Mechanism of tyrosine kinase 2 inhibitors in treatment of plaque psoriasis and their progress in clinical trials / 中国临床药理学与治疗学

As a chronic, immune-mediated inflammatory disease, plaque psoriasis has a great burden of disease and influences on patient's physical and mental health. In the past decade, plaque psoriasis treatment with biological agents achieved breakthrough development, while oral drugs with promising efficacy and safety are yet to be met. By cell signal transduction, the Janus kinase-signal transducer and activator of transcription pathway plays an important role in numerous immune-related diseases. Tyrosine kinase 2 (TYK2), a member of the JAK family, can impact on plaque psoriasis by regulating signaling and functional responses downstream of IL-12, IL-23, IFN. Deucravacitinib, a highly selective TYK2 inhibitor, has finished its phase 3 clinical trials and shown its efficacy and safety in treatment of plaque psoriasis. Several kinds of TYK2 inhibitors are under research and development at the moment. In this review, we demonstrate roles of JAK-STAT pathway and TYK2 in plaque psoriasis as well as updates on ongoing and recently completed trials of TYK2 inhibitors.

Change of Humoral Immunity in Early Stage of Acute Pancreatitis / 胃肠病学

Background:Impaired immune function occurs in the early stage of acute pancreatitis (AP). Aims:To explore the changes of serum immunoglobulins in the early stage of AP and their values in predicting the severity of the disease. Methods:A total of 164 AP patients diagnosed within 24 hours of onset from Jan. 2014 to Dec. 2014 at the First Affiliated Hospital of Soochow University were enrolled. The number of patients with mild,moderately severe,and severe AP (MAP, MSAP and SAP)were 103,47 and 14,respectively. Twenty-two healthy subjects were served as controls. Serum samples were collected within 48 hours of onset for detection of IgG,IgA,IgM,κ light chain and λ light chain levels. ROC curve and area under the curve (AUC)were used to assess the performance of these indices for predicting the disease severity. Results:A decline in varying degrees was observed in serum levels of IgA,IgM,κ light chain and λ light chain within 48 hours of onset of AP. The difference was statistically significant in serum IgM between MSAP,SAP groups and MAP group (P＜0.05). ROC curve showed that serum IgM had a moderate accuracy for differentiating MSAP and SAP from MAP (AUC＝0.723,95% CI:0.634-0.812);with cut-off value≤1.055 g/L,the sensitivity and specificity were 0.806 and 0.689,respectively. Conclusions:Serum levels of IgA,IgM,κ light chain and λ light chain decrease obviously in the early stage of AP,which suggests humoral immune dysfunction. Serum level of IgM may be used as a predictor for severity of AP in early stage of the disease.

Effect of motivational intervention on compliance,negative emotions and quality of life in elderly patients with biliary acute pancreatitis / 实用医学杂志

Objective To investigate the effects of motivational interview on compliance,negative emo-tions and quality of life in elderly patients with biliary acute pancreatitis. Methods 56 patients with senile biliary acute pancreatitis who underwent routine interventions from September 2015 to August 2016 were selected as the control group. Patients in the interventional intervention interviews between September 2016 and August 2017 56 cases of elderly patients with gallstone acute pancreatitis were selected as the observation group. Comparisons of treatment adherence,negative emotions and quality of life before and after intervention for one month were com-pared between the two groups. Results After 1 months'intervention,the treatment compliance of the observation group was better than that of the control group. The difference was statistically significant(P < 0.05). After 1 months' intervention,the negative emotion scores of the observation group were all lower than those of the control group,and the scores of all quality of life were significantly higher than those of the control group,the difference was statistically significant(P < 0.05). Conclusions The motivational interview is effective in elderly patients with biliary acute pancreatitis,which can effectively improve the treatment compliance,reduce the negative emo-tions and improve the quality of life,which is worth promoting.

Clinical significance of B7-H3, an expression membrane type of myeloid-derived suppressor cell in patients with acute pancreatitis / 中华急诊医学杂志

Objective To explore the clinical significance of B7 family homology factor-3 (B7-H3),an expression membrane type of myeloid-derived suppressor cell (MDSC),in patients with acute pancreatitis (AP).Methods A total of 63 patients with AP initially treated in the Emergency Department at the First Affiliated Hospital of Soochow University from January,2014 to December,2015 were selected.Of them,25 suffered from mild AP (MAP),20 had moderate AP (MSAP) and 18 had severe AP (SAP).Another 20 healthy subjects with matching age and gender served as the control group.All patients with AP conformed to the diagnostic criteria of Guidelines or Diagnosis and Treatment of Acute Pancreatitis set in 2013 in China.Patients with other underlying diseases that might influence the clinical outcomes were excluded,including those with tumors,autoimmune diseases,viral infections,trauma and other disorders.A flowcytometer was used to detect the expression rate of MDSC in peripheral venous blood and the expression of B7-H3 on MDSC membrane.The continuous monitoring was carried out for 24 h,48 h and 72 h in patients with AP.Results Compared with healthy subjects,the MDSC cells in patient groups 24 hours after AP onset increased notably (P ＜0.01) especially the highest increase in the SAP group,followed by the MSAP group and the lowest in the MAP group.There were significant differences in pairwise comparisons (P ＜ 0.05).From successive observation of each group,there was no significant difference in MDSC between the MAP group and the MSAP group 24 hours,48 hours and 72 hours after AP onset.However,MDSC reached its peak 48 hours after AP onset,but it declined 72 hours after AP onset in the SAP group (P ＜ 0.05).B7-H3 expressed significantly 24 hours after AP onset,but there was no expression of B7-H3 in the healthy group.Meanwhile,B7-H3 was expressed most highly in the SAP group,followed by the MSAP group and lowest in the MAP group.There were significant differences in expression of B7-H3 found in pairwise comparisons (P ＜ 0.05).The successive observation showed that there was no significant difference in B7-H3 expression between the MAP group and the MSAP group 24 hours,48 hours and 72 hours after AP onset.However,there was a trend of increase in B7-H3 expression as time prolonged found among 24 hours,48 hours and 72 hours after AP onset in the SAP group (P ＜ 0.05).Conclusions The expressions of MDSC and B7-H3 were high in AP,and there were significant differences in both expressions among MAP,MSAP and SAP groups.These phenomena offer clues in further understanding about the immunological disorders during AP giving better guidelines for clinical practice.

BISAP and APACHEⅡ scores in predicting the severity and organ failure of patients with acute pancreatitis / 中华胰腺病杂志

Objective To evaluate the clinical value of bedside index for severity in acute pancreatitis (BISAP) and APACHEⅡ score in predicting the severity and organ failure of acute pancreatitis (AP).Methods One hundred eighty-five patients of AP admitted to Department of Gastroenterology of First affiliated Hospital of Soochow University from January 2012 to December 2014 were studied retrospectively.According to BISAP score, patients who were ≥3 points were considered as high risk group, while ＜3 points were considered as low risk group.According to APACHEⅡ score, patients who were ≥ 8 points were considered as high risk group, while ＜ 8 points were considered as low risk group.According to the criteria of Pancreatic Diseases Group of Chinese Society of Gastroenterology of Chinese Medical Association, the patients were diagnosed as mild acute pancreatitis (MAP), moderately severe acute pancreatitis (MSAP), and severe acute pancreatitis (SAP).The BISAP, APACHEⅡ scores were calculated and compared between MAP group and MSAP + SAP group, respectively.The incidence of MSAP + SAP between high risk group and low risk group was also compared.The area of ROC curve (AUC) was used to evaluate the ability of BISAP and APACHEⅡ scoring system for predicting the severity of AP and the multiple organ dysfunction syndromes (MODS).Results Among 185 patients, MAP was identified in 101 patients, MSAP in 76 patients and SAP in 8 patients.Twenty-five MSAP patients developed organ dysfunction, and all the 8 SAP patients developed organ dysfunction.The BISAP scores of MSAP + SAP group and MAP group were (1.43 ± 0.89), (0.38 ± 0.61),andAPACHⅡ scores were (2.45± 1.36), (0.87± 0.62), the scores of MSAP+ SAP group were significantly higher than those in MAP group (P ＜0.01).In the 137 patients of low risk BISAP group, there were 47 MSAP + SAP patients (34.3％), while in the 48 patients of high risk BISAP group, there were 37 MSAP + SAP patients (77.0％);in the 153 patients of low risk APACHEⅡ group, there were 56 MSAP + SAP patients (36.6％), while in the 32 patients of high risk APACHEⅡ group, there were 28 MSAP + SAP patients (87.5％);the incidence of MSAP + SAP patients was significantly higher in high risk group than that in low risk group (P＜0.01).The AUC of BISAP, APACHEⅡ for MSAP+ MAP was 0.804 (95％ CI 0.738 ～ 0.870), 0.794 (95％ CI 0.725 ～ 0.863), and the AUC for organ dysfunction was 0.758 (95％ CI 0.686 ～0.830), 0.781 (95％ CI 0.710 ～0.852) , and the difference between BISAP and APACHE Ⅱ was not statistically significant (P ＞ 0.05).Conclusions The BISAP has the prediction ability for AP severity and prognosis similar to APACHEⅡ , and it consists of only 5 parameters and can be completed in the first 24 h of admission, therefore it is worth of clinical application.

Clinical significance of soluble B7-H3 in early evaluating the severity of patients with acute pancreatitis / 实用医学杂志

Objective To investigate the clinical value of sB7-H3 in predicting the severity of acute pancreatitis at early stage. Methods By using the double antibody sandwich ELISA method, the level of plasma sB7-H3 was measured at 24h after onset of abdominal pain in 75 patients with acute pancreatitis (MAP30, MSAP20, SAP25), and 20 healthy persons were enrolled in the controlgroup.The sensitivity and specificity correlations of sB7-H3 in acute pancreatitis with severity degree , as well as with the clinical detection index , were also evaluated. Results The level of plasma sB7-H3 at 24 h in the AP group was significantly higher than that in the healthy control ( HC) group (t = 3.925, P = 0.0002), however, no significant difference was found between the MAP groep and the HC group (P>0.05). The levels of plasma sB7-H3 in the MSAP and the SAP group were significantly higher than that in the HC group (P<0.05和P<0.001)or the MAP group (P<0.05 和P<0.01);The level of plasma sB7-H3 in the SAP group was also markedly higher than that in the MSAP group (P < 0.01). sB7-H3 had a linear positive correlation with LDH、hs-CRP、WBC(P<0.05). ALB had a linear negative correlation with and Ca (S)(P<0.05). By the cutoff of sB7-H3, the sensitivity and specificity to judgethe above moderate pancreatitis were 88.9%and 83.3%,and to judgethe SAP were 96%and 96%. Conclusion sB7-H3 has important clinical value to judge the severity of acute pancreatitis at early time with high sensitivity and specificity , with a linear correlation with the clinical severity index.

Testing and its clinical significance of plasma neutrophil gelatinase-associated lipocalin in patients with acute pancreatitis / 中华消化杂志

Objective To quantify the concentration of peripheral blood plasma neutrophil gelatinase-associated lipocalin (NGAL) in patients with acute pancreatitis (AP) and to explore its value in assessment of the severity of AP.Methods From June 2011 to March 2012,83 patients with AP were selected,among those 43 cases were mild acute pancreatitis (MAP) and 40 were severe acute pancreatitis (SAP).The control group included 30 healthy individuals.The peripheral blood of patients with AP and healthy controls was collected,and plasma was isolated after centrifuged.The concentration of NGAL in plasma was detected by enzyme-linked immunosorbent assay (ELISA).The t-test was performed for comparison between groups.The correlation between the concentration of NGAL in plasma and clinical parameters of AP was analyzed by Spearman rank order correlation analysis.The diagnosis value of the concentration of NGAL in SAP was evaluated by receiver operating characteristic (ROC) curve and area under the curve (AUC).Results The concentration of plasma NGAL in AP group ((10.30± 5.97)nmol/L) was higher than that in healthy control group ((1.94±1.35) nmol/L) and the difference was statistically significant (t=11.924,P＜0.01).The concentration of plasma NGAL in SAP group ((14.61 ±5.28) nmol/L) was higher than that in MAP group ((6.27±-3.09) nmol/L) and healthy control group,the differences was statistically significant (t=8.677 and 14.539,both P＜0.01).The concentration of plasma NGAL of AP patients was positively correlated with acute physiology and chronic health evaluation-Ⅱ score,Ranson score,bedside index for severity in acute pancreatitis score,computed tomography (CT) severity index,C-reactive protein,white blood cells and the days of hospitalization (r=0.651,0.556,0.514,0.620,0.320,0.458 and 0.346,all P＜0.05).The area under the ROC curve of plasma NGAL concentration in diagnosis of SAP was 0.926 (95％CI:0,870-0.983).The cutoff value of plasma NGAL level in diagnosis of SAP was 8.44 nmol/L.The sensitivity and specificity was 87.5 ％ and 88.9％,respectively.Conclusions Plasma NGAL level is correlated with the severity of patients with AP.NGAL may be one of the markers for the early diagnosis of SAP.

Therapeutic effect of nitrate on dextran sulfate sodium induced acute experimental colitis in mice / 中华消化杂志

Objective To investigate the effect of nitrate on acute experimental colitis in mice.Methods A total of 40 BALB/c mice were evenly divided into model group and treatment group.Model group were fed with 4％ dextran sulfate sodium (DSS) solution and treatment group were given 4％ DSS solution and nitrate (1.5 g/L) for seven days.The disease activity index (DAI) of mice was scored.The colon tissue of mice was taken for hematoxylin-eosin staining and myeloperoxidase (MPO)immunohistochemical staining observation.The MPO and activity of nitric oxide in colon tissue were measured by MPO and nitric oxide detecting kit.The data were analyzed by t test.Results At the 6th day and 7th day,the difference of DAI between treatment group and model group was statistically significant (t=5.12 and 6.72,P=0.012 and 0.008).At the 7th day,the tissue score of model group (2.5±0.5) was higher than that of treatment group (1.9±0.4) and the difference was statistically significant (t=3.82,P＜ 0.01).Compared with model group,the histopathological injury of colon tissue in treatment group mice significantly reduced and neutrophil infiltration also decreased.At the 7th day,the concentration of MPO,NO2-and NO3-of model group was (2.8±0.6) U/g,(10.4±4.3) mmol/g and (100.3±50.1) mmol/g respectively,treatment group was (1.5±0.3) U/g,(17.5±7.0) mmol/g and (190.7 ±85.3) mmol/g respectively.The differences were statistically significant (t=11.23,3.81 and 4.50,all P＜0.01).Conclusion Nitrate can reduce DSS-induced acute experimental colitis in mice.

Association of serum cytokines with pancreatic function in patients after acute pancreatitis / 中华消化杂志

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.