Effect of early fluid balance on the prognosis in severe acute pancreatitis / 中华危重病急救医学

OBJECTIVE@#To observe the correlation between early fluid resuscitation and prognosis in patients with severe acute pancreatitis (SAP).@*METHODS@#SAP patients admitted to the department of critical care medicine of the People's Hospital of Chuxiong Yi Autonomous Prefecture of Yunnan Province from June 2018 to December 2020 were enrolled and analyzed retrospectively. All patients were given the routine treatment according to their condition and relevant diagnostic According to their different prognosis, enrolled patients were divided into death group and survival group. The differences in gender, age, acute physiology and chronic health evaluation II (APACHE II) and Ranson score on admission between the two groups were analyzed. Taking 24 hours as an observation day, the fluid inflow, outflow, and net balance at the first, second, and third 24 hours after admission were recorded, and the ratio of the fluid inflow at the first 24 hours to the total fluid inflow in 72 hours (FV24 h-1 st) was calculated as a study index. Using 33% as the standard, compare the proportion of patients in the two groups who achieved FV24 h-1 st < 33%. The differences of various indicators between the two groups were compared, and the effect of early fluid balance on the prognosis of SAP patients was analyzed.@*RESULTS@#Eighty-nine patients were included in the study (41 in the death group, 48 in the survival group). There were no statistically significant differences on age (years old: 57.6±15.2 vs. 49.5±15.2), gender (male: 61.0% vs. 54.2%), APACHE II score (18.0±2.4 vs. 17.3±2.3), and Ranson score (6.3±1.4 vs. 5.9±1.2) between the death group and the survival group at the time of admission on the intensive care unit (ICU) (all P > 0.05). The fluid intake of the death group in the first 24 hours, the second 24 hours and the third 24 hours after admission to ICU was significantly higher than that of the survival group, and the difference was statistically significant (mL: 4 138±832 vs. 3 535±1 058, 3 883±729 vs. 3 324±516, 3 786±490 vs. 3 212±609, all P < 0.05), and the fluid inflow in the death group at the first 24 hours was greater than 4 100 mL. After treatment, the fluid outflow of the death group at the three 24-hour periods after admission on the ICU was an increasing trend, but it was still significantly less than that of the survival group at the three 24-hour periods (mL: 1 242±465 vs. 1 795±819, 1 536±579 vs. 2 080±524, 1 610±585 vs. 2 932±752, all P < 0.01). Due to the fact that the total fluid inflow and total fluid outflow in the three 24-hour periods in the death group were more than those in the survival group, the net fluid balances in the three 24-hour periods in the death group were still significantly more than those in the survival group finally (mL: 2 896±782 vs. 1 740±725, 2 347±459 vs. 1 243±795, 2 176±807 vs. 338±289, all P < 0.01). There was no difference in FV24 h-1 st between the death group and survival group [FV24 h-1 st > 33%: 56.1% (23/41) vs. 54.2% (26/48), P > 0.05].@*CONCLUSIONS@#Fluid resuscitation is an important method for early treatment of SAP, but it also has many adverse reactions. Fluid resuscitation indexes such as fluid inflow, outflow, net balance, and FV24 h-1 st within 24 to 72 hours after admission are related to the prognosis of patients with SAP, and can be used as indicators to evaluate the prognosis of SAP. The optimized fluid resuscitation strategy can improve the prognosis of patients with SAP.

Progress of intelligent-responsive insulin delivery mediated by glucose oxidase / 中国药科大学学报

@#The delivery of exogenous insulin is very important for the treatment of type 1 and advanced type 2 diabetes.Traditional injectable administration is prone to cause hypoglycemia, while the intelligent insulin system has the advantages of safety, long-term effectiveness, and high responsiveness.Glucose oxidase (GOx) can consume O2 and catalyze glucose to produce gluconic acid and H2O2.Therefore, the O2 level, H2O2 content and pH of GOx system are closely related to the glucose level in the system.This review introduces the application of GOx in closed-loop insulin delivery systems at home and abroad in recent years, which can be divided into single response and multiple response of pH-response, hypoxia-response, and H2O2-response according to the mechanism.It also discusses the opportunities and challenge facing by the application of GOx in the future.

Prophylactic and therapeutic efficacy of a chimeric monoclonal antibody specific for H5 haemagglutinin against lethal H5N1 influenza.

BACKGROUND: Recent outbreaks of highly pathogenic H5N1 viruses in humans indicate that no endogenous protection exists in the general population. Vaccination programmes against this new pathogen require synthesis of endogenous antibodies and cannot provide any immediate protection in the event of a pandemic. Passive immunization with humanized neutralizing monoclonal antibodies can prove to be promising in preventing a catastrophic pandemic. METHODS: A murine monoclonal antibody (mAb) 3B1 of immunoglobulin M isotype was switched to a chimeric immunoglobulin G1. BALB/c mice were used to study the protective efficacy of the chimeric mAbs against a lethal H5N1 virus challenge with strains from clades 1 and 2.1. Kinetics of the viral load were determined during the course of the treatment. RESULTS: The chimeric mAb, in passive administration, was able to protect 100% of the mice when challenged with H5N1 strains from clades 1 or 2.1. Prophylaxis at 1 day prior to challenge and treatment at 1 day after challenge with this mAb resulted in the clearance of the virus from the lungs of the infected mice within 6 days post-viral challenge. CONCLUSIONS: Passive immunotherapy using chimeric mAb 3B1 can be an effective tool in both the prophylaxis and treatment of highly pathogenic H5N1 infection, providing the immediate immunity needed to contain a future influenza pandemic.

Combination therapy using chimeric monoclonal antibodies protects mice from lethal H5N1 infection and prevents formation of escape mutants.

BACKGROUND: Given that there is a possibility of a human H5N1 pandemic and the fact that the recent H5N1 viruses are resistant to the anti-viral drugs, newer strategies for effective therapy are warranted. Previous studies show that single mAbs in immune prophylaxis can be protective against H5N1 infection. But a single mAb may not be effective in neutralization of a broad range of different strains of H5N1 and control of potential neutralization escape mutants. METHODS/PRINCIPAL FINDINGS: We selected two mAbs which recognized different epitopes on the hemagglutinin molecule. These two mAbs could each neutralize in vitro escape mutants to the other and in combination could effectively neutralize viruses from clades 0, 1, 2.1, 2.2, 2.3, 4, 7 and 8 of influenza A H5N1 viruses. This combination of chimeric mAbs when administered passively, pre or post challenge with 10 MLD50 (50% mouse lethal dose) HPAI H5N1 influenza A viruses could protect 100% of the mice from two different clades of viruses (clades 1 and 2.1). We also tested the efficacy of a single dose of the combination of mAbs versus two doses. Two doses of the combination therapy not only affected early clearance of the virus from the lung but could completely prevent lung pathology of the H5N1 infected mice. No escape variants were detected after therapy. CONCLUSIONS/SIGNIFICANCE: Our studies provide proof of concept that the synergistic action of two or more mAbs in combination is required for preventing the generation of escape mutants and also to enhance the therapeutic efficacy of passive therapy against H5N1 infection. Combination therapy may allow for a lower dose of antibody to be administered for passive therapy of influenza infection and hence can be made available at reduced economic costs during an outbreak.