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简介：AbstractBackground:Traumatic brain injury, one of the leading causes of death in adults under 40 years of age in the world, is frequently caused by mechanical shock, resulting in diffuse neuronal damage and long-term cognitive dysfunction. Many existing TBI animal models revival with expensive equipment or special room are needed or the processes of operations are complex and not easy to be widely used. Therefore, a simpler TBI model needs to be designed.Methods:Our TBI model is an innovation of the modeling method through air guns shutting rubber bullets. A core facet is the application of our designed rubber bullet impact device. It could focus the hitting power to the fixed site of the brain, thus triggering a mild closed head injury. Moreover, the degree of damage can be adjusted by the times of shots.Results:Our model induced blood-brain barrier leakage and diffused neuronal damage. Besides, it led to an increased level of Tau phosphorylation and resulted in cognitive dysfunction within several weeks post-injury.Conclusion:Our TBI model is not only simple and time-saving but also can simulate mild brain injuries in clinical. It is suitable for exploring pathobiological mechanisms as well as a screening of potential therapies for TBI.

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简介：AbstractPurpose:Traumatic brain injury (TBI) is one of the leading causes of disability and death in modern times, whose evaluation and prognosis prediction have been one of the most critical issues in TBI management. However, the existed models for the abovementioned purposes were defective to varying degrees. This study aims to establish an ideal brain injury state clinical prediction model (BISCPM).Methods:This study was a retrospective design. The six-month outcomes of patients were selected as the end point event. BISCPM was established by using the split-sample technology, and externally validated via different tests of comparison between the observed and predicted six-month mortality in validating group. TBI patients admitted from July 2006 to June 2012 were recruited and randomly divided into establishing model group and validating model group. Twenty-one scoring indicators were included in BISCPM and divided into three parts, A, B, and C. Part A included movement, pupillary reflex and diameter, CT parameters, and secondary brain insult factors, etc. Part B was age and part C was medical history of the patients. The total score of part A, B and C was final score of BISCPM.Results:Altogether 1156 TBI patients were included with 578 cases in each group. The score of BISCPM from validating group ranged from 2.75 to 31.94, averaging 13.64 ± 5.59. There was not statistical difference between observed and predicted mortality for validating group. The discrimination validation showed that the BISCPM is superior to international mission for prognosis and analysis of clinical trials (IMPACT) lab model.Conclusion:BISCPM is an effective model for state evaluation and prognosis prediction of TBI patients. The use of BISCPM could be of great significance for decision-making in management of TBI.

简介：AbstractObjective:Pseudoxanthoma elasticum (PXE) is a multisystem heritable disorder caused by mutations in the Abcc6 gene. The disease is characterized by ectopic mineralization of the skin, eyes, and arterial blood vessels. Previous studies have suggested that cardiovascular complications in patients with PXE are caused in part by premature atherosclerosis. The aim of this study is to determine the effect of an atherogenic diet on ectopic mineralization.Methods:We used Abcc6tm1JfK mice (Abcc6-/- mice) as an established preclinical model of PXE. The offspring at age of 4 weeks were divided into two groups and fed the standard control laboratory diet (control group) and the atherogenic diet. Serum lipid profiles and bile acids were measured, and steatosis and tissue mineralization were evaluated by histopathologic analysis and chemical calcium quantification assay, respectively.Results:After 50-58 weeks of feeding an atherogenic diet, the concentrations of total cholesterol, low-density lipoprotein/very-low-density lipoprotein cholesterol, and bile acids were significantly higher in the Abcc6-/- mice on the atherogenic diet (180.9 ± 14.8 g/L, 145.9 ± 12.9 g/L, and 9.7 ± 1.4 μmol/L, respectively) than in Abcc6-/- mice on a control diet (85.2 ± 4.8 g/L, 25.1 ± 5.5 g/L, and 3.3 ± 0.5 μmol/L, respectively) (P < 0.001). Hypercholesterolemia was accompanied by extensive lipid accumulation in the liver and aorta, a characteristic feature of steatosis. The direct calcium assay demonstrated significantly increased mineralization of the muzzle skin containing the dermal sheath of vibrissae (57.2 ± 4.4 μmol Ca/gram tissue on the atherogenic diet and 43.9 ± 2.2 μmol Ca/gram tissue on control diet; P < 0.01), a reproducible biomarker of the ectopic mineralization process in these mice. An increased frequency of mineralization was also observed in the kidneys and eyes of mice on the atherogenic diet (P < 0.01).Conclusion:These observations suggest that the atherogenic diet caused hypercholesterolemia and accelerated ectopic mineralization in the Abcc6-/- mice. Our findings have clinical implications for patients with PXE, a currently intractable disorder with considerable morbidity and occasional mortality.

简介：AbstractBackground:As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. The virus was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020. This study aimed to develop a mathematical model for calculating the transmissibility of the virus.Methods:In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probably be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market (reservoir) to people, we simplified the model as Reservoir-People (RP) transmission network model. The next generation matrix approach was adopted to calculate the basic reproduction number (R0) from the RP model to assess the transmissibility of the SARS-CoV-2.Results:The value of R0 was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58.Conclusions:Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea.

简介：AbstractObjective:Altered bile acid transformation induces low-grade chronic inflammation and may play an important role in the pathophysiology of polycystic ovary syndrome (PCOS). Liquiritincan regulate bile acid metabolism and anti-inflammatory properties; however, limited information is available regarding its therapeutic potential in PCOS.Methods:Female C57BL/6 mice were randomly assigned into four groups (n = 6 mice/group): the control, letrozole or dehydroepiandrosterone-induced PCOS groups, PCOS + 20 mg/kg liquiritin group, and control + liquiritin groups. After 21 days of treatment, the mice were euthanized, and the associated metabolism indications were investigated. Ovarian histological examinations were performed, and serum hormone concentration was measured. The expression of key genes involved in steroid hormone synthesis, ovarian follicle development, and ovulation was assessed.Results:Liquiritin reduced fasting blood glucose levels and increased insulin sensitivity compared to the PCOS group. Liquiritin also significantly decreased serum levels of total testosterone (P < 0.001) and dehydroepiandrosterone sulfate (P < 0.05) in the PCOS group. Histomorphological inspection of ovaries from the liquiritin group revealed fewer cystic dilated follicles than in the PCOS group. Moreover, liquiritinsignificantly (P < 0.01) decreased Cyp17a1, Cyp19a1, Fshr, Hsd3b2, Runx2, and Ccn2 mRNA expression compared to letrozole-induced PCOS.Conclusion:Liquiritin may be safe and helpful in ameliorating PCOS-associated hyperandrogenemia and hyperglycemia. However, clinical trials investigating different liquiritin dosages are needed to confirm these findings.

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简介：AbstractThe treatment of severe trauma, especially multiple injuries, requires multidisciplinary collaboration. The current study aims to highlight the challenges of consultation mode for severe trauma in general hospitals and emphasizes the need to create a new temporary-sustainable team. It suggests developing an information consultation mode and enforcing the fine management to improve the quality and safety of the medical treatment. The management mode of a temporary-sustainable team will reduce the cost and improve the treatment efficiency. Overall, a temporary-sustainable team has significant advantages over a traditional multidisciplinary team for severe trauma treatment.

简介：AbstractBackground:A deep learning model (DLM) that enables non-invasive hypokalemia screening from an electrocardiogram (ECG) may improve the detection of this life-threatening condition. This study aimed to develop and evaluate the performance of a DLM for the detection of hypokalemia from the ECGs of emergency patients.Methods:We used a total of 9908 ECG data from emergency patients who were admitted at the Second Affiliated Hospital of Nanchang University, Jiangxi, China, from September 2017 to October 2020. The DLM was trained using 12 ECG leads (lead I, II, III, aVR, aVL, aVF, and V1-6) to detect patients with serum potassium concentrations <3.5 mmol/L and was validated using retrospective data from the Jiangling branch of the Second Affiliated Hospital of Nanchang University. The blood draw was completed within 10 min before and after the ECG examination, and there was no new or ongoing infusion during this period.Results:We used 6904 ECGs and 1726 ECGs as development and internal validation data sets, respectively. In addition, 1278 ECGs from the Jiangling branch of the Second Affiliated Hospital of Nanchang University were used as external validation data sets. Using 12 ECG leads (leads I, II, III, aVR, aVL, aVF, and V1-6), the area under the receiver operating characteristic curve (AUC) of the DLM was 0.80 (95% confidence interval [CI]: 0.77-0.82) for the internal validation data set. Using an optimal operating point yielded a sensitivity of 71.4% and a specificity of 77.1%. Using the same 12 ECG leads, the external validation data set resulted in an AUC for the DLM of 0.77 (95% CI: 0.75-0.79). Using an optimal operating point yielded a sensitivity of 70.0% and a specificity of 69.1%.Conclusions:In this study, using 12 ECG leads, a DLM detected hypokalemia in emergency patients with an AUC of 0.77 to 0.80. Artificial intelligence could be used to analyze an ECG to quickly screen for hypokalemia.

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简介：AbstractObjective:To develop a downloadable three-dimensional (3D) study tool of the membranous labyrinth in order to facilitate the study of benign paroxysmal positional vertigo (BPPV).Background:The diagnosis and treatment of BPPV depend on an understanding of the anatomy of the vestibular labyrinth and its position relative to the head. To date, many illustrations have been made to explain principles of diagnosis and treatment of BPPV, but few have been based on anatomical studies of the membranous labyrinth.Methods:A previously reported 3D model of a human labyrinth was transposed to a 3D development software to allow the creation of markers along the semicircular ducts and utricle. These markers represent otoliths at different positions during movement of the model within the 3D environment. User-friendly tools were created to navigate the model, to allow clear documentation and communication of studied problems, and to study the model across relevant planes. The final model can be downloaded and is available for general useat https://bppvviewer.com/download/.Results:The model allows visualization of true membranous labyrinth anatomy in both ears simultaneously. The dependent portion of each semicircular duct, the planes of the cristae, and the position of the utricle can easily be visualized in any head position. Moveable markers can mark the expected progress of otolith debris with changes in head position and images can be captured to document simulations in various draw styles.Conclusion:This simple model could offer insights that lead to more accurate diagnosis and treatment of BPPV. It may also be useful as a tool to teach BPPV.

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简介：AbstractBackground:The relationship between macrocirculation and microcirculation remains controversial. The loss of coherence between microcirculation and macrocirculation has already been found in late-stage sepsis shock. The objective of this study was to determine the earliest possible time of detecting the loss of coherence between microcirculation and macrocirculation in early-stage endotoxemic shock.Methods:We randomized 24 female New Zealand white rabbits into two groups: endotoxemic shock group (n = 14) and control group (n= 10). Rabbits in the endotoxemic shock group were equipped with arterial and venous catheters and received an intravenous infusion of Escherichia coli lipopolysaccharide (LPS, 2 mg/kg over 10 min). Rabbits in the control group received the same dose of saline infusion. Microcirculatory perfusion parameters were assessed in the sublingual mucosa using sidestream dark-field video microscopy. Systemic hemodynamics and blood lactate levels were measured at baseline and over a 120-min period.Results:Ninety minutes after completing LPS infusion, all animals in the endotoxemic shock group developed a hypodynamic septic condition, characterized by low cardiac output and increased systemic vascular resistance; 120 min after completing LPS infusion, the mean arterial pressure decreased by 25% (P = 0.01), confirming ongoing endotoxemic shock. However, significant decreases in sublingual microcirculatory parameters of small vessels (microvascular flow index, perfused vessel density, and proportion of small perfused vessels) were observed 30 min after completing LPS infusion (P = 0.01, for all), and threshold decreases of 30% were found 60 min after completing LPS infusion (P = 0.001, for all) in the endotoxemic shock group. Lactate levels significantly increased to more than 2 mm/L at 90 min and more than 4 mm/L at 120 min in the endotoxemic shock group (P = 0.02 and P = 0.01, respectively).Conclusions:Changes in microcirculatory perfusion precede changes in macrocirculation and lactate levels in a rabbit model of endotoxemia shock. Microcirculation, macrocirculation, and oxygen metabolism are distinct in early-stage endotoxic shock.

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简介：AbstractBackground:Computed tomography images are easy to misjudge because of their complexity, especially images of solitary pulmonary nodules, of which diagnosis as benign or malignant is extremely important in lung cancer treatment. Therefore, there is an urgent need for a more effective strategy in lung cancer diagnosis. In our study, we aimed to externally validate and revise the Mayo model, and a new model was established.Methods:A total of 1450 patients from three centers with solitary pulmonary nodules who underwent surgery were included in the study and were divided into training, internal validation, and external validation sets (n = 849, 365, and 236, respectively). External verification and recalibration of the Mayo model and establishment of new logistic regression model were performed on the training set. Overall performance of each model was evaluated using area under receiver operating characteristic curve (AUC). Finally, the model validation was completed on the validation data set.Results:The AUC of the Mayo model on the training set was 0.653 (95% confidence interval [CI]: 0.613-0.694). After re-estimation of the coefficients of all covariates included in the original Mayo model, the revised Mayo model achieved an AUC of 0.671 (95% CI: 0.635-0.706). We then developed a new model that achieved a higher AUC of 0.891 (95% CI: 0.865-0.917). It had an AUC of 0.888 (95% CI: 0.842-0.934) on the internal validation set, which was significantly higher than that of the revised Mayo model (AUC: 0.577, 95% CI: 0.509-0.646) and the Mayo model (AUC: 0.609, 95% CI, 0.544-0.675) (P < 0.001). The AUC of the new model was 0.876 (95% CI: 0.831-0.920) on the external verification set, which was higher than the corresponding value of the Mayo model (AUC: 0.705, 95% CI: 0.639-0.772) and revised Mayo model (AUC: 0.706, 95% CI: 0.640-0.772) (P < 0.001). Then the prediction model was presented as a nomogram, which is easier to generalize.Conclusions:After external verification and recalibration of the Mayo model, the results show that they are not suitable for the prediction of malignant pulmonary nodules in the Chinese population. Therefore, a new model was established by a backward stepwise process. The new model was constructed to rapidly discriminate benign from malignant pulmonary nodules, which could achieve accurate diagnosis of potential patients with lung cancer.

简介：AbstractPurpose:To develop animal models of penetrating thoracic injuries and to observe the effects of the animal model-based training on improving the trainees’ performance for emergent and urgent thoracic surgeries.Methods:With a homemade machine, animal models of lung injuries and penetrating heart injuries were produced in porcine and used for training of chest tube drainage, urgent sternotomy, and emergent thoracotomy. Coefficient of variation of abbreviated injury scale and blood loss was calculated to judge the reproducibility of animal models. Five operation teams from basic-level hospitals (group A) and five operation teams from level III hospitals (group B) were included to be trained and tested. Testing standards for the operations were established after thorough literature review, and expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards. Tests were carried out after the training. Pre- and post-training performances were compared. Post-training survey using 7-point Likert scale was taken to evaluate the feelings of the trainees to these training approaches.Results:Animal models of the three kinds of penetrating chest injuries were successfully established and the coefficient of variation of abbreviated injury scale and blood loss were all less than 25%. After literature review, testing standards were established, and expert questionnaire results showed that the scientific score was 7.30 ± 1.49, and the feasibility score was 7.50 ± 0.89. Post-training performance was significantly higher in both group A and group B than pre-training performance. Post-training survey showed that all the trainees felt confident in applying the operations and were generally agreed that the training procedure were very helpful in improving operation skills for thoracic penetrating injury.Conclusions:Animal model-based simulation training established in the current study could improve the trainees’ performance for emergent and urgent thoracic surgeries, especially of the surgical teams from basic-level hospitals.

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简介：AbstractObjective:Mifepristone (RU486), one of the most common medications for artificial abortion, attenuates the immunoregulatory effects of progesterone. However, the specific immune regulatory mechanism of RU486 in abortion remains unknown. We intended to investigate the immunomodulatory effects of RU486 on abortion.Methods:Sixty female mice were divided into the control group (0 mg RU486) and RU486 group (2 mg/kg RU486). The uterus, peripheral blood, and spleen were obtained for isolation of specific cell types. The population and phenotype of immune cells in the decidua, peripheral blood, and spleen were analyzed using flow cytometry. Statistical differences between groups were determined using two-tailed t-test. For all statistical tests, P < 0.05 was considered statistically significant.Results:RU486 effectively induced abortion in pregnant mice, with a significantly higher number of decidual macrophages (dMφ) (control group = 25.55% ± 2.467%, RU486 group = 19.41% ± 1.423%; P < 0.05), especially the major histocompatibility complex IIhigh subset. No difference in Mφ number was observed in the spleen or peripheral blood. Moreover, the dMφ from mice with RU486-induced abortion displayed a remarkable activated phenotype, with increased expressions of inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin (IL)-12 but decreased expressions of arginase-1 and IL-10. We also found elevated levels of decidual CD4+ T-cells in the RU486 group that exhibited a higher level of the proinflammatory cytokine interferon-γ and a lower level of the anti-inflammatory cytokines, IL-4 and IL-10.Conclusions:We report a new mechanism of RU486-induced abortion via the regulation of innate cell Mφ activation and the adaptive response of CD4+ T-cells present in the decidua but not the periphery.

简介：AbstractBackground:As COVID-19 makes its way around the globe, each nation must decide when and how to respond. Yet many knowledge gaps persist, and many countries lack the capacity to develop complex models to assess risk and response. This paper aimed to meet this need by developing a model that uses case reporting data as input and provides a four-tiered risk assessment output.Methods:We used publicly available, country/territory level case reporting data to determine median seeding number, mean seeding time (ST), and several measures of mean doubling time (DT) for COVID-19. We then structured our model as a coordinate plane with ST on the x-axis, DT on the y-axis, and mean ST and mean DT dividing the plane into four quadrants, each assigned a risk level. Sensitivity analysis was performed and countries/territories early in their outbreaks were assessed for risk.Results:Our main finding was that among 45 countries/territories evaluated, 87% were at high risk for their outbreaks entering a rapid growth phase epidemic. We furthermore found that the model was sensitive to changes in DT, and that these changes were consistent with what is officially known of cases reported and control strategies implemented in those countries.Conclusions:Our main finding is that the ST/DT Model can be used to produce meaningful assessments of the risk of escalation in country/territory-level COVID-19 epidemics using only case reporting data. Our model can help support timely, decisive action at the national level as leaders and other decision makers face of the serious public health threat that is COVID-19.