Humans ; Asthma/drug therapy* ; Biological Therapy

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

【Objective】 To establish a management information system (referred to as the system) for plasma collection stations in Zhejiang province, so as to explore the current situation of plasma donors and implement effective supervision in Zhejiang. 【Methods】 The system was developed and connected to four plasma collection stations that were officially operating in Zhejiang in terms of plasma station setting and approval, as well as the publicity, recruitment and management of plasma donors, information management of the whole process of plasma collection, management of deferral plasma donors, plasma quality management and administrative supervision etc. Relevant plasma donor information was uploaded to the system by each plasma station, and information before (January 2016 to December 2020) and after (January 8, 2021 to June 2021) the system was collected. Information included the number of plasma donors/donations, demographic information of eligible plasma donors in the past 5 years, the type of plasma donors, and the deferral donors after the system was activated. The online approval of Plasma Donation Certificate and the intelligent supervision of key points of plasma apheresis stations in Zhejiang were also conducted. The frequency and composition ratio were described, and chi-square test was used for statistical analysis. 【Results】 The system (V1.0) was established and was officially launched on January 8, 2021, realizing the interconnection of blood donation and plasma donation information as well as the unified management of 24 quality indicators. Since the system was applied (January 8, 2021-June 2021), the proportion of donors both donated blood and plasma over the province was 3.56 (832/23 389), and 352 deferred donors were masked by the system. And 30.11% (106/352) , who intended to donate plasma, were deferred due to insufficient interval after blood donation; 11.65% (41/352) due to permanent masking in blood donations; 23.86% (23.86%) , who intended to donate blood, were deferred due to insufficient interval after plasma donation ( 84/352); 34.38% (121/352) due to permanent masking in plasma donations. The median approval rate of four plasma stations applying for Plasma Donation Certificate before the system (January 1, 2016 to January 7, 2021) and after the system (January 8 to June 2021) were 93.38% (10 609/11 361) vs 99.50% (2 602/2 615). Before the system was put into launch, the ratio of male to female donors and the proportion of regular donors showed an overall upward trend, while the age decreased slightly. The median proportion of women in the past 5 years was 61.52 %, significantly higher than that in last 6 months after the launch(58.86%). 【Conclusion】 The application of the system can realize information interconnection between blood centers and plasma collection stations in Zhejiang as well as the real-time supervision of plasma collection process, which is helpful to overcome the shortcomings in plasma donor management.

Inflammatory reaction dominated by defense response will arise against infection and trauma. As an important proinflammatory cytokine, high mobility group box 1 (HMGB1) is widely expressed in all nuclear cells to mediate the inflammatory response. However, the biological functions of HMGB1 in inflammation vary depending on the type of HMGB1 protein modification and the localization in the cell. HMGB1 protein will be modified as acetylation of lysine residues, methylation of lysine residues, oxidation of cysteine residues, phosphorylation of serine residues, glycosylation of asparagine residues, adenosine diphosphate-ribosylation and lactylation of the protein in the nucleus, migrate from the nucleus to the cytoplasm, and release into the extracellular compartment. Extracellular HMGB1 can bind to receptors for advanced glycation end products (RAGE) and Toll-like receptors, activate cells and regulate inflammatory responses. The authors review the research progress in regulatory mechanism of HMGB1 in inflammation response from aspects of its post-translational modifications, releases, biological roles and binding receptors, hoping to provide theoretical basis for finding the targets of inflammation intervention.

Objective:To evaluate the effect of propofol on proliferation, invasion and migration of human melanoma cells and role of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2)/matrix metalloproteinase (MMP) signaling pathway.Methods:SKMEL-5 cells were cultured in vitro and divided into 4 groups ( n=36 each) using the random number table method: control group (group C), propofol group (group P), COX-2 overexpression group (group COX-2), and COX-2 overexpression plus propofol group (group COX-2+ P). Propofol at the final concentration of 60 μmol/L was added in group P. The COX-2 overexpression plasmid pcDNA3.1-COX-2 was transfected into SKMEL-5 cells in group COX-2 and group COX-2+ P, and propofol at the final concentration of 60 μmol/L was added in group COX-2+ P.After incubation for 48 h, the cell proliferation rate was determined by CCK-8 method, the cell invasion and migration ability was determined by Transwell assay, the expression of COX-2 in cells was detected by Western blot, the expression of COX-2 mRNA in cells was detected by quantitative real-time polymerase chain reaction, and the concentrations of serum PGE2, MMP-2 and MMP-9 were determined by enzyme-linked immunosorbent assay. Results:Compared with group C, the cell proliferation rate was significantly decreased, the number of cell invasion and migration was decreased, the expression of COX-2 protein and mRNA was down-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were decreased in group P, and the cell proliferation rate was significantly increased, and the number of cell invasion and migration was increased, the expression of COX-2 protein and mRNA was up-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were increased in group COX-2 ( P<0.05). Compared with group P, the cell proliferation rate was significantly increased, and the number of cell invasion and migration was increased, the expression of COX-2 protein and mRNA was up-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were increased in group COX-2+ P ( P<0.05). Conclusions:Propofol can inhibit the proliferation, invasion and migration of human melanoma cells, and the mechanism may be related to inhibition of the COX-2/PGE2/MMP signaling pathway.

Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

Objective:To explore the feasibility and effectiveness of the construction of urban unmanned aerial vehicle (UAV) blood distribution system, and to provide a novel way for the distribution of emergency blood.Methods:The study was completed in Hangzhou from April 2019 to January 2021, and the main participants were from the Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang Province Blood Center and Hangzhou Fast Ant Network Technology Co., Ltd. Firstly, an unmanned aircraft delivery system was built for urban emergency blood and a special blood storage box for drones were developed. The drone was used to deliver blood products from Zhejiang Province Blood Center to Binjiang Campus, the Second Affiliated Hospital of Zhejiang University School of Medicine, and the following indicators were obtained: (1) flight time of the drone blood delivery; (2) real-time temperature of blood products during transportation; (3) Baidu map software was used to measure the blood delivery time of road traffic, which was compared with the flight time of the drone.Results:The urban drone blood delivery system consists of intelligent logistics drones, cryogenic blood storage tanks, unmanned logistics hub stations, and cloud-based operation control platforms. The drone route distance from Zhejiang Provincial Blood Center to Binjiang Campus, the Second Affiliated Hospital of Zhejiang University School of Medicine was 2.36±0.06 km, and the ground distance was 5.8 km, with 27 flights from April 12, 2019 to January 29, 2021, and the drone flight time was, shorter than the road travel time for a round trip [(6.37±0.35) min vs. (17.00±1.94) min]. At different time points of the day, UAV blood delivery could save 15.98-4.28 min, with an average saving of 10.62±1.87 min. Conclusions:Urban UAV blood delivery systems have the advantages of being fast, unaffected by ground traffic conditions, and can ensure the safety of blood products during transportation, and are worthy of further exploration.

Objective:To explore the threshold and diagnostic value of Chinese version of the Chelsea Physical Function Assessment Tool (CPAx-Chi) for ICU acquired weakness(ICU-AW).Methods:To learn the details and precautions of the CPAx-Chi scale, and then two researchers used the CPAx-Chi scale and MRC-Score scale to independently evaluate 200 patients who come from a comprehensive ICU in a top first-class hospital in Gansu Province simultaneously. The best cut-off point and value of the CPAx-Chi scale in the diagnosis of ICU-AW were determined by calculating the Receiver Operating Characteristic (ROC) curve, the Youden index(YI) and the consistency test that are all based on the MRC-Score≤48.Results:The ROC Area Under Curve(AUC) of the CPAx-Chi scale diagnosis ICU-AW which based on the MRC-Score≤48 were as follows: ROC AUC of group A was 0.899 (95% CI 0.862-1.025); ROC AUC of group B was 0.874 (95% CI 0.824-0.925). When the best cut-off point of CPAx-Chi scale for diagnosis ICU-AW was 31.5, the maximum YI=0.643, the sensitivity was 87%, and the specificity was 77% in group A; and the maximum YI= 0.62, the sensitivity was 75%, and the specificity was 87% in group B. Meanwhile, when the best cut-off point of CPAx-Chi scale for diagnosis ICU-AW was 30.5, the maximum YI=0.62, the sensitivity was 79%, and the specificity was 83% in group B. Taking the CPAx -Chi≤31 as the best cut-off point, the score differences in ICU-AW group and the non-ICU-AW group were not detected, A group ( F value was 4.53, P=0.035) or B group ( F value was 6.51, P=0.011). The consistency of CPAx -Chi≤31 and MRC-Score≤48 in the diagnosis of ICU-AW was high, and the Kappa=0.845 ( P=0.02) in the group A; the Kappa=0.839( P=0.04) in the group B, and the group differences were detected. Conclusions:CPAx-Chi≤31 is the best cut-off point for diagnosing ICU-AW, and has good sensitivity and specificity. CPAx-Chi scale can be popularized and applied in the critical care medicine in China.

Objective:To evaluate the effect of early mobilization on mortality in intensive care unit (ICU) patients with mechanical ventilation after discharge by Meta-analysis.Methods:Databases including SinoMed, China National Knowledge Infrastructure (CNKI), Wanfang data, PubMed, the Cochrane Library, Web of Science, and Embase were searched from inception to September 17th, 2020, to collect randomized controlled trials (RCT) about early mobilization on mortality of patients with mechanical ventilation in ICU after discharge, the references included in the literature were traced. The control group was given routine care, the experimental group was given early mobilization on the basis of the control group, including passive or active mobilization on the bed, sitting on the bed, standing by the bed, transferring to the bedside chair and assisting walking. The literature screening, data extracting, and the bias risk assessment of included studies were conducted independently by two reviewers. Stata 12.0 software was then used to perform Meta-analysis. Funnel plot was used to test publication bias.Results:A total of 10 RCT studies involving 1 323 patients were included, with 660 patients in the control group and 663 patients in the experimental group. The results of literature quality evaluation showed that 7 studies were grade A and 3 studies were grade B, indicating that the overall quality of included literatures was high. The Meta-analysis results showed that early mobilization did not increase the mortality of patients with mechanical ventilation in ICU after discharge [odds ratio ( OR) = 0.92, 95% confidence interval (95% CI) was 0.75-1.13, P = 0.449]. Subgroup analysis results showed that early mobilization had a tendency to reduce the mortality of ICU patients with mechanical ventilation at 3, 6 and 12 months after discharge, but the difference was not statistically significant (3-month mortality: OR = 1.02, 95% CI was 0.74-1.40, P = 0.927; 6-month mortality: OR = 0.95, 95% CI was 0.70-1.27, P = 0.712; 12-month mortality: OR = 0.60, 95% CI was 0.33-1.10, P = 0.101). Funnel plot showed that the distribution of included literatures was not completely symmetrical, suggesting that publication bias might exist. Conclusions:Early mobilization does not increase the mortality of ICU patients with mechanical ventilation after discharge. Although it tends to have a favorable outcome in reducing mortality, and has a trend to reduce the mortality. However, due to the small number of included literatures, small sample size and differences in the specific implementation of early mobilization among various studies, a large number of high-quality RCT studies are still needed for further verification.

The body is in a very complex pathophysiological state under trauma, including ischemia and hypoxia, inflammation caused by infection and tissue necrosis and accumulation of metabolic waste. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is involved in the regulation of a variety of cell behaviors, such as proliferation, apoptosis, differentiation, migration, epithelial-mesenchymal transition, autophagy and morphological maintenance. Under trauma, the expression of MALAT1 is significantly increased. In different injury models, the role of MALAT1 is slightly different, and the specific mechanism is unknown. The authors summarize the regulatory effects of MALAT1 on the body under traumatic conditions from the biological characteristics of MALAT1 and its role in different injury models, so as to provide references for clinical control of inflammation development and improvement of disease prognosis.