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Objective:To investigate the effects of exosomes of human nucleus pulposus cells (NPCs) on the differentiation of urine derived stem cells (USCs) into nucleus pulposus-like cells.Methods:USCs and NPCs were isolated and cultured in vitro. The exosomes of NPCs were extracted and detected by Western-blot. USCs cytoplasm was transfected with GFP lentivirus, while nucleus was transfected with DAPI dye. The NPCs exosomes were transfected with PKH26 dye. After co-incubation for 12 h, USCs and NPCs exosomes were observed by macroscopy. USCs differentiation was induced by NPCs exosomes and non-contact co-culture methods. The relative expression of marker gene mRNA of nucleus pulposus cells in each group and the absorbance at 450 nm wavelength were detected.Results:The isolated USCs had the ability to differentiate into osteocytes, adipocytes and chondrocytes with high expression of marker CD29 (99.57%), CD44 (97.46%) and CD73 (97.71%) and with low expression of negative proteins CD31 (0.59%) and CD45 (0.19%). The isolated NPCs highly expressed nuclear pulposus cell marker COL2A1, ACAN and SOX-9. The exosomes extracted from NPCs showed high expression of exosome marker CD63, CD81 and Tsg101. After 12 h co-incubation, NPCs exosomes fused with USCs membrane and appeared in the cytoplasm of USCs. At 3, 5 and 7 days of co-culture, the absorbance value of USCs cells in exosome group (0.44±0.004, 0.76±0.004, 0.82±0.006) was higher than that in co-culture group (0.39±0.022, 0.63±0.035, 0.69±0.012) ( P<0.05). The mRNA relative expression of USCs nucleus pulposus marker genes ACAN (1.80±0.31, 3.50±0.21, 5.35±0.31, 7.46±0.12), COL2A1 (1.43±0.15, 4.33±0.23, 6.89±0.22, 8.11±0.31), SOX-9 (2.21±0.13, 3.13±0.11, 3.96± 0.14, 4.52±0.26) and HIF-1α (1.45±0.16, 2.14±0.21, 4.31±0.41, 4.01±0.25) in exosomes group were significantly higher than those in the control group ( P<0.05) at the 3rd, 7th, 14th and 21st days. The mRNA relative expression of USCs nucleus pulposus marker genes ACAN (5.69±0.21, 6.69±0.13), COL2A1 (6.33±0.17, 7.89±0.15), SOX-9 (4.19±0.29, 4.38±0.12), HIF-1α (4.49±0.32, 4.96±0.26) in exosomes group were significantly higher than those ACAN (3.69±0.35, 5.13±0.23), COL2A1 (3.40±0.16, 6.79±0.19), SOX-9 (2.26±0.32, 3.69±0.26), HIF-1α (2.39±0.11, 3.96±0.13) in non-contact co-culture group ( P<0.05) at the 14th and 21st days. Conclusion:Human nucleus pulposus exosomes could induce differentiation of human USCs into nucleus pulposus-like cells in vitro. Compared with non-contact co-culture, exosomes have higher induction efficiency and can better maintain the proliferation activity of nucleus pulposus-like cells
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Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.
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Objective:To evaluate the volume changes of cervical longus and cervical extensor after anterior cervical discectomy and fusion (ACDF), and the correlation with the clinical efficacy of patients.Methods:All of 57 patients with cervical spondylotic myelopathy who underwent single-segment ACDF surgery from January 2013 to December 2018 were analyzed. The follow-up time was 23.0±4.8 months (range 16-34 months). All included subjects underwent MR examination within 1 week before operation and 3rd, 12th months after operation and at the last follow-up. The axial section cross section area (AxCSA) of the cervical longus and the ratio of length to short diameter line (RLS) at the level of each disc of C 2-C 7 were measured on the axial T2WI. Calculate the volume of the cervical longus based on the layer thickness. At the same time, measure the cervical extensor cross-sectional area (CESA) of the same level including the multifidus, cervical semispinous muscle, semispinous head, splinter head, and cervical splinter muscles, and compare CESA with the corresponding vertebral cross-sectional area (VBA). The ratio is analyzed as the volume of the neck extensor muscle, namely CESA/VBA. At the 3rd and 12th months after operation and at the last follow-up, the axial pain was assessed by visual analogue scale (VAS) for assessing pain, and the modified Japanese Orthopedic Association score (mJOA) and the neck dysfunction index (NDI) were used to assess the functional status of the cervical spine. Analyze the morphological changes of thecervical longus and extensor cervical muscles before and after the operation and during the follow-up period, and analyze the correlation with VAS, mJOA, and NDI. Results:Compared with the preoperative period, the average AxCSA of the surgical segment decreased at the 3rd and 12th months after the operation and at the last follow-up. The difference was statistically significant ( F=24.113, P<0.05), which was changed from 140.84±19.51 mm 2 respectively reduce to 117.74±17.15 mm 2 ( t=6.714, P<0.05), 116.37±18.67 mm 2 ( t=6.841, P<0.05) and 116.27±18.65 mm 2 ( t=6.873, P<0.05). Compared with preoperatively, they were reduced by 16.40%, 17.37% and 17.45%, respectively, while the average RLS of surgical segments increased slightly, and the difference was statistically significant ( F=22.612, P<0.05), which increased from preoperative 1.97±0.67 to 2.73±0.60 (38.58% increased, t=6.380, P<0.05), 2.82±0.64 (43.15% increased, t=6.926, P<0.05) and 2.74±0.62 (39.09% increased, t=6.368, P<0.05). The volume of thecervical longus of the patients decreased after the operation, and the difference was statistically significant ( F=64.511, P<0.05), which decreased from 8853.48±458.65 mm 3 before the operation to 7834.53±461.59 mm 3 (11.51% decreased, t=11.822, P<0.05), 7926.42±456.24 mm 3 (10.47% decreased, t=10.819, P<0.05), 7892.38±450.78 mm 3 (10.86% decreased, t=11.283, P<0.05). There were no statistically significant differences in the non-surgical segment AxCSA, RLS and the volume of thecervical longus at the 3rd and 12th months after surgery and the last follow-up ( P>0.05). There was no statistically significant difference of CESA and CESA/VBA compared to preoperative in the surgical segment and non-surgical segment ( P>0.05). Pearson correlation analysis showed that the volume of cervical longus and VAS at the 3rd month ( r=-0.308, P<0.05), the 12th month ( r=-0.210, P<0.05) and the last follow-up ( r=-0.404, P<0.05) were negatively correlated; Among the volume of cervical longus and NDI in the 3rd month ( r=-0.511, P<0.05), 12th month ( r=-0.518, P<0.05) and the last follow-up ( r=-0.352, P<0.05), there was a negative correlation; However, there was no statistically significant correlation between the cervical longus muscle volume and mJOA at each follow-up time point ( P>0.05); There was no significant correlation between CESA/VBA and VAS, NDI, and mJOA at the 3rd, 12th and last follow-up ( P>0.05). Conclusion:The volume and morphology of cervical longus after ACDF was significantly reduced compared with that before the operation, but the volume and morphology of the cervical extensor muscle did not change significantly. ACDF surgery mainly affects the cervical longus corresponding to the surgical segment, and the volume is negatively correlated with the VAS and NDI during follow-up.
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Objective@#To assess the effects of acute exposure to electronic cigarette ( e-cigarette ) on leukocyte and total protein levels in bronchoalveolar lavage fluid ( BALF ) and pulmonary surfactant protein expression in a mouse model, so as to provide insights into the elucidation of the mechanism underlying the damages to the respiratory system caused by e-cigarette.@*Methods@#Twenty-one C57BL/6N female mice were randomly divided into the blank control group, the solvent control group and the nicotine group. Mice in the solvent control group and the nicotine group were exposed to the solvent aerosol or e-cigarette aerosol containing 25 mg/mL nicotine for 3 hours daily, while mice in the blank control group were bred in clean air. Following 3-day exposure, mouse BALF and lung specimens were collected. The cell morphology was observed using microscopy following Wright-Giemsa staining and the leukocyte count was estimated in BALF, while the total protein expression was quantified using bicinchoninic acid ( BCA ) assay. In addition, the mRNA expression of pulmonary surfactant protein genes was detected in mouse lung specimens using quantitative real-time PCR ( qPCR ) assay.@*Results@#All mice in three groups grew well without obvious abnormality or death seen. Wright-Giemsa staining showed a higher number of mononuclear macrophages in mouse BALF in the nicotine group than in the blank control group and the solvent control group. The leukocyte counts were ( 2.00±0.77 )×107, ( 1.79±0.99 )×107 and ( 4.00±1.35 )×107 cells/L ( F=9.199, P=0.002 ), and the total protein levels were ( 0.16±0.03 ), ( 0.12±0.02 ) and ( 0.16±0.04 ) mg/mL in mouse BALF in the blank control group, solvent control group and nicotine group ( F=3.610, P=0.048 ), and the relative mRNA expression of pulmonary surfactant protein B (SP-B) and SP-D was 1.00±0.14, 0.82±0.12 and 0.74±0.07 ( F=5.491, P=0.028 ), and 1.00±0.06, 0.90±0.02 and 0.71±0.15 in mouse lung specimens, respectively ( F=10.460, P=0.005 ). The leukocyte count was significantly higher in the nicotine group than in the blank control group and solvent control group (P=0.007, 0.003), and the total protein content was higher in the nicotine group than in the solvent control group ( P=0.060 ), while the relative SP-B mRNA expression was lower in the nicotine group than in the blank control group ( P=0.025 ), and the relative SP-D mRNA expression was lower in the nicotine group than in the blank control group and solvent control group ( P=0.004, 0.041 ).@*Conclusion@#Acute exposure to e-cigarette results in elevated intrapulmonary inflammatory responses, pulmonary capillary barrier impairment and reduced pulmonary surfactant protein expression.
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Neonatal methemoglobinemia is a rare disorder characterized by cyanosis and hypoxemia, which could be caused congenitally by cytochrome b5 reductase enzyme deficiency or hemoglobin M disease, and could be acquired by the exposure to lidocaine, nitrites and other drugs.Blood gas analysis is a simple and accessible way to detect methomoglobin.Methemoglobinemia is related to numerous diseases in neonates, including diarrhea, acidosis, late-onset sepsis.Methylene blue is an effective drug for decreasing MetHb levels.Other therapeutic options, such as vitamin C, N-acetylcysteine and vitamin B2, could also be useful.This article reviews the progress of neonatal methemoglobinemia.
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Objective: To systematically evaluate the clinical effect of Xiaoke Decoction in the treatment of type 2 diabetes. Methods: Chinese databases such as CNKI, Wanfang, Weipu Chinese Biomedical Journal Database, and Chinese Medical Biological Literature Database, PubMed, Cochrane Library, Embase, and Web of Science were searched for English language literature from their inception until November 2019. A Meta-analysis was performed using RevMan 5.3 and Stata 12.0. Results: Thirty-eight studies were included in this study, with a total of 3757 patients. It was found that adding Xiaoke Decoction could improve total efficiency. The Xiaoke Decoction groups surpassed the western medicine groups regarding improvement in total efficiency (OR = 3.49; 95% CI: 2.78–4.39, P < 0.00001). Adding Xiaoke Decoction could lower the fasting plasma glucose (FPG) level. The Xiaoke Decoction groups surpassed the western medicine groups regarding reduction in FPG levels (MD = −1.14; 95% CI: −1.36 to 0.92, P < 0.00001). Adding Xiaoke Decoction could lower the 2 h postprandial blood glucose (2hPG) level. The Xiaoke Decoction groups surpassed the western medicine groups regarding reduction in 2hPG (MD = −1.40; 95% CI: −1.61 to 1.19, P < 0.00001). Adding Xiaoke Decoction could lower glycated hemoglobin (HbA1c). The Xiaoke Decoction groups surpassed the western medicine groups regarding reduction in HbA1c (MD = −0.77; 95% CI: −0.95 to 0.58, P < 0.00001). It was found that adding Xiaoke Decoction could lower the traditional Chinese medicine (TCM) syndrome score. The TCM syndrome scores among patients in the Xiaoke Decoction group were lower than those among patients in the control group after treatment (MD = −4.90; 95% CI: −7.22 to 2.57, P < 0.0001). At the same time, we conducted a subgroup and sensitivity analysis of age and intervention duration on the heterogeneity of total efficiency, FPG, 2hPG, HbAlc, and TCM syndrome score outcome indicators. For detecting publication bias, an egger test was conducted. Conclusion: Compared with western medicine alone, Xiaoke Decoction has more advantages for the treatment of type 2 diabetes with respect to total efficiency, FPG, 2hPG, HbAlc, and TCM syndrome score.
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Objective:To study the predictive value of hour-specific total serum bilirubin(TSB) nomogram combined with clinical risk factors in the risk of hyperbilirubinemia.Method:Perinatal clinical data of newborns born in Shanghai Pudong New Area Health Care Hospital for Women and Children, Shanghai Pudong New Area People's Hospital and Shanghai Pudong Hospital from August 2017 to July 2018 were collected in this prospective study. Transcutaneous bilirubin (TcB) was monitored before discharge from hospital. Enrolled neonates were followed up for 28 days. The patients were assigned to neonatal hyperbilirubinemia group (NHB) and non-hyperbilirubinemia group (Non-HB) according to the occurrence of hyperbilirubinemia. The predictive value of models for the risk of hyperbilirubinemia was evaluated by receiver operating characteristic (ROC) curves and Logistic regression analysis.Result:A total of 8 664 newborns were included in this study, with 1 196 cases of hyperbilirubinemia, with an incidence of 13.8%. Logistic regression analysis showed that maternal blood type O, premature rupture of membranes, male gender, gestational age 35~37 weeks, subcutaneous ecchymosis/cranial edema, and breastfeeding were independent risk factors for NHB ( P<0.05). The area under receiver operative characteristic curve (ROC) of predischarge bilirubin risk zone only was 0.874(95% CI 0.861~0.885, P<0.05)and for all independent risk factors was 0.664 (95% CI 0.647~0.680, P<0.05). The area under ROC curve was 0.891 (95% CI 0.880~0.902, P<0.05) by combining predischarge bilirubin risk zone with clinical risk factors. Conclusion:Predischarge bilirubin risk zone combined with clinical risk factors can reasonably predict neonatal hyperbilirubinemia well.
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Objective:To retrospectively analyze the clinical application of extracorporeal membrane oxygenation (ECMO) in severe adenovirus pneumonia, and to evaluate the application value of ECMO in children with severe adenovirus pneumonia.Methods:Children diagnosed with severe adenovirus pneumonia and intervened with ECMO in the Hunan Children′s Hospital from January 1, 2018 to December 31, 2019 were recruited in this study for analyzing.The gender, age, clinical manifestations, mechanical ventilation duration, ECMO duration, the length of hospital stay, complications and prognosis were collected and analyzed.Results:A total of 4 children were included in the study, involving 2 cases were successfully evacuated from ECMO.Finally, 3 children died, and 1 case survived.Three death cases had a longer than 18 days of duration from the onset to the start with ECMO.Their ventilator assist time before star-ting ECMO was 3-5 days, and ECMO intervention time was longer, with the maximum of 27.5 days.The survived case had an 11-day duration from the onset to the start with ECMO, and the ventilator assisted time and ECMO intervention time were 5 days, and less than 10 days, respectively.Conclusions:ECMO treatment for children with severe adenovirus pneumonia has a low success rate, but it is still the most important way to save children.Early application of ECMO can improve the prognosis of children with severe adenovirus pneumonia.
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Exosomes are vesicles with a double globular membrane of lipids that can be secreted by a variety of cells, including stem cells. Exosomes have unique biological characteristics and irreplaceable powerful functions which play an important role in intercellular communication. The various cytokines, signal proteins, lipids and regulatory nucleic acids contained in stem cell exosomes can play a protective role against the injury of kidney, liver, heart, blood vessels and nerves. Stem cell exosomes delay the process of intervertebral disc degeneration by inhibiting the apoptosis of nucleus pulposus cells and increasing the synthesis of extracellular matrix, etc. The mechanism of its role is mainly through miRNA and related signaling pathways. Exosomes contain complex components. Although the mechanism of action of exosomes in intervertebral discs has been preliminarily explored, the components contained in exosomes are complex and the specific situation has not been fully understood, which still needs further study. In this review, the characteristics and functions of stem cell exosomes, extraction, identification and storage methods, the impacttovarious other tissues, as well as the effects on intervertebral discs and their mechanisms were elaborated in order to provide a basis for the study of intervertebral disc degenerative diseases.
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Human milk plays an irreplaceable role in nutrition, immune promotion and psychological development of infants.And it can also decrease the risk of infectious disease, overweight/obesity, diabetes and other diseases.Therefore, the guidelines of various countries advocate that human milk is the optimal choice for infants.However, cases of food allergy in infants fed with human milk are common in clinical practice.Some studies have found that there are some active food antigens in human milk, which can stimulate immune responses and cause allergic symptoms in infants.At present, the mechanism of food allergy in infants fed with human milk is not clear, and this paper is to review the progress in this field in recent years.
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Lianhuaqingwen (LHQW) capsule, a herb medicine product, has been clinically proved to be effective in coronavirus disease 2019 (COVID-19) pneumonia treatment. However, human exposure to LHQW components and their pharmacological effects remain largely unknown. Hence, this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities. Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach, leading to detection of 132 LHQW prototype and metabolite components, which were absorbed
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Objective:To explore the effect of minimally invasivetransforaminal lumbar interbody fusion (MIS-TLIF) on lumbar multifidus muscle using MRI techniqueandits clinical significance.Methods:From September 2016 to July 2019, 23 patients who underwent MIS-TLIF surgery for unilateral symptomatic disc herniation in unilateral segments (L 3,4, L 4,5, L 5S 1) of Qingdao University Affiliated Hospital were studied. Their lumbar MR examination was performed 1 week before surgery, and 3 and 6 months after surgery. The axial section of multifidus muscle cross section area (AxCSA) was measured on the axial T2WI image of each intervertebral disc level before and after the operation. The ratio of long and short lines (RLS) was calculated, andthe ratio of axial section of muscle fat infiltration cross section area (FLSA) and AxCSAwasrecorded as FLSA/AxCSA. The changes of various indexes of multifidus muscle in the affected side and the healthy side of the lumbar spine before and after the operation were compared, and the effect of the MIS-TLIF procedure on the morphology of the multifidus muscle was observed. Magnetic resonance spectroscopy (MRS) measurements of the muscle cross-section of the affected side were performed before and 6 months after the operation. The integral value of intracellular lipid (IMCL) and extracellular lipid (EMCL) of 1H spectrum muscle cells was compared, while the degree of fat infiltration was measured. Results:Patients with single-segment lumbar disc herniation had larger AxCSAin the healthy side than the affected side before surgery in surgical level ( t=6.611, P<0.05), and the muscle AxCSAin the healthy side was larger than the affected side in non-surgical levels ( t=-6.682, P<0.05), both suggested preoperative muscle volume advantage in the healthy side; no difference in bilateral AxCSA at 3 months was found after surgeryin surgical levels ( t=0.197, P> 0.05)and non-surgical levels ( t=-1.631, P> 0.05), which suggested bilateral muscle volume equal advantageat short-term follow-up. The FLSA/AxCSA of affected segment before and after 3 months was 9.5%±3.8% and 8.7%±1.5%, and the difference was statistically significant ( t=3.163, P<0.05); the RLS of affected segment before and after 3 months was 3.3%±0.24% and 2.7%±0.83%, and the difference was statistically significant ( t=3.42, P<0.05). The medians of EMCL/IMCL before and after 6 months of MRS were 2.010 and 1.475, respectively, and EMCL decreased after 6 months ( Z=0.48, P<0.05). Conclusion:Patients with single-segment lumbar disc herniation have different morphology of bilateral multifidus muscle before surgery. MIS-TLIF has little effect on the multifidus muscle of the surgical side. MIS-TLIF significantly reduces extracellular lipid accumulation, promotes intracellular transfer, and increases intracellular fat metabolism. Its retention of muscle attachment points and limited fixation can also reshape compensatory muscle atrophy.
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Objective:To investigate the influencing factors for celiac lymph node metastasis in thoracic esophageal squamous cell carcinoma (TE-SCC), construct a prediction model of celiac lymph node metastasis in TE-SCC, and stratify the probability of celiac lymph node metastasis.Methods:The retrospective case-control study was conducted. The clinicopathological data of 443 patients with TE-SCC who underwent thoracoscopic and laparoscopic esophagectomy with systematic lymph node dissection in the First Affiliated Hospital of Zhengzhou University between March 2015 and April 2019 were collected. There were 259 males and 184 females, aged from 41 to 81 years, with a median age of 64 years. The nomogram prediction model was constructed based on the results of multivariate analysis of influencing factors for celiac lymph node metastasis in TE-SCC, of which calibration curve and decision curve were drawed. The predictive performance was evaluated using the concordance index. The score for celiac lymph node metastasis in TE-SCC predicted by nomogram model was used for further recursive partitioning analysis, and patients were stratified into risk subgroups using the decision-making tree model. Observation indicators: (1) celiac lymph node metastasis in TE-SCC; (2) analysis of influencing factors for celiac lymph node metastasis in TE-SCC; (3) construction of nomogram prediction model of celiac lymph node metastasis in TE-SCC; (4) construction of decision-making tree model of celiac lymph node metastasis in TE-SCC and risk subgroup analysis of celiac lymph node metastasis probability. Measurement data with skewed distribution were represented as M (range). Count data were represented as absolute numbers and percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data between groups was analyzed using the nonparametric rank sum test. Multivariate analysis was performed using the Logistic regression model. Based on Logistic regression model multivariate analysis, a new nomogram model was constructed using the RStudio 3.4 software. Results:(1) Celiac lymph node metastasis in TE-SCC: celiac lymph node metastasis was found in 89 of the 443 patients, with a celiac lymph node metastasis rate of 20.09%(89/443). (2) Analysis of influencing factors for celiac lymph node metastasis in TE-SCC. Results of univariate analysis showed that tumor location, tumor length, tumor differentiation degree, pathological T staging, nerve invasion, vessel invasion, and thoracic lymph node metastasis were related factors for celiac lymph node metastasis in TE-SCC ( χ2=12.177, Z=-2.754, -4.218, -4.254, χ2=3.908, 33.025, 30.387, P<0.05). Results of multivariate analysis showed that tumor location, vessel invasion, and thoracic lymph node metastasis were independent influencing factors for celiac lymph node metastasis in TE-SCC ( odds ratio=2.165, 3.442, 2.876, 95% confidence interval: 1.380-3.396, 1.787-6.633, 1.631-5.071, P<0.05). (3) Construction of nomogram prediction model of celiac lymph node metastasis in TE-SCC: based on the factors screened by multivariate analysis, including tumor location, vessel invasion, and thoracic lymph node metastasis, the nomogram prediction model of celiac lymph node metastasis in TE-SCC was established, with the concordance index of 0.846. The calibration curve showed a high consistency between the celiac lymph node metastasis probability estimated by the prediction model and the actual rate of celiac lymph node metastasis. The decision curve showed that the nomogram prediction model of celiac lymph node metastasis in TE-SCC had a good prediction value when the probability threshold was 0.001-0.819.(4) Construction of decision-making tree model of celiac lymph node metastasis in TE-SCC and risk subgroup analysis of celiac lymph node metastasis probability: patients were stratified into six risk subgroups using the decision-making tree model based on the celiac lymph node metastasis probability. The group A included patients with no vessel invasion+negative thoracic lymph node, group B included patients with no vessel invasion+the number of positive thoracic lymph nodes of 1-3, group C included patients with no vessel invasion+the number of positive thoracic lymph nodes of ≥4, group D included patients with vessel invasion+the number of positive thoracic lymph nodes of 0-2+upper or middle thoracic esophageal carcinoma, group E included patients with vessel invasion+the number of positive thoracic lymph nodes of 0-2+lower thoracic esophageal carcinoma, group F included patients with vessel invasion+the number of positive thoracic lymph nodes of ≥3. The group A was low-risk group with the celiac lymph node metastasis probability of 11%, group B and D were intermediate low-risk groups with the celiac lymph node metastasis probability of 27% and 21%, group C and E were the intermediate high-risk groups with the celiac lymph node metastasis probability of 56% and 55%, and group F was high-risk group with the celiac lymph node metastasis probability of 80%. Conclusions:The tumor location, vessel invasion, and thoracic lymph node metastasis are independent influencing factors for celiac lymph node metastasis in TE-SCC. Vessel invasion has the dominant influence on celiac lymph node metastasis, followed by the number of positive thoracic lymph nodes, and then the tumor location. Patients can be stratified into six risk subgroups based on the nomogram prediction model and decision-making tree model of celiac lymph node metastasis in TE-SCC.
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Objective:To explore the polymorphism of the uridine diphosphateglucuronosyl transferase 1A1 ( UGT1A1) gene in children of multiple nationalities with etiology-unknown neonatal hyperbilirubinemia in Qiubei County. Methods:Full-term neonates with unknown cause hyperbilirubinemia were collected.They were admitted to neonatal ward of Qiubei People′s Hospital from September 2017 to June 2018.All of them were performed UGT1A1 gene test. Results:A total of 100 neonates were enrolled in this study.Among them, 53 infants were Han, and others were minorities.Ten mutation sites of UGT1A1 gene were found.Five sites were never reported before and 4 sites could be pathogenic mutations.In addition, c.211G>A.was the most common genetic mutation, and 13 cases of homozygote and 32 cases of heterozygote were revealed by exome sequencing.The bilirubin levels of children with homozygote c. 211G>A were higher than those without the variation in this study and the differences were statistically significant ( t=2.621, P=0.008). The incidence of c. 211G>A mutation was similar between Han and minority nationalities.Among new-found mutations, c.1091C>CA heterozygous mutation was found in 19 children and in several nationalities, suggesting that this was a common UGT1A1 gene mutation in Qiubei County.Besides c. 211G>A and c. 1091C>CA were the most common variants.The incidence of c. 211G>A had no significant difference between Han and minority nationalities (χ 2=0.215, P=0.643). Neither had the incidence difference of c. 1091C>CA between Han and minority nationalities (χ 2=0.017, P=0.897). Conclusion:c. 211G>A and c. 1091C>CA mutations , which are distributed in both Han and minority nationalities, are common UGT1A1 mutations in Qiubei County.The distribution rate of c. 211G>A mutation is high in the population.The homozygous variation of c. 211G>A is associated with neonatal hyperbilirubinemia.
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BACKGROUND@#To date, there is no effective treatment for thromboangiitis obliterans (TAO). Anlotinib, as a third-line therapy, is recommended for patients with refractory advanced non-small cell lung cancer (NSCLC). We presented a case report of a patient suffering from right lung squamous cell carcinoma combined with thromboangiitis obliterans, and analyzed the treatment dilemma, which provided a new idea for the treatment of these two diseases.@*METHODS@#A patient of right lung squamous cell carcinoma complicated with TAO was admitted to the department of respiratory and critical care medicine of the Shanghai General Hospital in August 2018. The diagnosis and treatment was retrospectively analyzed, and the literature was reviewed.@*RESULTS@#The 73-year-old male patient complained of cough and sputum for 5 months and was diagnosed with NSCLC (T4N2M0, stage IIIb, performance status score 2) in right upper lung by tracheoscopy biopsy. Pigmentation in both lower extremities accompanied by weakened pulse of dorsal foot artery was confirmed. He had a history of smoking, and suspected vascular intermittent claudication and wandering phlebitis for more than one year. Ultrasound indicated multiple arterial occlusion in both upper and lower extremities and deep venous thrombosis in lower extremities. TAO was diagnosed. Peripherally inserted central catheter (PICC) implantation and intravenous infusion post implantation failed and he could not receive chemotherapy. Vascular endothelial growth factor (VEGF) signal pathway dysfunction is also involved in TAO. Anlotinib (12 mg qd po) was selected for treatment NSCLC and TAO, accordingly. He had partial response (PR) and the cancer kept stable for 14 months. At the same time, TAO improved.@*CONCLUSIONS@#Anlotinib effectively controlled the growth of NSCLC and improved TAO related symptoms. Anlotinib maybe normalize disordered growth of blood vessels through the VEGF signaling pathway, rather than simply inhibiting angiogenesis.
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Objective To investigate the characteristics of the adverse drug reaction (ADR) in the traditional Chinese medicine (TCM) treatment followed the "COVID-19 Diagnosis and Treatment Program (trial version 7)" during the medical observation period, and to provide a guideline for rational clinical drug use. Methods 9 TCM induced ADR were collected from CNKI, Wanfang database and PubMed. Statistical analysis was conducted on gender, age, occurrence time, involved system/organ, treatment, outcome and relevance evaluation. Results 61 literatures were collected according to the inclusion and exclusion criteria with 70 cases and 5 TCM prescriptions. There was no significant bias in gender. The age span was large. Most ADR occurred within 1 day after administration. The involved systems/organs are extensive, mainly on the skin and its accessories. The most common therapeutic drugs were antihistamines and steroids, and other medications are mainly for symptom treatment. The turnaround time was 1 h in most cases (47%). Conclusions During the observation period, the incident population was widely distributed and there was no obvious characteristics. Medication monitoring should be reinforced to reduce the ADR incidence.
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Tremendous efforts have been devoted to the enhancement of drug solubility using nanotechnologies, but few of them are capable to produce drug particles with sizes less than a few nanometers. This challenge has been addressed here by using biocompatible versatile -cyclodextrin (-CD) metal-organic framework (CD-MOF) large molecular cages in which azilsartan (AZL) was successfully confined producing clusters in the nanometer range. This strategy allowed to improve the bioavailability of AZL in Sprague-Dawley rats by 9.7-fold after loading into CD-MOF. The apparent solubility of AZL/CD-MOF was enhanced by 340-fold when compared to the pure drug. Based on molecular modeling, a dual molecular mechanism of nanoclusterization and complexation of AZL inside the CD-MOF cages was proposed, which was confirmed by small angle X-ray scattering (SAXS) and synchrotron radiation-Fourier transform infrared spectroscopy (SR-FTIR) techniques. In a typical cage-like unit of CD-MOF, three molecules of AZL were included by the -CD pairs, whilst other three AZL molecules formed a nanocluster inside the 1.7 nm sized cavity surrounded by six -CDs. This research demonstrates a dual molecular mechanism of complexation and nanoclusterization in CD-MOF leading to significant improvement in the bioavailability of insoluble drugs.
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Objective To explore the management strategy and indications for revisionary internal fixation after percutaneous kyphoplasty/percutaneous vertebroplasty (PKP/PVP) in cancellous vertebral fractures.Methods A retrospective analysis was made of the 676 cases of single-segment PKP/PVP at Department of Orthopaedics,The Affiliated Hospital to Qingdao University from January 2008 to January 2019.They were subjected to 4 different managements after their primary PKP/PVP:rehabilitation without any treatment in 637 cases,conservative treatment in 19 cases (including 3 ones who refused any revision),KP/VP revision in 12 cases and internal fixation revision in 8 cases.The rate of volume reduction after bone cement dispersion (Vx) was calculated using software Mimics 17.0 on the basis of primary CT data of all the patients.The correlation regression analysis was made between the revision rate and the approximate quantization value of Vx.The Glasgow Coma Score (GCS) of conscious state was used to evaluate the 39 patients after failure of their primary surgery before the surgical strategy for revision was worked out.The cobb angle,pelvic incidence angle (PI),pelvic inclination angle (PT),sacral inclination angle (SS),sagittal deviation (SVA),pain visual analogue scale (VAS) were measured and recorded before operation and at the last follow-up for the KP/VP revision group and internal fixation revision group,indicated as △cobb,△PI,△PT,△SS,△SVA and △VAS,respectively.The indexes were compared between the 2 groups.Results The incidence of osteoporotic vertebral fractures treated with internal fixation revision was 1.18％ (8/676).The correlation between Vx and revision rate was y =0.53 + 0.04x (P ＜ 0.05).The regression analysis showed that Vx was positively correlated with the revision rate (r2 =0.860,P =0.001) and the fitting curve was correlated (r2 =0.916,P =0.001).The GSC scores revealed 31 normal,6 mild disturbance and 2 moderate disturbance cases.There were no significant differences in gender,age or VAS scores between the KP/VP revision group and the internal fixation revision group (P ＞ 0.05).There was a significant difference in △cobb between the 2 revision groups (6.3° ± 7.5° versus 19.2° ± 14.8°) (P ＜0.05),but there were no significant differences between the 2 groups in △PI (4.1°±5.2° versus 3.3°±6.7°),△PT (0.7°±4.6° versus 0.4° ± 3.2°),△SS (3.7° ± 6.2° versus 3.1° ± 5.3°) or △SVA (-3.2 ± 11.9 mm versus-7.9 ± 9.5 mm) (P ＞ 0.05).Conclusions The outcomes of primary PKP/PVP have a great impact on the decision-making of internal fixation revision.The mode and extent of diffusion after initial vertebral cement perfusion are particularly related to the revision rate.The revision plan should depend on clinical symptoms.The internal fixation revision should be individualized to ensure the quality of life of the patients in line with the principles of "resolving symptoms" and "moderate correction".
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Vasovagal syncope (VVS) is the most common cause of unexplained syncope in children. The etiology of VVS is complex, and its diagnosis is mainly based on clinical manifestations and head-up tilt test (HUT) . It has been pointed out that neuroendocrine system plays an important role in the pathogenesis of syncope. HUT-induced syncope is accompanied by abnormal neurohumoral activation. The changes of plasma concentration of endothelin-1 and nitric oxide secreted by endothelial system before and after VVS syncope in children suggest that endothelial system is involved in the occurrence of VVS in children. This article reviews the research on the involvement of vascular endothelial system in the pathogenesis of VVS in children.
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Objective To investigate the effect of Anti TNF-α combined with p38 MAPK antisense oligonucleotide on renal funtion and TNF-α,p38MAPK protein expression at different ischemia-reperfusion points.Methods One hundred and twenty normal male Sprague-Dawley rats were divided into 4 groups by simple randomization:sham-operated (sham) group,ischemia-reperfusion (IR) group,Anti TNF-α + ischemia-reperfusion (Anti TNF-α + IR) group,Anti TNF-α and p38 MAPK antisense oligonucleotide + ischemia-reperfusion (combination preconditioning + IR) group.Each group comprised 30 rats.Anti TNF-α + IR group was subjected to ischemia-reperfusion injury with intravenous administration of Anti TNF-α (0.1 mg/kg) 5 min before reperfusion.Combination preconditioning + IR group was subjected to ischemia-reperfusion injury with intravenous administration of Anti TNF-α(0.1 mg/kg)and p38MAPK antisense oligonucleotide (5 mg/kg)5 min before reperfusion.IR group with the same injury was followed by saline administration in the same manner.Sham group was subjected to only anesthetization but not to ischemia.Detecting the plasma creatinine and plasma urea nitrogen and two-step inmunohistochemical methods were used to detect the changes of expression of TNF-α,p38 MAPK.The measurement data were compared with the t test and the count data were compared with Chi-square test.The date were expressed by ((x) ± s).Intergroup comparison translated by variance analysis.Results After reperfusion,the plasma urea nitrogen in the IR group was (15.86 ± 2.41),(21.13 ± 2.21),(25.47 ± 2.29),(30.51 ± 2.03),(35.56±2.47) μmol/L at 0,1,3,6 and 12 h,respectively,and was (25.61 ±5.40),(32.48 ±2.30) (68.20±1.20),(84.42 ±2.43),(96.15 ±2.23)at 0,1,3,6 and 12 h respectively,and still showed an increasing trend at 12 h.TNF-α mainly expressed in renal proximal convoluted tubules,gradually upregulate with duration of ischemia-reperfusion to 12h of reperfusion.p38MAPK mainly located at distal convoluted tubules,peaked at 6h of reperfusion.But these effects were offset by administration in combination preconditioning group (P ＜ 0.05).Conclusion Renal ischemia-reperfusion injury can be alleviated by Anti TNF-α and p38 MAPK antisense oligonucleotide treatment.