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ObjectiveTo observe the intervention effect of Huaiqihuang granules （HQH） on immunoglobulin A vasculitis nephritis （IgAVN） mice and explore the underlying therapeutic mechanism. MethodFifty SPF-grade male Kunming mice were randomly divided into a normal group， an IgAVN model group， a dexamethasone group （2.5 mg·kg-1·d-1）， a low-dose HQH group （4 g·kg-1·d-1）， and a high-dose HQH group （8 g·kg-1·d-1）. The mouse model was established using oral administration of gliadin combined with intravenous injection of India ink. After successful modeling， the mice were euthanized after 4 weeks of gastric gavage according to groups. The 24 h urinary total protein （24 h UTP）， urine β2-microglobulin （β2-MG）， serum total protein， albumin， IgA， etc. were detected in each group. Flow cytometry was used to determine the proportion of T helper 17 （Th17） cells in spleen cell suspension. Western blot was employed to detect the expression of adenosine 5'-monophosphate-activated protein kinase α （AMPKα）， phosphorylated AMPKα （p-AMPKα）， acetyl-CoA carboxylase 1 （ACC1）， and phosphorylated ACC1 （p-ACC1） in Th17 cells. Pathological changes in the spleen and kidneys were observed. ResultCompared with the normal group， the IgAVN model group showed significant increases in 24 h UTP， urine β2-MG， total cholesterol （P<0.05）， serum interleukin-17 （IL-17）， IgA， Th17 proportion in the spleen cell suspension， and IL-17 expression in the spleen tissue （P<0.01）， and significantly decreased serum total protein， albumin， p-AMPKα/AMPKα， and p-ACC1/ACC1 expression of Th17 cells （P<0.01）. Compared with the IgAVN model group， in the 4th week， the 24 h UTP， urine β2-MG， serum IL-17， IgA levels， and renal IgA deposition were significantly reduced in each treatment group （P<0.01）， and the Th17 proportion and IL-17 expression in spleen tissue were significantly decreased （P<0.05， P<0.01）. Serum albumin levels significantly increased （P<0.05）. Compared with the IgAVN model group， the dexamethasone group and the high-dose HQH group showed increases in serum total protein （P<0.01）， p-AMPKα/AMPKα， and p-ACC1/ACC1 expression of Th17 cells （P<0.05， P<0.01）. The high-dose HQH group showed a significant decrease in total cholesterol level （P<0.05）. Various treatment groups showed different degrees of improvement in spleen and kidney pathological changes. ConclusionHQH may affect Th17 cell differentiation by regulating the AMPK/ACC pathway， correcting immune inflammatory disorders， and exerting therapeutic effects on IgAVN.
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AIM:To observe the effect of icariin-astragaloside Ⅳ-puerarin mixture(Yin-Huang-Ge mixture,YHG)on cognitive function and ferroptosis amino acid metabolism pathway in hepcidin(HAMP)knockout APPswe/PS1dE9(APP/PS1 HAMP-/-)mice.METHODS:The mice were divided into 7 groups:negative control(C57BL/6 mice)group,APP/PS1 group,APP/PS1 HAMP-/-group,APP/PS1+YHG group,APP/PS1 HAMP-/-+YHG group,APP/PS1+de-ferasirox(DFX)group,and APP/PS1 HAMP-/-+DFX group,with 6 mice in each group.The YHG and DFX were adminis-tered intragastrically,while the mice in C57 group,APP/PS1 group and APP/PS1 HAMP-/-group were given intragastric administration of distilled water,once a day for 2 months.The iron content in mouse brain tissues was detected by tissue iron kit.The morphological changes of the mitochondria in hippocampal neurons were observed by transmission electron microscopy.Morris water maze was used to detect the learning and memory ability of the mice.The content of neuronal nu-clear antigen(NeuN)in mouse brain tissues was detected by immunofluorescence staining.The expression of glutathione(GSH)in mouse brain tissues was detected by biochemical kit.The expression levels of glutamate-cysteine ligase catalytic subunit(GCLC)and glutamatase 2(GLS2)in mouse brain tissues were detected by Western blot.RESULTS:Compared with C57BL/6 mice,the brain iron content of APP/PS1 mice was significantly increased(P＜0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P＜0.05),the brain neurons were seri-ously damaged(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P＜0.01).Compared with APP/PS1 mice,the brain iron content of APP/PS1 HAMP-/-mice was significantly increased(P＜0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P＜0.05),the brain neurons were seriously damaged(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P＜0.05).After treatment with YHG and DFX,the brain iron content was significantly decreased(P＜0.01),the mitochondrial damage was alleviated,the learning and memory ability was significantly increased(P＜0.05),the brain neuron damage was alleviated(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly increased(P＜0.05).CONCLUSION:The YHG can improve the cognitive function of APP/PS1 HAMP-/-mice,and its mechanism may be related to the regulation of ferroptosis amino acid metabolism and the enhancement of antioxidant capacity.
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Objective:To investigate the incidence and related risk factors of refeeding syndrome (RFS) in patients with severe stroke.Methods:Patients with severe stroke admitted to the Department of Neurology, the First Affiliated Hospital of Soochow University underwent nutritional treatment again after fasting between December 2017 and October 2022 were included retrospectively. The incidence of RFS in patients with severe stroke was summarized. Multivariate logistic regression models were used to analyze the independent risk factors for RFS. A restricted cubic spline model was used to explore the dose-response relationship between relevant indicators and RFS. Results:A total of 188 patients were included, including 108 males and 80 females, with a median age of 72 years (interquartile range, 63-77 years); 185 patients (98.4%) had ischemic stroke and 3 (1.6%) had cerebral hemorrhage; 59 (31.4%) received enteral nutrition, 36 (19.1%) received gastrointestinal decompression, 30 (16.0%) received mechanical ventilation; and 60 patients (31.9%) developed RFS. Multivariate logistic regression analysis showed that serum creatinine (odds ratio [ OR] 1.011, 95% confidence interval [ CI] 1.001-1.020; P=0.025), serum potassium ( OR 8.349, 95% CI 3.025-23.039; P<0.001), serum phosphorus ( OR 46.578, 95% CI 6.444-336.661; P<0.001) and diabetes ( OR 2.173, 95% CI 1.087-4.345; P=0.028) were the independent risk factors for the occurrence of RFS. The restricted cubic spline model analysis showed that there was a non-linear relationship between serum creatinine and RFS, and the increased risk of RFS showed an "S" shape with the increase of serum creatinine. When serum creatinine exceeded 70.68 μmoI/L, the risk of RFS continued to increase. There was no non-linear relationship between serum phosphorus and serum potassium and RFS. Conclusions:Serum creatinine, serum phosphorus, serum potassium and diabetes are the independent risk factors for RFS in patients with severe stroke. These risk factors should be utilized to identify the high-risk patients with RFS early and the targeted measures should be taken as soon as possible.
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The glucocorticoid receptor (GR) plays a critical role in signal transduction, expression of related genes and apoptosis of cancer cells. Hepatocellular carcinoma is characterized by high aggressiveness and mortality. In the exploration of the relationship between GR and hepatocellular carcinoma, numerous studies have shown that GR has an inhibitory effect on the growth of hepatocellular carcinoma cells, which provides new ideas and methods for the clinical application of GR in the treatment of hepatocellular carcinoma.
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OBJECTIVE@#To explore the genetic etiology of a child with Pitt-Hopkins syndrome.@*METHODS@#A child who had presented at the Medical Genetics Center of Gansu Provincial Maternal and Child Health Care Hospital on February 24, 2021 and his parents were selected as the study subjects. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing. Karyotype analysis was also carried out for the child, and her mother was subjected to ultra-deep sequencing and prenatal diagnosis upon her subsequent pregnancy.@*RESULTS@#The clinical manifestations of the proband included facial dysmorphism, Simian crease, and mental retardation. Genetic testing revealed that he has carried a heterozygous c.1762C>T (p.Arg588Cys) variant of the TCF4 gene, for which both parents had a wild-type. The variant was unreported previously and was rated as likely pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (ACMG). Ultra-deep sequencing indicated that the variant has a proportion of 2.63% in the mother, suggesting the presence of low percentage mosaicism. Prenatal diagnosis of amniotic fluid sample suggested that the fetus did not carry the same variant.@*CONCLUSION@#The heterozygous c.1762C>T variant of the TCF4 gene probably underlay the disease in this child and has derived from the low percentage mosaicism in his mother.
الموضوعات
Child , Female , Humans , Male , Pregnancy , Intellectual Disability/genetics , Mosaicism , Mothers , Mutation , Parents , Transcription Factor 4/geneticsالملخص
Objective:To investigate the application value of three dimensional (3D) imaging fusion navigation system (hereinafter referred as navigation system) in laparoscopic pan-creatic surgery.Methods:The retrospective and descriptive study was conducted. The clinical data of two volunteers, including volunteer 1 undergoing laparoscopic pancreaticoduodenectomy for cholangiocarcinoma and volunteer 2 undergoing laparoscopic pancreaticotomy + splenectomy for pancreatic cancer, who were admitted to the Second Hospital of Hebei Medical University from December 2020 to May 2021 were collected. The 2 volunteers were females, aged 68 years and 40 years, respectively. The self-developed navigation system was applied in laparoscopic simulator model test, including in rigid-body model and prosthesis model, and clinical test. Observation indicators: (1) results of model test; (2) results of clinical test. Measurement data with normal distribution were represented as Mean± SD. Results:(1) Results of model test. The rigid-body model or prosthesis model with occlusion can be seen in the laparoscopic visual field of the initial laparoscopic simulator. The rigid-body model or prosthesis model with occlusion and rigid-body model or prosthesis model without occlusion can be seen in the 3D visual reconstruction image of enhanced computer tomography (CT) examination. The rigid-body model or prosthesis model with occlusion can be seen in the laparoscopic visual field of the initial laparoscopic simulator after the 3D visual reconstruction image was superimposed and fused with the real-time laparoscopic image. Both of the rigid-body model and prosthesis model were in high consistency, with the distance error of marker points were (0.26±0.11)mm and (0.29±0.18)mm, respectively. (2) Results of clinical test. The abdominal organs and blood vessels with occlusion of the 2 volunteers can be seen in the initial laparoscopic visual field. The location of tumor, important organs and blood vessels can be seen in the navigation system using the 3D visual reconstruction image of enhanced CT examination. The location of tumor, important organs and important blood vessels can be seen in the laparoscopic visual field after the 3D visual reconstruction image was superimposed and fused with the real-time laparoscopic image. The distance error of marker points of the volunteer 1 was (1.36±0.57)mm and the distance error of marker points of the volunteer 2 was (1.24±0.33)mm.Conclusions:The self-developed navigation system can integrate the preoperative 3D visual reconstruction image of enhanced CT examination and the intraoperative real-time laparoscopic image with a good effect. The relationship between deep tissue and blood vessels which is not clarified in conventional laparoscopy can be shown in the navigation system assisted laparoscopic pancreatic surgery.
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Objective:To explore the influence of vibration operation on occupational psychological behavior of workers.Methods:From May to August 2021, a total of 384 workers from 20 factories in a city of Guangdong Province were selected as the research objects.According to the workers whether engaged in vibration operations, they were divided into the vibration group and the control group.There were 229 workers in the vibration group and 155 workers in the control group.The occupational stress scale, job burnout scale and job fatigue symptom scale were used for questionnaire survey, and IBM SPSS 24.0 software was used for statistical description and data analysis, and t-test was used for comparison of independent samples between the two groups, one-way ANOVA was used for comparison of means between multiple groups, and LSD test was used for further pin-pide comparison. Results:In the vibration group, the scores of cognitive behavioral stress(3.78±1.79), psychological stress response(4.15±2.29), physical stress(2.81±1.65) and total stress (10.74±5.11) were higher than those of the control group ((2.23±1.23), (2.30±1.62), (1.81±1.07), (6.34±2.88), t=9.31, 8.67, 6.68, 9.72, all P<0.01), and job burnout scale of emotional exhaustion (8.95±3.62), depersonalization (3.24±2.16) were higher than the control group ((5.37±2.72), (1.79±1.20), t=10.48, 7.59, both P<0.01). The score of personal achievement (26.20±2.47) was lower than that of control group ((29.73±2.52), t=13.64, P<0.01). In the job fatigue symptom scale of sleepiness (8.38±1.52), emotional restlessness (6.85±1.74), displeasure (6.38±1.57), sluggishness (8.94±2.05), visual fatigue (7.83±1.95), and total score (38.37±6.56) were higher than those of the control group ((7.89±1.29), (6.21±1.32), (5.61±1.29), (6.54±1.52), (6.67±2.02), (32.92±5.56), t=3.26, 3.90, 5.00, 12.45, 5.61, 8.48, all P<0.01)). There were significant differences in scores of occupational stress, occupational burnout and occupational fatigue symptom among different seniority groups (all P<0.01). The scores of occupational stress, job burnout and job fatigue symptoms of workers in 6-10 years and more than 10 years of service group were higher than those in 0-5 years of service group, and the differences were statistically significant ( P<0.05). Length of service was correlated with occupational stress, job burnout and job fatigue.There was a correlation between the scores of all dimensions and total score of the occupational stress scale and the scores of all dimensions of occupational burnout scale ( r=-0.67-0.63, P<0.01), as well as the scores of all dimensions and total score of the occupational fatigue symptom scale ( r=0.26-0.73, P<0.01). The direct effect of occupational stress on job fatigue was 0.417, and the mediating effect of occupational stress on job fatigue through job burnout was 0.127. Conclusion:Vibration work can lead to occupational stress, job burnout and job fatigue, which is an important factor affecting occupational psychology and occupational behavior.
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Objective:To compare and analyze the perioperative outcomes of jaundiced patients undergoing laparoscopic pancreaticoduodenectomy (LPD) using preoperative percutaneous transhepatic cholangial drainage (PTCD) versus endoscopic nasobiliary drainage (ENBD).Methods:The perioperative data of 173 patients who underwent LPD at the Second Hospital of Hebei Medical University from January 2016 to December 2020 and were treated preoperatively with either PTCD versus ENBD to alleviate jaundiced were retrospectively analyzed. There were 100 males and 73 females, with age of (60.4±10.8) years old. These patients were divided into the PTCD group ( n=126) and the ENBD group ( n=47). Clinical data including operation time, blood loss, transfusion volume, R 0 resection, and postoperative complications were compared. Results:There was no convension to open surgery. There were no significant differences in operation time, blood loss, transfusion volume, R 0 resection rate, pathological results and hospital stay between the two groups ( P>0.05). For the PTCD group, the pancreatic fistula rate was 10.3% (13/126) and the post-operative hemorrhage rate was 8.7% (11/126). They were both significantly lower than those of the ENBD group [25.5% (12/47) and 25.5% (12/47) respectively, P<0.05]. There were also significant differences in the postoperative complications according to the Clavien-Dindo classification system between the two groups ( P=0.008). Conclusion:Compared with ENBD, PTCD had the advantages of lower post-operative pancreatic fistula and post-operative hemorrhage rates, resulting in a better postoperative recovery.
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To develop a clinical diagnosis technique for bluetongue virus infection, we established serotype-specific methods to detect serotype 4 of bluetongue virus (BTV-4). Two monoclonal antibodies (mAbs) against VP2 protein of BTV-4, named 4A-1G7 and 4B-1B6, were used as competitive antibodies in the competitive enzyme-linked immunosorbent assays (C-ELISA). We detected 50 negative serum samples from sheep, goats and cattle by C-ELISA. The cut-off values of 4A-1G7 and 4B-1B6 mAbs were 49% and 40%, respectively. The results of the sensitivity, specificity and repeatability by detecting standard positive serum, were consistent with the general standard of Office International Des Epizooties. Furthermore, serum samples of BTV-4, BTV-18 and BTV-20 infection could be screened out through the combined C-ELISAs by 4A-1G7 and 4B-1B6 mAbs. Thus, this technique may diagnose BTV-4, BTV-18 and BTV-20 infections.
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To confirm the B cell epitope recognized by monoclonal antibody (MAb) 3G11 of bluetongue virus type 8 (BTV-8) VP2 protein prepared in our laboratory, antigen epitopes recognized by 3G11 were screened and identified by phage display technology. KLLAT sequence was found by sequencing of blue spot after four rounds panning and 283LL284 of common short peptide sequence was obtained after comparison to amino acid sequence of BTV-8 VP2 protein. The peptide sequences KLLAA, KALAT, KLAAT and KLLAT were synthesized and identified by indirect ELISA. KLLAA and KLLAT bound strongly with supernatant and as cites of 3G11 cells and reacted specifically with BTV-8 positive standard sera. Further sequence analysis showed that amino acid sequence 283LL284 was conserved among different serotypes of BTV-8 strains, and283LL284 was the key amino acids of antigen epitopes recognized by 3G11. This study laid the foundation to establish type 8 BTV specific immunological detection methods.