Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.

BACKGROUND:Spinal cord injury often leads to neurogenic bladder with hyperreflexia of the forced urethral muscle,but there is a lack of clear understanding of its pathogenesis and treatment,and establishing a stable and reliable animal model has an important impact on revealing its pathomechanisms and exploring therapeutic approaches.OBJECTIVE:To investigate the effect of the number of times to urinate on neurogenic model rats after complete spinal cord transection in order to improve the postoperative survival and modeling rate of neurogenic model rats.METHODS:Out of 46 female Sprague-Dawley rats,6 were selected as the sham-operated group using the random number table method,and the remaining 40 rats were randomly divided into 0,1,3,and 5 times daily urination groups after complete spinal cord transection modeling,with 10 rats in each group.The residual urine volume was measured every 3 days within 19 postoperative days,and the survival and modeling were observed on the 19th day after the operation,and urodynamics tests and contraction experiments of isolated forced urethra muscle strips were performed.RESULTS AND CONCLUSION:(1)Survival and modeling rate:there was 10%survival rate and 10%modeling rate in the group of 0 times daily urination;20%survival rate and 10%modeling rate in the group of 1 time daily urination;70%survival rate and 70%modeling rate in the groups of 3 and 5 times daily urination.(2)Residual urine volume:compared with the sham-operated group,the residual urine volume of the groups of 3 and 5 times daily urination was significant increased on postoperative days 3,6,9,12,and 15(P<0.01);the residual urine volume of the groups of 3 and 5 times daily urination was increased on the 18th day after surgery(P<0.05).Compared with the 3 times daily urination group,the residual urine volume was decreased in the 5 times daily urination group on the 6th day after surgery(P<0.05),while there was no significant difference in the residual urine volume between the 3 and 5 times daily urination groups on the 3rd,9th,12th,15th,and 18th days after surgery.(3)Urodynamics:Compared with the sham-operated group,the differential pressure at the point of leakage was significantly reduced(P<0.01)and the maximal volume was significantly increased(P<0.01)in the 3 and 5 times daily urination groups.There was no statistical difference in the differential pressure at the point of leakage and the maximal volume between the 3 and 5 times daily urination groups.(4)Muscle-strip contraction test of isolated detrusor muscles:Compared with the sham-operated group,the contraction amplitude and frequency of detrusor muscle strips were significantly reduced in the 3 and 5 times daily urination groups(P<0.01).There was no statistically significant difference in the contraction amplitude and frequency of detrusor muscle strips between the 3 and 5 times daily-urination groups.In conclusion,assisted urination is one of the keys to establish a successful neurogenic model of urethral reflexes,and there is no significant difference in the effects of urinating 3 or 5 times a day on the neurogenic model.It is recommended to urinate at least 3 times a day based on the actual workload and the modeling rate.

OBJECTIVE To develop a long-acting light-protective nanogel with both physical barrier and chemical clearance functions， and evaluate its performance. METHODS The photoprotective nanogel composed of mussel mucin and sodium hyaluronate was constructed based on a fullerenol-cerium oxide composite nano system， namely fullerenol-cerium oxide nanogel （FCN）， and was characterized. The antioxidant capacity of FCN was evaluated using in vitro free radical scavenging experiments； its UV shielding ability was assessed by using an SPF value detector； its biosafety was assessed according to the requirements of the Guidelines for Drug Safety Evaluation； skin adhesion was assessed using small animal 3D live imaging technology； its sun protection ability was assessed through skin sunscreen detection and histopathological observation. RESULTS The average particle sizes of cerium oxide and fullerenol nanoparticles in FCN were about 20 and 10 nm， respectively， and FCN exhibited good UV absorption and free radical scavenging abilities. SPF value of FCN was 58.95±0.82， and the ultraviolet A protection level value was 6.21±0.15. No pathogenic colonies such as Staphylococcus aureus， were detected in the nanogel， and the contents of lead， arsenic， mercury and cadmium all met the standards for pharmaceutical excipients； FCN group did not show any irritating reactions such as erythema， edema， or desquamation； blood biochemical indicators of the FCN group were within the normal reference range. The material clearance rate of mice in the artificial sweat flushing group was less than 30%， while the material clearance rate of mice in the dry cleaning group reached about 92%. The mice in the protective group did not show obvious erythema or ulcer formation throughout the experiment. Histopathology showed that the fibers were arranged in an orderly manner， and the number of collagen fibers was close to that of the control group. CONCLUSIONS The FCN formulation constructed in this study meets the relevant requirements of the Chinese Pharmacopoeia， has good safety and skin compatibility， and achieves dual synergistic protection of UV shielding and free radical scavenging.

Objective To observe the effects of electroacupuncture(EA)on TGF-β1/Smads signaling pathway and epithelial-mesenchymal transition(EMT)related proteins in rats with neurogenic bladder(NB)after spinal cord injury;To explore the possible mechanism of EA in improving NB fibrosis.Methods Totally 36 female SD rats were randomly selected,with 10 rats in the sham-operation group and the remaining 26 rats undergoing complete transection of the spinal cord beneath the T8 vertebrae to establish a NB rat model.The modeling rats were randomly divided into model group and EA group,with 10 rats in each group.EA group was applied to"Ciliao","Zhongji"and"Sanyinjiao",20 min per time,once a day for 7 days.The general condition of the rats in each group was observed,the ultrasound index of the bladder was detected by ultrasound technique,the bladder function of the rats was detected by urodynamics,the body mass of the rats and the wet weight of the bladder were recorded,and the bladder index was calculated.HE staining was used to observe bladder tissue morphology,the degree of bladder tissue fibrosis and bladder wall thickness were detected by Masson staining.The positive expressions of E-cadherin,N-cadherin and Vimentin in bladder tissue were detected by immunohistochemistry.The protein expressions of TGF-β1,p-Smad2/3,E-cadherin,N-cadherin and Vimentin were detected by Western blot.Results Compared with the sham-operation group,the upper and lower diameter,anteroposterior diameter,transverse diameter,bladder volume of the model group significantly increased(P<0.001),the maximum bladder pressure,leak point pressure difference,perfusion time and maximum bladder capacity significantly increased(P<0.001),the bladder index increased significantly(P<0.001),the bladder epithelial cells were thickened and arranged irregularly,the bladder collagen volume fraction and bladder wall thickness significantly increased(P<0.001),the expressions of TGF-β1,p-Smad2/3,N-cadherin and Vimentin in bladder tissue increased(P<0.01),and the expression of E-cadherin decreased(P<0.001).Compared with the model group,the upper and lower diameter,anteroposterior diameter,transverse diameter,bladder volume of the EA group decreased significantly(P<0.05),the maximum bladder pressure,leak point pressure difference,perfusion time and maximum bladder capacity significantly decreased(P<0.05),the bladder index significantly decreased(P<0.05),the thickness of the bladder epithelial cell layer became thinner and arranged more neatly,and the bladder collagen volume fraction and bladder wall thickness of the bladder were significantly reduced(P<0.05),the expressions of TGF-β1,p-Smad2/3,N-cadherin and Vimentin in bladder tissue significantly decreased(P<0.05),and the expression of E-cadherin significantly increased(P<0.05).Conclusion EA may reduce the EMT of bladder epithelial cells and decrease the degree of bladder tissue fibrosis by inhibiting the activation of the TGF-β1/Smads signaling pathway,thereby improving bladder function in NB rats after spinal cord injury.

Objective To observe the effects of electroacupuncture(EA)on TGF-β1/Smads signaling pathway and epithelial-mesenchymal transition(EMT)related proteins in rats with neurogenic bladder(NB)after spinal cord injury;To explore the possible mechanism of EA in improving NB fibrosis.Methods Totally 36 female SD rats were randomly selected,with 10 rats in the sham-operation group and the remaining 26 rats undergoing complete transection of the spinal cord beneath the T8 vertebrae to establish a NB rat model.The modeling rats were randomly divided into model group and EA group,with 10 rats in each group.EA group was applied to"Ciliao","Zhongji"and"Sanyinjiao",20 min per time,once a day for 7 days.The general condition of the rats in each group was observed,the ultrasound index of the bladder was detected by ultrasound technique,the bladder function of the rats was detected by urodynamics,the body mass of the rats and the wet weight of the bladder were recorded,and the bladder index was calculated.HE staining was used to observe bladder tissue morphology,the degree of bladder tissue fibrosis and bladder wall thickness were detected by Masson staining.The positive expressions of E-cadherin,N-cadherin and Vimentin in bladder tissue were detected by immunohistochemistry.The protein expressions of TGF-β1,p-Smad2/3,E-cadherin,N-cadherin and Vimentin were detected by Western blot.Results Compared with the sham-operation group,the upper and lower diameter,anteroposterior diameter,transverse diameter,bladder volume of the model group significantly increased(P<0.001),the maximum bladder pressure,leak point pressure difference,perfusion time and maximum bladder capacity significantly increased(P<0.001),the bladder index increased significantly(P<0.001),the bladder epithelial cells were thickened and arranged irregularly,the bladder collagen volume fraction and bladder wall thickness significantly increased(P<0.001),the expressions of TGF-β1,p-Smad2/3,N-cadherin and Vimentin in bladder tissue increased(P<0.01),and the expression of E-cadherin decreased(P<0.001).Compared with the model group,the upper and lower diameter,anteroposterior diameter,transverse diameter,bladder volume of the EA group decreased significantly(P<0.05),the maximum bladder pressure,leak point pressure difference,perfusion time and maximum bladder capacity significantly decreased(P<0.05),the bladder index significantly decreased(P<0.05),the thickness of the bladder epithelial cell layer became thinner and arranged more neatly,and the bladder collagen volume fraction and bladder wall thickness of the bladder were significantly reduced(P<0.05),the expressions of TGF-β1,p-Smad2/3,N-cadherin and Vimentin in bladder tissue significantly decreased(P<0.05),and the expression of E-cadherin significantly increased(P<0.05).Conclusion EA may reduce the EMT of bladder epithelial cells and decrease the degree of bladder tissue fibrosis by inhibiting the activation of the TGF-β1/Smads signaling pathway,thereby improving bladder function in NB rats after spinal cord injury.

Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.

BACKGROUND:Spinal cord injury often leads to neurogenic bladder with hyperreflexia of the forced urethral muscle,but there is a lack of clear understanding of its pathogenesis and treatment,and establishing a stable and reliable animal model has an important impact on revealing its pathomechanisms and exploring therapeutic approaches.OBJECTIVE:To investigate the effect of the number of times to urinate on neurogenic model rats after complete spinal cord transection in order to improve the postoperative survival and modeling rate of neurogenic model rats.METHODS:Out of 46 female Sprague-Dawley rats,6 were selected as the sham-operated group using the random number table method,and the remaining 40 rats were randomly divided into 0,1,3,and 5 times daily urination groups after complete spinal cord transection modeling,with 10 rats in each group.The residual urine volume was measured every 3 days within 19 postoperative days,and the survival and modeling were observed on the 19th day after the operation,and urodynamics tests and contraction experiments of isolated forced urethra muscle strips were performed.RESULTS AND CONCLUSION:(1)Survival and modeling rate:there was 10%survival rate and 10%modeling rate in the group of 0 times daily urination;20%survival rate and 10%modeling rate in the group of 1 time daily urination;70%survival rate and 70%modeling rate in the groups of 3 and 5 times daily urination.(2)Residual urine volume:compared with the sham-operated group,the residual urine volume of the groups of 3 and 5 times daily urination was significant increased on postoperative days 3,6,9,12,and 15(P<0.01);the residual urine volume of the groups of 3 and 5 times daily urination was increased on the 18th day after surgery(P<0.05).Compared with the 3 times daily urination group,the residual urine volume was decreased in the 5 times daily urination group on the 6th day after surgery(P<0.05),while there was no significant difference in the residual urine volume between the 3 and 5 times daily urination groups on the 3rd,9th,12th,15th,and 18th days after surgery.(3)Urodynamics:Compared with the sham-operated group,the differential pressure at the point of leakage was significantly reduced(P<0.01)and the maximal volume was significantly increased(P<0.01)in the 3 and 5 times daily urination groups.There was no statistical difference in the differential pressure at the point of leakage and the maximal volume between the 3 and 5 times daily urination groups.(4)Muscle-strip contraction test of isolated detrusor muscles:Compared with the sham-operated group,the contraction amplitude and frequency of detrusor muscle strips were significantly reduced in the 3 and 5 times daily urination groups(P<0.01).There was no statistically significant difference in the contraction amplitude and frequency of detrusor muscle strips between the 3 and 5 times daily-urination groups.In conclusion,assisted urination is one of the keys to establish a successful neurogenic model of urethral reflexes,and there is no significant difference in the effects of urinating 3 or 5 times a day on the neurogenic model.It is recommended to urinate at least 3 times a day based on the actual workload and the modeling rate.

Bone defect refers to the loss of bone structure caused by bone infections,bone tumors,congenital diseases,or severe trauma.Due to the increased incidence of high-energy injuries and the characteristics of anatomical structure,lower limb bone defects are particularly common and become the research difficulties in the field of traumatic orthopedics.Traditional treatment options include vascularized fibular grafting,open bone grafting,and bone transport technique,but these techniques have inherent limitations.In recent years,induced membrane technique has gradually been used for the reconstruction of segmental bone defects due to its standardized,simple and efficient operation procedures.Induced membrane technique consists two stages:the first stage is to generate an induced membrane with biological effects,the second stage is to fill the defect area with bone fillers(autologous bone,allogeneic bone,artificial bone or bioactive substances,etc.),then the filled bone graft material is fixed to the existing bone structure by specific fixation methods.In this paper,the basic research of induced membrane technique and the related research progress in the treatment of lower limb bone defect at home and abroad are reviewed,aiming to discuss its potential development direction for basis and clinic.

Objective:To systematically review the current situation and risk factors of social isolation among elderly people in Chinese communities.Methods:The research on social isolation of elderly people in Chinese communities was electronically searched on China National Knowledge Infrastructure, WanFang Data, VIP, China Biology Medicine disc, PubMed, Embase, Web of Science, and Cochrane Library. The search period was from database establishment to August 1, 2023. Two researchers independently conducted literature screening, quality evaluation, and data extraction, and used Stata 17.0 software to conduct Meta-analysis on the incidence and risk factors of social isolation among elderly people in the community.Results:A total of 29 articles were included, with a total of 49 713 samples. Meta-analysis showed that the incidence of social isolation among elderly people in Chinese communities was 29.5%. Advanced age, education below college level, poor self-rated health, lack of exercise, coexistence of chronic diseases, impaired daily living activities, hearing loss, depression, lack of spouse, low family care, low social support, and low social participation were the main risk factors for social isolation among elderly people in the community ( OR ranging from 1.57 to 3.34, P<0.05) . Conclusions:The incidence of social isolation among elderly people in Chinese communities is high, and there are many risk factors. Medical and nursing staff should strengthen early screening for social isolation among the elderly and provide early intervention for the risk factors.

Objective:To systematically evaluate the recurrence risk prediction model of diabetic foot ulcers (DFU) .Methods:Research on DFU recurrence risk prediction models was electronically searched in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and China Biomedical Service System. The search period was from database establishment to July 20, 2023. Two researchers independently screened literature and conducted data extraction and quality evaluation using the prediction model research data extraction table and the Prediction Model Risk of Bias Assessment Tool (PROBAST) .Results:A total of 8 articles were included, including 14 models. The area under the receiver operating characteristic (ROC) curve included in the model ranged from 0.660 to 0.940. The most common five predictors in the model were ulcers location, glycosylated hemoglobin, smoking, combined peripheral neuropathy and diabetes course. All 8 articles had a high risk of bias, mainly due to insufficient sample size, improper handling and reporting of missing data, and a lack of internal validation, which might lead to overfitting of the model. Only one article was subjected to external validation.Conclusions:The research on DFU recurrence risk prediction models is still in the development stage, and the predictive performance of various studies is still acceptable, but there is a high risk of bias. Future research still needs to use rigorous statistical analysis methods to construct new risk prediction models and improve internal and external validation.