Objective To explore the feasibility and value of dynamic contrast-enhanced (DCE-MRI) parameters in assessing early effects of anti-angiogenesis medicine in targeted therapy for tumors.Methods Twenty BALB/C-nu nude mice were injected subcutaneously with human colon cancer cells HT-29 to the right hind leg.The nude mice were evenly divided into the experimental group and control group with 10 mice in each group.The mice of experimental group were intraperitoneally injected with bevacizumab,and the control group were injected with the same volume of saline.DCE-MRI was performed before medication and one hour,24 h and 48 h after medication.The Ktrans,Kep,Ve and initial area under enhancement curve (iAUC) of DCE-MRI were analyzed.The animals were sacrificed 48 hours after medication.Microvessel density (MVD) of the tumors was detected by immunohistochemistry.One way analysis of variance was performed to analyze parameters of DCE-MRI.The Pearson correlation coefficient was used to analyze the correlation between parameters of DCE-MRI and MVD.Results Under DCE-MRI,the edge of subcutaneous colon cancer xenografts was obviously gradually enhanced,pseudo color indicated high perfusion,the strength degree of the central region was low and which meant low perfusion.The differences in Kep of different time point of experimental group were statistically significant (F=3.752,P=0.016) ; there as no significant difference in other parameters of DCE MRI (all P＞0.05).There was no significant difference in Ktrans and Kep before medication and one hour after medication (all P＞0.05).There were significant difference in Ktrans and Kep 24 hour and 48 hour after medication between experimental group (24 hour∶ (0.095 ± 0.039) min-1 and (0.297 ± 0.141) min-1,48 hour∶ (0.090±0.033) min 1 and (0.314±0.148) min-1) and control group (24 hour∶ (0.150±0.074) nin-1 and (0.494±0.126) min-1,48 hour∶ (0.171±0.045) min-1 and (0.441± 0.092) min-1) (F24h =4.824 and 11.386,F48h =22.605 and 5.455,all P＜0.05).There was no significant difference in Ve and iAUC between two groups at different time points (all P＜0.05).MVD of experimental group was lower than that of control group.Ktrans and Kep were positively correlated with MVD (r=0.745 and 0.400,both P＜0.05).Conclusion Ktrans and Kep parameters of DCE-MRI may be used in monitoring the earlier effects of anti-angiogenesis medicine in targeted therapy for colon cancer.

AIM:We generated transgenic mice of NKCC1-/-(homozygous mutant),NKCC1+/-(heterozygous)and NKCC1+/+(wild-type)that have a targeted disruption in the NKCC1 gene to investigate the role of Na-K-2Cl(NKCC1)channel in auditory function of the inner ear.METHODS:Hearing threshold and endocochlear potential(EP)were measured in the NKCC1-/-,NKCC1+/-and NKCC1+/+ mice by auditory brainstem response(ABR)and EP recordings,respectively.The inner ears of the mice were removed and examined morphologically with the light microscope.RESULTS:The auditory function of NKCC1+/+ mice was normal,the mean value for ABR thresholds in response to click sound was [(23.13?3.78)dB,SPL],EP was(98?16)mV.The mean value for ABR thresholds to click sound was elevated in NKCC1+/-mice [(38.49?12.29)dB,SPL],relative to that significantly increased in NKCC1+/+ mice(P

A CdTe/ZnSe quantum-dot submicrobead ( QBs ) , which exhibited fluorescence intensity approximately 2800-fold stronger than that of single quantum dots, was conjugated with the anti-histidine rich protein( HRP )-Ⅱ mAbs using N-( 3-( Dimethylamino ) propyl )-N'-ethylcarbodiimide hydrochloride ( EDC ) method as fluorescence probe. The goat anti-HRP-Ⅱ polyclonal antibodies and donkey anti-mouse polyclonal antibodies were sprayed onto the nitrocellulose membrane as test line and control line, respectively. The resultant fluorescence probes were introduced to the immunochromatographic strip for the quantitative determination of Plasmodium falciparum. For determination of Plasmodium falciparum in serum, the QBs based immunochromatographic strips exhibited a good dynamic linear range from 5 . 8 Parasite/μL to 8010 Parasite/μL with a limit of detection of 5. 8 Parasite/μL. The detection time of the proposed QBs based immunochromatographic strips for each sample was only 15 min. Moreover, the recovery rates of the intra-and inter-assay ranged from 93. 0% to 111. 9%, and 98. 3% to 115. 1% respectively, while the relative standard deviations ( RSDs) of intra-and inter-assay were below 5%.

Objective To study the pinoresinol diglucoside (PDG) on gene regulation role of ESF-1 cells in collagen secretion, to reveal PDG repair mechanisms on scalded skin.Methods The cells cultured in vitro were divided into the control group, the estradiol group and the three different PDG doses groups. The concentration of the high, medium and low dose groups were 100, 10, 1μmol/L, and that of estradiol group were 10-3μmol/L. The activity of proliferation was detected by MTT. Then collagen type I (Col I), collagen typeⅢ (ColⅢ), tissue inhibitors of metalloproteinase 1 (TIMP-1), tissue inhibitors of metalloproteinase 2 (TIMP-2) and matrix metalloproteinase 1 (MMP-1) expression levels of mRNA after administration of cells were detected by RT-PCR.Results Compared with the control group, the proliferation of ESF-1 cells (0.559 ± 0.027, 0.552 ± 0.034vs. 0.489 ± 0.027,P<0.05) in the estradiol and medium-dose PDG was significantly higher. The expression level of mRNA of ColⅠ(0.958 ± 0.021, 0.929 ± 0.031, 0.916 ± 0.015vs. 0.844 ± 0.022), ColⅢ (0.783 ± 0.038, 0.918 ± 0.021, 0.855 ± 0.017vs. 0.678 ± 0.024), TIMP-1 (0.939 ± 0.025, 0.889 ± 0.036, 0.853 ±  0.015 vs. 0.780 ± 0.023), TIMP-2 (0.507 ± 0.024, 0.655 ± 0.037, 0.572 ± 0.025vs. 0.405 ± 0.062) in the estradiol, low-, medium-dose PDG groups were significantly higher than those in the control group (P<0.05 or P<0.01). Besides, the MMP-1 (0.343 ± 0.038, 0.407 ± 0.046, 0.435 ± 0.037vs.0.519 ± 0.041) mRNA expression level in the middle and low dose PDG groups significantly decrease (P<0.05 orP<0.01). Conclusions The PDG could enhance the activity of ESF-1 cell proliferation, increase the expression of related collagen and tissue inhibitor of metalloproteinases and inhibit that of matrix metalloproteinases to repair scalded skin.

The distribution of the Na-K-2Cl co-transporter (NKCC1) in the cochlear K+ cycling pathway in cochlea and cochlear histological changes in the NKCC1 knockout mice were investigated. By using immunohistochemistry and toluidine blue staining, the localization of NKCC1 in cochlea of the C57BL/6J mice and the cochlear histological changes in the NKCC1 knockout mice were observed. It was found that the NKCC1 was expressed mainly in the stria marginal cells and the fibrocytes in the inferior portion of the spiral ligament in the adult C57BL/6J mice. Subpopulation of the fibrocytes in the suprastrial region and the limbus was also moderately immunoreactive. While in the cochlea of the NKCC1 knockout mice, Reissner's membrane was collapsed and scala media disappeared, accompanied with the loss of inner hair cells, outer hair cells and the support cells. The tunnel of Corti was often absent. All the findings suggested the localization of NKCC1 in the cochlea was closely correlated with cochlear K+ cycling. Loss of NKCC1 led to the destruction of the cochlear structures, and subsequently influenced the physiological function of cochlea.

This study examined the expression pattern of programmed cell death 5 (PDCD5) in cochlear hair cells and spiral ganglion neurons (SGNs) and its association with age-related hearing loss in mice. Sixty C57BL/6J (C57) mice at different ages were divided into four groups (3, 6, 9 or 12 months). PDCD5 expression was detected by using immunohistochemistry, real-time PCR and Western blot. Morphological change of the cochleae was also evaluated by using immunoassay. The results showed that the expression of PDCD5 had a gradual increase with ageing in both protein and RNA levels in C57 mice, as well as gradually increased apoptosis of cochlear hair cells and SGNs. In addition, we also found that caspase-3 activity was enhanced and its expression was enhanced with ageing. It is implied that overexpression of PDCD5 causes the increase in caspase-3 activity and the subsequent increase of apoptosis in cochlear hair cells and SGNs, and thereby plays a role in the pathogenesis of presbycusis. Thus, PDCD5 may be a new target site for the treatment and prevention of age-related hearing loss.

OBJECTIVE: To investigate the therapeutic effects of conventional treatment with different routes of administration of dexamethasone on sudden deafness. METHOD: Eighty-four patients with sudden deafness were included in this prospective randomized study. Twenty one patients (group 1) were treated with taking dexamethasone orally combined with conventional methods. Another 21 patients (group 2) were treated with intravenous dexamethasone injection combined with conventional methods. Group 3 (21 patients) were treated with intratympanic dexamethasone injection by the way of external ear combined with conventional methods. The other 21 patients (group 4) were treated with intratympanic dexamethasone injection by the way of pharyngotympanic tube combined with conventional methods. The hearing gains at 0.5, 1.0, 2.0, 4.0 kHz and the mean values were compared among four groups. RESULTS: The average hearing gains of 1, 2, 3 and 4 group was 21.3 dB, 27.5 dB, 43.2 dB and 48.1 dB respectively. Group 3 and group 4 had statistical difference compared with group 1 and group 2 in the average hearing gains. There was no obviously statistical difference between group 1 and group 2 and between group 3 and group 4. In patients with PTA < or = 70 dB, the average hearing gains at 0.5, 1.0, 2.0, 4.0 kHz had no obvious difference (P > 0.05) among four groups. However, in patients with PTA > 70 dB, there was statistical difference between group 1, 2 and group 3, 4 (P < 0.05), the hearing gains of group 3. 4 were apparently higher than that of group 1, 2. However, there was no significant difference of hearing gains between group 1 and group 2 (P > 0.05) and between group 3 and group 4 (P > 0.05). CONCLUSION The conventional drug treatment with taking dexamethasone orally or intravenous dexamethasone injection had no obvious effect on sudden deafness with PTA > 70 dB, but the conventional drug treatment with intratympanic dexamethasone injection is a useful treatment for sudden deafness. Comparison with whole body administration, intratympanic dexamethasone injection is more convenient to use in clinic, and with less prohibitions and complications. Patients with PTA > 70 dB should take intratympanic dexamethasone injection in early days.
Adult ; Dexamethasone ; administration & dosage ; therapeutic use ; Drug Administration Routes ; Female ; Hearing Loss, Sudden ; drug therapy ; Humans ; Male ; Middle Aged ; Prospective Studies ; Treatment Outcome

OBJECTIVE: L-type voltage-gated calcium channel subunit alpha1D-/- mice (homozygous mutant, knockout), alpha1D+/- (heterozygous) and alpha1D+/+ (wild-type) have played role in L-type voltage-gated calcium channel alpha1D subunit in auditory function of inner ear as well as sinoatrial node function of the mice. METHOD: Hearing threshold and endocochlear potential (EP) were measured in the alpha1D knockout mice, heterozygous mice and wild-type mice by auditory brainstem response(ABR), EP recordings and Electrocardiograph (ECG) respectively. To assessment of the vestibular function of the mice, the ability of Balancing was performed by a swim test and a horizontal cylinder test. RESULT: The auditory function of alD+/+ mice were normal, the mean value for ABR thresholds in response to click sound stimulus was (34.8 +/- 5.7) dB SPL,EP was (105.3 +/- 3.1) mV. The mean value for ABR thresholds in response to click sound stimulus was elevated in alpha1D+/- mice was (54.4 +/- 12.4) dB SPL, relative to that observed in alpha1D+/+ mice significantly increased (P < 0.05); EP of alpha1D+/- mice was about (75.8 +/- 9.9) mV. alpha1D-/- mice were completely deaf, the ABR wave form was not observed for even 100 dB SPL sound stimuli used and EP was still remain in (48.6 +/- 19.3) mV. alpha1D knockout mice were deaf and demonstrated no vestibular defect. alpha1D+/- and alpha1D-/- mice show significant sinus bradycardia with significant prolongation of the RR interval (146 +/- 1.4 and 244 +/- 2.9, respectively) comparing to the alpha1D+/+ wild-type mice (117 +/- 0.4) in the same littermates. In addition, the homozygous alpha1D-/- show a significant prolongation of the PR interval (53 +/- 0.5) compared to that of the a1D+/+ wild-type mice (38 +/- 0.3). CONCLUSION L-type voltage-gated calcium channel alpha1D subunit plays a critical role in calcium homeostasis in the inner ear. Mice lacking of alpha1D calcium channel gene would lead to influence auditory function and sinoatrial node dysfunction subsequently.
Animals ; Auditory Threshold ; Calcium Channels, L-Type ; genetics ; Deafness ; genetics ; physiopathology ; Electrocardiography ; Evoked Potentials, Auditory, Brain Stem ; Mice ; Mice, Knockout ; Sinoatrial Node ; physiopathology

The distribution of the Na-K-2Cl co-transporter (NKCC1) in the cochlear K+ cycling pathway in cochlea and cochlear histological changes in the NKCC1 knockout mice were investigated. By using immunohistochemistry and toluidine blue staining, the localization of NKCC1 in cochlea of the C57BL/6J mice and the cochlear histological changes in the NKCC1 knockout mice were observed. It was found that the NKCC1 was expressed mainly in the stria marginal cells and the fibrocytes in the inferior portion of the spiral ligament in the adult C57BL/6J mice. Subpopulation of the fibrocytes in the suprastrial region and the limbus was also moderately immunoreactive. While in the cochlea of the NKCC1 knockout mice, Reissner's membrane was collapsed and scala media disappeared, accompanied with the loss of inner hair cells, outer hair cells and the support cells.The tunnel of Corti was often absent. All the findings suggested the localization of NKCC1 in the cochlea was closely correlated with cochlear K+ cycling. Loss of NKCC1 led to the destruction of the cochlear structures, and subsequently influenced the physiological function of cochlea.

This study examined the expression pattern of programmed cell death 5 (PDCD5) in cochlear hair cells and spiral ganglion neurons (SGNs) and its association with age-related hearing loss in mice.Sixty C57BL/6J (C57) mice at different ages were divided into four groups (3,6,9 or 12 months).PDCD5 expression was detected by using immunohistochemistry,real-time PCR and Western blot.Morphological change of the cochleae was also evaluated by using immunoassay.The results showed that the expression of PDCD5 had a gradual increase with ageing in both protein and RNA levels in C57 mice,as well as gradually increased apoptosis of cochlear hair cells and SGNs.In addition,we also found that caspase-3 activity was enhanced and its expression was enhanced with ageing.It is implied that overexpression of PDCD5 causes the increase in caspase-3 activity and the subsequent increase of apoptosis in cochlear hair cells and SGNs,and thereby plays a role in the pathogenesis of presbycusis.Thus,PDCD5 may be a new target site for the treatment and prevention of age-related hearing loss.