ObjectiveTo investigate the effect of icariin （ICA） on the phenotype of dendritic cells （DCs） in heart tissue of the Dahl salt-sensitive myocardial remodeling model of rats and its regulation on the vitamin D system. MethodsMale Dahl salt-resistant rats were divided into a normal group， and male Dahl salt-sensitive rats were divided into a model group， low-， medium-， and high-dose ICA groups （30， 60， 120 mg·kg^-1·d^-1）， and Vitamin D group （3×10^-5 mg·kg^-1·d^-1）. In addition to the normal group， the other groups were given an 8% high salt diet to establish a myocardial remodeling model and received intragastric administration after successful modelling once a day for six weeks. The dynamic changes in tail artery blood pressure were monitored， and detection of cardiac ultrasound function in rats was performed. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the morphological changes in rat heart tissue. The phenotype of DCs and T helper cell 17 （Th17）/regulatory T cell （Treg） ratio were detected by flow cytometry. The mRNA and protein expression of vitamin D receptor （VDR）， 1α-hydroxylase （CYP27B1）， 24-hydroxylase （CYP24A1）， forkhead frame protein 3 （FoxP3）， solitaire receptor γt （RORγt）， myocardial type Ⅰ collagen （ColⅠ）， and type collagen （ColⅢ） in heart tissue was detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the normal group， the model group showed disordered arrangement and rupture of myocardial cells， nuclear condensation， significant edema of myocardial tissue， significant proliferation of collagen fibers in a network distribution， and a significant increase in tail artery blood pressure， left ventricular end diastolic diameter （LVEDD）， and left ventricular end systolic diameter （LVESD） （P<0.05）. The phenotype of cardiac DCs was CD40， CD80， and CD86， and the levels of major histocompatibility complex Ⅱ （MHC-Ⅱ）， Th17 cells， and Th17/Treg were significantly increased （P<0.05）. The mRNA and protein expression of CYP24A1 and RORγt in the heart， as well as the mRNA expression of ColⅠ and ColⅢ， were significantly increased （P<0.05）. The left ventricular ejection fraction （LVEF）， interventricular septal thickness （IVSD）， and left ventricular posterior wall thickness （LVPWD） were significantly decreased （P<0.05）. The phenotype of cardiac DCs such as CD11， CD11b， and Treg cells， were significantly reduced （P<0.05）， while the mRNA and protein expression of cardiac VDR， CYP27B1， and FoxP3 were significantly decreased （P<0.05）. Compared with the model group， the low-， medium-， and high-dose ICA groups and vitamin D group significantly reduced myocardial cell rupture and nuclear consolidation in rats. The high-dose ICA group and vitamin D group showed a small amount of myocardial cell rupture and nuclear consolidation， improving myocardial fiber arrangement to varying degrees and significantly reducing myocardial fiber rupture and proliferation. The tail artery blood pressure， LVEDD， and LVESD were significantly decreased in the low-， medium-， and high-dose ICA groups and vitamin D group （P<0.05）， and the phenotype of cardiac DCs including CD40， CD80， CD86， MHC-Ⅱ， Th17 cells， and Th17/Treg were significantly decreased （P<0.05）. The mRNA and protein expression of CYP24A1 and RORγt， and the mRNA expression of ColⅠ and ColⅢ in the heart were significantly decreased in the medium- and high-dose ICA groups and vitamin D group （P<0.05）. The LVEF， IVSD， and LVPWD of myocardial remodeling model rats in the low-， medium-， and high-dose ICA groups and vitamin D group were significantly increased （P<0.05）. The phenotypes of cardiac DCs including CD11， CD11b， and Treg cells were significantly increased in the medium- and high-dose ICA groups and the Vitamin D group （P<0.05）. The mRNA and protein expressions of VDR， CYP27B1， and FoxP3 in the heart were significantly increased in the medium- and high-dose ICA groups and vitamin D group （P<0.05）. ConclusionICA can regulate tail artery blood pressure， cardiac structural and functional damage， and myocardial tissue fibrosis and inhibit phenotype and functional maturation of DCs in heart tissue in the myocardial remodeling model of Dahl salt-sensitive rats. It can also affect the gene and protein expression of VDR， CYP24A1， and CYP27B1， achieving its intervention in Th17/Treg balance in the immune process of myocardial remodeling possibly by regulating vitamin D/VDR in heart tissue.

Objective:To explore the robust relationship between insomnia and type 2 diabetes mellitus by two-sample Mendelian randomization analysis to overcome confounding factors and reverse causality in observational studies.Methods:We identified strong,independent single nucleotide polymorphisms(SNPs)of insomnia from the most up to date genome wide association studies(GWAS)within European ancestors and applied them as instrumental variable to GWAS of type 2 diabetes mellitus.After excluding SNPs that were significantly associated with smoking,physical activity,alcohol consumption,educational attainment,obesity,or type 2 diabetes mellitus,we assessed the impact of insomnia on type 2 diabetes mellitus using inverse variance weighting(IVW)method.Weighted median and MR-Egger regression analysis were also conducted to test the robustness of the association.We calculated the F statistic of the selected SNPs to test the applicability of instrumental variable and F statistic over than ten indicated that there was little possibility of bias of weak instrumental variables.We further examined the existence of pleiotropy by testing whether the intercept term in MR-Egger regression was significantly different from ze-ro.In addition,the leave-one-out method was used for sensitivity analysis to verify the stability and relia-bility of the results.Results:We selected 248 SNPs independently associated with insomnia at the genome-wide level(P＜5 ×10-8)as a preliminary candidate set of instrumental variables.After clum-ping based on the reference panel from 1000 Genome Project and removing the potential pleiotropic SNPs,a total of 167 SNPs associated with insomnia were included as final instrumental variables.The F statistic of this study was 39.74,which was in line with the relevance assumption of Mendelian randomi-zation.IVW method showed insomnia was associated with higher risk of type 2 diabetes mellitus that po-pulation with insomnia were 1.14 times more likely to develop type 2 diabetes mellitus than those without insomnia(95％CI:1.09-1.21,P＜0.001).The weighted median estimator(WME)method and MR-Egger regression showed similar causal effect of insomnia on type 2 diabetes mellitus.And MR-Egger re-gression also showed that the effect was less likely to be triggered by pleiotropy.Sensitivity analyses pro-duced directionally similar estimates.Conclusion:Insomnia is a risk factor of type 2 diabetes mellitus,which has positively effects on type 2 diabetes mellitus.Our study provides further rationale for indivi-duals at risk for diabetes to keep healthy lifestyle.

ObjectiveTo investigate the effect of icariin （ICA）-mediated vitamin D system on peripheral blood dendritic cells （DCs） and helper T cells 17 （Th17）/regulatory T cells （Treg） balance in myocardial remodeling model of Dahl salt-sensitive rats. MethodFifty SPF Dahl salt-sensitive rats were divided into model group， vitamin D group （3×10^-5 mg·kg^-1·d^-1）， and high-， medium-， and low-dose ICA groups （120， 60， 30 mg·kg^-1·d^-1）， and 10 Dahl salt-resistant rats were used as normal group. The myocardial remodeling model was established by feeding rats with a high-salt diet containing 8% NaCl. After six weeks of modeling， the normal group and the model group were given an equal volume of ultrapure water by gavage， and other groups were continuously administrated for six weeks. Cardiac echocardiography， hematoxylin-eosin （HE） staining， and Masson staining were used to observe the pathological changes in cardiac structure and fibrosis. The levels of serum 25（OH）D₃， B-type N-terminal pro-brain natriuretic peptide （NT-ProBNP）， interleukin （IL）-17， transforming growth factor （TGF）-β₁， IL-12， and IL-10 were detected by enzyme-linked immunosorbent assay （ELISA）. The phenotype of peripheral blood DCs and the ratio of Th17/Treg cells of rats were detected by flow cytometry. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expressions of vitamin D receptor （VDR），1α-hydroxylase （CYP27B1）， and 24-hydroxylase （CYP24A1） in peripheral blood DCs of rats. ResultCompared with the control group， the rats in the model group had pathological changes such as disordered arrangement of myocardial cells and cytoplasmic hypertrophy and swelling. Myocardial collagen fibers proliferated significantly， and the arrangement of myocardial fibers was disordered. The levels of serum 25（OH）D₃ and IL-10 were significantly decreased， and the levels of serum IL-17， TGF-β₁， IL-6， IL-12， and NT-ProBNP were significantly increased （P<0.05）. The costimulatory molecules CD40， CD80， CD86， and MHC-Ⅱ were highly expressed in the peripheral blood DCs， and the expression of CD11 and CD11b was lower （P<0.05）. The proportion of Th17 cells in the peripheral blood was significantly increased， and the proportion of Treg cells was decreased. The ratio of Th17/Treg was increased （P<0.05）. The mRNA and protein expressions of CYP24A1 in peripheral blood DCs increased， and the mRNA and protein expressions of CYP27B1 and VDR decreased （P<0.05）. Compared with the model group， the arrangement of myocardial fibers in each drug administration group was relatively regular， and the swelling of myocardial cells was significantly reduced. The pathological morphology of myocardial tissue was improved to varying degrees. The pathological changes in myocardial tissue were improved and alleviated to varying degrees. The drug could reduce the serum levels of NT-ProBNP， IL-17， TGF-β₁， IL-6， and IL-12 and increase the level of serum 25（OH）D₃ and IL-10 （P<0.05）. The expression of costimulatory molecules CD40， CD80， CD86， and MHC-Ⅱ in the peripheral blood DCs of rats was decreased， and the expression of CD11 and CD11b molecules was increased （P<0.05）. The drug could reduce the proportion of Th17 cells in peripheral blood and the ratio of Th17/Treg cells and increase the proportion of Treg cells （P<0.05）. It could decrease the mRNA and protein expressions of CYP24A1 in peripheral blood DCs of rats and elevate the mRNA and protein expression of VDR and CYP27B1 （P<0.05）. ConclusionICA can regulate the phenotype of peripheral blood DCs and the ratio of Th17/Treg cells by regulating the vitamin D system and play a role in improving myocardial remodeling from the perspective of immune balance.

Objective:To analyze the distribution characteristics of UGT1A1 mutant genes (including enhancers, promoters, and exons 1-5) and further explore the correlation between UGT1A1 genotype and clinical phenotypes in patients with inherited hyperunconjugated bilirubinemia.Methods:Patients diagnosed with hereditary hyperunconjugated bilirubinemia at Nanjing Second Hospital from June 2015 to December 2022 were retrospectively analyzed. The UGT1A1 gene was examined using Sanger sequencing in all patients. Complete blood count, liver function, and abdominal imaging examinations were performed. Comparison of categorical variable data using χ2 testor Fisher percision tests. Comparison of continaous veriable data with normal distribution using t-test. Results:112 cases (male:female ratio 81:31, aged 9-70 years) had inherited hyperunconjugated bilirubinemia, with a total of 14 mutation sites identified, of which seven were confirmed mutations, and the frequency ranged from high to low: (TA)n accounted for 50%, c.211G>A (p.G71R) accounted for 49.10%, 1456T>G (p.Y486D) accounted for 16.96%, c.686C>A (p.R229W) accounted for 12.5%, 1091C>T (p.P364L) accounted for 8.04%, and c- 3279T>G accounted for 0.982%. Simultaneously, all patients had one to four mutations, of which only one mutation was the most common (55.36%), followed by two mutations (37.5%), and rare three and four mutations (5.36% and 1.78%). There was no statistical significance in total bilirubin (TBil) levels among the four groups ( F=0.652, P=0.583). One mutation was most common in (TA)n and c.211G>A (p.G71R), among which TA6/TA7 ( n=10) and TA7/TA7 ( n=14) mutations were statistically significant in TBil ( t=2.143, P=0.043). The c.211G>A (p.G71R) heterozygous ( n=9) and isolated ( n=15) mutation had no statistical significance in TBil ( t=0.382, P=0.706). The GS group accounted for 75%, the intermediate group accounted for 16.9%, and the CNS-Ⅱ group accounted for 8%. TBil was statistically significant among the three groups ( F=270.992, P<0.001). There was no statistically significant difference ( χ2=3.317, P=0.19) between mutation 1 (44 cases, 14 cases, and 4 cases, respectively) and mutations ≥ 2 (40 cases, 5 cases, and 5 cases, respectively) in the GS group, intermediate group, and CNS-II group. Conclusion:The number of UGT1A1 gene mutation sites may have no synergistic effect on TBil levels in patients with inherited hyperunconjugated bilirubinemia. TA7/TA7 mutations are not uncommon, and TBil levels are relatively high.

Background:With the increasing diversity of biological agents,the first-line biological agents for moderate-to-severe Crohn's disease(CD)and ulcerative colitis(UC)requires more precise positioning.Aims:To systematically evaluate the efficacy and safety of infliximab(IFX)and ustekinumab(UST)as first-line options for moderate-to-severe CD and UC.Methods:Randomized controlled trials(RCTs)on IFX and UST in treatment of moderate-to-severe CD and UC were retrieved from CNKI,Wanfang data,VIP,Chinese Science Citation Database and PubMed,Web of Science,Embase,ClinicalTrials,Cochrane Library from the date of database establishment to December 2023.An indirect meta-analysis was conducted to compare the efficacy and safety of IFX and UST in treatment of moderate-to-severe CD and UC.Results:Eleven RCTs were enrolled.No significant differences in clinical remission and maintenance rates of moderate-to-severe CD were found between IFX group and UST group(P>0.05),and no significant differences in serious adverse events and serious infection rates were found between these two groups(P>0.05).No significant differences in clinical remission and maintenance rates of moderate-to-severe UC were found between IFX group and UST group(P>0.05),and no significant differences in serious adverse events and serious infection rates were found between these two groups(P>0.05).Conclusions:Both IFX and UST can be served as first-line biological therapy for patients with moderate-to-severe CD.In view of the fact that IFX can increase the risk of tuberculosis,UST is recommended as first-line therapy for moderate-to-severe CD.For moderate-to-severe UC,IFX is an effective and safe first-line biological therapy,and UST can be served as an alternative.

Objective To minimize variations in treatment outcomes of L5/S1 percutaneous intervertebral radiofrequency thermocoagulation(PIRFT)arising from physician proficiency and achieve precise quantitative risk assessment of the puncture paths.Methods We used a self-developed deep neural network DWT-UNet for automatic segmentation of the magnetic resonance(MR)images of the L5/S1 segments into 7 key structures:L5,S1,Ilium,Disc,N5,Dura mater,and Skin,based on which a needle insertion path planning environment was modeled.Six hard constraints and 6 soft constraints were proposed based on clinical criteria for needle insertion,and the physician's experience was quantified into weights using the analytic hierarchy process and incorporated into the risk function for needle insertion paths to enhance individual case adaptability.By leveraging the proposed skin entry point sampling sub-algorithm and Kambin's triangle projection area sub-algorithm in conjunction with the analytic hierarchy process,and employing various technologies such as ray tracing,CPU multi-threading,and GPU parallel computing,a puncture path was calculated that not only met clinical hard constraints but also optimized the overall soft constraints.Results A surgical team conducted a subjective evaluation of the 21 needle puncture paths planned by the algorithm,and all the paths met the clinical requirements,with 95.24%of them rated excellent or good.Compared with the physician's planning results,the plans generated by the algorithm showed inferior DIlium,DS1,and Depth(P<0.05)but much better DDura,DL5,DN5,and AKambin(P<0.05).In the 21 cases,the planning time of the algorithm averaged 7.97±3.73 s,much shorter than that by the physicians(typically beyond 10 min).Conclusion The multi-constraint optimal puncture path planning algorithm offers an efficient automated solution for PIRFT of the L5/S1 segments with great potentials for clinical application.

Objective To minimize variations in treatment outcomes of L5/S1 percutaneous intervertebral radiofrequency thermocoagulation(PIRFT)arising from physician proficiency and achieve precise quantitative risk assessment of the puncture paths.Methods We used a self-developed deep neural network DWT-UNet for automatic segmentation of the magnetic resonance(MR)images of the L5/S1 segments into 7 key structures:L5,S1,Ilium,Disc,N5,Dura mater,and Skin,based on which a needle insertion path planning environment was modeled.Six hard constraints and 6 soft constraints were proposed based on clinical criteria for needle insertion,and the physician's experience was quantified into weights using the analytic hierarchy process and incorporated into the risk function for needle insertion paths to enhance individual case adaptability.By leveraging the proposed skin entry point sampling sub-algorithm and Kambin's triangle projection area sub-algorithm in conjunction with the analytic hierarchy process,and employing various technologies such as ray tracing,CPU multi-threading,and GPU parallel computing,a puncture path was calculated that not only met clinical hard constraints but also optimized the overall soft constraints.Results A surgical team conducted a subjective evaluation of the 21 needle puncture paths planned by the algorithm,and all the paths met the clinical requirements,with 95.24%of them rated excellent or good.Compared with the physician's planning results,the plans generated by the algorithm showed inferior DIlium,DS1,and Depth(P<0.05)but much better DDura,DL5,DN5,and AKambin(P<0.05).In the 21 cases,the planning time of the algorithm averaged 7.97±3.73 s,much shorter than that by the physicians(typically beyond 10 min).Conclusion The multi-constraint optimal puncture path planning algorithm offers an efficient automated solution for PIRFT of the L5/S1 segments with great potentials for clinical application.

The purpose of this paper is to systematically summarize the gene polymorphisms associated with osteoporosis(OP)susceptibility in Zhuang ethnic group in Guangxi.These genes mainly encode vitamin D receptor,estrogen receptor,calcitonin receptor,and adiponectin.The genotype and allele distribution frequency were compared between Zhuang ethnic group and other ethnic groups,which can clarify the existing genes and the potential gene polymorphism associated with OP in Zhuang ethnic group.The findings provide a representative solution for the subsequent research on the genes associated with OP susceptibility in ethnic minorities.

Humans ; Aortic Valve/surgery* ; Retrospective Studies ; Transcatheter Aortic Valve Replacement ; Sex Factors ; Heart Valve Prosthesis Implantation ; Treatment Outcome ; China ; Aortic Valve Stenosis/surgery* ; Risk Factors ; Risk Assessment

Humans ; Retrospective Studies ; Transcatheter Aortic Valve Replacement/adverse effects* ; Risk Assessment ; China ; Prognosis ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Risk Factors ; Aortic Valve