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ObjectiveTo construct and validate a clinical prediction model for diabetic kidney disease （DKD） based on optical coherence tomography angiography （OCTA）. MethodsThis study enrolled 567 diabetes patients. The random forest algorithm as well as logistic regression analysis were applied to construct the prediction model. The model discrimination and clinical usefulness were evaluated by receiver operating characteristic curve （ROC） and decision curve analysis （DCA）， respectively. ResultsThe clinical prediction model for DKD based on OCTA was constructed with area under the curve （AUC） of 0.878 and Brier score of 0.11. ConclusionsThrough multidimensional verification， the clinical prediction nomogram model based on OCTA allowed for early warning and advanced intervention of DKD.
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ObjectiveTo decipher the mechanism of Danshenyin in regulating platelet activation in the rat model of hyperlipidemia by means of proteomics and molecular biology. MethodWistar rats were randomized into blank， model， and Danshenyin groups （n=10） according to the blood lipid level. The rats in the blank group were fed with a basic diet， and those in the model and Danshenyin groups with a high-fat diet. All the rats had free access to water and food. The treatment began at the 9th week. The rats in the Danshenyin group were administrated with Danshenyin by gavage at a crude drug dose of 3.6 g·kg-1. The rats in the model and blank groups were administrated with an equal volume of normal saline according to body weight. At the 12th week， the tissue samples were collected for the measurement of related indicators， and the blood lipid level was measured by an automatic biochemical analyzer. The whole blood viscosity and plasma viscosity were measured by an automatic hemorheometer. The platelet proteome was determined by liquid chromatography-mass spectrometry. Western blotting was employed to determine the protein levels of platelet membrane glycoprotein 4 （CD36）， focal adhesion kinase （FAK）， phosphatidylinositol 4-phosphate 5-kinase （PIP5K）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， protein kinase B （Akt）， and phosphorylated protein kinase B （p-Akt）. ResultCompared with the model group， Danshenyin lowered the levels of total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） in the plasma （P<0.05）， elevated the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）， and reduced the platelet aggregation rate （P<0.05）. Compared with the blank group， the modeling up-regulated the expression of 44 proteins and down-regulated the expression of 12 proteins. Compared with the model group， Danshenyin up-regulated the expression of 21 proteins and down-regulated the expression of 22 proteins. Compared with the blank group， Danshenyin up-regulated the expression of 31 proteins and down-regulated the expression of 49 proteins. The gene ontology （GO） functional enrichment showed that the differentially expressed proteins were mainly involved in cholesterol transport and efflux， production of cytokines， dyslipidemia， and platelet activation. The Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment showed that the differentially expressed proteins were mainly involved in ECM-receptor interaction， peroxisome proliferators-activated receptors （PPAR）， focal adhesion， and PI3K/Akt signaling pathways. Danshenyin can significantly down-regulate the expression of CD36， FAK， PIP5K， PI3K， p-Akt （Ser473）， and p-Akt1/2/3 （Thr308）. ConclusionDanshenyin can restore the blood lipid level of hyperlipidemia rats and inhibit the platelet activation caused by abnormal lipid levels by down-regulating the CD36/PI3K/Akt signal cascade.
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Objective To analyze the differences of von Mises stress distribution in knee cartilage and meniscus in female with generalised joint hypermobility (GJH) and healthy female during drop jump landing. Methods The kinematic and ground reaction force (GRF) characteristics of knee joint in female with GJH and healthy female at the moment of peak vertical GRF (VGRF) during loading phase of drop jump landing were collected. The knee joint reaction force was calculated via inverse dynamics, and the combined force of knee joint along long axis of the femur was applied as the load. Based on three-dimensional (3D) finite element model of a female knee joint, numerical simulations were performed separately during drop jump landing of subjects in two groups, and von Mises stresses and stress distribution of knee cartilage and meniscus were calculated. Results At the moment of peak VGRF during drop jump landing, knee flexion and valgus angles in GJH group and control group showed a statistical significance (P<0. 05). Compared with control group, knee flexion angle decreased and valgus angle increased in GJH group. During drop jump landing, GJH group bore larger stress inside the knee joint, and stress distribution in weight-bearing areas of the medial and lateral tibiofemoral compartments was uneven, while the lateral femoral cartilage lateral condyle, the anterior and middle lateral of lateral tibial cartilage, the anterior angle and body lateral margin of lateral meniscus were stress concentration sites. Conclusions For females with GJH, the stability of knee joint decreases and force lines change in jumping events, due to the increased range of motion of knee joint and relaxation of joint capsule, which increases the risk of cartilage and meniscal injury in lateral knee joint. During jumping sports, females with GJH should especially prevent knee joint injury caused by altered force lines in frontal plane of knee joint.
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OBJECTIVE To investigate the effects and mechanism of Danshen decoction influencing platelet physiological characteristics and function in hyperlipidemia model rats based on platelet membrane glycoprotein 4 （CD36）/phosphatidylinositol 3- kinase （PI3K）/protein kinase B （Akt） signaling pathway. METHODS The hyperlipidemia model rats were induced by feeding high- fat diet， and then randomly divided into model group， simvastatin group （0.004 g/kg）， Danshen decoction high-dose and low-dose groups （3.6， 0.9 g/kg）， and blank group （fed with basic feed）， with 10 rats in each group. Rats in each administration group were intragastrically administered with corresponding drugs every day， and the other groups were intragastrically administered with equal volume of normal saline for 4 weeks. After the last administration， the contents of blood lipid biochemical indexes [total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）]， whole blood viscosity， plasma viscosity and fibrinogen （FIB）content in plasma， platelet-related parameters [platelet count （PLT）， platelet distribution width （PDW） and mean plateletvolume （MPV）] were detected. The levels of plateletphysiological characteristics and function-related factors [von Willebrand factor （vWF）， fibronectin （Fn）， phospholipase A2（PLA2）， thromboxane B2 （TXB2）， 6-keto-prostaglandin F1α （6-keto-PGF1α）， thromboxane A2 （TXA2）， prostaglandin I2 （PGI2）， cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， β-thromboglobulin （β-TG）]， platelet aggregation rate （maximum aggregation rate， 60 s aggregation rate， 180 s aggregation rate） and fibrinolytic system-related factors [tissue plasminogen activator （t-PA）， plasminogen activator inhibitor 1 （PAI-1）] and the expressions of CD36/PI3K/Akt signaling pathway-related proteins [CD36， focal adhesion kinase （FAK）， phosphatidylinositol 4-phosphate 5-kinase （PIP5K）， PI3K， phosphorylated Akt （p-Akt）， p-Akt1/2/3] in platelet were all determined. RESULTS Compared with blank group， the contents of TC， TG and LDL-C in plasma， whole blood viscosity， plasma viscosity， the plasma levels of FIB， PLT， MPV， vWF， Fn， PLA2， TXB2， TXA2， cGMP and β-TG， maximum platelet aggregation rate， 60 s aggregation rate， the expressions of PAI-1 in plasma， protein expressions of CD36， FAK， PIP5K， PI3K， p-Akt and p-Akt1/2/3 were significantly increased in the model group （P＜0.05）. The content of HDL-C and the levels of 6-keto-PGF1α， PGI2 and t-PA were significantly decreased （P＜0.05）. After the intervention of Danshen decoction， most of the above indexes were significantly reversed （P＜0.05）. CONCLUSIONS Danshen decoction can improve the physiological characteristics and function of platelets in hyperlipidemia model rats， and its mechanism may be related to the down-regulation of CD36/PI3K/Akt signaling pathway activity and the reduction of platelet activation.
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Objective@#To explore the association between digital devices usage and body weight overestimation in children and adolescents aged 7-18, in order to provide a scientific basis for body weight overestimation prevention in children and adolescents.@*Methods@#Based on the data of the Research Special Project for Public Welfare Industry of Health using stratified cluster sampling method in 2012, a tatal of 40 073 children and adolescents from 7 provinces with complete information were chosen. Ordinal multivariable Logistic regression model estimated the association between digital devices usage and body weight overestimation.@*Results@#A total of 4 276(11.8%) students with overestimation of body weight were detected, who spent >300 min/d time in digital devices(5.12%) than others (3.84%)( χ 2=19.14, P <0.01). Univariate analysis showed that students with time spent on digital devices >300 min/d had a higher risk in overestimation of body weight ( OR=1.36,95%CI=1.18-1.57,P <0.01) compared with students who spent on digital devices≤120 min/d. There was still a significant association after confounder adjustment ( OR=1.28, 95%CI= 1.10-1.48,P <0.05). Stratified analysis showed that the association between digital devices usage and overestimation of body weight were only observed in girls, 11-18 years old and non single child( P <0.05).@*Conclusion@#The time usage of digital devices is associated with overestimation of body weight in children and adolescents. It may helpful for children and adolescents to prevent overestimation of body weight by reducing time spent on digital devices.
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Objective:To investigate whether microRNA-21-5p (miR-21-5p) alleviates hyperoxia-induced acute lung injury (HALI) through activating the phosphatidylinositol 3 kinase/serine-threonine protein kinase (PI3K/Akt) signaling pathway by regulating apoptosis of type Ⅱ alveolar epithelial cell (AECⅡ).Methods:Seventy-two male Sprague-Dawley (SD) rats were divided into normozone-controlled group, HALI group, PI3K/Akt signaling pathway inhibitor LY294002+HALI group (LY+HALI group), miR-21-5p overexpression+LY294002+HALI group (miR-21-5p+LY+HALI group), miR-21-5p overexpression+HALI group (miR-21-5p+HALI group), and dimethyl sulfoxide (DMSO)+HALI group by random number table method with 12 rats in each group. Animal models of HALI were prepared using 95% concentrations of oxygen. The animals in the normozone-controlled group were fed normally under normoxia. Transfection of lung tissue by miR-21-5p adeno-associated viral vector AAV6-miR-21-5p was performed by instillation of 200 μL titer (1×10 12 TU/mL) through a tracheal catheter 3 weeks prior to modeling. DMSO and LY294002 were administered via the tail vein at 0.3 mg/kg 1 hour before modeling. After 48 hours of modeling, carotid artery blood was collected to detect oxygenation index (OI) and respiratory index (RI), and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect miR-21-5p expression. Lung tissue was collected, and the levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA), and the ratio of pulmonary wet/dry weight (W/D) was determined, and the pathological changes of lung histopathology were observed under the light microscopy after hematoxylin-eosin (HE) staining. Each group was purified AECⅡ cells from 6 rats, the apoptosis rate was detected by flow cytometry, and the expression levels of phosphatase and tensin homologous gene (PTEN), and proteins from the PI3K/Akt signaling pathway were detected by Western blotting. Results:Compared with the normozone-controlled group, alveolar septal thickening and massive inflammatory cell infiltration were found after hyperoxia exposure, RI, inflammatory factors, lung W/D ratio, pathological score, AECⅡ cells early apoptosis rate, PTEN protein expression and phosphorylation level of Akt were increased, while OI and miR-21-5p expression were decreased, indicating the successful preparation of the model. After pretreatment, LY294002 could aggravate the pathological injury of lung tissue in HALI rats, RI, inflammatory factors and lung W/D ratio were further increased, and OI was further reduced compared with HALI group. At the same time, it could promote the AECⅡ cell apoptosis, further up-regulate the expression of PTEN, and reduce the phosphorylation of Akt. However, miR-21-5p pretreatment could negatively regulate PTEN, activate PI3K/Akt signal pathway, inhibit AECⅡ cell apoptosis, and reduce HALI, which was shown by the decreased level of inflammatory factors in miR-21-5p+LY+HALI group compared with LY+HALI group [TNF-α (μg/L): 100.33±3.48 vs. 116.55±2.53, IL-6 (ng/L): 141.06±3.70 vs. 161.31±3.59, IL-1β (μg/L): 90.82±3.69 vs. 112.23±2.87, all P < 0.05], RI, lung injury pathology score, lung W/D ratio, and AECⅡ cell early apoptosis rate were significantly decreased [RI: 0.81±0.02 vs. 1.05±0.07, pathology score: 0.304±0.008 vs. 0.359±0.007, lung W/D ratio: 5.29±0.03 vs. 5.52±0.08, apoptosis rate: (27.20±2.34)% vs. (34.17±1.49)%, all P < 0.05], OI and expressions of miR-21-5p were significantly increased [OI (mmHg, 1 mmHg≈0.133 kPa): 266.71±2.75 vs. 230.12±4.04, miR-21-5p (2 -ΔΔCt): 2.21±0.13 vs. 0.33±0.03, both P < 0.05], and PTEN protein expression in AECⅡ cell was significantly reduced (PTEN/GAPDH: 0.50±0.06 vs. 0.93±0.06, P < 0.05), and phosphorylation level of Akt was significantly increased [phosphorylated Akt (p-Akt) protein (p-Akt/GAPDH): 0.86±0.05 vs. 0.56±0.06, P < 0.05]. Conclusion:miR-21-5p attenuates HALI by inhibiting AECⅡ cell apoptosis, possibly through negative regulation of PTEN to activate PI3K/Akt signaling pathway.
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Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4+ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8+ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.
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Mitophagy is the selective degradation of damaged mitochondria, and it is of great significance to maintain the normal quantity and quality of mitochondria to ensure cell homeostasis and survival. Necroptosis is a type of programmed cell necrosis that can be induced by excessive mitophagy. Reactive oxygen species (ROS) are produced mainly by mitochondria and can damage mitochondria. Hyperoxic acute lung injury (HALI) is a serious complication of clinical oxygen therapy, and its pathogenesis is not clear. Existing studies have shown that mitophagy and necroptosis are involved in the occurrence of HALI. There are many mechanisms regulating mitophagy and necroptosis, including tumor necrosis factor-α (TNF-α), E3 ubiquitin protein ligase (PINK1/Parkin) protein pathway encoded by PTEN-induced kinase 1/PARK2 gene, phosphoglycerate mutase 5 (PGAM5), etc. PGAM5 has been proved to be a key factor linking mitophagy and necroptosis. Previous studies of our team found that the mechanism of microRNA-21-5p (miR-21-5p) alleviating HALI was related to its pGAM5-mediated inhibition of mitophagy, but the mechanism of PGAM5-mediated mitophagy and necroptosis remains unclear. Therefore, this paper reviews the targets of PGAM5-mediated mitophagy and necroptosis, in order to find clues of lung protection of pGAM5-mediated mitophagy and necroptosis in HALI, and provide theoretical basis for subsequent basic research.
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【Objective】 The loss of iron stores is well documented in whole blood donors, and a large number of studies have confirmed that blood donors are at risk of iron deficiency. With the development of apheresis donation, more and more attention has been paid to the health of apheresis donors. However, little is known about the iron status of apheresis donors. In recent 10 years, iron status of apheresis donors has been studied at home and abroad, and iron deficiency was found common among them. There is no systematic study concerning apheresis donors iron deficiency at present. This article summarizes the literature, concerning the principles and preventive measures about iron deficiency in apheresis donors, and aims at improving the recruitment strategy and providing high-quality service for donors.
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【Objective】 To construct an index framework for the evaluation of blood service system resilience under emergency support, and improve the ability of blood centers to deal with emergencies. 【Methods】 The contents of evaluation index system were preliminarily determined through the literature analysis. The Delphi method and analytic hierarchy process(AHP) were used. Experts in relevant fields were consulted to determine the resilience evaluation of indicator framework. Six experts were invited to score the weight of resilience index and finally determined the weight of the index. 【Results】 The resilience evaluation index framework of blood service was established with 5 first-level indicators and 22 second-level indicators. The weights of first-level indicators economic resilience, social resilience, infrastructure resilience, organizational resilience and process resilience were 0.140, 0.071, 0.156, 0.225 and 0.408, respectively. 【Conclusion】 The established evaluation index framework of blood service system resilience is scientific, which provides a reference basis for evaluating the resilience of blood service system.
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To understand the current situation, progress, main contents, and the relevant assessment tools of family care in palliative for pediatric oncology patients, this paper reviewed the relevant literature on family care in palliative for pediatric oncology patients and its assessment tools at home and abroad. Taking family care in palliative care as the starting point, this paper discussed the effect of effective family care on improving the treatment outcome, quality of life, prognosis of pediatric oncology patients and the psychological problems of their families, and to provide a basis for continuing to improve the hospital-family-community care model for pediatric oncology patients, bringing into play the active role of family in palliative care, and promoting the continued development of family care for pediatric oncology patients.
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Pancreatic cancer is one of the most aggressive malignancies. The poor prognosis of pancreatic cancer patients is mainly attributed to low diagnostic rate at the early stage, highly aggressive nature coupled with the inadequate efficacy of current chemotherapeutic regimens. Novel therapeutic strategies are urgently needed for pancreatic cancer. MicroRNAs (miRNAs) play an important regulatory role in key processes of cancer development. The aberrant expression of miRNAs is often involved in the initiation, progression, and metastasis of pancreatic cancer. The discovery of tumor suppressor miRNAs provides prospects for the development of a novel treatment strategy for pancreatic cancer. We reviewed recent progress on the understanding of the role of miRNAs in pancreatic cancer, highlighted the efficient application of miRNAs-based therapies for pancreatic cancer in animal models and clinical trials, and proposed future prospects. This review focuses on the promise of integrating miRNAs into the treatment of pancreatic cancer and provides guidance for the development of precision medicine for pancreatic cancer.
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Animales , Humanos , Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias Pancreáticas/genética , PronósticoRESUMEN
Mitochondrial unfolded protein response (UPR mt) is a protein-toxic stress response, which regulates the communication from mitochondria to the nucleus. It is activated when a large number of unfolded or misfolded proteins accumulate in the mitochondria. The activation of UPR mt increases the expression of a series of chaperones and proteases, and maintains the homeostasis and function of mitochondrial proteins. Mitochondria play an important role in maintaining cardiomyocyte homeostasis. The damage of myocardial mitochondria leads to the metabolic disorder of cells suffering from ischemia/reperfusion injury. It is the key mechanism of myocardial cell death. This article mainly reviews the regulatory pathway of UPR mt and the research progress of UPR mt in myocardial ischemia/reperfusion injury (MIRI), in order to provide new ideas for the treatment of MIRI.
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Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by the destruction of the barrier function of alveolar epithelial cells and capillary endothelial cells and the recruitment of inflammatory cells, which leads to alveolar and interstitial edema, hyaline membrane formation and inflammatory infiltration of the lungs, etc. The mechanism is not completely defined. The current treatment plan focuses on comprehensive treatments such as ventilator support treatment, fluid management, and nutritional support, but the prognosis is still poor. Studies have shown that extracellular vesicle microRNA (miRNA) from different sources participate in regulating the function of epithelial cells, endothelial cells and phagocytes in different ways, thus aggravating or improving ALI, and have diagnostic, differential diagnosis and the therapeutic value. In this article, the mechanism, diagnostic and differerntial value of extracellular vesicle miRNA from different sources in ALI and the therapy of extracellular vesicle miRNA from stem cell in ALI are reviewed.
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Objective:To investigate reflectance confocal microscopic features of childhood scabies, and to analyze clinical significance of reflectance confocal microscopy (RCM) in the diagnosis and treatment of childhood scabies.Methods:A retrospective analysis was performed in 77 children with confirmed scabies at Department of Dermatology, Tianjin Children′s Hospital from April 2018 to October 2019. These patients were divided into negative treatment history group (61 cases) and positive treatment history group (16 cases) . All the patients underwent RCM and microscopic examination of skin scrapings.Results:Among the 77 children with scabies, positive microscopic examination results were found in 33 (42.86%) , including 28 in the negative treatment history group and 5 in the positive treatment history group. Burrows, sarcoptid mites or their eggs and fecal pellets were observed in 56 cases (72.73%) by RCM, including 49 (80.33%) in the negative treatment history group and 7 in the positive treatment history group. RCM showed a significantly increased overall positive rate compared with microscopy of skin scrapings ( χ2=14.08, P<0.05) . In the negative treatment history group, RCM also showed a significantly increased positive rate compared with microscopy of skin scrapings ( χ2=15.53, P < 0.05) . Conclusion:RCM is of high clinical value to the diagnosis and treatment of childhood scabies.
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Objective:To investigate the influence of unilateral periacetabular osteotomy (PAO) on the bony birth canal (BBC) in female patients with developmental dysplasia of the hip (DDH) by using pelvic 3D-CT maximum-inscribed-sphere (MIS) method.Methods:A total of 62 female DDH patients of childbearing age were included in the present study. The DICOM data of their pre- and post-operative pelvic CT was collected. The diameters of the MIS in 25 layers of the BBC were measured on the Medical Imaging Interaction Toolkit (MITK) platform. Lateral center edge angle (LCE), T?nnis angle and the distance between the medial margin of the femoral head and Kohler's line were measured on standing anteroposterior pelvic radiographs before and after unilateral PAO. Patients were divided into severe (LCE≤0°) and non-severe group (0°<LCE<20°) according to their LCE values.Results:After unilateral PAO, the BBC above the sciatic spine (1-20th layer) narrowed (0.86-5.95 mm, P<0.05). However, there was no change in levels below the sciatic spine (21-25th layer, P>0.05). The anterior margin of acetabular fragment (1-13th layer) narrowed significantly (4.23-5.95 mm) after unilateral PAO with the narrowest part (5.62-5.95 mm) locating at the inferior margin of pubic ramus and the region superior to the lateral margin of obturator foramen (5-10th layer). The narrowest part of BBC before and after the surgery occurred at the level of bilateral sciatic spines (20th layer). The diameter of MIS changed significantly from 105.34±7.16 mm pre-operatively to 104.47±7.06 mm post-operatively ( t=2.198, P=0.032). There was a positive correlation between the inward displacement of the hip center and the narrowing of the 1-20th layer of the BBC. The decrease of T?nnis angle was positively correlated with the narrowing of the 1-10th layer of the BBC. The increase of LCE was negatively correlated with the narrowing of 2-5th layer of the BBC ( P<0.05). The standardized coefficients were with statistical significance when comparing the distance between the Kohler's line and the medial margin of the femoral head to the size of the 1-20th layer of the BBC ( β=0.27-0.50, P<0.05). The height was positively correlated with the size of the narrowest part of the BBC before and after the surgery ( r=0.565, r=0.586, P<0.001). There was no difference between severe group and non-severe group in their extent of BBC narrowing before and after surgery ( t=-0.685-0.655, P>0.05). Conclusion:Unilateral PAO results in mild narrowing of the BBC superior to the sciatic spine. The narrowest part of the BBC is located at the sciatic spine. Unilateral PAO has slight effects on the narrowest position of the BBC. Normal delivery of a healthy fetus in female patients with DDH of childbearing age could not be affected by unilateral PAO in normal BBC settings.
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Objective:To investigate the expression and clinical relevance of micro RNA (miR)-324-5p in pancreatic cancer tissues, and to explore the effects and potential mechanisms of miR-324-5p on the proliferation and migration of pancreatic cancer cells.Methods:Real-time quantitative PCR was used to detect the expression of miR-324-5p in 34 pairs of pancreatic cancer and adjacent normal tissues resected at Peking University First Hospital from October 2018 to September 2019. The correlations between miR-324-5p expression and clinicopathological characteristics and prognosis of pancreatic cancer were analyzed using data from the Cancer Genome Atlas (TCGA) database. Real-time PCR was used to detect the expression of miR-324-5p in pancreatic cancer cell lines, and PANC-1 cell was used for functional study by overexpressing miR-324-5p via mimic transfection. CCK8 assay was used to evaluate cell proliferation. Both transwell and scratch wound healing assay were used to assess the cancer cell migration ability. Related proteins were detected by Western blot. The potential downstream target genes of miR-324-5p were selected using data from miRNA target genes predicted webs, in combination with functional analysis and their expressional correlation with miR-324-5p.Results:Data from TCGA database showed that the expression of miR-324-5p in tumor tissues was significantly lower than that in normal pancreatic tissues. And low level of miR-324-5p in pancreatic cancer was correlated with poor prognosis. Analysis of 34 pairs pancreatic cancer and adjacent normal tissues showed that miR-324-5p expression in tumor tissues (11.7±2.0) was significantly lower than that in adjacent normal tissues (70.9±14.4), and the pancreatic cancer patients who had the nerve invasion cancer showed low level of miR-324-5p (82.1%, 23/28) was significantly higher than that patients with high level of miR-324-5p (33.3%, 2/6). The expression of miR-324-5p in human pancreatic cancer cell line was also significantly lower than that in normal pancreatic ductal cells. CCK-8 assay showed that the proliferation ability of PANC-1 cell was significantly decreased when miR-324-5p was overexpressed. Transwell and wound healing assays showed that the capabilities of vertical migration and the horizontal movement were significantly inhibited in PANC-1 cell with miR-324-5p overexpressed [(30.11±5.2) and (174.6±27.0) μm, respectively] than those in control groups [(63.6±4.2) and (458.3±22.3) μm, respectively]. Moreover, Western blots showed a significant overexpression of miR-324-5p inhibited epithelial-mesenchymal transition (EMT). According to the data from miRNA target genes prediction and the functional analysis we found KLF3, MGAT3, PBX1 and ZNRF2 were considered as the potential downstream target genes of miR-324-5p.Conclusions:Our results indicated that miR-324-5p is lowly expressed and acts as the tumor suppressor gene in pancreatic cancer, and low level of miR-324-5p is correlated to a higher rate of nerve invasion and poor prognosis. In human pancreatic cancer cell, miR-324-5p may regulate EMT by directly inhibiting target genes such as KLF3, MGAT3, PBX1, ZNRF2, which in turn suppresses cancer cell proliferation and migration.
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Autophagy is a dynamic process that degrades intracellular proteins and damaged organelles, and maintains environmental stability within the cell and provides good conditions for cell survival. Hyperoxic acute lung injury (HALI) is one of the serious complications of clinical oxygen therapy. The pathogenesis of HALI is still unclear. There are studies having shown that autophagy is involved in the pathogenesis of HALI. There are many pathway mechanisms that regulate autophagy, including phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway, mitogen-activated protein kinase/extracellular signaling-regulated protein kinase (MAPK/ERK) signaling pathway, adenosine 5'-monophosphate-activated protein kinase/unc-51 like autophagy activating kinase 1 (AMPK/ULK1) signaling pathway, transforming growth factor β (TGF-β) and forkhead box O1 (FoxO1) and Ras guanosine triphosphatease superfamily member Rab11a, each of which is referred to as microRNA-21-5p (miR-21-5p) target gene having a role in regulating autophagy activity in many diseases. In this paper, the above-mentioned signaling pathways of miRNA-21-5p target genes regulating autophagy were reviewed in order to find clues about the mechanism of miRNA-21-5p regulating autophagy in HALI and provide a theoretical basis for subsequent basic research.
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Objective:To investigate the clinical characteristics, diagnosis, treatment and prognosis of patients with hypertrophic cranial pachymeningitis （HCP） associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) with optic nerve dysfunction.Methods:Clinical data of patients with MPO-ANCA associated HCP admitted to Beijing Tongren Hospital, Capital Medical University from 2008 to 2019 were collected and analyzed.Results:A total of 55 HCP patients were diagnosed, including five patients with MPO-ANCA associated HCP, two males and three females, with the onset ages ranging from 61 to 80 years.The main clinical manifestations were successively five cases of multiple cranial neuropathies, four cases of headache, four cases of chronic sinusitis, three cases of otitis media or mastoiditis，one case of cerebral infarction, while two cases of mild kidney involvement, all without lower airways involvement. Peripheral blood MPO-ANCA concentration and erythrocyte sedimentation rate were elevated in all patients, and protease 3-ANCA was negative. Cerebrospinal fluid protein content was elevated in three patients and leukocyte was increased in one patient. The abnormal frequency of gadolinium-enhanced MRI of brain scan was dura mater (five cases), optic nerve sheath (five cases), sinus mucosa (four cases), inner auditory tract meninges (three cases), orbital wall periosteum (two cases), and brain parenchyma (one case). All patients received glucocorticoid therapy, meanwhile two patients received cyclophosphamide treatment. Multiple cranial neuropathies and headache were improved，but the improvement of visual function damage was not obvious.Conclusions:MPO-ANCA associated HCP is a special type of HCP. Among the dural region involved, the optic nerve sheath is a common site of this disease, and the sinus mucosa and inner auditory canal meninges are also frequently involved. MPO-ANCA associated HCP should be distinguished, if patients with dural lesions, especially those accompanied by optic nerve sheath lesions, sinusitis, and middle ear mastoiditis.
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OBJECTIVE：To investigate the protective effect an d possible m echanism of Shenqi zhilong decoction （SZD） combined with Tripterygium polyglycoside tablets （TPT）on membranous nephropathy （MN）model rats. METHODS ：MN rat model was established by subcutaneous and caudal vein injecting cationic bovine serum albumin + incomplete Freund adjuvant emulsion for 6 weeks. At the 3rd week of modeling ，model rats were randomly divided into model control group ，SZD low-dose and high-dose groups （4，8 g/kg，by total crude drugs ），TPT group （9 mg/kg），low-dose and high-dose of SZD+TPT groups （same dose as single group ），with 10 rats in each group according to 24 h UTP and weight. Another 10 rats withoutmodeling were taken as blank control group. Blank control group was given equal amount of water intragastrically administration groups were given relevant medicine intragastrically，once a day ，for consecutive 4 weeks. The 24 h UTP of rats were detected one day before the last administration；1 h after the la st administration ，blood routine 中indexes（WBC，RBC，PLT），liver func tion indexes （TP，ALB，AST，ALT），blood lipid indexes （TC，TG，HDL-C，LDL-C）， the contents of glucose （GLU），urea nitrogen （BUN）and serum creatinine （Scr）were detected in each group. Uranyl acetate-lead citrate staining was used to observe ultrastructural changes of renal tissue. Immunohistochemical method was used to detect the protein expression of TGF-β1 and HPA- 1 in renal tissue. RESULTS ：Compared with blank control group ，in the model control group，the glomerular podocytes were widely fused or disappeared ，microvilli were formed ，basement membrane was heavily thickened，a large number of electron dense substance was deposited under the epithelium ，TGF-β1 and HPA- 1 positive cells were significantly increased ；24 h UTP ，PLT，the contents of TC ，TG and HDL-C ，the percentage of TGF-β1 and HPA- 1 positive cells were increased significantly ，while RBC ，the contents of TP and ALB were decreased significantly （P＜0.05 or P＜0.01）. Compared with model control group ，above ultrastructural changes of administration groups were improved to different extents ，and TGF-β1 and HPA- 1 positive cells were decreased. The 24 h UTP ，the percentage of TGF-β1 positive cells （except for SZD low-dose group），WBC（except for SZD alone groups and combination groups ），PLT and TC content （except for TPT group ），TG content （except for SZD low-dose alone and its combination group ），the percentage of HPA- 1 positive cells were decreased significantly ； the percentage of TGF-β1 positive cells in SZD high-dose+TPT group as well as the percentage of HPA- 1 positive cells in SZD+TPT groups were significantly lower than TPT group. RBC and GLU content （except for SZD low-dose group and TPT group ），TP and ALB content （except for SZD low-dose group ）were increased significantly ，while the content of GLU in SZD high-dose+TPT group was significantly higher than TPT tablets group （P＜0.05 or P＜0.01）. CONCLUSIONS ：SZD combined with TPT can relieve myelosuppression caused by TPT ，reduce proteinuria of MN model rats and improve pathological damage of renal tissue in rats. Its mechanism is related to the down-regulation of protein expression of TGF-β1 and HPA- 1，and the reduction of TC and TG content in the blood.