BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals ; Mice ; Chronic Kidney Disease-Mineral and Bone Disorder/genetics* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Sphingolipids/metabolism* ; Transcriptome/genetics* ; Signal Transduction/genetics* ; X-Ray Microtomography ; Adenine

Objective : To study the risk factors of poor prognosis in patients with hypertrophic cardiomyopathy(HCM) complicated with pulmonary hypertension(PH). Methods : Patients(n=154) diagnosed with HCM were selected.According to whether they were complicated with pH,the patients were divided into control group(n=119 cases) and case group(n=35 cases),and the baseline and echocardiographic data were compared and analyzed.Then the patients in the case group were divided into PH 1 group(n=25 cases) and PH 2 group(n=10cases) according to the degree of elevation of pulmonary artery systolic pressure(PASP).The patients were followed up and recorded whether the patients had adverse events within 2 years.Cox regression analysis was used to analyze the risk factors of poor prognosis in patients with HCM with PH.KM survival curves were plotted for the survival risk analysis of patients with HCM complicated with PH. Results : The prevalence of pH in HCM patients was 22.73%.Compared with the control group,women(48.57%) and patients with arrhythmia(42.86%) accounted for a larger proportion in the case group(P<0.01).Spearman correlation analysis of the patients in the case group showed that female,moderate and severe valve regurgitation were positively correlated with the changes of PASP.Atrial diameter,LACI,left ventricular mass fraction and E/e' value all increased with the increase of PASP level(P<0.05),and LVEF decreased with the increase of PASP level(P<0.001).The incidence of adverse events in HCM patients was 25.97%.Log Rank test showed that there was a statistically significant difference in the cumulative survival rate between PH 1 group and PH 2 group(P<0.001).Cox regression analysis showed that PASP(HR=1.123,95% CI=1.033-1.221) and E/e'(HR=1.131,95% CI=1.054-1.213) were independent risk factors for adverse events in HCM patients with PH within 2 years(P<0.05). Conclusion Both PASP levels and E/e' values are independent risk factors for developing poor prognosis in patients of HCM with PH.

Objective To explore the effect of miRNA-222-3p in endothelial progenitor cell-derived exosomes(EPCs-Exo)on skin wound healing in diabetic mice.Methods Endothelial progenitor cell(EPCs)derived from C57BL/6 mouse bone marrow were identified by fluorescence staining.Subsequently,EPCs-Exo isolated from the media of EPCs were identified,and high-throughput sequencing of EPCs-Exo miRNA was completed.The skin injury model of diabetic mice was established.According to different groups,the wounds were treated with externally ap-plied phosphate buffer solution(PBS)and EPCs-Exo;Subcutaneous injection of PBS,agomiR-222-3p,and an-tagomiR-222-3p at the edge of the wound was performed continuously for 14 days,and the wound healing rate was observed.Meanwhile,immunofluorescence methods were used to investigate the changes in the expression levels of ROS,CD31,and VEGF in the wound margin tissue before and after treatment.Results EPCs-Exo significantly ac-celerated skin wound healing in diabetic mice,reduced the level of ROS,and increased the expression level of VEGF and CD31 in the wound margin tissue(P＜0.05).High-throughput sequencing showed that miRNA-222-3p was highly expressed in EPCs-Exo.Local subcutaneous injection of miRNA-222-3p into wound margin tissue signifi-cantly promoted the skin wound healing of diabetic mice,reduced the level of ROS,and increased the expression level of VEGF and CD31 in the wound margin tissue(P＜0.05).Conclusion MiRNA-222-3p promotes wound healing in diabetic mice and plays an important role in EPCs-Exo promoting wound healing.

Objective:To identify the risk factors, and develop and validate a risk prediction model for abnormal bone mass in end-stage renal disease (ESRD) patients.Methods:It was a retrospective cross-sectional study. The clinical and laboratory data of ESRD patients who were hospitalized in the Department of Nephrology, Zhongda Hospital Affiliated to Southeast University from January 2022 to May 2023 were collected retrospectively. The patients were randomly divided into training and validation cohorts at a ratio of 7∶3. They were further divided into normal and abnormal bone mass groups according to the T value measured by dual-energy X-ray absorptiometry (DXA). Then, backward stepwise regression and least absolute shrinkage and selection operator (LASSO) were respectively used to develop the risk prediction model for abnormal bone mass in ESRD patients. Akaike information criterion (AIC), bayesian information criterion (BIC), and accuracy were used to evaluate the performance of these two models, after which the preferable model was selected. Moreover, the receiver operating characteristic (ROC) curve, calibration curve, Hosmer-Lemeshow test, and decision curve analyses (DCA) were applied to evaluate the diagnostic performance of the preferable model. Finally, a dynamic nomogram for individual assessment was constructed based on the preferable model.Results:A total of 254 ESRD patients were enrolled, including 160 (63.0%) males, 161 (63.4%) hemodialysis patients, and 202 (79.5%) patients with abnormal bone mass. There was no significant difference in the prevalence of abnormal bone mass between training group ( n=178) and validation group ( n=76) (79.2% vs. 80.3%, χ2=0.036, P=0.849). The final variables and variable parameters included in the LASSO and stepwise regression models were the same, which were five variables: age, body mass index, hypertension, diabetes, and osteocalcin. Both models also had the same AIC, BIC, and accuracy in the training group, which were 113.45, 132.54, and 0.837, respectively. Therefore, the LASSO model and the stepwise regression model performed consistently in this study and could be considered as the same model, hereafter referred to as the Model. The Model's area under the ROC curve in the training and validation groups was 0.923 (95% CI 0.884-0.963) and 0.809 (95% CI 0.675-0.943), respectively. The optimal cutoff for the training group was 0.858, with a sensitivity of 0.801, a specificity of 0.973 and an accuracy of 0.837; when this cutoff value was taken, the validation group's sensitivity was 0.689, specificity was 0.800, and accuracy was 0.711. The Model demonstrated excellent performance in the calibration curve, Hosmer-Lemeshow test ( P>0.05), and DCA. Finally, based on the five predictors of the Model, a dynamic nomogram was created for clinicians to enter baseline clinical parameters for early identification of high-risk patients with abnormal bone mass. Conclusions:A dynamic nomogram for abnormal bone mass in ESRD patients is constructed with good predictive performance based on the prediction model, which can be used as a practical approach for the personalized early screening and auxiliary diagnosis of the potential risk factors and assist physicians in making a personalized diagnosis for patients.

Objective:The study seeks to explore the factors influencing the psychological status and sleep quality of medical workers amid the ongoing COVID-19 pandemic, in order to provide data sources and theoretical basis for the development of relevant psychological intervention programs.Methods:Employing the convenience sampling method, general information questionnaire (age, gender, marital status, educational background, job status, etc.), Generalized Anxiety Disorder-7 and Patient Health Questionnaire, epidemic stress index scale, and sleep quality questionnaire were distributed to medical staff between February 18 and April 3, 2020, using the PEM mental health care platform of by ZhongShengKaiXin for medical staff issued. Descriptive, single factor, and correlation analyses, as well as multiple linear regression analysis were used to analyze the data.Results:Overall, 24, 845 questionnaires were collected from 23 provinces, of which 24, 687 were valid, with a recovery rate of 99.36%. The findings showed that the proportion of medical personnel with symptoms of anxiety and depression was 50.58% and 51.37%, respectively; 16.11% had poor or very poor anti-stress ability; and 71.78% reported poor or very poor sleep quality. There was a positive correlation between anxiety, depression, anti-stress ability, and sleep quality ( P<0.05). Anxiety was positively correlated with depression, stress tolerance, and sleep quality( r=0.787, 0.667, and 0.486, all P<0.001); depression was positively correlated with stress tolerance and sleep quality ( r=0.709 and 0.586, both P<0.001); and stress tolerance was positively correlated with sleep quality ( r=0.452, P<0.001). Multiple linear regression analysis results showed that age, gender, marital status, educational background, professional title, job status, and participation influenced the anxiety levels of medical personnel in the backdrop of the pandemic ( P<0.001). Depression levels of medical staff were influenced by gender, educational background, job position, and participation ( P<0.001), while gender, marital status, educational background, job position, and participation influenced the stress tolerance levels ( P<0.001). The sleep quality of medical workers was influenced by age, gender, job position, participation in the fight against the pandemic, and professional title ( P<0.001). Conclusions:Amid the ongoing COVID-19 pandemic, medical staff reported poor mental health status and sleep quality, which can be attributed to diverse factors. The research findings can be useful for assisting medical staff to strengthen their self-cognition, while also providing certain psychological counseling data and theoretical basis for management departments.

Incontinentia pigmenti (IP) is an X-linked dominant disease affecting the skin, teeth, eyes and central nervous system caused by mutations in the IKBKG gene. 95% of patients are female. Skin rash is the prominent manifestation and main diagnostic basis of IP, while external skin damagesare often the factors affecting the prognosis of IP. The diagnostic criteria for IP have been updated in recent years, and Sanger sequencing remains the gold standard for the detection and analysis of IKBKG mutations. IP patients should be fully evaluated, and active treatment should be given if eye retinopathy and nervous system damage are found.

Objective:To explore the optimization strategy of the Asia-Pacific colorectal screening (APCS) scoring system in the screening of colorectal neoplasms.Methods:From February to Decomber in 2016 and March to December in 2018, at Xijing Hospital of Air Force Military Medical University and the First Affiliated Hospital of Xi′an Medical University, patients who received opportunistic screening colonoscopy were enrolled. Before colonoscopy, the APCS score (low-risk zero to one points, medium-risk two to three points and high-risk four to seven points), body mass index (BMI), fecal occult blood test (FOBT) and plasma methylated Septin9 gene ( mSEPT9) of all patients were detected and recorded. The results of colonoscopy and biopsy pathology were taken as the gold standard, the efficacies of the above methods in screening colorectal neoplasms were compared to determine and optimize the screening efficiency of APCS scoring system. Chi-square test was used for statistical analysis. Results:A total of 494 patients were screened, of whom 133 cases were diagnosed with colorectal polyps, including 86 cases of colorectal adenomatous polyps (82 cases of non-progressive adenoma, and four cases of advanced-adenoma), and 47 cases of non-adenomatous polyps. According to the APCS score, the detection rate of colorectal adenomatous polyps of the high-risk group (33.3%, 33/99) was 2.02 and 3.76 times higher than those of the medium-risk group (16.5%, 39/237) and low-risk group (8.9%, 14/158), respectively (both Bonferroni correction test, both P<0.016). The detection rate of colorectal adenomatous polyps of patients with BMI>23.9 kg/m 2 was significantly higher than that of patients with BMI≤23.9 kg/m 2 (22.2%, 59/266 vs. 11.8%, 27/228), and the difference was statistically significant ( χ2=9.126, P=0.003). There was no statistically significant difference in the detection rate of colorectal adenomatous polyps between patients with positive- mSEPT9 expression and patients with negative- mSEPT9 expression (22.4%, 15/67 vs. 17.3%, 47/271) ( χ2=0.913, P=0.378). Among 158 low and medium risk patients (APCS score≤three points) who underwent simultaneous BMI measurement, FOBT and plasma mSEPT9 test, the detection rate of colorectal adenomatous polyps in patients with BMI>23.9 kg/m 2 was higher than that in patients with BMI≤23.9 kg/m 2 (17.8%, 16/90 vs. 5.9%, 4/68), and the difference was statistically significant ( χ2=4.957, P=0.030). The redetection efficacy of colorectal adenomatous polyps in patients with BMI>23.9 kg/m 2 and FOBT-positive was higher than that in patients with BMI≤23.9 kg/m 2 and FOBT-negative (28.1%, 9/32 vs. 8.0%, 4/50) and the difference was statistically significant ( χ2=5.942, P=0.027). In addition, the redetection rate of colorectal adenomatous polyps of patients with positive expression of FOBT and plasma mSEPT9 was also higher than that of patients with negative expression (5/14 vs. 12.9%, 12/93), and the difference was statistically significant ( χ2=4.738, P=0.045). Conclusions:When the APCS scoring system is used for sequential screening of colorectal tumors, the optinal choice of BMI replacement or combined with FOBT can improve the patients′ compliance and screening efficiency, which has significant clinical significance and promotion value in the early diagnosis and treatment of colorectal neoplasms.

Objective To determine the proportion of CD4+ CD25+ regulatory T (Treg) cells,mRNA expression of the forkhead box protein 3 (Foxp3) gene,and DNA methylation status of the Foxp3 promoter in peripheral CD4+ T cells from patients with Henoch-Sch(o)nlein purpura.Methods Totally,20 inpatients with Henoch-Sch(o)nlein purpura and 20 healthy controls were enrolled from Department of Dermatology,the Second Xiangya Hospital of Central South University between 2015 and 2016,and there were no significant differences in the gender and age between the two groups (both P ＞ 0.05).CD4+ T cells were isolated from the peripheral blood samples of these subjects.Real-time fluorescence-based quantitative PCR was performed to detect the mRNA expression of the Foxp3 gene,flow cytometry to determine the proportion of CD4 + CD25+ Treg cells,and sodium bisulfite sequencing PCR (BSP) to determine the DNA methylation status of the Foxp3 promoter.Statistical analysis was carried out with SPSS16.0 software by using two-sample t test for the comparison between the two groups,and linear correlation analysis for evaluating the correlations of the DNA methylation status of the Foxp3 promoter with clinical severity scores and the proportion of CD4+CD25+ Treg cells.Results Compared with the healthy control group,the Henoch-Sch(o)nlein purpura group showed significantly decreased mRNA expression of the Foxp3 gene in CD4+ T cells (0.380 ± 0.226 vs.1,t =9.503,P ＜ 0.01),proportion of CD4+CD25+ Treg cells (1.668％ ± 0.959％ vs.2.741％ ± 1.131％,t =2.552,P ＜ 0.05),but significantly increased DNA methylation status of the Foxp3 promoter (0.712 ± 0.164 vs.0.453 ± 0.147,t =3.610,P ＜ 0.01).In the Henoch-Sch(o)nlein purpura group,the DNA methylation status of the Foxp3 promoter was negatively correlated with the percentage of CD4+CD25+ Treg cells (r =-0.490,P ＜ 0.05),but positively correlated with the clinical severity scores (r =0.486,P ＜ 0.05).The DNA methylation level of the Foxp3 promoter was significantly higher in the patients with renal impairment than in those without renal impairment (P ＜0.05).Conclusion The patients with Henoch-Sch(o)nlein purpura showed increased DNA methylation status of the Foxp3 promoter in CD4+ T cells,decreased mRNA expression of the Foxp3 gene and proportion of CD4+CD25+ Treg cells,which may be related to the occurrence of Henoch-Sch(o)nlein purpura,and affect disease development and prognosis.

Objective To investigate the clinical features and prognosis of Kaposi varicelliform eruption with severe complications. Methods The clinical data of one child with Kaposi varicelliform eruption with severe complications was retrospectively analyzed. The related literatures were reviewed. Results A 5-month-old boy presented with recurrent rash on the head and face for 3 months and aggravated for 3 days. The skin lesions showed a characteristic of typical dome-shaped blisters with hemorrhagic crusting. At admission, the boy suffered with severe hypoproteinemia, hypocalcemia, and electrolyte disorder. The hypocalcemia was aggravated gradually. On the fifth day of admission, the boy had fever, convulsions, and tachycardia. Blood culture showed methicillin-resistant Staphylococcus aureus (MASA) infection. The diagnosis of sepsis was confirmed. At that very day, the boy started to have coagulopathy, so Fusidic and Vancomycin for anti-infection, Acyclovir for antivirus, intravenous infusion immunoglobulin, albumin, cryoprecipitate, plasma and calcium gluconate were administered, supplied with albumin and blood coagulation factor. The boy's condition gradually became stable and discharged on the 19th day after admission. Conclusions When Kaposi varicelliform eruption is complicated with hypoproteinemia and hypocalcemia, the critical illness is indicated. Clinicians should be alerted to the existence of sepsis, coagulation disorders, even septic shock and disseminated intravascular coagulation.

Objective To observe Thl7 cells,Treg cells and their related factors in peripheral blood of children with milk protein allergy and explore the influence of Yupingfeng granule on Th17 / Treg imbalance and its clinical effect.Methods 40 children with milk protein allergy were divided into two groups randomly:the conventional treatment group (n =20),Yupingfeng granule group (n =20).The conventional treatment group received conventional treatment for 2 months.On the basis of routine treatment,Yupingfeng granule group was additionally treated with Yuping feng granule.The serum Th17,Treg cell counts,interleukin (IL)-17 and transforming growth factor-β1 (TGF-β1) levels were detected,and the eczema area and severity index (EASI) score of rash in children was recorded.Results The levels of Th17 cells and IL-17 in allergy children were obviously increased compared with those of the normal children,while the Treg cells,and the TGF-β1 level were lower than those of the normal children (P ＜ 0.05).After treatment,the Thl7 cells,the IL-17 levels and ESAI scores of the conventional treatment group and the Yupingfeng granule group were lowered,while the Treg cells and the TGF-β1 levels were increased (P ＜ 0.05).Compared with the conventional treatment group,these indexes increased and decreased more significantly in the Yupingfeng granule group (P ＜ 0.05).Conclusions Milk allergy children have obvious imbalance of Thl7/Treg;the Yupingfeng granule can adjust this imbalance and alleviate the allergic symptoms of milk protein.