Endoscopic sphincterotomy plus large-balloon dilation vs endoscopic sphincterotomy for choledocholithiasis:A meta-analysis

AIM:To perform a meta-analysis of large-balloon dilation(LBD)plus endoscopic sphincterotomy(EST)vs EST alone for removal of bile duct stones.METHODS:Databases including PubMed,EMBASE,the Cochrane Library,the Science Citation Index,and important meeting abstracts were searched and evaluated by two reviewers independently.The main outcome measures included:complete stone removal,stone removal in the first session,use of mechanical lithotripsy,procedure time,and procedure-related complications.A fixed-effects model weighted by the Mantel-Haenszel method was used for pooling the odds ratio(OR)when heterogeneity was not significant among the studies.When a Q test or I2statistic indicated substantial heterogeneity,a random-effects model weighted by the DerSimonian-Laird method was used.RESULTS:Six randomized controlled trials involving835 patients were analyzed.There was no significant heterogeneity for most results;we analyzed these using a fixed-effects model.Meta-analysis showed EST plus LBD caused fewer overall complications than EST alone(OR=0.53,95%CI:0.33-0.85,P=0.008);sub-category analysis indicated a significantly lower risk of perforation in the EST plus LBD group(Peto OR=0.14,95%CI:0.20-0.98,P=0.05).Use of mechanical lithotripsy in the EST plus LBD group decreased significantly(OR=0.26,95%CI:0.08-0.82,P=0.02),especially in patients with a stone size larger than 15 mm(OR=0.15,95%CI:0.03-0.68,P=0.01).There were no significant differences between the two groups regarding complete stone removal,stone removal in the first session,post-endoscopic retrograde cholangiopancreatography pancreatitis,bleeding,infection of biliary tract,and procedure time.CONCLUSION:EST plus LBD is an effective approach for the removal of large bile duct stones,causing fewer complications than EST alone.

Toll-like receptor 5-mediated signaling enhances liver regeneration in mice

Background:Toll-like receptor 5(TLR5)-mediated pathways play critical roles in regulating the hepatic immune response and show hepatoprotective effects in mouse models of hepatic diseases.However,the role of TLR5 in experimental models of liver regeneration has not been reported.This study aimed to investigate the role of TLR5 in partial hepatectomy(PHx)-induced liver regeneration.Methods:We performed 2/3 PHx in wild-type(WT)mice,TLR5 knockout mice,or TLR5 agonist CBLB502 treated mice,as a model of liver regeneration.Bacterial flagellin content was measured with ELISA,and hepatic TLR5 expression was determined with quantitative PCR analyses and flow cytometry.To study the effects of TLR5 on hepatocyte proliferation,we analyzed bromodeoxyuridine(BrdU)incorporation and proliferating cell nuclear antigen(PCNA)expression with immunohistochemistry(IHC)staining.The effects of TLR5 during the priming phase of liver regeneration were examined with quantitative PCR analyses of immediate early gene mRNA levels,and with Western blotting analysis of hepatic NF-κB and STAT3 activation.Cytokine and growth factor production after PHx were detected with real-time PCR and cytometric bead array(CBA)assays.Oil Red O staining and hepatic lipid concentrations were analyzed to examine the effect of TLR5 on hepatic lipid accumulation after PHx.Results:The bacterial flagellin content in the serum and liver increased,and the hepatic TLR5 expression was significantly up-regulated in WT mice after PHx.TLR5-deficient mice exhibited diminished numbers of BrdU-and PCNA-positive cells,suppressed immediate early gene expression,and decreased cytokine and growth factor production.Moreover,PHx-induced hepatic NF-κB and STAT3 activation was inhibited in Tlr5–/–mice,as compared with WT mice.Consistently,the administration of CBLB502 significantly promoted PHx-mediated hepatocyte proliferation,which was correlated with enhanced production of proinflammatory cytokines and the recruitment of macrophages and neutrophils in the liver.Furthermore,Tlr5–/–mice displayed significantly lower hepatic lipid concentrations and smaller Oil Red O positive areas than those in control mice after PHx.Conclusions:We reveal that TLR5 activation contributes to the initial events of liver regeneration after PHx.Our findings demonstrate that TLR5 signaling positively regulates liver regeneration and suggest the potential of TLR5 agonist to promote liver regeneration.

Proteolysis targeting chimera technology:a novel strategy for treating diseases of the central nervous system

Neurological diseases such as stroke,Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease are among the intractable diseases for which appropriate drugs and treatments are lacking.Proteolysis targeting chimera(PROTAC)technology is a novel strategy to solve this problem.PROTAC technology uses the ubiquitin-protease system to eliminate mutated,denatured,and harmful proteins in cells.It can be reused,and utilizes the protein destruction mechanism of the cells,thus making up for the deficiencies of traditional protein degradation methods.It can effectively target and degrade proteins,including proteins that are difficult to identify and bind.Therefore,it has extremely important implications for drug development and the treatment of neurological diseases.At present,the targeted degradation of mutant BTK,mHTT,Tau,EGFR,and other proteins using PROTAC technology is gaining attention.It is expected that corresponding treatment of nervous system diseases can be achieved.This review first focuses on the recent developments in PROTAC technology in terms of protein degradation,drug production,and treatment of central nervous system diseases,and then discusses its limitations.This review will provide a brief overview of the recent application of PROTAC technology in the treatment of central nervous system diseases.

Porosity Calculation of Tight Sand Gas Reservoirs with GA-CM Hybrid Optimization Log Interpretation Method

Tight sand gas reservoirs are our country’s fairly rich unconventional natural gas resources, and their exploration and development is of prime importance. Sulige Gas Field which located in the northern Ordos Basin is tight sand gas reservoirs. It is typically featured by low porosity and low permeability, and the error of porosity calculation by traditional methods is larger. Multicomponent explanation model is built by analyzing the thin slice data, and the objective function is got according to the concept of optimization log interpretation method. This paper puts the Genetic Algorithm and the Complex Algorithm together to form the GA-CM Hybrid Algorithm for searching the optimal solution of the objective function, getting the porosity of tight sandstone gas reservoirs. The deviation got by this method is lesser compared with the core porosity, with a high reliability.

Physiological Responses of Limonium aureum Seeds to Ultra-drying

The seeds of Limonium aureum （L.） Hill. were dried from 8.92% to 2.88% moisture content in a desiccating container with silica gel. After ultra-drying the seeds were accelerated aged （50 ℃, 1 month）, and some physiological indices, including the electrical conductivity, dehydrogenase activity, superoxide dismutase （SOD）, peroxidase （POD）, glutathione reductase （GR）, ascorbate peroxidase （APX）, catalase （CAT）, volatile aldehydes and malondialdehyde （MDA） were tested. The results indicated that dehydrogenase, POD, SOD, GR, APX and CAT activities of the ultra-dry seeds were higher than the control seeds, while volatile aldehydes and malondialdehyde were lower than the control group. The results suggest that ultra-drying is beneficial for maintaining the vigor of L. aureum seeds at a high level. Thus, L. aureum seeds could be stored under ultra-dry conditions.

Initial exploration of the mechanism underlying H2O2-induced root horizontal bending in pea

It was reported that exogenous hydrogen peroxide(H2O2) can induce primary root bend in Arabidopsis and pea. However, the mechanism remains unclear. Here we explored the mechanism underlying this phenomenon by using the pea(Pisum sativum L.) variety ‘‘longwan No. 1''.The results showed that the endogenous indole-3-acetic acid(IAA) content decreased and gibberellin A3(GA3)content increased in the curving primary pea root induced by H2O2. Meanwhile, both of the two hormones asymmetrically distributed in the inside and outside parts of the curving root. Also, the starch content decreased due to the increased a-amylase activity in this process. However,exogenous Ca2?can relieve the horizontal bending of pea root induced by H2O2 and altered the contents of endogenous IAA and GA3. A working model was proposed:Exogenous H2O2 causes the increase in GA3 content, and GA3 stimulates the activity of a-amylase, which leads to the hydrolysis of starch, and then the root lost the gravityperceiving. The asymmetric distribution of IAA and GA3 in two sides of curving root may cause the horizontal bending.Exogenous Ca2?can relieve root bending through altering the endogenous IAA and GA3 contents.

Thermodynamics of Aromatic Cyclic Ester Polymerization in Bulk

We present here the thermodynamic investigation of in situ cascade polycondensation-coupling ring-opening polymerization(PROP)for three cyclic aromatic ester monomers,i.e.,cyclic oligo(2-methyl-1,3-propylene terephthalate)s(COMPTs),cyclic oligo(neopentylene terephthalate)s(CONTs)and cyclic oligo(2-methyl-2-propyl-1,3-propylene terephthalate)s(COMPPTs).The equibrium monomer to polymer weight ratio in bulk at different polymerization temperatures for each monomer was estimated by the size exclusion chromatography(SEC),and the thermodynamic parameters were estimated by Dainton equation.Quite different from the thermodynamics of aliphatic lactones polymerization,which is an exothermic process with entropy reduction,our results showed the polymerization thermodynamics for three cyclic aromatic ester monomers was a weak exothermic process with slight entropy increment,i.e.,a both enthalpy and entropy driving process.Among them,CONTs showed the largest value of enthalpy change,due to its symmetric dimethyl substitution onβ-position of propandiol segments.

Synthesis of Cyclic Oligo(ethylene adipate)s and Their Melt Polymerization to Poly(ethylene adipate)

We present here the first synthesis of cyclic oligo（ethylene adipate）s （COEAs） via pseudo-high dilution condensation reaction of adipoyl chloride with ethylene glycol, and the synthesis of corresponding poly（ethylene adipate） （PEA） via the melt polymerization of COEAs. The structure of COEAs was characterized and proved by 1H-NMR and MALDI-TOF mass measurements. The effects of organic base, reaction temperature and the ratio of adipoyl chloride to ethylene glycol on the yield of COEAs were studied, and the optimum reaction condition was revealed. PEA, a diacid and diol based semi-crystalline green aliphatic polyester, was synthesized by the melt polymerization of COEAs using Ti（n-C4H90）4 as catalyst and 1,10-decanediol as initiator at 200 ℃, which follows the polycondensation-coupling ring- opening polymerization method. Our strategy should be applicable to the synthesis of versatile aliphatic polyesters based on diacid and diol monomers, which have potential applications as biocompatible and biodegradable materials.

Special Odd-Even Effect of Degree of Oligomerization on Properties of Cyclic Oligoesters

We demonstrate here seven pure cyclic samples, which belongs to two series of oligoesters, cyclic oligo（trimethylene terephthalate）s （COTTs） and cyclic oligo（butylene terephthalate）s （COBTs）, showing odd-even effect of degree of oligomerization （repeating units number） on properties. The pentamer of COTT and trimer of COBT show much lower melting temperature, and the trimer of COTT and trimer of COBT show significant lower refractive index, which can be ascribed to the low packing density of cyclic oligoesters with odd number of degree of oligomerization. Our results reveal the discrete property change as a function of cyclic size of oligomers, which can be used to design materials with special properties.