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OBJECTIVE: To investigate the effect of Neferine (Nef) on diabetic nephropathy (DN) and to explore the mechanism of Nef in DN based on miRNA regulation theory. METHODS: A DN mouse model was constructed and treated with Nef. Serum creatinine (Crea), blood urea (UREA) and urinary albumin were measured in mice by kits, and renal histopathological changes and fibrosis were observed by hematoxylin-eosin staining and Masson staining. Renal tissue superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) activities were measured by enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the expression of nuclear factor E2-related factor 2 (Nrf2)/ heme oxygenase 1 (HO-1) signaling pathway-related proteins in kidney tissues. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-17-5p in kidney tissues. Subsequently, a DN in vitro model was constructed by high glucose culture of human mesangial cells (HMCs), cells were transfected with miR-17-5p mimic and/or treated with Nef, and we used qRT-PCR to detect cellular miR-17 expression, flow cytometry to detect apoptosis, ELISAs to detect cellular SOD, MDA, and GSH-Px activities, Western blots to detect Nrf2/HO-1 signaling pathway-related protein expression, and dual luciferase reporter gene assays to verify the targeting relationship between Nrf2 and miR-17-5p. RESULTS: Administration of Nef significantly reduced the levels of blood glucose, Crea, and UREA and the expression of miR-17-5p, improved renal histopathology and fibrosis, significantly reduced MDA levels, elevated SOD and GSH-Px activities, and activated Nrf2 expression in kidney tissues from mice with DN. Nrf2 is a post-transcriptional target of miR-17-5p. In HMCs transfected with miR-17-5p mimics, the mRNA and protein levels of Nrf2 were significantly suppressed. Furthermore, miR-17-5p overexpression and Nef intervention resulted in a significant increase in high glucose-induced apoptosis and MDA levels in HMCs and a significant decrease in the protein expression of HO-1 and Nrf2. CONCLUSION: Collectively, these results indicate that Nef has an ameliorative effect on DN, and the mechanism may be through the miR-17-5p/Nrf2 pathway.
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Benzilisoquinolinas , Diabetes Mellitus , Nefropatias Diabéticas , MicroRNAs , Humanos , Camundongos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Antioxidantes/farmacologia , MicroRNAs/genética , Glucose , Fibrose , Superóxido Dismutase/metabolismo , Ureia/farmacologia , Estresse OxidativoRESUMO
ObjectiveTo observe the effect of gastrodin on the steroid regulatory element-binding protein 1c (SREBP1c) signaling pathway in high-fat high-cholesterol diet (HFHC)-induced mice and explore the mechanism of gastrodin in the treatment of non-alcoholic fatty liver disease (NAFLD). MethodEight-week-old male C57BL/6J mice were used in vivo and divided into the following four groups, with six mice in each group: normal group, gastrodin group (50 mg·kg-1), model group, and model + gastrodin group (50 mg·kg-1). NAFLD model was established by feeding mice with HFHC for four weeks, and the mice were euthanized and the liver tissues were collected after four weeks. In vitro experiments were performed using Huh7 cells which were divided into five groups, and induced with free fatty acids (FFA, 200 μmol·L-1, oleic acid-palmitic acid 2∶1) to establish an NAFLD cell model. After 24 h, different concentrations of gastrodin (0, 5, 10, 20, and 40 μmol·L-1) were added to each group and cultured for another 24 h. Oil red O staining was used to detect lipid accumulation in mouse liver and Huh7 cells. Hematoxylin-eosin (HE) staining was used to observe pathological changes in liver tissue. Levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were measured using an automatic biochemical analyzer. Relevant assay kits were used to detect liver TC, TG, and FFA levels. Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the expression of lipid synthesis-related proteins fatty acid synthase (FASN), acetyl-CoA carboxylase 1 (ACC1), and stearoyl-CoA desaturase 1 (SCD1). ResultCompared with the normal group, the model group showed significantly increased serum TC, LDL-C, and TG levels (P<0.01), liver TC, TG, and FFA levels (P<0.01), increased lipid accumulation in Huh7 cells (P<0.01), and significantly increased expression levels of lipid synthesis-related genes SREBP1c, FASN, ACC1, and SCD1 in mice and Huh7 cells (P<0.01). Compared with the model group, after gastrodin treatment, the serum TC, LDL-C, and TG levels in mice significantly decreased (P<0.05, P<0.01), the severity of fatty liver disease improved significantly, liver TC, TG, and FFA levels decreased significantly (P<0.05, P<0.01), lipid accumulation in Huh7 cells decreased significantly (P<0.05, P<0.01), the expression levels of lipid synthesis-related genes SREBP1c, FASN, ACC1, and SCD1 in mice and Huh7 cells decreased significantly (P<0.05, P<0.01). ConclusionGastrodin can reduce hepatic lipid accumulation and blood lipid levels, improve HFHC-induced NAFLD, and its mechanism of action may be related to the regulation of the SREBP1c lipid synthesis-related signaling pathway.
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Objective To explore the current situation of evidence-based nursing practice in pain assess-ment by nurses in China to provide the decision-making data for maximizing to relieve the patient pain by car-rying out the pain assessment evidence-based nursing practice.Methods The non-probability sampling meth-od was used to conduct an online anonymous survey in 63 class 3A hospitals in the whole country.The ques-tionnaire included the general information questionnaire and evidence-based nursing practice scale for pain as-sessment.The evidence-based nursing practice scale for pain assessment included the pain screening,compre-hensive pain assessment,exchange with the patients and their households in the pain assessment,pain re-as-sessment,pain assessment tool selection and record.The 5 dimensions were compared by using item equaliza-tion.The data analysis was performed by the SPSS26.0.Results A total of 1 518 questionnaires were recov-ered,in which 1 482 questionnaires were valid with an effective recovery rate of 97.62%.The evidence-based nurse practice of pain assessment by nurse was(108.40±17.96)points,the pain screening was(12.87±2.23)points,the item average score was the highest[(4.29±0.74)points],the communication with the patients and their household was(23.69±4.93)points and the item average score was the lowest[(3.94±0.82)points].The regression analysis showed that whether receiving the pain training and whether distinguishing active pain and resting pain had a positive effect on the practical behavior(P<0.05).Conclusion The evi-dence-based nursing practice in pain assessment by nurses in the partial class 3A hospitals in China is in the upper medium level.However,the communication between the patients and their families is insufficient.Man-agers should constantly enrich the training content and methods,and guide nurses to strengthen the communi-cation between nurses and the patients.
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ObjectiveTo investigate the effect of oxaliplatin on the activation of hepatic stellate cells (HSCs), as well as the association of oxaliplatin with microRNA-30a-5p and autophagy. MethodsHSC-LX2 cells were cultured and divided into groups according to the following three protocols: control group, PDGF treatment group, oxaliplatin treatment group, oxaliplatin+PDGF treatment group; control group, microRNA-30a-5p transfection group, PDGF treatment group, microRNA-30a-5p transfection+PDGF treatment group; control group, 3-MA group, microRNA-30a-5p inhibitor group, microRNA-30a-5p inhibitor+3-MA group. Western Blot was used to measure the expression of HSC activation-related proteins (Collagen-I and alpha-smooth muscle actin [α- SMA]) and HSC autophagy-related proteins (Beclin-1, P62, and LC3B); LysoTracker staining and immunofluorescence assay were used to measure the expression of LC3B autophagosomes; RT-PCR was used to measure the expression level of microRNA-30a-5p; bioinformatics techniques were used to predict the potential targets of microRNA-30a-5p in HSCs. The independent-samples t test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsAfter the cells were treated with oxaliplatin, RT-PCR results showed that the oxaliplatin treatment group had a significantly higher expression level of microRNA-30a-5p than the control group (P<0.01); Western Blot showed that the oxaliplatin treatment group had significant reductions in the expression levels of the HSC activation-related proteins α-SMA and Collagen-Ⅰ and the autophagy-related proteins Beclin 1 and LC3BⅡ/Ⅰ (all P<0.001); immunofluorescence assay showed that the oxaliplatin treatment group had a significantly lower number of autophagosomes than the control group (P<0.05). After HSC-LX2 cells were transfected with microRNA-30a-5p mimic, compared with the control group, the microRNA-30a-5p mimic group had significant reductions in the expression levels of the autophagy-related proteins Beclin 1 and LC3BⅡ/Ⅰ (P<0.05) and the HSC activation-related protein Collagen-Ⅰ (P<0.001); after HSC-LX2 cells were transfected with microRNA-30a-5p inhibitor, Western Blot showed that compared with the control group, the microRNA-30a-5p inhibitor group had significant increases in the expression levels of the HSC activation-related proteins Collagen-Ⅰ and α-SMA and the autophagy-related protein Beclin 1 (t=2.41, 2.32, and 4.57, all P<0.05). Western Blot showed that compared with the control group, the microRNA-30a-5p inhibitor group had significant increases in the expression levels of the HSC autophagy-related protein Beclin 1 and the HSC activation-related protein α-SMA (both P<0.05), and after the treatment with the autophagy inhibitor 3-MA, there were no significant differences in the expression of these proteins between the two groups (P>0.05). The bioinformatics analysis using TargetScan, PicTar, and miRanda databases showed that the autophagy-related protein Beclin-1 might be a potential target of miRNA-30a-5p. ConclusionOxaliplatin can inhibit the activation of HSCs by upregulating the expression of microRNA-30a-5p, which provides new ideas and a new target for the treatment of liver fibrosis.
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Objective:To explore the value of radiomics and deep learning in predicting the efficacy of initial transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Methods:This was a cohort study. The imaging and clinical information of HCC patients treated with TACE in the Second Affiliated Hospital of Harbin Medical University from January 2015 to January 2021 were collected retrospectively. A total of 265 patients were divided into response group (175 cases) and non-response group (90 cases) according to the modified solid tumor efficacy evaluation criteria (mRECIST) 1 to 2 months after initial TACE. According to the proportion of 8∶2, the patients were randomly divided into training group (212 cases, 140 responders and 72 non-responders) and test set (53 cases, 35 responders and 18 non-responders). Univariate and multivariate logistic regression was used to screen clinical variables and construct a clinical model. The radiomics features were extracted from the preoperative CT images, and radiomics model was constructed after feature dimensionality reduction. Using the deep learning method, three residual network (ResNet) models (ResNet18, ResNet50 and ResNet101) were established, and their effectiveness was compared and integrated to build a deep learning model with best performance. Univariate and multivariate logistic regression was used to combine pairwise three models to establish the combined model. The receiver operating characteristic curve was used to evaluate the performance of the model to distinguish between TACE response and non-response groups.Results:In the test set, the area under the curve (AUC) of the clinical model and the radiomics model in the differentiation between response and non-response after TACE were 0.730 (95% CI 0.569-0.891) and 0.775 (95% CI 0.642-0.907). The AUC of ResNet18, ResNet50 and ResNet101 were 0.719, 0.748 and 0.533, respectively. The AUC for deep learning model obtained by integrating ResNet18 and ResNet50 was 0.806 (95% CI 0.665-0.946). After pairwise fusion, the combined deep learning-radiomics model showed the highest performance, with an AUC of 0.843 (95% CI 0.730-0.956), which was better than those of the deep learning-clinical model (AUC of 0.838, 95% CI 0.719-0.957) and the radiomics-clinical model (AUC of 0.786, 95% CI 0.648-0.898). Conclusions:The combined model of radiomics and deep learning has high performance in predicting the curative effect of TACE in patients with HCC before operation.
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Objective:To evaluate the effect of long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) on the radiosensitivity in breast cancer cells by regulating the miR-149-5p/ glutamic pyruvic transaminase 2 (GPT2) axis.Methods:Real-time reverse transcription PCR (RT-qPCR) was used to detect NEAT1, miR-149-5p and glutamic pyruvic transaminase 2 (GPT2) mRNA levels in human breast cells MCF-10A, and human breast cancer cells MCF-7, MDA-MB-231 and MDA-MB-468, respectively. MCF-7 cells were divided into 0, 2, 4, 6 and 8 Gy irradiation groups. MCF-7 cells were divided into NEAT1 knockdown (si-NEAT1) group and control (si-NC) group, NEAT1 knockdown +miR-149-5p knockdown (si-NEAT1+anti-miR-149-5p) group and control (si-NEAT1+anti-miR-NC) group, NEAT1 knockdown + GPT2 overexpression (si-NEAT1+GPT2) group and control (si-NEAT1+NC) group. On the basis of the above grouping, irradiate each group of cells with 4 Gy radiation for 2 h, denoted as IR+si-NEAT1, IR+si-NC, IR+si-NEAT1+anti-miR-149-5p, IR+si-NEAT1+anti-miR-NC, IR+si-NEAT1+GPT2, IR+si-NEAT1+NC groups. Subsequently, MCF-7 cells were irradiated at a dose of 4 Gy and divided into the IR+si-NEAT1, IR+si-NC, IR+si-NEAT1+anti-miR-149-5p, IR+si-NEAT1+anti-miR-NC, IR+si-NEAT1+GPT2 and IR+si-NEAT1+NC groups. RT-qPCR was used to detect NEAT1, miR-149-5p, GPT2 mRNA levels in cells. Colony formation assay was used to detect cell radiosensitivity. CCK-8 assay was adopted to detect cell proliferation ability. The binding sites of NEAT1 and miR-149-5p were predicted by StarBase database. The binding sites of miR-149-5p and GPT2 were predicted by Targetscan database, and validated by dual luciferase assay. Single factor ANOVA was used for inter-group comparisons. LSD- t test was used for pairwise comparison. Results:Compared with MCF-10A cells, NEAT1 and GPT2 mRNA levels in cell lines were up-regulated, whereas miR-149-5p level was down-regulated (all P<0.05). Compared with the 0 Gy dose group, NEAT1 and GPT2 mRNA levels were down-regulated, while miR-149-5p levels were up-regulated in the 2, 4, 6, and 8 Gy dose groups (all P<0.05). Knockdown of NEAT1 expression or radiation alone could enhance cell radiosensitivity, and reduce cell proliferation ability (all P<0.05). Simultaneous radiation treatment with knockdown of NEAT1 expression could strengthen the above effects upon cells (all P<0.05). Knockdown of miR-149-5p expression or overexpression of GPT2 could partially reverse the aforementioned effects of knockdown of NEAT1 expression (all P<0.05). Conclusion:Knockdown of NEAT1 expression enhances breast cancer cell radiosensitivity, and reduces cell proliferation ability by regulating the miR-149-5p/GPT2 signal axis.
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Objective To compare the incidence of catheter-related venous thrombosis between midline catheters and peripherally inserted central catheters.Methods Randomized controlled trials and cohort studies on the incidence of venous thrombosis associated with midline catheters and PICC catheters were searched from CNKI,Wanfang database,VIP database,Web of Science,PubMed,Embase and Cochrane Library from inception to December 31,2022.Review Manager 5.4 software and Stata 14.0 software were used to analyse and describe the outcome indicators.Results A total of 16 studies were included,including 12 cohort studies and 4 randomized controlled studies,with 21853 subjects.The results of the Meta-analysis showed that the incidence of catheter-related venous thrombosis per thousand catheter days of midline catheters was statistically significant compared with PICC[RR=2.74,95%CI(1.21,6.21),P=0.016].There was no significant difference in the incidence of catheter-related venous thrombosis compared with PICC[RR=0.85,95%CI=(0.70,1.03),P=0.101].In the subgroups,the incidence of superficial vein thrombosis in the midline catheter was significantly different from that in the PICC[RR=2.36,95%C/=(1.56,3.58),P<0.001].Conclusion The current evidence shows that the incidence rate of catheter-related venous thrombosis per thousand catheter days and superficial vein thrombosis was higher for midline catheters than PICCs.Therefore,in clinical practice,vascular access devices should be selected reasonably,and the occurrence and development of catheter-related superficial venous thrombosis should be paid attention to,and clinical screening should be effectively carried out on the basis of a full evaluation.
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ObjectiveTo investigate the role and mechanism of total saponins of Dioscorea (TSD) in mitigating nonalcoholic steatohepatitis (NASH) in mice. MethodForty-eight C57BL/6J mice were randomized into a normal group and a modeling group. The mice for modeling were fed with a high-fat and high-cholesterol diet + 20% fructose solution for 16 weeks and randomized into model, atorvastatin (4 mg·kg-1·d-1), and high-, medium-, and low-dose (200, 60, and 20 mg·kg-1·d-1) TSD groups. The mice were administrated with corresponding doses of drugs by gavage for 8 weeks. The mouse activity, liver index, levels of total cholesterol (TC), triglycerides (TG), and free fatty acids (FFAs) in the liver, and levels of TC, TG, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the serum were measured. Hematoxylin-eosin staining, Masson staining, oil red O staining, and transmission electron microscopy were employed to observe the pathological changes, lipid accumulation, and morphological changes of liver ultrastructure. Western blot was employed to determine the protein levels of AMP-activated protein kinase (AMPK), sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), and phosphorylated ACC (p-ACC) in the liver tissue. ResultCompared with the normal group, the activity of mice in the model group decreased(P<0.05, P<0.01), the levels of TC, TG, FFA and serum TC, TG, ALT, AST, GGT, IL-1β and TNF-α, liver coefficient and liver pathology scores were significantly increased, the expression of p-AMPK/AMPK and p-ACC proteins in liver tissues was significantly reduced, and the expressions of SREBP-1c and ACC proteins were significantly increased (P<0.01). Compared with the model group, atorvastatin increased the mouse activity (P<0.05), while each dose of TSD caused no significant changed in the mouse activity. The levels of TC, TG, FFA in liver and serum TC, TG, ALT, AST, GGT, IL-1β, TNF-α, liver coefficient and liver pathological score in TSD and atorvastatin groups were significantly decreased, and the expressions of p-AMPK/AMPK and p-ACC in liver tissue were significantly increased. The expressions of SREBP-1c and ACC were significantly decreased (P<0.05,P<0.01). ConclusionTSD may alleviate NASH in mice by regulating the AMPK/SREBP-1c/ACC signaling pathway to reduce lipid synthesis.
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Objective To assess the risk of nosocomial infection in patients with multiple myeloma during their first hospitalization. Methods Totally 480 patients with multiple myeloma who were hospitalized for the first time in department of hematology of West China Hospital, Sichuan University from August 2021 to August 2022 were included, and the nosocomial infection during treatment was statistically analyzed. The patients were divided into infected group and uninfected group. The independent influencing factors of nosocomial infection were analyzed and a prediction model was established. The reliability of the prediction model was analyzed by receiver operating characteristic curve (ROC). Results The incidence rate of nosocomial infection was 31.2% among 480 patients hospitalized for the first time. There were statistically significant differences in age, ISS staging, controlling nutritional status (CONUT) score, agranulocytosis, hemoglobin, and albumin between the infected group and the uninfected group (P<0.05). Logistic multivariate regression analysis showed that age, ISS staging, CONUT score, agranulocytosis, hemoglobin level, and albumin level were all independent correlated factors of nosocomial infection in patients with multiple myeloma hospitalized for the first time (P<0.05). The area under the ROC curve (AUC), sensitivity and specificity of multivariate logistic regression prediction model were 0.88 (95%CI: 0.840-0.920), 85.00% and 76.36%, respectively. Conclusion The incidence rate of nosocomial infection is high among patients with multiple myeloma in the first hospitalization. The prediction model established according to independent correlated factors of nosocomial infection has high predictive value on the occurrence of nosocomial infection.
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Objective:To understand the level of self-advocacy in young female breast cancer patients and analyze its influencing factors, so as to provide reference for clinical intervention.Methods:A total of 250 young female breast cancer patients from Puyang People′s Hospital and Puyang Oilfield General Hospital from May 2021 to June 2022 were selected as research objects by convenience sampling method. A cross-sectional survey was conducted using the general information questionnaire, Female Self-Advocacy in Cancer Survivorship, Cancer Distress Scales for Adolescent and Young Adults and Family Resilience Assessment Scale. Multiple stepwise linear regression was used to analyze the influencing factors of self-advocacy in young women with breast cancer.Results:A total of 235 young female breast cancer patients completed the survey. The total score for self-advocacy was (77.04 ± 12.76) points, the total score of psychological distress was (108.25 ± 18.36) points, and the total score of family resilience was (112.93 ± 25.20) points. Self-advocacy was negatively correlated with psychological distress ( r=-0.548, P<0.001), and positively correlated with family resilience ( r=0.596, P<0.001). Education level, personality type, family monthly income, perceived economic pressure, work status, fertility, intimate relationship, diagnosis time, psychological distress and family resilience were the influencing factors of self-advocacy of young female breast cancer patients ( R2=0.595, F=35.31, P<0.01). Conclusions:The level of self-advocacy of young female breast cancer patients should be further improved. Medical staff should take targeted measures according to influencing factors to improve their self-advocacy level.
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This paper reported a case of neonatal radial nerve palsy that was successfully treated by conservative therapy. The patient with 39 weeks of gestational age was born vaginally. On the 2nd day after birth, right wrist drop, decreased muscle strength in the right upper limb, the erythema patch, and the subcutaneous nodule on the upper arm were observed. Electromyography revealed acute denervation of the radial nerve. Based on the electromyography results combined with clinical evaluations, neonatal radial nerve palsy was diagnosed. The patient was treated with self-made simple splint fixation along with comprehensive treatment. At 15 days of age, the family members removed the splint fixation themselves (13 days of fixation). At the age of 20 days, the symptoms of right wrist drop had disappeared, and the grasp reflex and Moro reflex of both hands returned to normal. A follow-up electromyography conducted at six months after discharge showed no obvious abnormalities.
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Objective:To investigate the clinical and genetic characteristics of Prader-Willi syndrome (PWS).Methods:The clinical data and genetic characteristics of 2 children with PWS diagnosed in Hebei Provincial People's Hospital were retrospectively analyzed, and the relevant literature was reviewed.Results:Case 1, male, aged 6 years and 3 months, was presented to the hospital because of short stature, mild mental retardation, dysarthria, scoliosis, cryptorchidism, micropenis, long skull, narrow face, almond eyes, small mouth, thin upper lip, downward corners of the mouth, fair skin. He had hypotonia and feeding difficulties in infancy, and gradually became hyperappetitive. Bilateral cryptorchidism surgery was performed at 1.5 years old, but the effect was not good. Case 2, male, aged 4 years, presented to the hospital mainly due to obesity, hyperappetite, excessive weight gain, backward language and cognitive function, dysarthria, and scoliosis.The infant had feeding difficulties in the early stage, and bilateral cryptorchidism surgery at the age of 2 was not effective.Methylation specific polymerase chain reaction and methylation specific multilink probe amplification were used to detect the loss of the parent fragment in the key region (15q11-13) of PWS, which confirmed Prader-Willi syndrome.Conclusion:PWS is a rare hereditary disease with complex and diverse clinical manifestations and different characteristics in different age groups. It is highly susceptible to unexplained hypotonia and feeding difficulties in infancy. Children with short stature and obesity should be alert to the disease, which can be clearly diagnosed by molecular genetic techniques.
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Objective:To construct a nomogram for predicting the occurrence of renal allograft rejection based on the combination of multimodal ultrasound features and clinical data.Methods:The ultrasound findings and clinical characteristics of 102 patients with transplanted kidneys who underwent renal biopsy in the General Hospital of Eastern Theater Command from January 2021 to March 2022 were analyzed retrospectively. Patients were divided into rejection group and nephropathy group according to Banff transplant kidney pathological diagnostic criteria (2017 edition). Multivariate Logistic regression was used to screen independent predictors related to the status of rejection, and nomograms were drawn based on the independent predictors. The internal validation of the nomogram was carried out by Bootstrap method, and the ROC curve and calibration curve were utilized to evaluate the diagnostic efficacy of the nomogram.Results:Blood urea nitrogen concentration, renal aortic resistance index, absolute time to peak and cortical echo were independent predictors of rejection( OR=1.073, 1.078, 0.843, 0.205; all P<0.05). Incorporating blood urea nitrogen concentration, renal aortic resistance index, absolute peak time and cortical echo, the nomogram was constructed. The AUC of the predictive model was 0.814(95% CI=0.722-0.905) and the cutoff value was 0.67(corresponding to a total score of about 157 points). Both internal verification (AUC=0.788) and calibration curve demonstrated the clinical usefulness of the nomogram. Conclusions:The nomogram for predicting the occurrence of rejection in renal allograft patients based on multimodal ultrasound features and clinical data can guide the individualized treatment of patients with renal dysfunction.
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Objective:To explore the diagnostic value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in microcephaly.Methods:A total of 9 cases of microcephaly fetuses diagnosed by prenatal ultrasound or children with microcephaly diagnosed after birth were selected from the Sixth Affiliated Hospital of Guangzhou Medical University from January 2014 to August 2022.Karyotype analysis and/or CMA were used to detect. The cases with negative karyotype analysis and CMA results were further sequenced by trio-based WES (Trio-WES). Then the coding genes contained in the pathogenic copy number variation (CNV) fragments were analyzed by gene ontology (GO) enrichment. The genes related to the development of the central nervous system contained in the pathogenic CNV and the pathogenic genes found by Trio-WES were combined for gene interaction network analysis.Results:In this study, 9 cases of microcephaly were recruited, with the time of diagnosis ranged from 23 weeks of gestation to 7 years after birth, and the head circumference of fetus or children ranged from 18.3 to 42.5 cm (-7SD to -2SD). Karyotype analysis was detected in all 9 cases and no abnormality result was found. Eight cases were detected by CMA, and one abnormal was found. Five cases were detected by Trio-WES, and two cases were detected with likely pathogenic genes. The GO enrichment analysis of the coding gene in the 4p16.3 microdeletion (pathogenic CNV) region showed that: in biological process, it was mainly concentrated in phototransduction, visible light; in terms of molecular function, it was mainly concentrated in fibroblast growth factor binding; in terms of cell components, it was mainly concentrated in rough endoplasmic reticulum. Gene interaction network analysis suggested that CDC42 gene could interact with CTBP1, HTT and ASPM gene.Conclusions:CMA could be used as a first-line detection technique for microcephaly. When the results of chromosome karyotype analysis and/or CMA are negative, Trio-WES could improve the detection rate of pathogenicity of microcephaly.
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Objective:Rat model of RA complicated with pulmonary fibrosis were constructed to observe the degree of improvement of pulmonary fibrosis in RA rats by JAK2 inhibitor CEP33779 and the possible mechanisms.Methods:①The RA models were constructed by subcutaneous injection of 0.2 ml (1 mg/ml) of bovine type Ⅱ collagen into the tail of the rats on the day of modeling development (d0); intratracheal injection of 100 μl bleomycin (2.5 mg/kg) was used to induce pulmonary fibrosis model at d13. In vivo study: model rats were randomly divided into the normal group, pulmonary fibrosis group, pulmonary fibrosis CEP treatment group, RA complicated with pulmonary fibrosis group, and RA complicated pulmonary fibrosis CEP treatment group. Rats in the treatment group was given CEP (10 ml/kg) qd by gavage from d14 to week 4. The right hind foot of the rats was measured for joints swelling and the arthritis index score were measured, lung compliance (Cst) and lung specific gravity were measured. In addition, the pathological changes of the left lung were observed by HE and Masson staining, and the extracellular matrix level of the right lung was measured by protein immunoblotting (WB). ② In vitro study: TGF-β 1 (10 ng/ml) was applied to stimulate human embryonic lung fibroblasts (HFL1) for 24 h and 48h, and p-JAK2 expression was detected by immunofluorescence. After HFL1 inoculation of culture plates, the control group, TGF-β 1 stimulation group, TGF-β 1+ LY2109761 (TGFβ-R1/2 inhibitor group, 0.5 mmol/L and 2 mmol/L) group, TGF-β 1+CEP (0.1 mmol/L and 1.0 mmol/L) group were co-incubated for 48 h, and the expression levels of TGFβ-R2, α-SMA, JAK2, and Col 1 were measured by WB. Comparisons between multiple groups were made by Tukey′s test, and comparisons between the two groups were analyzed by independent t-test. Results:① In vivo study, compared with the control group (1.45±0.04), joint swelling was increased at d13 [(2.54±0.16) in RA+PF+Vehicle group, t=16.02, P<0.001], and the mean arthritis index score and toe volume were decreased 3 days after CEP treatment(d16) [(2.89±0.11), t=5.78, P<0.001; (1.92±0.13), t=6.85, P<0.001]. For rats with pulmonary fibrosis, all had different degrees of lung enlargement, increased lung specific gravity, decreased Cst, and increased lung inflammation and fibrosis[(0.96±0.06), t=19.76, P<0.001; (0.26±0.09), t=17.64, P<0.001; (3.63±1.51), t=6.00, P<0.001; (1.75±0.71), t=5.84, P<0.001]. After CEP gavage, rats that had RA complicated with pulmonary fibrosis had reduced lung swelling, decreased lung specific gravity, increased Cst [(0.82±0.05), t=5.76, P<0.001; (0.43±0.18), t=2.31, P=0.038], and the scores of pulmonary fibrosis and inflammation [(3.00±1.00); (1.56±0.52)] all showed a trend of decrease, but did not reach statistical difference CEP inhibited the expression of TGF-β 1, TGFβ-R2, α-SMA, Fn and JAK2 in lung tissue of pulmonary fibrosis rats, and the differences among the five groups were statistically significant ( F=9.02, P=0.017; F=4.86, P=0.048; F=6.57, P=0.032; F=11.26, P=0.010; F=13.32, P=0.007). ② In vitro study, TGF-β 1 stimulated HFL1 showed stronger phosphorylated JAK2 (p-JAK2) fluorescent signal WB showed a significant increase in the expression of TGFβ-R2, α-SMA, JAK2 and Col1, and after LY and CEP intervention, the above proteins were reduced in a concentration-dependent manner, with statistically significant differences among all five groups ( F=337.30, P<0.001; F=20.61, P<0.001; F=100.60, P<0.001; F=180.90, P<0.001). Conclusion:JAK2 inhibitors can ameliorate RA-related pulmonary fibrosis, and the mechanism may be through interfering with the "crosstalk" between JAK2 and TGF-β 1 signaling pathway.
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Post-transplant lymphoproliferative disorder (PTLD) is a solid organ or hematopoietic stem cells transplant associated syndrome, and central nervous system PTLD(CNS-PTLD) is extremely rare. A case of CNS-PTLD occurring after 24 years of kidney transplant was reported, and pathological examination proved it to be diffuse large B cell lymphoma. Cerebrospinal fluid next generation sequencing and pathological examination supported that Epstein-Barr virus infection was associated with it.
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Objective:To discuss the value of pubo-femoral distance(PFD) in the diagnosis of infants with developmental dysplasia of the hip(DDH).Methods:Nine hundred and thirty-one infants with DDH and normal infants diagnosed by clinical examination and ultrasonography were involved from February 2022 to June 2023 in Beijing Jishuitan Hospital. The ultrasonographic examination included Graf method and pubo-femoral distance measurement. Statistical analysis was made on the measurements of PFD of different types of hips.Results:Among all the hips, 1 359 hips were Graf type Ⅰ, 274 hips were Graf type Ⅱa, 166 hips were Graf type Ⅱb, 31 hips were Graf type Ⅱc, 7 hips were Graf type D, 13 hips were Graf type Ⅲ, and 12 hips were Graf type Ⅳ. The PFD of these hips were (0.34±0.07)cm, (0.35±0.08)cm, (0.35±0.08)cm, (0.51±0.11)cm, (0.67±0.09)cm, (0.95±0.26)cm, (1.27±0.30)cm, respectively. There was no significant difference in PFD between hips of Graf Ⅰ, Graf Ⅱa and Graf Ⅱb ( P>0.05), but there was significant difference in PFD between hips of the other Graf types ( P<0.05). The area under curve(AUC) of the PFD for the diagnosis of stability of the hips in infants was 0.959 with the cut-off value of 0.435 cm, the sensitivity and specificity were 88.9% and 90.4%, respectively. Conclusions:The PFD has great value in the evaluation of the stability of hip joint, and the cut-off value is 0.435 cm.
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Objective:To assess the risk of venous thromboembolism (VTE) and anticoagulation-related bleeding of acute critical emergency patients staying in the emergency department at least 72 h, so as to improve the ability of emergency physicians to identify risk factors of VTE and their awareness of safety prevention in these patients.Methods:Multicenter emergency internal medicine patients meeting the inclusion criteria at the same time were collected. Padua and Caprini scores were used to evaluate the risk of VTE and the HAS-BLED score was used to assess the risk of anticoagulation-related bleeding.Results:A total of 930 emergency patients from 7 medical centers were enrolled in our study from January 15, 2021 to March 15, 2021. The proportion of high-risk population with VTE was 50.22% with Padua score and 78.49% with Caprini score, respectively. The proportion of high-risk bleeding (HAS-BLED score) was 40.43%.Conclusions:More than half of the acute critical ill patients who stay in emergency department for more than 72 h are at high risk of VTE. This group of patients have a relatively low risk of anticoagulation-related bleeding.
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OBJECTIVE To optimize extraction technology of couplet medicinals of Astragalus membranaceus-Puerariae lobatae. METHODS With contents of puerarin,daidzin,calycosin-7-O-β-D-glucopyranoside,daidzein,calycosin and formononetin and the yield of dry extract as index,the analytic hierarchy method was used to determine the weight coefficient of each index and calculate the comprehensive score. The effects of solid-liquid ratio, extraction times and extraction time on the comprehensive score were investigated by single factor test. The level of each factor was determined. By multi-index comprehensive scoring method, using comprehensive scores of above 7 indexes as indexes,the extraction technology of couplet medicinals of A. membranaceus-P. lobata was optimized by orthogonal experiment,and the validation tests were conducted. RESULTS The weight coefficient for the contents of puerarin,daidzin,calycosin-7-O-β-D-glucopyranoside,daidzein,calycosin and formononetin and the yield of dry extract were respectively 0.304 7,0.065 2,0.185 8,0.185 8,0.107 8,0.107 8 and 0.042 7. The optimal extraction technology was determined as follows: solid-liquid of 1∶8(g/mL),extracting 3 times and for 1 h each time. RSD of each evaluation index in the validation test results was lower than 3.00% (n=3). CONCLUSIONS The optimized extraction technology for A. membranaceus-P. lobata is stable and feasible.