Objective To analyze expression of interleukin (IL)-23p19 and IL-23 receptor (IL-23R) in inflammatory bowel disease (IBD),and the role in the induction of peripheral blood T cell activation and proinflammatory cytokine secretion.Methods Peripheral blood (PB) and intestinal mueosal biopsies were collected from 12 patients with Crohn's disease (CD),25 patients with ulcerative colitis (UC) and 20 healthy controls.Expression of IL-23p19 was determined by immunohistochemistry and RT-PCR.IL-23R expression in CD4+,CD8+ T and NK cells from peripheral blood and lamina propria was analyzed by flow eytometry.Peripheral blood mononuclear ceils (PBMC) were isolated and cultured under stimulation with IL-23 and anti-CD3,and the levels of tumor necrosis factor α (TNFα) interferon (IFN)γ and IL-2 were determined by enzyme-linked immunosorbent assay (ELISA).Results The expression of II.-23p19 was significantly increased in inflamed mucosa of CD at both the transcriptional and translational levels compared with that in UC and healthy controls.IL-23R was mainly expressed in PB- and lamina propria-CD4+,CD8+T cells and NK cells from IBD patients,and markedly increased compared with controls (P＜0.05).IL-23 strongly triggered PBMC from IBD patients to produce significantly higher levels of IFN-γ,TNF-α and IL-2(P＜0.05).Conclusions IL-23p19 and IL-23R are highly expressed in IBD,particularly in CD,and may play an important role in the induction of T cell activation and proinflammatory cytokine secretion,suggesting that targeted therapy directed against IL-23 may have a therapeutic role in IBD.

Objective To evaluate the effect of enteral nutrition (EN) versus total parenteral nutrition(TPN) on gut barrier function in patients with severe acute pancreatitis (SAP). Methods Sixtythree patients with SAP enrolled from 4 hospitals were randomly assigned into EN group(29 cases) and TPN group(34 cases). EN group patients were fed via a spiral nasojejunal feeding tube placed routinely by endoscopy or fluoroscopy, and TPN group patients were nourished intravenously with TPN during the same period. The changes of serum endotoxin, diamine oxidase, and urinary excretion of lactulose and mannitol ratio (L/M) were observed. Results Plasma concentration of endotoxin were markedly decreased in EN group as compared with that in TPN group at the 7th,14th ,21th day of entry trial [(39. 30 ± 15. 82) EU/L vs (73.05 ±21.16) EU/L,(22.64 ±14.31) EU/L vs (49.34 ±24.54) EU/L,(14.81 ± 10.93)EU/L vs ( 30. 08 ± 14. 10 ) EU/L, P ＜ 0. 05]. Plasma concentration of diamine oxidase were markedly decreased in EN group as compared with that in TPN group at the 7th, 14th day of entry trial [(9. 97 ± 3. 84)U/Lvs (19.89±9.89)U/L,(5.42±1. 84) U/Lvs (8.79 ±4.08) U/L, both P ＜ 0. 05]. The urinary L/M decreased significantly in EN group than those in TPN group at the 7th, 14th,21th day of entry trial (0.28 ±0.25 vs 0. 65 ±0.45,0.21 ±0. 18 vs 0.54 ±0.41,0.08 ±0.04 vs 0.29 ±0.06, all P＜0.05).Conclusion EN has better effect on improving intestinal barrier function than TPN in treatment of patients with SAP.

ObjectiveTo investigate the effect of vasostatin on the migration of pancreatic cancer endothelial cells.Methods Ad-vasostatin with different concentrations of vasostatin was used to transfect pancreatic cancer endothelial cells.Ad-LacZ transfection and PBS was used as control.The effect of vasostatin gene mediated by adenovirus on the migration of pancreatic cancer endothelial cells was measured by woundhealing assay,transwell migration assay,and tube formation assay.ResultsThe scratched lines in PBS group and Ad-LacZ group were almost healed 48 hours later,while the lines in Ad-vasostatin group were rarely healed.At the MOI of 1,2,5,the migration rate of Ad-Laz group was ( 84.7 ± 2.6) ％,(80.7 ± 1.7 ) ％ and (81.3±4.0)％,while the corresponding values were (77.7 ±2.1)％,(67.3 ±2.1)％ and (38.8 ±2.1 ) ％ in Ad-vasostatin group.Transwell migration assay indicated that the number of migrated cells in Advasostatin group was inhibited in a dose-dependant manner,at the MOI of 5,the migration became significantly decreased (F=180.88,P ＜0.05).At the MOI of 1,5,10,the number of tubes in Ad-LacZ group was 118±6,120±6 and 82±5,while the corresponding values were 65±4,21±4 and 4 ±1 in Ad-vasostatin group.The number of tubes of pancreatic cancer endothelial cells was inhibited by Ad-vasostatin in a dose-dependant manner,at the MOI of 10, it was difficult to form the tubes (F-300.85,P＜0.05). Conclusions The vasostatin gene mediated by adenovirus has a significant inhibitory effect on the migation of pancreatic cancer endothelial cells in vitro in a dose-dependent manner.

Objective To assess the effect of continuous early enteral nutrition(EEN)combined with intestinal mucosal protective agents on gut barrier function in patients with severe acute pancreatitis.Methods A total of 79 patients with severe acute pancreatitis selected from four centers between May 2004 to June 2006 were enrolled and divided into EEN combined with intestinal mucosal protective agents group(combined group,n=39)and total parenteral nutrition(TPN)group(n=40).The patients were received either EEN or TPN when homeostasis were achieved within 72 hours after onset.The patients in combined group were administered pepti-2000 variant combined with glutamine,arginine and intestinal mucosal protective agents.The patients in TPN group were administered through a central vein.APACHE-Ⅱ score was recorded every week;The concentration of serum amylase,plasmic diamine oxi dase(DAO)and endotoxin were mesured on day 1,7,14 and 21 as well as urinary excretion of lactulose (L)and mannitol(M).Complications,lenth and charges of hospital stay were recorded.Results There was no death in both groups.The APACHE-Ⅱ score decreased on day 7,but lower in combined group (6.00±1.60)than that in TPN group(7.08±2.34)(P＜0.05).On day 7,14 and 21,the concentrations of endotoxin in combined group was(39.30±15.82),(22.64±14.31),(14.81±10.93)Eu/L,respectively,urinary L/M ratio was 0.28±0.25,0.21±0.18 and 0.08±0.04,respectively,IFABP-c was 15.62±5.26),(5.46±1.18)and(3.26±0.94)pg/ml,respectively.All of these parameters were significantly lower than those in TPN group(P＜0.05).The infectious rates including pancreatic,peritoneal and respiratory infection in TPN group were much higher than that in combined group(26.47% vs 3.44%,P＜0.01).The composition of flora fecal remained unchange in combined group rather than TPN group.The mean hospital stay was shorter in combined group[(20.0±5.7)days]compared to TPN groups[(34.5±12.9)days].The charges were also significantly lower in combined group,with average cost of RMB 25,900±14,200,while it was 46,800±4,030 in TPN group.Conclusions EEN combined with intestinal mucosal protective agents can improve gut barrier function via reducing the gut permeability,improving the hypoperfusion,maintaining the integrity and gut fecal flora.It might reduce the course and charges of hospital stay.

Objective To investigate the effect of cytokines on pancreatic function in patients after acute pancreatitis(AP) and its mechanisms. Methods Fifty-nine patients (mild in 25 and severe in 34) after AP and 20 healthy controls were enrolled in the study. Serum levels of cytokines including hepatocyte growth factor (HGF), epidermal growth factor(EGF), basic fibroblast growth factor (bFGF), regeneration protein(Reg)-1 and Reg-4 were determined using enzyme-linked immunosorbent assay (ELISA). Fasting blood-glucose, insulin, C-peptide and fecal elastase 1 (FE1) were detected for evluation of endocrine and exocrine pancreatic function. The association of pancreatic function with clinical parameters and serum cytokines was analyzed. Results The expression of FE1 was lower in patients [(205.9±18.3) μg/g] after AP in comparison with the controls [(333.9±19.7) μg/g, P<0. 01], but levels of fasting blood-glucose, C-peptide and insulin were higher in patients group (P<0.01). Serum level of HGF was higher in patients with insufficient pancreatic exoerine [(983.76±372.65) pg/ml] than those with normal exocrine function [(263.44±110. 35) pg/ml]. Meanwhile,EGF level was higher in patients with DM after AP [(704.41±190. 37) pg/ml] than those without DM [(360. 03±48.39) pg/mh P<0.05]. There was a negatively correlation between FE1 and HGF (P ＜0. 01). The abnormal fasting blood glucose was correlated with CT grading (P<0. 05).Conclusions The patients after AP develope insufficient exocrine and endocrine function. Serum EGF and HGF may be associated with restoration of pancreatic endocrine and exocrine function.

AIM: To explore the role of ZKSCAN3 in acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: After verifying the efficacy of ZKSCAN3 siRNA, male C57BL/6 mice were randomly divided into 4 groups (n = 8): control group(group A), LPS group (group B), scrambled siRNA group (group C) and ZKSCAN3 siRNA group (group D). Mice in groups A and B were given 1 mL of PBS via tail vein; mice in groups C were given corresponding doses of PBS containing scrambled siRNA; and mice in group D were given corresponding doses of RNase-free PBS containing ZKSCAN3 siRNA (50 μg). After 24 hours, mice in groups B, C, and D were instilled with LPS solution (5 mg/kg) through tracheal intubation to create an ALI model; group A was given the corresponding dose of PBS (20 ΜL). The samples were collected and tested 24 hours after the modeling administration. RESULTS: Compared with group B, silencing ZKSCAN3 gene expression reduced SOD activity and Bcl-2 level; while MDA, Bax and caspase-3 increased; correspondingly, the content of protein and cells in BAL, the apoptosis rate of lung tissue and the pathological score significantly increased (P < 0.05).CONCLUSION: Silencing ZKSCAN3 gene expression aggravates the lung injury caused by LPS, which may aggravate the pathological damage of lung tissue in mice by weakening the antioxidant function and aggravating tissue necrosis.

Objective To observe the incidence of pericardial tamponade(PT)after left atrial appendage closure(LAAC)in patients with non-valvular atrial fibrillation(NVAF),and to explore its related factors and outcomes.Methods NVAF patients who were hospitalized and treated with LAAC in Department of Cardiology of our hospital from August 2014 to March 2023 were selected for the study.The general clinical data,preoperative transthoracic echocardiography and transesophageal echocardiography data,results of routine preoperative laboratory tests,intraoperative data and follow-up data of the patients were collected through the hospital medical record management system.The enrolled patients were classified into the non-PT group(n=8)and the PT group(n =1184)according to whether PT occurred after LAAC or not.The incidence of PT,related risk factors and outcomes were statistically analyzed.Results This study included 639 males(53.6%)and 553 females(46.4%),with an average age of 68.1±9.65 years.The CHA2 DS2-VASc score was 4.51±1.72,and the HAS-BLED score was 3.36±1.09.PT occurred in 8 cases(0.67%),among them,6 cases occurred 1 to 33 h after LAAC,and 2 cases occurred on day 19 and day 27 after LAAC.As for the results of transesophageal echocardiography(TEE)and LAA angiography,compared with the non-PT group,the PT group had the significantly larger maximum caliber of the LAA(P=0.025,P=0.015),smaller maximum depth of the LAA(P=0.028,P=0.031),and lower success rate of one-time placement of the occluder(P=0.031);The occluder compression rate of the PT group was significantly greater than that of the non-PT group(P=0.046).Multivariate analysis showed that larger maximum diameter of LAA,smaller average effective depth of LAA and larger compression rate of occluder were the main risk factors for PT.All the 8 PT patients were cured by stopping antithrombotic drugs,pericardiocentesis or surgical drainage.During a mean follow-up of 39±27 months,there were no device-related thrombosis(DRT),ischemic stroke,systemic embolism and other complications in the PT group.Conclusion The incidence of PT after LAAC is low,which is related to the large diameter of LAA,the relatively insufficient depth of the LAA and the large compression rate of the occlude.PT can be cured by stopping antithrombotic drugs and pericardiocentesis/surgical drainage.

Objective To optimize the spray drying process of Banlangen(Isatidis Radix)formula granules based on quality by design(QbD)concept.Methods Using powder yield and the contents of uridine,adenosine,guanosine,and(R,S)-goitron as the critical quality attributes(CQAs),Plackett-Burman design was used to screen out critical process parameters(CPPs)for inlet temperature,spray pressure,liquid temperature,pump speed,and liquid relative density.The central-composite design(CCD)test was used to optimize the CPPs,which were screened.Based on the quadratic polynomial regression model,the design space of spray drying process of Banlangen(Isatidis Radix)formula granules was established,and further validated by experiments.Results Plackett-burman test results show that liquid relative density and inlet velocity are the key parameters for the study.The variance analysis results of CCD test showed that the constructed model in a good prediction ability,since the P-values of model was less than 0.01 and P-values of items lack of fit was more than 0.05.The optimized design space of CPPs was the liquid relative density 1.05-1.08,and pump speed 30%-40%.Conclusion Based on the QbD concept,the design space for the spray drying process of Banlangen(Isatidis Radix)formula granules can improve the stability of its process and help ensure the consistency of product quality.