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Volume 8 ， Issue 2 ， 2021
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Abstract：Background:Our objective was to identify possible associations between clinical and laboratory variables and the risk of developing acute kidney injury (AKI) in severely injured patients admitted to the Intensive Care Unit (ICU) for whom creatine kinase (CK) levels were available.Methods:For this retrospective observational study, we analyzed adult trauma patients admitted to the ICU from 2011 to 2015 at Fundación Valle del Lili (FVL) University Hospital. Our primary outcome was the incidence of AKI. Multivariate regression analysis was used to assess risk factors for this outcome.Results:A total of 315 patients were included. The trauma mechanisms were blunt (n=130), penetrating (n=66) and blast (n=44) trauma. The median [interquartile range, IQR) of injury severity score (ISS) was 21 (16–29). AKI developed in 75 patients (23.8%). Multivariate regression analysis revealed that the thoracic abbreviated injury scale (AIS) value (median (IQR) in the AKI group: 3 (0–4)], Acute Physiology and Chronic Health Evaluation (APACHE II) score [median (IQR) in the AKI group: 18 (10–27)], CK greater than 5000 U/L, lactic acid concentration at admission, and dobutamine administration were independently associated with AKI.Conclusions:We found that age, APACHE II score, thoracic trauma, lactic acidosis, and dobutamine administration were independently associated with AKI. Trauma surgeons need to be aware of the increased odds of AKI if one of these factors is identified during the evaluation and treatment of injured patients.Keywords：Rhabdomyolysis;Wounds and injuries;Acute kidney injury;Critical care;Trauma6|1|0Updated：2023-02-28 -
Abstract：Background:p53 and DIRAS3 are tumor suppressors that are frequently silenced in tumors. In this study, we sought to determine whether the concurrent re-expression of p53 and DIRAS3 could effectively induce head and neck squamous cell carcinoma (HNSCC) cell death.Methods:CAL-27 and SCC-25 cells were treated with Ad-DIRAS3 and rAd-p53 to induce re-expression of DIRAS3 and p53 respectively. The effects of DIRAS3 and p53 re-expression on the growth and apoptosis of HNSCC cells were examined by TUNEL assay, flow cytometric analysis and MTT. The effects of DIRAS3 and p53 re-expression on Akt phosphorylation, oncogene expression, and the interaction of 4E-BP1 with eIF4E were determined by real-time PCR, Western blotting and immunoprecipitation analysis. The ability of DIRAS3 and p53 re-expression to induce autophagy was evaluated by transmission electron microscopy, LC3 fluorescence microscopy and Western blotting. The effects of DIRAS3 and p53 re-expression on HNSCC growth were evaluated by using an orthotopic xenograft mouse model.Results:TUNEL assay and flow cytometric analysis showed that the concurrent re-expression of DIRAS3 and p53 significantly induced apoptosis (P<0.001). MTT and flow cytometric analysis revealed that DIRAS3 and p53 reexpression significantly inhibited proliferation and induced cell cycle arrest (P<0.001). Mechanistically, the concurrent re-expression of DIRAS3 and p53 down-regulated signal transducer and activation of transcription 3 (STAT3) and upregulated p21WAF1/CIP1 and Bax (P<0.001). DIRAS3 and p53 re-expression also inhibited Akt phosphorylation, increased the interaction of eIF4E with 4E-BP1, and reduced the expression of c-Myc, cyclin D1, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), epidermal growth factor receptor (EGFR) and Bcl-2 (P<0.001). Moreover, the concurrent re-expression of DIRAS3 and p53 increased the percentage of cells with GFP-LC3 puncta compared with that in cells treated with control adenovirus (50.00%±4.55% vs. 4.67%±1.25%, P<0.001). LC3 fluorescence microscopy and Western blotting further showed that DIRAS3 and p53 re-expression significantly promoted autophagic activity but also inhibited autophagic flux, resulting in overall impaired autophagy. Finally, the concurrent re-expression of DIRAS3 and p53 significantly decreased the tumor volume compared with the control group in a HNSCC xenograft mouse model [(3.12±0.75) mm3 vs. (189.02±17.54) mm3, P<0.001].Conclusions:The concurrent re-expression of DIRAS3 and p53 is a more effective approach to HNSCC treatment than current treatment strategies.Keywords：DIRAS3;p53;apoptosis;Autophagy;Head and neck squamous cell carcinoma4|0|1Updated：2023-02-28 -
Abstract：Background:Generation of neurons is essential in cell replacement therapy for neurodegenerative disorders like Parkinson’s disease. Several studies have reported the generation of dopaminergic (DA) neurons from mouse and human fibroblasts by ectopic expression of transcription factors, in which genetic manipulation is associated with potential risks.Methods:The small molecules and protein factors were selected based on their function to directly induce human fetal lung IMR-90 fibroblasts into DA neuron-like cells. Microscopical, immunocytochemical, and RT-qPCR analyses were used to characterize the morphology, phenotype, and gene expression features of the induced cells. The whole-cell patch-clamp recordings were exploited to measure the electrophysiological properties.Results:Human IMR-90 fibroblasts were rapidly converted into DA neuron-like cells after the chemical induction using small molecules and protein factors, with a yield of approximately 95% positive TUJ1-positive cells. The induced DA neuron-like cells were immunopositive for pan-neuronal markers MAP2, NEUN, and Synapsin 1 and DA markers TH, DDC, DAT, and NURR1. The chemical induction process did not involve a neural progenitor/stem cell intermediate stage. The induced neurons could fire single action potentials, which reflected partially the electrophysiological properties of neurons.Conclusions:We developed a chemical cocktail of small molecules and protein factors to convert human fibroblasts into DA neuron-like cells without passing through a neural progenitor/stem cell intermediate stage. The induced DA neuron-like cells from human fibroblasts might provide a cellular source for cell-based therapy of Parkinson’s disease in the future.Keywords：Human fibroblasts;Dopaminergic neurons;Parkinson’s disease;Small molecules;Reprogramming;Transdifferentiation9|0|0Updated：2023-02-28 -
Abstract：Background:Acute mountain sickness (AMS) is the mildest form of acute altitude illnesses, and consists of nonspecific symptoms when unacclimatized persons ascend to elevation of ≥2500 m. Risk factors of AMS include: the altitude, individual susceptibility, ascending rate and degree of pre-acclimatization. In the current study, we examined whether physiological response at low altitude could predict the development of AMS.Methods:A total of 111 healthy adult healthy volunteers participated in this trial; and 99 (67 men and 32 women) completed the entire study protocol. Subjects were asked to complete a 9-min exercise program using a mechanically braked bicycle ergometer at low altitude (500 m). Heart rate, blood pressure (BP) and pulse oxygen saturation (SpO2) were recorded prior to and during the last minute of exercise. The ascent from 500 m to 4100 m was completed in 2 days. AMS was defined as ≥3 points in a 4-item Lake Louise Score, with at least one point from headache wat 6–8 h after the ascent.Results:Among the 99 assessable subjects, 47 (23 men and 24 women) developed AMS at 4100 m. In comparison to the subjects without AMS, those who developed AMS had lower proportion of men (48.9% vs. 84.6%, P<0.001), height (168.4±5.9 cm vs. 171.3±6.1 cm, P=0.019), weight (62.0±10.0 kg vs. 66.7±8.6 kg, P=0.014) and proportion of smokers (23.4% vs. 51.9%, P=0.004). Multivariate regression analysis revealed the following independent risks for AMS: female sex (odds ratio (OR)=6.32, P<0.001), SpO2 change upon exercise at low altitude (OR=0.63, P=0.002) and systolic BP change after the ascent (OR=0.96, P=0.029). Women had larger reduction in SpO2 after the ascent, higher AMS percentage and absolute AMS score. Larger reduction of SpO2 after exercise was associated with both AMS incidence (P=0.001) and AMS score (P<0.001) in men but not in women.Conclusions:Larger SpO2 reduction after exercise at low altitude was an independent risk for AMS upon ascent. Such an association was more robust in men than in women.Trial registration:Chinese Clinical Trial Registration, ChiCTR1900025728. Registered 6 September 2019.Keywords：High altitude;Exercise testing;Sex differences;Acute mountain sickness;Individual susceptibility4|0|0Updated：2023-02-28 -
Abstract：Background:Plasma expanders are widely used for acute normovolemic hemodilution (ANH). However, existing studies have not focused on large-volume infusion with colloidal plasma expanders, and there is a lack of studies that compare the effects of different plasma expanders.Methods:The viscosity, hydrodynamic radius (Rh) and colloid osmotic pressure (COP) of plasma expanders were determined by a cone-plate viscometer, Zetasizer and cut-off membrane, respectively. Sixty male rats were randomized into five groups with Gelofusine (Gel), Hydroxyethyl Starch 200/0.5 (HES200), Hydroxyethyl Starch 130/0.4 (HES130), Hydroxyethyl Starch 40 (HES40), and Dextran 40 (Dex40), with 12 rats used in each group to build the ANH model. ANH was performed by the withdrawal of blood and simultaneous infusion of plasma expanders. Acid-base, lactate, blood gas and physiological parameters were detected.Results:Gel had a lower intrinsic viscosity than HES200 and HES130 (P<0.01), but at a low shear rate in a mixture of colloids, red cells and plasma, Gel had a higher viscosity (P<0.05 or P<0.01, respectively). For hydroxyethyl starch plasma expanders, the COP at a certain concentration decreases from 11.1 mmHg to 6.1 mmHg with the increase of Rh from 10.7 nm to 20.2 nm. A severe ANH model, with the hematocrit of 40% of the baseline level, was established and accompanied by disturbances in acid-base, lactate and blood gas parameters. At the end of ANH and 60 min afterward, the Dex40 group showed a worse outcome in maintaining the acid-base balance and systemic oxygenation compared to the other groups. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) decreased significantly in all groups at the end of ANH. The DBP and MAP in the Dex40 group further decreased 60 min after the end of ANH. During the process of ANH, the Dex40 group showed a drop and recovery in SBP, DBP and MAP. The DBP and MAP in the HES200 group were significantly higher than those in the other groups at some time points (P<0.05 or P<0.01).Conclusions:Gel had a low intrinsic viscosity but may increase the whole blood viscosity at low shear rates. Rh and COP showed a strong correlation among hydroxyethyl starch plasma expanders. Dex40 showed a worse outcome in maintaining the acid-base balance and systemic oxygenation compared to the other plasma expanders. During the process of ANH, Dex40 displayed a V-shaped recovery pattern for blood pressure, and HES200 had the advantage in sustaining the DBP and MAP at some time points.Keywords：Acute normovolemic hemodilution;Plasma expander;Acid-base;Lactate;Blood gas;Physiological parameters4|0|0Updated：2023-02-28
RESEARCH
- Abstract：The effects of coronaviruses on the respiratory system are of great concern, but their effects on the digestive system receive much less attention. Coronaviruses that infect mammals have shown gastrointestinal pathogenicity and caused symptoms such as diarrhea and vomiting. Available data have shown that human coronaviruses, including the newly emerged SARS-CoV-2, mainly infect the respiratory system and cause symptoms such as cough and fever, while they may generate gastrointestinal symptoms. However, there is little about the relation between coronavirus and digestive system. This review specifically addresses the effects of mammalian and human coronaviruses, including SARS-CoV-2, on the digestive tract, helping to cope with the new virus infection-induced disease, COVID-19.Keywords：Mammal coronaviruses;Human coronaviruses;Digestive system;Coronavirus disease 2019 (COVID-19)4|0|0Updated：2023-02-28
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Abstract：Compared with non-degradable materials, biodegradable biomaterials play an increasingly important role in the repairing of severe bone defects, and have attracted extensive attention from researchers. In the treatment of bone defects, scaffolds made of biodegradable materials can provide a crawling bridge for new bone tissue in the gap and a platform for cells and growth factors to play a physiological role, which will eventually be degraded and absorbed in the body and be replaced by the new bone tissue. Traditional biodegradable materials include polymers, ceramics and metals, which have been used in bone defect repairing for many years. Although these materials have more or fewer shortcomings, they are still the cornerstone of our development of a new generation of degradable materials. With the rapid development of modern science and technology, in the 21st century, more and more kinds of new biodegradable materials emerge in endlessly, such as new intelligent micro-nano materials and cell-based products. At the same time, there are many new fabrication technologies of improving biodegradable materials, such as modular fabrication, 3D and 4D printing, interface reinforcement and nanotechnology. This review will introduce various kinds of biodegradable materials commonly used in bone defect repairing, especially the newly emerging materials and their fabrication technology in recent years, and look forward to the future research direction, hoping to provide researchers in the field with some inspiration and reference.Keywords：Biodegradable materials;Bone defects;bone repair;Intelligent material;Modular fabrication14|2|0Updated：2023-02-28 -
Abstract：Military drill injury is a significant part of military medical research. The increase of training intensity and changes in training methods lead to differences in injury types. The ideal therapeutic modality should allow rapid healing at a reasonable cost and minimize impact on patients’ life. Platelet-rich plasma (PRP), a platelet concentrate, is rich in a variety of growth factors and widely used clinically as a minimally invasive treatment. It plays an important role in injury repair and rehabilitation. In this article, we review the therapeutic role of PRP in military drill injury and its possible underlying mechanisms, with a focus on plantar fasciitis, stress fractures and other common injuries, in order to provide basic support for military reserve.Keywords：Military drill injury;Platelet-rich plasma (PRP);Plantar fasciitis;Stress fracture;Rehabilitation4|0|0Updated：2023-02-28 -
Abstract：Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused millions of infections and deaths worldwide since its emergence in December 2019. As there is little or no natural immunity in the human population or specific anti-COVID-19 drugs, researchers from the government, academia and industry are developing vaccines at an unprecedented speed to halt the pandemic. In this review, the results of animal experiments and clinical trials on several vaccine technical platforms are summarized, and several challenges are also discussed to further promote the development, evaluation and application of vaccines during the challenging situation of the global pandemic.Keywords：Severe acute respiratory syndrome coronavirus 2;Coronavirus disease 2019;vaccine;Vaccine candidate;Clinical trials4|0|1Updated：2023-02-28 - Abstract：Microwave radiation has been widely used in various fields, such as communication, industry, medical treatment, and military applications. Microwave radiation may cause injuries to both the structures and functions of various organs, such as the brain, heart, reproductive organs, and endocrine organs, which endanger human health. Therefore, it is both theoretically and clinically important to conduct studies on the biological effects induced by microwave radiation. The successful establishment of injury models is of great importance to the reliability and reproducibility of these studies. In this article, we review the microwave exposure conditions, subjects used to establish injury models, the methods used for the assessment of the injuries, and the indicators implemented to evaluate the success of injury model establishment in studies on biological effects induced by microwave radiation.Keywords：Microwave radiation;Injury model;Biological effects;Methods;Biological indicators;Review4|0|0Updated：2023-02-28
REVIEW
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Abstract：Background:Soft tissue reconstruction is typically conducted after evacuation from theater of operations. If circumstances do not allow timely evacuation, however, defect site may need to be reconstructed in the combat zone.Case presentation:A total of 41 patients with extremity soft tissue defect were treated using pedicled flaps by a single orthopedic surgeon during four deployments in Chad, Afghanistan and Mali between 2010 and 2017. The mean age was 25.6 years. A total of 46 injury sites in extremities required flap coverage: 19 combat-related injuries (CRIs) and 27 non-combat related injuries (NCRIs). Twenty of the injury sites were infected. Overall, 63 pedicled flap transfers were carried out: 15 muscle flaps, 35 local fasciocutaneous flaps and 13 distant fasciocutaneous flaps. The flap types used did not differ for CRIs or NCRIs. Mean follow-up was 71 days. Complications included deep infection (n=6), flap failure (n=1) and partial flap necrosis (n=1). Limb salvage rate was 92.7% (38/41).Conclusions:Soft tissue defect can be managed with simple pedicled flaps in theatre of operations if needed. Basic reconstructive procedures should be part of the training for military orthopedic surgeons.Trial registration:Retrospectively registered in January 2019 (2019-0901-001).Keywords：Pedicled flaps;Limited resources;War surgery;Reconstruction;Training4|0|0Updated：2023-02-28
CASE SERIES
- Abstract：Sepsis is a life-threatening condition that is characterized by multiple organ dysfunction due to abnormal host response to various pathogens, like bacteria, fungi and virus. The differences between viral and bacterial sepsis are indeed of great significance to deepen the understanding of the pathogenesis of sepsis, especially under pandemics of SARS-CoV-2 infection.Keywords：Severe acute respiratory syndrom coronavirus 2;Coronavirus disease 2019;sepsis;bacteria;Virus;infection;Host response6|0|0Updated：2023-02-28
LETTER TO THE EDITOR
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