BACKGROUNDPost-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is regarded as one of the worrisome complications of endoscopic retrograde cholangiopancreatography (ERCP). Results of randomized controlled trials evaluating the preventive effect of ulinastatin and gabexate mesylate (GM) on PEP are contradictory. The present study was designed to evaluate the prophylactic effect of ulinastatin and GM on PEP with meta-analyses of randomized controlled trials (RCTs).

METHODSFive electronic databases were searched for RCTs evaluating the preventive effect of ulinastatin and GM on PEP. Summary effects were assessed with the methods recommended by the Cochrane Collaboration.

RESULTSTwelve studies involving 5105 participants were included in our meta-analyses. Administration of ulinastatin decreased the incidence of PEP only at sufficient doses (OR, 0.39; 95%CI, 0.19 to 0.81; P = 0.01). Number needed to treat (NNT) was 6. And administration of ulinastatin also reduced the incidence of post-ERCP hyperamylasemia (PEHA) (OR, 0.40; 95%CI, 0.28 to 0.58; P < 0.000 01). Slow infusion of high-dose GM was effective for PEP prevention (OR, 0.44; 95%CI, 0.25 to 0.79; P = 0.006), and rapid infusion of low-dose GM also showed efficacy for PEP prophylaxis (OR, 0.37; 95%CI, 0.20 to 0.69; P = 0.002). NNT was 7 and 6 respectively. However, administration of GM at low doses and by slow infusions was ineffective (OR, 0.99; 95%CI, 0.64 to 1.55; P = 0.98). Administration of GM had the tendency to reduce PEHA rate, but not to a statistical significance (OR, 0.86; 95%CI, 0.73 to 1.01; P = 0.06). When low-quality studies were excluded, the meta-analysis with two high-quality studies indicated that ulinastatin did not reduce the rate of PEP (OR, 0.63; 95%CI, 0.32 to 1.26; P = 0.19) and PEHA incidence (OR, 0.80; 95%CI, 0.31 to 2.07; P = 0.64). The meta-analysis with six high-quality studies showed that GM administration decreased PEP incidence (OR, 0.52; 95%CI, 0.29 to 0.91; P = 0.02), while was not efficacious for PEHA prevention (OR, 0.88; 95%CI, 0.74 to 1.04; P = 0.12).

CONCLUSIONSUlinastatin and GM may be of value for the prophylaxis of PEP. GM should be administered at high doses and by rapid infusions. And the doses of ulinastatin should be sufficient. However, the conclusions are not overwhelming. More large-sample size and high-quality RCTs are still needed to elucidate whether administrations of the two drugs really have prophylactic effect on PEP.

Cholangiopancreatography, Endoscopic Retrograde ; adverse effects ; Gabexate ; therapeutic use ; Glycoproteins ; therapeutic use ; Humans ; Pancreatitis ; prevention & control

Drugs, Chinese Herbal ; therapeutic use ; Glycoproteins ; therapeutic use ; Humans ; Paraquat ; poisoning ; Poisoning ; drug therapy

OBJECTIVETo observe the effect of sodium bicarbonate combined with ulinastatin on cholinesterase activity for patients with acute phoxim pesticide poisoning.

METHODSA total of 67 eligible patients with acute phoxim pesticide poisoning, Who were admitted to the emeryency department of hospital from March 2011 to February 2014, Acording to different treatments au patients were randomly divided into the conventional treatment group (n=34) and the sodium bicarbonate+ulinastatin group (n=35) . The conventional treatment group were given thorough gastric lavage with water, the sodium bicarbonate + ulinastatin group were given gastric lavage with 2% sodium bicarbonate solution. Both groups were given such treatments as catharsis, administration of oxygen, fluid infusion, diuresis, and antidotes such as atropine and pralidoxime methylchloride. On the basis of comprehensive treatment, people in the sodium bicarbonate+ulinastatin group were given 5% sodium bicarbonate injection and ulinastatin. The clinical effect of the two groups were compared.

RESULTSThe serum cholinesterase activity of the sodium bicarbonate+ulinastatin group was significantly higher than the conventional treatment group from the 5th day, and the difference was statistically significant (P<0.05) . The total atropine dosage, total pralidoxime methylchloride dosage and hospitalization days were better than the conventional treatment group, and the differences were statistically significant (P<0.05) . The difference in the time of atropinization between the two groups was not statistically significant (P>0.05) . The results of arterial blood pH, HCO3- of the sodium bicarbonate + ulinastatin group were higher than the conventional treatment group, and the difference of HCO3- at the 10th day was statistically significant (P<0.05) .

CONCLUSIONSSodium bicarbonate combined with ulinastatin can improve the therapeutic effect and reduce complications in the treatment of acute phoxim pesticide poisoning, and have beneficial effects on the recovery of cholinesterase activity.

Atropine ; therapeutic use ; Cholinesterases ; metabolism ; Glycoproteins ; therapeutic use ; Humans ; Organophosphate Poisoning ; drug therapy ; Organothiophosphorus Compounds ; poisoning ; Pesticides ; poisoning ; Pralidoxime Compounds ; therapeutic use ; Sodium Bicarbonate ; therapeutic use

COVID-19 is known for its magical infectivity, fast transmission and high death toll based on the large number of infected people. From the perspective of the clinical manifestation, autopsy examination and pathophysiology, the essence of COVID-19 should be viewed as a sepsis induced by viral infection, and has the essential characteristics as sepsis induced by other pathogens. Therefore, in addition to etiological and supportive treatment, immunomodulatory therapy is also appropriate to severe COVID-19. Although there is still a lack of consensus on immunotherapy for sepsis so far, relatively rich experiences have been accumulated in the past decades, which will help us in the treatment of severe COVID-19. This article will elaborate immunotherapy of sepsis, though it may not be consistent.
Adrenal Cortex Hormones ; therapeutic use ; Betacoronavirus ; Coronavirus Infections ; complications ; Glycoproteins ; therapeutic use ; Humans ; Immunologic Factors ; therapeutic use ; Pandemics ; Pneumonia, Viral ; complications ; Sepsis ; drug therapy ; etiology ; Thymalfasin ; therapeutic use

Acute Lung Injury ; chemically induced ; drug therapy ; Animals ; Endotoxins ; Glycoproteins ; therapeutic use ; Male ; Propofol ; therapeutic use ; Rats ; Rats, Sprague-Dawley

Adult ; Female ; Gas Poisoning ; drug therapy ; Glycoproteins ; therapeutic use ; Humans ; Male ; Middle Aged ; Quinuclidines ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the therapeutic effect of ulinastatin combined with thymosin α1 in the treatment of severe sepsis in rats.

METHODSNormal Wistar rats were subject to cecal ligation and puncture (CLP) to establish models of severe sepsis. The rats were then randomized into 4 groups for treatment with saline (control), ulinastatin, thymosin α1, or the combination of the latter two injected through the caudal vein or subcutaneously at 6, 24, 48 and 72 h after modeling. The mortality rate was recorded daily and the rats were executed at 24, 48, 72 and 96 h after CLP to harvest the heart, liver, spleen, lung, kidney and small intestines for pathological examination. The spleen of the rats were taken for detection of apoptosis of the spleen cells.

RESULTSThe mortality rate of the septic rats in the combined treatment group was decreased significantly (P=0.0325). The control group showed the most severe organ damage, which was moderate in single drug treatment group and the mildest in combined treatment group. Obvious spleen cell apoptosis was found in the control group, and was significantly ameliorated in the combined treatment group[(47.4∓10.9)% vs (39.3∓11.4)%, P=0.0000].

CONCLUSIONCombined treatment with ulinastatin and thymosin α1 can significantly improve the prognosis and ameliorate organ damage and spleen cell apoptosis in rats with sever sepsis.

Animals ; Apoptosis ; Drug Therapy, Combination ; Glycoproteins ; therapeutic use ; Male ; Rats ; Rats, Wistar ; Sepsis ; drug therapy ; pathology ; Spleen ; cytology ; pathology ; Thymosin ; analogs & derivatives ; therapeutic use

BACKGROUNDOur previous study had demonstrated that ulinastatin (UTI) had a neuroprotective effect in experimental autoimmune encephalomyelitis (EAE). Methylprednisolone has been recommended to be a standard drug in multiple sclerosis (MS) therapies. The present study was to investigate the protective effects of UTI combined methylprednisolone in EAE.

METHODSMice were divided into a UTI treatment group, a methylprednisolone treatment group, a combined treatment group with UTI and methylprednisolone, a normal saline treatment group, and a normal control group. EAE mice were induced in groups receiving different combined treatments, or respective monotherapies. Demyelination was evaluated by Solochrome cyanin staining. 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)/ myelin basic protein (MBP)/ the precursor form of nerve growth factor (proNGF)/p75/ inducible nitric oxide synthase (iNOS) proteins in cerebral cortex of EAE were detected by Western blotting.

RESULTSThe combined treatment group had a lower clinical score (0.61 ± 0.06) and demyelinating score (1.33 ± 0.33) than the groups with normal saline (clinical score: 1.39 ± 0.08, P < 0.001; demyelinating score: 2.75 ± 0.49, P < 0.05) or monotheraphies. Compared with the saline treated EAE group, UTI combined methylprednisolone significantly increased expressions of CNP (1.14 ± 0.06 vs. 0.65 ± 0.04, P < 0.001), MBP (1.28 ± 0.14 vs. 0.44 ± 0.17, P < 0.001), and decreased expressions of proNGF (1.08 ± 0.10 vs. 2.32 ± 0.12, P < 0.001), p75 (1.13 ± 0.13 vs. 2.33 ± 0.17, P < 0.001), and iNOS (1.05 ± 0.31 vs. 2.17 ± 0.13, P < 0.001) proteins in EAE. Furthermore, UTI combined methylprednisolone could significantly upregulate MBP (1.28 ± 0.14 vs. 1.01 ± 0.15, P < 0.05) expression and downregulate iNOS (1.05 ± 0.31 vs. 1.35 ± 0.14, P < 0.05) expression compared to methylprednisolone treatment EAE group. And proNGF expression was significantly lower in combined treatment (1.08 ± 0.10) than that in UTI (1.51 ± 0.24, P < 0.05) or methylprednisolone (1.31 ± 0.04, P < 0.05) treatment group.

CONCLUSIONCombination treatment of UTI with methylprednisolone was shown to protect EAE, suggesting that combination therapy is a potential novel treatment in MS.

Animals ; Drug Combinations ; Encephalomyelitis, Autoimmune, Experimental ; drug therapy ; Female ; Glycoproteins ; administration & dosage ; therapeutic use ; Methylprednisolone ; administration & dosage ; therapeutic use ; Mice ; Mice, Inbred C57BL ; Multiple Sclerosis ; drug therapy

Heat shock protein gp96 is a highly conserved and monomorphic glycoprotein in the endoplasmic reticulum. It functions as molecular chaperone and can associate with a variety of antigenic peptides noncovalently in vivo and in vitro. Recent studies have indicated that gp96 molecules participate in major histocompatibility complex class I-restricted antigen presentation pathway. Immunization of mice with gp96 preparations isolated from cancer cells can elicit a cancer-specific protective T cell immune response that is recallable, which is a prerequisite for gp96 as a therapeutic vaccine against cancers. The immunogenicity of gp96 molecules has been attributed to the antigenic peptides associated with them. These phenomena provide a new pathway for cancer immunotherapy. The mechanism that the gp96-peptide complex induces specific immune response and the explorations for gp96-peptide complex as a therapeutic cancer vaccine are reviewed.
Animals ; Antigens, Neoplasm ; immunology ; therapeutic use ; Cancer Vaccines ; therapeutic use ; Humans ; Immunotherapy ; Membrane Glycoproteins ; immunology ; metabolism ; Molecular Chaperones ; immunology ; Neoplasms ; immunology ; therapy ; Peptides ; immunology ; metabolism

OBJECTIVETo use a lectin microarray to study the alteration of glycan affinity profiles of serum glycoproteins during the hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) seroconversion in patients with chronic hepatitis B (CHB) following treatment with antiviral therapy,and to explore its biological significance.

METHODSCHB patients were divided into the following four groups:untreated HBeAg-positive,HBeAg seroconversion after anti-HBV therapy,HBsAg loss after anti-HBV therapy,and healthy individuals (controls).Serum samples were collected from each participant,depleted of high abundance proteins and analyzed by a lectin microarray containing 50 lectins.The lectin-affinity glycan profiles of serum proteins were partially verified by lectin blotting.Between-group differences were analyzed by one-way analysis of variance,and pairwise comparisons were carried out with the Student-Newman-Keuls (SNK) method.

RESULTSThe results from the lectin microarray and lectin blotting assay showed significantly reduced affinity for 16 lectins in the untreated HBeAg-positive group compared to the control group (P less than 0.05);in addition,the specific glycan profiles of the untreated HBeAg-positive group included decreased terminal and core fructose,GalNAc alpha-Thr/Ser (T,Tn-antigen),GalNac alpha,terminal beta1-4,and beta-D galactose,bisecting and/or GlcNAc,mannose and Sia.However,the HBeAg seroconversion after anti-HBV therapy group showed enhanced binding of PSA,MPL and the above-mentioned 16 lectins (P less than 0.05),suggesting that the reduced serum glycoprotein glycan structures returned to normal or slightly higher than healthy levels after the therapy-induced seroconversion.Comparison of the group with HBsAg loss after anti-HBV therapy to the group with HBeAg seroconversion after anti-HBV therapy showed the binding ability of ten lectins (AAL,ACL,HAL,HPL,RCA-I,LEL,STL,PHA-E,NML and PCL) were weakened to near control levels and six lectins (VAL,LCA,GNL,PSA,MPL and JAC) were significantly strengthened (all P less than 0.05). These findings implied that the glycan containing terminal fructose, GalNacalpha, terminal beta1-4 galactose,and bisecting GlcNAc glycan structures dropped to near control levels, while the terminal beta-D-galactose residues and core fructose structure increased significantly.

CONCLUSIONThe glycan structures of serum glycoproteins are closely related to HBeAg and HBsAg seroconversion in CHB patients.It is possible that a special lectin binding glycan involving the terminal beta-D-galactose residues and core fructose may act as sugar markers associated with the disappearance of serum HBsAg during anti-HBV therapy for CHB.

Antiviral Agents ; therapeutic use ; Galactose ; Glycoproteins ; blood ; Hepatitis B e Antigens ; Hepatitis B, Chronic ; drug therapy ; Humans ; Phytohemagglutinins ; Polysaccharides ; analysis