Objective:To investigate the impact of blood pressure outcomes on the risk of arteriosclerosis in non-hypertensive populations.Methods:This study was a retrospective cohort study. All data were derived from Kailuan Cohort. Non-hypertensive individuals who completed two brachial-ankle pulse wave velocity (baPWV) measurements between January 2014 and December 2019 (using the first measurement as the baseline and the second as the follow-up) were enrolled, and clinical data such as blood pressure and baPWV were collected. According to the blood pressure level at baseline and follow-up, participants were divided into new-onset hypertension group (no hypertension at baseline but diagnosed at follow-up) and non-hypertension group (no hypertension at both baseline and follow-up). Multiple linear regression and multivariate logistic regression were used to analyze the impact of new-onset hypertension on arteriosclerosis progression. Subgroup analysis further classified participants into six blood pressure transition categories: normal-maintained, normal-to-high-normal, normal-to-hypertensive, high-normal-to-normal, high-normal-maintained, and high-normal-to-hypertensive groups. Multivariate logistic regression analysis was used to assess the impact of different blood pressure outcomes on arteriosclerosis progression.Results:A total of 7 049 participants were enrolled, with the age of (40.45±9.04) years, including 3 645 males (51.71%). There were 800 cases in the new-onset hypertension group and 6 249 individuals in the non-hypertension group. During follow-up, arteriosclerosis occurred in 2 154 cases (30.56%). Multivariable linear regression analysis revealed a positive correlation between new-onset hypertension and baPWV levels. The baPWV in the new-onset hypertension group was significantly higher by 63.94 cm/s compared to the non-hypertension group ( β=63.94, P<0.01). Additionally, the risk of arteriosclerosis in the new-onset hypertension group was 2.09 times that of the non-hypertension group ( OR=2.09, 95% CI: 1.77-2.46, P<0.01). Subgroup analysis revealed significantly higher arteriosclerosis risks in normal-to-high-normal ( OR=1.65, 95% CI 1.38-1.98, P<0.01), normal-to-hypertensive ( OR=2.47, 95% CI 1.70-3.59, P<0.01), high-normal-maintained ( OR=1.50, 95% CI 1.21-1.86, P<0.01), and high-normal-to-hypertensive groups ( OR=2.86, 95% CI 2.20-3.73, P<0.01) than normal-maintained group, except for a non-significant difference in high-normal-to-normal group ( OR=0.95, 95% CI 0.74-1.20, P>0.05). Conclusion:Blood pressure outcome in non-hypertensive populations is closely related to arteriosclerosis risk. Progression to or maintenance of high-normal blood pressure or higher levels substantially increases arteriosclerosis risk, while regression from high-normal to normal blood pressure shows no significant increase in arteriosclerosis risk.

Rapid cycle deliberate practice (RCDP) has emerged as an effective teaching method for enhancing skill proficiency. This study introduces the characteristics and theoretical foundations of RCDP, explains key points in instructional design and implementation strategies, and provides a comprehensive analysis of its application in medical education. Additionally, the potential value and development prospects of RCDP in simulation-based medical education in China are explored. This study aims to provide theoretical support and practical guidance for the further promotion and deeper implementation of the RCDP teaching method in China.

Rapid cycle deliberate practice (RCDP) has emerged as an effective teaching method for enhancing skill proficiency. This study introduces the characteristics and theoretical foundations of RCDP, explains key points in instructional design and implementation strategies, and provides a comprehensive analysis of its application in medical education. Additionally, the potential value and development prospects of RCDP in simulation-based medical education in China are explored. This study aims to provide theoretical support and practical guidance for the further promotion and deeper implementation of the RCDP teaching method in China.

Objective:To investigate the impact of blood pressure outcomes on the risk of arteriosclerosis in non-hypertensive populations.Methods:This study was a retrospective cohort study. All data were derived from Kailuan Cohort. Non-hypertensive individuals who completed two brachial-ankle pulse wave velocity (baPWV) measurements between January 2014 and December 2019 (using the first measurement as the baseline and the second as the follow-up) were enrolled, and clinical data such as blood pressure and baPWV were collected. According to the blood pressure level at baseline and follow-up, participants were divided into new-onset hypertension group (no hypertension at baseline but diagnosed at follow-up) and non-hypertension group (no hypertension at both baseline and follow-up). Multiple linear regression and multivariate logistic regression were used to analyze the impact of new-onset hypertension on arteriosclerosis progression. Subgroup analysis further classified participants into six blood pressure transition categories: normal-maintained, normal-to-high-normal, normal-to-hypertensive, high-normal-to-normal, high-normal-maintained, and high-normal-to-hypertensive groups. Multivariate logistic regression analysis was used to assess the impact of different blood pressure outcomes on arteriosclerosis progression.Results:A total of 7 049 participants were enrolled, with the age of (40.45±9.04) years, including 3 645 males (51.71%). There were 800 cases in the new-onset hypertension group and 6 249 individuals in the non-hypertension group. During follow-up, arteriosclerosis occurred in 2 154 cases (30.56%). Multivariable linear regression analysis revealed a positive correlation between new-onset hypertension and baPWV levels. The baPWV in the new-onset hypertension group was significantly higher by 63.94 cm/s compared to the non-hypertension group ( β=63.94, P<0.01). Additionally, the risk of arteriosclerosis in the new-onset hypertension group was 2.09 times that of the non-hypertension group ( OR=2.09, 95% CI: 1.77-2.46, P<0.01). Subgroup analysis revealed significantly higher arteriosclerosis risks in normal-to-high-normal ( OR=1.65, 95% CI 1.38-1.98, P<0.01), normal-to-hypertensive ( OR=2.47, 95% CI 1.70-3.59, P<0.01), high-normal-maintained ( OR=1.50, 95% CI 1.21-1.86, P<0.01), and high-normal-to-hypertensive groups ( OR=2.86, 95% CI 2.20-3.73, P<0.01) than normal-maintained group, except for a non-significant difference in high-normal-to-normal group ( OR=0.95, 95% CI 0.74-1.20, P>0.05). Conclusion:Blood pressure outcome in non-hypertensive populations is closely related to arteriosclerosis risk. Progression to or maintenance of high-normal blood pressure or higher levels substantially increases arteriosclerosis risk, while regression from high-normal to normal blood pressure shows no significant increase in arteriosclerosis risk.

BACKGROUND:Exercise training can improve osteoporosis,but its effects and mechanisms on senile osteoporosis are not fully understood. OBJECTIVE:To observe the effect of treadmill exercise on osteoporosis and wnt/β-catenin signal pathway in aged rats. METHODS:Sixteen 24-month-old male Sprague-Dawley rats were randomly divided into osteoporosis group(n=8)and treadmill group(n=8)and eight 6-month-old male Sprague-Dawley rats were used as young control group.The model of senile osteoporosis was replicated by natural aging and the rats in the treadmill group were treated with treadmill exercise once a day,5 days a week,for 8 weeks.Levels of bone metabolic markers such as type I collagen cross-linked C-terminal peptide,tartrate resistant acid phosphatase,osteocalcin and bone specific alkaline phosphatase were detected by ELISA;bone mineral density of the left femur and L5 was measured by dual energy X-ray;bone scanning and bone microstructure quantitative analysis were performed by bone micro-CT;and the mRNA and protein expression levels of wnt3a,β-catenin,LRP5,DKK1 and GSK3β were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the young control group,the osteoporosis group showed a reduction in serum bone specific alkaline phosphatase and osteocalcin levels(P<0.05),bone mineral density of the femur and L5,the number of tibia and L4 bone trabeculae,bone volume,bone volume fraction(P<0.05),and mRNA and protein expression of wnt3a,β-catenin,and LRP5 in bone marrow tissue(P<0.05)as well as an increase in serum levels of tartrate resistant acid phosphatase and type I collagen cross-linked C-terminal peptide(P<0.05),the intertrabecular space between the tibia and L4,structural model index(P<0.05),and mRNA and protein expression of DKK1 and GSK3 β in bone marrow tissue(P<0.05).In addition to the reduced number of trabeculae in the tibia and L4 vertebrae,the trabeculae were structurally disturbed and sparsely aligned and fractured.Compared with the osteoporosis group,the treadmill group showed an increase in serum bone specific alkaline phosphatase and osteocalcin levels(P<0.05),bone mineral density of the femur and L5(P<0.05),the number of tibial trabeculae,bone volume,bone volume fraction(P<0.05),mRNA and protein expression of wnt3a,β-catenin,and LRP5 in bone marrow tissue(P<0.05)but a reduction in the serum levels of tartrate resistant acid phosphatase and type I collagen cross-linked C-terminal peptide,L4 trabecular space,tibial trabecular space,structural model index,and mRNA and protein expression of DKK1 and GSK3 β in bone marrow tissue(P<0.05).In addition to the increased number of tibial and L4 trabeculae,the trabeculae were arranged in a regular and dense pattern and were connected to a network.To conclude,treadmill exercise may improve osteoporosis in aged rats by activating the wnt/β-catenin signal pathway.

Objective To investigate the effect of bone marrow mesenchymal stem cells(BMSC)transplantation on rats with painful diabetes peripheral neuropathy(PDPN).Methods Fourteen SPF grade male GK rats were randomly divided into model group and treat-ment group,with 7 rats in each group.Seven Wistar rats of the same-sex and same-age were used as the normal group.The treatment group received intraperitoneal injection of BMSC for 6 weeks of treatment.Detection of thermal pain threshold;take the sciatic nerve and observe the pathological morphological changes of the sciatic nerve using hematoxylin-eosin(HE)staining and Masson staining;Western blot was used to detect the expression of JAK2/STAT3 signaling pathway related proteins p-JAK2 and p-STAT3.Results After treat-ment with BMSC,the thermal pain threshold of rats increased slightly;the sciatic nerve injury was repaired,the infiltration of inflammato-ry cells was alleviated,and the phenomenon of demyelination was improved;the expression of pathway related proteins p-JAK2 and p-STAT3 decreased.Conclusion BMSC transplantation can alleviate inflammatory response,repair sciatic nerve,and alleviate pain by in-hibiting the JAK2/STAT3 signaling pathway.

OBJECTIVE: To prepare customized porous silicone orbital implants using embedded 3D printing and assess the effect of surface modification on the properties of the implants. METHODS: The transparency, fluidity and rheological properties of the supporting media were tested to determine the optimal printing parameters of silicone. The morphological changes of silicone after modification were analyzed by scanning electron microscopy, and the hydrophilicity and hydrophobicity of silicone surface were evaluated by measuring the water contact angle. The compression modulus of porous silicone was measured using compression test. Porcine aortic endothelial cells (PAOECs) were co-cultured with porous silicone scaffolds for 1, 3 and 5 days to test the biocompatibility of silicone. The local inflammatory response to subcutaneous porous silicone implants was evaluated in rats. RESULTS: The optimal printing parameters of silicone orbital implants were determined as the following: supporting medium 4% (mass ratio), printing pressure 1.0 bar and printing speed 6 mm/s. Scanning electron microscopy showed that the silicone surface was successfully modified with polydopamine and collagen, which significantly improved hydrophilicity of the silicone surface (P < 0.05) without causing significant changes in the compression modulus (P > 0.05). The modified porous silicone scaffold had no obvious cytotoxicity and obviously promoted adhesion and proliferation of PAOECs (P < 0.05). In rats bearing the subcutaneous implants, no obvious inflammation was observed in the local tissue. CONCLUSION Poprous silicone orbital implants with uniform pores can be prepared using embedded 3D printing technology, and surface modification obviously improves hydrophilicity and biocompatibility of the silicone implants for potential clinical application.
Animals ; Rats ; Swine ; Silicon ; Orbital Implants ; Endothelial Cells ; Porosity ; Silicones ; Printing, Three-Dimensional

Objective·To investigate the effect of F-box only protein 38(FBXO38)on the ocular melanoma proliferation and the potential regulatory pathway.Methods·Human skin cutaneous melanoma A375 and human uveal melanoma OMM2.3 cell lines with FBXO38 knockdown and overexpression were constructed by FBXO38 short hairpin RNA(shRNA)and FBXO38 overexpression plasmids respectively.Knockdown and overexpression efficiency of FBXO38 at transcription and protein levels were verified by using quantitative real-time PCR(qRT-PCR)and Western blotting.The effects of FBXO38 on melanoma cell proliferation were detected through clonal formation assay,BrdU immunofluorescence staining and CCK8 cell proliferation assay.By using The Cancer Genome Atlas(TCGA)database,differentially expressed genes were analyzed in the high and low expression groups of FBXO38.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment was performed to reveal the signaling pathways associated with FBXO38.CCK8 cell proliferation assay was used to detect the inhibition rates of the signaling pathway inhibitors on cells with different FBXO38 expression levels.qRT-PCR and Western blotting were used to detect whether the signaling pathway was activated after knocking down FBXO38.Results·qRT-PCR and Western blotting verified that mRNA and protein expression levels of FBXO38 in FBXO38 knockdown A375 and OMM2.3 cell lines decreased compared with the control group,while the expression levels of FBXO38 in the overexpression cell lines increased compared with wild type group(P＜0.05).Clonal formation assay,BrdU immunofluorescence staining and CCK8 cell proliferation assay showed that FBXO38 knockdown significantly enhanced the proliferation of A375 and OMM2.3 cells(P＜0.05),while overexpression of FBXO38 inhibited melanoma cell proliferation(P＜0.05).Enrichment analysis showed that in skin cutaneous melanoma and uveal melanoma,FBXO38 expression influenced the phosphoinositide 3-kinase/protein kinase B(PI3K-Akt)pathway activation.Compared with those in the control group,the inhibition rates of P13K inhibitor LY294002 and mTOR1 inhibitor Everolimus in the FBXO38 knockdown group significantly improved(P＜0.05),while their inhibition rates of the overexpression group significantly decreased compared with those of control cells(P＜0.05).Western blotting results showed that after knocking down FBXO38,expression levels of PTEN,P21 and P53 proteins decreased,while expression level of MDM2 protein increased.The qRT-PCR results showed a significant decrease in P53 transcription level(P＜0.05)and a significant increase in MDM2 transcription level in FBXO38 knockdown cells(P＜0.05).Conclusion·FBXO38 plays a role in regulating the proliferation of ocular melanoma,and this regulatory effect is related to the PI3K-Akt signaling pathway.

Objective Using of cumulative live birth rate(CLBR)per oocytes retrieved cycle,to assess the clinical outcomes of in vitro fertilization or intracytoplasmic sperm injection(IVF/ICSI),and to explore impact factors on CLBR following utilization of all fresh and frozen embryos in one complete IVF/ICSI cycle using gonadotropin-releasing hormone(GnRH)agonist, GnRH-antagonist and clomiphene mild stimulation protocols. Methods Of the patients who underwent IVF/ICSI from January 1st, 2014 to December 31st, 2015 in the First Affiliated Hospital, Nanjing Medical University, a total of 6 142 oocytes retrieved cycles were included. The clinical and laboratory parameters of different ovarian stimulation protocols, and the effects of the age, number of oocytes retrieved and number of embryos available on the CLBR of each oocytes retrieved cycle were analyzed.Results The CLBR was 69.0%(2 004/2 906)in the GnRH-agonist protocol versus 67.4%(644/955)in the GnRH-antagonist protocol (P>0.05); the CLBR of clomiphene mild stimulation protocol was 53.2%(1 215/2 281),significantly lower than those of the other two protocols (all P<0.05). The CLBR significantly decreased with age increased. When divided into four groups according to the patients′ age, we found that CLBR were not statistically significant using three different protocols in the 20-25 years old group(all P>0.05).There was a strong association between the number of oocytes retrieved and embryos available on CLBR. CLBR rose significantly with an increasing number of oocytes up to 6, then the rising trend slowed down. Patients were categorized into four groups according to the number of oocytes retrieved,CLBR was significantly higher using GnRH-antagonist protocol (50.0%)than mild stimulation protocol(37.0%)in low ovarian responder(0-4 oocytes)group(P<0.05). The CLBR were no significant difference among three protocols in normal(10-15 oocytes)and high responders(≥15 oocytes)group(all P>0.05).The incidence rate of ovarian hyperstimulation syndrome in GnRH-agonist protocols(5.2%,152/2 906)were significantly higher than those of GnRH-antagonist(4.4%, 42/955)and clomiphene mild stimulation protocols(1.5%,34/2 281;all P<0.05).Conclusions CLBR is an important index to assess the clinical outcomes of IVF/ICSI. Age, number of oocytes retrieved and embryos available could affect CLBR obviously. According to the different age and ovarian response of patients, we should design ovarian stimulation protocols based on target oocytes number in order to get higher CLBR and reduce complications.

Objective To evaluate the relations between hypertensive disorders (HDP) in pregnancy and early-term birth.Methods A total of 3 474 pregnant women were consecutively recruited.Demographic information was collected in early pregnancy.HDP was diagnosed in the first,second and third trimesters,respectively.On the basis of precise evaluation on gestation age,early-term birth was defined as gestational age of 37-38 weeks + 6 days.Logistic regression models were conducted to examine the associations between HDP and early-term birth.Results The current study included 3 260 pregnant women,with the rates of HDP,pregnancy-induced hypertension syndrome and pre-eclampsia as 6.0％ (n=194),4.2％ (n=137) and 1.8％ (n=57),respectively.After controlling for potential confounders,no significant differences between pregnancy-induced hypertension syndrome and early-term birth (OR=1.49,95％C1:0.94-2.36) were found.Pre-eclampsia appeared to have increased the risk of early-term birth (OR=4.46,95％ CI:2.09-9.54).Conclusion Pre-eclampsia could significantly increase the risk of early-term birth.This finding suggested that early detection and intervention programs were helpful in reducing the risk of early-term birth.