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 investigate the changes and symmetry of facial soft tissue during posed smile, to analyze the feature of posed smile in different gender, and verify the reproducibility of posed smile. METHODS: Three-dimensional (3D) facial images of 41 adults (16 males and 25 females with an average age of 26.76±2.70 years) which were taken by FaceScan three-dimensional sensor, including one rest position and two posed smile images. Then these images were imported into 3D soft tissue analysis software for model repositioning. 3D morphable model method (3DMM) was carried out to automatic landmarks setting. After that, the measurement of the eyes, cheeks, nose and perioral area were carried out for 3D soft tissue analysis. Finally, the changes and symmetry of the soft tissues between the two expression states and the gender differences during the posed smiles were compared. Meanwhile, the reproducibility of posed smile was statistically tested. RESULTS: Compared with the rest position, except for nasolabial angle (1.45°±7.65°), the measurements of 3D soft tissue in other region were changed in posed smile (P < 0.001). It should be noted that the eye region was also significantly changed (P < 0.001). Furthermore, the prominent feature of posed smile was that the alar base length became longer, the upper and lower vermilions were narrow and thin, and the mentolabial furrows became shallow. Meanwhile the chin extended anteriorly while the mouth retracted; During posed smile, the labial fissure asymmetry [2.78 (1.73, 3.49) mm], mid-infraorbital asymmetry [2.36 (1.22, 3.27) mm] and outercanthal asymmetry [2.31(1.29, 2.80) mm] were most apparent. Compared with the rest position, the asymmetry was not significantly increased except for cheilion and alar curvature points during the posed smile (P>0.05). In the posed smile, the changes of the right palpebral fissure height and the thickness of lower vermilion (|Li-Stoi| _z) of males were greater than those of females (P < 0.05), and asymmetry of exocanthion and cheekbone increased more than that of females (P < 0.05). There was no obvious difference between the two posed smiles. CONCLUSION In this study, during the posed smile the soft tissues of the eyes, cheeks, nose, lips and chin changed in different degrees, and the asymmetry of cheilion and alar curvature point was greater than that of the rest position; In addition, the reproducibility of posed smile was excellent, which can be a reference for clinical aesthetics and functional research of smile.
Humans ; Smiling/physiology* ; Female ; Male ; Adult ; Imaging, Three-Dimensional/methods* ; Face/anatomy & histology* ; Young Adult ; Facial Expression

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective:In order to improve the normativity and integrity of informed consent exemption from ethical review of retrospective clinical trials initiated by investigators in hospital settings, protecting the legitimate rights and interests of research participants, and improving the efficiency of ethical review.Methods:According to the relevant ethical review regulations at all levels and combined with the practical experience of ethical management in the second affiliated hospital of Wenzhou medical university in Zhejiang province, the present research took the primary review of clinical research projects initiated by investigators at the above institution as the research objectives, analyzed the problems existing during the application and ethical review of informed consent exemption, and summarized the construction and implementation effect of the hospital's clinical research ethical management system.Results:Main problems in the application for exemption of informed consent and ethical review were poor understanding of the essence of informed consent, insufficient consideration of privacy protection, the risk of abuse of informed consent exemption and inadequate effort of ethical review. With the aim of improving the standardization of ethical review of exempt consent, it was recommended to clarify the scope of exemption review, formulate strict exemption procedures, and strengthen the ethics training of all relevant personnel.Conclusions:Standardizing the ethical review management of investigator-initiated retrospective clinical trials contributes to protecting the legal rights and interests of research participants, and promoting the high-quality development of the ethical review norms of clinical research.

Objective To investigate the efficacy of extracorporeal shock wave therapy(ESWT)combined with ultrasound-guided corticosteroid injection(CSI)for the treatment of primary frozen shoulder(PFS).Methods Ninety-nine patients with PFS who visited the pain department of the Affiliated Hospital of Xuzhou Medical University between April 2024 and July 2024 were enrolled and randomly divided into three groups according to the randomized number table method:ESWT group(T group),CSI group(I group),and combined treatment group(TI group),with 33 patients in each group.Visual analogue scale(VAS)scores,shoulder range of motion(SROM),and Constant-Murley shoulder scores(CMS)were recorded before treatment and at 1,4,8,and 12 weeks post-treatment.Additionally,the patients'Ascens Insomnia Scale(AIS)scores were recorded before treatment and 1 month after treatment.The occurrence of adverse effects and the use of remedial medications during the treatment period were also documented.Results Compared with pre-treatment,VAS scores decreased,and SROM and CM scores improved at all time points after treatment in all three groups(P<0.05).AIS scores also decreased in all three groups at 1 month post-treatment(all P<0.05).Intergroup comparisons revealed that the TI group exhibited signifi-cantly lower VAS pain scores,greater SROM(forward flexion and backward extension),and higher CM scores at 4,8,and 12 weeks post-treatment compared to the T and I groups(Bonferroni-corrected P<0.05).No statistically significant differences were observed between the T and I groups for these measures(Bonferroni-corrected P>0.05).Additionally,there were no statistically significant differences in AIS scores or adverse effects occurrence among the three groups at 1 month post-treatment(P>0.05).Conclusion The combined treatment demonstrated greater efficacy compared to trigger point extracorporeal shock wave therapy alone and periapical steroid injection alone,resulting in significant improvement in the patient's clinical symptoms and quality of life.

Objective To investigate the efficacy of extracorporeal shock wave therapy(ESWT)combined with ultrasound-guided corticosteroid injection(CSI)for the treatment of primary frozen shoulder(PFS).Methods Ninety-nine patients with PFS who visited the pain department of the Affiliated Hospital of Xuzhou Medical University between April 2024 and July 2024 were enrolled and randomly divided into three groups according to the randomized number table method:ESWT group(T group),CSI group(I group),and combined treatment group(TI group),with 33 patients in each group.Visual analogue scale(VAS)scores,shoulder range of motion(SROM),and Constant-Murley shoulder scores(CMS)were recorded before treatment and at 1,4,8,and 12 weeks post-treatment.Additionally,the patients'Ascens Insomnia Scale(AIS)scores were recorded before treatment and 1 month after treatment.The occurrence of adverse effects and the use of remedial medications during the treatment period were also documented.Results Compared with pre-treatment,VAS scores decreased,and SROM and CM scores improved at all time points after treatment in all three groups(P<0.05).AIS scores also decreased in all three groups at 1 month post-treatment(all P<0.05).Intergroup comparisons revealed that the TI group exhibited signifi-cantly lower VAS pain scores,greater SROM(forward flexion and backward extension),and higher CM scores at 4,8,and 12 weeks post-treatment compared to the T and I groups(Bonferroni-corrected P<0.05).No statistically significant differences were observed between the T and I groups for these measures(Bonferroni-corrected P>0.05).Additionally,there were no statistically significant differences in AIS scores or adverse effects occurrence among the three groups at 1 month post-treatment(P>0.05).Conclusion The combined treatment demonstrated greater efficacy compared to trigger point extracorporeal shock wave therapy alone and periapical steroid injection alone,resulting in significant improvement in the patient's clinical symptoms and quality of life.

Objective:In order to improve the normativity and integrity of informed consent exemption from ethical review of retrospective clinical trials initiated by investigators in hospital settings, protecting the legitimate rights and interests of research participants, and improving the efficiency of ethical review.Methods:According to the relevant ethical review regulations at all levels and combined with the practical experience of ethical management in the second affiliated hospital of Wenzhou medical university in Zhejiang province, the present research took the primary review of clinical research projects initiated by investigators at the above institution as the research objectives, analyzed the problems existing during the application and ethical review of informed consent exemption, and summarized the construction and implementation effect of the hospital's clinical research ethical management system.Results:Main problems in the application for exemption of informed consent and ethical review were poor understanding of the essence of informed consent, insufficient consideration of privacy protection, the risk of abuse of informed consent exemption and inadequate effort of ethical review. With the aim of improving the standardization of ethical review of exempt consent, it was recommended to clarify the scope of exemption review, formulate strict exemption procedures, and strengthen the ethics training of all relevant personnel.Conclusions:Standardizing the ethical review management of investigator-initiated retrospective clinical trials contributes to protecting the legal rights and interests of research participants, and promoting the high-quality development of the ethical review norms of clinical research.

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 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.