Aim To analyze the blocking effect of ( ± ) doxazosin [ ( ± ) DOX ] , ( -) doxazosin [ ( -) DOX] and ( +) doxazosin [( +) DOX] on the vaso-constriction of rat isolated mesenteric arterioles media-ted by α1-adrenoceptors. Methods The vasoconstric-tion induced by phenylephrine ( Phe) in the rat isola-ted mesenteric arterioles ( the second- and third-order branches) was recorded using DMT wire myograph sys-tem 620M, and theα1-adrenoceptor antagonistic activ-ity of ( ± ) DOX and its enantiomers was analyzed. Results The inner diameter of second- and third-or-der branches of the rat mesenteric artery was (162. 5 ± 5. 3) μm (n=11) and (103. 1 ± 2. 3) μm (n=23), respectively. The values of normalized preload of the second-and third-order branches, which were calculat-ed by the LabChart software, were (2. 93 ± 0. 51) mN ( n =11 ) and ( 2. 64 ± 0. 50 ) mN ( n =23 ) ( P >0. 05 ) . Vasoconstrictive responses to Phe in the sec-ond-order branche of rat mesenteric artery under nor-malized preloads were not significantly different from those under 5 mN preload;however, the Emax values of the Phe-induced vasoconstriction under 10 mN, 15 mN and 20 mN preloads were decreased by 12%, 29%and 43% ( P<0. 01 ) respectively compared with those under normalized preload. The concentration-response curves for Phe were shifted to right in a concentration dependent manner by ( -) DOX or ( +) DOX at 0. 001 , 0. 01 and 0. 1 μmol · L-1 without significant change in their Emax values in the second-and third-or-der branches of rat mesenteric artery. Schild plot anal-ysis indicated that ( -) DOX, ( +) DOX and ( ± ) DOX non-competitively inhibited the vasoconstrictive responses to Phe in the second-order branches, and the rank order of pKB values was ( +) DOX ( 8. 67 ± 0. 10 ) , ( ± ) DOX ( 8. 53 ± 0. 090 ) , ( -) DOX (7. 85 ± 0. 09). However, schild plot analysis indica-ted that ( -) DOX and ( +) DOX competitively inhibi-ted the vasoconstrictive responses for Phe in the third-order branch, and the rank order of their pKB values was ( ± ) DOX ( 8. 68 ± 0. 17 ) , ( +) DOX ( 8. 48 ± 0. 10 ) , ( -) DOX ( 7. 48 ± 0. 140 ) . Conclusion The α1-adrenoceptor blocking activity of ( -) DOX is much weaker than that of ( +) DOX or ( ± ) DOX in the rat isolated mesenteric arterioles, and there is a tendency to enhance the activity of ( ± ) DOX in third-order branches of the rat mesenteric artery though theα1-adrenoceptor blockade effect of ( ± ) DOX is not significantly different from ( +) DOX.

Aim To study the mechanisms of inotropic responses to doxazosin enantiomers in the isolated rat atrium.Methods We analyzed the positive inotropic response to (-)doxazosin and the negative inotropic response to (+)doxazosin in the left atrium of rat u-sing receptor-pharmacological technique.Results In the preparation treated with verapamil,the positive in-otropic responses to 3 μmol·L-1 (-)doxazosin were significantly inhibited from the control level (245.7 1 ± 44.29)mg to (172.50 ±43.34)mg,(P<0.05).In the preparation treated with methylene blue,the posi-tive inotropic responses to 3 μmol·L-1 (-)doxazosin were significantly potentiated from the control level (245.7 1 ±44.29 )mg to (303.33 ±45 .90 )mg,(P<0.05 ).In the preparation treated with H-89 ,the positive inotropic responses to 3,10 and 30 μmol · L-1 (-)doxazosin were (338.57 ±96.86 ) mg, (471.43 ±107.61)mg and (520.00 ±103.44)mg, which were significantly (P<0.05 ~0.01)larger than the control levels of (245.71 ±44.29)mg,(314.29 ±90.34)mg and (357.14 ±68.49 )mg.Treatment with phenoxybenzamine,atropine,propranolol or indo-methacin did not significantly affect the responses to doxazosin enantiomers.Conclusion The positive ino-tropic responses to (-)doxazosin in the isolated left a-trium of rat are partially involved in L-type Ca2+chan-nels and intracellular cGMP level.However,α-adre-noceptors,muscarinic receptors,β-adrenoceptors and cyclooxygenases are not related to the responses to doxazosin enantiomers.

Objective In order to observe central responses during naturally occurring urinary bladder storage in healthy subjects,we examined brain areas that control strong bladder sensation by resting-state functional magnetic resonance imaging (rs-fMRI).Methods 44 healthy subjects (19 men and 25 women,between 22 and 50 years of age) were screened in the study from October 2014 to October 2016.All subjects were right-handed and scanned twice under the following two conditions:empty bladder (bladder volume ＜ 10 ml)and full bladder (‘strong desire to void’,bladder volume between 200 and 400 ml)without the use of filling with a catheter.Brain imaging softwares (SPM8,DPABI,REST) were adopted to analyze the difference in brain-blood perfusion between these two conditions.Voxel-based analysis of the regional homogeneity (ReHo) was performed to analyze rs-fMRI data including the main excitatory regions and inhibitory areas,peak value (X-axis,Y-axis,Z-axis),clusters size (active volume unit:number of voxel),T value (the excitatory and inhibitory extent of brain active regions).Results The rs-fMRI scans of 44 healthy subjects were analyzed.Nine subjects were excluded because of excessive head movements of more than 1.5 mm and 1.5° in rotation.Data sets were obtained from 35 subjects in two states of bladder,empty bladder and strong desires to void.Increased activity during strong desire to void was observed in the prefrontal cortex (PFC),anterior cingulate cortex (ACC),hypothalamus,temporal lobes and left caudate nucleus.Conclusions There are significant changes in the brain's ReHo during the strong sensation to void.The results suggest that the PFC,the ACC,hypothalamus,temporal lobes and left caudate nucleus play a role in the cerebral control of bladder storage without artificial bladder filling in healthy people.

Objective To evaluate the efficacy of the intravesical injection of botulinum toxin A (BTX-A) and bladder hydrodistention plus sodium hyaluronate (Cystistat) instillation in patients with interstitial cystitis/bladder pain syndrome (IC/BPS).Methods We retrospectively reviewed 153 women with IC/BPS from January 2003 to December 2015.Of the 153 patients,77 were treated with BTX-A(group A),the average age was (56.0 ± 4.1) years old.76 underwent bladder hydrodistention plus sodium hyaluronate (Cystistat) instillation (group B),the average age was (58.0 ± 3.3) years old.The patients were evaluated using the O'Leafy-Saint score,visual analog scale pain score,urinary frequency record and quality of life questionnaire before treatment and 1 week,1,3,6 and 12 months after treatment.Results In group A,only 2 had acute urinary retention,27 received a repeat injection,and 28 were lost to follow-up.In group B,3 had urinary tract infection,15 switched to BTX-A injection at 6 months because the treatment of hydrodistention plus Cystistat instillation is not good.31 were lost to follow-up.BTX-A was shown to remain effective for up to 6 months after treatment.After repeated Chinese BTX-A injections,symptoms improved significantly.Hydrodistention plus Cystistat remained effective for up to 3 months after treatment.Conclusions Intravesical injection of BTX-A is a effective therapeutic option for patients with IC/BPS.The average duration of the effect of one dose of Chinese BTX-A was 6 months.Repeated injection of BTX-A is effective.

Objective:To observe the changes of macular structure and microvessels in eyes with diabetes macular ischemia (DMI).Methods:A retrospective case study. From January 2023 to July 2023, 23 patients of 31 eyes diagnosed with DMI at Tangshan Ophthalmological Hospital were included in this study. Among them, there were 14 males with 23 eyes; Female cases with 8 eyes. Age were (59.5±4.6) years old. According to the DMI grading standard formulated by the research group for early treatment of diabetes retinopathy, the patients were divided into mild DMI group, moderate DMI group, and severe DMI group, with 8, 12, and 11 eyes respectively. The blood flow density (VD), perfusion area (FA), small vessel VD (SVD), inner retinal capillary plexus VD, FA, and outer retinal, choroidal, and ganglion cell complex (GCC) thickness within 1 mm of the macular fovea in retinal superficial vascular plexus (SVP)were measured using a scanning frequency light source optical coherence tomography instrument. The changes in macular structure and microvasculature in the affected eyes of different degrees of DMI groups were compared and observed. Inter group comparisons were conducted using one-way ANOVA or Kruskal Wallis H-test. Spearman correlation analysis was used to analyze the correlation between DMI severity and GCC, outer retina, choroid thickness, VD, FA and SVP VD, SVD and FA in inner retina. Results:The GCC ( F=70.670), outer retinal thickness ( H=12.393), VD ( F=105.506), SVD ( H=25.300), FA ( F=107.655), and VD ( H=24.098) and FA ( H=25.300) of the retinal SVP in the mild, moderate, and severe DMI groups were compared, and the differences were statistically significant ( P<0.05). There was no statistically significant difference in choroidal thickness ( H=2.441, P>0.05). Pairwise comparison between groups: VD, SVD, FA of GCC thickness and SVP, and VD of inner retina were statistically significant between severe DMI group and moderate DMI group, and between moderate DMI group and mild DMI group ( P<0.05). The thickness of outer retina was statistically significant between severe DMI group and moderate DMI group ( P<0.05). Inner retinal FA: there were statistically significant differences between severe DMI group, moderate DMI group and mild DMI group ( P<0.05). The correlation analysis results showed that GCC ( r s=-0.918), outer retinal thickness ( r s=-0.448), and inner retinal VD ( r s=-0.894) and FA ( r s=-0.918), as well as VD ( r s=-0.919), SVD ( r s=-0.924), and FA ( r s=-0.939) of retinal SVP, were all negatively correlated with the degree of DMI ( P<0.05). There was no correlation between choroidal thickness and degree of DMI ( r s=-0.081, P>0.05). Conclusion:The thickness of GCC, outer retina and choroid, the VD, SVD, and FA of the retinal SVP, the VD and FA of inner retina are all reduced in eyes with different degrees of DMI, while all of them are negatively correlated with the degree of DMI, except for choroid thickness.

OBJECTIVE To analyze the influential factors of cardioto xicity in patients with positive breast cancer of human epidermal growth factor receptor 2（HER-2）treated by trastuzumab combined with chemotherapy. METHODS From April 2017 to January 2021，200 HER-2 positive breast cancer patients receiving pirarubicin + cyclophosphamide combined with sequential paclitaxel+trastuzumab were collected from our hospital. According to the presence or absence of cardiotoxicity ，the patients were divided into cardiotoxicity group and non-cardiotoxicity group. The clinical data and echocardiographic results of the patients were collected，and the influential factors of cardiotoxicity were analyzed. RESULTS Among 200 patients，43 patients suffered from cardiotoxicity with the incidence of 21.5％. The proportion of patients with cardiotoxicity during pirarubicin+cyclophosphamide therapy accounted for 5.5％（11/200），and the proportion of patients with cardiotoxicity during sequential paclitaxel+trastuzumab therapy accounted for 20.5％（41/200）；the latter was significantly higher than the former （P＜0.01）. At the same time ，the decrease of left ventricular ejection fraction during sequential therapy of paclitaxel and trastuzumab was significantly higher than that during pirarubicin+cyclophosphamide therapy [ 14％（12％，17％）vs. 7％（3％，10％），P＜0.001]. Compared with patients without cardiotoxicity ，the proportion of patients with cardiotoxicity with a history of hyperlipidemia was significantly higher （P＜ 0.01），while the proportion of patients receiving dexrazoxane was significantly lower （P＜0.01）. Results of binary Logistic regression analysis showed that the history of hyperlipidemia [OR ＝3.672，95％ CI（1.499，8.992），P＝0.004] and the use of dextrazoxane [OR ＝0.154，95％ CI（0.072，0.330）， P＜0.001] were associated with the occurrence of cardiotoxicity. CONCLUSIONS Hyperlipidemia is an independent risk factor for cardiotoxicity induced by pirarubicin + cyclophosphamide combined with sequential paclitaxel+trastuzumab in HER 2 positive breast cancer patients ，while the use of dextrazoxane is a protective factor.