BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.

Objective: To investigate the status of heat illness, knowledge awareness and adaptive behaviors of heat wave knowledge among food delivery riders, so as to provide a basis for optimizing heat wave response measures for food delivery riders. Methods: In November 2022, food delivery riders from a large food delivery platform in Ningbo City, Zhejiang Province were selected as survey subjects using a cluster sampling method. A self-designed electronic questionnaire was used to select demographic information, work status, lifestyle behaviors and disease history, heat illness status, knowledge awareness and adaptive behaviors of heatwave. Results: A total of 911 questionnaires were distributed, and 830 valid questionnaires were recovered, resulting in a valid response rate of 91.11%. Among the respondents, 796 (95.90%) were male, and 818 (98.55%) worked full-time. The mean age was (27.75±8.00) years. A total of 470 respondents (56.63%) had a work tenure of less than 1 year. The primary working hours were 8-<12 hours, with 504 people accounting for 60.72%. There were 108 cases of heatstroke, with an occurrence rate of 13.01%. And 286 people reported heat-related symptoms, with an occurrence rate of 34.46%. The overall awareness rate of heat wave knowledge was 73.22%, while the awareness rate of heat warning signal classification was relatively low at 9.04%. The heat wave cognition score was (5.86±1.31) points. There were statistically significant differences in heat wave cognition scores among food delivery riders of different ages, educational levels, family annual income, work tenures, and work durations (all P<0.05). Regarding positive adaptive behaviors, the number of riders paying attention to weather forecasts and actively learning about preventive measures was higher (734 people each, accounting for 88.43%). Regarding negative adaptive behaviors, the number of riders who often drank ice-cold beverages was higher (509 people, accounting for 61.33%). The heat wave adaptive behavior score was (6.88±1.77) points. There were statistically significant differences in adaptive behavior scores among riders with different educational levels, family annual income, work tenures, and smoking frequency (all P<0.05). Conclusions The occurrence rates of heatstroke and heat-related symptoms among food delivery riders are relatively high. The knowledge awareness and adaptive behaviors regarding heat wave are at a moderate level. It is suggested to strengthen health education, reinforce risk cognition of heat wave, and promote positive adaptive behaviors among food delivery riders.

Purpose: To evaluate the efficacy and safety of modified four-flanged intrascleral fixation of foldable intraocular lenses (IOLs) using a 1-inch 30-gauge needle for extraocular suture threading. Methods: This retrospective case series included 20 eyes of 20 patients who underwent four-flanged intrascleral IOL fixation using a 1-inch 30-gauge needle, with at least 6 months of follow-up. We modified the original Canabrava technique by inserting a foldable IOL through a 2.4-mm clear corneal incision with a standard injector and performing extraocular suture threading with a 1-inch 30-gauge needle. Collected data included uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), intraocular pressure, spherical equivalent (SE), prediction error (PE), and corneal and lens astigmatism. Postoperative complications and IOL centration were also evaluated. Results: Visual acuity improved significantly over the 6-month follow-up; mean preoperative logMAR UCVA was 1.25 ± 0.66 (Snellen equivalent, 20 / 355) and improved to 0.35 ± 0.19 (20 / 45), and logMAR BCVA improved from 0.53 ± 0.38 (20 / 70) to 0.15 ± 0.09 (20 / 30) (p < 0.05). The mean postoperative SE at 6 months was –0.61 ± 1.08 diopters, and PE was –0.25 ± 0.86 diopters. No significant changes in endothelial cell density were observed. Corneal astigmatism remained stable, and lens astigmatism was reduced after surgery, although not significantly. Postoperative complications included one case each of hypotony and vitreous hemorrhage, both resolved with medical therapy. No IOL redislocation, decentration, tilt, or flange-related issues occurred. Conclusions Modified four-flanged intrascleral IOL fixation using a 1-inch 30-gauge needle provides stable IOL fixation by pairing a robust suture with the smallest suitable needle. Extraocular suture threading reduces intraocular manipulation, simplifying the procedure and resulting in favorable visual outcomes and low complication rates.

Skeletal muscle atrophy is closely associated with oxidative stress-induced inflammatory responses,which lead to the activation of catabolic pathways and the loss of myotube integrity. Dillapiole, a phenylpropanoid compound derived from several aromatic plants, has been reported to exhibit anti-inflammatory and antioxidant properties, suggesting its potential benefits in conditions characterized by muscle wasting. This study aimed to investigate whether dillapiole attenuates hydrogen peroxide (H2O2 )-induced muscle atrophy in C2C12 myotubes and to elucidate its regulatory effects on key atrogenes. C2C12 myoblasts were differentiated into myotubes and then exposed to H2O2 to induce oxidative stress-mediated atrophy in the presence or absence of dillapiole. These findings indicate that dillapiole protects C2C12 myotubes against H2O2-induced muscle atrophy primarily by attenuating oxidative stress–associated inflammatory responses and suppressing the expression of Atrogin-1 and MuRF1.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.

Background: Radioactive iodine treatment (RAIT) is an essential therapy for differentiated thyroid cancer. However, unforeseen complications arising during thyroid hormone withdrawal (THW) can lead to Cancellation of the scheduled treatment. This study aimed to identify cases in which THW-RAIT was discontinued due to THW-related complications and to explore potentially preventable causes to improve patient management. Methods: Among 4,174 patients who underwent THW-RAIT between 2012 and 2024, 39 did not complete the planned treatment. After excluding Cancellations unrelated to THW, 11 (0.26%) patients with unexpected THW-related medical issues were analyzed. Results: The median age of the included patients was 61 years (range, 23 to 70), and 10 were male. The reasons for THW-RAIT Cancellation were hyponatremia (n=1), abnormal liver function (n=1), renal dysfunction (n=3), and combined liver and renal dysfunction (n=6). The patient with hyponatremia was taking a thiazide diuretic. Most cases of liver dysfunction were associated with prior use of herbal medications, whereas renal dysfunction was linked to diuretic or nonsteroidal anti-inflammatory drug use, pre-existing conditions such as single kidney or diabetic nephropathy, or inadequate oral intake during low-iodine preparation. Two cases of concurrent liver and renal dysfunction were attributed to rhabdomyolysis following intense exercise or heavy physical labor. Conclusion Enhanced patient education, comprehensive pre-treatment assessment, and careful avoidance of high-risk medications are essential to prevent THW-related complications and minimize disruptions in RAIT.

Purpose: Although lower body strength and size are often regarded as symbols of masculinity, their relationship to testosterone is unclear. This study aimed to determine the correlation between lower body strength, size, and testosterone levels. Materials and Methods: Serum testosterone levels, waist circumference, and body mass index (BMI) were measured in 69 men with erectile dysfunction (age >40 years). The circumferences of the thigh and calf were measured, and the muscle strength of the knee joints was evaluated using an isokinetic dynamometer. Patients were classified into three groups according to testosterone levels (group 1, <230 ng/dL; group 2, 230 to 350 ng/dL; group 3, >350 ng/dL). Differences in calf and thigh circumference, bilateral knee extension, and flexion strength between the three groups were investigated using a one-way analysis of variance. Pearson’s chi-square test was used to assess differences in lifestyle habits and underlying diseases. A partial correlation analysis was conducted to determine the association between testosterone levels and lower body size and strength. Results: There was no difference in BMI among the three groups, but waist circumference was significantly larger in group 1 than in groups 2 and 3. When comparing weight-adjusted values, bilateral thigh circumference showed a significant difference among the three groups. There was also a significant difference between the three groups in the weight-adjusted left calf circumference and in the weight-adjusted right knee extension strength. The partial correlation test showed a significant positive correlation between thigh and calf circumference values adjusted for weight and serum testosterone levels. Weight-adjusted knee extension strength demonstrated a significant positive correlation with serum testosterone levels. Conclusions Weight-adjusted thigh and calf circumferences, along with the thigh-to-waist ratio, showed a positive correlation with testosterone levels. Weight-adjusted knee extension strength was positively correlated with testosterone levels. Therefore, a robust thigh and strong lower body are related to testosterone.

Enzymatic cascade catalysis has emerged as an effective means to enhance the sensitivity of biosensors due to its remarkable amplification effect on electrochemical signals.However,the most used natural enzymes have high specificity and high catalytic activity,but are susceptible to environmental factors,easy denaturation and inactivation,and high cost,which limit their practical applications.Additionally,the majority of nanozymes with excellent catalytic activity cannot be directly used as redox probes.The redox signal can only be required under high potentials in strong acid/alkali solutions,or functionalized with electroactive substances.To tackle this problem,herein,AuNPs(glucose oxidase-like activity)and Mn,Zr dual-doped CeO2 nanozymes(Mn,Zr-CeO2,peroxidase-like activity)were used as model enzymes to construct a high-performance nanozymes cascade catalytic system.Owing to high Ce4+/Ce3+ratio and a considerable number of oxygen vacancies,Mn,Zr-CeO2 nanozymes exhibited excellent peroxidase-like activity and could generate amplified electrochemical signals in neutral medium at low potentials.Furthermore,the porous structure of Mn,Zr-CeO2 nanozymes could accelerate the mass transfer of intermediate H2O2,thereby enhancing the efficiency of enzymatic cascade catalysis.As a result,a label-free electrochemical biosensor was constructed for sensitive detection of the cancer marker miRNA-21 at physiological pH,with a detection limit as low as 32.5 fmol/L.This strategy offered a novel approach for the development of a new generation of high-performance nanozymes cascade platforms,which could be widely applied in the fields such as biotechnology,bioanalysis,and disease diagnosis.