BACKGROUND:Cell-free therapy is a research hotspot in the field of medical cosmetic anti-aging.It is still unknown for paracellular secretion of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles loaded with the antiaging drug α-ketoglutaric acid to delay skin aging.OBJECTIVE:To investigate the effect of the anti-aging agent α-ketoglutarate engineered human umbilical cord mesenchymal stem cell-derived small extracellular vesicles in a D-galactose-induced model of dermal fibroblast senescence.METHODS:(1)Biological characteristics of primary human umbilical cord mesenchymal stem cells were identified by osteogenic-lipogenic differentiation staining and flow cytometry.(2)The small extracellular vesicles derived from human umbilical cord mesenchymal stem cell were obtained by using differential-ultracentrifugation.α-Ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles were constructed by electroporation,and biologically characterized by transmission electron microscopy and nanoparticle tracking analyzer,while the encapsulation rate was assessed using high-performance liquid chromatography.(3)The effect of α-ketoglutarate on the proliferative capacity of dermal fibroblasts was assessed by CCK-8 and Edu cell proliferation assay kits.(4)The effect of α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles on delaying the senescence of dermal fibroblasts was evaluated by reactive oxygen species detection kit,western blot assay,and cellular immunofluorescence.RESULTS AND CONCLUSION:(1)The obtained human umbilical cord mesenchymal stem cell and human umbilical cord mesenchymal stem cell-small extracellular vesicles were biologically compatible.(2)There was no toxic effect on dermal fibroblasts when α-ketoglutarate was used in the concentration range of 0.5-8 mmol/L.(3)D-gal induced senescence in dermal fibroblasts,while α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles treatment reduced the level of oxidative stress,DNA damage,and collagen loss,which was further verified that α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles could effectively slow down the skin aging process.

BACKGROUND:Cell-free therapy is a research hotspot in the field of medical cosmetic anti-aging.It is still unknown for paracellular secretion of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles loaded with the antiaging drug α-ketoglutaric acid to delay skin aging.OBJECTIVE:To investigate the effect of the anti-aging agent α-ketoglutarate engineered human umbilical cord mesenchymal stem cell-derived small extracellular vesicles in a D-galactose-induced model of dermal fibroblast senescence.METHODS:(1)Biological characteristics of primary human umbilical cord mesenchymal stem cells were identified by osteogenic-lipogenic differentiation staining and flow cytometry.(2)The small extracellular vesicles derived from human umbilical cord mesenchymal stem cell were obtained by using differential-ultracentrifugation.α-Ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles were constructed by electroporation,and biologically characterized by transmission electron microscopy and nanoparticle tracking analyzer,while the encapsulation rate was assessed using high-performance liquid chromatography.(3)The effect of α-ketoglutarate on the proliferative capacity of dermal fibroblasts was assessed by CCK-8 and Edu cell proliferation assay kits.(4)The effect of α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles on delaying the senescence of dermal fibroblasts was evaluated by reactive oxygen species detection kit,western blot assay,and cellular immunofluorescence.RESULTS AND CONCLUSION:(1)The obtained human umbilical cord mesenchymal stem cell and human umbilical cord mesenchymal stem cell-small extracellular vesicles were biologically compatible.(2)There was no toxic effect on dermal fibroblasts when α-ketoglutarate was used in the concentration range of 0.5-8 mmol/L.(3)D-gal induced senescence in dermal fibroblasts,while α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles treatment reduced the level of oxidative stress,DNA damage,and collagen loss,which was further verified that α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles could effectively slow down the skin aging process.

Objective To explore the distribution characteristics and influencing factors of nasal colonized bacteria of healthcare workers(HCWs)in pediatric intensive care unit(PICU).Methods A cross-sectional study was con-ducted.Nasal swab specimens from 104 HCWs in the PICU of a hospital were collected for bacterial culture and an-timicrobial susceptibility testing.According to the identification and antimicrobial susceptibility testing results of strains,distribution characteristics of colonized bacteria was analyzed.Basic information of studied subjects were collected through questionnaire survey,and risk factors for colonized bacterial infection were conducted using logis-tic regression analysis.Results Among 104 specimens,colonized bacteria were detected from 66 specimens,with an overall detection rate of 63.46％.Gram-positive bacteria was mainly Staphylococcus aureus,with a detection rate of 34.62％(n=36),out of which methicillin-resistant Staphylococcus aureus(MRSA)accounted for 2.88％(n=3).Gram-negative bacteria was mainly Klebsiella spp.,with a detection rate of 21.15％(n=22).Multiva-riate logistic regression analysis showed that HCWs with junior professional titles(OR=11.400,95％CI:2.329-55.801,P=0.003)was an independent risk factor for Staphylococcus aureus colonization,and male(OR=4.260,95％CI:1.160-15.653,P=0.029)was an independent risk factor for Klebsiella spp.colonization.Conclusion Nasal cavity of HCWs in PICU has a high detection rate of colonized bacteria,with Staphylococcus aureus and Klebsiella spp.being the major colonized bacteria.

BACKGROUND:Currently,research both domestically and internationally on patellofemoral pain syndrome has explored the kinematics and dynamics during daily activities such as stair ascent and descent,and walking. However,there is a lack of studies examining the lower limb biomechanical characteristics of young female patients with patellofemoral pain syndrome in different squatting conditions.OBJECTIVE:To investigate the lower limb biomechanical characteristics among young female patients with patellofemoral pain syndrome in different functional states of the subtalar joint,providing theoretical support for the clinical treatment of various types of patellofemoral pain syndrome.METHODS:A total of 33 participants were included in this study. There were 10 subjects in the healthy control group (group C). The other 27 subjects with patellofemoral pain syndrome were divided into two groups according to the foot posture index:14 subjects in the normal subtalar joint group (group A,foot posture index 0-6 points) and 13 subjects in the abnormal subtalar joint group (group B,foot posture index 7-12 points). The biomechanical indices of thesubjects in each group were collected and compared when they walked on stairs at normal speed. The kinematic indices included the three-dimensional joint angles of the hip and knee and the sagittal plane joint angles of the ankle at the initial contact moment and the moment of maximum knee flexion angle during the stance period. The dynamic indices included the three-dimensional joint torques of the hip and knee and the sagittal plane joint torques of the ankle at the moment of maximum knee flexion angle during the stance period. The surface electromyography indices included the root mean square amplitudes of the vastus medialis,vastus lateralis,rectus femoris,semitendinosus and semimembranosus,biceps femoris,and gluteus medius in the pre-activation stage and the buffering stage.RESULTS AND CONCLUSION:(1) At the initial ground contact moment,group A exhibited a greater knee flexion angle (P<0.05),greater hip external rotation angle (P<0.01),and smaller knee external rotation angle (P<0.01) compared to group B. Compared to group C,group A showed a greater knee flexion angle and smaller hip flexion angle (both P<0.01). Group B demonstrated a greater knee external rotation angle and smaller hip external rotation angle and hip flexion angle (all P<0.01) compared to group C. (2) At the moment of maximum knee flexion,group A had a smaller knee valgus angle (P<0.05),smaller knee external rotation angle (P<0.05),and greater knee flexion angle (P<0.01) compared to group B. Compared to group C,group A showed a smaller knee valgus angle (P<0.05),smaller hip flexion angle (P<0.01),and smaller hip external rotation angle (P<0.05). Group B had a smaller knee flexion angle,hip flexion angle,hip external rotation angle,and greater knee external rotation angle (all P<0.01) compared to group C. Additionally,group A exhibited a greater hip internal rotation moment (P<0.05) and plantarflexion moment (P<0.01) compared to group C. (3) At normal speed during the staircase buffering phase,group C showed higher activation levels than group A in the vastus lateralis (P<0.05),vastus medialis (P<0.01),gluteus medius (P<0.01),and biceps femoris (P<0.05). Group C also had higher activation levels than group B in the vastus medialis (P<0.01),gluteus medius (P<0.01),and biceps femoris (P<0.05). Additionally,group A showed higher activation in the semitendinosus and semimembranosus muscles compared to group B (P<0.05). (4) These findings indicate that young female patients with patellofemoral pain syndrome have stiffer hip and knee joint buffering while descending stairs,potentially compensated by the ankle joint. Low muscle activation levels contribute to patellofemoral pain,with those having normal subtalar joints but experiencing pain showing the lowest and most abnormal activation. ③ Abnormal biomechanics in the normal subtalar joint group are mainly due to insufficient hip and knee flexion. Abnormal biomechanics in the abnormal subtalar joint group are mainly due to excessive subtalar joint pronation.

Reduced or interrupted blood flow is an important pathological and physiological process in femoral head necrosis,so understanding the blood flow of the femoral head can help better understand the progression of femoral head necrosis.With the continuous development and improvement of imaging technology,the technical methods for detecting the blood flow of the femoral head are gradually being widely applied,allowing clinical physicians to better understand the blood flow situation of patients with femoral head necrosis.However,at present,the prognosis prediction of femoral head necrosis still mainly revolves around factors such as the area and angle of femoral head necrosis.Therefore,this article explores imaging techniques covering studies such as femoral head vascular imaging or blood flow perfusion parameters,summarizes their application research progress in femoral head necrosis blood flow assessment,and aims to provide more objective basis for exploring the prevention and prognosis of femoral head necrosis from the perspective of femoral head blood flow.

Objective:To explore the cardioprotective effects of icariin (ICA) against radiation-induced cardiac disease (RICD) in C57BL/6 mice.Methods:A total of 48 female C57BL/6J mice aged 6-8 weeks were randomly divided into three groups: the control group (CON), the irradiation group (IR), and the irradiation combined with icariin group (IR+ ICA), with 16 mice in each group. The IR and IR+ ICA groups received a single cardiac irradiation at a dose of 30 Gy, while the CON group received no radiation treatment. The IR+ ICA group was treated with ICA (70 mg·kg -1·d -1) two weeks before irradiation until the end of the experiment through intragastric administration. In contrast, the CON and IR groups were treated with an equal volume of vehicle solution (0.5% sodium carboxymethyl cellulose, NaCMC) via intragastric administration. The mice′s mental status, food intake, body weight, and survival rates were monitored during the experiment. At two weeks post-irradiation, the venous blood of the mice was collected and serum was separated for the enzyme-linked immunosorbent assays (ELISA) of creatine kinase MB isoenzyme (CK-MB) and cardiac troponin T (cTnT/TNNT2). At 12 weeks post-irradiation, the cardiac function of the mice was assessed using echocardiography. After the mice were euthanized under anesthesia, the histopathological changes and fibrosis degree of their myocardial tissues were assessed using hematoxylin and eosin (HE) and Masson′s trichrome staining, followed by the calculation of collagen volume fraction (CVF). The differential gene expression of brain natriuretic peptide (BNP), transforming growth factor-β (TGF-β), and interleukin-6 (IL-6) in the cardiac tissues of the mice was detected using real-time reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis-related proteins and proteins associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway were determined using Western blotting. The survival curves of the mice were plotted using Kaplan-Meier, and the survival differences of the mice among various groups were compared using the log-rank test. Results:After irradiation, the mice in the IR group showed lethargy, as well as decreased food intake and activity, while these symptoms in the IR+ ICA group were significantly alleviated. At two weeks post-irradiation, the CK-MB and cTnT levels of the IR group were significantly elevated compared with the CON group ( t = 5.28, 8.89, P < 0.01). At 12 weeks post-irradiation, the mice in the IR group exhibited significantly decreased body weight ( t = 2.47, P < 0.05) and decreased survival rates ( HR = 8.25, 95% CI: 1.157-58.770, P < 0.05) compared with the CON group. Echocardiography revealed that the IR group featured decreased left ventricular ejection fraction (EF), decreased fractional shortening (FS), and increased left ventricular end-diastolic diameter (LVDD) compared with the CON group ( t = 7.02, 4.45, P < 0.05). Histopathological examination revealed that the IR group suffered from cardiomyocyte edema, disordered arrangement, and increased fibrosis, with an elevated CVF. The IR group exhibited significantly upregulated gene expression of BNP, TGF-β, and IL-6 in cardiac tissues compared with the CON group ( t = 4.23, 6.39, 4.61, P < 0.05). After-irradiation, the IR group exhibited upregulated apoptosis-related proteins Cleaved Caspase-3 and Bax ( t = 6.29, 9.54, P < 0.05), decreased Bcl-2 expression ( t = 8.20, P < 0.001), and decreased phosphorylation levels of PI3K and Akt ( t = 6.47, 3.42, P < 0.001). The symptoms of the mice were partially ameliorated after treatment with ICA. Specifically, the mice in the IR+ ICA group exhibited higher body weight ( t = 5.13, P < 0.001) and significantly higher survival rates ( HR = 0.121, 95% CI: 0.017-0.864, P < 0.05) than the IR group. Compared to the IR group, the IR+ ICA group showed elevated cardiac function indicators EF and FS( t = 3.23, 3.05, P < 0.05), and reduced LVDD ( t = 3.02, P < 0.05). The histopathological analysis revealed mitigated edema and disordered arrangement of cardiomyocytes in the IR+ ICA group. Furthermore, the IR+ ICA group exhibited significantly lower BNP, TGF-β, and IL-6 expression levels than the IR group ( t = 2.83, 4.15, 2.96, P < 0.05). The expression of apoptosis-related proteins Cleaved Caspase-3 and Bax was lower ( t = 3.23, 3.24, P < 0.05), Bcl-2 expression was higher ( t = 5.92, P < 0.001), and restored phosphorylation levels of PI3K and Akt ( t = 2.89, 8.35, P < 0.001). Conclusions:Icariin has protective effects against the RICD. It alleviates cardiomyocyte apoptosis possibly by upregulating the phosphorylation levels of PI3K and Akt.

Objective To explore the distribution characteristics and influencing factors of nasal colonized bacteria of healthcare workers(HCWs)in pediatric intensive care unit(PICU).Methods A cross-sectional study was con-ducted.Nasal swab specimens from 104 HCWs in the PICU of a hospital were collected for bacterial culture and an-timicrobial susceptibility testing.According to the identification and antimicrobial susceptibility testing results of strains,distribution characteristics of colonized bacteria was analyzed.Basic information of studied subjects were collected through questionnaire survey,and risk factors for colonized bacterial infection were conducted using logis-tic regression analysis.Results Among 104 specimens,colonized bacteria were detected from 66 specimens,with an overall detection rate of 63.46％.Gram-positive bacteria was mainly Staphylococcus aureus,with a detection rate of 34.62％(n=36),out of which methicillin-resistant Staphylococcus aureus(MRSA)accounted for 2.88％(n=3).Gram-negative bacteria was mainly Klebsiella spp.,with a detection rate of 21.15％(n=22).Multiva-riate logistic regression analysis showed that HCWs with junior professional titles(OR=11.400,95％CI:2.329-55.801,P=0.003)was an independent risk factor for Staphylococcus aureus colonization,and male(OR=4.260,95％CI:1.160-15.653,P=0.029)was an independent risk factor for Klebsiella spp.colonization.Conclusion Nasal cavity of HCWs in PICU has a high detection rate of colonized bacteria,with Staphylococcus aureus and Klebsiella spp.being the major colonized bacteria.

BACKGROUND:Protein is one of the essential nutrients for the human body and is a key component of human cell tissue.Protein supplementation can promote the synthesis of myofibrillar protein and play a key role in strength training.However,the interaction mechanism and signaling pathway between protein and exercise are still unclear.OBJECTIVE:To explore the mechanism of interaction between exercise and protein,and to optimize the benefits of protein supplementation on exercise performance.METHODS:Using"sports,proteins,amino acids,polypeptide,interaction mechanisms,signaling pathway"as Chinese and English search terms,we searched WanFang Data,CNKI,VIP,and PubMed databases respectively.Articles were screened according to the inclusion criteria,and finally 73 articles were included in the review.RESULTS AND CONCLUSION:Current research on protein supplementation promoting exercise performance mainly focuses on promoting muscle growth,endurance improvement,and body recovery through protein supplementation,but there are differences in the existing experimental results.The interaction mechanism between protein molecules and proteins in the body is not yet clear.The research on the interaction mechanism between exercise and peptides is still in its infancy.Exercise can stimulate the full absorption of external protein intake,which can affect the mechanism of protein molecules in the body.Supplementing peptide nutrition can more accurately affect the body's state,thus better eliminating the phenomena of"sub-health"and"modern diseases."Therefore,studying the interaction mechanism between exercise and proteins is particularly important,delving into the specific mechanisms by which amino acids act on the body,and further exploring the interaction mechanism between exercise and peptides.

Lemborexant is a new drug for the treatment of insomnia.It is a dual orexin receptor antagonist that competitively binds to two orexin receptors,OX1R and OX2R,inhibits orexin neuro-transmission,and regulates the sleep-wake rhythm.This article comprehensively reviews the discovery of the drug target,basic information,clin-ical studies,safety assessment,and limitation anal-ysis of lemborexant,aiming to provide a compre-hensive understanding of the current research sta-tus and achievements of this drug in clinical prac-tice.

To explore the application of sequential analysis in post-market safety dynamic surveillance of vaccines. Under the dynamic monitoring data of vaccines post-market approval, this research introduces the fundamental principles of maximizing sequential probability ratio test (MaxSPRT) and Bayesian sequential analysis, employing R software. Through an example of dynamic safety monitoring data of vaccines post-market approval, we analyze using the MaxSPRT and Bayesian sequential analysis. The MaxSPRT identified a safety signal in week 4 ( P<0.05), while Bayesian sequential analysis indicated that the 95% highest density interval for the RR value at week 4 is 1.13-3.27, suggesting the first appearance of a safety signal at week 4. The MaxSPRT and Bayesian sequential analysis effectively leverage continuously accumulating dynamic monitoring data, thereby serving as a valuable method for post-market safety surveillance of vaccines.