OBJECTIVE To investigate the effect of anxiolytics and antidepressants on anxiety-and/or depression-like behaviours induced by designing a Liang′s contextual-stress box, (Liang′s box) in mice . METHODS Liang′s box was composed of a central area and three peripheral arms. Buspirone (0.5 and 1.0 mg·kg-1) and mianserin (0.25 and 0.5 mg·kg-1) were injected to mice intraperitoneally and the following behavioral indexes were recorded: ① latency to the central area(CA), ② CA-time, ③ CA-distance,④distance traveled in the peripheral area (PA-distance)⑤number of the transitions, and ⑥global activity. RESULTS ①Buspirone 0.5 and 1.0 mg · kg-1 decreased the latency to CA by as much as 71.9%(P<0.05) and 77.9%(P<0.05), but dose-dependently increased the CA-time by 59.5% and 73.8%(P<0.05) respectively. Although buspirone 0.5 and 1.0 mg · kg-1 obviously reduced the shuttle number(P<0.05), it did not have significant pharmacological effects on the CA-and PA-distance or global activity.②Mianserin 0.25 and 0.5mg·kg-1 decreased the latency to CA by as much as 72.4%(P<0.05) and 82.3%(P<0.05), but dose-dependently increased the CA-time by 39.1%and 43.9%(P<0.05), respec?tively. Mianserin enhanced the shuttle number(P<0.05) and CA-distance(P<0.05) in a dose-dependent manner, but it had no obvious pharmacological effects on the PA-distance or global activity. CONCLUSION Anxiety-and/or depression-like behaviors can be stimulated by Liang′s box in mice, which may be used as a novel animal model of anxiety and depression comorbidity to study its pathophysiological mecha?nisms, screen and evaluate certain new anxiolytics and antidepressants.

Objective To investigate the exact protocol eliciting the hippocampal CA1 long-term depression (LTD) of rats in vivo and the effect of amyloid β-protein (Aβ) on the LTD.Method By applying test stimulation to Schaffer collateral in hippocampal CA1 region in rats,recorded the in vivo field excitatory postsynaptic potentials (fEPSPs) ;further,observed the induction of LTD with different low frequency stimulation (LFS) and investigated the effect of Aβ25-35 on the LTD.Results Prolonged LFS (1,5 and 10 Hz) but not paired-pulse stimulus (PPS) effectively elicited the LTD in the hippocampal CA1 region,with significantly decreased amplitude of fEPSPs after LFS ; 1 Hz 900 pulses group induced a stronger LTD,being (63.7 ± 3.8) ％ at 120 min post-LFS,lower (P ＜ 0.05) than (75.1 ± 3.2) ％ in 600 pulses group ; different frequencies (1,5 and 10 Hz) of LFS with same pulses induced similar degree of LTD,the amplitude of fEPSPs were (63.7 ± 3.8) ％,(61.2 ± 3.6) ％ and (59.8 ± 3.9) ％ respectively,without significant differences between any two groups (P ＞ 0.05) ; after applying 12.5 nmol and 25 nmol Aβ25-35,the amplitude of fEPSPs decreased to (63.2 ± 3.8) ％ and (46.8 ± 3.9) ％,respectively,and lower and than that in control ((73.9 ± 3.0) ％,P ＜ 0.05).Conclusion Prolonged LFS effectively induced in vivo hippocampal LTD of rats,which provides an important electrophysiological protocol for the study of synaptic plasticity; Aβ25-35 injection dont affect the baseline synaptic transmission,but dose-dependently enhance the in vivo hippocampal LTD of rats,indicating that Aβ-induced LTD facilitation may be involved the early impairment of learning and memory in Alzheimer's disease.

Objective To evaluate the effect of fingolimod(FTY720) on angiotensin Ⅱ(AngⅡ)-induced renal oxidative stress in rats and its possible mechanisms.Methods Thirty-six male Sprague-Dawley rats were divided into three groups through random number tables:AngⅡ infusion group(twelve rats,infusion of AngⅡvia subcutaneous osmotic pumps),0.9% sodium hydrochloride solution infusion group(twelve rats,infusion of equal volume of 0.9% sodium hydrochloride solution via subcutaneous osmotic pumps) and FTY720 intervention group(twelve rats,intra-gastric administration of FTY720 besides AngⅡ infusion).Urine samples were collected for 24 hours every week.Blood samples and kidneys were collected when rats were sacrificed at day 14 and 28 d respectively.MDA and T-SOD assay Kits were used to detect the concentrations of MDA and T-SOD in serum and kidney homogenates.Renal pathological changes were observed by light microscope.The expression of Nox4 in the kidneys was evaluated by immunohistochemistry.Results Compared with 0.9% sodium hydrochloride solution infusion rats of the same period,AngⅡ-infused rats developed significant proteinuria.The concentration of serum creatinine,urea nitrogen,AngⅡ and MDA were increased(P<0.05),T-SOD was significantly decreased on days 14 and 28(P<0.05),the serum albumin was significantly increased on day 28(P<0.05),while FTY720 partially reversed these changes.The renal tissue of AngⅡ-infused rats presented mesangial cells proliferation,mesangial matrix deposition,tubular epithelial cells effacement,sclerosis and atrophy in part of the glomerular.FTY720 can alleviate these changes.Immunohistochemistry showed that Nox4 was primarily located in the distal tubule.The expression of Nox4 was significantly increased in AngⅡ-infused rats as compared with that of 0.9% sodium hydrochloride solution infused group rats,and FTY720 administration prevented the change effectively.Conclusion AngⅡ-induced renal injury could be attenuated by FTY720 via preventing oxidative stress.

During growth and progression, the microenvironment of tumors suffers a series of abnormal characteristics, which include hypoxia, acid pH, increased oxidative stress, excess glutathione (GSH), as well as certain overexpressed enzymes. Although affect or limit the cancer therapeutic outcomes, these factors provide possible approaches to strategies for cancer detection and novel therapy at the same time. Recently, based on these properties of the tumor microenvironment (TME), various kinds of responsive nano-platforms have been continuously developed and applied in cancer theranostics preliminarily. Thus, this review would introduce the typical features of TME firstly, then detailly summarize the design principles and research progress of corresponding hypoxia-responsive, pH-responsive, redox-responsive, enzyme-responsive, dual-responsive and multi-responsive nano-platforms. Finally, the challenges and the perspectives of the TME-responsive nano-platforms are briefly discussed.

Objective:To detect the value of utilizing bpMRI in prostate biopsy in the detection of prostate cancer with PSA≤20ng/ml.Methods:The clinical data of 394 patients who underwent prostate biopsy in the First Affiliated Hospital of Nanjing Medical University from November 2017 to October 2019 were retrospectively analyzed. Of all the patients, 177 underwent modified systematic biopsy, named TRUS group, 217 patients accepted pre-biopsy bpMRI examination, undergoing modified systematic biopsy if Prostate Imaging Reporting and Data System (PI-RADS) score < 3 or MRI-TRUS cognitive fusion targeted prostate + systematic biopsy if PI-RADS score ≥ 3, named MRI group. The median age of TRUS group was 66 (61, 74) years old, prostate specific antigen (PSA) was 9.52 (7.26, 12.30) ng / ml, and prostate volume (PV) was 36.84 (28.95, 57.72)ml. The median age of MRI group was 66 (59, 72) years old, PSA was 8.84 (6.65, 12.16) ng/ml, and PV was 39.45 (29.25, 58.69)ml. There was no difference in above parameters between the two groups. The χ 2 test was used to compare the detection rate of prostate cancer and clinically significant prostate cancer (CsPCa) between the two groups. Results:There was no significant difference in the detection rates of prostate cancer between TRUS group and MRI group [51.41% (91/177) vs. 48.39% (105/ 217), P = 0.550], but the detection rates of CsPCa were significantly different [26.55% (47/177) vs. 36.41% (79/217), P = 0.037]. In patients with PSA ≤ 10 ng / ml, there was no significant difference in the detection rates of prostate cancer between the two groups [43.62% (41/94) vs. 43.08% (56/130), P = 0.936], but there was a significant difference in the detection rates of CsPCa [17.02% (16/94) vs. 28.46% (37/130), P = 0.047]. There was no significant difference in the detection rates of prostate cancer [60.24% (50/83) and 56.17% (48/87), P= 0.504] and the detection rates of CsPCa [37.35% (31/83) vs. 48.28% (42/87), P = 0.150] between the two groups. The total detection rates of the last two needles in TRUS group and MRI group were 23.16% (41/177) and 36.63% (86/217), respectively, with significant difference ( P=0.001); the detection rates of CsPCa in the last two needles were 11.86% (26/177) and 29.03% (63/ 217), respectively, with significant difference ( P < 0.001). In MRI group, the detection rates of prostate cancer in patients with PI-RADS score <3, 3, 4, 5 were 21.21% (7/33), 25.84% (23/89), 73.24% (52/71), 95.83% (23/24), respectively; the detection rates of CsPCa were 12.12% (4/33), 17.98% (16/89), 54.93% (39/71), 83.33% (23/24), respectively. Conclusions:In patients with PSA ≤ 20 ng / ml, prostate biopsy based on bpMRI may improve the detection of CsPCa, especially in patients with PSA ≤ 10 ng/ml.

To study the changes of metabolites in rat urine after treatment of Aristolochia fangchi decoction by metabonomic method.

Objective To investigate the role of AcrAB-TolC efflux pump in fluoroquinolones resistance by Shigella. spp and to explore the significance of AcrAB-TolC efflux pump on mutation of acrR, soxS and marOR as well as on drug re?sistence. Methods Drug resistant bacteria were selected by Kirby-Bauer disk diffusion test. After addition of efflux pump inhibitor carbonylcyanide-m-chlorophenylhydrazone (CCCP), change of minimal inhibitory concentration (MIC)s of nilidixic acid, Levofloxacin, ofloxacin, ciprofloxacin and Norfloxacin were examined. The DNA binding region of acrA, acrB, soxS, acrR and marOR gene in these mutants were amplified by PCR and sequenced. Results Among the 159 clinical isolates of Shigella,11 strains are resistant to fluoroquinolone. After the addition of CCCP, MICs of 2 fluoroquinolone resistant strains decreased; the MICs of 7 fluoroquinolone resistant strains did not change; MICs of 2 fluoroquinolone resistant strains in?creased. The corresponding nucleotides C, A, T, T on the 36th to 39th of marOR gene were missing, showing by sequencing, in fluoroquinolone resistent strains which might be regulated by the efflux pump gene AcrAB-TolC. Conclusion Efflux pump inhibitor could restrain the activity of efflux partially. The mutations of marOR might play an important role in fluoroquino?lone resistent by shigella.

Objective To investigate the correlation between the quantitative results,the semi-quantitative scores from ultrasound elastography and the distribution of myofibroblasts (MFS)in breast tumor,and to analyze the value of quantitative results and the semi-quantitative score from ultrasound elastography in the diagnosis of breast tumor.Methods Thirty eight patients with breast lesions underwent ultrasound elasticity examinations,tissue dispersion quantitative analysis technique was used to assess the 11 characteristic quantities and the corresponding strain ratios in all lesions,and the score of ultrasonic elastography was evaluated.38 cases were divided into benign and malignant group according to pathological diagnosis results.The expression levels of CD34 andα-SMA protein in breast tissue were examined by immunohistochemistry.The distribution patterns of MFS in breast tumor were analyzed. The correlation between the quantitative results, the semi-quantitative scores from ultrasound elastography and the distribution of MFS in breast tumor was studied.Results The expression level of CD34 in malignant group was significantly higher than that in benign group, while the expression level of α-SMA was significantly higher than that in benign group;the differences in the expression levels of CD34 andα-SMA between benign and malignant breast tumor patients were statistically significant (P < 0.01 ).The masses observed in malignant group by elastography were shown in blue,while most of the masses in benign group were shown in green.There were statistically significant differences between two groups in elastography scores (P < 0.05 ). There was a anegative correlation between the CD34 expression in tumor tissue and the score of ultrasound elastography (r=-0.423 7,P =0.027 3).There was a negative correlation between the CD34 expression and the score of ultrasound elastography (r=-0.423 7,P =0.027 3),while the positive correlation was found between theα-SMA expression and the score of ultrasound elastography (r=0.397 0,P =0.014 2).The CD34 expression was significantly correlated with the average relative strain value,entropy,area ratio of low-strain region,kurtosis, skewness and inverse difference moment (P <0.05).Among the 11 characteristics,CD34 was positively correlated with the average relative strain value (r=0.385 6,P =0.016 8)and entropy (r=0.380 5,P =0.018 5);CD34 was negatively correlated with area ratio of low-strain region (r = - 0.351 7,P = 0.030 4),kurtosis (r =-0.427 7,P =0.007 4),skewness (r=-0.394 6,P =0.014 2),inverse difference moment (r = -0.344 3, P =0.034 3),angular second moment (r = - 0.484 9,P = 0.002 0)and strain ration (r = - 0.379 0,P =0.047 5);CD34 was not correlated with standard deviation,complexity and contrast (P > 0.05).The α-SMA espression was positively correlated with kurtosis (r = 0.356 9,P = 0.027 8),skewness (r = 0.323 0,P =0.047 9),area ratio of low-strain region (r=0.382 0,P =0.021 6)and strain ratio (r=0.403 3,P =0.012 0). Conclusion The features and its scores of ultrasound elastography are correlated with the distribution of MFS in breast tumor,suggesting that the ultrasound elastography is very informative and helpful in the diagnosis of breast tumor.

Objective To assess the value of susceptibility-weighted imaging (SWI) in staging hepatic fibrosis (HF) in rabbits. Methods Sixty healthy rabbits were randomly divided into HF group (n=44), control group (n=16). Rabbits in the HF group and supplementary group were injected subcutaneously with 50%CCl4 oily solution to establish hepatic fibrosis model. On the basis of preliminary test, 8 rabbits in the HF group and 4 rabbits in the control group were selected randomly at the 4th, 5th, 6th, 10th week after CCL4 injection ,respectively , to undergo liver MR scan,including conventional axial T1WI, T2WI and axial SWI, DWI scan. All rabbits were sacrificed after MR scan and the tissue of liver were sampled for pathological test and hepatic fibrosis staging. Rabbits were classified into group F0, F1-2 and F3-4 based on pathological results. Liver signal intensity (SI), and liver-to-muscle SI ratio were measured on SWI images and ADC values were measured on DWI images correspondently. One-way ANOVA analysis was performed to compare difference in liver SI, liver-to-muscle SI ratio and ADC values among group F0 (no fibrosis), F1-2 (mild-moderate fibrosis) and F3-4 (severe fibrosis) . Spearman correlation analysis was performed to correlate pathological staging and liver SI, liver-to-muscle SI ratio and ADC values. Receiver operating characteristic (ROC) curve analysis was performed to compare the diagnostic performance of SWI and DWI for staging HF. Results Two and 5 rabbits in the HF group died at the 5th and the 6th week after CCL4 injection , respectively due to acute hepatic necrosis, hepatorrhexis and systemic failure. Seven rabbits in supplementary group were used as supplement. Of the 16 rabbits in the control group, 1 was excluded from the study due to liver fibrosis. Fifteen rabbits in group F0, sixteen rabbits in group F1-2 and sixteen rabbits in group F3-4 underwent MRI and were included into this study. Liver-to-muscle SI ratio in group F0, F1-2 and F3-4 were 0.973 ± 0.020, 0.880 ± 0.090 and 0.649 ± 0.140, respectively. Liver SI were 378 ± 45, 374 ± 19 and 317 ± 34. ADC values were (1.473 ± 0.320) × 10-3, (1.311 ± 0.310) × 10-3 and (0.942 ± 0.180) × 10-3mm2/s. There were statistically significant differences in liver SI, liver-to-muscle SI ratio and ADC values among group F0, F1-2 and F3-4 (F=46.571,15.803 and 15.317, P< 0.01). Liver-to-muscle SI ratio was highly negatively correlated with HF staging (r=-0.818,P<0.01), while liver SI and ADC values were moderately correlated with HF staging (r=-0.565,-0.630;P<0.01). Area under ROC curve (AUC) of liver-to-muscle SI ratio, liver SI and ADC value for differentiating hepatic fibrosis stage F0 and stage F1-4 were 0.916, 0.695 and 0.768, while the AUC for differentiating hepatic fibrosis stage F0-2 and stage F3-4 were 0.951, 0.904 and 0.900. Conclusion Liver-to-muscle SI ratio on SWI provide added diagnostic value and could be an useful parameter for staging hepatic fibrosis.