1.Extracellular vesicles deliver thioredoxin to rescue stem cells from senescence and intervertebral disc degeneration via a feed-forward circuit of the NRF2/AP-1 composite pathway.
Xuanzuo CHEN ; Sheng LIU ; Huiwen WANG ; Yiran LIU ; Yan XIAO ; Kanglu LI ; Feifei NI ; Wei WU ; Hui LIN ; Xiangcheng QING ; Feifei PU ; Baichuan WANG ; Zengwu SHAO ; Yizhong PENG
Acta Pharmaceutica Sinica B 2025;15(2):1007-1022
Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.
2.Effect of Q Chromatography on the Recovery of Human Plasminogen in Affinity Chromatography
Shenglan YUE ; Taojing LI ; Juan LI ; Yan PENG ; Lianzhen LIN ; Yanxiang ZHOU ; Feifei WANG ; Chen ZHU ; Shang WANG ; Deming JI ; Shuangying ZENG ; Yong HU ; Zhijun ZHOU
Chinese Journal of Blood Transfusion 2025;38(10):1382-1388
Objective: To compare quality control (relative purity and specific activity) and process control [plasminogen (Pg) antigen recovery and potency recovery] indexes of samples before and after adding the Q chromatography step to the full chromatography process of human Pg, thereby determining whether the addition of this step could improve Pg recovery by affinity chromatography. Methods: A Q chromatography step was added before the Pg affinity chromatography in the original Pg chromatography process. The loading solution, flow through solution and eluate of Q chromatography and Pg affinity chromatography were collected. The potency of coagulation factor Ⅱ (FⅡ), Ⅶ (FⅦ), Ⅷ (FⅧ), Ⅸ (FⅨ), and Ⅹ(FⅩ) were detected by the coagulation method, the total protein content was detected by the BCA method, and the Pg potency was detected by the chromogenic substrate method. The content of specific plasma proteins was detected by immunoturbidimetry, the potency recovery of coagulation factors was calculated, and the flow direction of coagulation factors was analyzed. The recovery of different plasma protein antigens were calculated, and the distribution of impurity proteins was analyzed. The relative purity and specific activity of Pg, antigen content, and potency recovery in the target fractions were calculated and compared with the original process indicators, so as to determine the effect of adding Q chromatography on the original process. Furthermore, the reproducibility after process modification was assessed. Results: 100% of FⅡ, FⅩ, and FⅨ, 87.81% of FⅧ, and 40.44% of FⅦ in filtered plasma were removed by Q chromatography. The residual FⅦ (53.26%) and FⅧ (13.30%) in Q flow-through fraction were completely removed by Pg affinity chromatography. In both the original process (without Q-chromatography) and the modified process (with Q-chromatography), non-target plasma proteins mainly existed in the flow-through fraction of Pg affinity chromatography. The antigen recovery of IgM, ceruloplasmin (CER), and fibronectin (FNC) in Q-chromatography flow-through fraction were reduced. In contrast, antigen recovery of other plasma proteins [IgG, IgA, Pg, albumin (AlB), alpha-1-antitrypsin (AAT), and fibrinogen (Fg)] were all >90%, which were consistent with the protein composition and proportion in the original affinity chromatography loading solution. Compared with the recovery rate of Pg antigen in the original process (74.4%), the total recovery of Pg antigen in the modified process was significantly increased (89.97%). Compared with the recovery of IgG (97.48%) and Fg (95.32%) in the Pg affinity flows-through fraction of the original process, the modified process resulted in a slight reduction in the recovery of IgG (94.60%), while the recovery of Fg was not affected (95.05%). The potency recovery rate, specific activity, and relative purity of Pg after Q chromatography were 99.3%, 0.016 U/mg, and 0.15%. These values were the same as those of Pg affinity chromatography loading solution by the original process, indicating that introduction of Q chromatography did not affect subsequent Pg affinity chromatography. Compared with the recovery of Pg antigen in three batches of the original process (66.49±1.02)%, the recovery of Pg antigen in the affinity chromatography eluent of the modified process [five batches; (77.43±4.43)%] was significantly improved. Furthermore, the potency recovery was (86.80±4.28)%, the relative purity was (81.99±1.25)%, the specific activity was (8.679±1.073)U/mg, and the process was reproducible. Conclusion: The addition of Q chromatography could improve the recovery of Pg affinity chromatography in the full chromatography process.
3.Analysis of the association between serum γ-aminobutyric acid levels and the risk of type 2 diabetes mellitus
Yingtan Nie ; Yanfang Li ; Jinke Han ; Feifei Wu ; Xiaodan Wang ; Li Lin ; Zhen Yan
Acta Universitatis Medicinalis Anhui 2025;60(1):136-141
Objective :
To explore the association between serum γ-aminobutyric acid ( GABA) levels and the risk of developing type 2 diabetes( T2DM) .
Methods :
187 cases of T2DM patients attending the hospital were selected as the T2DM group,and 187 cases of non-T2DM population attending the same period of time were selected as the control group according to age ( ± 3 years) and gender 1 ∶ 1.On-site questionnaires and physical examination were conducted for the study subjects,and serum levels of GABA,Malondialdehyde ( MDA) and activities of superoxide dismutase ( SOD) and Glutathione peroxidase ( GSH-Px) were detected by using ELISA kits.The differences in the levels of GABA and oxidative stress indicators ( SOD,GSH-Px,MDA) between the two groups were compared, and the correlation between GABA and oxidative stress indicators was analyzed by Spearman's method; GABA and oxidative stress indicators were divided into three groups according to their control quartiles,respectively [low level group ( Q1: <P25) ,medium level group ( Q2: P25 -P75) ,high level group ( Q3: >P75) ],and conditional logistic regression was applied to analyze the relationship between GABA,oxidative stress indicators and the risk of develo- ping T2DM; the dose-response relationship between GABA,oxidative stress indicators and the risk of developing T2DM was analyzed by using restricted cubic spline ( RCS) .
Results :
T2DM group ( P<0. 05) .Spearman's correlation analysis showed that GABA level was positively correlated with SOD and GSH-Px activities and negatively correlated with MDA level ( P<0. 001) .Conditional logistic regression analysis showed that medium levels of SOD and GSH-Px as well as medium and high levels of GABA were protective factors for T2DM compared with low levels in each group ( P<0. 05) .RCS results showed that a negative dose-response relationship between GABA,GSH-Px and the risk of developing T2DM,and SOD showed a trend of decreasing and then increasing the risk of developing T2DM ( P<0. 05) .
Conclusion
Serum GABA levels have been associated with the risk of developing T2DM.As serum GABA levels increase,the risk of developing T2DM may decrease.
4.Relationship of parental anger expression and symptoms in children with oppositional defiant disorder
Feifei SI ; Ting HE ; Liangliang YANG ; Mengjie ZHAO ; Min DONG ; Lu LIU ; Xiuyun LIN
Chinese Mental Health Journal 2024;38(3):254-259
Objective:This study is to investigate the relationship of parental anger expression and symptoms in children with oppositional defiant disorder(ODD).Methods:Forty-six children with ODD and 46 age-gender-matched normal children participated.The Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),guided the diagnoses.Parental anger expression and children's anger management were assessed using the State-Trait Anger Expression Inventory-2 and Children Emotion Management Scales.Results:ODD symptoms were directly predicted by maternal anger index(AI)(β=0.13,P<0.05)and anger expression-out(AX-O)(β=0.25,P<0.05).Children's anger cope(AC)played a mediating function to maternal AI through ODD symptoms,occupying 13%of the total effect;their AC and anger dysregulation(AD)played a mediating function to maternal AX-Othrough ODD symptoms,accounting for 29%and 18%of the total effect,respectively.Conclusion:It sug-gests that anger cope and anger dysregulation in children with oppositional defiant disordermay may play a media-ting role between maternal anger expression and oppositional defiant disorder symptoms.
5.Relationship between parenting style and emotional behavior problems in children with development dyslexia
YIN Feifei, ZHANG Jing, ZHONG Lin, LI Dan, XIAO Xinyu, ZUO Pengxiang
Chinese Journal of School Health 2024;45(7):988-992
Objective:
To explore the relationship between parenting style and emotional behavior problems in children with development dyslexia (DD), so as to provide reference for family support and intervention measures.
Methods:
From June to September 2023, 201 children in DD group and typically developing matched by age and sex were selected from the students in grades 3-6 of 4 primary schools in a district of Xinjiang by random cluster sampling method. The Childrens Version of the Parenting Style Scale and the Strength and Difficulty Scale were administered, and the occurrence of childrens emotional behavior problems and parentingstyles in the two groups were compared by Chisquare test and Wicoxon rank sum test. The correlation between parents parenting styles and childrens emotional behavior problems was analyzed by generalized linear regression.
Results:
The detection rates of emotional behavior problems were 45.77% in DD group and 15.42% in normal control children group. The differences in parenting styles between fathers and mothers of the DD group and the normal control group were statistically significant in terms of emotional warmth, parenting anxiety, and overprotection (Z=4.02, 29.03; 4.94, 26.32; 23.47, 5.30, P<0.05). Generalized linear regression analysis showed that father affective warmth was positively correlated with emotional symptoms, hyperactivity, peer interaction problems and prosocial behaviors (β=0.08, 0.05, 0.05, 0.09, P<0.05). The emotional warmth of mothers in DD group was negatively correlated with emotional symptoms, conduct problems, hyperactivity and peer interaction problems (β=-0.18, -0.08, -0.07, -0.08, P<0.05).
Conclusions
Parenting style is an important factor affecting the emotional behavior problems of DD children. Improving parenting style can reduce the occurrence of emotional behavior problems of DD children.
6.Summary of the best evidence for the prevention and management of stoma prolapse in enterostomy patients
Feifei ZHAO ; Jinchen HU ; Hong HUANG ; Lin LIU ; Xiaohong HUANG
Chinese Journal of Practical Nursing 2024;40(10):779-785
Objective:To summarize the relevant evidence for prevention and management of stoma prolapse in patients with enterostomy, so as to provide reference for the clinical prevention and management of stoma prolapse measures.Methods:According to the evidence-based resource "6S" evidence pyramid model, systematically searched about the evidence of enterostomy patients prolapse prevention and management in UpToDate, BMJ best practice, Guidelines International Network, National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, National Guideline Clearinghouse, CNKI, Wanfang database,VIP Database, SinoMed,etc. The search time limit was from 30 January 2017 to 30 May 2023, 2 researchers independently evaluated the quality of the literature, selected and extracted the evidence.Results:A total of ten articles were included, including one clinical decision, five guidelines, one expert consensus, one evidence, one systematic review, one position statement. Through analysis, 20 best evidences were identified, including perioperative evaluation, preoperative colostomy site marking, reducing abdominal pressure, enterostomy prolapse nursing, health education and the follow-up.Conclusions:Best evidence summary for the prevention and care of stoma prolapse in enterostomy patients provides evidence-based reference for clinical application. Nurses should carefully select and apply evidence in combination with clinical situations and patients′ wishes, so as to develop a personalised stoma prolapse prevention and management programme for patients with enterostomy.
7.Application of whole-course multi-disciplinary nutrition model in hip surgery in elderly patients
Xiahe CHEN ; Yangxun LYU ; Qifan CHEN ; Zhou LIN ; Feifei LIAO
China Modern Doctor 2024;62(22):17-21
Objective To analyze the application effect of whole-course multi-disciplinary nutrition model in elderly patients undergoing hip surgery.Methods A total of 90 elderly patients undergoing hip surgery admitted to Wenzhou Central Hospital from October 2021 to December 2023 were selected and divided into control group and study group according to random number table method,with 45 cases in each group.The control group was treated with dietary management model,while the study group was treated with whole-course multi-disciplinary nutrition model.Recovery,nutritional status,quality of life,hip function and satisfaction were compared between two groups.Results The hospital stay and fracture healing time in study group were significantly shorter than those in control group(P<0.05).After intervention,prealbumin(PA),albumin(Alb),hemoglobin(Hb),dimensions scores of 36-item short form health survey(SF-36)and Harris hip scores of patients in two groups were significantly higher than before intervention(P<0.05).PA,Alb,Hb,dimensions scores of SF-36 and Harris hip scores in study group were significantly higher than those in control group(P<0.05).The satisfaction of patients in study group was significantly higher than that in control group(χ2=5.075,P=0.024).Conclusion The application of whole-course multi-disciplinary nutrition model in hip surgery in elderly patients can improve their nutritional status,improve their quality of life,enhance hip function,and facilitate postoperative recovery.
8.Application of Artificial Intelligence Compressive Sensing Technology in MRI of the Ankle Joint
Xuetao JIANG ; Tianxin CHENG ; Feifei LI ; Ying YUAN ; Lin JIANG ; Jie WEI ; Hui XU
Chinese Journal of Medical Imaging 2024;32(11):1164-1169
Purpose To explore the feasibility of artificial intelligence compressed sensing(ACS)technique in ankle joint MRI.Materials and Methods From September to October 2023,32 healthy volunteers who underwent ankle joint scanning in Beijing Friendship Hospital,Capital Medical University were prospectively collected.MRI of the ankle joint based on ACS and parallel imaging(PI)technology was performed on 3.0T MR.The sagittal proton density weighted imaging(PDWI),coronary PDWI,transverse PDWI and sagittal T1WI were acquired,and all data were divided into test group and control group,with ACS to accelerate the multiples of 5(ACS 5.0)in test group,whereas PI speed ratio of 2(PI 2.0)in control group,respectively.The signal intensity of talus,achilles tendon and cartilage were measured,the signal intensity and standard deviation of the long hallux flexor were obtained,and the signal noise ratio(SNR)and contrast to noise ratio(CNR)were calculated via long hallux flexor as background noise.The data of objective and subjective evaluation of the two sequences were statistically analyzed,and the image quality of each sequence was evaluated via the standard reference of PI 2.0.Results SNR and CNR in ACS group were higher than those in PI group,and the anatomical structure of sagittal PDWI sequence between the two groups had statistical significance(t=-2.937,-1.981,-4.058,-3.879,P<0.05).There were significant differences in cartilage SNR and talus CNR in coronal PDWI sequence(t=-3.310,-3.567;P=0.002,P<0.001).In terms of axial PDWI sequence,there were statistically significant differences in talus CNR and cartilage CNR between ACS and PI groups(t=-4.270,-4.382,P<0.05).The subjective evaluation of the image quality scores of the two groups by the two diagnostic imaging doctors showed a strong observer consistency(Kappa=0.977,P=0.009).There was no significant difference in image quality scores between the two groups(Z=-0.248,-0.747,<0.001,-0.071,P>0.05).The total collection time of ACS group and PI group was 337 s and 610 s,respectively.Compared with PI group,the total scanning time of ACS group was shortened by 44.8%.Conclusion ACS based MRI of the ankle joint can not only shorten the scan time,but also ensure and further improve the image quality,with feasibility.
9.Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture (version 2024)
Yun HAN ; Feifei JIA ; Qing LU ; Xingling XIAO ; Hua LIN ; Ying YING ; Junqin DING ; Min GUI ; Xiaojing SU ; Yaping CHEN ; Ping ZHANG ; Yun XU ; Tianwen HUANG ; Jiali CHEN ; Yi WANG ; Luo FAN ; Fanghui DONG ; Wenjuan ZHOU ; Wanxia LUO ; Xiaoyan XU ; Chunhua DENG ; Xiaohua CHEN ; Yuliu ZHENG ; Dekun YI ; Lin ZHANG ; Hanli PAN ; Jie CHEN ; Kaipeng ZHUANG ; Yang ZHOU ; Sui WENJIE ; Ning NING ; Songmei WU ; Jinli GUO ; Sanlian HU ; Lunlan LI ; Xiangyan KONG ; Hui YU ; Yifei ZHU ; Xifen YU ; Chen CHEN ; Shuixia LI ; Yuan GAO ; Xiuting LI ; Leling FENG
Chinese Journal of Trauma 2024;40(9):769-780
Hip fracture in the elderly is characterized by high incidence, high disability rate, and high mortality and has been recognized as a public health issue threatening their health. Surgery is the preferred choice for the treatment of elderly patients with hip fracture. However, lower extremity deep venous thrombosis (DVT) has an extremely high incidence rate during the perioperative period, and may significantly increase the risk of patients′ death once it progresses to pulmonary embolism. In response to this issue, the clinical guidelines and expert consensuses all emphasize active application of comprehensive preventive measures, including basic prevention, physical prevention, and pharmacological prevention. In this prevention system, basic prevention is the basis of physical and pharmacological prevention. However,there is a lack of unified and definite recommendations for basic preventive measures in clinical practice. To this end, the Orthopedic Nursing Professional Committee of the Chinese Nursing Association and Nursing Department of the Orthopedic Branch of the China International Exchange and Promotive Association for Medical and Health Care organized relevant nursing experts to formulate Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture ( version 2024) . A total of 10 recommendations were proposed, aiming to standardize the basic preventive measures for lower extremity DVT in elderly patients with hip fractures during the perioperative period and promote their subsequent rehabilitation.
10.Sensory neuronal exosomes induce the senescence of nucleus pulposus stem cells and promote the occurrence of intervertebral disc degeneration
Yizhong PENG ; Sheng LIU ; Songfeng CHEN ; Kanglu LI ; Feifei PU ; Wei WU ; Xiangcheng QING ; Hui LIN ; Xuanzuo CHEN ; Zengwu SHAO
Chinese Journal of Orthopaedics 2024;44(8):532-543
Objective:To investigate the role and molecular mechanism of sensory neuron-derived exosomes (nExo) in mediating intervertebral disc degeneration (IDD).Methods:A rat IDD model was constructed, with nExo injected into the intervertebral disc. After 4 weeks, the degenerative grades of operated discs were evaluated using histological staining, while the senescent phenotype of nucleus pulposus stem cells (NPSC) in the tissue was evaluated using immunofluorescence staining. For in vitro experiments, 24 hours after the treatment of nExo to NPSC, immunoblotting, flow cytometry, or senescence-associated β-galactosidase staining was applied to evaluate the senescent phenotype of NPSC. Transcriptomics analysis was applied to identify the key molecules that mediate nExo-induced cells senescence. After 4 weeks of injecting nExo and TXN into the rat tail disc degeneration model.Results:nExo increased the degenerative grades of IDD and increased the proportion of TEK +p16 + and TEK +p21 + cells (from 36.32% ±4.04%, 33.69% ±4.56% in IDD group to 56.41% ±5.26%, 50.14% ±8.49% in IDD+nExo group, respectively; t=7.420, P<0.001; t=4.184, P<0.0019, respectively) in the disc tissue. Besides, nExo promoted the expression of p16 and p21 in NPSC and increased the percentage of cells with positive senescence-associated β-galactosidase staining (from 7.32%±1.73% to 58.22%±11.38%, t=7.658, P=0.002), while the percentage of G2/M cells was downregulated (from 18.10%±1.32% to 1.60%±0.67%, t=19.290, P<0.001). Transcriptomic analysis showed that the differential genes of CTRL vs. nExo were closely related to cell senescence, and TXN was screened by intersecting the differential gene set with the cellular senescence gene sets from the published database. Furthermore, we verified that nExo decreased the content of TXN in NPSC, while exogenous TXN downregulated the expression of p16 and p21 in NPSC, reduced the positive cell rate of senescence-associated β-galactosidase staining (from 58.84%±3.99% to 21.68%±8.16%, t=7.048, P=0.021), increased the percentage of G2/M cells (from 1.21%±0.34% to 15.26%±2.60%, t=9.259, P=0.001). TXN significantly reduced the grade of disc tissue degeneration (histological score: 14.33±0.82 in the nExo group; 8.17±1.17 in the nExo+TXN group, t=10.590, P<0.001), significantly increased the content of extracellular matrix (from 10.94±4.35 μg/mg to 50.55±12.16 μg/mg, t=7.512, P<0.001), and reduced the proportion of TEK +p16 + and TEK +p21 + double-positive cells (from 54.92%±4.21% and 60.31%±9.02% to 27.93%±3.26% and 33.75%±8.07%, respectively; t=12.430, P<0.001; t=5.375, P<0.001, respectively). Conclusion:nExo promotes cell senescence and IDD by downregulating TXN in NPSC.


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