C3aR in the medial prefrontal cortex modulates the susceptibility to LPS-induced depressive-like behaviors through glutamatergic neuronal excitability.

Complement activation and prefrontal cortical dysfunction both contribute to the pathogenesis of major depressive disorder (MDD), but their interplay in MDD is unclear. We here studied the role of complement C3a receptor (C3aR) in the medial prefrontal cortex (mPFC) and its influence on depressive-like behaviors induced by systematic lipopolysaccharides (LPS) administration. C3aR knockout (KO) or intra-mPFC C3aR antagonism confers resilience, whereas C3aR expression in mPFC neurons makes KO mice susceptible to LPS-induced depressive-like behaviors. Importantly, the excitation and inhibition of mPFC neurons have opposing effects on depressive-like behaviors, aligning with increased and decreased excitability by C3aR deletion and activation in cortical neurons. In particular, inhibiting mPFC glutamatergic (mPFCGlu) neurons, the main neuronal subpopulation expresses C3aR, induces depressive-like behaviors in saline-treated WT and KO mice, but not in LPS-treated KO mice. Compared to hypoexcitable mPFCGlu neurons in LPS-treated WT mice, C3aR-null mPFCGlu neurons display hyperexcitability upon LPS treatment, and enhanced excitation of mPFCGlu neurons is anti-depressant, suggesting a protective role of C3aR deficiency in these circumstances. In conclusion, C3aR modulates susceptibility to LPS-induced depressive-like behaviors through mPFCGlu neuronal excitability. This study identifies C3aR as a pivotal intersection of complement activation, mPFC dysfunction, and depression and a promising therapeutic target for MDD.

Detection and segmentation of multi-class artifacts in endoscopy.

Endoscopy may be used for early screening of various cancers, such as nasopharyngeal cancer, esophageal adenocarcinoma, gastric cancer, colorectal cancer, and bladder cancer, and performing minimal invasive surgical procedures, such as laparoscopy surgery. During this procedure, an endoscope is used; it is a long, thin, rigid, or flexible tube having a light source and a camera at the tip, which facilitates visualization inside the affected organs on a screen and helps doctors in diagnosis.

Predictive factors and clinical effect of optimized cardiac resynchronization therapy.

The aim of this study was to assess the effectiveness of cardiac resynchronization therapy (CRT) by intracardiac delay optimization using echocardiography. Sixty-five patients were implanted with a CRT device randomly assigned to receive simultaneous biventricular pacing or echo-optimized sequential CRT. Forty-two patients were defined as responders and 23 patients were classified as non-responders. During a 12-month follow-up period, the positive response rate, QRS duration, New York Heart Association class, mitral insufficiency grade, left ventricular end-systolic volume and LV end-diastolic volume were similar in the optimized and non-optimized groups (P>0.05), whereas 6-minute walking distance, quality-of-life score, left ventricular (LV) ejection fraction and aortic velocity time integral were significantly improved in the optimized group (P<0.05). The baseline QRS durations of the responders and non-responders were similar (P>0.05), whereas heart failure aetiology, clinical and echocardiographic measurements showed significant differences (P<0.05). The mean decrease in QRS duration after 12 months of CRT used for separating responders and non-responders was significantly different (P<0.05), and significant differences were observed in the mean decrease of QRS duration between responders and non-responders (P<0.05). Echocardiographic optimization may further improve the effectiveness of CRT. Moreover, severe mitral regurgitation and greater LV volume are likely to indicate a poor response to CRT.

[Sorption and desorption characteristics of different structures of organic phosphorus onto aluminum (oxyhydr) oxides].

The sorption and desorption characteristics of four kinds of organic phosphorus with different molecular structures (glycerophosphate (GP), glucose-6-phosphate (G6P), adenosine triphosphate (ATP), and myo-inositol hexakisphosphate (IHP)) on three kinds of aluminum (oxyhydr)oxides (amorphous Al(OH)3, boehmite, and alpha-Al2O3) were studied. The underlying mechanisms were also illustrated. Results showed that the maximum sorption amounts of OP onto Al (oxyhydr)oxides, on a per gram dry weight basis, decreased as following: amorphous Al(OH)3 > boehmite > alpha-Al2O3. This mainly related to the mineral crystallinity and surface heterogeneity. With the exception of sorption of IHP on amorphous Al (OH)3, the maximum sorption density decreased with increasing molecular weight (MW) of OP, following the order: GP > G6P > ATP > IHP. However, the sorption amount of IHP on amorphous Al (OH)3 was much higher than those of other OP, due to the transformation of surface complexes of IHP to surface precipitation and thus enhancing the sorption. The sorption kinetics results showed that sorption of OP underwent the first onset rapid sorption, i. e. a certain amount of sorption occurred within an onset extremely short period, and a following long and slow sorption process. Amorphous Al (OH)3 had the greatest onset rapid sorption density, and the onset rapid sorption density of OP on Al (oxyhydr) oxides decreased with increasing MW. Desorption capacities of OP by KCl and citrate solutions related to the surface affinity between OP and boehmite. Initial desorption percentages by KCl decreased in the order: G6P (10.53%) > GP(6.91%) > ATP (3.06%) > IHP (0.8%). The maximum desorption percentages of OP by citrate were 4-5 times greater than those by KCl. During resorption process of P by KCl, the maximum desorption rate achieved after a fast desorption in a few hours, followed by diffusion-resorption during which the desorption percentage gradually decreased. Specially, both diffusion-resorption and surface precipitation promoted the resorption of IHP on mineral surface. Conclusively, the strong specific sorption of OP occurs on the surface of Al (oxyhydr) oxides, and molecular structure and size of OP as well as the crystallinity and crystal structure of minerals are the key factors affecting the interfacial reactions and environmental behaviors of OP.

[Value of protein array in the diagnosis of Helicobactor pylori infection in children].

OBJECTIVE: To study the value of multiple Helicobacter pylori (H.pylori) antibody detection by protein array in the diagnosis of H.pylori infection in children. METHODS: Biopsy specimens obtained by gastroscopy from 120 children with digestive system symptoms were detected by rapid urease test (RUT) and modified Giemsa staining. Positivity in both RUT and Giemsa staining was the "gold criterion" of H.pylori infection. Serum samples of these patients were obtained and the antibodies against cytotoxin associated gene A protein (CagA), vacuolating toxin A (VacA), urease, heat shock protein 60 (Hsp60) and RdxA (nitroreductase) were detected by protein array technique. RESULTS: H.pylori infection was identified according to the "gold criterion" in 60 children. Compared with the "gold criterion", the goodness of fit and the coefficient of contingency in the diagnosis of H.pylori infection of the following four groups antibody detection were all statistically significant (P<0.001): anti-Ure antibody alone, anti-Ure antibody combined with anti-CagA antibody, anti-Ure antibody combined with anti-VacA antibody and anti-Ure antibody combined with anti-CagA and anti-VacA antibody. The sensitivity, specificity and accuracy of the detection of anti-Ure antibody combined with anti-CagA antibody for the diagnosis of H.pylori infection were 81.7%, 91.7% and 86.7%, respectively. The antibody detection showed a high positive predictive value (90.7%) and a high negative predictive value (83.3%). CONCLUSIONS: The antibody detection by protein array, especially the detection of anti-Ure antibody combined with anti-CagA antibody, is valuable in the diagnosis of H.pylori infection.

HepaCAM induces G1 phase arrest and promotes c-Myc degradation in human renal cell carcinoma.

Hepatocyte cell adhesion molecule (hepaCAM) encodes a generally inactive phosphorylated glycoprotein which mediates cancer cell proliferation, migration, and differentiation. We have reported that hepaCAM is down-regulated in renal cell carcinoma (RCC) and takes responsibility of cell growth inhibition. However, the precise mechanisms of hepaCAM inhibits cell growth is still unknown. In this study, we demonstrated that re-expression of hepaCAM can cause an accumulation in G0/G1 phase in 786-0 cells. This reaction was accompanied by a substantial reduction of c-Myc expression through using an ectopic hepaCAM expression system. Furthermore, we found a comparable decrease in proliferation and G0/G1 accumulation of 786-0 and RC-2 cells after treatment with a small molecule c-Myc inhibitor, 10058-F4. This indicated that the down regulation of c-Myc was an essential process in controlling growth inhibitory actions of hepaCAM. Nevertheless, re-expression of hepaCAM results in apparent reduction of c-Myc protein with no corresponding reduction of c-Myc mRNA. This suggests that this reaction might take place at a post-transcriptional level rather than transcriptional one. Consistent with these findings, hepaCAM decreased c-Myc stability by increasing the proportion of c-Myc phosphorylation on T58 which can be abrogated by a proteasomal inhibitor (MG132). Thus, our research implies that the decrease in c-Myc protein expression, resulting from ectopic expression of hepaCAM, may contribute to the inhibition of proliferation in these cells.

[Value of aVR lead four steps algorithm on differential diagnosis of wide QRS complex tachycardia].

OBJECTIVE: The aVR lead four steps is a new algorithm for differential diagnosis of wide QRS complex tachycardia (WCT). The study explores the clinical value of this new algorithm on differential diagnosis of WCT. METHODS: Application of aVR lead four steps to analysis the electrocardiogram of patients with WCT proved by electrophysiological study. Every step's accuracy rate, sensitivity and specificity to differential diagnosis of ventricular tachycardia (VT) were calculated. The first step diagnosed VT according to presence of an initial R wave in the aVR lead. The second step diagnosed VT according to width of an initial r or q wave > 40 ms in the aVR lead. The third step diagnosed VT according to notching on the initial downstroke of a predominantly negative QRS complex in the aVR lead. The fourth step diagnosis VT according to ventricular activation-velocity ratio (Vi/Vt) in the aVR lead, Vi/Vt ≤ 1 suggested VT. Results derived from aVR lead four steps algorithm were compared with results derived from Brugada and Vereckei four steps algorithm. RESULTS: A total of 113 patients with WCT were analyzed (31 supraventricular tachycardia, SVT and 82 ventricular tachycardia, VT). The accuracy rate of differential diagnosis VT is 91.2%, sensitivity is 90.2% and specificity is 77.4%. The accuracy and sensitivity of the aVR lead four steps algorithm for differential diagnosis of WCT were superior to the Brugada Vereckei four steps algorithm (P < 0.05). The specificity of the Vereckei four steps algorithm was superior to aVR lead and Brugada four steps algorithm (P < 0.05), while the specificity of the aVR lead four steps algorithm was similar as Brugada four steps algorithm (P > 0.05). CONCLUSIONS: The aVR lead four steps algorithm is associated with excellent accuracy rate, sensitivity for differential diagnosis of WCT. This algorithm is simple and could be easily learned and applied by physician.

[Viable myocardium detecting by CARTO voltage mapping in swine model of acute myocardial infarction].

OBJECTIVE: To evaluate the accuracy and practicability of detecting viable myocardium by CARTO voltage mapping in swine model of acute myocardial infarction (MI). METHODS: MI was induced in 13 anesthetized swines via occluding the distal of left anterior descending coronary arteries by angioplasty balloon for 60-90 minutes. The viable myocardium detection by CARTO voltage mapping was made after reconstruction of the left ventricle using CARTO and the results were compared with TTC staining. The standard of CARTO voltage to detect viable myocardium was 0.5 - 1.5 mV while viable myocardium showed pink color by TTC staining. RESULTS: Eleven out of 13 swines survived the operation and 2 swines died of ventricular fibrillation at 45 and 65 minutes post ischemia. Left ventricle was divided into 16 segments and 176 segments from 11 swines were analyzed. Viable myocardium detected by CARTO voltage mapping was identical as identified by TTC staining (Kappa = 0.816, P < 0.001). Taken the TTC result as standard, the sensitivity, specificity and accuracy rate of CARTO voltage mapping are 71.8%, 96.5% and 90.9% respectively. CONCLUSION: CARTO voltage mapping could be used as a reliable tool to detect viable myocardium in this model.

[Safety and efficacy of intraoperative defibrillation threshold measured by defibrillation safety margin in 52 patients with implantable cardioverter defibrillator].

OBJECTIVE: To observe the safety and efficacy of implantable cardioverter defibrillator (ICD) intraoperative defibrillation threshold (DFT) measured by defibrillation safety margin (DSM). METHODS: Fifty-two patients underwent ICD implantation were enrolled in this study (25 single chamber ICD, 23 double chamber ICD, 4 three chamber ICD). DFT was measured by DSM method. All patients were followup regularly. RESULTS: DFT was (13.27 ± 2.95) J and DSM was (17.40 ± 2.89) J in this patient cohort. There were no serious intraoperative complications. Malignant ventricular arrhythmia occurred in 38 patients post ICD, 469 episodes of nonsustained ventricular tachycardia (VT) were spontaneously terminated, 265 episodes were sustained VT and 245 (92.5%) episodes were successfully terminated by 1 antitachycardia pace treatment (ATP), 13 (4.89%) episodes successfully terminated by 2 ATP, and ATP failed to terminate VT in 7 (2.64%) episodes and VTs were terminated by low energy cardioversion. All 141 episodes of ventricular fibrillation (VF) were successfully identified, and 14 episodes spontaneously terminated before discharging, 127 VF episodes (91.34%) were terminated by 1 energy shock, defibrillation energy was (12.84 ± 3.18) J, 11 (12.2%) VF episodes were terminated by 2 energy shocks, defibrillation energy was (16.36 ± 2.34) J. CONCLUSION: It is safe and feasible to use defibrillation threshold measured by DSM for patients receiving ICD implantation.

[Efficacy of biofeedback therapy in children with functional constipation].

OBJECTIVE: To evaluate the benefits of biofeedback therapy in children with functional constipation caused by pelvic floor dysfunction (PFD). METHOD: Anorectal manometry (PC Polygraf HR, Medtronic) was performed in children with functional constipation according to the diagnostic criteria of Rome III. Among them, 47 cases with PFD were trained with biofeedback therapy (PC Polygraf HR, Medtronic) according to the degree of cooperation. They received the treatment twice every week, and those in whom the therapy was performed at least three times were enrolled to evaluate the efficacy in this study. RESULT: A total of 27 cases (20 male and 7 female) in whom the procedure was performed at least three times were eligible for inclusion into this study. The mean age of them was (6.7 + or - 2.2) years (range 4 to 12 years), and the mean duration of symptoms was (3.0 + or - 2.3) years with a range of 6 months to 8 years. Among them, 16 cases received the biofeedback training more than 5 times, while 8 cases more than 7 times. The rectal maximum contraction pressure during defecation was increased significantly with the number of biofeedback training before treatment and after 3, 5, and 7 times of treatment was (36.2 + or - 10.4), (45.1 + or - 9.5), (47.6 + or - 9.1), and (47.8 + or - 8.8) mm Hg (1 mm Hg = 0.133 kPa) respectively (P < 0.01). The potential of electromyography of external anal sphincter decreased progressively, but had not reached significance. Follow-up continued for 3 to 12 months by telephone, the clinical response to biofeedback treatment was evaluated as excellent (complete resolution of constipation), good (improvement of constipation), partial or poor (no improvement of constipation). The response was excellent in 13 cases (48.1%), good in 8 (29.6%), partial in 3 (11.1%), and 2 (7.5%) cases had no improvement, and 1 case was lost to follow-up, and the rate of success was 88.9% (24/27). CONCLUSION: Biofeedback therapy is a safe and effective treatment option for functional constipation due to PFD in children probably by increasing the rectal maximum contraction pressure during defecation.

[Pathogenic effects of primary duodenogastric reflux on gastric mucosa of children].

OBJECTIVE: Duodenogastric reflux (DGR) is a reverse flow of duodenal juice into stomach through pylorus composed of bile acid, pancreatic secretion, and intestinal secretion. The increased entero-gastric reflux results in mucosal injury that may relate not only to reflux gastritis but also esophagitis, gastric ulcers, carcinoma of stomach and esophagus. However, the exact mechanisms of gastric mucosal damage caused by DGR are still unknown. The objective of the present study is to investigate the pathogenic effect of primary DGR on gastric mucosa in children, and to explore the correlation of DGR with clinical symptoms, Hp infection and intragastric acidity. METHOD: Totally 81 patients with upper gastrointestinal manifestations were enrolled and they were graded according to the symptom scores and underwent endoscopic, histological examinations and 24-hour intra-gastric bilirubin was monitored with Bilitec 2000. Of the 81 cases, 51 underwent the 24-hour intra-gastric pH monitoring by ambulatory pH recorder simultaneously. The total fraction time of bile reflux was considered as a marker to evaluate the severity of DGR. The total fraction time of bile reflux was compared between the patients with positive and negative results under endoscopy and histologically, respectively. The correlations of the total fraction time of bile reflux with clinical symptom score, Hp infection, intragastric acidity were analyzed respectively. RESULT: The total fraction time of bile reflux in the patients with hyperemia and yellow stain gastric antral mucosa under endoscopy was significantly higher than that without those changes [17.1% (0.5% approximately 53.2%) vs. 6.5% (0 approximately 58.6%), Z = -1.980, P < 0.05; 19.8% (0.5% approximately 58.6%) vs. 8.8% (0 approximately 38.0%), Z = -2.956, P < 0.01 respectively]. Histologically, the cases with intestinal metaplasia had significantly higher total fraction time of bile reflux than in the cases without intestinal metaplasia [29.0% (1.9% approximately 58.6%) vs. 14.3% (0 approximately 53.7%), Z = -2.026, P < 0.05], but no significant difference was found either between the cases with and without chronic inflammation (P > 0.05) or between the cases with and without active inflammation (P > 0.05). The severity of bile reflux was positively correlated with the score of abdominal distention (r = 0.258, P < 0.05), but no correlation with either the severity of intragastric acid (r = -0.124, P > 0.05), or Hp infection (r = 0.016, P > 0.05) was found. CONCLUSION: Primary DGR could cause gastric mucosal lesions manifested mainly as hyperemia and bile-stained gastric antral mucosa under endoscopy and the gastric antral intestinal metaplasia histologically in children. There was no significant correlation between DGR and gastric mucosal inflammatory infiltration. DGR had no relevance to Hp infection and intragastric acidity. We conclude that DGR is probably an independent etiological factor and might play a synergistic role in the pathogenesis of gastric mucosal lesions along with gastric acid and Hp infection.