Mining and analysis of adverse drug event signals related to mepolizumab / 中国药房

OBJECTIVE To provide reference for rational clinical use of mepolizumab. METHODS The reporting odds ratio method and Bayesian confidence propagation neural network method were used to conduct signal mining and analysis of adverse drug event （ADE） reports related to mepolizumab in the United States Food and Drug Administration Adverse Event Reporting System from the first quarter of 2016 to the third quarter of 2022. RESULTS A total of 57 501 ADE reports were extracted with mepolizumab as the primary suspect drug， involving 16 358 patients. Among these reports， the proportion of males （23.51%） was lower than females （50.48%）. The reporting countries were primarily the United States （51.91%） and Canada （29.94%）. Consumers （71.18%） constituted the main reporting population. A total of 172 ADE-positive signals were identified， mainly involving 13 system organ classes such as the respiratory， thoracic and mediastinal disorders （41.63%）， as well as infectious and parasitic diseases （14.16%）. There were 60 high-risk signals， including 15 that were explicitly mentioned or related to adverse reactions in the drug instructions of mepolizumab and 45 signals （such as asthmatic crisis， sputum discoloured， purulent sputum， sleep disorder due to a general medical condition） were newly identified high-risk signals. Among them， 11 high-risk signals exhibited gender or age differences. CONCLUSIONS When clinically using mepolizumab， in addition to the adverse reactions mentioned in the drug instruction， special attention should also be given to changes in the nature of sputum， painful respiration， and sleep disorders.

Development of a Blocking ELISA Kit for Detection of ASFV Antibody Based on a Monoclonal Antibody Against Full-Length p72.

BACKGROUND: African swine fever virus (ASFV) is the etiologic agent of African swine fever (ASF), a disease of highly contagious and significant threat to pork production. At present, the sensitive detection methods are the keys to the disease control. OBJECTIVE: Full-length p72 is produced by a eukaryotic system, and its monoclonal antibody (mAb) 34C10 is subsequently recovered. A blocking ELISA kit for detection of ASFV antibody is developed based on p72 trimers and 34C10. METHODS: Full-length p72 is expressed and is used as an immunogen to prepare a panel of monoclonal antibodies. The mAb 34C10 is verified by immunofluorescence and tested by ELISAs with positive serums. The constant affinity of 34C10 is then confirmed. A blocking ELISA kit is further developed and is compared with two commercial kits. RESULTS: The mAb 34C10 is specifically bound to p72 protein, and it exhibits a blocking effect to positive serum. The immunofluorescence assay experiment shows that 34C10 could bind to p72 expressed by baculoviruses, and the binding affinity of 34C10 is found to be as high as 1.85 × 1011 L/mol. The blocking ELISA kit shows high coincidence with a commercial ELISA kit. The sensitivity between these two kits is 97.6% (95%, CI: 90.65-99.58), and the specificity between them is 100% (95%, CI: 98.34-100). CONCLUSIONS: The blocking ELISA developed in this study may have great potential for diagnosis of ASF. The structure of the antigen p72 is found to be a key factor for the performance of the kit. HIGHLIGHTS: For the first time, the eukaryotic expressed full-length p72 protein is used to recover the monoclonal antibody, and it is coated as antigen during the development of the blocking ELISA kit. This study sheds new light on the development of the blocking ELISA kits, especially for the development of a diagnostic kit for the contagious virus with bio-safety problems.

Research progress on malignant tumor after lung transplantation / 器官移植

Lung transplantation has become the most effective treatment of end-stage lung diseases. Along with persistent optimization of lung transplantation technique and perioperative management, the short-term clinical efficacy after lung transplantation has been significantly improved, whereas the long-term clinical prognosis remains unoptimistic. Besides chronic lung allograft dysfunction, postoperative malignant tumors also threaten the long-term survival of the recipients. Common malignant tumors following lung transplantation include nonmelanoma skin cancer, posttransplant lymphoproliferative disease and lung cancer. After solid organ transplantation, a large majority of the recipients require lifelong immunosuppressive therapy. The intensity of immunosuppressive therapy for the lung transplant recipients is generally higher than other organ transplant recipients. Immunosuppression is the main factor which leads to the impairment of anti-tumor immune monitoring function and promotes the incidence and development of malignant tumors. In this article, the risk factors, prevention and treatment of the most common malignant tumors after lung transplantation were reviewed, aiming to provide reference for comprehensive diagnosis and treatment of malignant tumors following lung transplantation.

Progress in clinical application of urgent lung transplantation / 器官移植

Lung transplantation is the only effective treatment of end-stage lung diseases. Nevertheless, shortage of donor lungs has become increasingly prominent worldwide. A large quantity of patients died while waiting for lung transplantation. Urgent lung transplantation is a prioritized allocation strategy for donor lung transplantation according to the urgency of diseases, aiming to shorten the waiting time for donor lungs and reduce the fatality of patients on the waiting list for lung transplantation. However, no consensus has been reached worldwide on the definition, criteria and application of the terminology of urgent lung transplantation. In addition, the survival and net benefits of lung transplant recipients based on this allocation system are still controversial. On the basis of previous clinical research on urgent lung transplantation, the definition criteria, risk factors, survival outcomes, limitations and optimization measures were explicitly elucidated in this article, aiming to provide theoretical reference for comprehensive evaluation of the feasibility of urgent lung transplantation and further optimizing the allocation system of donor lungs.

ScRNA-seq discover cell cluster change under OAB: ACE2 expression reveal possible alternation of 2019-nCoV infectious pathway

ObjectivePrevious study indicated that bladder cells which express ACE2 were a potential infection route of 2019-nCov. This study observed some differences of bladder cell cluster and their ACE2 expression between OAB mice and healthy mice, indicating the change of infectious possibility and pathway under overactive bladder (OAB) circumstance. Material and methodPubic dataset acquisition was used to get ACE2 expression in normal human bladder and mice bladder (GSE129845). We built up over OAB model and studied the impact on cell typing and ACE2 expression. By way of using single-cell RNA sequencing (scRNA-seq) technique, bladder cell clustering and ACE2 expression in various cell types were measured respectively. ResultIn pubic database (healthy human and mice bladder), ACE2 expression in humans and mice is concentrated in bladder epithelial cells. The disappearance of umbrella cells, a component of bladder epithelial, was found in our OAB model. In the two mouse bladder samples, ACE2 expression of epithelial cells is 34.1%, also the highest of all cell types. ConclusionThe disappearance of umbrella cell may alternate the infection pathway of 2019-nCov and relate to the onset and progression of OAB.

Role of body mass index on acute kidney injury patients after cardiac surgery / 中华肾脏病杂志

Objective To explore the association between BMI and the risk of developing cardiac surgery associated acute kidney injury (CS-AKI),mortality of AKI and AKI requiring renal replacement therapy (AKI-RRT) after cardiac surgery.Methods Clinical data of patients undergoing cardiac surgery from January 2011 to December 2015 in Zhongshan Hospital of Fudan University were prospectively collected.Patients were divided into four groups according to BMI classification of Chinese population.Adjustment for selection bias was further assessed using propensity score method (PSM) to evaluate the role of BMI in the development of AKI.Results A total of 8442 patients were enrolled,among which 1092 patients successfully matched through PSM.The AKI incidences were respectively 30.3％,33.3％,38.6％ and 46.8％ in four BMI groups (P ＜ 0.01) before PSM.The AKI incidences were respectively 31.9％,35.2％,42.5％ and 42.9％ in four BMI groups (P=0.016) after PSM.The risk of developing AKI increased by 19.9％ as the BMI increased per 5 kg/m2 (95％ CI:1.070-1.344,P=0.002).The hospital mortality of patient (overall,AKI,AKI-RRT) in four groups was not statistically different after PSM (P ＞ 0.05),but overweight group always had the lowest mortality.Conclusions BMI is a risk factor for AKI after cardiac surgery,and the AKI incidence increases with increasing BMI in a certain range.

The existing situation and long-term quality of life in extremely low birth weight infants / 国际儿科学杂志

Extremely low birth weight infants (ELBW)are those premature babies whose birth weight are below 1 000 g.In recent years,with the rapid development of perinatal medicine,survival rates of the ELBW in the developed countries has reached more than 80％,but with the increase of survival rates,the present living situation and the long-term quality of life begin to attract the neonatal physicians' attention.The growth and nutrition status of ELBW are not as well as those full maturity,neither do the certain problems,including long-term respiratory system,nervous system,education and employment.