Mpox, previously known as monkeypox, is a zoonotic disease caused by the mpox virus(MPXV), which has shown a trend of spreading globally in recent years and poses a threat to public health security. To address the potential mpox epidemic, the development of vaccine has become crucial. Nonclinical pharmacodynamics studies are an important part of vaccine development, which evaluate the immunogenicity and protective effect of vaccines in animal models, providing key evidence of efficacy to support clinical trials. This article will explore the key technical points of nonclinical pharmacodynamics studies for mpox vaccines, in combination with the nonclinical efficacy studies of similar products and the technical documents recently released, in order to provide some reference for the development of such products.

In recent years,in order to meet urgent clinical needs alleviate the shortage of rare disease drugs in China,a series of policies encouraging the research and development of rare disease drugs has been introduced.Enzyme replacement therapy(ERT)is a standard treatment for rare congenital metabolic disorders,especially for enzyme deficiency diseases.Due to the complexity and heterogeneity of drug molecules for rare enzyme replacement therapy,the evaluation of animal models is a major challenge in non-clinical development and evaluation.This article introduces the latest research progress in the development of rare enzyme replacement therapy drugs at home and abroad,put forward some thoughts and suggestions on the non-clinical evaluation(pharmacology,pharmacokinetics,and toxicology)of such products based on representative literature,combined with review practice.

Objective:To analyze the consistency and correlation of indirect calorimetry (IC) and Harris-Benedict estimation method (H-B) in measuring energy consumption in patients with severe acute pancreatitis (SAP), as well as the characteristics of energy metabolism at resting state of SAP patients with different etiologies, and so as to guide the formulation of clinical energy nutrition support program.Methods:From February 1 to December 31, 2019, 61 SAP patients admitted into the intensive care unit of the First Affiliated Hospital of Nanchang University were enrolled. Collected relevant data of patients, such as the etiology of SAP, whether mechanical ventilation was needed, as well as the metabolic status. All SAP patients accepted IC test on the first day after admission to intensive care unit. According to the energy consumption measured by IC (hereinafter referred to as IC value) and the energy consumption measured by H-B (hereinafter referred to as H-B value), SAP patients were determined to be in high, normal or low metabolic state. Bland-Altman method and Pearson linear regression were used to analyze the consistency and correlation of the two methods in measuring energy consumption, and the linear equation was fitted. Paired t test was used for statistical analysis. Results:Among the 61 SAP patients, 13 cases were biliary SAP, 30 cases were hyperlipidemic SAP, 6 cases were alcoholic SAP, and 12 cases were SAP of other causes or unknown causes. Nineteen cases needed mechanical ventilation and 42 cases did not need mechanical ventilation. There were 70.5% (43/61) of SAP patients in high metabolic state, 13.1%(8/61) of SAP patients in normal metabolic state, and 16.4% (10/61) of SAP patients in low metabolic state. The IC value in 61 SAP patients was higher than H-B value((8 604.7±367.8) kJ/d vs. (6 491.2±133.7) kJ/d), and the difference was statistically significant ( t=5.95, P<0.001). The IC value in patients with hyperlipidemic, alcoholic and biliary SAP was (8 815.2±537.9), (7 631.2±890.5), and (8 108.0±933.1) kJ/d, respectively, and the H-B value was (6 869.6±204.5), (5 916.8±153.7), and (5 974.2±200.9) kJ/d, respectively. The IC value in patients with biliary or hyperlipidemic SAP were higher than H-B value, and the differences were statistically significant( t=2.29 and 3.38, both P<0.05). The IC value and H-B value in SAP patients with mechanical ventilation and without mechanical ventilation were (10 485.0±741.1) and (6 462.6±222.8) kJ/d, (6 595.1±364.7) and (6 503.2±166.7) kJ/d, respectively. The IC value in SAP patients with mechanical ventilation was higher than H-B value and the IC value in SAP patients without mechanical ventilation, and the differences were statistically significant ( t=4.71 and 5.20, both P<0.001). The consistency analyzed by Bland-Altman method showed that the two methods had obvious biases, and the average bias value was 92.2 kJ/d. The result of Pearson linear regression analysis indicated that there was a linear relationship between two methods ( r=0.44, P<0.001). The linear equation fitted by the univariate regression was Y=1.240 6 X+ 154.42, in which X was the H-B value and Y was the IC value. Conclusions:SAP patients are mostly in a hypermetabolic state in the early stages of the disease. The IC value is higher than H-B value, and it is recommended to use IC to measure energy consumption in SAP patients.

Objective To develop transgenic mice harboring the fusion gene of mutant amyloid precursor protein and two types of fluorescent protein for the future study on Alzheimer's disease.Methods The fusion gene CFP-54 bp-YFP-C99 was introduced into mice by mieroinjection.The presence of CFP-54 bp-YFP-C99 was confirmed by PCR in the founders.Results CFP-54 bp-YFP-C99 gene was injected into pronucleus of 2202 zygotes and 1806 injected eggs were implanted into 56 foster mothers, 13 of which were pregnant.There were 13 foster mothers who borne 52 offspring and 32 of them survived.Recipient mouse pregnancy rate was 23.2% (13/56) and the integration rate was 3.9% (2/52).Conclusion CFP-54 bp-YFP-C99 transgenic mice is obtained, but the transgenic efficiency is low.