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Objective:This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score, and renal venous Doppler waveform (RVDW) pattern in predicting 28-day renal dysfunction in critically ill patients and establish nomogram model.Methods:This was a prospective, observational study. Critically ill patients admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from January 2018 to October 2022 were included. Patients underwent renal ultrasound examination to obtain RRI, PDU score and RVDW pattern within 24 h after ICU admission. The following clinical variables were collected during the renal ultrasound examination session, including heart rate, mean arterial pressure, type and dose of vasoactive drugs, oxygen therapy parameters, and average urine volume per hour derived from a period of 6 h prior to the ultrasound examination. The data on duration of AKI and mortality were recorded on the 28th day of follow-up. Patients were divided into 28-day normal renal function group and 28-day renal dysfunction group according to 28-day renal dysfunction. 28-days of renal dysfunction was defined as failure to achieve renal function recovery within 28 days of ICU admission. The difference of each index between the two groups was compared. Associated factors for 28-day renal dysfunction were determined by univariate and multivariate COX regression analyses. A nomogram was developed based on the independently factors associated with 28-day renal dysfunction. Survival receiver operator characteristic (ROC) curves were plotted to assess diagnostic performance in predicting 28-day renal dysfunction. Delong’s test was used to compare area under the curves (AUC) between each predictor.Results:187 patients were enrolled for the final analysis: 97 with no AKI, 48 with AKI stage 1, 24 with AKI stage 2, and 18 with AKI stage 3 upon enrollment. At 28-day follow up, 16 patients had renal dysfunction and 2 required continuous renal replacement therapy (CRRT). The multivariate COX regression showed that RVDW and SCr upon enrollment were the independent risk predictors. Nomogram based on RVDW and SCr upon enrollment showed the best performance in predicting 14-day renal dysfunction (AUC = 0.918, 95% CI:0.871-0.964, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05). Nomogram also showed the best performance in predicting 28-day renal dysfunction (AUC = 0.924, 95% CI:0.865-0.983, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05) except for SCr upon enrollment. The optimal cutoff for nomogram in predicting 28-day renal dysfunction was ≤89.5 (sensitivity, 81.2%; specificity, 90.6%; Youden index, 0.719). Kaplan-Meier analysis showed that the median duration of renal dysfunction in the groups with total nomogram score >85.9 and ≤85.9 was 0 and 22 days (HR=0.220, 95% CI:0.129-0.376, P<0.001). Conclusions:SCr and RVDW pattern within 24 h from ICU admission were independent factors associated with 28-day renal dysfunction in critically ill patients. The value of the nomogram model based on these two factors in predicting 28-day renal dysfunction is superior to each single intrarenal Doppler spectrum indicator and clinical indicator.
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Objective To investigate the CT and MRI findings of different types of small round cell tumor(SRCT)in the nasal cavity and sinuses.Methods A retrospective analysis was conducted on the imaging data and clinical data of 35 SRCT patients confirmed by pathology.Thirty-one SRCT patients underwent CT examination,and 19 SRCT patients underwent MRI examination.Results There were 20 cases of tumors that invaded the nasal cavity and 19 cases involved the sinuses,including 11 cases of the maxillary sinus,7 cases of the ethmoid sinus,2 cases of the sphenoid sinus,and 1 case of the frontal sinus.CT findings of SRCT were all soft tissue masses.Lymphoma was relatively homogeneous with mild bone destruction,and usually involved nasal vestibular skin.Rhabdomyosarcoma(embryonic type)happened at an early age and easily caused bone destruction and metastasis.Melanoma generally occurred in the nasal septum and nasal cavity,which was prone to bleeding.Small cell neuroendocrine carcinoma was heterogeneous,with moderate to significant enhancement,bone absorption and destruction were often noticed.The MRI manifestations of SRCT were equal or long signal on T1WI,high signal on T2WI,and significant diffusion limitation on diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)except for melanoma.On contrast-enhanced images,lymphoma showed mild to moderate enhancement,rhabdomyosarcoma showed typical"grape sign",and small cell neuroendocrine carcinoma showed"sieve"and"map-like"obvious enhancement.Typical melanoma showed a high signal on T1WI and a low signal on T2WI and usually caused bleeding.The MRI findings were related to the presence of melanoma and hemorrhage within the lesion.Conclusion SRCT of the nasal cavity and sinuses have a high degree of malignancy and poor prognosis,CT and MRI have many similar manifestations.Combining clinical data,bone destruction,MRI enhancement,and DWI sequence can effectively distinguish different types of SRCT,as well as squamous cell carcinoma of the nasal cavity and sinuses and adenoid cystic carcinoma.
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Background@#Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. @*Methods@#In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. @*Results@#Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. @*Conclusions@#We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.
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Objective To quickly observe the tonic effects of Cervi Colla on enriching blood,strengthening bones and anti-aging in zebrafish model.Methods Glyphosate(Gly)was used to construct the erythrocyte injury model in adult zebrafish,and methotrexate(MTX)was used to construct the hematopoietic function injury model of juvenile zebrafish.Prednisolone(Pred)was used to establish the inhibition model of bone formation in zebrafish larvae.The ocular cell apoptosis model of zebrafish larvae was established by dibutyl phthalate(DBP).Results Cervi Colla could improve the Gly-induced abnormal erythrocyte nucleus in adult zebrafish and promote the expression of hematopoietic factors SCL and GATA1.Cervi Colla improved Pred-induced inhibition of bone formation in juvenile zebrafish,and promoted the expression of osteoblast-related gene ALP and Runx2a.The number of ocular cell apoptosis induced by DBP was decreased,and the expression of anti-apoptotic factor Bcl-2 was promoted.Conclusion Cervi Colla has significant effects on protecting erythrocyte,protecting hematopoiesis,protecting bone formation and anti-apoptosis.These effects may be related to replenish blood,anti-osteoporosis,and anti-aging.This study provides a scientific basis for the clinical application of Cervi Colla,and lays a foundation for further development and application.
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The present study investigated the chemical constituents from the aerial parts of Glycyrrhiza uralensis. The ethanol extract of the aerial parts of G. uralensis was separated and purified by different column chromatographies such as macroporous resin, silica gel, and Sephadex LH-20, and through preparative HPLC and recrystallization. Thirteen compounds were isolated and identified as(2S)-6-[(Z)-3-hydroxymethyl-2-butenyl]-5,7,3'-trihydroxy-4'-methoxy-dihydroflavanone(1),(2S)-8-[(E)-3-hydroxymethyl-2-butenyl]-5,7,3',5'-tetrahydroxy-dihydroflavanone(2), α,α'-dihydro-5,4'-dihydroxy-3-acetoxy-2-isopentenylstilbene(3), 6-prenylquercetin(4), 6-prenylquercetin-3-methyl ether(5), formononetin(6), 3,3'-dimethylquercetin(7), chrysoeriol(8), diosmetin(9),(10E,12Z,14E)-9,16-dioxooctadec-10,12,14-trienoic acid(10), 5,7,3',4'-tetrahydroxy-6-prenyl-dihydroflavanone(11), naringenin(12), dibutylphthalate(13). Compounds 1-3 are new compounds, and compounds 10 and 13 are isolated from aerial parts of this plant for the first time.
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Glycyrrhiza uralensis/composition chimique , Parties aériennes de plante/composition chimiqueRésumé
OBJECTIVE@#To evaluate the decompensation effectiveness and alveolar bone remodeling of mandibular anterior teeth after preoperative orthodontic treatment in high-angle patients with skeletal class Ⅱ malocclusion using lateral cephalogram and cone-beam computed tomography (CBCT).@*METHODS@#Thirty high-angle patients with skeletal class Ⅱ malocclusion who had received preoperative orthodontic treatment and orthognathic surgery in Peking University School and Hospital of Stomatology between Ja-nuary 2017 and August 2022 and had taken lateral cephalogram and CBCT before and after preoperative orthodontic treatment were selected. Items were measured with lateral cephalogram including: The lower central incisor (L1)-Frankfort plane angle (L1-FH), the L1-mandibular plane angle (L1-MP), the L1-nasion-supramental angle (L1-NB) and the vertical distance from the incisal edge of lower central incisor to NB line (L1-NB distance), etc. The incidence of dehiscence/fenestration and the length of dehiscence at labial side (d-La) and lingual side (d-Li) were measured using CBCT. Pearson correlation analysis was used to evaluate the correlation between the changes of d-Li of L1 and age, duration of preoperative orthodontic treatment and the cephalometric measurements before preoperative orthodontic treatment to screen out risk factors affecting the periodontal risk of preoperative orthodontic treatment in high-angle patients with skeletal class Ⅱ malocclusions.@*RESULTS@#After preoperative orthodontic treatment, L1-FH, L1-MP, L1-NB and L1-NB distances changed by 11.56°±5.62°, -11.13°±5.53°, -11.57°±5.43° and (-4.99±1.89) mm, respectively, and the differences were all statistically significant (P < 0.05). Among the 180 measured mandibular anterior teeth, 45 cases with labial dehiscence/fenestration before preoperative orthodontic treatment (T0) had no longer labial dehiscence/fenestration after preope-rative orthodontic treatment (T1); 142 cases without lingual dehiscence/fenestration at T0 had lingual dehiscence/fenestration at T1. After preoperative orthodontic treatment, the d-La of lower lateral incisors (L2), lower canines (L3) and lower anterior teeth (L1+L2+L3) decreased by (0.95±2.22) mm, (1.20±3.23) mm and (0.68±2.50) mm, respectively, and the differences were statistically significant (P < 0.05); the d-Li of L1, L2, L3 and L1+L2+L3 increased by (4.43±1.94) mm, (4.53±2.35) mm, (3.19±2.80) mm and (4.05±2.46) mm, respectively, and the differences were statistically significant (P < 0.05). The increase of d-Li of L1 was positively correlated with L1-FH (r=0.373, P=0.042).@*CONCLUSION@#This study showed that high-angle patients with skeletal class Ⅱ ma-locclusion could achieve ideal decompensation effect of mandibular anterior teeth after preoperative orthodontic treatment with bilateral mandibular first premolars extracted, but the lingual periodontal risk of mandibular anterior teeth was increased. This risk could be correlated to L1-FH before preoperative orthodontic treatment, which should be paid more attention in the design of orthodontic-orthognathic surgical treatment.
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Humains , Malocclusion de classe III , Malocclusion de classe II/chirurgie , Os de la face , Incisive , Procédures de chirurgie orthognathique , Tomodensitométrie à faisceau conique , MandibuleRésumé
Mitophagy is one of the important targets for the prevention and treatment of myocardial ischemia/reperfusion injury (MIRI). Moderate mitophagy can remove damaged mitochondria, inhibit excessive reactive oxygen species accumulation, and protect mitochondria from damage. However, excessive enhancement of mitophagy greatly reduces adenosine triphosphate production and energy supply for cell survival, and aggravates cell death. How dysfunctional mitochondria are selectively recognized and engulfed is related to the interaction of adaptors on the mitochondrial membrane, which mainly include phosphatase and tensin homolog deleted on chromosome ten (PTEN)-induced kinase 1/Parkin, hypoxia-inducible factor-1 α/Bcl-2 and adenovirus e1b19k Da interacting protein 3, FUN-14 domain containing protein 1 receptor-mediated mitophagy pathway and so on. In this review, the authors briefly summarize the main pathways currently studied on mitophagy and the relationship between mitophagy and MIRI, and incorporate and analyze research data on prevention and treatment of MIRI with Chinese medicine, thereby provide relevant theoretical basis and treatment ideas for clinical prevention of MIRI.
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Humains , Mitochondries/métabolisme , Mitophagie/génétique , Lésion de reperfusion myocardique , Protein kinases/métabolismeRésumé
Systemic lupus erythematosus combined with chorea is relatively rare in China,and there are no unified diagnostic criteria or specific ancillary tests.Therefore,it is confirmed by exclusionary clinical diagnosis.To improve the understanding of this disease among rheumatologists,we report the clinical data of a patient with systemic lupus erythematosus combined with chorea admitted to the Department of Rheumatology and Immunology in the First Affiliated Hospital of Jinan University in January 2022.Furthermore,we review the relevant literature in the past 10 years and summarize the clinical features of these cases.
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Humains , Chorée/diagnostic , Lupus érythémateux disséminé/complications , Chine , Hospitalisation , HôpitauxRésumé
Objective:To investigate the clinical efficacy of neuroendoscopic hematoma removal versus soft channel drainage in the treatment of chronic subdural hematoma. Methods:The clinical data of 102 patients with chronic subdural hematoma who received treatment in Jincheng People's Hospital from May 2018 to May 2020 were retrospectively analyzed. They were divided into the neuroendoscopy group ( n = 50) and the soft channel group ( n = 52) according to different surgical methods. Perioperative indexes, hematoma clearance rate, China Stroke Scale score, the activity of daily living score, and oxidative stress indexes were compared between the two groups. All patients were followed up for 3 months. The incidence of complications during the follow-up period was calculated. Results:The retention time of the drainage tube in the neuroendoscopy group was shorter than that in the soft channel group [(2.45 ± 0.63) days vs. (3.30 ± 0.78) days, t = 6.06, P < 0.001]. The length of hospital stay in the neuroendoscopy group was shorter than that in the soft channel group [(7.14 ± 1.65) days vs. (9.07 ± 2.11) days, t = 5.15, P < 0.001]. The hematoma clearance rate at postoperative 7 days in the neuroendoscopy group was higher than that in the soft channel group [(93.45 ± 5.50)% vs. (81.86 ± 7.24)%, χ2 = 9.12, P < 0.001]. There were no significant differences in operation time and intraoperative blood loss between the two groups (both P > 0.05). At postoperative 30 days, the China Stroke Scale score in the neuroendoscopy group was lower than that in the soft channel group [(12.74 ± 2.23) points vs. (18.67 ± 2.45) points, t = 12.79, P < 0.001]. The activity of daily life score in the neuroendoscopy group was significantly higher than that in the soft channel group [(77.69 ± 7.11) points vs. (91.35 ± 7.25) points, t = 9.60, P < 0.001]. At postoperative 7 days, glutathione peroxidase level in the neuroendoscopy group was significantly lower than that in the soft channel group [(130.75 ± 13.66) U/L vs. (148.60 ± 14.64) U/L, t = 6.37, P < 0.001]. Malondialdehyde level in the neuroendoscopy group was significantly lower than that in the soft channel group [(5.11 ± 0.65) nmol/L vs. (6.19 ± 0.74) nmol/L, t = 7.83, P < 0.001]. Superoxide dismutase level in the neuroendoscopy group was significantly higher than that in the soft channel group [(275.60 ± 22.33) U/L vs. (254.60 ± 18.55) U/L, t = 5.15, P < 0.001]. There was no significant difference in the incidence of complications between the two groups ( P > 0.05). Conclusion:Compared with soft channel drainage, neuroendoscopic hematoma removal can obtain better short-term curative effects and less oxidative stress response in the treatment of chronic subdural hematoma. Neuroendoscopic hematoma removal does not increase the incidence of postoperative complications and is highly safe.
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Objective:To explore the team construction and treatment strategy of the Diabetic Foot-Multidisciplinary Team.Methods:The clinical data of 19 patients with severe ischemic diabetic foot treated by our Diabetic Foot-Multidisciplinary Team Center from Apr 2021 to Mar 2022 were collected, and the overall amputation rate, above-ankle major amputation rate, minor amputation rate and mortality, Diabetic Foot-Multidisciplinary Team consultation discipline participation rate and treatment participation degree were retrospectively analyzed.Results:Nineteen patients (15 males and 4 females) were enrolled, aged 26 to 94 (68.6±14.2). All were with severe ischemic diabetic foot ulcer:Rutherford grade 5 or up and dysfunction in 2 or more organs. Complications included arteriosclerosis obliterans of the lower extremities in 18 cases, heart diseases in 18, hypertension in 15, and renal insufficiencies in 10. The overall amputation rate was 36.8%, major amputation rate in 21.1%, minor amputation rate in 15.8%, and mortality rate was 15.8%. A total of 16 disciplines participated in Diabetic Foot-Multidisciplinary Team; the main participating disciplines were vascular surgery (19 times), endocrinology (12 times), and cardiology (11 times). The main treatment disciplines were vascular surgery (14 times), plastic surgery (3 times), and cardiology (2 times).Conclusion:For the diagnosis and treatment of diabetic foot, it is necessary to set up a multidisciplinary team as early as possible to control the causes of diabetic foot ulcer, prevent the recurrence of diabetic foot ulcer, reduce the mortality and amputation rate, and improve the quality of life of patients.
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OBJECTIVE@#To analyze the association between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years, and to provide suggestions for the prevention and control of metabolic syndrome in Chinese children and adolescents.@*METHODS@#Data were collected from the research project "Development and Application of Technology and Related Standards for Prevention and Control of Major Diseases among Students" of public health industry in 2012. This project is a cross-sectional study design. A total of 65 347 students from 93 primary and secondary schools in 7 provinces including Guangdong were selected by stratified cluster random sampling method. Given the budget, 25% of the students were randomly selected to collect blood samples. In this study, 10 176 primary and middle school students aged 7 to 17 years with complete physical measurements and blood biochemical indicators were selected as research objects. Chi-square test was used to compare the distribution differences of growth patterns under different demographic characteristics. Birth weight, waist circumference and blood biochemical indexes were expressed in the form of mean ± standard deviation, and the differences among different groups were compared by variance analysis. Binary Logistic regression model was used to analyze the relationship between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years.@*RESULTS@#The prevalence of metabolic syndrome in children and adolescents was 6.56%, 7.18% in boys and 5.97% in girls. The risk of metabolic syndrome was higher in the catch-down growth group than in the normal growth group (OR=1.417, 95%CI: 1.19-1.69), and lower in the catch-up growth group(OR=0.66, 95%CI: 0.53-0.82). After adjusting for gender, age and so on, the risk of developing metabolic syndrome in the catch-down growth group was higher than that in the normal growth group (OR=1.25, 95%CI: 1.02-1.52), but there was no significant difference between the catch-up growth group and the normal growth group (OR=0.79, 95%CI: 0.62-1.01). Stratified analysis showed that the association between different growth patterns and metabolic syndrome was statistically significant in the 7-12 years group, urban population, and Han Chinese student population.@*CONCLUSION@#There is a correlation between different growth patterns and metabolic syndrome in children and adolescents. The risk of developing metabolic syndrome in children and adolescents with catch-down growth is higher than that in the normal growth group, which suggests that attention should be paid to the growth and development of children and adolescents, timely correction of delayed growth and prevention of adverse health outcomes.
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Mâle , Femelle , Humains , Enfant , Adolescent , Syndrome métabolique X/épidémiologie , Études transversales , Étudiants , Population urbaine , Asiatiques , Chine/épidémiologie , PrévalenceRésumé
OBJECTIVE@#To investigate the status of depression and social anxiety in children and adolescents, and to analyze the association between body fat distribution and depression, social anxiety in children and adolescents.@*METHODS@#A total of 1 412 children aged 7 to 18 years in Beijing were included by stratified cluster random sampling method. Body fat distribution, including total body fat percentage (total BF%), Android BF%, Gynoid BF% and Android-to-Gynoid fat ratio (AOI), were obtained by dual-energy X-ray absorption method. Depression and social anxiety were evaluated by Children Depression Inventory and Social Anxiety Scale for Children. Multivariate linear regression and restricted cubic spline analysis were used to estimate the linear and non-linear correlation between body fat distribution and depression and social anxiety.@*RESULTS@#13.1% and 31.1% of the children and adolescents had depressive symptoms and social anxiety symptoms respectively, and the detection rate of depression and social anxiety in the boys and young groups was significantly lower than those in the girls and old groups. There was no significant linear correlation between total BF%, Android BF%, Gynoid BF%, AOI and depression and social anxiety in the children and adolescents. However, total BF% and Gynoid BF% had significant nonlinear correlation with depression, showing an inverted U-shaped curve relationship with the tangent points of 26.8% and 30.9%, respectively. In terms of the nonlinear association of total BF%, Android BF%, Gynoid BF% and AOI with depression and social anxiety, the change trends of the boys and girls, low age group and high age group were consistent. The overall anxiety risk HR of body fat distribution in the boys was significantly higher than that in the girls, and the risk HR of depression and social anxiety were significantly higher in the high age group than those in the low age group.@*CONCLUSION@#There was no significant linear correlation between body fat distribution and depression and social anxiety in children and adolescents. Total BF% and depression showed an inverted U-shaped curve, mainly manifested in Gynoid BF%, and this trend was consistent in different genders and different age groups. Maintaining children and adolescents' body fat distribution at an appropriate level is the future direction of the prevention and control of depression and social anxiety in children and adolescents.
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Humains , Femelle , Enfant , Mâle , Adolescent , Études transversales , Rayons X , Dépression/épidémiologie , Absorptiométrie photonique/méthodes , Indice de masse corporelle , Répartition du tissu adipeux , Anxiété/épidémiologie , Tissu adipeux , Composition corporelleRésumé
Objective @#To explore the regulatory role of microRNA⁃455 ⁃3p ( miR⁃455 ⁃3p) in lymphangiogenesis of rat silicosis model , and to investigate the effect of miR⁃455 ⁃3p targeted regulation of vascular endothelial growth factor C (VEGF⁃C) on the tubular structure formation of human lymphatic endothelial cells ( HLECs) .@*Methods@#The rats were randomly divided into the silicosis model group and the normal control group. The silicosis model group were injected with silicon dioxide (SiO2 )dust suspension , and the control group was injected with the same amount of normal saline. HE , Masson and immunohistochemistry staining were used to observe the pathological changes and lymphangiogenesis of lung tissue. The expression levels of miR⁃455 ⁃3p and VEGF⁃C in lung tissues of rats were detected by Quantitative real⁃time PCR ( RT⁃qPCR) and Western blot; The miR⁃455 ⁃3p inhibitors and negative controls ( NC) were transfected into HLECs , and the expression levels of miR⁃455 ⁃3p and VEGF⁃C in cells were detected by RT⁃qPCR and Western blot. The migration ability of HLECs was detected by scratch test , the ability of tubular structure formation was detected by matrigel tube formation test , and dual luciferase experiments were used to verify the targeting relationship between miR⁃455 ⁃3p and VEGF⁃C.@*Results @#Compared with the normal control group , in the silicosis model group , a large number of inflammatory cells gathered and collagen gradually deposited in the pulmonary interstitium , and there was lymphatic hyperplasia in the lung. The expression of miR⁃455 ⁃3p in the lung tissue was lower than that in the control group , and the expression of VEGF⁃C was higher than that in the control group ; After transfection with HLECs , compared with the NC group , the expression of miR⁃455 ⁃3p in the cells of the Inhibitors group decreased , the expression of VEGF⁃C increased , and the ability of cell migration and tubular structure formation increased(P < 0. 05) ; VEGF⁃C was confirmed as a target gene of miR⁃455 ⁃3p by the dual luciferase experiments.@*Conclusion @#miR⁃455 ⁃3p can affect the tubular structure formation ability of HLECs and regulate lymphangiogenesis by targeting the expression of VEGF⁃C.
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The human telomeric i-motif (htel-iM) is a unique higher-order DNA structure formed by the cytosine-rich (C) sequences at the end of human telomeres. Studies have shown that htel-iM plays a significant role in the transcriptional regulation of telomeric repeat-containing RNA (TERRA) ‚ maintenance of telomere function and inhibition of telomerase activity. Thus‚ it is closely related to the development and progression of many cancers and is a promising new target for cancer treatment therapy. Compared to other nucleic acid higher-order structures such as G-quadruplexes‚ the stability of htel-iM is much weaker and affected by many factors like buffer pH‚ ionic conditions and molecular crowding environments. Therefore the existence of the iM structures in near neutral physiological conditions has been uncertain for a long time. Recently‚ using in-vitro screened small molecule ligands to selectively recognize and stabilize htel-iM provides a new strategy for the exploration of the biological relevance of htel-iM. Thus it has become a research hotspot to take telomere as a cancer treatment target. However‚ so far the reported small molecule ligands selectively targeting the htel-iM are far from sufficient compared with those targeting other higher-order nucleic acid structures. In this review‚ the discovery and the characteristic of the iM structures are briefly described‚ with an emphasis on the in-vitro affecting factors of the htel-iM structure‚ the reported htel-iM ligands and its biological relevance and regulation mechanisms‚ which will be helpful in further exploration of the htel-iM structure and ligand screening in near physiological conditions‚ and understanding the mechanism and developing novel therapeutic strategies for cancer treatment targeting the htel-iM structures.
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Background The pathogenesis of silicosis is complex and treatment methods are limited. SiO2-induced increase of transforming growth factor-β1 (TGF-β1) can activate fibroblasts to promote collagen deposition, ultimately leading to fibrosis. Previous studies have confirmed that lipid metabolism plays an important role in the progression of silicosis. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) mediates mitochondrial dysfunction and lipid metabolism pathways in diabetic models, but its role in silicosis has not been elucidated. Objective To investigate the effect of PGC1α on lipid metabolism disorder of macrophages induced by SiO2 and its effect on the progression of silicosis fibrosis. Methods (1) Macrophages were divided into four groups by transfecting and silencing PGC1α and its control sequence in macrophages and followed by SiO2 stimulation: negative control group (transfected with si-NC for 48 h), si-PGC1α group (transfected with si-PGC1α for 48 h), SiO2 stimulation group (stimulated with 50 μg·mL−1 SiO2 for 36 h after transfection with si-NC for 48 h), and si-PGC1α+SiO2 group (stimulated with 50 μg·mL−1 SiO2 for 36 h after transfection with si-PGC1α for 48 h). Western blot and cell immunofluorescence were used to test PGC1α expression, 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY 493/503) and total cholesterol (TC) and free cholesterol (FC) kits were used to test lipid accumulation, and the Oroboros2k-Oxygraph respiratory test system (O2K) was used to assess the effects of PGC1α on mitochondrial respiratory chain. ELISA kits were used to test TGF-β1 expressed in the macrophage supernatant. (2) Lung fibroblasts were divided into the same four groups as above, and stimulated with the supernatant of macrophages in the above groups. The expression of collagen Ι (COL Ι), E-cadherin (Eca), and fibronectin (FN) were detected by cell immunofluorescence and Western blot to further evaluate the effect of silencing PGC1α on fibrosis. Results The protein expression level of PGC1α stimulated by SiO2 was decreased, and the relative expression level of PGC1α was 0.78 times that of the control group (P<0.05). After transfection with si-PGC1α, the expression of PGC1α was decreased, and the relative protein expression level of the si-PGC1α group was 0.86 times that of the control group (P<0.05). Compared with the SiO2 stimulation group, the staining area of BODIPY 493/503 in the si-PGC1α+SiO2 group was enhanced, and the cholesterol-related indexes [TC, FC and cholesterol ester (CE)] were increased to 1.38, 1.10, and 2.26 times those in the SiO2 stimulation group (P<0.05). The activity of mitochondrial complex Ι was decreased, and the level of complex Ι in the si-PGC1α+SiO2 group was 0.63 times that in the SiO2 stimulation group (P<0.05). The secretion of TGF-β1 by macrophages increased, and the level of TGF-β1 in the si-PGC1α+SiO2 group was 1.15 times that of the SiO2 stimulation group (P<0.05). In addition, after stimulation of primary lung fibroblasts with macrophage supernatant, silencing PGC1α increased the expression levels of COL Ι and FN, while decreased the expression of Eca. The protein levels of COL Ι, FN, and Eca in the si-PGC1α+SiO2 group were 1.39, 1.18, and 0.82 times those in the SiO2 stimulation group, respectively (P<0.05). Conclusion Silencing PGC1α exacerbates SiO2-induced lipid metabolism disorder, inhibits mitochondrial respiratory chain, and aggravates the fibrosis induced by SiO2, suggesting that PGC1α may participate silicosis fibrosis by regulating mitochondrial respiratory chain and lipid metabolic disorder induced by SiO2.
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Objective:To understand the status of continuing care needs of patients with cleft lip and palate after discharge, and to analyze the influencing factors.Methods:Using convenience sampling method, 401 patients with cleft lip and palate and their nursing families who underwent sequential treatment of cleft lip and palate in Peking university hospital of stomatology from April to August 2021 were selected as the research objects. The general information questionnaire and self-made continuous nursing needs assessment table were used to investigate patients with cleft lip and palate current situation of continuous nursing needs and analyze the influencing factors.Results:The total score of continuing care needs of patients with cleft lip and palate was (91.53±12.07). From high to low, the demand dimensions were health promotion demand, disease self-care demand, doctor-patient communication demand and psychosocial support demand. The results of multivariate linear regression analysis showed that the mode of payment, the number of operations, the intention of rehabilitation guidance, the mode of continuation service and the expected continuation service cycle were the influential factors for the continuing nursing needs of patients with cleft lip and palate ( R2=0.282, F=27.16, P<0.05). Conclusion:Patients with cleft lip and palate have a high demand for continuing nursing. Individualized and effective continuous nursing intervention measures should be developed according to the needs of patients to promote the rehabilitation of patients.
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OBJECTIVE To prep are folate-targeted miR- 221 antisense oligonucleotide (anti-miR-221)delivery system ,and to preliminarily evaluate its in vitro anti-cancer effect on hepatocellular carcinoma. METHODS Folate-targeted anti-miR- 221 liposomes(FRL)were prepared by thin-film dispersion method ;the particle size ,Zeta potential and encapsulation efficiency were determined. The delivery efficiency of folate-targeted anionic liposome in human hepatoma HepG 2 cells was determined by in vitro cellular uptake experiment using calcein as the model drug. Flow cytometry was used to detect the effects of FRL on the apoptosis and cell cycle of HepG 2 cells. RESULTS The particle size of prepared FRL was (172.70±3.76)nm,Zeta potential was (-1.16± 0.15)mV and encapsulation efficiency was (83.53±1.85)%. In vitro cellular uptake experiments showed that folate-targeted anionic liposome successfully delivered calcein to HepG 2 cells,and the delivery efficiency in targeted group was higher than that of non-targeted liposome group (P<0.01). Apoptosis experiment results showed that the apoptotic rate of HepG 2 cells treated with FRL was significantly higher than that of non-targeted liposome (P<0.01). In cell cycle experiment ,FRL could shorten the S phase fraction of HepG 2 cells and induced arrest in the G 0/G1 and G 2/M phases. CONCLUSIONS FRL can encapsulate anti-miR-221 well and deliver it to hepatocellular carcinoma HepG 2 cells successfully ,and has a good in vitro anti-hepatoma effect in inducing apoptosis and cell cycle regulation.
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@#In this study, the conjugate of eicosapentaenoic acid (EPA) and hyaluronic acid (HA) was synthesized and the anti-hepatoma activities in vitro were evaluated.The hyaluronic acid-eicosapentaenoic acid (HA-EPA)nanoparticle was synthesized by linking eicosapentaenoic acid with hyaluronic acid with cystamine.The structure of HA-EPA was characterized by nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy (FT-IR).Laser particle sizer and Zeta potential analyzer were used to detect the size and potential of HA-EPA.MTT assay was used to detect the anti-proliferative effect of HA-EPA on HepG2, Huh-7 and LX-2 cells in vitro.The effects of HA-EPA nanoparticles on the proliferation and apoptosis of HepG2 cells in vitro were investigated by EdU staining and TUNEL staining. The apoptosis was further confirmed by flow cytometry.The effect of HA-EPA nanoparticles on the migration and invasion of HepG2 cells was demonstrated by transwell and invasion experiments.The results of 1H NMR showed that HA-EPA was successfully synthesized, and the grafting rate of EPA on HA was (40 ± 5) %. The structure of HA-EPA was further confirmed by FT-IR.The particle size was (162.5 ± 10.2) nm, and the potential was -(4.47 ± 0.31) mV.MTT results showed that, with the prolongation of drug treatment time, HA-EPA showed a better inhibitory effect on the activity of HepG2 and Huh-7 cells than EPA under the same EPA content.After treated for 48 hours, the toxicity of HA-EPA to LX-2 cells was less than that of EPA.The results of 24-hour proliferation, apoptosis, migration and invasion of HepG2 showed that, the graft of hyaluronic acid improved the ability of EPA to inhibit proliferation, promote apoptosis, migration and invasion of HepG2 cells (P < 0.001), indicating that grafting of HA can significantly enhance the inhibitory effect of EPA on liver cancer with some role in reducing toxicity.
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Objective:To investigate the relationship between serum leukocyte-associated immunoglobulin-like receptor 2 (LAIR2) expression and cellular immune function, prognosis in patients with non-small cell lung cancer.Methods:From April 2016 to April 2017, 90 patients with non-small cell lung cancer who were treated in Shangqiu first people’s Hospital were taken as the lung cancer group, and they were grouped into the survival group and the death group according to whether the patients died within 5 years. Another 84 patients with benign pulmonary mass were selected as the control group. The levels of CD4+[ (28.26±5.14) % vs (47.02±6.73) %], CD8+ [ (23.76±5.84) % vs (30.12±6.03) %] and CD4+/CD8+ [ (1.17±0.30) % vs (1.56±0.50) %] in peripheral blood immune cells were detected by flow cytometry; the serum LAIR2 level was detected by enzyme-linked immunosorbent assay (ELISA) , and the average serum LAIR2 level of patients with non-small cell lung cancer was applied as the boundary, and they were grouped into a low LAIR2 expression group and a LAIR2 high expression group; Pearson correlation was applied to analyze the correlation between serum LAIR2 level and immune cell level in patients with non-small cell lung cancer; Kaplan-Meier curve was applied to analyze the relationship between serum LAIR2 level and 5-year survival rate of patients with non-small cell lung cancer; and multivariate COX regression analysis was applied to analyze the factors affecting 5-year mortality in patients with non-small cell lung cancer.Results:The level of serum LAIR2 [ (69.55±13.12) ng/ml vs. (20.64±7.13) ng/ml] in the lung cancer group was significantly higher than that in the control group, and the levels of CD4 +, CD8 + and CD4+/CD8+ were significantly lower than those in the control group ( P<0.05) . The serum LAIR2 level in patients with TNM stage III+IV (77.32±13.09) ng/ml, poorly differentiated tissue (78.14±13.26) ng/ml, and lymph node metastasis (79.02±13.81) ng/ml was significantly higher than that in patients with TNM stage I+II (64.37±12.89) ng/ml, medium/well differentiated tissue (64.32±12.73) ng/ml, and no lymph node metastasis (62.92±12.85) ng/ml ( P<0.05) . The levels of CD4 +, CD8 + and CD4 +/CD8 + in the LAIR2 high expression group were significantly lower than those in the LAIR2 low expression group ( P<0.05) . Serum LAIR2 level in patients with non-small cell lung cancer was negatively correlated with CD4+, CD8+ and CD4+/CD8+ levels ( r=-0.510, -0.496, -0.494, P<0.05) . The 5-year survival rate of patients with high LAIR2 expression was lower than that of patients with low LAIR2 expression ( r=6.375, P<0.05) . LAIR2 was an independent risk factor for 5-year death in patients with non-small cell lung cancer ( P<0.05) . Conclusion:LAIR2 is highly expressed in serum of patients with non-small cell lung cancer, and its expression level is closely related to cellular immune function and prognosis.
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OBJECTIVE@#To confirm the improvement of cardiac function and quality of life (QOL) in patients with chronic heart failure (CHF) via Chinese medicine (CM) Qishen Taohong Granule (, QTG).@*METHODS@#This study was a single-center, prospective, randomized, controlled clinical trial. Seventy-six patients from 27 to 84 years old diagnosed with CHF New York Heart Association (NYHA) class II or III in stage C were enrolled and randomly assigned at a 1:1 ratio to receive QTG or trimetazidine (TMZ), in addition to their standard medications for the treatment of CHF. The study period was 4 weeks. The primary outcomes included cardiac function evaluated by NYHA classification and left ventricular ejection fraction (LVEF), as well as QOL evaluated by CHF Integrated Chinese and Western Medicine Survival Scale (CHFQLS). The secondary outcomes included 6-min walking test (6MWT), CM syndrome score, symptom and sign scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP). All indices were measured at baseline and the end of the trial.@*RESULTS@#At the 4-week follow-up period, the effective rate according to NYHA classification in the QTG group was better than that in the TMZ group (74.29% vs. 54.29%, P<0.05). But there was no significant difference in post-treatment level of LVEF between the two groups (P>0.05). The CHFQLS scores improved by 13.82±6.04 vs. 7.49±2.28 in the QTG and TMZ groups, respectively (P<0.05). Subgroup analysis of the CHFQLS results showed that physiological function, role limitation and vitality were significantly higher in the QTG group than in the TMZ group (15.76±7.85 vs. 7.40±3.36, P<0.05; 16.00±8.35 vs. 10.53±4.64, P<0.05; 15.31±8.09 vs. 7.89±4.60, P<0.05). Compared with TMZ group, treatment with QTG also demonstrated superior performance with respect to 6MWT, CM syndrome, shortness of breath, fatigue, gasping, general edema and NT-proBNP level. No significant adverse reactions or adverse cardiac events occurred during treatment in either group.@*CONCLUSION@#In addition to conventional treatments, the use of QTG as an adjuvant therapy significantly improved cardiac function and QOL in patients with CHF class II or III in stage C. [Registration No. ChiCTR1900022036 (retrospectively registered)].