Repetitive Low-Level Blast Exposure via Akt/NF-κB Signaling Pathway Mediates the M1 Polarization of Mouse Alveolar Macrophage MH-S Cells.

Repetitive low-level blast (rLLB) exposure is a potential risk factor for the health of soldiers or workers who are exposed to it as an occupational characteristic. Alveolar macrophages (AMs) are susceptible to external blast waves and produce pro-inflammatory or anti-inflammatory effects. However, the effect of rLLB exposure on AMs is still unclear. Here, we generated rLLB waves through a miniature manual Reddy-tube and explored their effects on MH-S cell morphology, phenotype transformation, oxidative stress status, and apoptosis by immunofluorescence, real-time quantitative PCR (qPCR), western blotting (WB) and flow cytometry. Ipatasertib (GDC-0068) or PDTC was used to verify the role of the Akt/NF-κB signaling pathway in these processes. Results showed that rLLB treatment could cause morphological irregularities and cytoskeletal disorders in MH-S cells and promote their polarization to the M1 phenotype by increasing iNOS, CD86 and IL-6 expression. The molecular mechanism is through the Akt/NF-κB signaling pathway. Moreover, we found reactive oxygen species (ROS) burst, Ca2+ accumulation, mitochondrial membrane potential reduction, and early apoptosis of MH-S cells. Taken together, our findings suggest rLLB exposure may cause M1 polarization and early apoptosis of AMs. Fortunately, it is blocked by specific inhibitors GDC-0068 or PDTC. This study provides a new treatment strategy for preventing and alleviating health damage in the occupational population caused by rLLB exposure.

Prenatal phthalate exposure and birth size: a systematic review and meta-analysis.

Phthalates are common endocrine disruptors. The placental barrier can be crossed by phthalates and may have a negative impact on the health of the fetus. However, the association between prenatal exposure to phthalates and birth size is still debatable. Here, we performed this meta-analysis to assess the relationship between prenatal phthalates exposure and birth size. Eighteen studies were finally included by searching PubMed, Embase, Scopus, Ovid, and Web of Science databases and standardized regression coefficients and standard errors were used to pool effect size. Our results showed that prenatal exposure to MMP (=-0.04, 95%CI: -0.08, -0.01) and MEP (=-0.01, 95%CI: -0.01, -0.002) was significantly associated with birth weight. However, no significant associations were identified for phthalate exposure with birth length, head circumference and chest circumference. Because the limiting of studies, more high-quality case-control studies or cohort studies are urgently needed to draw the best conclusions.

Aberrant mitochondrial DNA methylation and declined pulmonary function in a population with polycyclic aromatic hydrocarbon composition in particulate matter.

Air pollution exposure has been found to be associated with epigenetic modification of the mitochondrial genome, which could subsequently induce adverse health outcomes. However, very limited studies exist regarding the association between fine particulate matter (PM2.5) exposure and pulmonary function at the molecular level of mitochondrial epigenetic changes. This study aimed to investigate the association of platelet mitochondrial DNA (mtDNA) methylation with occupational PM2.5 exposure and pulmonary function. First, 768 participants were occupationally exposed to polycyclic aromatic hydrocarbon (PAH)-enriched PM2.5 in a coke-oven plant in East China. The levels of PM2.5, PAH components bound to PM2.5, and urinary PAH metabolites in the workplace environment were measured as an internal dose, respectively. mtDNA methylation was measured by bisulfite pyrosequencing of two genes of ATP synthase (MT-ATP6 and MT-ATP8). Mediation analysis was conducted to evaluate the role of mtDNA methylation in pulmonary alteration induced by PAH. A decreasing trend of platelet mtDNA methylation was observed with increase in PM2.5 exposure across all participants. As an important PAH metabolite in urine, 1-hydroxypyrene (1-OHP) was significantly negatively associated with FEV1/FVC (Forced Expiratory Volume in 1s/Forced Vital Capacity) ratio. The participants with high serum folate levels (≥10 nmol/L) showed positive association between MT-ATP6 methylation and FEV1/FVC ratio. Mediation analysis suggested that MT-ATP6 methylation mediated the significant association of urinary 1-OHP with FEV1/FVC. Our findings suggested the methylation of platelet mitochondrial gene MT-ATP6 and FEV1/FVC to be negatively associated with PM exposure. Platelet mtDNA methylation acted as an intermediary between PAH exposure and lung function decline. The mitochondrial epigenetic regulation in platelets, in response to PM exposure, might be involved in subsequent progress of abnormal pulmonary function.

Patient delay in a coronavirus disease 2019 (COVID-19) outbreak in Tianjin, China from January to February 2020.

BACKGROUND: Patient delay of COVID-19 patients occurs frequently, which poses a challenge to the overall epidemic situation. In this study, we aimed to evaluate the extent of patient delay, explore its factors, and investigate the effects of patient interval on epidemic situation. METHODS: A retrospective cohort study was conducted with 136 COVID-19 patients in Tianjin, China. Factors associated with patient delay were explored using logistic regression models. The relationship was investigated by spearman correlation analysis and mean absolute error between patient interval of lagging days and epidemic situation. RESULTS: The factors associated with patient delay of COVID-19 patients were mainly the imported cases, the first presentation to a tertiary hospital, close contacts and spatial accessibility to fever clinic. The longer the patient intervals of lagging days, the greater the number of new-onset and confirmed cases in 3-4 and 5-7 days after the first day symptoms, respectively. CONCLUSION: Identification and quarantine of close contacts, promoting the spatial accessibility to fever clinics and creating public awareness are crucial to shortening patient delays to flat the curve for COVID-19.

Low DEDD expression in breast cancer cells indicates higher sensitivity to the Bcl-2-specific inhibitor ABT-199.

As a proapoptotic death effect domain (DED)-containing protein, DED-containing DNA-binding protein (DEDD) has been demonstrated to inhibit tumor growth, invasion and metastasis in our previous studies. Here, we demonstrated that knockdown of DEDD in MCF-7 cells resulted in characteristic drug resistance to doxorubicin and paclitaxel, and overexpression of DEDD in MDA-MB-231 cells increased their sensitivity to doxorubicin and paclitaxel. The expression levels of DEDD were positively correlated with Bcl-2 in breast cancer cell lines as well as in human breast cancer tissue. Knockdown of DEDD downregulated the transcriptional activity of the bcl-2 gene and shortened the time for Bcl-2 degradation. DEDD interacts with and stabilizes Bcl-2, and breast cancer cells with low DEDD expression were more sensitive to treatment with a BH3 mimetic, ABT-199, than were those with high DEDD expression. In total, our findings highlight a new strategy for treating breast cancer with no/low DEDD expression by targeting Bcl-2 with the BH3 mimetic ABT-199.

Myoglobin Mediates Autophagy of NRK-52E in Rat Renal Tubular Epithelial Cells Via the Pink1/Parkin Signaling Pathway.

BACKGROUND The aim of this study was to investigate whether myoglobin mediates the autophagy of NRK-52E via the Pink1/Parkin signaling pathway. MATERIAL AND METHODS Differentially-expressed genes were selected by PCR chip analysis of the autophagy signaling pathway. RT-PCR and Western blot analyses were used to detect the expressions of Pink1/Parkin and autophagy-related proteins in myoglobin-treated NRK-52E. LC3 double-labeled lentivirus was used to infect NRK-52E for observing autophagy. The role of myoglobin mediates autophagy was evaluated through Pink1-siRNA inhibition of the Pink1/Parkin signaling pathway. RESULTS Myoglobin acted on NRK-52E, caused differential expressions of Pink1, Parkin, and Beclin 1, increased apoptosis, and decreased cell viability. myoglobin increased the levels of Pink1, Beclin 1 and ATG5, decreased the levels of P62 and Parkin. The level of LC3II/LC3I showed significant elevation in NRK-52E cells at after incubated with 100 µmol/L myoglobin. Inhibiting Pink1/Parkin signaling pathway through Pink1-siRNA could alleviate myoglobin induced apoptosis, decrease the levels of Pink, Beclin1, ATG5, LC3II/LC3I, and elevate the levels of Parkin and P62. Moreover, the autophagy spots were reduced after silencing Pink1 in myoglobin-treated NRK-52E. CONCLUSIONS Myoglobin mediates the autophagy of NRK-52E in rat renal tubular epithelial cells via the Pink1/Parkin signaling pathway.

Emerging medical therapies in crush syndrome - progress report from basic sciences and potential future avenues.

Crush injury is a disease that is commonly found in victims of earthquakes, debris flows, mine disasters, explosions, terrorist attacks, local wars, and other accidents. The complications that arise due to the crush injury inflicted on victims give rise to crush syndrome (CS). If not treated in time, the mortality rate of CS is very high. The most important measure that can be taken to reduce mortality in such situations is to immediately start treatment. However, the traditional treatment methods such as fluid resuscitation, diuresis, and hemodialysis are not feasible enough to be carried out at the disaster scene. So there is a need for developing new treatments that are efficient and convenient. Because it is difficult to diagnose in the disaster area and reach the treatment equipment and treat on time. It has become a new research needs to be directed into identifying new medical treatment targets and methods using the etiology and pathophysiological mechanisms of CS. In recent years, a large number of new anti-oxidant and anti-inflammatory drug therapies have been shown to be highly efficacious in CS rat/mouse models. Some of them are expected to become specific drugs for the emergency treatment of a large number of patients who may develop CS in the aftermath of earthquakes, wars, and other disasters in the future. Hence, we have reviewed the latest research on the medical therapy of CS as a source for anyone wishing to pursue research in this direction.

Damage-Associated Molecular Patterns and Their Signaling Pathways in Primary Blast Lung Injury: New Research Progress and Future Directions.

Primary blast lung injury (PBLI) is a common cause of casualties in wars, terrorist attacks, and explosions. It can exist in the absence of any other outward signs of trauma, and further develop into acute lung injury (ALI) or a more severe acute respiratory distress syndrome (ARDS). The pathogenesis of PBLI at the cellular and molecular level has not been clear. Damage-associated molecular pattern (DAMP) is a general term for endogenous danger signals released by the body after injury, including intracellular protein molecules (HMGB1, histones, s100s, heat shock proteins, eCIRP, etc.), secretory protein factors (IL-1ß, IL-6, IL-10, TNF-α, VEGF, complements, etc.), purines and pyrimidines and their derived degradation products (nucleic acids, ATP, ADP, UDPG, uric acid, etc.), and extracellular matrix components (hyaluronic acid, fibronectin, heparin sulfate, biglycan, etc.). DAMPs can be detected by multiple receptors including pattern recognition receptors (PRRs). The study of DAMPs and their related signaling pathways, such as the mtDNA-triggered cGAS-YAP pathway, contributes to revealing the molecular mechanism of PBLI, and provides new therapeutic targets for controlling inflammatory diseases and alleviating their symptoms. In this review, we focus on the recent progress of research on DAMPs and their signaling pathways, as well as the potential therapeutic targets and future research directions in PBLI.

Protective effect of mild-induced hypothermia against moderate traumatic brain injury in rats involved in necroptotic and apoptotic pathways.

AIM: To investigate the protective effect of hypothermia (HT) on brain injury in moderate traumatic brain injury (TBI) rat models and the potential mechanisms, especially the involvement of RIPK1 in apoptosis and necroptosis. METHODS: Adult Sprague-Dawley rats were randomized to four groups: sham+normothermia (sham+NT), sham+hypothermia (sham+HT), moderate TBI+normothermia (TBI+NT) and moderate TBI+hypothermia (TBI+HT). The sham+HT and TBI+HT groups were submitted to 32°C for 6 hours. The regional cerebral blood flow (rCBF) was assessed 24 hours after TBI; 24 and 48 hours after TBI, the modified neurological severity score (mNSS) was assessed. Immediately after behavioural tests, rats were sacrificed to harvest the brain tissues. RESULTS: mNSS scores were lower in the TBI+HT group compared with the TBI+NT group (p < 0.01) and cerebral blood flow was better (p < 0.01). H&E staining of the cortex and ipsilateral hippocampus showed pyknotic and irregularly shaped neurons in TBI+NT rats, which were less frequent in TBI+HT rats. The TBI+NT and TBI+HT groups showed higher TNF-α, TRAIL, FasL, FADD, caspase-3, caspase-8, PARP-1, RIPK-1 and RIPK-3 levels than the sham+NT group (all p < 0.05), but the levels of these proteins were all lower in the TBI+HT group compared with the TBI+NT group (all p < 0.01). CONCLUSION: HT treatment significantly reduced RIPK-1 upregulation, which may inhibit necroptosis and apoptosis pathways after moderate TBI.

Analyses of the Disease Spectrum of Children After the Lushan Earthquake.

UNLABELLED: : An earthquake with a magnitude of 7.0 struck Lushan in Sichuan Province in China on April 20, 2013. Uniformed pediatricians visited the area where the epicenter was located to provide emergency relief care for children 10 days after the earthquake. OBJECTIVES: The aims of the study were to analyze the features of the disease spectrum of children in Baoxing at early time after Lushan earthquake and to provide basis information, which will be useful for the arrangement of the medical resources of pediatrics in the medical relief after Lushan earthquake in similar situation in the future. METHODS: A total of 220 case files were classified and analyzed. These files provided information regarding pediatric patients whose conditions were diagnosed and treated in the mobile hospital established by the Affiliated Hospital of Logistical University of Chinese People's Armed Police Forces in Baoxing from April 20, 2013 to April 30, 2013. The demographic data of all these patients were collected and the disease spectrum was analyzed. RESULTS: Children's ages differed. A total of 59 patients were neonates, infants, and toddlers (27%); 111 were school-aged children (50%) and 50 were adolescents (23%). Common diseases and injuries include respiratory tract infection, dermatosis, and trauma, which were observed 10 days after the earthquake. Trauma was mainly accidental injury. The morbidity rate of infectious diseases was low. CONCLUSIONS: Pediatricians have an important role in the early treatment and subsequent control of infectious diseases during earthquakes.

A descriptive analysis of injury triage, surge of medical demand, and resource use in an university hospital after 8.12 Tianjin Port Explosion, China.

OBJECTIVE: The 8.12 Tianjin Port Explosion in 2015 caused heavy casualties. Pingjin Hospital, an affiliated college hospital in Tianjin, China participated in the rescue activities. This study aims to analyze the emergency medical response to this event and share experience with trauma physicians to optimize the use of medical resource and reduce mortality of critical patients. METHODS: As a trauma centre at the accident city, our hospital treated 298 patients. We retrospectively analyzed the data of emergency medical response, including injury triage, injury type, ICU patient flow, and medical resource use. RESULTS: There were totally 165 deaths, 8 missing, and 797 non-fatal injuries in this explosion. Our hospital treated 298 casualties in two surges of medical demand. The first one appeared at 1 h after explosion when 147 wounded were received and the second one at 4 h when 31 seriously injured patients were received, among whom 29 were transferred from Tianjin Emergency Center which was responsible for the scene injury triage. After reexamination and triage, only 11 cases were defined as critical ill patients. The over-triage rate reached as high as 62.07%. Seventeen patients underwent surgery and 17 patients were admitted to the intensive care unit. CONCLUSIONS: The present pre-hospital system is incomplete and may induce two surges of medical demand. The first one has a much larger number of casualties than predicted but the injury level is mild; while the second one has less wounded but almost all of them are critical patients. The over-triage rate is high. The hospital emergency response can be improved by an effective re-triage and implementation of a hospital-wide damage control.

Development of atom transfer radical polymer-modified gold nanoparticle-based enzyme-linked immunosorbent assay (ELISA).

In this work, a novel enzyme-linked immunosorbent assay (ELISA) with a low limit of detection and high sensitivity was developed using atom transfer radical polymer (ATRP)-modified gold nanoparticles (AuNPs). Clear signal amplification was achieved by introducing an abundance of horseradish peroxidase (HRP) to the AuNPs, because of the ATRP modification. This result suggested that the new ELISA was able to detect antigens in complex mixtures, and the limit of detection (LOD) was lower than that of conventional ELISA by a factor of 81. The new ELISA strategy greatly decreased the LOD during analysis and exhibited excellent reproducibility, stability, and feasibility. Therefore, it is a promising technique with many potential applications in biochemistry and medical science research.

MiR-15a-16 represses Cripto and inhibits NSCLC cell progression.

MicroRNAs (miRNAs) are small noncoding RNAs that have important roles in cancer. The altered expressions of miRNAs and their target genes are frequently detected in various tumors. In this study, downregulation of miR-15a-16 in nonsmall cell lung cancer (NSCLC) was found to be inversely correlated with Cripto. Results from the Luciferase reporter assay and Western blot analysis also confirmed that Cripto is a direct target of miR-15a-16. In addition, transfection of miR-15a-16 expression plasmid inhibited the invasion ability and promoted the apoptosis of NCI-H23 and NCI-H358 cells. Moreover, miR-15a-16 overexpression suppressed tumor growth in vivo. These findings clearly suggest that the downregulation of miR-15a-16 with Cripto amplification may be involved in the development of NSCLC.

What else should hemostatic materials do beyond hemostasis: A review.

Massive blood loss due to injury is the leading cause of prehospital deaths in disasters and emergencies. Hemostatic materials are used to realize rapid hemostasis and protect patients from death. Researchers have designed and developed a variety of hemostatic materials. However, in addition to their hemostatic effect, hemostatic materials must be endowed with additional functions to meet the practical application requirements in different scenarios. Here, strategies for modifications of hemostatic materials for use in different application scenarios are listed: effective positioning at the site of deep and narrow wounds to stop bleeding, resistance to high blood pressure and wound movement to maintain wound formation, rapid and easy removal from the wound without affecting further treatment after hemostasis is completed, and continued function when retained in the wound as a dressing (such as antibacterial, antiadhesion, tissue repair, etc.). The problems encountered in the practical use of hemostatic materials and the strategies and progress of researchers will be further discussed in this review. We hope to provide valuable references for the design of more comprehensive and practical hemostatic materials.

Association of residential greenness, air pollution with adverse birth outcomes: Results from 61,762 mother­neonatal pairs in project ELEFANT (2011-2021).

BACKGROUND: Emerging evidence has demonstrated the benefits of greenness exposure on human health, while conflicts remain unsolved in issue of adverse birth outcomes. METHODS: Utilizing data from project ELEFANT spanning the years 2011 to 2021, we assessed residential greenness using the NDVI from MODIS data and residential PM2.5 exposure level from CHAP data. Our primary concerns were PTD, LBW, LGA, and SGA. Cox proportional hazard regression model was used to examine the association of residential greenness and air pollution exposure with risk of adverse birth outcomes. We performed mediation and modification effect analyses between greenness and air pollutant. RESULTS: We identified 61,762 mother­neonatal pairs in final analysis. For per 10 µg/m3 increase in PM2.5 concentration during entire pregnancy was associated with 19.8 % and 20.7 % increased risk of PTD and LGA. In contrast, we identified that an 0.1 unit increment in NDVI were associated with 24 %, 43 %, 26.5 %, and 39.5 % lower risk for PTD, LBW, LGA, and SGA, respectively. According to mediation analysis, NDVI mediated 7.70 % and 7.89 % of the associations between PM2.5 and PTD and LGA. Residential greenness could reduce the risk of PTD among mothers under 35 years old, living in rural areas, primigravidae and primiparity.. CONCLUSIONS: In summary, our results highlighted the potential of residential greenness to mitigate the risk of adverse birth outcomes, while also pointing to the adverse impact of PM2.5 on increased risk of multiple adverse birth outcomes (PTD and LGA). The significant mediation effect of NDVI emphasizes its potential as an important protective factor of PM2.5 exposure. Additionally, the identification of susceptible subgroups can inform targeted interventions to reduce adverse birth outcomes related to air pollution and lack of green spaces. Further research and understanding of these associations can contribute to better public health strategies aimed at promoting healthier pregnancies and birth outcomes.

Recent progress in the effect of magnetic iron oxide nanoparticles on cells and extracellular vesicles.

At present, iron oxide nanoparticles (IONPs) are widely used in the biomedical field. They have unique advantages in targeted drug delivery, imaging and disease treatment. However, there are many things to pay attention to. In this paper, we reviewed the fate of IONPs in different cells and the influence on the production, separation, delivery and treatment of extracellular vesicles. It aims to provide cutting-edge knowledge related to iron oxide nanoparticles. Only by ensuring the safety and effectiveness of IONPs can their application in biomedical research and clinic be further improved.

Progress in the Application of Portable Ultrasound Combined with Artificial Intelligence in Pre-Hospital Emergency and Disaster Sites.

With the miniaturization of ultrasound and the development of artificial intelligence, its application in disaster scenes and pre-hospital emergency care has become more and more common. This study summarizes the literature on portable ultrasound in pre-hospital emergency and disaster scene treatment in the past decade and reviews the development and application of portable ultrasound. Portable ultrasound diagnostic equipment can be used to diagnose abdominal bleeding, limb fracture, hemopneumothorax, pericardial effusion, etc., based on which trauma can be diagnosed pre-hospital and provide guiding suggestions for the next triage and rescue; in early rescue, portable ultrasound can guide emergency operations, such as tracheal intubation, pericardial cavity puncture, and thoracic and abdominal puncture as well as improve the accuracy and timeliness of operation techniques. In addition, with the development of artificial intelligence (AI), AI-assisted diagnosis can improve the diagnosis level of ultrasound at disaster sites. The portable ultrasound diagnosis system equipped with an AI robotic arm can maximize the pre-screening classification and fast and concise diagnosis and treatment of batch casualties, thus providing a reliable basis for batch casualty classification and evacuation at disaster accident sites.

A Medical Image Segmentation Method Based on Improved UNet 3+ Network.

In recent years, segmentation details and computing efficiency have become more important in medical image segmentation for clinical applications. In deep learning, UNet based on a convolutional neural network is one of the most commonly used models. UNet 3+ was designed as a modified UNet by adopting the architecture of full-scale skip connections. However, full-scale feature fusion can result in excessively redundant computations. This study aimed to reduce the network parameters of UNet 3+ while further improving the feature extraction capability. First, to eliminate redundancy and improve computational efficiency, we prune the full-scale skip connections of UNet 3+. In addition, we use the attention module called Convolutional Block Attention Module (CBAM) to capture more essential features and thus improve the feature expression capabilities. The performance of the proposed model was validated by three different types of datasets: skin cancer segmentation, breast cancer segmentation, and lung segmentation. The parameters are reduced by about 36% and 18% compared to UNet and UNet 3+, respectively. The results show that the proposed method not only outperformed the comparison models in a variety of evaluation metrics but also achieved more accurate segmentation results. The proposed models have lower network parameters that enhance feature extraction and improve segmentation performance efficiently. Furthermore, the models have great potential for application in medical imaging computer-aided diagnosis.

Research progress of portable extracorporeal membrane oxygenation.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is primarily used for the supportive treatment of patients suffering from severe cardiopulmonary failure. With the continued development of ECMO technology, the relevant scenarios also extend pre-hospital and inter-hospital. In order to meet the needs of emergency treatment in communities, disaster sites and battlefields, inter-hospital transfer and evacuation; miniaturized and portable ECMO has become a current research hotspot. AREA COVERED: The paper first introduces the principle, composition and common modes of ECMO and summarizes the research status of portable ECMO, Novalung and wearable ECMO, analyzes the characteristics and shortcomings of existing equipment. finally, we discussed the focus and development trend of portable ECMO technology. EXPERT OPINION: Currently, portable ECMO has many applications in interhospital transport and there are various studies on portable and wearable ECMO devices, but the development of portable ECMO still faces many challenges. In the future, research related to integrated components, rich sensor arrays, Intelligent ECMO system and lightweight technology can make future portable ECMO more suitable for pre-hospital emergency and interhospital transport.

The Role of Long Noncoding RNAs in Intestinal Health and Diseases: A Focus on the Intestinal Barrier.

The gut is the body's largest immune organ, and the intestinal barrier prevents harmful substances such as bacteria and toxins from passing through the gastrointestinal mucosa. Intestinal barrier dysfunction is closely associated with various diseases. However, there are currently no FDA-approved therapies targeting the intestinal epithelial barriers. Long noncoding RNAs (lncRNAs), a class of RNA transcripts with a length of more than 200 nucleotides and no coding capacity, are essential for the development and regulation of a variety of biological processes and diseases. lncRNAs are involved in the intestinal barrier function and homeostasis maintenance. This article reviews the emerging role of lncRNAs in the intestinal barrier and highlights the potential applications of lncRNAs in the treatment of various intestinal diseases by reviewing the literature on cells, animal models, and clinical patients. The aim is to explore potential lncRNAs involved in the intestinal barrier and provide new ideas for the diagnosis and treatment of intestinal barrier damage-associated diseases in the clinical setting.