Colorectal cancer(CRC)ranks the third in incidence and mortality rate among human tumors. Tumor relapse,me?tastasis and drug resistance remain the main obstacle to the success of CRC treatments. Compared to traditional chemotherapy ,target therapy seems to treat tumors in more precise and rational fashion with good response and often less toxic side-effect. Although target agents provide hope for more effective therapy,recent clinical studies have shown only modest benefit from target therapy similar to tra?ditional chemotherapy. Primary and secondary resistance to target agents is still observed and contributes to CRC treatment failure. The review summarizes research progress in the mechanism of drug resistance to target therapy in CRC treatment.

Objective To study the characteristic of salvianolic acid(SA) binding to bovine serum albumin(BSA) and the structure-performance relationship.Methods The interactions between BSA and four natural SA(SAⅠ,rosmaric acid;SAⅡ,lithosperic acid;SAⅢ,salvianolic acid A;and SAⅣ,salvianolic acid B) were investigated by fluorescence and ultraviolet spectroscopy.Results The intrinsic fluorescence of BSA was quenched by SA via forming SA-BSA complexes and non-radiation energy transfer.The parameters of SA-BSA binding process,such as the static apparent association constant KA,the number of binding site n,the efficiency of energy transfer E,the spatial distance r were obtained,and the thermodynamic constants ?G,?H,and ?S were calculated.Conclusion The results indicate that SAⅢ bounds to BSA mainly through a hydrophobic force and the other three SA-BSA interactions are mainly driven by hydrogen bond and Van der Waals' force.Y,a comprehensive binding parameter constructing from the equation Y=lg (KA?E?n/r),could be used to reflect the interaction extent of SA-BSA system.The Y value changes with the number of free phenolic hydroxyl and molecule volume and decreases in the order of SAⅢ→SAⅣ→SAⅡ→SAⅠ.The results from correlation analysis indicate that it could be possible to estimate SA-BSA binding extent from hydrophobic parameter clogP and topo-polar surface area per unit of molecular weight tPSA/Mr of SA molecule.

OBJECTIVETo explore the clinical application of mandibular-driven simultaneous maxillo-mandihular distraction to correct hemifacial microsomia with rapid prototyping technology.

METHODSThe patient' s skull resin model was manufactured with rapid prototyping technology. The osteotomy was designed on skull resin model. According to the preoperative design, the patients underwent Le Fort I osteotomy and mandibular ramus osteotomy. The internal mandible distractor was embedded onto the osteotomy position. The occlusal titanium pin was implanted. Distraction were carried out by mandibular-driven simultaneous maxillo-mandihular distraction 5 days after operation.

RESULTSThe distraction in five patients was complete as designed. No infection and dysosteogenesis happened. The longest distance of distraction was 28 mm, and the shortest distance was 16 mm. The facial asymmetry deformity was significantly improved at the end of distraction. The ocelusal plane of patients obviously improved.

CONCLUSIONSRapid prototyping technology is helpful to design precisely osteotomy before operation. Mandibular-driven simultaneous maxillo-mandibular distraction can correct hemifacial microsomia. It is worth to clinical application.

Face ; abnormalities ; surgery ; Facial Asymmetry ; congenital ; surgery ; Goldenhar Syndrome ; surgery ; Humans ; Hyperplasia ; surgery ; Mandible ; surgery ; Maxilla ; surgery ; Osteogenesis, Distraction ; methods ; Osteotomy ; methods ; Osteotomy, Le Fort

OBJECTIVETo investigate the chemical constituents of the aerial roots of Ficus microcarpa.

METHODThe solvent extraction and silica gel and Sephadex LH-20 column chromatography were used to isolate and purify the constituents. The chemical structures were elucidated by physicochemical properties and the analysis of spectroscopic data.

RESULTEight compounds were obtained and identified as (2S, 3S, 4R) -2-[(2'R) -2' - hydroxypentracosanoylamino]- heptadecane -1, 3, 4-triol (1), 12, 20 (30) -ursa-dien-3alpha-ol (2), epifriedelanol (3), alpha-amyrin acetate (4), beta-sitosterol (5), beta-daucosterol (6), hexacosanoic acid (7), heneicosanoic acid (8), respectively.

CONCLUSIONCompound 1 was a new compound and named as microcarpaceramide A. Compound 2 was isolated from the aerial roots of F. microcarpa for the first time.

Ficus ; chemistry ; Magnetic Resonance Spectroscopy ; Organic Chemicals ; analysis ; isolation & purification ; Plant Roots ; chemistry ; Spectrometry, Mass, Electrospray Ionization

BACKGROUNDTo investigate epidemiology and HLA typing of highly exposed to HIV but persistently seronegative subjects (HEPS) in commercial blood donors in China.

METHODSThis was a cohort study for epidemiologic characteristics of highly exposed but persistently seronegative subjects. PCR with sequence-specific primer and PCR-SSP for HLA typing were applied.

RESULTSEight HEPS were identified. Compared HLA typing with seropositive couple, high frequency of HLA-a24, HLA-B40 genotyping was observed.

CONCLUSIONHighly exposed to HIV but persistently seronegative subjects in commercial blood donors in China had high frequency of HLA-A24 and HLA-B40 genotype.

Adolescent ; Adult ; Blood Donors ; China ; epidemiology ; Cohort Studies ; Female ; HIV ; immunology ; HIV Antibodies ; blood ; HIV Infections ; epidemiology ; virology ; HIV Seronegativity ; HLA Antigens ; genetics ; HLA-A Antigens ; genetics ; HLA-A24 Antigen ; Histocompatibility Testing ; methods ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Young Adult

Objective:To study the antisense oligonucleotide mediated inhibition on telomerase activity and cell proliferation of GBC-SD cell.Methods:We design the antisense,sense,and random oligonucleotide with phosphoric acid modification for the hTR(Human Telomerase RNA)template sequence.MTT and PCR methods were used to observe the inhibition on telomerase activity and cell proliferation of GBC-SD cell ,and fibroblast cells were used as control group.Results:PS-ODN can lead to the reduction of cell survival rate of GBC-SD cell,wich dosage dependence.Tne experimental group cell detected by scanning electron appeared apoptotic feature.Conclusion:PS-ODN can inhibit telomerase activity of GBC-SD cell effectively and induce the cell apoptosis.

Since the diccovery of neural stem cells (NSCs) in the embryonic and adult mammalian central nerous system, it provided novel ideas forneurogenesis as the potential of proliferation and differentiation of NSCs. One of the ways to promote the clinical application of neural stem cells (NSCs) is searching effective methods which regulate the proliferation and differentiation.This is also a problem urgently to be solved in medical field. Plenty of earlier studies have shown that traditional chinese medicine can promote the proliferation and differentiation of NSCs by regulating the related signaling pathway in vivo and in vitro. The reports of Chinese and foreign literatures on regulating the proliferation and differentiation of neural stem cells in recent ten years and their target and signaling pathways is analyzed in this review.The traditional chinese medicine regulate proliferation and differentiation of NSCs by the signaling pathways of Notch,PI3K/Akt, Wnt/β- catenin, and GFs. And, those signaling pathways have cross- talk in the regulation progress. Moreover, some traditional Chinese medicine, such as astragalus,has a variety of active ingredients to regulate proliferation and differentiation of NSCs through different signaling pathways. However, to accelerate the clinical application of neural stem cells, the studies aboutthe proliferation and differentiation of NSCs and Chinese medicine should be further deepened, the mechanism of multiple targets and the comprehensive regulation function of traditional Chinese medicine should be clarified.

OBJECTIVE: To evaluate the long-term efficacy and safety of ultrasound-guided percutaneous nephrolithotomy (PCNL) in the treatment of patients with solitary kidney stones. METHODS: The clinical data of 22 patients with solitary kidney stones treated with PCNL in Peking University People's Hospital from September 2008 to June 2014, with the follow-up data of more than 5 years were analyzed retrospectively. Perioperative indicators, postoperative stone free rate (SFR) and incidence of complications were recorded. Ultrasonography was used to evaluate the long-term stones recurrence rate. Serum creatinine and estimated glomerular filtration rate (eGFR) were used to assess the long-term renal function. RESULTS: In this group of 22 patients, the average age was (50.3±11.8) years, with 10 cases of anatomic solitary kidneys, 12 functional solitary kidneys, and the median stone diameter was 1.65 (1.1-3.9) cm. All the patients had multiple stones, including 7 cases of staghorn stones. The median pre-operative serum creatinine was 104.5 (60.0-460.0) μmol/L, and the mean eGFR was (60.3±29.4) mL/min, showing no statistically significant difference compared with that before surgery. The mean operative time was (88.2±42.0) min, and there were 11 cases of single-channel and double-channel PCNL. The median serum creatinine on the first day after surgery was 102.0 (63.0-364.0) μmol/L, and the mean eGFR was (58.0±25.1) mL/min. The mean postoperative hospital stay was (8.7±5.2) days. In this group, 5 patients (22.7%) presented short-term complications, among which 4 patients presented postoperative infection and massive hemorrhage at the same time, which improved after conservative treatment, and 1 patient presented pleural injury and improved after closed thoracic drainage. Two patients (9.1%) developed long-term complications, and ureteral stricture occurred 3 months after operation, which improved after balloon dilatation. The median follow-up time was 6.2 (4.7-11.1) years. The median serum creatinine at the last follow-up was 104.0 (72.4-377.0) μmol/L, and the mean eGFR was (60.1±23.7) mL/min, showing no statistically significant difference compared with that before surgery. Renal function decreased in 6 patients (27.3%). Initial and final SFR were 72.7% and 100%, respectively. During the 6.2-year follow-up, 9 patients (40.9%) experienced recurrence of kidney stone. After stone recurrence, 13 lithotomy surgeries were performed, and the SFR by the latest follow-up was 63.6%. CONCLUSION This study had the longest follow-up time for patients with solitary kidney stones after PCNL reported at home and abroad. Ultrasound-guided standard PCNL was safe and effective in the treatment of solitary kidney stones. Long-term follow-up results showed that the recurrence rate of kidney stones was still high, but the long-term renal function was stable after operation, and some patients showed mild renal function decline.
Adult ; Humans ; Kidney Calculi ; Middle Aged ; Nephrolithotomy, Percutaneous ; Retrospective Studies ; Solitary Kidney/surgery* ; Treatment Outcome

OBJECTIVETo provide a sound cell source for further ex-vivo gene therapy for chronic pain, we attempt to develop an immortalized rat astrocyte cell line that expresses enkephalin regulated by doxycycline.

METHODSRetrovirus infection method was employed to develop an immortalized rat astrocyte cell line that could express enkephalin regulated by doxycycline. The hPPE gene expression level of immoralized astroyte cells (IAC)/ hPPE was detected by RT-PCR, indirect immunofluorescence staining and radioimmunoassay.

RESULTSIAC carrying Tet-on system transfected with preproenkephalin gene could secrete enkephalin that was regulated by doxycycline in a dose-dependent manner and hPPE gene activation could be repeated in on-off-on cycles through administration or removal of doxycycline.

CONCLUSIONAn immortalized rat astrocyte cell line that secrete enkephalin under the control of doxycycline is established successfully, which provides a research basis for transgenic cell transplantation for analgesia.

Animals ; Anti-Bacterial Agents ; pharmacology ; Astrocytes ; Cell Line, Transformed ; Chronic Disease ; Doxycycline ; pharmacology ; Enkephalins ; genetics ; metabolism ; Genetic Therapy ; methods ; Genetic Vectors ; Neurotransmitter Agents ; genetics ; metabolism ; Pain Management ; Protein Precursors ; genetics ; metabolism ; Rats ; Retroviridae ; genetics

OBJECTIVETo study the effects of salvianolic acid A on content of cytochrome P450,cytochrome b5 and CYP1A2, CYP2E1 activities of rats.

METHODThe rats were randomly divided into two groups and each group contained 5 male rats and 5 female rats. One is control group, another is dosage group. The dosage group was injected salvianolic acid A into a rat tail vein at doses of 20 mg x kg(-1) x d(-1) for 5 days. The control group was injected placebo into a rat tail vein at the same doses as the dosage group. The content of cytochrome P450 and cytochrome b5 of rats were assayed using UV and CYP1A2, CYP2E1 activities were evaluated using probe substrate.

RESULTAfter salvianolic acid A was injected into rats tail vein for 5 days, the total content of cytochrome P450 and cytochrome b5 and CYP1A2 and CYP2E1 activities have no statistical significance of differences than the control group.

CONCLUSIONSalvianolic acid A has no effects on CYP1A2 and CYP2E1 activities, indicating that there is no internation between salvianolic acid A and the drugs metabolized by CYP1A2 or CYP2E1.

Animals ; Caffeic Acids ; pharmacology ; Chromatography, High Pressure Liquid ; Cytochrome P-450 CYP1A2 ; metabolism ; Cytochrome P-450 CYP2E1 ; metabolism ; Cytochrome P-450 Enzyme System ; metabolism ; Cytochromes b5 ; metabolism ; Female ; Lactates ; pharmacology ; Male ; Microsomes, Liver ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley