OBJECTIVETo study changes of left ventricular remodeling (LVR) in hypertension patients with carotid atherosclerosis (CAS) of phlegm-dampness syndrome (PDS).

METHODSDoppler ultrasonography data of CAS were observed in 223 hypertension patients with CAS (as the hypertension group, including 119 patients of the PDS group and 104 of the non-PDS group), 81 CAS patients with non-hypertension, and 19 non-hypertension non-CAS patients (as the control group). The difference in the degree of LVR was compared among the above groups.

RESULTSThe left ventricular posterior wall thickness (LVPWT), inter ventricular septum thickness (IVS), E/A were higher in the hypertension group than in the non-hypertension group (P < 0.05). The left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVESD), stroke volume (SV) were higher in the soft plaque hypertension group and the soft plaque non-hypertension group than in the hard plaque group, the thickening intimal group, and the normal intimal group (P < 0.01 , P < 0.05). The LVEDD, LVESD, and SV were higher, and the ejection fraction (EF) was lower in the PDS hypertension group than in the non-PDS hypertension group (all P < 0.05). Of them, LVEDD, LVESD, and SV were higher in the soft plaque group than in the hard plaque group (P < 0.01), the thickening intimal group (P < 0.01) and the normal intimal group (P < 0.05). There was no statistical difference in PDS hypertension between the soft plaque group and the hard plaque group (P > 0.05).

CONCLUSIONThe hypertension patients with CAS of PDS might be correlated to LVR, and LVR was more obviously in the soft plaque patients.

Aged ; Aged, 80 and over ; Carotid Artery Diseases ; diagnosis ; diagnostic imaging ; physiopathology ; Case-Control Studies ; Female ; Humans ; Hypertension ; diagnosis ; diagnostic imaging ; physiopathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Ultrasonography ; Ventricular Remodeling

In order to investigate the effect of N-tosyl-L-phenylalnylchloromethyl ketone (TPCK) and dexamethasone (Dex) on expression of nuclear transcription factor-kappaB (NF-kappaB) in childhood acute lymphoblastic leukemia (ALL) and its significance, so as to provide the experimental basis for corresponding clinical treatment of ALL, in which NF-kappaB is taken as a target. The biotin-streptavidin method was used to detect the expression of NF-kappaB P65 protein and the effects of TPCK and Dex at clinically relevant dosage on activity of NF-kappaB P65 protein in 20 childhood ALL patients. The results indicated that the expression of NF-kappaB P65 protein was strongly diminished and reached to negative level at 2 hours by treatment with 40 micromol/L TPCK, the positive expression of NF-kappaB P65 protein was (2.5 +/- 1.6)%. TPCK had a time-dependent inhibitory effect on ALL cells cultured in vitro. The expression of NF-kappaB P65 protein in ALL cells was strongly inhibited by clinically relevant concentration of dexamethasone 5.0 microg/ml for 24 hours in vitro. The positive expression was (25.0 +/- 3.0)%, there was significant difference, as compared with untreated ALL cells (T=55, P<0.01). It is concluded that TPCK and Dex can inhibit NF-kappaB activity. Inhibition of NF-kappaB activity may be one of the effect mechanism of dexamethasone on ALL cells. Inhibition of NF-kappaB conduction pathway may have a significant value in childhood ALL treatment.
Bone Marrow Cells ; pathology ; Cells, Cultured ; Child ; Child, Preschool ; Dexamethasone ; pharmacology ; Female ; Humans ; Infant ; Leukocytes, Mononuclear ; pathology ; Male ; NF-kappa B ; biosynthesis ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; Protein Synthesis Inhibitors ; pharmacology ; Tosylphenylalanyl Chloromethyl Ketone ; pharmacology ; Tumor Cells, Cultured

OBJECTIVE: To build the multiple drug resistant human laryngeal cancer cell line and investigate its characteristics. METHOD: Human laryngeal cancer cells were exposed in stepwise escalating concentration of Taxol until the resistant cell line was developed. The IC50 and the resistance folds of multidrug resistance were detected by an ATP assay. The differences of cell cycle distribution, apoptosis, and Rhodamine accumulation between Hep-2 and Hep-2T cells were studied through flow cytometry. The MDR1 and MRP1 gene were detected through realtime quantitative RT-PCR, and the corresponding protein was detected through western-blotting. RESULT: A multidrug resistance cell line-Hep-2T induced by Taxol was effectively developed, whose drug resistance was 104 times that of Hep-2 cells. Doxorubicin, Gemcitabine, 5-Fu, Cisplatin all increased the drug resistance by 46.78, 1.95, 2.50, 1.05 folds. The cell cycle distribution altered. The apoptosis of Hep-2 cells was quite greater than that of Hep-2T cells (45.32% vs 4.26%, P < 0.01, flow cytometry), (54.47 +/- 48.95 vs 9.84 +/- 12.53 P < 0.01, hoechst staining) after Hep-2 and Hep-2T exposed to Taxol at IC50 to Hep-2. The copy ratio of MDR1/GAPDH mRNA of Hep-2T was 64.2 +/- 36.7 times that of Hep-2 (P < 0.05), while MRP1/GAPDH of Hep-2T was only 1.20 +/- 0.09 folds more than that of Hep-2 (P < 0.05). The proteins of MDR1/P-gp were greatly over expressed in Hep-2T cells compared with Hep-2 cells (P < 0.01) whose was in the same trend (P < 0.05), while the elevated expression of MRP1 was lower than that of MDR1/P-gp. CONCLUSION When considering the possible methods to reverse MDR of SCCHN, more emphasis should be laid on MDR1/P-gp, and when combining this with chemotherapy the non-P-gp substrate chemotherapeutic agents should be considered. At the same time, more attention should be paid to the changes of cell cycle distribution during the drug selection.
Cell Culture Techniques ; methods ; Cell Line, Tumor ; drug effects ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Humans ; Paclitaxel ; pharmacology

In the retina, pH fluctuations may play an important role in adapting retinal responses to different light intensities and are involved in the fine tuning of visual perception. Acidosis occurs in the subretinal space (SRS) under pathological conditions such as age-related macular degeneration (AMD). Although it is well known that many transporters in the retinal pigment epithelium (RPE) cells can maintain pH homeostasis efficiently, other receptors in RPE may also be involved in sensing acidosis, such as acid-sensing ion channels (ASICs). In this study, we investigated whether ASIC1a was expressed in the RPE cells and whether it was involved in the function of these cells. Real-time RT-PCR and Western blotting were used to analyze the ASIC1a expression in ARPE-19 cells during oxidative stress induced by hydrogen peroxide (H(2)O(2)). Furthermore, inhibition or over-expression of ASIC1a in RPE cells was obtained using inhibitors (amiloride and PCTx1) or by the transfection of cDNA encoding hASIC1a. Cell viability was determined by using the MTT assay. The real-time RT-PCR and Western blotting results showed that both the mRNA and protein of ASIC1a were expressed in RPE cells. Inhibition of ASICs by amiloride in normal RPE cells resulted in cell death, indicating that ASICs play an important physiological role in RPE cells. Furthermore, over-expression of ASIC1a in RPE cells prolonged cell survival under oxidative stress induced by H(2)O(2). In conclusion, ASIC1a is functionally expressed in RPE cells and may play an important role in the physiological function of RPE cells by protecting them from oxidative stress.
Acid Sensing Ion Channels ; metabolism ; Cell Line ; Humans ; Ion Channel Gating ; physiology ; Oxidative Stress ; physiology ; Retinal Pigment Epithelium ; cytology ; metabolism

OBJECTIVETo study the correlation of multislice spiral CT features and vascular endothelial growth factor (VEGF) expressions and microvessel density (MVD) in renal cell carcinoma (RCC).

METHODSFourth-seven patients with pathologically confirmed RCC were examined by multislice spiral CT, and VEGF expressions and MVD of the RCC and the adjacent normal tissues were determined by immunohistochemistry with specific monoclonal antibodies.

RESULTSVEGF expression and MVD in the RCC and adjacent normal tissues increased with the pathological grades of RCC (P<0.05), VEGF expression was found to significantly correlate with MVD (r=0.67, P<0.01). The positive expression of VEGF and MVD were associated with the findings by multislice spiral CT scan of tumor size, intratumor necrosis, cystic degeneration, intensity signal, lymph node metastases, invasion of the renal vein or inferior vena cava, and invasion of the adjacent organs or distant metastases (P<0.01).

CONCLUSIONMultislice spiral CT findings can be indicative of the histopathology of RCC, and some CT findings are closely correlated with MVD and VEGF expressions in RCC, which may help evaluate the biological behavior and malignancy of the tumor and predict tumor invasion and metastasis.

Adult ; Aged ; Carcinoma, Renal Cell ; blood supply ; diagnostic imaging ; metabolism ; Female ; Humans ; Kidney Neoplasms ; blood supply ; diagnostic imaging ; metabolism ; Male ; Microcirculation ; Middle Aged ; Tomography, Spiral Computed ; methods ; Vascular Endothelial Growth Factor A ; biosynthesis

Objective To compare the changes of antrum and fundus cross‐sectional area ( CSA ) measured by bedside ultrasonography on gastric insufflation during anesthesia induction in non‐obese female patients and analyze the relationships between these changes as well as postoperative nausea and vomiting ( PONV ) . Methods Fourty‐six patients scheduled for elective gynecological laparoscopic operations were enrolled in the study . T he patients w ho appeared the comet‐tail artifacts were defined as gastric insufflation positive group( GI+ group) ,w hile the ones without comet‐tail artifacts were defined as gastric insufflation negative group( GI‐ group) . Blood oxygen saturation ( SPO 2 ) ,end‐expiratory partial pressure of CO 2 ( PET CO2 ) ,tidal volume( T V ) were recorded after 180 seconds ventilation in both groups . T he longitudinal and anteroposterior diameters of gastric antrum and fundus were measured before and after facemask ventilation respectively and the corresponding CSA were calculated . T he cutoff values of prediction of gastric insufflation were determined according to the ROC curve and the corresponding sensitivity and specificity were calculated . PONV of the two groups were also recorded . Results T he analysis was based on the remaining 41 data sets actually . T here were 13 patients in GI‐group and 28 ones in GI+ group . Compared with GI‐group ,the changes of T V and fundus CSA in GI+ group had significantly differences( P ＜0 .05) ; w hile compared with before mask ventilation ,the changes of antrum and fundus CSA in both groups had significantly differences ( P ＜0 .05).T he areas of antrum and fundus CSA under the ROC curve (95% CI) were 0 .67 and 0 .80 ,with cut‐off value 3 .19 cm2 and 24 .90 cm2 ,sensitivity 0 .93 and 0 .93 and specificity 0 .39 and 0 .69 ,respectively .T he incidence of PONV in GI+ group was higher than that in GI‐group( P ＜0 .05). Conclusions Changes of fundus CSA by ultrasonography might be superior to antrum CSA in gastric insufflation caused by 20 cm H2 O peak airway pressure of facemask ventilation during anesthesia induction . Gastric insufflation caused by positive pressure ventilation is related with PONV for young female patients undergoing gynecological laparoscopic operation .

Objective To evaluate the effect of facemask ventilation with different pressures on perioperative complications in the patients undergoing gynecological laparoscopic surgery. Methods Seven-ty-five American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes, aged 18-60 yr, with body mass index of 18-24 kg∕m2 , scheduled for elective gynecological laparoscopic surgery under general anesthesia, were divided into 3 groups ( n=25 each) using a random number table method: 10 cmH2 O group ( group P10) , 15 cmH2 O group ( group P15) and 20 cmH2 O group ( group P20) . The pres-sure for facemask ventilation was 10, 15 and 20 cmH2 O during induction of anesthesia in group P10, group P15 and group P20, respectively. Before facemask ventilation ( T0 ) and at 180 s of facemask ventilation ( T1 ) , longitudinal and anteroposterior diameters of the antral area in the supine position were measured u-sing ultrasonography, the antral cross-sectional area was calculated, and the development of serious flatu-lence was recorded. The development of hypoxemia, tidal volume and end-tidal pressure of carbon dioxide in each group were recorded at T1 . The operation time and occurrence of postoperative flatulence and nausea and vomiting were recorded. Results Compared with group P10, the incidence of serious flatulence and postoperative flatulence and nausea and vomiting was significantly increased, and the incidence of hypox-emia was decreased in group P15 and group P20, and tidal volume was increased at T1 in group P20 ( P<0. 05) . Compared with group P15, the incidence of serious flatulence was significantly increased ( P<0. 05) , and no significant change was found in the incidence of hypoxemia and postoperative flatulence and nausea and vomiting in group P20 ( P>0. 05) . There was no significant difference in the end-tidal pressure of carbon dioxide at T1 or antral cross-sectional area at T0 and T1 among the three groups ( P>0. 05) . Con-clusion Pressure of 10-15 cmH2 O for facemask ventilation is optimal during induction of general anesthe-sia and can ensure adequate oxygen supply and reduce perioperative complications in the patients undergoing gynecological laparoscopic surgery.

Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer (TNBC). Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2) or docetaxel 75 mg/m(2) every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response (pCR), which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Thirty-nine (90.7%) patients were at clinical stages IIB-IIIC. Thirty-seven (86%) completed 4-6 cycles of preoperative chemotherapy, and objective response rate (ORR) was 81.4% (35/43). Forty-two patients underwent radical surgery subsequently. The pCR rate was 14.3% (6/42). The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting (88.4%, 38/43) and neutropenia (88.4%). After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally advanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Chemoradiotherapy, Adjuvant ; methods ; Disease-Free Survival ; Epirubicin ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; methods ; Neoplasm Recurrence, Local ; pathology ; prevention & control ; Neoplasm, Residual ; pathology ; prevention & control ; Paclitaxel ; administration & dosage ; Taxoids ; administration & dosage ; Treatment Failure ; Treatment Outcome ; Triple Negative Breast Neoplasms ; drug therapy ; pathology

OBJECTIVE Paeoniflorin (PF) and albiflorin (AF) are the major active components of total peony glucosides(TPG)from Paeonia lactiflora Pal,which have many biological activities such as anti-inflammatory, antioxidation and anti-hypertension effects. The drug-drug pharmacokinetic interaction among PF,AF and TPG,the pharmacokinetic comparisons of AF between hypoxia and normoxia,the transport of AF cross the blood-brain barrier cell model and the transport of AF/PF/TPG cross Caco-2 cell model were investigated.METHODS A highly sensitive and rapid UPLC-MS method with multiple-reaction monitoring(MRM)scanning via electrospray ionization(ESI)source operating both in the positive and negative ionization mode was successfully developed and validated for simultaneous quantitation of PF and AF in rat plasma after an oral administration of PF,AF and TPG. RESULTS The validated and developed UPLC-MS/MS method was successfully applied to simultaneously determine the AF and PF concentration in rat plasma and investigate pharmacokinetic interactions after a single intragastrical ad-ministration of PF,AF,co-administration of PF with AF and TPG,respectively.The elimination of both PF co-administered with AF and PF in TPG were slower than those for PF alone and the distribution in the tissues was wider.The combination of PF with AF or TPG could significantly increase the values of the AUC, MRT and t1/2of the drug PF, and reduce the values of CL of PF. From a comparison of the main pharmacokinetic parameters among AF alone, AF combined with PF and AF in TPG, the values of the MRT and t1/2of AF in TPG were greater than that of AF alone,and there were statistically signifi-cant differences in these parameters(P<0.05,P<0.01).It was also noticed that AUC and Cmaxof PF in hypoxia rats were significantly decreased compared with that of normaxia rats, suggesting that there was a decreased exposure of PF in rats under hypoxia. The multiple active components in TPG may lead to DDIs between some P-gp substrates. CONCLUSION The clinical performance of total peony glucosides would be better than that of single constitute. The outcomes of the study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage.

Objective To explore the possible role of parvalbumin (PV)-positive interneuron in the pathogenesis of increased susceptibility to epileptic seizures in FMR1 gene knockout (FMR1 KO)mice. Methods Immunohistochemistry was employed to determine the expression of PV in CA1 and CA3 regions of the hippocampus, the striate cortex, the temporal auditory cortex and the piriform cortex of FVB strain FMR1 KO mice and wild type (WT) controls at the age of 2, 4 and 6 w. Western blotting was used to detect the level of PV in the cerebral cortex and hippocampus of the above mice. Results The numbers of PV-positive interneuron in CA1 and CA3 regions of the hippocampus, the striate cortex,the temporal auditory cortex and the piriform cortex of FMR1 KO mice at the age of 2 and 4 w were significantly decreased as compared with those in the age-matched WT mice (P<0.05). The level of PV in the cerebral cortex and hippocampus in FMR1 KO mice at the age of 2 and 4 w was also significantly decreased than that in the age-matched WT mice (P<0.05). Conclusion Decreased numbers of PV-positive interneuron and level of PV might induce the increased susceptibility to epileptic seizures inFMR1 KO mice.