Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. In particular, increasing evidence has showed that astrocyte-mediated neuroinflammation is involved in the pathogenesis of PD. As a precious traditional Chinese medicine, bear bile powder (BBP) has a long history of use in clinical practice. It has numerous activities, such as clearing heat, calming the liver wind and anti-inflammation, and also exhibits good therapeutic effect on convulsive epilepsy. However, whether BBP can prevent the development of PD has not been elucidated. Hence, this study was designed to explore the effect and mechanism of BBP on suppressing astrocyte-mediated neuroinflammation in a mouse model of PD. PD-like behavior was induced in the mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg·kg^-1) for five days, followed by BBP (50, 100, and 200 mg·kg^-1) treatment daily for ten days. LPS stimulated rat C6 astrocytic cells were used as a cell model of neuroinflammation. THe results indicated that BBP treatment significantly ameliorated dyskinesia, increased the levels of tyrosine hydroxylase (TH) and inhibited astrocyte hyperactivation in the substantia nigra (SN) of PD mice. Furthermore, BBP decreased the protein levels of glial fibrillary acidic protein (GFAP), cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS), and up-regulated the protein levels of takeda G protein-coupled receptor 5 (TGR5) in the SN. Moreover, BBP significantly activated TGR5 in a dose-dependent manner, and decreased the protein levels of GFAP, iNOS and COX2, as well as the mRNA levels of GFAP, iNOS, COX2, interleukin (IL) -1β, IL-6 and tumor necrosis factor-α (TNF-α) in LPS-stimulated C6 cells. Notably, BBP suppressed the phosphorylation of protein kinase B (AKT), inhibitor of NF-κB (IκBα) and nuclear factor-κB (NF-κB) proteins in vivo and in vitro. We also observed that TGR5 inhibitor triamterene attenuated the anti-neuroinflammatory effect of BBP on LPS-stimulated C6 cells. Taken together, BBP alleviates the progression of PD mice by suppressing astrocyte-mediated inflammation via TGR5.
Humans ; Mice ; Rats ; Animals ; Aged ; Middle Aged ; Parkinson Disease/pathology* ; Astrocytes/pathology* ; Powders/therapeutic use* ; Ursidae/metabolism* ; NF-kappa B/metabolism* ; Neuroinflammatory Diseases ; Neurodegenerative Diseases/metabolism* ; Cyclooxygenase 2/metabolism* ; Lipopolysaccharides/pharmacology* ; Bile ; Mice, Inbred C57BL ; Microglia ; Disease Models, Animal

Objective:To explore the status of HIV infection, time trends and related factors of MSM in Harbin from 2009 to 2018 and provide evidences for comprehensive prevention and control strategies of MSM HIV/AIDS.Methods:From April to July during 2009-2018, continuous cross-sectional studies were conducted on MSM recruited through snowball sampling. The unified questionnaire was used to collect demographic, behavioral, and serological information. The SPSS 23.0 software was used for statistical analysis, and the Joinpoint 4.8.0.1 software was applied to the annual percent change (APC) for time trends analysis using the Joinpoint regression model.Results:A total of 4 813 MSM were surveyed in Harbin from 2009 to 2018. The overall HIV antibody positive rate was 11.3 % ( 543/4 813). Joinpoint regression analysis showed that there was an increase in the HIV antibody positive rate from 2009 to 2015, while the segmentation point was in 2015 ( Z=4.2, P<0.05) but, there was a decrease from 2015 to 2018( Z=-1.3, P=0.3). The positive rate of syphilis antibody was 12.9% (621/4 813). There was a decrease in the positive rate of syphilis antibodies from 2009 to 2013 ( Z=-2.8 ,P<0.05). There was a decrease in the positive rate of syphilis antibodies from 2013 to 2018 ( Z=-0.7, P=0.5). Results from multiple logistic aggression analysis showed that the risk factors associated with the prevalence of HIV infection including network recruitment (a OR=1.307, 95% CI: 1.057-1.617), age 30 and above (a OR=1.905, 95% CI: 1.235-2.939) and syphilis antibody positive (a OR=4.728, 95% CI: 3.751-5.961). Protective factors appeared: knowledge of HIV/AIDS (a OR=0.598, 95% CI: 0.433-0.825) and consistent use of condom during anal sex in the past six months (a OR=0.683, 95% CI: 0.550-0.850). Conclusions:The HIV antibody positive rate peaked in 2015 among MSM in Harbin from 2009 to 2018, first increased and then decreased. The positive rate of syphilis antibody showed a decreasing trend. Intervention models based on social media software, age 30 and above and syphilis antibody-positive need to be explored. It also promotes condom use and referral for syphilis among MSM.

OBJECTIVE：To systematically evaluate clinical efficacy of L-carnitine in the treatment of male infertility ，and to provide evidence-based reference for clinical treatment of male infertility. METHODS ：Retrieved from CNKI ，Wanfang database ， VIP，CBM，PubMed，Embase and the Cochrane library ，randomized controlled trials （RCTs）about L-carnitine and other chemical drugs in the treatment of male infertility were collected during the inception to Apr. 12th，2020. After data extraction of included literatures and quality evaluation with modified Jadad scale ，Meta-analysis was conducted by using RevMan 5.3 software. RESULTS：A total of 8 RCTs were included ，with 520 patients. The results of Meta-analysis showed that compared with other chemical drugs ，L-carnitine could significantly enhance the semen volume [MD＝0.55，95％CI（0.20，0.91），P＝0.002] and sperm mortality rate [MD＝1.60，95％CI（0.50，2.69），P＝0.004] of male infertility patients ，with statistical significance. There was no statistical significance in sperm count [MD＝4.00，95％ CI（－3.15，11.15），P＝0.27]，the percentage of forward motile sperm [MD＝12.58，95％CI（－3.87，29.03），P＝0.13]，and the percentage of inducing pregnancy rate [OR＝0.85，95％CI（0.47，1.52），P＝ 0.58] of male infertility patients. CONCLUSIONS ：L-carnitine can significantly improve the semen volume and sperm mortality of male infertility patients ，and has the same effects as other drugs on improving sperm count ，percentage of forward motile sperm and percentage of inducing pregnancy rate.

Aged ; Cholecystectomy, Laparoscopic ; methods ; Cholelithiasis ; complications ; diagnosis ; surgery ; Clinical Laboratory Techniques ; Coronavirus Infections ; complications ; diagnosis ; Elective Surgical Procedures ; methods ; Follow-Up Studies ; Humans ; Infection Control ; methods ; Male ; Pandemics ; Patient Safety ; Pneumonia, Viral ; complications ; diagnosis ; Postoperative Care ; methods ; Risk Assessment ; Singapore ; Treatment Outcome

Objective To compare the efficacy of different concentrations of pyruvate-based peritoneal dialysis solution for peritoneal resuscitation in a rat model of hemorrhagic shock.Methods Forty SPF healthy male Sprague-Dawley rats,weighing 200-250 g,were assigned to 4 groups (n=10 each) using a random number table method:sham operation group (S group),routine Ⅳ resuscitation group (VR group),and intraperitoneal resuscitation with different concentrations of pyruvate-based peritoneal dialysis solution groups (PY1 group,PY2 group).The animals were anesthetized with pentobarbital sodium 400 mg/kg.Hemorrhagic shock was induced by withdrawing blood from the left femoral artery until mean arterial pressure (MAP) was reduced to 30-40 mmHg and maintained for 60 min,and the animals were then resuscitated by infusion of shed blood.In VR group,hemorrhagic shock was resuscitated by retransfusion of autologous blood and with normal saline 2 times the volume of blood loss at 1 h after hemorrhagic shock.Routine Ⅳ resuscitation was performed,and 40 and 80 mmol/L peritoneal dialysis solution 20 ml were intraperitoneally infused for 30 min at the same time in PY1 and PY2 groups,respectively.MAP was recorded before blood-letting (T0),at 5,30 and 60 min of shock (T1-3) and 5,30,60,90 and 120 min after the end of resuscitation (T4-8).Blood samples were collected at T8 for blood gas analysis,and pH value,partial pressure of oxygen (PaO2),partial pressure of carbon dioxide (PaCO2),base excess (BE),and bicarbonate ion concentration (HCO3-) were recorded.Results Compared with S group,MAP was significantly decreased at T1-8 in VR and PY1 groups and at T1-7 in PY2 group,and pH value,PaO2,BE and HCO3-were significantly decreased,and PaCO2 was increased in VR group (P＜0.05).Compared with VR group,MAP at T4-8,pH value,PaO2,BE and HCO3-were significantly increased,and PaCO2 was decreased in PY1 and PY2 groups (P＜0.05).Compared with PY1 group,MAP at T6-8 and pH value were significantly increased (P＜0.05),and no significant change was found in PaO2,PaCO2,BE or HCO3-in PY2 group (P＞0.05).Conclusion Peritoneal resuscitation with 80 mmol/L pyruvate-based peritoneal dialysis solution produces better efficacy than 40 mmol/L in a rat model of hemorrhagic shock.

Objective To evaluate the effect of pyruvate peritoneal resuscitation on Janus kinase (JAK) /signal transducer and activator of transcription (STAT) signaling pathway in intestinal tissues of rats with hemorrhagic shock.Methods Twenty-four healthy male Sprague-Dawley rats,weighing 200-300 g,were divided into 3 groups (n=8 each) using a random number table method:sham operation group (S group),intravenous resuscitation group (VR group),and peritoneal resuscitation with pyruvate group (PY group).Hemorrhagic shock was induced by blood-letting and infusing blood withdrawn with mean arterial pressure reduced to 30-40 mmHg for 60 min in pentobarbital-anesthetized rats.Hemorrhagic shock was resuscitated with autologous blood and normal saline 2 times the volume of blood withdrawn at the end of hemorrhagic shock in group VR.Pyruvate was intraperitoneally infused for 30 min using a micro-perfusion pump simultaneously with the intravenous resuscitation in group PY.The animals were sacrificed at 2 h after resuscitation,and intestinal tissues were obtained for determination of malondialdehyde (MDA) content (by thiobarbituric acid method),superoxide dismutase (SOD) activity (using xanthine oxidase method),myeloperoxidase (MPO) activity (using chemical colorimetry),and expression of phosphorylated STAT3 (pSTAT3),phosphorylated JAK2 (p-JAK2) and caspase-3 expression (by Western blot).Results Compared with group S,the MDA content and MPO activity were significantly increased,the SOD activity was decreased,and the expression of p-STAT3,p-JAK2 and caspase-3 was up-regulated in the other two groups (P＜0.05).Compared with group VR,the MDA content and MPO activity were significantly decreased,the SOD activity was increased,and the expression of p-STAT3,p-JAK2 and caspase-3 was down-regulated in group PY (P＜0.05).Conclusion The mechanism by which peritoneal resuscitation with pyruvate mitigates intestinal damage may be related to inhibiting activation of JAK/STAT signaling pathway in the rats with hemorrhagic shock.

As a complex system, the topology of human's brain network has an important effect on further study of brain's structural and functional mechanism. Graph theory, a kind of sophisticated analytic strategies, is widely used for analyzing complex brain networks effectively and comparing difference of topological structure alteration in normal development and pathological condition. For the purpose of using this analysis methodology efficiently, it is necessary to develop graph-based visualization software. Thus, we developed VisConnectome, which displays analysis results of the brain network friendly and intuitively. It provides an original graphical user interface (GUI) including the tool window, tool bar and innovative double slider filter, brain region bar, runs in any Windows operating system and doesn't rely on any platform such as Matlab. When importing the user-defined script file that initializes the brain network, VisConnectome abstracts the brain network to the ball-and-stick model and render it. VisConnectome allows a series of visual operations, such as identifying nodes and connection, modifying properties of nodes and connection such as color and size with the color palette and size double slider, imaging the brain regions, filtering the brain network according to its size property in a specific domain as simplification and blending with the brain surface as a context of the brain network. Through experiment and analysis, we conclude that VisConnectome is an effective visualization software with high speed and quality, which helps researchers to visualize and compare the structural and functional brain networks flexibly.
Brain ; physiology ; Connectome ; Humans ; Software

Objective To observe the efficacy of continuous renal replacement therapy (CRRT) combined with hemoperfusion (HP) on patients with severe acute aconitine poisoning. Methods One patient suffered from severe acute aconitine poisoning was admitted into the Department of Critical Care Medicine of Affiliated Hospital of Guizhou Medical University, besides the gastric lavage and multi-organ supportive conventional therapies, CRRT combined with HP was given to the patient and his clinical data of life vital signs and other parameters were observed. Results After the patient underwent 4 episodes of CRRT (102 hours in total) and HP (8 hours in total) based on the conventional treatment, 4 days later, the disease situations were gradually stabilized, all of their parameters became gradually normal, the patient successfully weaned off from mechanical ventilation, the via mouth tracheal intubation was pulled out and the patient was transferred out of department of critical care medicine. Conclusion In the patient with acute aconitine poisoning, it is necessary to use CRRT combined with HP as early as possible, that can effectively eliminate the toxicant in the body and quickly correct the electrolytic and acid-base disturbances, so as the above combine method can improve the patient's prognosis and elevate the successful rescue rate.

Objective To evaluate the role of M3 receptors in penehyclidine hydrochloride ( PHC)-induced reduction of lipopolysaccharide ( LPS)-induced injury to human pulmonary microvascular endotheli-al cells ( PMVECs) . Methods Human PMVECs transfected with M3 shRNA were seeded in 6-well plates (2 ml∕hole) or in culture flasks (4 ml∕flask) at the density of 1×105 cells∕ml and divided into 5 groups ( n=5 each) using a random number table method: control group ( group C) , LPS group, PHC plus LPS group ( group P+LPS) , LPS plus M3 shRNA transfection group ( group LPS+shRNA) , and PHC plus LPS plus M3 shRNA transfection group ( group P+LPS+shRNA) . Group C received no mediation, and LPS was added at the final concentration of 0. 1 μg∕ml in the other groups. PHC 2 μg∕ml was added at 1 h before adding LPS in P+LPS and P+LPS+shRNA groups. The cells were transfected with plasmid containing 2. 5 nmol∕L M3 receptor shRNA in LPS+shRNA group and P+LPS+shRNA group. Contents of filamentous actin ( F-actin) in endothelial cells were measured by flow cytometry at 1 h after adding LPS. The expression of myosin light chain kinase ( MLCK) and VE-cadherin protein was examined by immunofluorescence. The ex-pression of nuclear factor kappa B ( NF-κB) p65 and IκB was detected by Western blot. Contents of tumor necrosis factor-alpha ( TNF-α) and interleukin-6 ( IL-6) were determined by enzyme-linked immunosorbent assay. The M3 receptor mRNA transcription was detected by real-time polymerase chain reaction at 10, 30 and 60 min after adding LPS. Results Compared with group C, F-actin content was significantly de-creased, the expression of VE-cadherin and IκB was down-regulated, the contents of TNF-αand IL-6 were increased, and the expression of MLCK and NF-κB p65 was up-regulated in LPS and P+LPS groups ( P<0. 05) . Compared with group C, the expression of M3 receptor mRNA was significantly up-regulated in group LPS ( P<0. 05) , and no significant change was found in group P+LPS ( P>0. 05) . Compared with group LPS, F-actin content was significantly increased, the expression of VE-cadherin and IκB was up-reg-ulated, the contents of TNF-αand IL-6 were decreased, and the expression of MLCK, NF-κB p65 and M3 receptor mRNA was down-regulated in group P+LPS and group LPS+shRNA ( P<0. 05) . Compared with group P+LPS, F-actin content was significantly increased, the expression of VE-cadherin and IκB protein was up-regulated, TNF-α and IL-6 contents were decreased, and the expression of MLCK, NF-κB p65 and M3 receptor mRNA was down-regulated in group P+LPS+shRNA ( P<0. 05) . Conclusion PHC re-duces LPS-induced injury to human PMVECs through interfering with M3 receptors and inhibiting NF-κB-mediated inflammatory responses.