[Objective]Depression is a common mental illness with a profound impact on physical health.Depression has been associated with a higher risk of bacterial infection;however,whether this relationship is causal and how depression affects infection remains unclear.Therefore,we aimed to investigate the effects of depressive phenotype in infected mice by constructing a chronic unpredictable mild stress(CUMS)model.[Methods]Mice were induced with CUMS for 4 weeks.The depressive phenotype was evaluated using behavioral tests.Subsequently,the mice were intraperitoneally injected with Klebsiella pneumoniae to establish bacterial infection.Serum and abdominal tissues were collected 48 h after infection.Hematoxylin-eosin(HE)staining was used to observe the pathological changes in the tissues,and enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of inflammatory factors.In addition,the fecal samples collected before infection were analyzed for 16S rDNA gene of gut microbiota,and the expression levels of NF-κB/NLRP3 signaling pathway in colon tissues of uninfected mice were detected.[Results]Behavioral tests showed that compared with the control mice,CUMS mice had significantly lower body weight(P<0.0001,t=5.426),lower sucrose preference rate(P<0.001,t=4.937),increased swimming stationary time(P<0.001,t=16.37),and decreased time spent in the central area of the open field(P<0.01,t=3.575).Survival analysis showed that compared with the control mice,the survival rate of CUMS mice significantly decreased after infection(P<0.05).Additionally,histochemical staining showed that tissue damage in the liver(P<0.05,t=4.025),kidney(P<0.05,t=2.828),and mesentery(P<0.01,t=5.367)significantly increased.Furthermore,ELISA results showed that the levels of the inflammatory cytokines IL-6(P<0.01,t=3.365),IL-1β(P<0.01,t=4.061),TNF-α(P<0.01,t=4.460)and LPS(P<0.0001,t=27.24)were elevated.The difference was statistically significant.According to 16S rDNA sequencing,CUMS-induced changes in the intestinal bacterial community structure of mice,making them significantly different from the control mice.Compared with the control mice,the expression levels of NF-κB(P<0.01,t=6.825)and NLRP3(P<0.001,t=9.561)were upregulated in CUMS mice.[Conclusion]The CUMS model was successfully constructed and CUMS mice developed more severe bacterial infection.Gut microbiota was dysregulated and the expression of NF-κB/NLRP3 signaling pathway was up-regulated in CUMS mice,which was related to the susceptibility to bacterial infection.

Objective:To investigate the effects of histone deacetylase 6 (histone deacetylase 6, HDAC6) on oopherectomy (OOX) induced osteoporosis (OP) bone loss by binding to the promoter region of heat-shock protein 70 (HSC70) and regulating it’s acetylation.Methods:OP mouse model was established by using OOX methods. Then the mice were divided into sham operation group, OOX group, OOX+shHDAC6 group, OOX+shNC group and OOX+shHDAC6+shHSC70 group. The micro-CT system and Western blot experiment were used to detect the bone microscopic parameters of the mouse right femur and the protein expression levels of osteoblast-specific transcription factors. In vitro experiments, Westwen blot, alkaline phosphatase (ALP) staining and Alizarin Red S (ARS) staining were used to determine the effects of HDAC6 and HSC70 on the osteogenic differentiation of MC3T3-E1 cells. QRT-PCR was used to detect the expression levels of HDAC6 and HSC70 in tissue or cells. The relationship between HDAC6 and HSC70 was analyzed by ChIP experiment.Results:Compared with sham group, the expression of bone mineral density (BMD) , trabecular bone number (Tb. N) , trabecular thickness (Tb.th) and bone volume fraction (BV/TV) in the right femur of OOX group mice were decreased, the expression of TB. Sp was increased, protein expression of OSX and RUNX2 was increased. At the same time, compared with sham group (1±0.11) , the expression of HDAC6 was increased in OOX group (2.33±0.19) ( t=10.56, P<0.001) . Compared with pcDNA3.1-NC group, the protein level of Osterix (OSX) and runt-related transcription factor 2 (RUNX2) , ALP activity and mineralized area in pcDNA3.1-HDAC6 group were decreased (all P<0.05) . ChIP analysis showed that compared with the pcDNA3.1-NC group (5.26±0.47) , the acetylation level of the HSC70 promoter region in the pcDNA3.1-HDAC6 group (2.37±0.21) was significantly reduced ( t=9.72, P<0.001) . Compared with pcDNA3.1-HDAC6 group, the expression of OSX and RUNX2, ALP activity and mineralization were increased in pcDNA3.1-HDAC6+ pcDNA3.1-HSC70 group (all P<0.05) . Compared with OOX+shHDAC6 group, the expression of OSX and RUNX2 protein, BMD, Tb.N, Tb.th and BV/TV were decreased but the expression of Tb. Sp was increased in OOX+ shHDAC6+ shHSC70 group. Conclusions:HDAC6 regulates the acetylation level of HSC70 and then affects OOX-induced OP bone loss. Inhibition of HDAC6 can significantly improve OP bone loss.

Objective:To investigate the potential mechanism and effects of LncRNA BBOX1-AS1 in radiosensitivity of ovarian cancer.Methods:qRT-PCR was used to explore BBOX1-AS1, miR-185-5p expression in OC tissue and cells. Dual luciferase reporter assay was used to confirm the interaction of BBOX1-AS1, miR-185-5p and RHOA. MTT assay and flow cytometry were used to detect the proliferation and apoptosis of OC cells.Results:BBOX1-AS1 was up-regulated in OC tissue and cells, compared with the cell proliferative activity at 2, 3, 4 day (0.89±0.07) (1.48±0.13) (1.69±0.15) in si-NC group, proliferative activity in si-BBOX1-AS1 group (0.59±0.06) (0.97±0.09) (1.21±0.10) was obviously down-regulated (all P<0.05) . Compared with si-NC group (6.24±0.28) , silencing of BBOX1-AS1 induced apoptosis (12.07±1.33) (all P<0.05) . miR-185-5p was down-regulated in OC tissue and cells, the targeting relationship between BBOX1-AS1 and miR-185-5p, RHOA and miR-185-5p was confirmed. Inhibition of miR-185-5p reversed the effects of BBOX1-AS1 on OC cells (all P<0.05) . Conclusion:LncRNA BBOX1-AS1 inhibits radiotherapy sensitivity of OC cells via regulating miR-185-5p/RHOA axis.

Background/Aims: Gastroparesis is commonly seen in patients with diabetes and functional dyspepsia with no satisfactory therapies. Dysautonomia is one of the main reasons for the imbalanced motility. We hypothesized that spinal cord stimulation (SCS) is a viable therapy for gastroparesis via the autonomic modulation to improve gastric motility. The aim is to find an optimal method of SCS for treating gastroparesis. Methods: Eight healthy-female dogs were implanted with a gastric cannula, a duodenal cannula, 2 multi-electrode spinal leads, and an implantable pulse generator. Gastric motility index (MI) was used to determine the best stimulation location/parameters of SCS. Optimized SCS was used to improve glucagon-induced gastroparesis. Results: With fixed parameters, SCS at Thoracic 10 (T10) was found most effective for increasing gastric MI (37.8%, P = 0.013). SCS was optimized with different parameters (pulse width: 0.05-0.6 msec, frequency: 5-500 Hz, motor threshold: 30-90%) on T10. Our findings revealed that 0.5 msec, 20 Hz with 90% motor threshold at T10 were the best parameters in increasing MI. Glucagon significantly delayed gastric emptying, and this inhibitory effect was partially blocked by SCS. Gastric emptying at 120 minutes was 25.6% in the control session and 15.7% in glucagon session (P = 0.007 vs control), while it was 22.9% with SCS session (P = 0.041 vs glucagon). SCS with the optimal parameters was found to maximally enhance vagal activity and inhibit sympathetic activity assessed by the spectral analysis of heart rate variability. Conclusions SCS with optimized stimulation location and parameters improves gastric motility in healthy-dogs and accelerates gastric emptying impaired by glucagon via enhancing vagal activity.

Objective To evaluate the clinical efficacy and safety of domestic BuMA biodegradable drug eluting coronary stent in elderly coronary heart disease patients over 75 years old with shortened duration of clopidogrel treatment. Methods 100 elderly patients who received coronary angiography and PCI were included, and they were randomly divided into the observation group ( n=50, received oral clopidogrel for 9 months) and the control group (n=50, received oral clopidogrel for 12 months). The occurance of angina pectoris, AMI, bleeding events and the results of control angiography were compared between the two groups after 12 months of follow-up. Results All the 100 patients were followed up in 12 months after discharge. 4 patients ( 8. 0%) in the observation group and 3 patients ( 6. 0%) in the control group had recurrent angina. Control coronary angiography 12 months later showed no restenosis in the stents. There was no significant difference between the two groups in the recurrence of angina pectoris and coronary stent restenonsis. No acute myocardial infarction,cliniacl bleeding events and late stent thrombosis occurred in the two groups. Conclusions The application of the domestic BuMA biodegradable drug eluting stent for the treatment of coronary heart disease patients over 75 years old is safe and effective with shortened duration of clopidogel treatment.