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.

OBJECTIVETo investigate the effects of advanced glycosylation end products (AGEs) modified bovine serum albumin (AGE-BSA) on the expression of reactive oxygen species (ROS) and monocyte chemoattractant protein-1 (MCP-1) in human renal mesangial cells (HRMCs).

METHODSHRMCs were cultured in vitro with medium containing different doses of AGE-BSA or BSA (50,100, 200, 400 mg/L) for 48 hours, or with AGE-BSA (200 mg/L) for different times (12, 24, 48, 72 h). Immunocytochemistry assay was used to estimate the protein level of RAGE. The ROS in cells were measured by flow cytometry and the mRNA expression of MCP-1 were analyzed by semi-quantiative reverse transcription-polymerase chain reaction (RT-PCR) after treatment with AGE-BSA or BSA.

RESULTSThe protein level of RAGE was upregulated in the HRMCs with AGE-BSA. The expression of ROS and MCP-1 significantly enhanced by incubation of AGE-BSA in a time- and dose-dependent manner. The effects of AGE-BSA-induced up-regulation of ROS and MCP-1 level was significantly blocked by neutralizing antibodies to RAGE, while the expression of ROS and MCP-1 stood nearly unchanged after cultured with huamn IgG.

CONCLUSIONThe expression of ROS and MCP-1 in HRMCs is induced by AGE-BSA through RAGE, which may have potential effects in the pathgenic mechanism of diabetic nephropathy.

Cells, Cultured ; Chemokine CCL2 ; metabolism ; Glycation End Products, Advanced ; pharmacology ; Humans ; Mesangial Cells ; drug effects ; metabolism ; Oxidative Stress ; drug effects ; Reactive Oxygen Species ; metabolism ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; metabolism ; Serum Albumin, Bovine ; pharmacology

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 explore the cognitive status of amyotrophic lateral sclerosis (ALS) patients, and to explore the involved cognitive domains, subtypes and risk factors of mild cognitive impairment in ALS ( ALS-MCI).Methods Twenty-nine cases of ALS and 58 healthy volunteers were included.The severity of the bulbar and spinal functions of the patients was evaluated by the Improved Norris Scale.According to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition-Revised( DSM-Ⅳ-R) criteria of dementia, ALS cases were classified as demented and non-demented.For non-demented ALS cases, the common cognitive batteries evaluating mental state, verbal memory, executive, attentional and visuospatial abilities were performed.Hamilton Anxiety Scale ( HAMA) and Hamilton Depression Scale (HAMD) were evaluated too.They were further classified into ALS-cognitively normal (ALS-CogNL) and ALS-MCI groups according to Petersen criteria of MCI.Risk factors possibly correlated with ALS-MCI were analyzed by comparing the differences in age, age of onset, duration of the disease, sites of onset, symptoms of bulbar and limb function between ALS-CogNL and ALS-MCI groups.Results Among 29 ALS cases, 14 (48.3% ) cases with cognitively normal( ALS-CogNL), 15 cases (51.7% ) with ALS-MCI,and none with dementia were identified.Among 15 ALS-MCI cases, 12 cases with executive dysfunction, 8 cases with memory deficits,9 cases with attention impairment and none with visuospatial impairment were found.ALSMCI cases could be further classified into three subtypes; 1 case with amnestic MCI (aMCI) ,6 cases with single domain non-memory MCI ( sdMCI), and 8 cases with multiple domains slightly impaired MCI (mdMCI).Between ALS-MCI and ALS-CogNL groups, there were significant differences (t = -2.435,- 2.576, both P ＜ 0.05) in education ((8.7 ± 2.8) years vs (11.3 ± 3.0) years) and Improved Norrisscale (bulbar score: (28.4 ± 7.7) scores vs ( 34.0 ± 3.4) scores) , however, no significant differences in sex, age, age of onset, duration,site of onset,HAMA or HAMD scores,and Improved Norris scale( spinal score) were found.Conclusions Cognitive deficits commonly exist in ALS patients.For the involved domains, executive dysfunction is the most common, deficits of attention and memory are also common, and deficit in visuospatial function is not found.The most common subtype of ALS-MCI is mdMCI.Severe bulbar symptoms and lower education may be the risk factors of ALS-MCI.