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.

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.

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．

Objective:To explore the optimal pulse oxygen saturation (SpO 2) range during hospitalization for patients with sepsis. Methods:A case-control study design was employed. Demographic information, vital signs, comorbidities, laboratory parameters, critical illness scores, clinical treatment information, and clinical outcomes of sepsis patients were extracted from the Medical Information Mart for Intensive Care-Ⅳ (MIMIC-Ⅳ). A generalized additive model (GAM) combined with a Loess smoothing function was employed to analyze and visualize the nonlinear relationship between SpO 2 levels during hospitalization and in-hospital all-cause mortality. The optimal range of SpO 2 was determined, and Logistic regression model along with Kaplan-Meier curve were utilized to validate the association between the determined range of SpO 2 and in-hospital all-cause mortality. Results:A total of 5?937 patients met the inclusion criteria, among whom 1?191 (20.1%) died during hospitalization. GAM analysis revealed a nonlinear and U-shaped relationship between SpO 2 levels and in-hospital all-cause mortality among sepsis patients during hospitalization. Multivariable Logistic regression analysis further confirmed that patients with SpO 2 levels between 0.96 and 0.98 during hospitalization had a decreased mortality compared to those with SpO 2 < 0.96 [hypoxia group; odds ratio ( OR) = 2.659, 95% confidence interval (95% CI) was 2.190-3.229, P < 0.001] and SpO 2 > 0.98 (hyperoxia group; OR = 1.594, 95% CI was 1.337-1.900, P < 0.001). Kaplan-Meier survival curve showed that patients with SpO 2 between 0.96 and 0.98 during hospitalization had a higher probability of survival than those patient with SpO 2 < 0.96 and SpO 2 > 0.98 (Log-Rank test: χ2 = 113.400, P < 0.001). Sensitivity analyses demonstrated that, with the exception of subgroups with smaller sample sizes, across the strata of age, gender, body mass index (BMI), admission type, race, heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, respiratory rate, body temperature, myocardial infarction, congestive heart failure, cerebrovascular disease, chronic liver disease, diabetes mellitus, sequential organ failure assessment (SOFA), simplified acute physiology score Ⅱ (SAPSⅡ), systemic inflammatory response syndrome score (SIRS), and Glasgow coma score (GCS), the mortality of patients with SpO 2 between 0.96 and 0.98 was significantly lower than those of patients with SpO 2 < 0.96 and SpO 2 > 0.98. Conclusions:During hospitalization, the level of SpO 2 among sepsis patients exhibits a U-shaped relationship with in-hospital all-cause mortality, indicating that heightened and diminished oxygen levels are both associated with increased mortality risk. The optimal SpO 2 range is determined to be between 0.96 and 0.98.

Objective:To investigate the necessity of adaptive re-planning during radiotherapy for nasopharyngeal carcinoma (NPC) and its impact on dose improvement.Methods:Clinical data of 89 NPC patients admitted to Sun Yat-sen University Cancer Center from July 2014 to December 2017 were retrospectively analyzed. All patients received 25+7 rounds of adaptive re-planning during radiotherapy. Plan-A was defined as the initial CT scan-based 25-fraction radiotherapy plan, while plan-B was defined as the re-planned 7-fraction radiotherapy plan based on a subsequent CT scan. The changes in the target and parotid gland volumes were compared between plan-A and plan-B. Plan-I was a one-time simulation of plan-A extended to 32 fraction radiotherapy plan, and plan-II was generated through registration and fusion of the plan-A and plan-B for adaptive re-planning. The differences in dose metrics, homogeneity index (HI), conformity index (CI), and dose to organs at risk (OAR) were compared between plan-I and plan-II. Statistical analysis was performed by using paired t-test. Results:Compared with plan-A, the gross tumor volume of massive bleeding lesions (GTV nx) and parotid gland volume of plan-B were decreased by 13.14% and 11.12%, respectively (both P<0.001). While planning clinical target volume of metastatic lymph nodes (PCTV nd) of plan-B was increased by 7.75%( P<0.001). There were significant changes in the lymph nodes of plan-A and plan-B. The D mean, D 5%, D 95% of massive bleeding lesions planning target volume (PTV nx) and D 5% of high risk planning target volume (PTV1) in plan-II were all significantly higher than those in plan-I (all P<0.05). The CI of PTV nx and PTV1 in plan-II was closer to 1 than that in plan-I. In all assessed OAR, the D mean, D 50%, and D max of plan-II were significantly lower than those of plan-I (all P<0.05). Conclusions:During radiotherapy, NPC patients may experience varying degrees of primary tumor shrinkage, parotid gland atrophy, and lymph node changes. It is necessary to deliver re-planning and significantly improve the dose of target areas and OAR.

Objective To construct a nomogram prediction model for major adverse cardiovascular events(MACE)within 1 year after percutaneous coronary intervention(PCI)in elderly patients with acute coronary syndrome(ACS).Methods A retrospective analysis was conducted on 551 patients with diagnosed ACS and undergoing PCI in Department of Cardiovascular Medicine of Air Force Medical Center from 1 January 2020 to 1 April 2022.According to the occurrence of MACE during 1 year of follow-up,they were classified into MACE group(n=176)and non-MACE group(n=375).Risk factors for the occurrence of MACE in elderly ACS patients within 1 year after PCI were analysed using univariate and multivariate logistic regression,a nomogram prediction model was constructed,and the predictive power of the model was assessed using the area under the ROC curve(AUC).Results The MACE group had significantly higher Gensini score,systemic immune-inflammation index,and GRACE score,but obviously lower prognostic nutritional index than the non-MACE group(P＜0.01).Multivariate logistic regression analysis showed that recent smoking(OR=2.222,95％CI:1.361-3.628,P=0.010),hyperlipidaemia(OR=1.881,95％CI:1.145-3.089,P=0.013),prognostic nutritional index(OR=4.645,95％CI:2.788-7.739,P=0.001),LVEF(OR=5.177,95％CI:3.160-8.483,P=0.001),systemic immune-inflammation index(OR=5.396,95％CI:3.179-9.159,P=0.001),and preoperative di-agnosis of non-STEMI(OR=2.829,95％CI:1.356-5.901,P=0.006)or STEMI(OR=3.451,95％CI:1.596-7.463,P=0.002)were independent influencing factors for occurrence of MACE after PCI in elderly ACS patients.ROC curve analysis showed that the AUC value of the nomo-gram model for predicting MACE within 1 year after PCI in elderly ACS patients was 0.888.Con-clusion Our developed nomogram model is simple and practical,and can effectively predict the occurrence of MACE within 1 year after PCI in elderly ACS patients.And external validation should be carried out to ensure its generality.

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 Childrens Version of the Parenting Style Scale and the Strength and Difficulty Scale were administered, and the occurrence of childrens emotional behavior problems and parentingstyles in the two groups were compared by Chisquare test and Wicoxon rank sum test. The correlation between parents parenting styles and childrens 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.

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.

ObjectiveTo analyze the prevalence of myopia among the primary school students in Shanghai, and to explore its relationship with sleep duration and sleep quality, providing references for precise myopia prevention. MethodsA cross-sectional survey and random sampling were employed. Between April and May 2023, a total of 1 889 students from grades 1 to 5 in Jiading District, Shanghai, were selected for vision testing and a questionnaire on children’s sleeping habits and relevant factors were conducted using the Children’s Sleep Habits Questionnaire (CSHQ) in Chinese. The relationship between myopia and sleep patterns was analyzed using chi-square tests and a multivariate logistic regression model. ResultsThe overall myopia rate among the primary school students in Jiading District, Shanghai, was 35.6%. The results of univariate analysis showed that in the myopia group, the incidences of sleep disturbance and sleep anxiety were lower compared to children without myopia, while the incidences of sleep continuity and parasomnias were higher than there in the non-myopia group (χ²=12.816, 10.292, 10.971, 3.917, all P<0.05). Additionally, among the elementary school students with an average daily sleep duration of less than 10 hours, the prevalence of myopia was higher. The multivariate logistic regression analysis revealed that factors such as being female (OR=1.291, 95%CI: 1.044‒1.597), higher grade levels (2^nd grade: OR=2.174, 95%CI: 1.471‒3.212; 3^rd grade:OR=3.850, 95%CI: 2.648‒5.598; 4^th grade: OR=8.906, 95%CI: 6.154‒12.890; 5^th grade: OR=12.299, 95%CI: 8.433‒17.937), having one parent (OR=2.250, 95%CI: 1.757‒2.881) or both parents(OR=3.623, 95%CI: 2.719‒4.827) with myopia, and parasomnias (OR=1.518, 95%CI: 1.065‒2.163) were associated with a higher detection rate of myopia. ConclusionThe prevalence of myopia is notably high among the primary school students in Jiading District, Shanghai, and there is an association between the occurrence of myopia and parasomnias.

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.