Thoracic aortic aneurysm (TAA) significantly endangers the lives of individuals with Marfan syndrome (MFS), yet the intricacies of their biomechanical origins remain elusive. Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA, with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin (mTOR) signaling cascade. We uncovered that activation of the mTOR complex 1 (mTORC1) within smooth muscle cells, instigated by the oscillatory wall shear stress (OSS) that stems from disturbed flow (DF), is a catalyst for TAA progression. This revelation was corroborated through both an MFS mouse model (Fbn1 ^+/C1039G) and clinical MFS specimens. Crucially, our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS. Therapeutic administration of rapamycin suppresses mTORC1 activity, leading to the attenuation of aberrant SMC behavior, reduced inflammatory infiltration, and restoration of extracellular matrix integrity-collectively decelerating TAA advancement in our mouse model. These insights posit the mTORC1 axis as a strategic target for intervention, offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.

Calvarial stem cells are essential for maintaining the health and function of the craniofacial complex and the central nervous system.Under physiological conditions,these stem cells primarily reside within specialized microenvironments known as stem cell niches,located in the bone marrow,periosteum,and sutures of cranial bones.The heterogeneous cellular populations within the microenvironment dynamically regulate the quantity and function of stem cells.Due to their distinct spatial distribution,these stem cells exhibit unique functional characteristics and play crucial roles in the development and progression of various diseases,as well as in relevant therapeutic applications.Herein,we summarize the latest research advances concerning various types of calvarial stem cells,elaborating on their respective functions,microenvironmental regulation,and therapeutic potential,thereby providing new perspectives for both basic research and clinical applications in this field.

Objective : To analyze the differential expression profile of miRNAs in amniotic fluid exosomes of fetu- ses with Down syndrome (DS) and provide insights for identifying novel biomarkers for the prenatal diagnosis of DS . Methods : Amniotic fluid samples were collected from fetuses with DS and chromosomally normal fetuses . Exo- somes were isolated from the amniotic fluid and subjected to high-throughput sequencing. Differentially expressed miRNAs were identified , and target genes were predicted using TargetScan and miRanda. Target genes located on chromosome 21 were selected , and their biological functions and associated diseases were analyzed using Gene- Cards , HGNC , NCBI Gene , UniProtKB/Swiss-Prot , Ensembl , and OMIM databases . GO and KEGG enrichment analyses were performed to investigate the biological functions of the enriched genes . Results : A total of 59 differ- entially expressed miRNAs were identified , including 31 upregulated and 28 downregulated miRNAs . Based on a fold change > 2 and P < 0. 05 , 10 upregulated and 9 downregulated miRNAs with the highest expression levels were selected . Key miRNAs included hsa-let-7b-5p , hsa-let-7c-5p , hsa-let-7b-3p _ 1ss22CT , and hsa-miR-199b-5p , with BACH1 and IFNAR1 identified as their shared target genes . GO analysis revealed that the enriched target genes were primarily involved in protein binding , metal ion binding , transferase activity , DNA binding , transcriptional regulation by RNA polymerase Ⅱ , and nucleotide binding. KEGG pathway analysis indicated that the target genes were mainly associated with metabolic pathways , cancer-related pathways , the PI3K-Akt signaling pathway , and the Rap1 signaling pathway . Conclusion Differential expression of miRNAs in amniotic fluid exosomes was ob- served between DS fetuses and those with normal karyotypes . Combined analysis with placental miRNAs revealed hsa-miR-199b-5p as a common differentially expressed miRNA in both DS amniotic fluid and placenta. It is hypoth- esized that BACH1 and IFNAR1 , shared target genes of hsa-miR-199b-5p , hsa-let-7b-5p , hsa-let-7c-5p , and hsa- let-7b-3p_1ss22CT , may play a role in the pathogenesis of DS .

ObjectiveTo investigate the potential targets and mechanisms of Draconis Sanguis (DS), a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl (D. Sanguis, Xue Jie), in the treatment of myocardial infarction (MI).MethodsWe explored the potential mechanisms of DS in the treatment of MI using network pharmacology, bioinformatic techniques, and transcriptomic analysis, followed by validation through in vivo and in vitro experiments.ResultsNetwork pharmacology and bioinformatic analyses identified five genes (Fpr1, Glul, Mme, Mmp9, and Pla2g7) as potential targets for MI treatment. Moreover, DS significantly ameliorated cardiac function, inflammatory responses, and MI-induced myocardial fibrosis in vivo. Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI. Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene. Furthermore, DS reduced the expression of Pla2g7 (P = .0009), NLRP3 (P = .003), interleukin-18 (P .001), and interleukin-1β (P = .004) mRNAs in vivo.ConclusionsThe results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response. This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.

Thoracic aortic aneurysm(TAA)significantly endangers the lives of individuals with Marfan syndrome(MFS),yet the intricacies of their biomechanical origins remain elusive.Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA,with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin(mTOR)signaling cascade.We un-covered that activation of the mTOR complex 1(mTORC1)within smooth muscle cells,instigated by the oscillatory wall shear stress(OSS)that stems from disturbed flow(DF),is a catalyst for TAA progression.This revelation was corroborated through both an MFS mouse model(Fbn1+/C1039G)and clinical MFS specimens.Crucially,our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS.Therapeutic administration of rapamycin suppresses mTORC1 activity,leading to the attenuation of aberrant SMC behavior,reduced inflammatory infiltration,and restoration of extracellular matrix integrity—collectively decelerating TAA advancement in our mouse model.These insights posit the mTORC1 axis as a strategic target for intervention,offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.

Objective:To investigate the effect of aucubin(AU)on mitochondrial autophagy in the hippocampus of ischemic stroke(IS)rats by regulating the pten-induced kinase protein 1(PINK1)/cytoplasmic E3-ubiquitin ligase(Parkin)signaling pathway.Methods:The IS rat model was established by middle cerebral artery occlusion(MCAO),and was randomly divided into IS group,low-dose AU group(AU-L),medium-dose AU group(AU-M),high-dose AU group(AU-H),and high-dose AU combined with 3-MA group(AU-H+3-MA).The rats without liga-tion were used as the Sham surgery group.Zea Longa score was used to evaluate the neurological function of rats.TTC staining was used to detect the percentage of cerebral infarction volume.The microstructures of mitochondria were observed by transmission electron microscopy,and the changes of autophagy protein-microtubule associated protein light chain 3B(LC3B)and p62 were detected by immunohistochemistry.Hippocampal apoptosis was detected by TUNEL.PINK1/Parkin-related protein expression in hippocampus was detected by Western blot.Results:Neurological function score of IS rats was increased(P＜0.05),cerebral infarction was observed by TTC staining,the expression of mito-chondrial autophagy protein p62 in hippocampus was up-regulated(P＜0.05),the expression of LC3B was down-regu-lated(P＜0.05),the number of autophagosomes was decreased(P＜0.05),and apoptosis in hippocampus was in-creased(P＜0.05),the expression of PINK1 and ARKIN protein in hippocampus was down-regulated(P＜0.05).After AU intervention,the neural function score of rats was decreased,the percentage of cerebral infarction volume was reduced,the positive expression of p62 in hippocampus was down-regulated(P＜0.05),the positive expression of LC3B was up-regulated(P＜0.05),and the number of autophagosomes was increased(P＜0.05),the apoptosis of hippocampus was decreased(P＜0.05),and the expression of PINK1 and ARKIN protein in hippocampus was in-creased(P＜0.05).3-MA blocked the therapeutic effect of AU and aggravated the nerve injury in rats.Conclusion:AU promotes hippocampal mitochondrial autophagy and improves neurological damage in IS rats by activating the PINK1/Parkin signaling pathway.

Objective:To investigate the effect of aucubin(AU)on mitochondrial autophagy in the hippocampus of ischemic stroke(IS)rats by regulating the pten-induced kinase protein 1(PINK1)/cytoplasmic E3-ubiquitin ligase(Parkin)signaling pathway.Methods:The IS rat model was established by middle cerebral artery occlusion(MCAO),and was randomly divided into IS group,low-dose AU group(AU-L),medium-dose AU group(AU-M),high-dose AU group(AU-H),and high-dose AU combined with 3-MA group(AU-H+3-MA).The rats without liga-tion were used as the Sham surgery group.Zea Longa score was used to evaluate the neurological function of rats.TTC staining was used to detect the percentage of cerebral infarction volume.The microstructures of mitochondria were observed by transmission electron microscopy,and the changes of autophagy protein-microtubule associated protein light chain 3B(LC3B)and p62 were detected by immunohistochemistry.Hippocampal apoptosis was detected by TUNEL.PINK1/Parkin-related protein expression in hippocampus was detected by Western blot.Results:Neurological function score of IS rats was increased(P＜0.05),cerebral infarction was observed by TTC staining,the expression of mito-chondrial autophagy protein p62 in hippocampus was up-regulated(P＜0.05),the expression of LC3B was down-regu-lated(P＜0.05),the number of autophagosomes was decreased(P＜0.05),and apoptosis in hippocampus was in-creased(P＜0.05),the expression of PINK1 and ARKIN protein in hippocampus was down-regulated(P＜0.05).After AU intervention,the neural function score of rats was decreased,the percentage of cerebral infarction volume was reduced,the positive expression of p62 in hippocampus was down-regulated(P＜0.05),the positive expression of LC3B was up-regulated(P＜0.05),and the number of autophagosomes was increased(P＜0.05),the apoptosis of hippocampus was decreased(P＜0.05),and the expression of PINK1 and ARKIN protein in hippocampus was in-creased(P＜0.05).3-MA blocked the therapeutic effect of AU and aggravated the nerve injury in rats.Conclusion:AU promotes hippocampal mitochondrial autophagy and improves neurological damage in IS rats by activating the PINK1/Parkin signaling pathway.

Objective To explore the effect of melatonin(MT)-modified PEEK implant assisted by polydopamine(PDA)coating on osteointegration in osteoporotic rats.Methods MT was adhered to PEEK implants with PDA coating as carrier.The physicochemical properties of the materials were analyzed by SEM image,water contact angle,FTIR and protein adsorption experiment.OVX-rBMSCs were inoculated on the surface of PEEK sheet and cultured.The cytoskeleton was stained and cell adhesion morphology was observed.Cell proliferation activity was evaluated by CCK-8 assay;key enzyme activities for osteogenic differentiation were analyzed by ALP stai-ning,and expression levels of osteoblast-related genes COL-1,Runx2,OPN,OCN,BMP-2 and ALP were detected by quantitative real-time PCR.In addition,implants were implanted into the femur of osteoporotic rats and bone volume on the implant surface was de-tected and quantified by Micro-CT.Results MT was successfully loaded on PEEK;the cell adhesion was better,and the proliferation activity and osteogenic differentiation ability were significantly higher than those of control group(P＜0.01).In the rat osteoporosis mod-el,there was more new bone formation around the modified PEEK implant(P＜0.01).Conclusion MT-modified PEEK implants have excellent biocompatibility and improve osteointegration in an osteoporotic environment.

Objective To evaluate the feasibility of confirming syphilis reactive blood donors.Methods The serum of donors with anti-TP reaction by ELISA were confirmed by treponema pallidum particle agglutination(TPPA)and Western blotting(WB).The results of two confirmation methods that were negative,suspicious or inconsistent were followed up and compared.At the same time,the analytical index values of the screening reagent A,B and C and their combinations were e-valuated and compared using the the receiver operating characteristic curve(ROC curve)based on the results of the two confirmation methods.Results The positive rate of 223 ELISA anti-TP reactive samples(including 124 double-reagent ELISA reactive samples and 99 single-reagent ELISA reactive samples)was 57.40%confirmed by TPPA and 38.57%con-firmed by WB(89.52%vs 17.17%by TPPA and 52.42%vs 21.21%by WB for double-reagent and single-reagent ELISA reactive samples).The confirmed negative rate of TPPA was 35.43%and that of WB was 42.60%(6.45%vs 71.72%of TP-PA and 29.84%vs 58.59%of WB for double-reagent and single-reagent ELISA reactive samples).According to Kappa test,the confirmed results between the two methods were not consistent,especially for those single-regent ELISA reactive sam-ples.Thirty six cases were followed up successfully,of which 17(47.22%)confirmed changes in the test results but the changes were irregular.Based on the confirmed results of TPPA and WB,the ROC curve analysis was performed on the anti-TP screening S/CO values of double-reagent ELISA reactive samples.When combining ELISA screening reagents as A/B and A/C,the optimal S/CO values of reagent A were 1.815,5.73 and 10.205,16.165,respectively.Conclusion TPPA and WB have poor consistency in the confirmation of ELISA anti-TP reactive blood samples,and the outcome of follow-up confirmation is unclear.The S/CO threshold of ROC curve is affected by the combination of confirmatory screening reagents,and it is difficult to confirm the results of ELISA anti-TP reactive blood donors.

Objective To compare the effects of three kinds of artificial hydronephrosis in percutaneous nephrolithotomy.Methods A total of 120 patients who underwent single-tract percutaneous nephrolithotomy in the Eighth Hospital of Wuhan from May 2020 to April 2022 were selected and divided equally into three groups according to different methods of artificial hydronephrosis.Patients in group A were received preoperative indwelling ureteral catheter and injection of normal saline through ureteral catheter to dilate renal pelvis and form artificial hydronephrosis.Patients in Group B were placed with double J catheters before surgery,and the bladder was filled with physiological saline through the catheter.The renal pelvis was dilated through the double J catheters,resulting in artificial hydronephrosis.Patients in Group C were received intravenous injection of furosemide and stimulated diuretic method to actively dilate renal pelvis to form hydronephrosis.The one-time puncture success rate,channel establishment time,overall operation time,stone clearance rate and incidence of surgical complications of percutaneous nephrolithotomy after hydronephrosis were compared among the three groups.Results The operation was successfully completed in the three groups.There was no significant difference in the one-time puncture success rate and channel establishment time between group A and group B(P>0.05),which were all higher than group C(P<0.05).The overall operation time of group B was shorter than that of group A and group C(P<0.05).There were no significant differences in stone clearance rate and surgical complications among the three groups(P>0.05).Conclusion Preoperative indwelling of double J tubes to create artificial kidney hydronephrosis has advantages such as high success rate of one-time puncture,short channel establishment time,and surgical time.