Objective:Bidirectional causal associations of 41 cytokines with atopic dermatitis(AD)were explored based on a Mendelian randomization(MR)approach.Methods:Pooled data from genome wide association study(GWAS)of 41 cytokines and AD were utilized for instrumental variable(IV)screening,and single nucleotide polymorphism(SNP)affecting the results of MR analyses was excluded by the MR-PRESSO outlier test as well as by the MR Steiger filtering method.Two-sample bidirectional MR analyses were performed using inverse variance weighting(IVW),MR-Egger regression,and weighted median methods(WM).MR-Egger intercept term test and Cochran's Q test were performed to test the pleiotropy and heterogeneity of IV,and MR results were visu-alized by scatterplots,funnel plots,and leave-one-out plots.Results:Forward MR analysis showed that MIG(IVW:OR=0.89;95%CI:0.81～0.97;P=0.006)reduced the risk of AD development.In contrast,IL-5(IVW:OR=1.17;95%CI:1.01～1.36;P=0.042)and IL-18(MR Egger:OR=1.17;95%CI:1.03～1.33;P=0.030)increased the risk of AD development.Inverse MR analysis showed a potential causal association between AD and increased MIG(IVW:Beta=0.10;95%CI:0.02～0.17;P=0.014).None of the sensitivity analyses indicated pleiotropy and heterogeneity of the included IV.Conclusion:MIG may be an important marker in the progression of AD with a potential bidirectional causal association with risk of morbidity.IL-5 and IL-18 have a potential positive causal association for AD.

Objective:Bidirectional causal associations of 41 cytokines with atopic dermatitis(AD)were explored based on a Mendelian randomization(MR)approach.Methods:Pooled data from genome wide association study(GWAS)of 41 cytokines and AD were utilized for instrumental variable(IV)screening,and single nucleotide polymorphism(SNP)affecting the results of MR analyses was excluded by the MR-PRESSO outlier test as well as by the MR Steiger filtering method.Two-sample bidirectional MR analyses were performed using inverse variance weighting(IVW),MR-Egger regression,and weighted median methods(WM).MR-Egger intercept term test and Cochran's Q test were performed to test the pleiotropy and heterogeneity of IV,and MR results were visu-alized by scatterplots,funnel plots,and leave-one-out plots.Results:Forward MR analysis showed that MIG(IVW:OR=0.89;95%CI:0.81～0.97;P=0.006)reduced the risk of AD development.In contrast,IL-5(IVW:OR=1.17;95%CI:1.01～1.36;P=0.042)and IL-18(MR Egger:OR=1.17;95%CI:1.03～1.33;P=0.030)increased the risk of AD development.Inverse MR analysis showed a potential causal association between AD and increased MIG(IVW:Beta=0.10;95%CI:0.02～0.17;P=0.014).None of the sensitivity analyses indicated pleiotropy and heterogeneity of the included IV.Conclusion:MIG may be an important marker in the progression of AD with a potential bidirectional causal association with risk of morbidity.IL-5 and IL-18 have a potential positive causal association for AD.

Objective:The triply periodic minimal surface(TPMS)Gyroid porous scaffolds were built with identical porosity while varying pore sizes were used by fluid mechanics finite element analysis(FEA)to simulate the in vivo microenvironment.The effects of scaffolds with different pore sizes on cell adhesion,proliferation,and osteogenic differentiation were evaluated through calculating fluid velocity,wall shear stress,and permeability in the scaffolds.Methods:Three types of gyroid porous scaffolds,with pore sizes of 400,600 and 800 μm,were established by nTopology software.Each scaffold had di-mensions of 10 mm × 10 mm × 10 mm and isotropic internal structures.The models were imported to the ANSYS 2022R1 software,and meshed into over 3 million unstructured tetrahedral elements.Boun-dary conditions were set with inlet flow velocities of 0.01,0.1,and 1 mm/s,and outlet pressure of 0 Pa.Pressure,velocity,and wall shear stress were calculated as fluid flowed through the scaffolds using the Navier-Stokes equations.At the same time,permeability was determined based on Darcy's law.The compressive strength of scaffolds with different pore sizes was evaluated by ANSYS 2022R1 Static struc-tural analysis.Results:A linear relationship was observed between the wall shear stress and fluid veloci-ty at inlet flow rates of 0.01,0.1 and 1 mm/s,with increasing velocity leading to higher wall shear stress.At the flow velocity of 0.1 mm/s,the initial pressures of scaffolds with pore sizes of 400,600 and 800 μm were 0.272,0.083 and 0.079 Pa,respectively.The fluid pressures were gradually decreased across the scaffolds.The average flow velocities were 0.093,0.078 and 0.070 mm/s,the average wall shear stresses 2.955,1.343 and 1.706 mPa,permeabilities values 0.54 × 10-8 1.80 × 10-8 and 1.89 × 10-8 m2 in the scaffolds with pore sizes of 400,600 and 800 μm.The scaffold surface area proportions according with optimal wall shear stress range for cell growth and osteogenic differentiation were calcula-ted,which was highest in the 600 μm scaffold(27.65％),followed by the 800 μm scaffold(17.30％)and the 400 μm scaffold(1.95％).The compressive strengths of the scaffolds were 23,26 and 34 MPa for the 400,600 and 800 μm pore sizes.Conclusion:The uniform stress distributions appeared in all gyroid scaffold types under compressive stress.The permeabilities of scaffolds with pore sizes of 600 and 800 μm were significantly higher than the 400 μm.The average wall shear stress in the scaffold of 600μm was the lowest,and the scaffold surface area proportion for cell growth and osteogenic differentiation the largest,indicating that it might be the most favorable design for supporting these cellular activities.

Objective:To investigate the effect of bone mesenchymal stem cells derived exosomes (BMSC-Exo) on improving hippocampal microangiogenesis, energy metabolism, and behaviors in depression mouse models.Methods:(1) Mouse bone marrow mesenchymal stem cells were isolated and cultured to extract BMSC-Exo; BMSC-Exo morphology was observed by transmission electron microscopy, BMSC-Exo particle diameter ranges were determined by Zetaview analyzer, and expressions of CD9 and CD63 in BMSC-Exo were detected by Western blotting. (2) Depression models were established in 2 mice by chronic unforeseeable mild stress (CUMS); 24 h after stereotaxic injection of phosphate buffer solution (PBS) or DiR labeled BMSC-Exo, BMSC-Exo uptake was detected by in vivo imaging system. (3) Thirty-six mice were randomly divided into control group, model group and BMSC-Exo group ( n=12); CUMS was used to establish depression models in the latter 2 groups; brain stereotaxic injection of 1 μL BMSC-Exo was given to mice in the BMSC-Exo group after modeling, and same amount of PBS was given to the control group; behaviors were observed by forced swimming test (FST), tail suspension test (TST) and open field test (OFT); hippocampal microvascular length and number were detected by alkaline phosphatase staining; energy metabolism in the hippocampus was detected by micro positron emission tomography/computed tomography (mPET/CT); glucose transporter 1 (GLUT1) expression in the hippocampus was detected by Western blotting. Results:(1) BMSC-Exo had a typical disk-like vesicle-like structure with particle size of (100.5±1.4) nm; Western blotting confirmed that CD9 and CD63 expressed in BMSC-Exo. (2) In vivo imaging showed no fluorescence in the brain and liver after PBS injection, but obvious local fluorescence after BMSC-Exo injection. (3) Compared with the control group, the model group and BMSC-Exo group had significantly longer rest time in FST and TST and shorter movement distance and time in the central region of OFT ( P<0.05); compared with the model group, BMSC-Exo group had significantly shorter rest time in FST and TST and longer movement distance and time in the central region of OFT ( P<0.05). Compared with the control group, the model group and BMSC-Exo group had significantly decreased standard uptake value (SUV) of regions of interest, microvascular length and number, and GLUT1 expression in the hippocampus ( P<0.05); compared with the model group, the BMSC-Exo group had significantly higher SUV, microvascular length and number, and GLUT1 expression in the hippocampus ( P<0.05). Positive correlations were noted between hippocampal microvascular length and SUV and between microvascular number and SUV in the 3 groups ( r=0.540, P<0.001; r=0.600, P<0.001). Conclusion:BMSC-Exo could promote microangiogenesis energy metabolism in the hippocampus to improve depression-like behaviors in depression mouse models.

Objective:The aim of noise quality management for ICU patients was to explore the clinical feasibility of noise quality management.Methods:A randomized controlled trial method and convenient sampling method were used to select 240 patients treated in the ICU of Shanghai Fengxian District Central Hospital from April 2021 to March 2023 as the study objects. According to the time of admission, 120 patients admitted from April 2021 to March 2022 were divided into the control group. A total of 120 patients admitted to hospital from April 2022 to March 2023 were included in the intervention group. The control group was given routine care, and noise quality management was implemented in the intervention group on the basis of routine care. The noise decibel value, sleep quality, incidence of delirium and patient satisfaction of the two groups were compared.Results:In the intervention group, there were 69 males and 51 females, aged (56.08 ± 5.74) years old. The control group included 68 males and 52 females, aged (56.11 ± 5.72) years old. The decibels of day and night in ICU of the intervention group were (42.62 ± 1.33) and (38.72 ± 1.28) dB, which were lower than those of the control group (67.49 ± 2.36) and (59.65 ± 2.37) dB, with statistically significant differences ( t=100.57, 85.12, both P<0.05). Total score of sleep quality of patients in the intervention group (78.40 ± 5.86) was higher than that of the control group (60.49 ± 6.25), with statistically significant differences ( t=24.32, P<0.05). The incidence of delirium in the intervention group 12.50%(15/120), was lower than that in the control group 26.67%(32/120) with a statistically significant difference ( χ2=7.65, P<0.05). Satisfaction of patients in the intervention group 97.50%(117/120) was higher than that in the control group 90.00%(108/120), with a statistically significant difference ( χ2=5.76, P<0.05). Conclusions:The application of noise quality management for ICU patients is conducive to improving the overall environment of the ward, improving the sleep quality of patients, reducing the occurrence of patients′ delirium and improving patient satisfaction.

Objective To investigate current management of external auditory canal irrigation among the nurses in otolaryngology in Guangdong Province,and to provide a reference for development and promotion of a standardised procedure.Methods From January to February in 2022,a total of 48 head nurses or nursing backbone in otolaryngology department of 48 hospitals from 21 major cities in Guangdong Province were selected by convenience sampling.A questionnaire proposed by Otolaryngology Nursing Committee of Guangdong Nursing Association was used to investigate the knowledge,operation procedure and training management in external auditory canal irrigation.Results A total of 48 head nurses or nursing backbone responded to the survey.The survey revealed that 34(70.8%)of the participants had mastered the knowledge of external auditory canal irrigation and 38(79.2%)of them had mastered the knowledge on the irrigation indications.In terms of operation procedure,syringe was applied as irrigator in 43(89.6%)hospitals,disposable irrigation needle was applied as flushing connector in 24(50.0%)hospitals,body surface temperature test of operator or patient was carried out in 24(50.0%)hospitals and adjusted flushing pressure was applied according to patients'feedback in 37(77.1%)hospitals.Regarding the training of external auditory canal irritation,35(72.9%)hospitals did not ask patients to sign an informed consent before,29(60.4%)hospitals required qualifications for operator and 45(93.7%)hospitals had the training programs.Conclusions The knowledge of external auditory canal irrigation of otolaryngology nurses in Guangdong province needs to be improved.The management of procedure and training of external auditory canal irrigation shall be standardised.It is suggested that the profession should draw up the external auditory canal irrigation standard,and all hospitals strengthen the management and training in order to promote the standardisation of specialised nursing together.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood. Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival. Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group.Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity. Conclusions The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood. Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival. Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group.Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity. Conclusions The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood. Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival. Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group.Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity. Conclusions The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.

Objective:To investigate the effects of human umbilical cord mesenchymal stem cells exosomes (hucMSC-Exo) on depression-like behavior and polarization dynamic transition of hippocampal microglia in chronic unpredictable mild stress(CUMS) mice.Methods:The hucMSC was isolated, cultured, and the 5th generation hucMSC-Exo was extracted by ultracentrifugation and identified.Biological markers of CD9 and CD63 of hucMSC-Exo were detected by Western blot.A total of 12 SPF grade male C57BL/6J mice were randomly selected to establish depression model by CUMS method at the same time, and relevant behavioral experiments, including opening field test (OFT) and forced swimming test (FST) were used to detect changes of depression-like behavior in CUMS mice. After modeling, 12 mice were randomly divided into two groups, with 6 mice in each group. One group of mice was the exosome treatment group (CUMS+ Exo group) after stereotactic brain injection of hucMSC-Exo in the hippocampus, and the other group was the CUMS group. The expression of inflammatory signals in the hippocampus of mice in both groups were detected by micro PET/CT scanning technique. The proportion of M2-type microglia and M1-type microglia in the hippocampus of mice was detected by tissue immunofluorescence. β3-tubulin immunofluorescence staining was used to detect the length changes of neuronal axons in the depressed cell model constructed with corticosterone (CORT). EdU staining was used to detect neuronal proliferation. TUNEL staining was used to observe the apoptosis of neurons in the hippocampus of mice.Statistical analysis was conducted by GraphPad 8.0 software, and t-test was used for inter group comparison. Results:Under the electron microscope, hucMSC-Exo showed typical " double-layer cup-like" small vesicle-like changes and the particle diameter was about 100 nm.Western blot confirmed the expression of lconic proteins of CD9 and CD63. In the micro PET/CT scans, the uptake of [18F]DPA-714 in the CUMS+ Exo group was lower than that of the CUMS group, and the difference was statistically significant ((0.91±0.02)g/mL, (0.81±0.05)g/mL, t=4.54, P=0.001 1). In the opening field test, the percentage of central path length ((3.40±0.44)%, (5.17±0.90)%, t=4.33, P=0.001 5) and the time spent on the central path ((7.04±0.60)s, (10.22±1.41)s, t=6.02, P=0.000 1) in CUMS+ Exo group were higher than those in CUMS group, while the total distances of the two groups were not statistically significant ( t=0.48, P>0.05). In the forced swimming test, the immobility time in the CUMS+ Exo group was less than that in the CUMS group ((152.33±7.28) s, (133.50±4.32) s, t=5.45, P=0.000 3). In tissue immunofluorescence experiments, compared with the CUMS group, the proportion of M2-type microglia of hippocampus in the CUMS+ Exo group((0.33±0.04), (0.59±0.12), t=5.11, P=0.000 5)increased and the proportion of M1-type microglia ((0.56±0.06), (0.41±0.03), t=5.15, P=0.000 4) decreased in the CUMS+ Exo group. β3-tubulin-labeled immunofluorescence results showed an increase of neuronal axon length in the CORT+ Exo group compared with that in the CORT group((3.99±0.99) μm, (6.76±1.11) μm, t=6.10, P=0.000 1). The results of cell proliferation test showed an increase of proliferation rate in the CORT+ Exo group compared with that in the CORT group((0.74±0.07), (0.64±0.03), t=3.32, P=0.001 8). In the TUNEL staining experiment, the apoptosis rate of neurons in the hippocampal region of mice in the CUMS+ Exo group was lower than that of CUMS group ((0.24±0.04), (0.39±0.04), t=6.11, P=0.000 1). Conclusion:hucMSC-Exo can promote the conversion of M1 polarized microglia to M2 type microglia to alleviate depression-like behavior and reduce neuronal apoptosis in CUMS mice.