Due to advances in treatment methods, the survival rate and quality of life of cancer patients have been improved. Radiation-induced vascular injury (RIVI) is a common adverse reaction following radiotherapy, mainly manifested as capillary injury and atherosclerosis in the irradiated area. Radiotherapy induces RIVI in the cerebral vessels, carotid arteries, coronary arteries, and large arteries through mechanisms such as endothelial cell injury and senescence, oxidative stress and inflammatory responses, angiogenesis, and vascular remodeling. In this review research progress in the pathological features, pathophysiological mechanisms, clinical manifestations, prevention and treatment strategies of RIVI was summarized, aiming to provide insights for future research on RIVI.

Due to advances in treatment methods, the survival rate and quality of life of cancer patients have been improved. Radiation-induced vascular injury (RIVI) is a common adverse reaction following radiotherapy, mainly manifested as capillary injury and atherosclerosis in the irradiated area. Radiotherapy induces RIVI in the cerebral vessels, carotid arteries, coronary arteries, and large arteries through mechanisms such as endothelial cell injury and senescence, oxidative stress and inflammatory responses, angiogenesis, and vascular remodeling. In this review research progress in the pathological features, pathophysiological mechanisms, clinical manifestations, prevention and treatment strategies of RIVI was summarized, aiming to provide insights for future research on RIVI.

Objective To construct microscale rectangular hydrogel grooves and to investigate the morphology and alignment of human umbilical vein endothelial cells(HUVECs)under spatial constraints.Vascular endothelial cell morphology and alignment are important factors in vascular development and the maintenance of homeostasis.Methods A 4-arm polyethylene glycol-acrylate(PEG-acrylate)hydrogel was used to fabricate rectangular microgrooves of the widths of 60 μm,100 μm,and 140 μm.The sizes and the fibronectin(FN)adhesion of these hydrogel microgrooves were measured.HUVECs were seeded onto the FN-coated microgrooves,while the flat surface without micropatterns was used as the control.After 48 hours of incubation,the morphology and orientation of the cells were examined.The cytoskeleton was labelled with phalloidine and the orientation of the cytoskeleton in the hydrogel microgrooves was observed by laser confocal microscopy.Results The hydrogel microgrooves constructed exhibited uniform and well-defined morphology,a complete structure,and clear edges,with the width deviation being less than 3.5%.The depth differences between the hydrogel microgrooves of different widths were small and the FN adhesion is uniform,providing a micro-patterned growth interface for cells.In the control group,the cells were arranged haphazardly in random orientations and the cell orientation angle was(46.9±1.8)°.In contrast,the cell orientation angle in the hydrogel microgrooves was significantly reduced(P<0.001).However,the cell orientation angles increased with the increase in hydrogel microgroove width.For the 60 μm,100 μm,and 140 μm hydrogel microgrooves,the cell orientation angles were(16.4±2.8)°,(24.5±3.2)°,and(30.3±3.5)°,respectively.Compared to that of the control group(35.7%),the number of cells with orientation angles<30° increased significantly in the hydrogel microgrooves of different widths(P<0.001).However,as the width of the hydrogel microgrooves increased,the number of cells with orientation angles<30° gradually decreased(79.9%,62.3%,54.7%,respectively),while the number of cells with orientation angles between 60°-90° increased(P<0.001).The cell bodies in the microgrooves were smaller and more rounded in shape.The cells were aligned along the direction of the microgrooves and corresponding changes occurred in the arrangement of the cell cytoskeleton.In the control group,cytoskeletal filaments were aligned in random directions,presenting an orientation angle of(45.5±3.7)°.Cytoskeletal filaments were distributed evenly within various orientation angles.However,in the 60 μm,100 μm,and 140 μm hydrogel microgrooves,the orientation angles of the cytoskeletal filaments were significantly decreased,measuring(14.4±3.1)°,(24.7±3.5)°,and(31.9±3.3)°,respectively.The number of cytoskeletal filaments with orientation angles<30° significantly increased in hydrogel microgrooves of different widths(P<0.001).However,as the width of the hydrogel microgrooves increased,the number of cytoskeletal filaments with orientation angles<30° gradually decreased,while the number of cytoskeletal filaments with orientation angles between 60°-90° gradually increased(P<0.001).Conclusion Hydrogel microgrooves can regulate the morphology and orientation of HUVECs and mimic to a certain extent the in vivo microenvironment of vascular endothelial cells,providing an experimental model that bears better resemblance to human physiology for the study of the unique physiological functions of vascular endothelial cells.Nonetheless,the molecular mechanism of spatial constraints on the morphology and the assembly of vascular endothelial cell needs to be further investigated.

Oxidative stress is increasingly recognized as a major contributor to the pathophysiology of Alzheimer's disease(AD),particularly in the early stages of the disease.The multiplicity advantages of stem cell transplantation make it fascinating therapeutic strategy for many neurodegenerative diseases.We herein demonstrated that human dental pulp stem cells(hDPSCs)mediated oxidative stress improvement and neuroreparative effects in in vitro AD models,playing critical roles in regulating the polarization of hyperreactive microglia cells and the recovery of damaged neurons.Importantly,these therapeutic effects were reflected in 10-month-old 3xTg-AD mice after a single transplantation of hDPSCs,with the treated mice showing significant improvement in cognitive function and neuropathological features.Mechanistically,antioxidant and neuroprotective effects,as well as cognitive enhancements elicited by hDPSCs,were at least partially mediated by Nrf2 nuclear accumulation and downstream antioxidant enzymes expression through the activation of the AKT-GSK3β-Nrf2 signaling pathway.In conclusion,our findings corroborated the neuroprotective capacity of hDPSCs to reshape the neuropathological microenvironment in both in vitro and in vivo AD models,which may be a tremendous potential therapeutic candidate for Alzheimer's disease.

Oxidative stress is increasingly recognized as a major contributor to the pathophysiology of Alzheimer's disease(AD),particularly in the early stages of the disease.The multiplicity advantages of stem cell transplantation make it fascinating therapeutic strategy for many neurodegenerative diseases.We herein demonstrated that human dental pulp stem cells(hDPSCs)mediated oxidative stress improvement and neuroreparative effects in in vitro AD models,playing critical roles in regulating the polarization of hyperreactive microglia cells and the recovery of damaged neurons.Importantly,these therapeutic effects were reflected in 10-month-old 3xTg-AD mice after a single transplantation of hDPSCs,with the treated mice showing significant improvement in cognitive function and neuropathological features.Mechanistically,antioxidant and neuroprotective effects,as well as cognitive enhancements elicited by hDPSCs,were at least partially mediated by Nrf2 nuclear accumulation and downstream antioxidant enzymes expression through the activation of the AKT-GSK3β-Nrf2 signaling pathway.In conclusion,our findings corroborated the neuroprotective capacity of hDPSCs to reshape the neuropathological microenvironment in both in vitro and in vivo AD models,which may be a tremendous potential therapeutic candidate for Alzheimer's disease.

ObjectiveTo explore the imbalance of paravertebral muscle group for patients with unilateral lumbar disc herniation. MethodsFrom January, 2022 to January, 2023, 30 patients with unilateral lumbar disc herniation (observation group) and 30 healthy people matching in general data (control group) were measured the tension and stiffness of multifidus and erector spinae with MyotonPRO, while the observation group was assessed with Visual Analogue Scale (VAS) for pain and Japanese Orthopaedic Association (JOA) score, and the time of disease was also recorded. ResultsThe mean of bilateral tension and hardness of multifidus and erector spinae was more in the observation group than in the control group (|t| > 5.407, P < 0.001), and the tension and hardness of multifidus and erector spinae of the affected side were more than those of the unaffected side in the observation group (|t| > 11.219, P < 0.001). The tension and hardness of multifidus and erector spinae of the affected side were positively correlated with VAS score (r > 0.942, P < 0.001), and negatively correlated with JOA score (|r| > 0.886, P < 0.001). ConclusionThe tension and hardness of multifidus and erector spinae of the affected side increase after unilateral lumbar disc herniation, resulting in asymmetry.

ObjectiveTo evaluate the inter-rater and test-retest reliability of echo intensity of ultrasound image for quality of quadriceps femoris in patients with knee osteoarthritis (KOA). MethodsFrom March to December, 2021, 33 patients with unilateral KOA in Guangdong Provincial Second Hospital of Traditional Chinese Medicine were included. Ultrasound was used to observe the cross sections of rectus femoris (RF), vastus medialis (VM) and vastus lateralis (VL), and the images were saved. Two independent raters analyzed the average gray value of the picture with the Image J. One of the raters repeated the measurement. The intra-class correlation coefficient (ICC), standard error of measurement (SEM), minimum detectable change (MDC) and coefficient of variation (CV) were calculated and the Bland-Altman charts were drawn. ResultsThe gray value was higher in the RF, VM and VL in the affected side than in the healthy side (t > 2.262, P < 0.05). The inter-rater reliability was excellent, with ICC 0.982 to 0.995, SEM 1.60 to 3.82, CV 1.49% to 5.90%, and MDC value 4.43 to 10.59. The test-retest reliability of the rater was excellent, with ICC 0.969 to 0.990, SEM 2.37 to 5.41, CV 2.22% to 4.84%, and MDC value 6.57 to 15.00. Bland-Altman charts analysis showed that the consistency was good. ConclusionThe quadriceps femoris muscle quality is different between the affected and the healthy sides in patients with unilateral KOA. It is reliable to evaluate muscle echo intensity by Image J.

Organoids are three-dimensional structures formed by self-organizing growth of cells in vitro, which own many structures and functions similar with those of corresponding in vivo organs. Although the organoid culture technologies are rapidly developed and the original cells are abundant, the organoid cultured by current technologies are rather different with the real organs, which limits their application. The major challenges of organoid cultures are the immature tissue structure and restricted growth, both of which are caused by poor functional vasculature. Therefore, how to develop the vascularization of organoids has become an urgent problem. We presently reviewed the progresses on the original cells of organoids and the current methods to develop organoids vascularization, which provide clues to solve the above-mentioned problems.
Humans ; Organoids ; Neovascularization, Pathologic ; Technology

Objective:To investigate the correlation between the location and volume of cerebral microbleeds (CMBs) and lacunar infarction (LI) in patients with cerebral small vessel disease (CSVD).Methods:Participants from the CSVD cohort in the Department of Neurology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School of Nanjing University from February 2017 to March 2019 were enrolled retrospectively. All participants underwent magnetic resonance imaging scans, standardized clinical assessment and diagnosis. AccuBrain, an automatic brain segmentation and quantification software developed by the Chinese University of Hong Kong, was used to quantitatively analyze the volume of CMBs and white matter hyperintensities (WMHs). Ordered multi-class logistic regression analysis was used to determine the independent influencing factors of LI, and then multiple linear regression analysis was used to investigate the correlation between the volume of deep or infratentorial CMBs (DI-CMBs) and the number of LI. Results:A total of 317 patients with CSVD were included in the analysis, including 214 (67.5%) in the non-LI group, 43 (13.6%) in the single LI group, and 60 (18.9%) in the multiple LI group. The comparison of the three groups showed that older age, male, smoking, drinking, history of previous stroke or transient ischemic attack (TIA), lower levels of high-density lipoprotein cholesterol, larger CMBs and WMHs volume, higher enlarged perivascular spaces (EPVS) grade might be the risk factors for LI. Ordinal multivariable logistic regression analysis showed that male (odds ratio [ OR] 2.058, 95% confidence interval [ CI] 1.084-3.909; P=0.027), previous stroke or TIA history ( OR 1.962, 95% CI 1.089-3.535; P=0.025), larger WMH volume ( OR 8.716, 95% CI 4.034-18.832; P<0.001), higher EPVS grade ( OR 1.915, 95% CI 1.292-2.839; P=0.001), larger DI-CMB volume ( OR 1.022, 95% CI 1.006-1.038; P=0.008) or more DI-CMB number ( OR 1.187, 95% CI 1.005-1.403; P=0.044) were the independent related factors of LI. Multiple linear regression analysis showed that there was a significant correlation between the volume of DI-CMB and the number of LI ( r=0.330, P<0.001). Conclusion:In patients with CSVD, there is a significant correlation between DI-CMBs and LI.

Objective:To explore the correlation between immediate hypersensitivity induced by pegylated liposomal doxorubicin (PLD) and the plasma anti-polyethylene glycol (anti-PEG) antibody in advanced breast cancer patients.Methods:The study was designed as a prospective and noninterventional study. The subjects were selected from advanced breast cancer patients in Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, who received monotherapy with PLD (an IV infusion of PLD 50 mg/m 2 in 5% glucose solution 250 ml for 90 minutes without pretreatment with dexamethasone or other drugs). Anti-PEG antibody before administration were detected for all the patients and antibody level >2 ng/L was defined as positive. Blood in patients who had hypersensitivity within 30 minutes after the start of infusion was collected (finding the opportunity as soon as possible) and IgE, C3, and C4 levels in serum were detected. According to whether there was an immediate hypersensitivity reaction, the patients were divided into hypersensitivity group and non-hypersensitivity group and the clinical characteristics and plasma anti-PEG antibody carrying status in patients between the 2 groups were compared; according to anti-PEG antibody carrying status, the patients were divided into anti-PEG antibody positive group and negative group and the clinical characteristics and the incidence of hypersensitivity in patients between the 2 groups were compared. Results:A total of 12 patients were included in the study, aged from 37 to 68 years with a median age of 50 (37-68) years. Ten patients had previously used non-pegylated anthracyclines and the median cumulative dose was 329 (185, 418) mg/m 2 after a doxorubicin equivalent dose conversion. Seven patients developed hypersensitivity within 2-18 minutes after the start of infusion. Between the hypersensitivity group and the non-hypersensitivity group, differences in clinical characteristics such as age, height, weight, body surface area, previous application of anthracyclines, and the cumulative doses in patients were not significant (all P>0.05); the difference in positive rate of anti-PEG antibodies in patients was also not statistically significant (4/7 vs. 2/5, P=1.000). Among the 12 patients, 6 were positive for anti-PEG antibody and 6 were negative and the differences in the above-mentioned clinical characteristics or the incidence of hypersensitivity (3/6 vs. 4/6) in patients between the 2 groups (all P>0.05) were not significant. In the hypersensitivity group, IgE, C3, and C4 levels in serum were detected in 4 patients. Two patients with positive anti-PEG antibody had increased IgE levels (404 and 545 μg/L, respectively), 1 of which had also increased C4 level (486 mg/L); the other 2 patients with negative anti-PEG antibody had normal IgE, C3, and C4 levels. Conclusions:It has not been found that PLD-induced immediate hypersensitivity is related to the anti-PEG antibody, which may be due to the small sample size of the study. It cannot be ruled out that anti-PEG antibody may be involved in the induction of the IgE-mediated immediate hypersensitivity, which may also be mediated by complement in some patients.