Toward Antifragility: Social Defeat Stress Enhances Learning and Memory in Young Mice Via Hippocampal Synaptosome Associated Protein 25.

Social adversity not only causes severe psychological diseases but also may improve people's ability to learn and grow. However, the beneficial effects of social adversity are often ignored. In this study, we investigated whether and how social adversity affects learning and memory in a mouse social defeat stress (SDS) model. A total of 652 mice were placed in experimental groups of six to 23 mice each. SDS enhanced spatial, novelty, and fear memory with increased synaptosome associated protein 25 (SNAP-25) level and dendritic spine density in hippocampal neurons among young but not middle-aged mice. Chemogenetic inhibition of hippocampal CaMK2A+ neurons blocked SDS-induced enhancement of learning or memory. Knockdown of SNAP-25 or blockade of N-methyl-D-aspartate (NMDA) receptor subunit GluN2B in the hippocampus prevented SDS-induced learning memory enhancement in an emotion-independent manner. These findings suggest that social adversity promotes learning and memory ability in youths and provide a neurobiological foundation for biopsychological antifragility.

The modified pancreatic stent system for prevention of post-ERCP pancreatitis: a case-control study.

BACKGROUND: Prophylactic pancreatic stents after endoscopic retrograde cholangiopancreatography (ERCP) can help prevent post-ERCP pancreatitis. However most of the pancreatic stents need to be removed by another ERCP. The aim of this observational study was to investigate the feasibility and effectiveness of the modified pancreatic stent system for prevention of post-ERCP pancreatitis. METHODS: From November 2013 to November 2015, a total of 230 patients who had prophylactic pancreatic stent placed for prevention of post-ERCP pancreatitis at a single institution were identified and stratified. In this case-control design, 150 patients received an ordinary pancreatic stent, and 80 patients received the modified pancreatic stent. The main outcome measures were the difficulty level and complications of pancreatic stent placement and extraction between the two groups. RESULTS: In ordinary group, the average time of pancreatic stent and nasal biliary drainage placement was 3.5 ± 0.6 min. There were 13 cases of stent proximal migration (8.7%), 20 cases of stent spontaneous abscission (13.3%), 5 cases of acute pancreatitis (3.3%) (2 cases for stent abscission) and 7 cases of hyperamylasemia (4.7%) after ERCP. One hundred thirty patients received extra duodenoscope (86.7%) to remove the stent, and 4 cases had acute pancreatitis and 5 patients had hyperamylasemia after removing the proximal migratory stents. In modified group, the average time of pancreatic stent system placement was 4.9 ± 0.7 min, but there was only one case of stent abscission (1.3%), 2 cases of acute pancreatitis (2.5%) and 3 cases of hyperamylasemia (3.8%). The new pancreatic stents were removed directly under x-ray without complication. CONCLUSIONS: The modified pancreatic stent system has the same effect of preventing post-ERCP pancreatitis, lower rate of stents proximal migration and spontaneous abscission, and the advantage of easier removed compared with ordinary pancreatic stent.

Choledochoscopic high-frequency needle-knife electrotomy for treatment of anastomotic strictures after Roux-en-Y hepaticojejunostomy.

BACKGROUND: Anastomotic stricture is a complex and substantial complication following Roux-en-Y hepaticojejunostomy. Initially, endoscopic and percutaneous approaches are often attempted, but the gold standard remains surgical biliary reconstruction, especially for refractory stricture. However, this solution leaves much room for improvement, due to the challenging nature of the biliary reconstruction procedure, in which anastomotic stricture may still occur. AIMS: To investigate the feasibility and effectiveness of choledochoscopic high-frequency needle-knife electrotomy as an intervention in the treatment of anastomotic strictures following Roux-en-Y hepaticojejunostomy. METHODS: From February 2010 to October 2014, clinical data was collected and retrospectively compared for patients who underwent balloon dilation or/and choledochoscopic high-frequency needle-knife electrotomy for the treatment of anastomotic strictures after Roux-en-Y hepaticojejunostomy. RESULTS: A total of 38 patients underwent successful choledochoscopic treatment and all the anastomotic strictures were removed successfully, 19 of which were treated with electrotomy, 7 with balloon dilation, and 12 with both electrotomy and balloon dilation. Among these groups,the average operating times were 6.9 ± 2.4 min,10.1 ± 6.8 min, and 20.2 ± 13.5 min, respectively. The average stent supporting times were 6.3 ± 0.7 months, 6.5 ± 0.6 months, and 6.1 ± 0.4 respectively. The mean follow-up after stent removal was 42.1 ± 27.4 months, and in 26.3 % (5/19), 28.5 % (2/7) and 16.7 % (2/12) of cases, recurrent anastomotic stricture occurred. Of these 9 total patients with recurrent anastomotic, two patients were successfully rescued by full-covered self-expanding removable metal stents and 7 patients by electrotomy combined with balloon dilation. CONCLUSIONS: Choledochoscopic high-frequency needle-knife electrotomy is both feasible and safe in the treatment of anastomotic stricture after Roux-en-Y hepaticojejunostomy, with a similar long-term outcome to balloon dilation in treating anastomotic stricture after Roux-en-Y hepaticojejunostomy. A combination of choledochoscopic electrotomy concurrent with balloon dilation should be recommended based on the low rate of recurrence.

Choledochoscopic high-frequency needle-knife electrotomy as an effective treatment for intrahepatic biliary strictures.

BACKGROUND AND AIM: Hepatolithiasis is associated with the presence of intrahepatic biliary strictures, and balloon dilatation is the main approach. However, this method is difficult to implement if the bile duct distal to the stricture is blocked by stones. Therefore, alternative methods need to be explored to effectively treat hepatolithiasis. The aim of this study is to investigate the feasibility and effectiveness of choledochoscopic high-frequency needle-knife electrotomy for the treatment of intrahepatic biliary strictures. METHODS: Clinical data of 58 patients suffering from intrahepatic bile duct strictures from January 2011 to January 2013 were retrospectively analyzed. Choledochoscopic electrotomy was used to resolve the strictures. RESULTS: One hundred thirty-four sites of intrahepatic bile duct strictures were discovered. The average operating time of electrotomy is 5.6 min (range, 1 ∼ 15 min). Structured bile duct tissue bleeding occurred in eight sites (8/134, 6.0%) but were resolved by endoscopic high-frequency electric cautery. After the operations, 14 cases of cholangitis (14/58, 24.1%), three cases of delayed hemobilia, one case of liver abscess (1/58, 1.7%), and seven cases of stenting exodus (7/58, 12.1%) were observed despite conservative treatment and stenting reset. The average supporting time was 7.0 months (6 ∼ 9 months). No abnormal bile duct structure or presence of stone was found according to choledochoscopy. The follow-up period ranged from 12 to 48 months. Hepatolithiasis recurred in five (5/58, 8.6%) patients, and the cumulative recurrent probability of intrahepatic bile duct stricture was 5.2% (7/134). CONCLUSIONS: Choledochoscopic high-frequency needle-knife electrotomy could be considered as a simple, safe, and effective complementary approach for treating intrahepatic biliary strictures.

Clinical analysis and significance of cholangiography for biliary cast/stone after orthotopic liver transplantation.

Cholangiography is an important method for the diagnosis of biliary complications after orthotopic liver transplantation. The cholangiography after orthotopic liver transplantation presents special challenges, especially in patients with biliary cast/stone and biliary stenosis. We described the T-tube cholangiography combined therapeutic fibro-choledochoscopy for the diagnosis and treatment of biliary cast following after orthotopic liver transplantation. Fourteen patients who developed biliary cast/stone after liver transplantation were analyzed retrospectively. The complications were divided into three temporal stages, early, medium, and late. Hepatic functions and the characteristics of the bile duct were observed by T-tube cholangiography and endoscopy. The biliary cast after liver transplantation was divided into three categories: Solitary, multiple, and columnar. Three months after liver transplantation, bile ducts appeared fuzzy by T-tube cholangiography, but no evidence of biliary cast was found. The bile duct was feculent with flocculation during the middle stage 3-6 months after liver transplantation. At six months after transplantation, bile ducts (especially intrahepatic bile ducts) were distended; cholangiectasis was obvious with biliary cast. The intrahepatic bile duct stricture was observed on occasion by T-tube cholangiography and the intrahepatic bile duct could be thin and distended, and resembled withered branches or strings of beads. The intrahepatic bile ducts even disappeared at this stage; hepatic functions were usually unacceptable and the icterus gradually aggravated. Four cases were diagnosed earlier according to the categories of stone and stage. Curative therapy was performed promptly and the clinical outcome was acceptable. Biliary tracts of the transplanted livers could be observed by T-tube channels and biliary complications were treated effectively by therapeutic fibro-choledochoscopy. It is necessary to combine T-tube cholangiography with fibro-choledochoscopy for the diagnosis and treatment of biliary complications after orthotopic liver transplantation.

Efficacy of diet restriction with or without probiotic for treatment of patients with IBS-D: Phase I-II clinical trial.

BACKGROUND AND AIM: Diet is a major contributor to irritable bowel syndrome (IBS) and is also a powerful tool for treatment of IBS. This study compared two diets and explored the effectiveness of the diets when combined with a probiotic for treatment of IBS-D patients. METHODS: Phase I, patients were randomized into groups; control, cold/spicy/fried restricted diet (CSF res diet), IgG positive restricted diet (IgG res diet), and a combination both diets (CSF + IgG res diet). Phase II, patients were randomized into IgG res diet + placebo and IgG res diet + probiotic. Both interventions were 12 weeks in duration. Symptom Severity Scale (IBS-D-SSS) and IgG titer were assessed at the beginning and the end of the study. RESULTS: Totals of 214 and 167 patients completed the two parts of the study, respectively. After intervention, IBS-D-SSS and TIgG grade were significantly improved compared to baseline, with results similar to the control group. In general, there were decreases in IBS-D-SSS and TIgG grade that were significantly different among the groups. There were exceptions; no differences were observed for IBS-D-SSS between the IgG res diet and CSF + IgG res diet, or TIgG grade between the CSF res diet, IgG res diet, and CSF + IgG res diet. However, the CSF res diet and IgG res diet had a synergistic effect that decreased IBS-D-SSS and TIgG titer, with a greater contribution by the IgG res diet. Therefore, we evaluated the IgG res diet with either placebo or probiotic and found that IBS-D-SSS and TIgG grade decreased from baseline. There was a significant decrease in IBS-D-SSS with the probiotic but TIgG grade was not significantly different between the IgG diet + placebo and IgG diet + probiotic diet. CONCLUSIONS: Both the CSF res diet and IgG res diet improved IBS symptoms and demonstrated synergy, although the IgG res diet had a greater contribution. Further, when intolerant foods cannot be eliminated from a diet, avoiding uncooked, cold, spicy, fried, and alcoholic foods is a superior choice. The IgG res diet combined with Bifidobacteria was the best dietary choice and may function though a non-IgG pathway.

[Effect of PP333 treatment on seed yield and root of Flemingia philippinensis].

OBJECTIVE: To study the effect of PP333 treatment on seed yield,medicinal materials yield and quality of Flemingia Philippinensis. METHODS: The experiment was in split plot design for PP333 in main plot and in planting density subplot. RESULTS: The seed yield of 600 mg/L (PP333) + 60 plants/m2 (planting density) was the highest. The medicinal materials yield of 600 mg/L (PP333) + 90 plants/m2 (planting density) was the highest. The quality of 900 mg/L( PP333) + 60 plants/m2 (planting density) was the best. CONCLUSION: The appropriate density of PP333 and planting can improve seed yield,medicinal materials yield and quality of Flemingia Philippinensis.

A case-control study on the association of intestinal flora with ulcerative colitis.

The association between intestinal flora and ulcerative colitis (UC) was studied in order to provide a basis and method for clinical treatment. Fresh fecal samples were collected from 30 active UC patients and 10 healthy controls. The intestinal flora DNA from each sample was extracted and 16S rRNA gene sequencing was carried out using HiSeq platform to identify the intestinal flora in fecal samples. The richness and diversity of intestinal flora in UC patients were significantly lower than those in healthy control group (P < 0.05). Significant differences were observed between the intestinal flora-species of UC patients and healthy controls. Synergistetes (P < 0.01) and Firmicutes (P < 0.05), along with probiotics Veillonella (P < 0.01), Ruminococcus and Coprococcus (P < 0.05) in the UC patients were lower than that in the healthy controls significantly. Furthermore, compared with the control group, Tenericutes (P < 0.01) and intestinal pathogenic bacteria, including Bacteroides (P < 0.01), Escherichia and Sutterella (P < 0.05) were significantly increased. The incidence of UC is significantly associated with the changes in intestinal flora. Changes in intestinal flora may lead to a decrease in the diversity of intestinal flora or to the enrichment of a particular intestinal flora.

[Focused extracorporeal shock wave therapy with centrifugal exercise for the treatment of greater trochanteric pain syndrome].

OBJECTIVE: To explore the clinical efficacy of focused extracorporeal shock wave therapy with centrifugal exercise in the treatment of greater trochanteric pain syndrome. METHODS: From September 2017 to June 2019, 53 eligible cases of greater trochanteric pain syndrome were randomly divided into observation group (29 cases) and control group (24 cases). In observation group, there were 8 males and 21 females, aged from 38 to 62 years old with an average of (49.96±6.39) years old; the course of disease ranged from 6 to 13 months with an average of (8.58±1.99) months;treated with focused extracorporeal shock wave therapy with centrifugal exercise. In control group, there were 5 males and 19 females, aged from 39 to 62 years old with an average of (52.79±5.86) years old;the course of disease ranged from 6 to 14 months with an average of (9.04±2.51) months;treated with centrifugal exercise alone. Visual analogue scale (VAS) and hip Harris score were measured before ESWT treatment and at 1, 2, and 6 months to evaluate relieve degree of pain and functional recovery of hip joint, respectively. RESULTS: At 1 month after treatment, there were no significant differences in VAS, hip Harris score and treatment success rate (all P>0.05). At 2 months after treatment, VAS score in observation group (3.20±0.81) was lower than that of control group (3.87±0.61, P=0.002), there were no significant differences in hip Harris score score between observation group (81.93±2.43) and control group (82.12±2.34, P=0.770), the treatment success rate in observation group (58.62%, 17 / 29) was higher than that of control group (29.16%, 7 / 24) (P=0.032). At 6 months after treatment, VAS score in observationgroup (2.24±0.68) was lower than that of control group (3.12±0.53, P<0.001), hip Harris score score in observation group(85.10±1.75) was higher than that of control group (83.66±1.78)(P=0.005), there were no significant differences in treatment success rate between observation group (82.75%, 24 / 29) and control group (62.50%, 15 / 24)(P=0.096). CONCLUSION: In treatment of greater trochanteric pain syndrome, focused extracorporeal shock wave therapy with centrifugal exercise could significantly relieve symptoms of lateral hip pain, improve functional recovery of hip joint with good safety. This treatment strategy is worthy of application and promotion in clinical practice.

[Influence of MRD Status in Newly Diagnosed MM Patients with VGPR and Above after Treatment on Clinical Prognosis].

OBJECTIVE: To investigate the influence of MRD status in newly diagnosed MM patients with VGPR and above after treatment on clinical prognosis. METHODS: Clinical data of 210 newly diagnosed MM patients with VGPR and above after treatment in Fifth People's Hospital of Chendu city. from January 2010 to January 2018 were collected and retrospectively analyzed. The patients were divided into 2 groups: group A (152 patients with MRD-) and group B (58 patients with MRD+). The influencing factors of progression free survival and overall survival of patients were analyzed, and the correlation between MRD status and high-risk cytogenetic abnormalities, treatment plan and response to treatment were evaluated. RESULTS: There were no significant difference in clinical characteristics between the patients in 2 groups (P＞0.05). Single factor analysis showed that ASCT and MRD status were related with progression free survival of patients with newly diagnosed MM (P＜0.05). Multivariate analysis by Cox regression model showed that MRD+ persistence was the independent risk factor for progression free survival of patients with newly diagnosed MM (P＜0.05). The cumulative progression free survival rate in 2-year with follow-up of patients in group A was significantly higher than that in B group (P＜0.05). The median progression free survival time and overall survival time of patients with persistent MRD- were significantly longer than those of MRD+ (P＜0.05). The single factor analysis showed that MRD- maintenance time was the influencing factor of PFS and OS time of newly diagnosed MM patients (P＜0.05). The cumulative overall survival rate in 2-year with follow-up of patients with MRD- maintenance for 6 months was significantly higher than that of patients with MRD- maintenance for＜6 months (P＜0.05). The cumulative progression free survival rate and overall survival rate in 2 years with follow-up of patients with MRD- maintenance for ≥12 months were significantly higher than those of MRD-maintenance for ＜12 months（P＜0.05）. The median progression free survival time of patients with MRD- was significantly longer than that of patients with MRD+ who had≥ one kind of high-risk cytogenetic abnormality (P＜0.05). The MRD- rate of patients received ASCT was significantly higher than that of patients without ASCT (P＜0.05). The median progression free survival time of patients with MRD- was significantly longer than that of patients with MRD+ (P＜0.05). The maintenance time of MRD- in patients with bortezomib treatment was significantly longer than that of patients without bortezomib treatment in population with MRD- (P＜0.05). The median progression free survival time of patients with bortezomib treatment was significantly longer than patients without bortezomib treatment (P＜0.05). CONCLUSION: MRD+ maintenance in newly diagnosed MM patients with VGPR and above after treatment closely relates with poor long-term prognosis, however, the MRD- maintenance time can be used for prognosis evaluation. MRD+ suggests that patients possess the possibility of early recurrence, and dynamic monitoring of MRD status in treatment can be helpful to clinical determination of treatment opportunity for relapsed MM patients.

Different cell death modes of pancreatic acinar cells on macrophage activation in rats.

BACKGROUND: The pathogenesis of acute pancreatitis is complex and largely unclear. The aim of this study was to explore the relationship between modes of cell death in pancreatic acinar cells, the release of cell contents and the inflammatory response of macrophages. METHODS: Our experiment included four groups: group A (the control group), group B (AR42J cells overstimulated by caerulein), group C (AR42J cells treated with lipopolysaccharide and caerulein), and group D (AR42J cells treated with octreotide and caerulein). Apoptosis and oncosis, and the release of amylase and lactate dehydrogenase (LDH) from AR42J cells were detected. Rat macrophages were stimulated by 1 ml supernatant of culture medium of AR42J cells. Finally, NF-kappaB activation and TNF-alpha and IL-1beta secretion by macrophages were detected. RESULTS: Oncotic cells in group C increased while apoptotic cells decreased (P < 0.05); cells in group D had the inverse reaction. The release of amylase and LDH changed directly with the occurrence of oncosis. The transcription factor NF-kappaB was activated and secretion of TNF-alpha and IL-1beta were significantly higher in group C than in group B (P < 0.05); in group D, these actions were significantly lower than in group B (P < 0.05). This trend was in line with changes in amylase and LDH production. CONCLUSION: There is a close relationship between modes of pancreatic acinar cell death, the release of cell contents and the inflammatory reaction of macrophages.

Efficacy of cognitive behavioral therapy in children and adolescents with insomnia: a systematic review and meta-analysis.

Insomnia is highly prevalent in children and adolescents. However, the efficacy of cognitive behavioral therapy for insomnia (CBT-i) in children and adolescents remains controversial. Therefore, this systematic review and meta-analysis aimed to assess the efficacy of CBT-i in children and adolescents. We conducted a search of PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO to select primary studies evaluating CBT-i in children and adolescents that were primarily diagnosed through standardized diagnostic criteria. The primary outcomes of the meta-analysis included sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency (SE%). Six randomized controlled trials and four open-label trials met all inclusion criteria. A total of 464 participants (ranging from 5-19 years of age) were included. Based on the results from sleep logs, a significant pooled effect size was observed for SOL and SE%. However, no significant pooled effect size was found for WASO or TST. Results from actigraphy were consistent with the sleep logs. A significant pooled effect size was observed for SOL and SE%, and no significant pooled effect size was found for WASO or TST. CBT-i might be effective in the treatment of children and adolescents with insomnia.

[The receptor-dependent and non-receptor-dependent mechanism of melatonin activated BKCa channels in middle cerebral artery myocyte].

OBJECTIVE: To investigate the mechanisms through which myocyte large-conductance Ca2+-activated K+ (BKCa) channels mediate the vasodilation effects of melatonin on cerebral arteries (CAs). METHODS: Middle cerebral arteries (MCA) were obtained from 8-week-old male Wistar rats after anaesthetized. Middle cerebral arterial smooth muscle cells were enzymatically isolated. Whole cell recording mode of patch clamp technique was used to measure the current density of BKCa channel and voltage-gated potassium (KV) channel before and after adding melatonin. Currents density of melatonin on BKCa channels with melatonin receptor inhibitor 2-phenyl-N-acetyl (luzindole) was recorded using whole cell recording mode and open probability (Po) was recorded using single-channel attached recording mode. The conductance (G) and average open time (To) and off time (Tc) of the BKCa channel were detected before and after the addition of melatonin in the internal-outward mode. RESULTS: ① Melatonin markedly increased the whole-cell BKCa channel current density but not the voltage-gated potassium (KV) channel current density. ② Luzindole (1 µmol/L) greatly suppressed melatonin-induced increase of BKCa channel current density. ③ The Po of BKCa channel was significantly increased by melatonin (100 µmol/L) under cell attached recording mode, which was markedly inhibited by luzindole (1 µmol/L). ④ In inside-outside recording mode, melatonin (1 µmol/L, 100 µmol/L) reduced both To and Tc of BKCa channel, and Tc was reduced much more than To. CONCLUSIONS: Melatonin mediates vasodilation of MCA through the activation of BKCa channels via both melatonin receptor dependent and independent mode.

Endoscopic Sphincterotomy for Gallbladder Muddy Stones or Sludge in Patients With Papillary Disease: A Retrospective Study.

BACKGROUND: The formation of gallbladder stones is associated with dysfunctional contraction and duodenal papilla diseases. However, endoscopic sphincterotomy can improve the contraction of the gallbladder and resolve duodenal papilla disease. AIM: The aim of the study was to assess the feasibility and effectiveness of endoscopic sphincterotomy in the treatment of muddy stones or sludge in the gallbladder during papillary disease. METHODS: The clinical data of 53 patients with gallbladder muddy stones or sludge undergoing endoscopic sphincterotomy were retrospectively analyzed. RESULTS: A total of 53 patients received successful endoscopic sphincterotomy with no serious complications. Sphincterotomy did not significantly lower resting gallbladder volume from 63.2±10.8 to 50.1±5.9 mL (P>0.05), but significantly increased gallbladder ejection fraction from 0.41±0.13 to 0.63±0.16 (P<0.01), as measured by the lipoid food test. The static liver and gallbladder imaging examination also showed an increase in gallbladder ejection fraction from 0.45±0.08 to 0.68±0.11 (P<0.01). In addition, the choledochus pressure reduced from 21.9±4.0 to 15.6±2.5 mm Hg, and the gallbladder muddy stones or sludge disappeared after endoscopic sphincterotomy. At the end of the follow-up period, there was no relapse of sludge or muddy stones in the gallbladder. CONCLUSIONS: The formation of gallbladder muddy stones or sludge is associated with papilla disease. Endoscopic sphincterotomy can resolve papilla disease, decrease gallbladder bile stasis, improve gallbladder evacuation, and prevent the formation of gallbladder stones.

[Effects of bone marrow mesenchymal stem cells on the proliferation of hepatocytes and cirrhotic fat-storing cells in vitro].

OBJECTIVE: To investigate the differentiation of bone marrow mesenchymal stem cells (BMSCs) and the effects of BMSCs on the proliferation of cirrhotic fat-storing cells (CFSC) and hepatocytes in vitro. METHODS: BMSCs and hepatocytes were isolated and harvested from the bone marrow and livers of rats. A co-culture system was set up by transwell inserts in which the two chambers were separated by a semipermeable membrane. BMSCs labeled with PKH26 were cultured with hepatocytes/CFSC in the co-culture system and also in a cell-cell direct contact culture system. Anti-albumin and anti-smooth muscle alpha-actin (alpha-SMA) antibodies were tested by using fluorescence immunocytochemistry. BMSCs and hepatocytes/CFSC cultured alone served as controls. The proliferation level of hepatocytes in the co-culture system was measured. CFSC were cultured with the conditional medium of BMSCs, and their quantities were measured microscopically. RESULTS: Expression of albumin was observed in the hepatocytes of the two culture systems after they were cultured for 72 h but the albumin levels were higher in the cell-cell direct contact culture system (P<0.01). As compared to the controls, the number of hepatocytes was larger in the co-culture system (P<0.01). No expression of alpha-SMA in CFSC was observed in either culture system. The proliferation of CFSC was inhibited by the conditional medium of BMSCs. The longer the time of the co-culturing the more significant was the CFSC growth suppression (P<0.01). CONCLUSIONS: BMSCs can be induced into hepatocytes by a local micro-environment formed by hepatocytes. BMSCs may promote proliferation of hepatocytes and inhibit proliferation of CFSC.

Isolation and Characterization of Encephalomyocarditis Virus from Dogs in China.

Encephalomyocarditis virus (EMCV) is as a potential zoonotic agent with a wide host range. Here, we describe an EMC virus isolate, identified as EMCV C15, which was successfully obtained from the serum of dogs from animal hospitals. Virus production in cell culture was confirmed by EMCV-specific real-time RT-PCR, indirect immunofluorescence assays and electron microscopy. In addition, the open reading frame sequence (ORF) of the EMCV C15 virus was determined. From sequence comparison and phylogenetic analysis among 24 reference EMCV strains, it appears that the EMCV C15 strain is closely genetically related to strain BEL2887A/91 (>99.0% nucleotide identity). In artificially challenged dogs, the heart and brain were important targets of EMCV C15. This study provides genetic and pathogenic characterization of the EMCV C15 strain isolated in Beijing and calls for sustained surveillance of EMCV infection in China to support better prevention and control of the disease.

Activation of protein kinase A in the amygdala modulates anxiety-like behaviors in social defeat exposed mice.

BACKGROUND: Social defeat (SD) stress induces social avoidance and anxiety-like phenotypes. Amygdala is recognized as an emotion-related brain region such as fear, aversion and anxiety. It is conceivable to hypothesize that activation of amygdala is involved in SD-dependent behavioral defects. RESULTS: SD model was established using C57BL/6J mice that were physically defeated by different CD-1 mice for 10 days. Stressed mice exhibited decreased social interaction level in social interaction test and significant anxiety-like behaviors in elevated plus maze and open field tests. Meanwhile, a higher phosphorylation of PKA and CREB with a mutually linear correlation, and increased Fos labeled cells in the basolateral amygdala (BLA) were observed. Activation of PKA in the BLA by 8-Br-cAMP, a PKA activitor, significantly upregulated pCREB and Fos expression. To address the role of PKA activation on SD stress-induced social avoidance and anxiety-like behaviors, 8-Br-cAMP or H-89, a PKA inhibitor, was continuously administered into the bilateral BLA by a micro-osmotic pump system during the 10-day SD period. Neither H-89 nor 8-Br-cAMP affected the social behavior. Differently, 8-Br-cAMP significantly relieved anxiety-like behaviors in both general and moderate SD protocols. H-89 per se did not have anxiogenic effect in naïve mice, but aggravated moderate SD stress-induced anxiety-like behaviors. The antidepressant clomipramine reduced SD-induced anxiety and up-regulated pPKA level in the BLA. CONCLUSIONS: These results suggest that SD-driven PKA activation in the basolateral amygdala is actually a compensatory rather than pathogenic response in the homeostasis, and modulating amygdaloid PKA may exhibit potency in the therapy of social derived disorders.

Opposite Sex Contact and Isolation: A Novel Depression/Anxiety Model.

To mimic human mood disorders, traditional chronic stresses and social defeat stress have been developed and widely applied. However, these active stresses do not mimic the emotional flaws induced by stresses, and their input levels vary greatly. Also, emotional stresses resulting from social unobtainability remain largely elusive due to the lack of useful animal models. In this study, we developed a mouse model named "opposite sex contact and isolation" (OSCI) and found that OSCI induced significant social avoidance, anhedonia, and anxiety. These behavioral defects developed differently after 7 days of OSCI. The social avoidance behavior was self-curable while anxiety gradually worsened but was alleviated by re-pairing with the same female partner. Corresponding to the behavior changes, the plasma corticosterone and phosphorylated cAMP response element binding protein levels were decreased in the nucleus accumbens of the mice that experienced isolation. Together, this study has developed a novel strategy for depression/anxiety modeling and shows that OSCI may be a useful tool for studying the lovelorn/lovesick type of depression.

Identification and functional characterization of a novel fungal immunomodulatory protein from Postia placenta.

In this study, a previously unknown fungal immunomodulatory protein (FIP), here called FIP-ppl, was identified from the basidiomycete fungus Postia placenta by searching its genome sequence database using known FIPs as baits, which was the first basidiomycete FIP to be identified outside the order of edible macro fungi. The gene FIP-ppl was synthesized and expressed in Escherichia coli to produce a glutathione S-transferase (GST) fusion protein. The fusion protein was purified on a GST affinity column and the protein tag was removed using in situ thrombin cleavage. The purified recombinant protein (rFIP-ppl) displayed hemagglutination activity toward rabbit red blood cells but not against human red blood cells. RFIP-ppl stimulated mouse splenocyte cell proliferation and enhanced interleukin-2 (IL-2) release. Antitumor assays indicated that rFIP-ppl had significant cell proliferation inhibitory activity and apoptotic effects in human tumor cells with more pronounced inhibiting proliferation and inducing apoptotic effects on gastric tumor cells (MGC823) than against hepatoma (HepG2) cells. This study confirms an alternative means of identifying, producing, and isolating new FIPs. It may provide convenient access to FIP-ppl with potential human therapeutic applications.