutive seventy-two tube feeding patients admitted in the Department of Neurology Intensive Care Unit in Xijing Hospital were enrolled in this research.The type and concentration of pathogens from gastric contents were collected, while samples from upper respiratory tract and pharynx were detected dynamically at the same time.Results (1)The group with new onset HAP was higher in gastric juice pH (6.4(5.4,6.4) vs 5.4 (2.5, 6.4), Z=-2.37, P=0.01); (2) The isolation rate of colonized bacteria in gastric cavity was associated with the pH of gastric juice , achieving 60.8% ( 42/69 ) in HAP group; ( 3 ) When the gastric juice pH was >4, the isolation rate of Gram-negative bacilli in gastric cavity obviously increased (63.6%(28/44) vs 35.7%(10/28),χ2 =5.323, P=0.021); (4)The same pathogens were found in stomach-pharynx-upper respiratory tract in 7 cases ( 17.5%) of the total 40 HAP patients.Conclusion Increased gastric juice pH was associated with gastric colonization , especially Gram-negative bacilli , and may lead to a higher incidence of new onset HAP in patients on enteral feeding.