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The classical manifestation of COVID-19 is pulmonary infection. After host cell entry via human angiotensin-converting enzyme II (hACE2), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can infect pulmonary epithelial cells, especially the AT2 (alveolar type II) cells that are crucial for maintaining normal lung function. However, previous hACE2 transgenic models have failed to specifically and efficiently target the cell types that express hACE2 in humans, especially AT2 cells. In this study, we report an inducible, transgenic hACE2 mouse line and showcase three examples for specifically expressing hACE2 in three different lung epithelial cells, including AT2 cells, club cells, and ciliated cells. Moreover, all these mice models develop severe pneumonia after SARS-CoV-2 infection. This study demonstrates that the hACE2 model can be used to precisely study any cell type of interest with regard to COVID-19-related pathologies.
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COVID-19 , Humanos , Animais , Camundongos , Camundongos Transgênicos , SARS-CoV-2 , Células Epiteliais , Células Epiteliais Alveolares , Modelos Animais de DoençasRESUMO
Carrier-phase noise limits both the performance and the maximum operation range of coherent LiDAR. To address this issue, we propose a carrier-phase-noise-canceled LiDAR based on an auxiliary interferometer and adaptive filters. Compared to previous methods, this approach is calibration-free and offers higher compensation accuracy, as well as applicability of dynamic target detection. Experiments of range-Doppler imaging for stationary targets and rotating extended targets have been performed, and the detection results close to the theoretical resolution were obtained at the round trip distance to the target beyond 981 times and 106 times coherence length, respectively.
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OBJECTIVES: To design a deep learning-based framework for automatic segmentation and detection of intracranial aneurysms (IAs) on magnetic resonance T1 images and test the robustness and performance of framework. METHODS: A retrospective diagnostic study was conducted based on 159 IAs from 136 patients who underwent the T1 images. Among them, 127 cases were randomly selected for training and validation, and 32 cases were used to assess the accuracy and consistency of our algorithm. We developed and assembled three convolutional neural networks for the segmentation and detection of IAs. The segmentation and detection performance of the model were compared with the ground truth, and various metrics were calculated at the voxel level, IAs level, and patient level to show the performance of our framework. RESULTS: Our assembled model achieved overall Dice, voxel-level sensitivity, specificity, balanced accuracy, and F1 score of 0.802, 0.874, 0.9998, 0.937, and 0.802, respectively. A coincidence greater than 0.7 between the aneurysms predicted by the model and the ground truth was considered as a true positive. For IAs detection, the sensitivity reached 90.63% with 0.58 false positives per case. The volume of IAs segmented by our model showed a high agreement and consistency with the volume of IAs labeled by experts. CONCLUSION: The deep learning framework is achievable and robust for IAs segmentation and detection. Our model offers more clinical application opportunities compared to digital subtraction angiography (DSA)-based, CTA-based, and MRA-based methods. CLINICAL RELEVANCE STATEMENT: Our deep learning framework effectively detects and segments intracranial aneurysms using clinical routine T1 sequences, showing remarkable effectiveness and offering great potential for improving the detection of latent intracranial aneurysms and enabling early identification. KEY POINTS: â¢There is no segmentation method based on clinical routine T1 images. Our study shows that the proper deep learning framework can effectively localize the intracranial aneurysms. â¢The T1-based segmentation and detection method is more universal than other angiography-based detection methods, which can potentially reduce missed diagnoses caused by the absence of angiography images. â¢The deep learning framework is robust and has the potential to be applied in a clinical setting.
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PURPOSE: We used Anakinra to inhibit the expression of IL-1ß based on the model of spinal cord injury in the rat stomach and explored whether it had a certain neuroprotective effect after spinal cord injury. MATERIALS AND METHODS: The spinal cord injury model of four segments (T5-T8) was prepared by using vascular clamp. Thirty rats were randomized to the control group and the experimental group, and the control group used normal saline, while the experimental group used Anakinra after spinal cord injury. The spinal cord tissue was extracted at 6 h and 24 h after the operation to carry out the histopathological evaluation and to analyze the contents of IL-1ß and malondialdehyde and the activities of glutathione peroxidase and superoxide dismutase. RESULTS: Edema and inflammatory cell infiltration were obviously seen after spinal cord injury, the IL-1ß level in serum was significantly increased, but the activity of glutathione peroxidase, superoxide dismutase and catalase was decreased in the control group compared with the experimental group. The experimental group could increase the activity of antioxidant enzymes, but had no significant effect on malondialdehyde. CONCLUSIONS: Anakinra had a certain protective effect through the inhibition of IL-1ß on spinal cord injury.
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Regulação da Expressão Gênica/fisiologia , Interleucina-1beta/metabolismo , Sistema Nervoso/metabolismo , Traumatismos da Medula Espinal/patologia , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Glutationa Peroxidase/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Masculino , Malondialdeído/metabolismo , Prognóstico , Ratos , Ratos Wistar , Traumatismos da Medula Espinal/metabolismo , Superóxido Dismutase/metabolismo , Fatores de TempoRESUMO
The study was designed to investigate whether serum hepatitis B virus (HBV) RNA is a strong surrogate marker for intrahepatic HBV covalently closed circular DNA (cccDNA) compared with serum HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg) in HBeAg-positive chronic hepatitis B (CHB) patients. Serum HBV RNA, HBV DNA, HBsAg, HBeAg, and intrahepatic cccDNA were quantitatively detected at baseline (n = 82) and 96 weeks (n = 62) after treatment with nucleos(t)ide analogue (NUC) in HBeAg-positive CHB patients. The correlations among serum HBV RNA, HBV DNA, HBsAg, HBeAg, and intrahepatic cccDNA levels were then statistically analyzed. The results showed that pretreatment intrahepatic cccDNA levels correlated better with serum HBV DNA levels (r = 0.36, P < 0.01) than with serum HBV RNA levels (r = 0.25, P = 0.02), whereas no correlations were found between pretreatment intrahepatic cccDNA levels and HBsAg (r = 0.15, P = 0.17) or HBeAg (r = 0.07, P = 0.56) levels. At 96 weeks after NUC treatment, intrahepatic cccDNA levels correlated well with HBsAg levels (r = 0.39, P < 0.01) but not with serum HBV RNA, HBV DNA, and HBeAg levels (all P > 0.05). Besides, the decline in the intrahepatic cccDNA level from baseline to week 96 correlated better with the reduction in the serum HBsAg levels than with the decreases in the levels of the other markers (for the HBsAg decline, r = 0.38, P < 0.01; for the HBV DNA decline, r = 0.35, P = 0.01; for the HBV RNA decline, r = 0.28, P < 0.05; for the HBeAg decline, r = 0.18, P = 0.19). In conclusion, the baseline serum HBV RNA level or its decline after 96 weeks of NUC therapy correlated with the corresponding intrahepatic cccDNA level, while it was less than that seen with serum HBV DNA at baseline and HBsAg (or its decline) at 96 weeks after treatment, respectively.
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DNA Circular/sangue , DNA Viral/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/diagnóstico , RNA Viral/sangue , Adolescente , Adulto , Antivirais/uso terapêutico , DNA Circular/genética , DNA Viral/genética , Feminino , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/virologia , Humanos , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico , RNA Viral/genética , Adulto JovemRESUMO
OBJECTIVE: To explore the expressions of cancerous inhibitor of protein phosphatase 2A (CIP2A) and osteopontin (OPN) and evaluate their roles in bladder cancer. METHODS: RNA was isolated from 38 cases of patients with bladder cancer and 12 cases of normal bladder tissue by TRIzol method from May 2010 to December 2012. And reverse transcription (RT)-PCR was used to detect the expressions of CIP2A and OPN. The expression levels of CIP2A and OPN in 99 cases of patients with bladder cancer and 12 cases of normal tissue were detected by immunohistochemical staining. RESULTS: The positive expression rate of CIP2A mRNA and OPN mRNA were 76.32% (29/38) and 92.11% (35/38) in bladder cancer while there was no expression in normal tissue (both P < 0.05). The positive rates of CIP2A and OPN protein were 63.64% (63/99)and 84.85% (84/99)in cases of bladder cancer tissues while CIP2A was not detected in normal tissues. The positive expression rate of OPN in normal tissues was 2/12 (both P < 0.05). The CIP2A and OPN proteins were both expressed in 58/99 cases of bladder cancer tissues while neither of them was expressed in 13 cases. In 8 cases, CIP2A was expressed while OPN was not. In another 20 cases, OPN was expressed while CIP2A was not (r = 0.300, P < 0.05). CONCLUSIONS: The expression levels of CIP2A and OPN in tissue of bladder cancer are higher than those of normal controls. And CIP2A and OPN may be used as indicators of biological behaviors and serve as new molecular diagnostic markers for bladder cancer.
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Neoplasias da Bexiga Urinária , Autoantígenos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , Osteopontina , RNA MensageiroRESUMO
OBJECTIVE: To explore the expression of cancerous inhibitor of PP2A (CIP2A) and evaluate its role in bladder cancer. METHODS: RT-PCR was used to detect the expression of CIP2A mRNA from 38 cases of patients with bladder cancer and 12 cases of normal bladder tissue. The CIP2A protein expression levels in 99 cases of patients with bladder cancer and 12 cases of normal tissue was detected by immunohistochemical staining . And the serum contents of CIP2A protein of 38 patients with bladder cancer and 40 normal controls were detected by ELISA. RESULTS: The expression of CIP2A mRNA was detected in 29/38 cases (76.32%) of bladder cancer. And there was no expression in normal tissue (P < 0.05). The positive rate of CIP2A protein was 63.64% in 99 cases of bladder cancer tissues and no expression detected in normal tissues(P < 0.05). ELISA results showed that the serum content of CIP2A in patients with bladder cancer was significantly higher than that in normal controls (median:0.015 2 vs 0.001 8 ng/L, P < 0.05). CONCLUSIONS: The tissue and serum expressions of CIP2A in patients with bladder cancer are higher than those in normal controls. And CIP2A may be used as an indicator of the biological behavior of bladder cancer.
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Neoplasias da Bexiga Urinária , Autoantígenos , Biomarcadores Tumorais , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , RNA MensageiroRESUMO
Metal ion interference therapy (MIIT) has emerged as a promising approach in the field of nanomedicine for combatting cancer. With advancements in nanotechnology and tumor targeting-related strategies, sophisticated nanoplatforms have emerged to facilitate efficient MIIT in xenografted mouse models. However, the diverse range of metal ions and the intricacies of cellular metabolism have presented challenges in fully understanding this therapeutic approach, thereby impeding its progress. Thus, to address these issues, various amplification strategies focusing on ionic homeostasis and cancer cell metabolism have been devised to enhance MIIT efficacy. In this review, the remarkable progress in Fe, Cu, Ca, and Zn ion interference nanomedicines and understanding their intrinsic mechanism is summarized with particular emphasis on the types of amplification strategies employed to strengthen MIIT. The aim is to inspire an in-depth understanding of MIIT and provide guidance and ideas for the construction of more powerful nanoplatforms. Finally, the related challenges and prospects of this emerging treatment are discussed to pave the way for the next generation of cancer treatments and achieve the desired efficacy in patients.
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Introduction: Acute Respiratory Distress Syndrome (ARDS) poses a significant health challenge due to its high incidence and mortality rates. The emergence of SARS-CoV-2 has added complexity, with evidence suggesting a correlation between COVID-19 induced ARDS and post-COVID symptoms. Understanding the underlying mechanisms of ARDS in COVID-19 patients is crucial for effective clinical treatment. Method: To investigate the potential role of ferroptosis in SARS-CoV-2 induced ARDS, we conducted a comprehensive analysis using bioinformatics methods. Datasets from the Gene Expression Omnibus (GEO) were utilized, focusing on COVID-19 patients with varying ARDS severity. We employed weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and single-cell sequencing to identify key genes associated with ferroptosis in ARDS. Hub genes were validated using additional GEO datasets and cell experiment. Result: The analysis discerned 916 differentially expressed genes in moderate/severe ARDS patients compared to non-critical individuals. Weighted Gene Co-expression Network Analysis (WGCNA) unveiled two modules that exhibited a positive correlation with ARDS, subsequently leading to the identification of 15 hub genes associated with ferroptosis. Among the noteworthy hub genes were MTF1, SAT1, and TXN. Protein-protein interaction analysis, and pathway analysis further elucidated their roles. Immune infiltrating analysis highlighted associations between hub genes and immune cells. Validation in additional datasets confirmed the upregulation of MTF1, SAT1, and TXN in SARS-CoV-2-induced ARDS. This was also demonstrated by qRT-PCR results in the BEAS-2B cells vitro model, suggesting their potential as diagnostic indicators. Discussion: This study identifies MTF1, SAT1, and TXN as hub genes associated with ferroptosis in SARS-CoV-2-induced ARDS. These findings provide novel insights into the molecular mechanisms underlying ARDS in COVID-19 patients and offer potential targets for immune therapy and targeted treatment. Further experimental validation is warranted to solidify these findings and explore therapeutic interventions for ARDS in the context of COVID-19.
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COVID-19 , Ferroptose , Perfilação da Expressão Gênica , Síndrome do Desconforto Respiratório , SARS-CoV-2 , Humanos , Ferroptose/genética , COVID-19/genética , COVID-19/imunologia , Síndrome do Desconforto Respiratório/genética , SARS-CoV-2/fisiologia , Transcriptoma , Redes Reguladoras de Genes , Biologia Computacional/métodosRESUMO
Sono-immunotherapy faces challenges from poor immunogenicity and low response rate due to complex biological barriers. Herein, we prepared MCTH nanocomposites (NCs) consisting of disulfide bonds (S-S) doped mesoporous organosilica (MONs), Cu-modified protoporphyrin (CuPpIX), mitochondria-targeting triphenylphosphine (TPP), and CD44-targeting hyaluronic acid (HA). MCTH NCs efficiently accumulate at the tumor site due to the overexpressed CD44 receptors on the membrane of the cancer cells. Under the function of HAase and glutathione (GSH), MCTH degrades and exposes TPP to deliver CuPpIX to the mitochondrial site and induce a reactive oxygen species (ROS) burst in situ under ultrasound irradiations, thereby causing severe mitochondria dysfunction. This cascade-targeting ability of MCTH NCs not only reinforces oxidative stress in cancer cells but also amplifies immunogenic cell death (ICD) to stimulate the body's immune response and alleviate the tumor immunosuppressive microenvironment. These NCs significantly enhance the infiltration of immune cells into the tumor, particularly CD8+ T cells, for a powerful antitumor sono-immunotherapy. The proposed cascade-targeting strategy holds promise for strengthening sono-immunotherapy for prostate cancer treatment and overcoming the limitations of traditional immunotherapy.
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Background: Patients with age-related hearing loss (ARHL) often struggle with tracking and locating sound sources, but the neural signature associated with these impairments remains unclear. Materials and methods: Using a passive listening task with stimuli from five different horizontal directions in functional magnetic resonance imaging, we defined functional regions of interest (ROIs) of the auditory "where" pathway based on the data of previous literatures and young normal hearing listeners (n = 20). Then, we investigated associations of the demographic, cognitive, and behavioral features of sound localization with task-based activation and connectivity of the ROIs in ARHL patients (n = 22). Results: We found that the increased high-level region activation, such as the premotor cortex and inferior parietal lobule, was associated with increased localization accuracy and cognitive function. Moreover, increased connectivity between the left planum temporale and left superior frontal gyrus was associated with increased localization accuracy in ARHL. Increased connectivity between right primary auditory cortex and right middle temporal gyrus, right premotor cortex and left anterior cingulate cortex, and right planum temporale and left lingual gyrus in ARHL was associated with decreased localization accuracy. Among the ARHL patients, the task-dependent brain activation and connectivity of certain ROIs were associated with education, hearing loss duration, and cognitive function. Conclusion: Consistent with the sensory deprivation hypothesis, in ARHL, sound source identification, which requires advanced processing in the high-level cortex, is impaired, whereas the right-left discrimination, which relies on the primary sensory cortex, is compensated with a tendency to recruit more resources concerning cognition and attention to the auditory sensory cortex. Overall, this study expanded our understanding of the neural mechanisms contributing to sound localization deficits associated with ARHL and may serve as a potential imaging biomarker for investigating and predicting anomalous sound localization.
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Scalp high-frequency oscillations (sHFOs) are a promising non-invasive biomarker of epilepsy. However, the visual marking of sHFOs is a time-consuming and subjective process, existing automatic detectors based on single-dimensional analysis have difficulty with accurately eliminating artifacts and thus do not provide sufficient reliability to meet clinical needs. Therefore, we propose a high-performance sHFOs detector based on a deep learning algorithm. An initial detection module was designed to extract candidate high-frequency oscillations. Then, one-dimensional (1D) and two-dimensional (2D) deep learning models were designed, respectively. Finally, the weighted voting method is used to combine the outputs of the two model. In experiments, the precision, recall, specificity and F1-score were 83.44%, 83.60%, 96.61% and 83.42%, respectively, on average and the kappa coefficient was 80.02%. In addition, the proposed detector showed a stable performance on multi-centre datasets. Our sHFOs detector demonstrated high robustness and generalisation ability, which indicates its potential applicability as a clinical assistance tool. The proposed sHFOs detector achieves an accurate and robust method via deep learning algorithm.
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Aprendizado Profundo , Epilepsia , Humanos , Eletroencefalografia/métodos , Couro Cabeludo , Reprodutibilidade dos Testes , Epilepsia/diagnósticoRESUMO
The magneto-electro-elastic (MEE) medium is a typical intelligent material with promising application prospects in sensors and transducers, whose thermal contact response is responsible for their sensitivity and stability. An effective thermal contact model between a moving sphere and a coated MEE medium with transverse isotropy is established via a semi-analytical method (SAM) to explore its thermal contact response. First, a group of frequency response functions for the magneto-electro-thermo-elastic field of a coated medium are derived, assuming that the coating is perfectly bonded to the substrate. Then, with the aid of the discrete convolution-fast Fourier transform algorithm and conjugate gradient method, the contact pressure and heat flux can be determined. Subsequently, the induced elastic, thermal, electric and magnetic fields in the coating and substrate can be obtained via influence coefficients relating the induced field and external loads. With the proposed method, parametric studies on the influence of the sliding velocity and coating property are conducted to investigate the thermal contact behavior and resulting field responses of the MEE material. The sliding velocity and thermal properties of the coating have a significant effect on the thermal contact response of the MEE material; the coupled multi-field response can be controlled by changing the coating thickness between ~0.1 a0 and a0.
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The increase in drug resistance and invasion caused by biofilm formation brings enormous challenges to the management of Candida infection. Aspirin's antibiofilm activity in vitro was discovered recently. The spectrophotometric method and the XTT {2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide} reduction assay used for data generation make it possible to evaluate fungal biofilm growth accurately. The combined use of the most commonly used methods, the fractional inhibitory concentration index (FICI) and a newly developed method, the ΔE model, which uses the concentration-effect relationship over the whole concentration range instead of using the MIC index alone, makes the interpretation of results more reliable. As an attractive tool for studying the pharmacodynamics of antimicrobial agents, time-kill curves can provide detailed information about antimicrobial efficacy as a function of both time and concentration. In the present study, in vitro interactions between aspirin (acetylsalicylic acid [ASA]) and amphotericin B (AMB) against planktonic cells and biofilm cells of Candida albicans and C. parapsilosis were evaluated by the checkerboard microdilution method and the time-kill test. Synergistic and indifferent effects were found for the combination of ASA and AMB against planktonic cells, while strong synergy was found against biofilm cells analyzed by FICI. The ΔE model gave more consistent results with FICI. The positive interactions in concentration were also confirmed by the time-kill test. Moreover, this approach also revealed the pharmacodynamics changes of ASA and synergistic action on time. Our findings suggest a potential clinical use for combination therapy with ASA and AMB to augment activity against biofilm-associated infections.
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Anfotericina B/farmacologia , Antifúngicos/farmacologia , Aspirina/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Testes de Sensibilidade MicrobianaRESUMO
The challenging synthesis of a fused C3-symmetric trilactam (1) was executed in racemic and enantiomerically pure form. The rigidity, symmetry and high density of hydrogen bonding motifs make 1 an attractive candidate for self-assembly study, which revealed different hydrogen bond patterns in the crystals of rac-1-d3 and (+)-(SSS)-1.
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Lactamas , Ligação de Hidrogênio , Lactamas/síntese química , EstereoisomerismoRESUMO
It is difficult to observe the nucleation mechanism of inclusions in real-time. In this study, the nucleation process of zirconium oxide inclusions was systematically studied by classical nucleation theory and first principles. Zr deoxidized steel with 100 ppm Zr addition was processed into metallographic samples for scanning electron microscopy energy-dispersive spectroscopy observation. The electrolytic sample was analyzed by micro X-ray diffraction and transmission electron microscopy, and the zirconium oxide in the sample was determined to be ZrO2. The nucleation rate and radius of the ZrO2 inclusions were calculated by classical nucleation theory, and they were compared with the experimental values. There was a considerable difference between the experimental and theoretical values of the nucleation rate. The effect of the nucleation size was analyzed by first-principles calculation, and the thermodynamic properties of ZrO2 clusters and nanoparticles were analyzed by constructing (ZrO2)n (n = 1-6) clusters. The thermodynamic properties of ZrO2 calculated by first principles were consistent with the values in the literature. Based on two-step nucleation theory, the nucleation pathway of ZrO2 is as follows: Zratom + Oatom â (ZrO2)n â (ZrO2)2 â core (ZrO2 particle)-shell ((ZrO2)2 cluster) nanoparticle â (ZrO2)bulk.
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Coffin-Siris syndrome (CSS) (OMIM #135900) involves multiple congenital malformations, including hypotonia, short stature, sparse scalp hair, a coarse face, prominent eyebrows, a wide mouth, delayed bone age, and hypoplastic or absent fifth fingers/toes or nails, together with developmental delay. The cause of CSS is suggested to be related to alterations in the BRG- or HRBM-associated factor (BAF) pathway in humans. In this gene family, pathogenic variations in the AT-rich interactive domain-containing protein 1B (ARID1B) gene are revealed to be a significant element causing neurodevelopmental disability in patients with CSS. Herein, we describe the clinical features and gene variations in four Chinese patients with CSS. All the patients shared common features of short fifth fingers/toes or hypoplastic nails, coarse facial features, thick eyebrows, long cilia, a flat nasal bridge, a broad nose, a wide mouth, a high palate, and hypotonia. Besides, they had an intellectual disability, language, and motor developmental delay. Candidate genes were screened for variations using polymerase chain reaction (PCR) and sequencing. The variations were sequenced by next-generation sequencing and confirmed by first-generation sequencing. Exome sequencing suggested four de novo variations in the ARID1B gene in four unrelated patients. These included two frameshift variations (c.3581delC, c.6661_6662insG) and two nonsense variations (c.1936C>T, c.2248C>T). Of the four variations, three variations were novel. The results in our present study broaden the understanding of the disease and further interpret the molecular genetic mechanism of these rare variations in CSS.
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Deformidades Congênitas da Mão , Deficiência Intelectual , Micrognatismo , Humanos , Proteínas de Ligação a DNA/genética , Hipotonia Muscular/complicações , Micrognatismo/genética , Micrognatismo/patologia , Deformidades Congênitas da Mão/genética , Deformidades Congênitas da Mão/patologia , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Fatores de Transcrição/genéticaRESUMO
Immunity and inflammation are well established factors in the pathogenesis of pulmonary arterial hypertension (PAH). We aimed to investigate whether dexamethasone (Dex), a potent immunosuppressant, could prevent the development of monocrotaline (MCT)-induced PAH in rats as compared with pyrrolidine dithiocarbamate (PDTC) and its effect on the immune mechanism. PAH in rats (n = 66) was induced by MCT (50 mg/kg) injected intraperitoneally. Two days after MCT treatment, Dex (1.0 mg/kg) and PDTC (100 mg/kg) were administered once daily for 21 days. Samples were collected at 7, 14, and 21 days. Dex effectively inhibited MCT-induced PAH and reduced the T-helper (Th) 1 dominant cytokine response (interferon-γ) but up-regulated the Th2 one (interleukin 4). It increased the number of CD4+ T cells and decreased the number of CD8+ T cells around pulmonary arteries, upregulated the mRNA expression of fractalkine and downregulated that of CX3CR1 in the lung. Serum levels of interferon γ and interleukin 4 did not significantly differ from that of controls. Dex attenuated the process of MCT-induced PAH through its immunomodulatory property. Dex could be an appropriate therapy for PAH, although more studies are needed to define the appropriate treatment regimen.
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Dexametasona/farmacologia , Glucocorticoides/farmacologia , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/prevenção & controle , Monocrotalina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Receptor 1 de Quimiocina CX3C , Quimiocina CX3CL1/genética , Quimiocina CX3CL1/metabolismo , Hipertensão Pulmonar Primária Familiar , Hipertensão Pulmonar/imunologia , Hipertensão Pulmonar/patologia , Interferon gama/sangue , Interferon gama/genética , Interleucina-4/sangue , Interleucina-4/genética , Pulmão/citologia , Pulmão/patologia , Pulmão/fisiologia , Masculino , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Wistar , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismoRESUMO
Forests play a key role in regulating the global carbon cycle, a substantial portion of which is stored in aboveground biomass (AGB). It is well understood that biodiversity can increase the biomass through complementarity and mass-ratio effects, and the contribution of environmental factors and stand structure attributes to AGB was also observed. However, the relative influence of these factors in determining the AGB of Quercus forests remains poorly understood. Using a large dataset retrieved from 523 permanent forest inventory plots across Northeast China, we examined the effects of integrated multiple tree species diversity components (i.e., species richness, functional, and phylogenetic diversity), functional traits composition, environmental factors (climate and soil), stand age, and structure attributes (stand density, tree size diversity) on AGB based on structural equation models. We found that species richness and phylogenetic diversity both were not correlated with AGB. However, functional diversity positively affected AGB via an indirect effect in line with the complementarity effect. Moreover, the community-weighted mean of specific leaf area and height increased AGB directly and indirectly, respectively; demonstrating the mass-ratio effect. Furthermore, stand age, density, and tree size diversity were more important modulators of AGB than biodiversity. Our study highlights that biodiversity-AGB interaction is dependent on the regulation of stand structure that can be even more important for maintaining high biomass than biodiversity in temperate Quercus forests.
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OBJECTIVE: This study aimed to observe the application effect of emergency treatment mode of damage-control orthopedics (DCO) in pelvic fracture complicated with multiple fractures. METHODS: Ninety-four patients with pelvic fracture complicated with multiple fractures in our hospital were recruited and divided into two groups according to the random number table method, with 47 cases in each group. Patients in the control group received traditional methods for emergency treatment (early complete treatment), and patients in the research group received DCO for emergency treatment (treatment performed in stages according to patient's physiological tolerance, with simplified initial surgery, followed by ICU resuscitation, and finally definitive surgery). The two groups were compared in terms of mortality, the incidence of acidosis and hypothermia three days after the first surgery, surgery-related indexes (time of the first surgery, blood transfusion volume, intraoperative blood loss, recovery time of temperature, and length of hospital stay), coagulation function indexes (activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT) and fibrinogen (FIB)), postoperative reduction of fracture, complication rate, and quality of life. RESULTS: The incidences of acidosis, hypothermia, and mortality three days after the first surgery in the research group were lower than those in the control group (P<0.05). Compared with the control group, the research group experienced shorter time of the first surgery, less intraoperative blood transfusion volume, less intraoperative blood loss, shorter recovery time of body temperature, and shorter length of hospital stay (P<0.05). Seven days after surgery, PT, TT and APTT decreased and FIB increased in both groups (P<0.05), PT, TT and APTT in the research group were lower than those in the control group (P<0.05), while FIB was higher (P<0.05). The good rate of reduction in the research group was higher than that in the control group (P=0.025). The incidence of complications in the research group was lower than that in the control group (P=0.049). Six months after surgery, the scores of physiological function (PF), body pain (BP), role physical (RP), emotional function (EF), social function (SF), vitality, and general health (GH) of the research group were higher than those of the control group (P<0.05), but there was no significant difference in mental health (MH) between the two groups (P>0.05). CONCLUSION: The emergency treatment mode of DCO is effective in pelvic fracture complicated with multiple fractures, which can effectively improve postoperative reduction of patients, improve the coagulation function, reduce complications, and improve the quality of life.