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Objective To investigate the effects of force on mechanical stability of FLNa-Ig21/αⅡbβ3-CT complex and the regulation mechanism.Methods The FLNa-Ig21/αⅡbβ3-CT crystal structures were taken from the PDB database.The stability of the complexes in a physiological environment as well as the unfolding path and mechanical stability induced by mechanical forces were analyzed using equilibrium and steered molecular dynamics simulations.Results During the equilibration,the survival rate of most salt bridge and hydrogen bonds was below 0.5,and the interactions between FLNa-Ig21 and αⅡbβ3-CT was relatively weak.During stretching at a constant velocity,the complex could withstand a tensile force of 70-380 pN,and its mechanical strength depended on the force-induced dissociation path.Under a constant force of 0-60 pN,the complexes exhibited a slipping-bond trend,and the force increase facilitated the breakage of the R995-D723 salt bridge and the activation of αⅡbβ3 integrin.Conclusions The force-induced allostery of αⅡbβ3-MP enhanced the complex mechanical strength and delayed FLNa-Ig21 dissociation from αⅡbβ3-CT.After breaking through the 20 pN threshold,force positively regulated the activation of αⅡbβ3 integrin.These results provide insights into the molecular mechanism of αⅡbβ3 activation and the development of related targeted drugs.
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Objective:To explore the efficacy and safety of endoscopic radial incision (ERI) for congenital membranous duodenal stenosis (MDS).Methods:The clinical data of 13 children with MDS receiving ERI in the Department of Gastroenterology of Xi'an Children's Hospital from May 2017 to December 2021 were reviewed and analyzed. The perioperative management, surgical procedures, postoperative complications and follow-up were summarized.Results:There were 5 boys and 8 girls with a median disease duration of 8 (2-20) months, and the median age of diagnosis was 13 months (5-30 months). The septum of 10 cases (10/13) was located in the descending part of the duodenum, and that of 3 cases (3/13) in the horizontal part. The papilla of 1 case (1/13) opened on the septum, that of 3 cases (3/13) within 5 cm of the mouth side of the septum, and that of 9 cases (9/13) within 5 cm of the anal side of the septum. The median diameter of the septal aperture was 3 mm (2-6 mm). All 13 children successfully underwent ERI with a median operation time of 20 min (15-32 min). The average surgical incision was 3 strokes (2-4 strokes), and the endoscope with outer diameter 9.9 mm could pass stenosis after ERI. The median incision diameter was 10 mm (10-12 mm). All patients achieved relief of clinical symptoms after ERI. One patient (1/13) suffered from the postoperative delayed bleeding, which was stopped by endoscopic titanium clamping. No intestinal perforation or duodenal papilla injury occurred, and median postoperative hospital stay was 6 days (5-10 days). The upper gastrointestinal angiogram and gastroscopy were repeated 3 months after ERI, and the median diameter of stenosis was 12 mm (10-15 mm), which was significantly dilated compared with before. The mean body weight increase at 1 month after ERI was 1.20 kg (0.50-1.80 kg), and the mean body weight increase at 3 months was 3.50 kg (2.50-4.00 kg), which reached the normal body weight of the same age.Conclusion:ERI is safe and effective for the treatment of MDS in children, and shows good clinical application and promotion value.
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Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC50 = 0.33 μmol·L-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L-1, 21.2% inhibition at 1 μmol·L-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.
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Activity-based protein (proteomic) profiling (ABPP) has emerged as a key component of the broad field of chemical techniques capable of directly analyzing enzyme activity in living systems. With the deepening of research on electrophilic warheads and nucleophilic amino acids, and the continuous proposal and improvement of effective development strategies, the application of amino acid-targeting active probes in various biological systems has facilitated the identification, development of new targets in various disease contexts and discovery of inhibitors. The purpose of this review is to summarize the latest progress in the design and application of active probes targeting specific amino acids, in order to provide support for the further development of amino acid-targeted covalent inhibitordrugs.
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OBJECTIVES@#To establish a new method for evaluating the brain maturation of preterm infants based on the features of electroencephalographic activity.@*METHODS@#A prospective study was conducted on the video electroencephalography (vEEG) and amplitude-integrated electroencephalography (aEEG) recordings within 7 days after birth of preterm infants who had a postmenstrual age (PMA) of 25-36 weeks and met the inclusion criteria. The background activity of aEEG+conventional electroencephalography (cEEG) was scored according to the features of brain maturation as a new evaluation system and was compared with the aEEG evaluation system. The correlations of the evaluation results of the two methods with gestational age (GA), PMA, and head circumference were evaluated. The intervals of the total scores of aEEG+cEEG and aEEG were calculated for preterm infants with different PMAs and were compared between groups. The consistency of the new scoring system was evaluated among different raters.@*RESULTS@#A total of 52 preterm infants were included. The total scores of aEEG+cEEG and aEEG were positively correlated with GA, PMA, and head circumference (P<0.05), and the correlation coefficient between the total scores of the two systems and PMA and GA was >0.9. The normal score intervals for aEEG+cEEG and aEEG scoring systems were determined in preterm infants with different PMAs as follows: infants with a PMA of less than 28 weeks had scores of 13.0 (11.0, 14.0) points for aEEG+cEEG and 6.0 (4.0, 7.0) points for aEEG; infants with a PMA between 28 and 29+6 weeks had scores of 16.0 (14.5, 17.0) points for aEEG+cEEG and 8.0 (6.0, 8.0) points for aEEG; infants with a PMA between 30 and 31+6 weeks had scores of 18.0 (17.0, 21.0) points for aEEG+cEEG and 9.0 (8.0, 10.0) points for aEEG; infants with between 32 and 33+6 weeks had scores of 22.0 (20.0, 24.5) points for aEEG+cEEG and 10.0 (10.0, 10.8) points for aEEG; infants with a PMA between 34 and 36 weeks had scores of 26.0 (24.5, 27.5) points for aEEG+cEEG and 11.0 (10.0, 12.0) points for aEEG. There were significant differences in the total scores of aEEG+cEEG and aEEG among the different PMA groups (P<0.05). There was a high consistency between different raters when using the scoring system to evaluate the brain maturation of preterm infants (κ=0.86).@*CONCLUSIONS@#The aEEG+cEEG scoring system established in this study can quantitatively reflect the brain maturation of preterm infants, with a good discriminatory ability between preterm infants with different PMAs and high consistency between different raters.
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Humanos , Recién Nacido , Encéfalo , Electroencefalografía , Edad Gestacional , Recien Nacido Prematuro , Estudios ProspectivosRESUMEN
The binding of talin-F0 domain to ras-related protein 1b (Rap1b) plays an important role in the formation of thrombosis. However, since talin is a force-sensitive protein, it remains unclear whether and how force regulates the talin-F0/Rap1b interaction. To explore the effect of force on the binding affinity and the dynamics mechanisms of talin-F0/Rap1b, molecular dynamics simulation was used to observe and compare the changes in functional and conformational information of the complex under different forces. Our results showed that when the complex was subjected to tensile forces, there were at least two dissociation pathways with significantly different mechanical strengths. The key event determining the mechanical strength difference between the two pathways was whether the β4 sheet of the F0 domain was pulled away from the original β1-β4 parallel structure. As the force increased, the talin-F0/Rap1b interaction first strengthened and then weakened, exhibiting the signature of a transition from catch bonds to slip bonds. The mechanical load of 20 pN increased the interaction index of two residue pairs, ASP 54-ARG 41 and GLN 18-THR 65, which resulted in a significant increase in the affinity of the complex. This study predicts the regulatory mechanism of the talin-F0/Rap1b interaction by forces in the intracellular environment and provides novel ideas for the treatment of related diseases and drug development.
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Simulación de Dinámica Molecular , TalinaRESUMEN
In resting platelets, the 17 th domain of filamin a (FLNa17) constitutively binds to the platelet membrane glycoprotein Ibα (GPIbα) at its cytoplasmic tail (GPIbα-CT) and inhibits the downstream signal activation, while the binding of ligand and blood shear force can activate platelets. To imitate the pull force transmitted from the extracellular ligand of GPIbα and the lateral tension from platelet cytoskeleton deformation, two pulling modes were applied on the GPIbα-CT/FLNa17 complex, and the molecular dynamics simulation method was used to explore the mechanical regulation on the affinity and mechanical stability of the complex. In this study, at first, nine pairs of key hydrogen bonds on the interface between GPIbα-CT and FLNa17 were identified, which was the basis for maintaining the complex structural stability. Secondly, it was found that these hydrogen bonding networks would be broken down and lead to the dissociation of FLNa17 from GPIbα-CT only under the axial pull force; but, under the lateral tension, the secondary structures at both terminals of FLNa17 would unfold to protect the interface of the GPIbα-CT/FLNa17 complex from mechanical damage. In the range of 0~40 pN, the increase of pull force promoted outward-rotation of the nitrogen atom of the 563 rd phenylalanine (PHE 563-N) at GPIbα-CT and the dissociation of the complex. This study for the first time revealed that the extracellular ligand-transmitted axial force could more effectively relieve the inhibition of FLNa17 on the downstream signal of GPIbα than pure mechanical tension at the atomic level, and would be useful for further understanding the platelet intracellular force-regulated signal pathway.
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Filaminas/metabolismo , Complejo GPIb-IX de Glicoproteína Plaquetaria/metabolismo , Simulación de Dinámica Molecular , Ligandos , Unión Proteica , Plaquetas/metabolismo , Factor de von Willebrand/metabolismoRESUMEN
PURPOSE@#The rapid development of winter sports requires investigation on injuries in Chongli district, Zhangjiakou city, one of the ski sites of the 2022 Winter Olympics. Careful evaluation is required to observe which injuries are caused under what circumstances, and then we can make corresponding preventive measures and recommendations based on the results.@*METHODS@#In this retrospective study, the data of injury cases at ski resorts in China (Chongli district) and Japan were analyzed to provide a reference for the ongoing injury prevention at ski resorts. We collected data on injuries at Wanlong and Fulong ski resorts in Chongli district during the 2017-2018 and 2018-2019 ski seasons. We referred to the skiing injury report issued in February 2020 of a nationwide ski safety statistical service - Japan Ski Safety Association. The causes of injury and specific injured body parts were analyzed based on the data of Chinese and Japanese ski resorts. Statistical significance has been calculated using the Chi-square test.@*RESULTS@#During the 2019-2020 ski season in Japanese ski resorts, the number of reported injuries per 10,000 skiers was 0.93, of which 457 (17.3%) were over 50 years old, accounting for a large proportion of injuries, meanwhile in Chongli ski resort, the injury rate of skiers aged 50 and over was 7.1%. The knee joint (23.7% at Wanlong ski resort and 28.4% in Japanese ski resorts) was the most injured body part among Chongli and Japanese skiers. Among snowboarders, shoulder joint injury (17.7% in Japanese ski resorts) was the most common, and injury on hands and fingers (16.3% in Wanlong ski resorts) was the most common. Head injury rates are similar in Chongli, China and Japanese ski resorts (8.2% and 8.7%, respectively).@*CONCLUSION@#Our analysis demonstrated that injury data recorded among young skiers was higher in Chinese ski resorts (Chongli district) than that in Japanese ski resorts, and elderly skiers made up a larger proportion of skiing injuries in Japanese resorts. Thus, according to our research, the protection of knee joints, shoulder joints, and hands and fingers should be taken seriously. It should pay attention to the teaching of ski poles (for finger protection), and use protective devices such as knee pads, helmets, etc.
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Anciano , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Traumatismos en Atletas/prevención & control , Esquí/lesiones , Japón/epidemiología , China/epidemiologíaRESUMEN
OBJECTIVES@#To explore a new method for electroencephalography (EEG) background analysis in neonates with hypoxic-ischemic encephalopathy (HIE) and its relationship with clinical grading and head magnetic resonance imaging (MRI) grading.@*METHODS@#A retrospective analysis was performed for the video electroencephalography (vEEG) and amplitude-integrated electroencephalography (aEEG) monitoring data within 24 hours after birth of neonates diagnosed with HIE from January 2016 to August 2022. All items of EEG background analysis were enrolled into an assessment system and were scored according to severity to obtain the total EEG score. The correlations of total EEG score with total MRI score and total Sarnat score (TSS, used to evaluate clinical gradings) were analyzed by Spearman correlation analysis. The total EEG score was compared among the neonates with different clinical gradings and among the neonates with different head MRI gradings. The receiver operating characteristic (ROC) curve and the area under thecurve (AUC) were used to evaluate the value of total EEG score in diagnosing moderate/severe head MRI abnormalities and clinical moderate/severe HIE, which was then compared with the aEEG grading method.@*RESULTS@#A total of 50 neonates with HIE were included. The total EEG score was positively correlated with the total head MRI score and TSS (rs=0.840 and 0.611 respectively, P<0.001). There were significant differences in the total EEG score between different clinical grading groups and different head MRI grading groups (P<0.05). The total EEG score and the aEEG grading method had an AUC of 0.936 and 0.617 respectively in judging moderate/severe head MRI abnormalities (P<0.01) and an AUC of 0.887 and 0.796 respectively in judging clinical moderate/severe HIE (P>0.05). The total EEG scores of ≤6 points, 7-13 points, and ≥14 points were defined as mild, moderate, and severe EEG abnormalities respectively, which had the best consistency with clinical grading and head MRI grading (P<0.05).@*CONCLUSIONS@#The new EEG background scoring method can quantitatively reflect the severity of brain injury and can be used for the judgment of brain function in neonates with HIE.
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Recién Nacido , Humanos , Hipoxia-Isquemia Encefálica/diagnóstico por imagen , Estudios Retrospectivos , Lesiones Encefálicas , Electroencefalografía , Curva ROCRESUMEN
Objective:To investigate the diagnostic and therapeutic value of one-time biliopancreatic-duct-imaging-system (eyeMax)-assisted endoscopic retrograde appendicitis therapy (ERAT) for children.Methods:A total of 11 children who were diagnosed as having uncomplicated acute appendicitis by imaging in Xi′an Children′s Hospital from August to November 2022 were enrolled. All patients received subscope-assisted ERAT. Subscope was intubated into the appendix cavity to observe the mucosa directly. Appendicitis was treated through cleansing, fecalith extraction, stent drainage. The clinical manifestations under subscope were recorded, as well as the treatment success rate, intubation success rate, the effective rate, complication incidence during and after the operation.Results:The age of 11 children was 7.93±2.67 years old. Appendix intubation was successful in all patients. Congestion and swelling of the mucosa in appendiceal orifice and appendix cavity were seen under the subscope in 11 children. There were 6 cases with appendiceal fecaliths, 8 cases with pus and 6 cases with luminal distortion or stenosis. Perforation was observed in 1 case during the operation and no other complication occurred. All patients were treated under subscope, including flushing appendiceal cavity (11 cases), fecalith extraction with extraction basket (3 cases), and appendiceal drainage with stenting (2 cases). The symptoms and signs were relieved after the operation, and the effective rate within 48 hours was 10/11. There were no procedure-related complications or recurrence during postoperative follow-up for 1 week to 4 months.Conclusion:Acute appendicitis could be diagnosed by observing the appendix cavity directly under one-time biliopancreatic-duct-imaging-system-assisted ERAT, and also could be treated with the system, where appendix could be preserved and radiation damage could be avoided with safety and effectiveness.
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Objective:To evaluate the prognosis of off-pump coronary artery bypass grafting combined(OPCABG) with coronary endarterectomy(CE) treating the diffuse coronary artery disease.Methods:From January 2012 to December 2014, the clinical data of 2 496 OPCABG patients in our department were retrospectively analyzed, and they were divided into OPCABG group and OPCABG+ CE group. After 1∶1 matching via the propensity score matching method, the perioperative prognosis, long-term survival and adverse cardiovascular and cerebrovascular events(MACCE) were compared between the two groups.Results:A total of 238 pairs of patients were included after propensity score matching. The incidence of postoperative AMI in the OPCABG+ CE group was significantly higher than that in the OPCABG group(5.04% vs. 1.68%, P=0.042). With an average follow-up of 7.3 years, there was no significant difference in the cumulative survival rate(92.44% vs. 88.65%, P=0.159) and long-term MACCE(10.92% vs. 15.13%, P=0.173) between the two groups. Compared with the OPCABG group, the recurrence of angina pectoris(CCS grade Ⅲ-Ⅳ) in the OPCABG+ CE group increased significantly(20.16% vs. 12.60%, P=0.026). Conclusion:The risk of early AMI and long-term angina recurrence after OPCABG+ CE is significantly increased, but the long-term survival and MACCE of OPCABG+ CE and OPCABG are comparable.
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Objective@#To analyze the epidemiological characteristics and trends of chronic disease mortality among children aged 0-14 in China during 2012-2021, so as to provide scientific basis for the formulation of prevention strategies for chronic diseases in children.@*Methods@#The descriptive epidemiological analysis was conducted for chronic disease mortality among children aged 0-14 during 2012 to 2021 from China Cause of Death Surveillance Data Set, and the Joinpoint regression models were used to analyze the average annual percentage change (AAPC) of child chronic disease mortality.@*Results@#From 2012 to 2021, the mortality rates of chronic diseases among children aged 0-14 years in China (23.33/100 000, 19.54/100 000, 19.27/100 000, 17.69/ 100 000 , 16.87/100 000, 16.44/100 000, 14.49/100 000, 13.79/100 000, 11.61/100 000, 9.43/100 000)showed a decreasing trend (AAPC=-7.94%, P <0.01). The overall mortality rates for boys and girls and for chronic diseases were decreasing in both urban and rural areas (AAPC=-8.44%, -7.05%, -8.42%, -6.77%, P <0.05). The average annual mortality rate of chronic diseases was higher in boys (16.81/100 000) than in girls (13.96/100 000) ( χ 2=526.44, P <0.01). The average annual mortality rate from chronic diseases among children was higher in urban (15.98/100 000) than in rural areas (13.46/100 000) in the central region, and higher in rural (19.75/100 000) than in urban areas (15.96/100 000) in the western region ( χ 2=117.63, 190.25, P < 0.01 ). Except for malignant tumors, the trend of overall mortality rates of congenital abnormalities, neurological and mental disorders, cardiovascular diseases, and digestive system diseases were all decreasing (AAPC=-11.48%, -2.92%, -7.82%, -12.51 %, P <0.05).@*Conclusions@#The overall mortality rate of chronic diseases in children in China shows a downward trend during 2012-2021, but the situation of chronic disease prevention and control is still severe. Targeted prevention strategies should be adopted, focusing on the prevention and health care of males, children under 5 years old.
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Objective To investigate the efficacy of bevacizumab combined with paclitaxel and platinum-based chemotherapy in advanced metastatic cervical cancer and its effect on T lymphocyte subsets and tumor markers. Methods Sixty patients with advanced metastatic cervical cancer (treated in our hospital) were randomly divided into control (30 cases) and treatment (30 cases) groups. All patients were given radiotherapy; the control group received paclitaxel and platinum-based chemotherapy, whereas the treatment group received the same with added bevacizumab. The pain conditions (visual analog score (VAS)) and quality of life (Karl Fischer quality of life (KPS)), clinical efficacy, T lymphocyte subset levels (CD3+, CD4+, and CD8+), tumor markers (carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), and squamous epithelial carcinoma-associated antigen (SCCA)) and adverse reactions were compared between the two groups. Results The VAS score, serum CA125, CEA, SCCA, and CD8+ level were significantly reduced in both groups after treatment (P < 0.05), and it significantly decreased in the treatment group compared with the control group (P < 0.05). KPS score, CD3+, and CD4+ levels significantly increased after treatment in the two groups (P < 0.05), and compared with the control group, the treatment group significantly increased (P < 0.05). Moreover, the total effective rate (66.67%) was significantly higher than that in the control group (40.00%) (P < 0.05), and no significant difference existed in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion Bevacizumab combined with paclitaxel and platinum-based chemotherapy can effectively reduce the pain and improve the immune function and quality of life of patients with advanced metastatic cervical cancer. This chemotherapy is also safe and effective.
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Objective To explore how hyaluronic acid ( HA) in extracellular matrix regulates the adhesion ofCD44+tumor cells. Methods MDA-MB-231 cells or HL60 cells were perfused in a parallel plate chamber. Themovement of cells over immobilized HA was observed and analyzed to obtain the characteristics of cell adhesionand rolling. Results The adhesion number of MDA-MB-231 cells on HA substrate was positively regulated by HAconcentration, but not by HA molecular weight. Compared with physically adsorbed HA, immobilized HA byavidin-biotin could significantly improve the cell adhesion ratio. With the increase of shear stress in the range of30-50 mPa, the rolling velocity of cells increased and the adhesion ratio decreased, but the tether lifetime of cellswas not affected. In the same flow field, compared with MDA-MB-231 cells, HL60 cells with low expression ofCD44 rolled more quickly on immobilized HA, with shorter tether lifetime and much lower adhesion ratio(<1. 5% ). Conclusions Fluid shear stress might mediate the rolling velocity of MDA-MB-231 cells by regulatingthe CD44-HA association rate rather than their dissociation rate. The interaction between CD44 and HA is involved in the initial adhesion of HL60 cells, but it does not play a major role. This study will provide references for the design of anti-tumor drugs.
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PURPOSE@#To retrospectively analyze the clinical outcomes of meniscus repair with simultaneous anterior cruciate ligament (ACL) reconstruction and explore the causes of failure of meniscus repair.@*METHODS@#From May 2013 to July 2018, the clinical data of 165 patients who were treated with meniscus surgery and simultaneous ACL reconstruction, including 69 cases of meniscus repair (repair group) and 96 cases of partial meniscectomy (partial meniscectomy group) were retrospectively analyzed. The exclusion criteria were as follows: (1) ACL rupture associated with fracture, collateral ligament injury, or complex ligament injury; (2) a history of knee surgery; or (3) a significant degree of osteoarthritis. The 69 patients in the repair group were divided into the non-failure group (62 cases) and the failure group (7 cases) depending on the repair effect. Postoperative outcomes of the repair group and the partial meniscectomy group were compared. General conditions and postoperative outcomes of the failure group and the non-failure group were compared. During the median follow-up period of 28 months (range, 4 - 65 months) after the second arthroscopy, postoperative outcomes of seven patients in the failure group were summarized. SPSS 25.0 statistical software was used for statistical analysis. A p value less than 0.05 was considered statistically significant.@*RESULTS@#Seven patients in the failure group who underwent the second arthroscopy were followed up for (30 ± 17.4) months and their postoperative outcomes were summarized. Compared with the partial meniscectomy group, the International Knee Documentation Committee scores of patients in the repair group improved significantly (p = 0.031). Compared with the non-failure group, more patients in the failure group were younger than 24 years (p = 0.030). The median follow-up period was 39.5 months. All patients recovered well after subsequent partial meniscectomy and relieved clinical symptoms. Visual analog scale scores decreased significantly (p = 0.026), and the International Knee Documentation Committee and Lysholm scores improved significantly (p = 0.046 for both).@*CONCLUSION@#The failure rate of meniscus repair in this study was 10.1% (7/69), all of which were medial meniscus tears. However, the surgical outcomes of ACL reconstruction were not affected, and there might be a role for graft protection. Therefore, meniscus retears can be successful treated by performing subsequent partial meniscectomy in patients with repair failure.
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Humanos , Lesiones del Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior , Meniscos Tibiales/cirugía , Menisco , Estudios RetrospectivosRESUMEN
Artificial Intelligence (AI) is an interdisciplinary subject developed on the basis of computer technology, cybernetics, mathematics, philosophy and brain science. The purpose of AI is to study new ways to extend the intelligence of human brain in various fields. In recent years, the rapid development of AI technology has brought innovation to medical science and health care. During the pandemic of coronavirus disease 2019 (COVID-19) AI has been widely used in epidemiological investigation and outbreak prediction, clinical diagnosis and treatment, hospital management, research and development of new drugs and vaccines. The application of AI has reduced the clinical workload and the consumption of medical resources, greatly assisted the battle against COVID-19.This article introduces the progresses on the applications of AI technology to provide information for its further application in the fighting against COVID-19.
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ObjectiveTo investigate the effects of micro-fertilizer containing rare earth of different types and concentrations on the growth,yield and quality of Angelica sinensis. MethodOn the basis of the single-factor randomized block design, the growth and index components of Angelica sinensis were determined with rare earth-containing nitrate and chloride micro-fertilizers of different concentrations as foliar fertilizers. ResultSpraying 0.8 g·mL-1 rare earth-containing chloride micro-fertilizer could increase the economic yield of A. sinensis, with the fresh yield per mu (1 mu≈667 m2) reaching 855.4 kg and the dry yield per mu 350.7 kg,which increased by 15.16% and 28.70% respectively compared with that in the control group CK1. Spraying 1.2 g·mL-1 rare earth-containing nitrate micro-fertilizer could promote the growth and development of A. sinensis and significantly increase the content of index components, with the plant height reaching 93.05 cm,the stem diameter 15.60 mm,the root diameter 16.10 mm,the main root length 36.5 cm,and the number of leaves 11.25 pieces per plant, which increased by 32.76%,31.98%,41.98%,53.36%,and 45.16%, respectively, compared with those in the control group CK2. Besides, the content of ferulic acid,volatile oil,ligustilide, and extract was 0.96%,0.41%,0.30% and 48.76%,respectively,which increased by 12.94%,17.14%,11.11%, and 12.07%,respectively,compared with that in the control group CK2. ConclusionSpraying 0.8 g·mL-1 rare earth-containing chloride micro-fertilizer and 1.2 g·mL-1 rare earth-containing nitrate micro-fertilizer can promote the growth and development of A. sinensis,improve the medicinal properties,and increase yield and quality. Rare earth-containing micro-fertilizers can be applied in the standardization of A. sinensis cultivation, which can change the production status of A. sinensis that depends on chemical fertilizers and single fertilization, and promote the green, organic and ecological cultivation of A. sinensis.
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Objective:To evaluate the safety and effectiveness of capsule endoscopy for the diagnosis of intestinal diseases in children.Methods:Clinical data of 113 pediatric patients who received capsule endoscopy in Xi'an Children's Hospital from October 2018 to September 2020 were retrospectively analyzed. The completion rate, passage time of stomach and small intestine, lesion detection rate, adverse reactions and complications of capsule endoscopy were analyzed.Results:Among 113 pediatric patients, 78 (69.03%) were male and 35 (30.97%) were female. The age was (99.8±44.7) months (9-195 months), and 31 (27.43%) were under 7 years old. The minimum weight was 9 kg and the minimum height was 70 cm. Eighty-seven pediatric patients (76.99%) swallowed capsules orally (the oral group) with the minimum age of 4 years and 3 months. Capsules were implanted in 26 pediatric patients (23.01%) under gastroscopy (the gastroscopic group), with the maximum age of 9 years and 2 months. Unexplained abdominal pain (47.79%) and unexplained gastrointestinal bleeding (31.89%) were common in the pediatric patients. The completion rate of capsule endoscopy was 97.35% (110/113), and the detection rate of lesions in small intestine was 31.81% (35/110). The passage time of small intestine in the gastroscopic group was significantly longer than that of the oral group (461.04±129.27 min VS 288.23±107.84 min, t=5.646, P<0.01). There was no significant difference in the passage time of stomach or small intestine among different genders, different ages or different endoscopic examination results ( P>0.05). The positive results of capsule were not correlated with the method of ingestion ( P=0.401, OR=2.562, 95% CI:0.284-23.077), gender ( P=0.154, OR=2.352, 95% CI:0.726-7.616), age ( P=0.949, OR=1.007, 95% CI:0.816-1.242), examination reason ( P=0.246) or small intestine passage time ( P=0.219, OR=1.003, 95% CI:0.998-1.008). No complications such as capsule retention occurred in any pediatric patient. Conclusion:Capsule endoscopy in children is noninvasive, rapid and simple, which can improve the diagnostic rate of small intestinal diseases in children, and can be further promoted in pediatric patients.
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Osteoarthritis (OA) is one of the most common geriatric motor system diseases in the clinical practice. Aging, whose hallmark is cellular senescence, is an important factor leading to the occurrence and development of OA, but its exact role in the pathological development of OA is not completely clear. Studies have proved that targeting senescence can effectively treat aging-related diseases. In this study, the heterozygous mouse model of Cdkn2a-e (Luc-2A-tdTomato-2a-CreerT2-Wpre-PA)1 was established by the CRISPR/ Cas9 technique. The expression of Cdkn2a (p16, p16INK4a), a classical marker of senescence, can be traced in vivo in mice. We then utilized anterior cruciate ligament transection (ACLT) to induce OA in Cdkn2a mice, and we hope to verify the relationship between aging and the occurrence and development of OA and visualize aging changes during OA development through the mice model. In this study, 10-12 weeks old Cdkn2a mice were randomly divided into no surgery control group, sham operation group and ACLT group. OA model was constructed in mice by ACLT operation. After surgery for 4 weeks, animals were collected for fluorescence imaging detection in vivo, which showed that local fluorescence expression of Cdkn2a increased in knee joints of mice in the ACLT group four weeks after surgery (P < 0. 05) . The Safranin O-Fast Green Staining of mouse knee tissue sections showed degeneration of the knee cartilage in the ACLT group at 4 weeks after surgery (P < 0. 05) . Immunohistochemical staining of Cdkn2a was performed on the knee tissue of mice. Compared with the other two groups, Cdkn2a staining on the cartilage surface of the knee tissue of mice in the ACLT group was deeper. The results showed that the OA model induced by surgery showed local aging, which further verified the relationship between aging and OA. At the same time, the Cdkn2a tracer mouse model can reflect the aging progress of mice in vivo, with combination of imaging examinations, so that the occurrence and progress of the relationship between aging and OA can be observed in real time. This heterozygous mouse model of Cdkn2a-e(Luc-2A-tdTomato-2a-CreerT2-Wpre-PA) 1 is not only useful for mechanism research of aging and OA diseases, but also beneficial for finding more potential therapy targets to OA and aging.
RESUMEN
Osteoarthritis (OA) is a common degenerative disease of the motor system with a high morbidity and disability rate. The pathogenesis of OA is not clear at present. Previous studies believe that the pathogenesis of OA is mainly related to trauma factors, while recent studies have shown that metabolic factors, including abnormal cholesterol metabolism, are also closely related to OA. The treatment of OA is mainly symptomatic treatment at the early stage and surgical treatment at the late stage, and there is no specific drug. Previously, BNTA, a small molecule drug with cartilage protective effects, has been shown to have a good effect on OA caused by trauma, but its effect on OA caused by high cholesterol remains unclear. In order to explore the therapeutic effect of BNTA on OA caused by high cholesterol and its mechanism, the OA model of rats was constructed by adopting high cholesterol diets, and paraffin sections of knee joints were taken for histological evaluation. Lipid accumulation in chondrocytes of rats was assessed by oil red O staining. The expression of genes and proteins related to anabolism, catabolism and cholesterol metabolism in chondrocytes was assessed by RT-qPCR, immunofluorescence and immunohistochemistry. The results showed that BNTA could alleviate OA pathological manifestations and improve the OARSI (Osteoarthritis Research Society International) score in the OA model of high cholesterol rats. In rat chondrocytes, BNTA can promote the expression of anabolism-related genes col2, sox9 and acan, inhibit the expression of catabolism-related genes mmp13 and adamts5, and improve the lipid accumulation caused by high cholesterol in rat chondrocytes. BNTA can up-regulate Insig1 expression in rat chondrocytes and the OA model of high cholesterol rats. This study confirmed that high cholesterol can aggravate OA in vivo and in vitro, and can increase lipid accumulation in rat chondrocytes. Taken together, BNTA can alleviate OA phenotypes induced by high cholesterol and improve abnormal lipid accumulation in chondrocytes, possibly by inhibiting cholesterol biosynthesis in cells by upregulating Insig1, thereby alleviating abnormal lipid accumulation.