Multidrug resistance(MDR) is the leading cause of treatment failure in cancer therapy. Overexpression of the ATP-binding cassette (ABC) transporter family increases the cellular efflux, decreases the effectiveness of chemotherapeutic agents,and results in MDR. In particular,overexpression of P-glycoprotein and its encoding genes(mdr1) is the major mechanism. It is feasible for overcoming MDR by studying the factors affecting mdr1 gene expression so as to block the expression of mdr1. Pregnane X receptor(PXR) can regulate the expression of MDR proteins, suggesting that it be possible to overcome drug resistance by regulating PXR. In this paper,the relation between PXR and MDR and recent development of PXR antagonists to pharmacologically modulate PXR are reviewed. The review proposes that selectively preventing the elevation of MDR levels by regulating PXR rather than non-selectively inhibiting the MDR activity by using MDR inhibitors can be a less toxic approach to overcome drug resistance during cancer therapy.

OBJECTIVE: To explore the clinical application value of using needle electrode in transurethral plasmakinetic resection of bladder tumor around ureteral orifice. METHODS: Retrospective analysis was performed on the clinical data of 16 cases who had bladder tumors around ureteral orifice and underwent transurethral resection using plasmakinetic needle electrode in Department of Urology, Peking University International Hospital from June 2015 to December 2019. There were nine cases with the tumor of one to two centimeters from the ureteral orifice. The rest of the seven cases had tumor that was within one centimeter from the ureteral orifice, including two cases whose ureteral orifice was invaded by the tumor. All the patients studied were diagnosed before surgery and contraindications were excluded. The plasmakinetic needle electrode was used to treat the tumor with en bloc resection, and all the excised tissue was sent for pathological examination. Intravesical chemotherapy and postoperative follow-ups were performed. Statistical analysis was performed on the operation time, the incidence of obturator nerve reflex, the peri-operative bleeding, the parameters of indwelling ureteral catheter or double-J stent, the incidence of postoperative hydronephrosis, the clinical stage of tumor, and the recurrence rate. RESULTS: The operation was successfully completed for all the sixteen cases. The operation time was 16 to 57 minutes, with an average of (32.6±11.8) minutes. No obvious obturator nerve reflex and perioperative bleeding occurred in all the patients. Ureteral catheters were indwelled prior to the operation of tumor resection in seven cases. Four of the seven cases had the ureteral catheters remained while the rest three were replaced by double-J stent after surgery. Postoperative pathological analysis showed that all the tumors were urothelial carcinoma, including 9 cases of low grade and 7 cases of high grade. Pathological staging: 10 cases were in Ta stage, 5 cases in T1 stage, and 1 case in T2a stage. All tumor bases and lateral margins were negative. All the patients received 3-56 months, with an average of (26.0±18.1) months of follow-up. There was no case of upper urinary tract hydronephrosis or tumor recurrence. CONCLUSION The transurethral plasmakinetic resection of bladder tumor using needle electrode can realize en bloc tumor resection without obturator nerve reflex and reduce the risk of ureteral orifice injury. It is a safe and effective surgical method for treating bladder tumors around the ureteral orifice.
Carcinoma, Transitional Cell ; Electrodes ; Humans ; Neoplasm Recurrence, Local ; Retrospective Studies ; Urinary Bladder Neoplasms/surgery*

Humans ; Neck ; Solitary Fibrous Tumors

OBJECTIVE: To investigate berberine's potential to enhance the sensitivity of doxorubicin-resistant human leukemia cell lines (K562/DOX) to doxorubicin in vitro. METHODS: MTT assay was performed to determine the effect of berberine on the sensitivity of K562/DOX cells to doxorubicin. Doxorubicin accumulation assay was performed by Arrary Scan VTI HCS600 High-Contents. The effect of berberine on doxorubicin-induced cell apoptosis was tested by PI/Hoechst 33342 assay. The efflux activity of P-gp was investigated by measuring the accumulation of the rhodamine 123 after treatment with berberine. RESULTS: μmol · L-1 of berberine, as a wild dose, reduced IC50 of doxorubicin to K562/DOX cells by 1.5 times. 1 μmol · L-1 of berberine showed the enhancement effect on doxorubicin-induced apoptosis. The increase of doxorubicin and rhodamine 123 accumulation was observed in K562/ DOX cells treated with 1 μmol · L-1 of berberine which indicated the inhibition of the activity of P-gp. CONCLUSION: Berberine is shown to effectively enhance chemosensitivity of K562/DOX cells to Dox by inhibiting the efflux activity of P-gp.

Mind map is an effective and intuitive knowledge organization and presentation tool which can help computer teaching commendably. We can use Mind Map to design and organize the whole teaching process, including preparing, designing, guiding, analyzing and reviewing. This way can turns tedious logic of computer teaching into imagery thinking and helps medical students improv-ing their learning effect of computer courses.

Two parental strains BY-14 and BY-6,with high leavening ability in lean and sweet dough respectively,were selected.Through spore production and separation,two haploids with opposition types were selected for cross-breeding.At last one hybridization strain was obtained,with good fermentation ability as BY-14 in lean dough and better than BY-6 by 25%in sweet dough.

Objective To investigate the effects of sulforaphane (SFN) on proliferation and invasion of human small cell lung cancer NCI-H446 and the activity of matrix metalloproteinase (MMP) -9.Methods NCI-H446 cells were cultured with 0,25,50,100 μmol/L SFN for 24 ～ 72 h,then MTT assay was employed to detect cell proliferation.Chamber invasion assay was used to study the cell invasion,and gelatin zymography assay was implied in MMP-9 enzyme activity.Results After treatment of 25,50,100μmol/L SFN,the growth of NCI-H446 cells were inhibited.When cells were incubated with 25,50,100μmol/L of SFN for 72h,the inhibition ratio was ( 11.1 ± 2.26 ) ％,( 25.2 ± 3.24 ) ％ and ( 44.6 ±4.2) ％,respectively,the difference was statistically significant compared with the solvent control group ( t =10.685,8.417,5.264,P ＜0.05 ).Chamber invasion assay showed that NCI-H446 cell invasion could be reduced.25,50,100 μmol/L of SFN could decrease the trans-membrane cells to (48.6 ± 1.84)％,(35.4 ± 2.22) ％ and (27.8 ± 1.36) ％,and it was statistically significant compared with the solvent control group ( t =6.341,5.562,4.925,P ＜0.05 ),respectively.In addition,MMP-9 activity was significantly inhibited by SFN.25,50,100 μmol/L of SFN could decrease the gray value of MMP-9 to 764 ±18.4,685 ± 14.74 and 638 ± 21.54 ( control group 822 ± 12.53,t =4.971,7.582,11.235,respectively,P ＜0.05).Conclusions SFN can inhibit NCI-H446 cells growth,invasion and the activity ofMMP-9.

Objective To evaluate the effects of different doses of propofol or isoflurane on the cochlear blood flow (CBF) in guinea pigs.Methods Fifty-four adult male guinea pigs,aged 3 months,weighing 400-500 g,were randomly divided into 6 groups (n =9 each).In P1,P2 and P3 groups,propofol was infused for 115 min at 10,20 and 40 mg· kg-1 · h-1,respectively,after a loading dose of 5 mg/kg was injected over 5 min.In S1,S2 and S3 groups,isoflurane was inhaled for 120 min with end-tidal concentrations of 1％,2％ and 3 ％,respectively.Mean arterial pressure and CBF were recorded before administration (baseline,T1) and during the period of drug administration.Distortion product otoacoustic emission (DPOAE) was measured at T1,at the end of administration (T2) and 1 h after administration (T3).Five animals in each group were sacrificed and organs of Corti were harvested for observation of morphology of out hair cells by scanning electron microscopy.Results Propofol decreased MAP and increased CBF and DPOAE amplitude in a dose-dependent manner.Isoflurane decreased MAP and CBF in a dose-dependent manner.1％ isoflurane increased DPOAE amplitude,however,2％ and 3％ isoflurane decreased it and caused damage to out hair cells.Conclusion Propofol induces an increase in CBF in guinea pigs,while high concentration of isoflurane induces a decrease in CBF.Isoflurane inhibits CBF autoregulation,which makes CBF more sensitive to perfusion pressure,thus causing damage to hearing function.This is the reason why high concentration of isoflurane induces a decrease in CBF.

Objective To investigate the effects of sodium aescinate(SA)on oxidative stress and pulmonary function during acute exacerbation of chronic obstructive pulmonary disease(COPD).Methods One hundred and twenty patients with COPD were randomly divided into two groups:the control group(n =60) and the treatment group(n =60).All patients were treated with routine anti-infection,oxygen inhalation,relieving phlegm and anti-asthma The treatment group took SA in addition to the routine beteropathy.The changes of serum SOD,MDA,GSH-Px,T-AOC,pulmonary functions and 6 minute walk distance(6MWD) were detected before and after two-week treatment in patients of the two groups to compare with 60 healthy subjects.Results The total effective rate in the treatment group was 91.67％,while 76.67％ in the control group.The difference was statistically significant(x2 =5.065,P ＜0.05).Serum MDA level in both groups were comparatively higher than the healthy controls(9.25±1.55) μmol/L vs.(9.74±1.50) μmol/L vs.(2.06±0.29) μmol/L,P ＜0.001),while the levels of SOD,GSH-Px and T-AOC were lower than the healthy controls[SOD:(91.14±9.54) kU/L vs.(90.61±8.01) kU/L vs.(116.63±6.57) kU/L; GSH-Px:(139.38±36.56) U vs.(137.57±34.19) U/L vs.(189.34±35.54) U/L; T-AOC:(6.48±1.15) kU/L vs.(6.39±1.13) kU/L vs.(13.34±1.23)kU/L;P < 0.001].After treatment,all indexes of the two groups were obviously ameliorated in comparison with before treatment(P ＜ 0.001),but the level of MDA[(4.56±1.39) μmol/L]in the treatment group decreased more greatly than in the control groups(P ＜ 0.001).The levels of SOD[(103.85±7.07) kU/L],GSH-Px[(169.65±34.51) U/L],T-AOC[(10.52±1.09) KU/L],forced expiratory volume in 1 second/forced vital capacity(FEV1/FVC)[(60.49±6.11)％],FEVI％[(76.62±6.35)％]and 6MWD [(394.83±10.11)m]increased considerably more than those in the control group(P ＜ 0.001).Conclusion Oxidative stress might be involved in the course of acute exacerbation of COPD.Sodium aeseinate can improve the pulmonary functions by ameliorating the oxidative stress during acute exacerbation in patients with COPD.

AIM:To investigate the inhibitory effects of recombinant human Mullerian inhibiting substance on cell proliferation in human ovarian carcinoma cells (OVCAR8 and SKOV3 cell lines). METHODS:The expression of MISIIR protein and the localization of MISIIR protein were analyzed by Western blotting and confocal spectral microscopy,respectively. Cell apoptosis and cell cycle were detected by flow cytometry (FCM). Cell viability was determined via MTT method. Clone formation test was used to detect oncogenicity in vitro.RESULTS:The MISIIR protein expression in OVCAR8 cells but not in SKOV3 cells was observed. MISIIR expression was seen on the OVCAR8 cell surface and in the cytoplasm with both antibodies. After treated with rhMIS for 48 h,the cell viability was significantly decreased in OVCAR8 cells. rhMIS inhibited the oncogenicity of OVCAR8 cells greatly. The cell apoptosis of OVCAR8 cell exposed to 10 mg/L rhMIS was (31.3±2.1)%,and OVCAR8 cells in the G_1 phase were increased by (70.4±3.0)%. Compared to SKOV3 cells the differences were significant (P<0.01). CONCLUSION:Recombinant human Mullerian inhibiting substance suppresses the growth of MISIIR-positive ovarian cancer cells by inducing apoptosis and cell cycle arrest. We predict that rhMIS might be a new target to treat human ovarian malignancies.