In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.

Genetic factors are often involved in the pathogenesis of young adult stroke, and its subtype, atherosclerotic type of large arteries, may be caused by a combination of genetic and environmental factors, but little is known about its underlying pathogenesis. To provide clues for better understanding of identifying relevant stroke etiological genetic factors and adopting effective preventive strategies, the role of genetic factors in atherosclerosis and related risk factors was described, and the possible genetic mechanisms of large-artery atherosclerotic stroke in young people were explored, which may be further investigated in future research in the following areas: etiological typing of stroke in young people and the related genetic mechanisms; modifiable vascular risk factors and the development of secondary prevention strategies; high-resolution vascular imaging magnetic resonance imaging in the etiological typing of stroke in young people and the pathogenesis of premature atherosclerosis and vulnerable plaques.

Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

Aim To study the diastolic effect and mechanism of farrerol on isolated pulmonary arteries of C57BL/6J mice.Methods After anesthesia,mouse lung tissue was quickly removed and placed into the 4 ℃ K-H buffer,pulmonary arteries were isolated under the microscope and cut into 2 mm long vascular rings for spare use.(1)The effect of farrerol on the resting tension of isolated mouse pulmonary arteries:in the resting state,the active mouse pul-monary artery rings were treated with different concentrations of farrerol(10-6,3×10-6,10-5,3×10-5 and 10-4 mol/L).(2)Farrerol relaxed mouse pulmonary artery experiment:pulmonary arteries were contracted using phenylephrine(PE,1 μmol/L)or KCl(60 mmol/L),and when the contraction reached the platform,different concentrations of farrerol(10-6,3×10-6,10-5,3×10-5 and 10-4 mol/L)was added.(3)Farrerol inhibited pulmonary artery contraction experi-ment:under conditions with or without the addition of farrerol,pulmonary arteries were contracted using different concen-trations of PE(10-9,3×10-9,10-8,3 × 10-8,10-7,3×10-7 and 10-6 mol/L)or KCl(20,30,40,60,80 and 120 mmol/L),and the pulmonary artery muscle tension was recorded.(4)Calcium free and recalcification experiments:under conditions with or without the addition of farrerol,the changes of isolated mouse pulmonary artery tension were meas-ured in the state of calcium free or recalcification { 2.5 mmol/L[Ca2+]ex }.(5)The relationship between farrerol in-duced relaxation of isolated mouse pulmonary arteries and potassium ion channels:firstly,60 mmol/L KCl solution was used to contract the mouse pulmonary arteries until the platform.Then,3 mmol/L aminopyridine(4-AP),2 mmol/L tet-raethylammonium(TEA),30 μmol/L BaCl2,and 10 μmol/L glibenclamide(Gli)were added and treated for 15 min.Subsequently,the pulmonary arteries were relaxed using a concentration gradient of farrerol.Results Farrerol had no significant effect on the mouse pulmonary arteries in the resting state,but had a concentration-dependent relaxing effect on the mouse pulmonary arteries pre-contracted with PE and KCl.While the pretreatment of 3×10-5 mol/L farrerol could sig-nificantly reduce the maximum contraction of mouse pulmonary arteries induced by PE and KCl(P＜0.01),as well as sig-nificantly reduce the contraction of mouse pulmonary arteries induced by KCl under calcium free or recalcification conditions(P＜0.01).Addition of the voltage-dependent potassium ion channel blocker 4-AP significantly reduced the maximum diastolic rate of mouse pulmonary arteries induced by farrerol(P＜0.01),while addition of the high conductivity calcium activated potassium ion channel blocker TEA,inward rectifying potassium ion channel blocker BaCl2,or ATP sensitive po-tassium ion channel blocker Gli had no significant effect on the vasodilation effect of farrerol(P＞0.05).Conclusion Farrerol has a relaxing effect on isolated mouse pulmonary arteries,and its mechanism may be related to open voltage-de-pendent potassium ion channels.

Aim To study the diastolic effect and mechanism of farrerol on isolated pulmonary arteries of C57BL/6J mice.Methods After anesthesia,mouse lung tissue was quickly removed and placed into the 4 ℃ K-H buffer,pulmonary arteries were isolated under the microscope and cut into 2 mm long vascular rings for spare use.(1)The effect of farrerol on the resting tension of isolated mouse pulmonary arteries:in the resting state,the active mouse pul-monary artery rings were treated with different concentrations of farrerol(10-6,3×10-6,10-5,3×10-5 and 10-4 mol/L).(2)Farrerol relaxed mouse pulmonary artery experiment:pulmonary arteries were contracted using phenylephrine(PE,1 μmol/L)or KCl(60 mmol/L),and when the contraction reached the platform,different concentrations of farrerol(10-6,3×10-6,10-5,3×10-5 and 10-4 mol/L)was added.(3)Farrerol inhibited pulmonary artery contraction experi-ment:under conditions with or without the addition of farrerol,pulmonary arteries were contracted using different concen-trations of PE(10-9,3×10-9,10-8,3 × 10-8,10-7,3×10-7 and 10-6 mol/L)or KCl(20,30,40,60,80 and 120 mmol/L),and the pulmonary artery muscle tension was recorded.(4)Calcium free and recalcification experiments:under conditions with or without the addition of farrerol,the changes of isolated mouse pulmonary artery tension were meas-ured in the state of calcium free or recalcification { 2.5 mmol/L[Ca2+]ex }.(5)The relationship between farrerol in-duced relaxation of isolated mouse pulmonary arteries and potassium ion channels:firstly,60 mmol/L KCl solution was used to contract the mouse pulmonary arteries until the platform.Then,3 mmol/L aminopyridine(4-AP),2 mmol/L tet-raethylammonium(TEA),30 μmol/L BaCl2,and 10 μmol/L glibenclamide(Gli)were added and treated for 15 min.Subsequently,the pulmonary arteries were relaxed using a concentration gradient of farrerol.Results Farrerol had no significant effect on the mouse pulmonary arteries in the resting state,but had a concentration-dependent relaxing effect on the mouse pulmonary arteries pre-contracted with PE and KCl.While the pretreatment of 3×10-5 mol/L farrerol could sig-nificantly reduce the maximum contraction of mouse pulmonary arteries induced by PE and KCl(P＜0.01),as well as sig-nificantly reduce the contraction of mouse pulmonary arteries induced by KCl under calcium free or recalcification conditions(P＜0.01).Addition of the voltage-dependent potassium ion channel blocker 4-AP significantly reduced the maximum diastolic rate of mouse pulmonary arteries induced by farrerol(P＜0.01),while addition of the high conductivity calcium activated potassium ion channel blocker TEA,inward rectifying potassium ion channel blocker BaCl2,or ATP sensitive po-tassium ion channel blocker Gli had no significant effect on the vasodilation effect of farrerol(P＞0.05).Conclusion Farrerol has a relaxing effect on isolated mouse pulmonary arteries,and its mechanism may be related to open voltage-de-pendent potassium ion channels.

Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

Genetic factors are often involved in the pathogenesis of young adult stroke, and its subtype, atherosclerotic type of large arteries, may be caused by a combination of genetic and environmental factors, but little is known about its underlying pathogenesis. To provide clues for better understanding of identifying relevant stroke etiological genetic factors and adopting effective preventive strategies, the role of genetic factors in atherosclerosis and related risk factors was described, and the possible genetic mechanisms of large-artery atherosclerotic stroke in young people were explored, which may be further investigated in future research in the following areas: etiological typing of stroke in young people and the related genetic mechanisms; modifiable vascular risk factors and the development of secondary prevention strategies; high-resolution vascular imaging magnetic resonance imaging in the etiological typing of stroke in young people and the pathogenesis of premature atherosclerosis and vulnerable plaques.

As a common clinical disease, fracture is often accompanied by pain, swelling, bleeding as well as other symptoms and has a high disability rate, even threatening life, seriously endangering patients' physical and psychological health and quality of life. Medical practitioners take many strategies for the treatment of fracture healing, including Traditional Chinese Medicine (TCM). In the early stage of fracture healing, the local fracture is often in a state of hypoxia, accompanied by the expression of hypoxia inducible factor-1α (HIF-1α), which is beneficial to wound healing. Through literature mining, we thought that hypoxia, HIF-1α and downstream factors affected the mechanism of fracture healing, as well as dominated this process. Therefore, we reviewed the local characteristics and related signaling pathways involved in the fracture healing process and summarized the intervention of TCM on these mechanisms, in order to inspirit the new strategy for fracture healing, as well as elaborate on the possible principles of TCM in treating fractures based on the HIF molecular mechanism.

BACKGROUND:In clinical application,simple interspinous fixation without additional interbody fusion has similar fixation effects to pedicle screw and rod fusion internal fixation,and can effectively reduce the range of motion of the responsible segment and the stress of the articular process.However,after simple placement of the new interspinous fusion fixation device BacFuse,the stress at the root of the spinous process is relatively concentrated,and the spinous fracture is prone to occur.If an intervertebral fusion cage is inserted in conjunction with interspinous fixation,Von Mises stress can theoretically be dispersed to reduce the risk of spinous fracture.However,there are few studies on biomechanics and finite element analysis. OBJECTIVE:To observe the biomechanical stability of interspinous fixation-assisted endoscopic interbody fusion in the treatment of severe lumbar spinal stenosis. METHODS:The normal finite element model M0 of the L4-L5 segment of the lumbar spine was established by Mimics,Geomagic,Solidworks,and ANSYS software based on the lumbar CT images of a 26-year-old adult male volunteer excluding spinal diseases.On the basis of M0,the immediate model M1 after endoscopic decompression combined with interbody fusion,the interspinous fixation device(BacFuse)model M2 after endoscopic decompression,and the interspinous fixation(BacFuse)model M3 after endoscopic-assisted interbody fusion were established.The same stress was applied to the upper surface of the L4 vertebral body in the four groups,and the lower surface of the L5 vertebral body was fixed and supported.The range of motion and the extreme Von Mises stress of the endplate bone and the posterior ligament complex of the vertebral body were analyzed under six working conditions of flexion,extension,left/right bending,and left/right rotation. RESULTS AND CONCLUSION:(1)Compared with model M0,the range of motion value of model M1 increased significantly under six working conditions.Model M2 and model M3 had a significant reduction in range of motion.(2)Compared with model M0,the maximum stress of the vertebral body in model M1 did not change significantly under the six working conditions.The maximum stress at the rear of the M2 vertebral body increased significantly.(3)Compared with model M1,the maximum stress of model M3 did not change significantly under the six working conditions.Compared with model M2,the maximum stress of model M3 decreased significantly.(4)Compared with the model M0,the extreme Von Mises stress of the L4 and L5 endplates of the model M1 was significantly increased.The extreme Von Mises stress in L4 and L5 endplates of models M2 and M3 decreased slightly.Compared with model M1,the Von Mises stress of the bone under the L4 and L5 endplate of models M2 and M3 was significantly reduced.(5)It is concluded that the implantation of BacFuse can effectively reduce the bone stress under the endplate during simple interbody fusion,decrease the risk of cage subsidence,diminish the risk of facet joint fracture on the decompression side,and provide a good stable environment for interbody fusion.The placement of an intervertebral fusion cage can reduce the stress of the root of the spinous process,which is beneficial to decrease the risk of fracture of the root of the spinous process.