[Objective] To analyze the influencing factors of repeat blood donor lapsing using a zero-inflated poisson regression model (ZIP). [Methods] The blood donation behavior of 12 498 whole blood donors from 2020 was tracked until December 31, 2023. The factors influencing the frequency of blood donations in a given year was analyzed using ZIP, and donors with 0 blood donation in that year were considered to have lapsed. The changes in relevant influencing factors associated with each blood donation were measured and modeled for analysis. [Results] The zero-inflated part of ZIP showed that the risk of lapsing of male blood donors was 2.24 times that of female blood donors (OR 95% CI:1.864-2.696, P<0.001); the risk of lapsing of the 35-44 age group and over 45 age group was respectively 40% (OR 95% CI:0.455-0.790, P<0.001) and 61%(OR 95% CI:0.268-0.578, P<0.001) lower than that of the under 25 age group; the risk of lapsing for those who have donated blood twice and ≥3 times was respectively 50% (OR 95% CI:0.405-0.609, P<0.001) and 81% (OR 95% CI:0.154-0.225, P<0.001) lower than that of first-time donors; the risk of lapsing of those with junior high or high school education was 1.2 times that of those with a college degree or higher (OR 95% CI:1.033-1.384, P<0.05); the risk of lapsing for the divorced group was 2.02 times that of the married group (OR 95% CI:1.445-2.820, P<0.001); the risk of lapsing for those with an income (Yuan) of 10 000 to 50 000, 50 000 to 100 000 and more than 100 000 was respectively 0.67 (OR 95% CI:0.552-0.818, P<0.001), 0.72 (OR 95% CI:0.591-0.884, P=0.002) and 0.67 (OR 95% CI:0.535-0.834, P<0.001) times that of those with an income (Yuan) of less than 10 000. The results of the Poisson part are consistent with the results of the zero-inflated part in terms of age and education level. [Conclusion] Blood donor lapsing is overall related to factors such as gender, age, donation frequency, education, marital status and family income. It's essential to care for those blood donors prone to lapse to retain more regular blood donors.

ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.

Human naïve pluripotent stem cells (PSCs) hold great promise for embryonic development studies. Existing induction and culture strategies for these cells, heavily dependent on MEK inhibitors, lead to widespread DNA hypomethylation, aberrant imprinting loss, and genomic instability during extended culture. Here, employing high-content analysis alongside a bifluorescence reporter system indicative of human naïve pluripotency, we screened over 1,600 chemicals and identified seven promising candidates. From these, we developed four optimized media-LAY, LADY, LUDY, and LKPY-that effectively induce and sustain PSCs in the naïve state. Notably, cells reset or cultured in these media, especially in the LAY system, demonstrate improved genome-wide DNA methylation status closely resembling that of pre-implantation counterparts, with partially restored imprinting and significantly enhanced genomic stability. Overall, our study contributes advancements to naïve pluripotency induction and long-term maintenance, providing insights for further applications of naïve PSCs.
Humans ; DNA Methylation/drug effects* ; Genomic Instability ; Pluripotent Stem Cells/metabolism* ; Cell Culture Techniques/methods* ; Cells, Cultured

Objective: To preliminarily develop a multidimensional blood donor role scale based on role theory and systematically compare the psychosocial characteristic differences between award-winning donors and first-time donors in Guangzhou, and to provide an empirical reference for formulating differentiated donor retention strategies. Methods: A cross-sectional survey design was adopted. A random sample of award-winning donors and concurrently sampled first-time donors yielding 1 361 valid responses collected (721 from the award group, 640 from the first-time group). Exploratory factor analysis was used to assess the scale structure. Data were post-stratified and weighted according to the gender and age distributions of the general donor population. Independent samples t-tests, multivariate analysis of covariance (MANCOVA), and generalized linear models were employed to compare dimensional scores between the two groups. A paired t-test was conducted to analyze the annual donation frequency of award-winning donors before and after receiving the award. Results: Exploratory factor analysis yielded a 5-factor structure, including Role Identity and Expectations, Role Adaptation and Maintenance, Role Environment and Experience, Role Relationships and Conflict, and Role Incentives and Rewards, with a cumulative variance contribution rate of 56.43%. The scale demonstrated good internal consistency reliability (Cronbach's α=0.906). Known-group validity test showed that award-winning donors scored significantly higher than first-time donors on Role Identity and Expectations (t=4.366, P<0.001, d=0.240), Role Adaptation and Maintenance (t=5.436, P<0.001, d=0.500), and Role Relationships and Conflict (t=4.844, P<0.001, d=0.220). These differences remained significant after controlling for selected demographic variables (MANCOVA, Wilks' λ=0.943, P<0.001). Generalized linear models suggested that donation frequency was an independent predictor for these dimensions. Additionally, the annual donation frequency of award-winning donors was slightly higher after receiving the award than before (t=2.007, P=0.045). Conclusion: The preliminary blood donor role scale demonstrates acceptable reliability and validity and can effectively distinguish groups with different donation behavior characteristics. The study reveals that award-winning donors exhibit more positive psychological characteristics across multiple role identity dimensions and maintain their donation behavior after receiving an award. External incentives and internal role identity may jointly contribute to behavioral persistence. The findings provide a preliminary reference for further exploring the formation pathways of donor role identity and developing differentiated donor retention strategies.

Purpose::To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis.Methods::A total of 282 healthy young male volunteers aged 18 -20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conformed to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q 1, Q 3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. Results::Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4% (66 cases). These patients showed higher percentages of lean body mass ( p = 0.001), total body water (TBW, p=0.006), extracellular water ( p=0.020) and intracellular water ( p=0.010) as well as a larger ratio of basal metabolic rate/total weight ( p=0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat ( p=0.001) and body fat mass index ( p=0.002) were lower. Logistic regression analysis showed that TBW percentage > 65.35% ( p=0.050, odds ratio =3.114) and 3rd space water > 0.95% ( p=0.045, odds ratio =2.342) were independent risk factors for lower extremity muscle injuries. Conclusion::TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

  Objective  To establish a model that can predict the occurrence of acute kidney disease (AKD) in liver cirrhotic patients and evaluate its performance.  Methods  Liver cirrhotic patients who hospitalized in the department of gastroenterology of the First Hospital of Lanzhou University from January 2017 to January 2022 were retrospectively included. They were divided into AKD and non-AKD groups according to whether they were combined with AKD during hospitalization, and were randomized into training and validation sets in a 7∶3 ratio. The clinical data of patients in the two groups were collected, and LASSO regression and multifactorial Logistic regression were used to screen the influencing factors for the occurrence of AKD in patients with liver cirrhosis and to establish a prediction model. The model was then evaluated by using the receiver operating characteristic curve, the calibration curve and the clinical decision curve.  Results  A total of 796 cases of liver cirrhotic patients who met the inclusion and exclusion criteria were enrolled. Among them, 103 cases were in the AKD group and 693 cases were in the non-AKD group; 561 cases were in the training set and 235 cases were in the validation set. The results of LASSO regression and multifactorial Logistic regression showed that a history of diabetes (OR=2.922, 95% CI: 1.290-6.564, P=0.009), hepatic encephalopathy (OR=6.210, 95% CI: 2.278-17.479, P < 0.001), gastrointestinal bleeding (OR=2.501, 95% CI: 1.236-5.073, P=0.011), ascites (OR=3.219, 95% CI: 1.664-6.539, P < 0.001), male (OR=0.477, 95% CI: 0.254-0.879, P=0.019), hemoglobin (OR=0.987, 95% CI: 0.975-0.999, P=0.044), albumin (OR=0.952, 95% CI: 0.911-0.991, P=0.023), and prothrombin time (OR=0.865, 95% CI: 0.779-0.920, P < 0.001) were the independent influences on the occurrence of AKD in liver cirrhotic patients, and were used to construct a prediction model. The area under the curve of the model in the training set and validation set for predicting the occurrence of AKD in liver cirrhotic patients was 0.895 (95% CI: 0.865-0.925) and 0.869 (95% CI: 0.807-0.930), respectively. The calibration curves showed that the model had good fit and consistency and the clinical decision curves showed that the use of the model for predicting the risk of AKD could benefit liver cirrhotic patients overall.  Conclusions  A prediction model for the occurrence of AKD in liver cirrhotic patients was established based on eight influencing factors, including gender, history of diabetes, and hepatic encephalopathy. It was validated to have good discrimination, calibration, and clinical utility, and is expected to assist in the clinical early screening and identification of liver cirrhosis-associated AKD.

Objective To establish a mouse model of pregnancy pain-depression comorbidity induced by chronic unpredictable stress(CUS),complete Freund's adjuvant(CFA),and formalin,and to systematically evaluate the associated phenotypes and preliminarily explore the pathological basis of the comorbidity.Methods Eight-week-old C57BL/6J female mice were randomly strarified divided into a control group(no intervention before pregnancy)and a CUS model group(CUS intervention before pregnancy)based on sucrose preference test(SPT)data.After completing the CUS treatment,female and male mice were paired and mated.Pain was induced by injecting 50％CFA and 5％formalin in the right hind foot during pregnancy to create a model of pregnancy pain-depression comorbidity.The experiment was divided into 8 subgroups:control-blank group,CUS-blank group,control-CFA group,CUS-CFA group,control-formalin group,CUS-formalin group,control-CFA+formalin group,and CUS-CFA+formalin group,with 10 mice in each group.The mice in each group were subject to behavioral tests,including the SPT,forced swimming test,tail suspension test,and open field test before and after CUS intervention,during pregnancy,and after delivery.Pain sensitivity changes were measured using mechanical allodynia and thermal hyperalgesia tests.Mice were then euthanized.Levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in hippocampus,as well as cortisol and adrenocorticotropic hormone(ACTH)in serum,were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with the control-blank group,the CUS-blank group showed a significant depression-like behavior with reduced pain threshold(P＜0.001).The control-CFA+formalin group showed a decrease in pain threshold after both CFA injection and formalin injection(P＜0.01).Compared with the control-blank and control-formalin groups,the pain threshold was significantly lower in the CUS-formalin group(P＜0.01),with a sequential decrease among the three.Compared with the control-blank and control-CFA groups,the pain threshold was significantly lower in the CUS-CFA group(P＜0.001),with a sequential decrease among the three.Compared with the control-blank and control-CFA+formalin groups,the mechanical pain threshold of mice in the CUS-CFA+formalin group was significantly lower(P＜0.001)and the thermal radiation tolerance time was shorter(P＜0.01),both with sequential decreases among the three.Compared with the control-CFA+formalin and the CUS-blank groups,the CUS-CFA+formalin group had a significantly lower percentage of sucrose preference(P＜0.001),longer immobility time during the forced swimming test(P＜0.001)and tail suspension test(P＜0.001),reduced central exploration time in the open field test(P＜0.001),reduced total exploration distance(P＜0.001),and reduced percentage of distance traveled for central exploration(P＜0.001).Compared with the control-CFA+formalin and CUS-blank groups,the serum cortisol and ACTH levels of the CUS-CFA+formalin group were significantly higher(P＜0.01),and the levels of IL-6 and TNF-α in the hippocampus were higher(P＜0.05).Conclusion The combination of CUS+CFA+formalin injections is an ideal method for establishing a C57BL/6J mouse model of pregnancy pain-depression comorbidity.The behavioral changes in model mice may be attributed to the regulation of inflammatory response in hippocampus and hormone levels in the hypothalamic-pituitary-adrenal(HPA)axis.

[Objective] To explore the characteristics of lifestyle behaviors and mental health status among blood donors in Guangzhou, and to investigate the correlation between donation frequency and these factors. [Methods] A cross-sectional study was conducted among 13 042 whole blood donors from 17 street blood donation sites of Guangzhou Blood Center from May to August 2020. Descriptive analysis was used to describe the characteristics of lifestyle behaviors and mental health status among blood donors in Guangzhou. Ordinal multinomial logistic regression model was used to analyze the correlation between donation frequency and these factors. [Results] It was found that some of 13 042 blood donors had unhealthy habits, such as 6.8% (698/10 214，2 828 missing values) had severe tobacco dependence, 30.6% (3 997/13 042) had low exercise levels, 38.8%（5 056/13 042）had poor sleep quality, and 2.2% (271/12 159，883 missing values) had alcohol dependence. In addition, 2.8% (364/13 042) and 1.3% (172/13 042) of the donors may have moderate to severe depression and anxiety symptoms, respectively. The results of the ordinal multinomial logistic regression model showed that exercise level was significantly negatively correlated with the degree of depression and anxiety among blood donors. With the decrease in exercise level, the possibility of depression and anxiety among donors increased significantly. BMI, household income, education level, marital status, donation frequency, alcohol consumption and smoking had no significant correlation with the mental health status of donors. [Conclusion] Improving the exercise habits of blood donors may help enhance their mental health level. It is recommended that blood station staff strengthen the content of exercise when providing health education to blood donors to maintain a healthy lifestyle. It also suggests that there may be a certain degree of under-diagnosis of mental health problems in the process of health consultation before blood donation, and conducting more comprehensive and effective mental health assessments for blood donors is recommended.

Objective To study the pharmacokinetic characteristics of lamotrigine tablets in Chinese healthy subjects under fasting and fed conditions,and to evaluate the bioequivalence and safety profiles between the domestic test preparation and the original reference preparation.Methods Twenty-four Chinese healthy male and female subjects were enrolled under fasting and fed conditions,18 male and 6 female subjects under fasting conditions,17 male and 7 female subjects under fed conditions.A random,open,single-dose,two preparations,two sequences and double-crossover design was used.Plasma samples were collected over a 72-hour period after give the test or reference preparations 50 mg under fasting and fed conditions.The concentration of lamotrigine in plasma was detected by liquid chromatography-tandem mass spectrometry,and the main pharmacokinetic parameters were calculated to evaluate the bioequivalence by WinNonLin 8.1 program.Results The main pharmacokinetic parameters of single-dose the tested and reference preparations were as follows:The fasting condition Cmax were(910.93±248.02)and(855.87±214.36)ng·mL-1;tmax were 0.50(0.25,4.00)and 1.00(0.25,3.50)h;t1/2 were(36.1±9.2)and(36.0±8.2)h;AUC0_72h were(27 402.40±4 752.00)and(26 933.90±4 085.80)h·ng·mL-1.The fed condition Cmax were(701.62±120.67)and(718.95±94.81)ng·mL-1;tmax were 4.00(1.00,5.00)and 4.00(0.50,5.00)h;t1/2 were(44.2±12.4)and(44.0±12.0)h;AUC0-72h were(30 253.20±7 018.00)and(30 324.60±6 147.70)h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of Cmax and AUC0-72 hfor the test preparation and reference preparation were all between 80.00％and 125.00％under fasting and fed conditions.Conclusion Two kinds of lamotrigine tablets are bioequivalent,and have similar safety in Chinese healthy male and female subjects under fasting and fed conditions.