Background/Aims: Metabolic syndrome is common in patients with acute pancreatitis and its components have been reported to be associated with infectious complications. In this post hoc analysis, we aimed to evaluate whether metabolic abnormalities impact the effect of immuneenhancing thymosin alpha-1 (Tα1) therapy in acute necrotizing pancreatitis (ANP) patients. Methods: All data were obtained from the database for a multicenter randomized clinical trial that evaluated the efficacy of Tα1 in ANP patients. Patients who discontinued the Tα1 treatment prematurely were excluded. The primary outcome was 90-day infected pancreatic necrosis (IPN) after randomization. Three post hoc subgroups were defined based on the presence of hyperglycemia, hypertriglyceridemia, or both at the time of randomization. In each subgroup, the correlation between Tα1 and 90-day IPN was assessed using the Cox proportional-hazards regression model. Multivariable propensity-score methods were used to control potential bias. Results: Overall, 502 participants were included in this post hoc analysis (248 received Tα1 treatment and 254 received matching placebo treatment). Among them, 271 (54.0%) had hyperglycemia, 371 (73.9%) had hypertriglyceridemia and 229 (45.6%) had both. Tα1 therapy was associated with reduced incidence of IPN among patients with hyperglycemia (18.8% vs 29.7%: hazard ratio, 0.80; 95% confidence interval, 0.37 to 0.97; p=0.03), but not in the other subgroups. Additional multivariate regression models using three propensity-score methods yielded similar results. Conclusions Among ANP patients with hyperglycemia, immune-enhancing Tα1 treatment was associated with a reduced risk of IPN (ClinicalTrials.gov, Registry number: NCT02473406).

Programmed cell death ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) cascade is an effective therapeutic target for immune checkpoint blockade (ICB) therapy. Targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity. Using flow cytometry-based assay, we identify tubeimoside-1 (TBM-1) as a promising antitumor immune modulator that negatively regulates PD-L1 level. TBM-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of PD-L1. Furthermore, TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma (LLC) and B16 melanoma tumor xenograft

Objective To observe the clinical outcomes and safety of continuous negative pressure irrigation (NPI) and endoscopic necrosectomy(ED) for treating infected pancreatic necrosis(IPN). Methods A retrospective review of the data of 163 severe acute pancreatitis(SAP) patients with IPN who were treated by four-step drainage from January 2012 to December 2013 at the SAP therapy center of Nanjing General Hospital was performed. All patients were divided into 7 groups including PCD alone, PCD+NPI, PCD+NPI+ED, PCD+ON, PCD +NPI +ON, PCD +ED +ON and PCD +NPI +ED +ON group based on the drainage strategy of percutaneous catheter drainage(PCD),NPI, ED and open necrosectomy(ON), and the feasibility and safety were analyzed. Results All the patients underwent PCD therapy. Each patient underwent a median of 3 drainage procedures and the median total drainage duration was 11 days. No significant procedure-related complication was observed. Around 40% of the patients recovered after receiving PCD alone. Thirty-four patients(20.9%) underwent ON. The mean hospitalization duration was 38 days and the mean ICU stay was 19 days. There were 25 cases with new-onset organ functional failure,26 patients with sepsis,32 patients with gastric and intestinal fistula,34 patients with intra-abdominal bleeding,8 patients with portal vein thrombosis and 3 patients with gastric outlet obstruction. 28 patients(17.2%) died. Conclusions This four-step approach is effective in treating IPN when compared with other step-up strategies. NPI and ED could offer distinct clinical efficacy without adding no extra risk to patients.

Objective To evaluate the dose variation of target coverage and organs at risk ( OARs) among four planning strategies using spot-scanning carbon-ion radiotherapy for non-small cell lung cancer ( NSCLC) . Methods Ten NSCLC patients utilizing gating motion control were selected to receive dose calculation over multiple acquired 4DCT images. Four optimizing strategies consisted of intensity-modulated carbon-ion therapy ( IMCT-NoAS ) , IMCT combined with internal gross tumor volume ( IGTV ) assigned muscle ( IMCT-ASM ) , single beam optimization ( SBO ) ( SBO-NoAS ) and SBO combined with IGTV assigned muscle (SBO-ASM).The initial plan was re-calculated after the 4DCT data were reviewed and then compared with the initial plan in the dosimetry. Results For re-calculation plans with two reviewing CTs,all four strategies yielded similar planning target volume ( PTV ) coverage. Merely IMCT-NoAS strategy presented with relatively significant variations in dose distribution. Dose variation for OARs between initial and re-calculated plans:for all four strategies,V20 of ipsilateral lung was increased by approximately 2. 0 Gy (relative biological effective dose,RBE),V30 of heart was increased by approximately 1. 0 Gy (RBE) for both IGTV assigned muscle strategies,whereas decreased by approximately 0. 2 Gy ( RBE) for both IGTV non-assigned muscle strategies. The maximum dose of spinal cord was changed by 2. 5 Gy ( RBE ) . Conclusions Carbon-ion radiotherapy is sensitive to the anatomic motion within the tumors along the beam path. When the tumor motion along the head-foot (H-F) direction exceeds 8 mm,SBO-ASM strategy provides better dose coverage of target. Strategies with IGTV assignment may result in dose overshoot to a position deeper than the initial planning dose distribution.

Objective: To evaluate the efficacy and safety of Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea (AAD) in infants and young children. Method: From November 2012 to September 2013, ten research units of large teaching hospitals or children′s hospitals participated in this multicenter randomized controlled clinical trial. Hospitalized young children aged between 1 month and 3 years (nongastrointestinal infection and antibiotic therapy required)were involved in our study. The children were randomly divided into control group and prevention group by means of block random allocation method. The control group received antibiotic therapy and other conventional treatment. The prevention group was given additional Saccharomyces boulardii (250 mg/d) orally. Diarrhea rates of two groups were compared both during the usage of antibiotics and within 14 days after the antibiotics withdrawal. The adverse reactions of Saccharomyces boulardii were observed all through this study. The results were analyzed by χ² test or Kruskal-Wallis test or t test. Result: Totally 408 cases (213 cases in prevention group and 195 cases in control group) were enrolled. The age ranged from 1 month to 3 years, with an average age of 1.14 years. The basic diseases were parenteral infections: 368 cases with different kinds of respiratory tract infections or pneumonia, 10 cases of bacterial meningitis, 9 cases with septicemia or sepsis, 6 cases with pertussis or pertussis like syndrome, 5 cases with urinary infection, 5 cases with skin or subcutaneous tissue infections, 3 cases of Kawasaki disease, one with scarlet fever and one with congenital syphilis. During the administration of antibiotics, the incidence of AAD in prevention group was 10.3% (22 cases), which was significantly lower than that of control group (57 cases, 29.2%, χ²=23.296, P<0.05). Within 14 days after the discontinuation of antibiotics, the percent of new diarrhea cases in prevention group (2.4%, 5/213) was also significantly lower than that in control group (16.4%, 32/195, χ²=23.4, P<0.05). Further analysis revealed that the rate of AAD in children less than or equal to 1 year old (25.1%, 52/207) was significantly higher than that of over 1 year old (13.4%, 27/201, χ²=8.922, P<0.05). The incidence of AAD in children treated with antibiotics for more than 5 days was 22.2%(60/270), which was significantly higher than that of less than or equal to 5 days (13.8%, 19/138, χ²=4.180, P<0.05). Although no significant difference was observed, the AAD rate of patients with combined use of two antibiotics was higher than that of using one. During the antibiotic therapy, compared with the control group, the risk of AAD in children under 1 year old was reduced by 52% (χ²=9.217, P<0.05), and 91% (χ²=20.35, P<0.05) in the children over 1 year old in prevention group. The risk of AAD of prevention group decreased by 66% (χ²=13.67, P<0.05) in patients treated with one antibiotics, and 65% in children with combined use of antibiotics (χ²=10.57, P<0.05). In patients treated with antibiotics for less than or equal to 5 days, the risk of AAD decreased by 74% in prevention group (χ²=7.38, P<0.05); and 63% if the course lasted for over 5 days (χ²=16.87, P<0.05). Within 14 days after the withdrawal of antibiotics, compared with the control group, the risk of diarrhea in the prevention group decreased by 82% (χ²=13.35, P<0.05) in infants (≤1 year old) and 93% (χ²=12.00, P<0.05) in children (>1 year old); the risk of diarrhea was reduced by 86% (χ²=9.57, P<0.05) and 87% (χ²=17.71, P<0.05) respectively in prevention group with single and combined use of antibiotics. In patients treated with antibiotics for more than 5 days, the risk of diarrhea in prevention group was reduced by 63% (χ²=22.79, P<0.05), while there was no significant difference if the antibiotics course was less than or equal to 5 days (χ²=2.97, P>0.05). No adverse effects related with Saccharomyces boulardii were observed in our study. Conclusion Saccharomyces boulardii is effective and safe to prevent AAD of infants and young children both during the usage of antibiotics and up to 14 days after drug discontinuance. It can be one of the drugs of for choice prevention of AAD in infants and young children. Trial registration Chinese Clinical Trial Tegister, ChiECRCT-2012-25.

Objective To explore the value of post processing technique of dual source CT in diagnosing peripheral PE.Methods One hundred and fifty patients with suspected PE were underwent dual source CT scan,and 20 of the all patients met the criterion. The raw CT data were reconstructed by the pulmonary embolism detection (PED)software,double energy perfusion imaging (DEPI)and CT pulmonary artery angiography (CTPA).The PED,DEPI and CTPA map were analyzed by 2 senior doctors in cardiovascular diagnosis profession.According to the diagnosis standard of PE,the location,number of the emboli in segmental and sub-segmental pulmonary arteries were respectively recorded on the PED and DEPI map.We calculated the detection rate,evaluated the significant difference and evaluated the diagnosis consistency between the DEPI and CTPA map.Results Emboli were found in 30 segmental and 40 sub-segmental arteries on the CTPA map with the detection rate of 7.50% and 5.00%,respectively.Emboli were found in 48 segmental and 62 sub-segmental arteries on PED map with the detection rate of 12.00% and 7.75%,respectively.There was significant difference between the CTPA and PED map (χ2 =4.60,5.06,P<0.05).The DEPI and PED map had higher consistency in diagnosing PE.The Kappa coefficient was 0.94 if the PED map was regarded as the reference standard,Among 48 cases with segmental PE detected by the PED map,there were 13 cases of complete filling defects and 35 cases of partial filling defects.Among 13 cases of complete filling defects,there were perfusion defect in 10, and perfusion thin in 3 on the DEPI map.Among 35 cases of partial filling defects,there were perfusion defect in 2,perfusion thin in 29,and perfusion normal in 4 on the DEPI map.Conclusion The PED map combined the DEPI map of dual source CT can significantly improve the diagnosis rate of peripheral PE and has a high clinical value.

Objective To investigate the clinical effect of magnesium sulfate combined with nifedipine in the treatment of patients with pregnancy induced hypertension( HDCP) .Methods Retrospective study was used in this study and 116 patients with HDCP from January 2013 to July 2015 in department of obstetrics and gynecology from our hospital were divided into two groups, including routine group of 62 patients who received routine treatment +magnesium sulfate) and combination group of 54 patients who received routine treatment +magnesium sulphate +nifedipine.The clinical effect was analyzed after five days’ continuous treatment.Results The systolic blood pressure, diastolic blood pressure,24h urinary protein, random urine protein /creatinine,serum homocysteine (Hcy) and CRP values in combination group were lower than routine group (P<0.05).There were no statistical difference in maternal uterine inertia, neonatal asphyxia, fetal distress, postpartum hemorrhage rate between the two groups after the treatment.But the rate of cesarean section in the combination group(50.00%)was significantly lower than that in the routine group(68.25%)(P <0.05).Conclusion Magnesium sulfate combined with nifedipine in the treatment of patients with HDCP had better antihypertensive effect, and would not increase fetal adverse birth outcomes incidence and significantly reduce the rate of cesarean section.

Objective To explore the status of histone acetylation modification and their regulatory effect to hMSH2 gene and hMLH1 gene expression in acute leukemia. Methods Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of hMSH2 and hMLH1 mRNA, and Western blot was used to measure the expression of histone H3, H4, HDACi, hMSH2 and hMLH1 protein in mononuclear cells of 56 acute leukemia patients and 30 healthy volunteers. The mononuclear cells of 30 acute leukemia patients were treated with histone deacetylase inhibitors trichostatin A (TSA), and measured the expression difference of histone H3, H4, HDAC1, hMSH2 and hMLH1 in the mononuclear cells treated with TSA. Results The protein expression levels of hMSH2, hMLH1, histone H3 and histone H4 in those mononuclear cells of acute leukemia patients were 0.4610±0.1211, 0.4013±0.1143, 0.4103±0.1241 and 0.4251±0.1081, respectively, which were significantly decreased comparing with those of healthy volunteers (0.9461±0. 1841, 0.996±0.2021, 0.8971±0. 1194 and 0.9513±0.1953) (t = 3.341, 3.935, 2.843 and 3.575,respectinely, P ＜0.05). The protein expression levels of HDAC1 (0.8841±0.2018) of acute leukemia patients was significantly increased comparing with those of healthy volunteers (0.5142±0.1340) (t= 2.634, P ＜0.05).After treatment with TSA for 48 hours, the protein expression of hMSH2 was increased nearly 1.5-fold, hMLH1 about 1.6-fold, H3 about 2.9-fold and H4 about 3.4-fold comparing with the negative control groups (P ＜0.05),while the protein expression of HDAC1 were decreased comparing with the negative control groups by 40 %.Conclusion There was an low expression phenomenon of histone acetylation in acute leukemia, and histone acetylation played an important role in regulation of the mismatch repair gene expression in acute leukemia.

Objective: To investigate the effects of Fufang Jiangzhi No. 3, a compound traditional Chinese herbal medicine, on cholesterol-bile acid metabolism in rabbits with hypercholesterolemia and to explore the mechanism. Methods: Twenty-four male New Zealand white rabbits were randomly assigned into normal control group, untreated group and Fufang Jiangzhi No. 3 group, with 8 rabbits in each group. Rabbits in the untreated group and Fufang Jiangzhi No. 3 group were fed high cholesterol diet to induce hypercholesterolemia. After 4-week treatment, serum total cholesterol and bile acid contents were assessed. Activity of cholesterol 7alpha-hydroxylase (CYP7A1) in liver tissues was measured by enzyme-linked immunosorbent assay. The expressions of CYP7A1, bile salt export pump (BSEP) and small heterodimer partner (SHP) mRNAs in liver tissues were observed by real-time fluorescent quantitative polymerase chain reaction. Results: Compared with the normal control group, serum total cholesterol and bile acid contents in the untreated group were increased (P<0.01). Activity of CYP7A1 and expression of CYP7A1 mRNA were decreased and expressions of BSEP and SHP mRNAs were increased in liver tissues in the untreated group as compared with the normal control group (P<0.01). Serum total cholesterol level, and expressions of BSEP and SHP mRNAs in the Fufang Jiangzhi No. 3 group were lower than those in the untreated group (P<0.01). The CYP7A1 activity and expression of CYP7A1 mRNA in the Fufang Jiangzhi No. 3 group were increased as compared with the untreated group (P<0.01), however, there was no significant difference in bile acid between the Fufang Jiangzhi No. 3 group and the untreated group. Conclusion: Fufang Jiangzhi No. 3 can up-regulate the expression of CYP7A1 mRNA, raise the activity of CYP7A1, and inhibit the expressions of BSEP and SHP mRNAs to regulate the metabolism of total cholesterol in rabbits.