1.Mechanism of Shaoyaotang in Modulating MDSCs-related Immunosuppressive Microenvironment in Prevention and Treatment of Colitis-associated Carcinogenesis
Xue CHEN ; Chenglei WANG ; Bingwei YANG ; Haoyu ZHAI ; Ying WU ; Weidong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):10-19
ObjectiveTo explore the mechanism of Shaoyaotang in the prevention and treatment of colitis-associated carcinogenesis (CAC) based on myeloid-derived suppressor cells (MDSCs)-related immunosuppressive microenvironment. MethodsA total of 140 six-week-old SPF FVB male mice were randomly divided into seven groups: Blank group, Shaoyaotang without model group (7.12 g·kg-1), model group, sulfasalazine group (0.52 g·kg-1), Shaoyaotang low-dose group (3.56 g·kg-1), Shaoyaotang medium-dose group (7.12 g·kg-1) and Shaoyaotang high-dose group (14.24 g·kg-1), with 20 mice in each group. The blank control group and the Shaoyaotang without model group received a single intraperitoneal injection of physiological saline (10 mg·kg-1), while the other five groups were given a single intraperitoneal injection of azoxymethane (AOM) (10 mg·kg-1). After 1 week, the mice were given drinking water containing 2% dextran sulfate sodium (DSS) for 1 week, followed by normal drinking water for 2 weeks. This cycle was repeated three times over a total period of 14 weeks to establish the CAC mouse model. Each group was administered gavage once daily for 2 weeks starting on the 14th day of the experiment, followed by three times a week until the end of the experiment. The body weight of the mice was recorded weekly. Mice were sacrificed on the 28th and 98th days of the experiment. After dissection, the colon length, colon weight, spleen weight, tumor size, and tumor number were measured. Hematoxylin and eosin (HE) staining was used to assess the pathological morphology of colon tumor tissue. Flow cytometry was used to detect MDSCs, regulatory T cells (Tregs), CD4+ T cells, CD8+ T cells, and the CD4+/CD8+ T cell ratio in the spleen. Immunohistochemistry was used to detect the expression levels of programmed cell death protein-1 (PD-1), programmed cell death ligand 1 (PD-L1), phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated nuclear factor-κB (p-NF-κB), and hypoxia-inducible factor 1α (HIF-1α) in the colon tissue. ResultsOn day 14, compared with the blank group, the body weight of the model group was significantly reduced (P<0.01), reaching its lowest point on day 28 (23.39 ± 0.95 ) g. On days 28 and 98, compared with the blank group, the colon length in the model group was significantly shortened (P<0.01), the colon index significantly increased (P<0.01), the spleen index significantly increased (P<0.01), and the tumor load significantly increased (P<0.01). HE staining showed that in the model group, tumor cells, a large number of inflammatory cell infiltrates, goblet cell disappearance, and crypt loss were observed. In each dose group of Shaoyaotang, the damage to the colonic mucosa, inflammatory cell infiltration, and crypt structure destruction were alleviated. Compared with the model group, the body weight of mice in each dose group of Shaoyaotang increased. On day 98, the colon length was significantly increased (P<0.01), the colon index significantly decreased (P<0.01), the spleen index significantly decreased (P<0.01), and the tumor burden significantly decreased (P<0.01) in each Shaoyaotang dose group. On days 28 and 98, MDSCs and Tregs in the spleen of the medium- and high-dose Shaoyaotang groups were significantly reduced (P<0.01), while CD4+ T cells and the CD4+/CD8+ T cell ratio were significantly increased (P<0.01). The proportion of CD8+ T cells in the spleen and the expression levels of PD-1 and PD-L1 in the colon tissues of mice in each Shaoyaotang dose group were significantly increased to varying degrees (P<0.05, P<0.01). On days 28 and 98, the expression of p-AMPK-positive cells in the colon tissue of the medium- and high-dose Shaoyaotang groups was significantly increased (P<0.01), while the expression of p-NF-κB and HIF-1α was significantly reduced (P<0.01). ConclusionShaoyaotang can regulate MDSC recruitment and modulate the immune function of T lymphocyte subsets to inhibit the occurrence and development of AOM/DSS-induced CAC in mice. The mechanism may be related to the activation of the AMPK/NF-κB/HIF-1α pathway.
2.Exploring Multi-target Effect of Erzhiwan on Improving Myocardial Injury in Ovariectomized Mice Based on Non-targeted Metabolomics
Ying YANG ; Jing HU ; Pei LI ; Ruyuan ZHU ; Zhiguo ZHANG ; Haixia LIU ; Yanjing CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):74-84
ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected, 40 female C57BL/6 mice were randomly divided into sham operation group, model group, estrogen group(estradiol valerate, 1.3×10-4 g·kg-1), Erzhiwan low and high dose groups(3.12, 9.36 g·kg-1), with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage, and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function, hematoxylin-eosin(HE) staining was used to observe myocardial morphological changes, and enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of estrogen, N-terminal pro-brain natriuretic peptide(NT-proBNP), hypersensitive troponin T(hs-TnT), total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C), interleukin(IL)-1β, IL-18 and tumor necrosis factor-α(TNF-α). The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS), and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase(PI3K) and protein kinase B(Akt) in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the protein expression levels of PI3K, Akt, phosphorylated(p)-Akt were detected by Western blot. ResultsCompared with the sham operation group, the model group showed abnormal cardiac function, increased myocardial fiber space, cardiomyocyte atrophy, sarcoplasmic aggregation, and occasional dissolution or rupture of muscle fiber, the level of estrogen in the serum was decreased, the levels of NT-proBNP, hs-TnT, IL-1β, IL-18, TNF-α, TG, TC and LDL-C were increased, and the level of HDL-C was decreased(P<0.01). Compared with the model group, Erzhiwan could increase the level of estrogen, improve the abnormal cardiac function, reduce the pathological injury of myocardial tissue, decrease the levels of myocardial injury markers(NT-proBNP, hs-TnT) and inflammatory factors(IL-1β, IL-18, TNF-α), decrease the levels of TG, TC, LDL-C, and increased the level of HDL-C(P<0.01). The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan, which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway, PI3K-Akt pathway, cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG) pathway and other metabolic pathways. Compared with the sham operation group, the levels of phosphatidylcholine(PC, 11 types) and phosphatidylethanolamine(PE, 5 types) in mouse myocardial tissue of the model group were increased(P<0.05, P<0.01), and the mRNA and protein expressions of PI3K and p-Akt were decreased(P<0.05, P<0.01). Compared with the model group, the levels of PC(11 types) and PE(5 types) were decreased(P<0.05, P<0.01) in myocardial tissue of Erzhiwan group, the mRNA and protein expressions of PI3K and p-Akt were elevated(P<0.01). ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice, improve the abnormal cardiac function, improve lipid metabolism disorder, and reduce the levels of myocardial injury markers and inflammatory factors, which involves a number of signaling and metabolic pathways in the heart, among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.
3.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine: Atopic Dermatitis
Junfeng LIU ; Xiumei MO ; Mei MO ; Hongyi LI ; Ying LIN ; Xiaoxiao ZHANG ; Dacan CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):244-252
Atopic dermatitis (AD) is a common pruritic and chronic inflammatory dermatosis in clinical practice and is one of the diseases responding specifically to traditional Chinese medicine (TCM). With the launch of biological agents and small molecule drugs and the development and implementation of guidelines of diagnosis and treatment, clinical pathways of treatment of moderate to severe AD, and consensus on the whole-process management of AD, the clinical efficacy of moderate to severe AD has been significantly improved. However, there are still many unmet clinical needs that require more effective methods to meet. In response to the Opinions of the CPC Central Committee and the State Council on Facilitating the Inheritance, Innovation, and Development of Traditional Chinese Medicine and the spirit of the National Conference on TCM, the China Association of Chinese Medicine organized more than 20 experts in TCM dermatology, Western medicine dermatology, interdisciplinary fields, and industries to discuss the difficulties and advantages of TCM in the treatment of AD. TCM treatment for AD can not only improve rash and relieve itching but also solve many concomitant syndromes. The abundant external treatment methods of TCM have advantages for different special populations and rash characteristics. The concept of treating disease before its onset in TCM is in line with the chronic disease management mode of prevention and treatment of atopic march and prevention of recurrence. In addition, TCM therapy can reduce the use of topical glucocorticoids and has good safety. Regarding the comorbidity of AD, equal emphasis on TCM and Western medicine and multidisciplinary joint treatment should be advocated to achieve maximum benefit for patients. The exchange of TCM and Western medicine has clarified the positioning and advantages of TCM intervention in AD, providing guidance for clinical and scientific research.
4.An Ethnic Minority Perspective: Association Between Negative Life Events and Depressive Symptoms in Yi Adolescents in China
Qingqing XIAO ; Xiaozhen SONG ; Shoukang ZOU ; Ying WANG ; Tuge WAQI ; Li YIN
Psychiatry Investigation 2025;22(4):405-411
Objective:
This study explored whether anxiety and core self-evaluation mediate the relationship between negative life events and depressive symptoms in adolescents of the Yi ethnic minority in China.
Methods:
In this cross-sectional study, a convenience sample of 627 Yi adolescents 10–19 years old (252 males, 40.2%) from primary, middle and high schools in Liangshan Prefecture in China completed the Adolescent Self-Rating Life Events Checklist (ASLEC) to report on negative life events, the Second Edition of the Beck Depression Inventory (BDI-II) to report on depressive symptoms, the Core Self-Evaluations Scale (CSES) to describe core self-evaluation, and the Screen for Child Anxiety-Related Emotional Disorders (SCARED) to report anxiety symptoms.
Results:
In Pearson correlation analysis, total score and dimension subscores on the ASLEC correlated positively with total score and dimension subscores on the SCARED survey as well as with total score on the BDI. Total ASLEC score and dimension subscores correlated negatively with total CSES score. Mediation analysis indicated that negative life events affected depressive symptoms directly, as well as indirectly via core self-evaluation (mediating effect was 0.087; 95% confidence interval [CI], 0.063–0.113; p<0.001). The chain-mediated pathway effect was significant (mediating effect was 0.017; 95% CI, 0.011–0.026; p<0.001).
Conclusion
Yi adolescents in Liangshan Prefecture show certain prevalence of anxiety and depression, and they score relatively low on core self-evaluation. In this ethnic group, negative life events can affect depressive symptoms directly as well as indirectly through chain-mediated effects of anxiety and core self-evaluation.
5.Lactate Transferase Function of Alanyl-transfer t-RNA Synthetase and Its Relationship With Exercise
Ying-Ying SUN ; Zheng XING ; Feng-Yi LI ; Jing ZHANG
Progress in Biochemistry and Biophysics 2025;52(6):1337-1348
Lactylation (Kla), a protein post-translational modification characterized by the covalent conjugation of lactyl groups to lysine residues in proteins, is widely present in living organisms. Since its discovery in 2019, it has attracted much attention for its role in regulating major pathological processes such as tumorigenesis, neurodegenerative diseases, and cardiovascular diseases. By mediating core biological processes such as signal transduction, epigenetic regulation, and metabolic homeostasis, lactylation contributes to disease progression. However, the lactylation donor lactyl-CoA has a low intracellular concentration, and the specific enzyme catalyzing lactylation is not yet clear, which has become an urgent issue in lactate research. A groundbreaking study in 2024 found that alanyl-transfer t-RNA synthetase 1/2 (AARS1/2), members of the aminoacyl-tRNA synthetase (aaRS) family, can act as protein lysine lactate transferases, modifying histones and metabolic enzymes directly with lactate as a substrate, without relying on the classical substrate lactyl-CoA, promoting a new stage in lactate research. Although exercise significantly increases lactate levels in the body and can induce changes in lactylation in multiple tissues and cells, the regulation of lactylation by exercise is not entirely consistent with lactate levels. Research has found that high-intensity exercise can induce upregulation of lactate at 37 lysine sites in 25 proteins of adipose tissue, while leading to downregulation of lactate at 27 lysine sites in 22 proteins. The level of lactate is not the only factor regulating lactylation through exercise. We speculate that the lactate transferase AARS1/2 play an important role in the process of lactylation regulated by exercise, and AARS1/2 should also be regulated by exercise. This review introduces the molecular biology characteristics, subcellular localization, and multifaceted biological functions of AARS, including its canonical roles in alanylation and editing, as well as its newly identified lactate transferase activity. We detail the discovery of AARS1/2 as lactylation catalysts and the specific process of them as lactate transferases catalyzing protein lactylation. Furthermore, we discuss the pathophysiological significance of AARS in tumorigenesis, immune dysregulation, and neuropathy, with a focus on exploring the expression regulation and possible mechanisms of AARS through exercise. The expression of AARS in skeletal muscle regulated by exercise is related to exercise time and muscle fiber type; the skeletal muscle AARS2 upregulated by long-term and high-intensity exercise catalyzes the lactylation of key metabolic enzymes such as pyruvate dehydrogenase E1 alpha subunit (PDHA1) and carnitine palmitoyltransferase 2 (CPT2), reducing exercise capacity and providing exercise protection; physiological hypoxia caused by exercise significantly reduces the ubiquitination degradation of AARS2 by inhibiting its hydroxylation, thereby maintaining high levels of AARS2 protein and exerting lactate transferase function; exercise induced lactate production can promote the translocation of AARS1 cytoplasm to the nucleus, exert lactate transferase function upon nuclear entry, regulate histone lactylation, and participate in gene expression regulation; exercise induced lactate production promotes direct interactions between AARS and star molecules such as p53 and cGAS, and is widely involved in the occurrence and development of tumors and immune diseases. Elucidating the regulatory mechanism of exercise on AARS can provide new ideas for improving metabolic diseases and promote health through exercise.
6.Effects of Shugan jieyu capsules on the pharmacokinetics of voriconazole,rivaroxaban and apixaban in rats
Ying LI ; Chunhui SHAN ; Yizhen SONG ; Yinling MA ; Zhi WANG ; Caihui GUO ; Zhanjun DONG
China Pharmacy 2025;36(12):1470-1475
OBJECTIVE To investigate the effects of multiple doses of Shugan jieyu capsules on the pharmacokinetics of voriconazole, rivaroxaban and apixaban in rats. METHODS Male SD rats were randomly divided into voriconazole group (30 mg/kg), rivaroxaban group (2 mg/kg), apixaban group (0.5 mg/kg), Shugan jieyu capsules+voriconazole group (145 mg/kg+30 mg/kg), Shugan jieyu capsules+rivaroxaban group (145 mg/kg+2 mg/kg), Shugan jieyu capsules+apixaban group (145 mg/kg+0.5 mg/kg), with 6 rats in each group. After the rats in each group were consecutively administered solvent (0.5% sodium carboxymethyl cellulose solution) or Shugan jieyu capsules by intragastric gavage for 8 days, they were respectively given voriconazole, rivaroxaban and apixaban solution by intragastric gavage on the 8th day. Blood samples were then collected at different time points (in voriconazole group, rivaroxaban group and corresponding drug combination groups, blood was collected before administration and at 0.17, 0.34, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-administration; in apixaban group and corresponding drug combination group, blood was collected before administration and at 0.08, 0.17, 0.25, 0.34, 0.5, 0.75, 1, 3, 5, 7, 10 and 12 hours post-administration). Ultra-high performance liquid chromatography-tandem mass spectrometry method was employed to determine the mass concentrations of voriconazole, rivaroxaban and apixaban in rat plasma. The main pharmacokinetic parameters of these drugs were calculated using a non-compartmental model, and the comparisons were made between groups. RESULTS Compared with single drug group, after multiple administrations of Shugan jieyu capsules, AUC0-t, AUC0-∞ and cmax of voriconazole were significantly decreased, while CLz/F was significantly increased, and tmax was also significantly prolonged (P<0.05). For rivaroxaban and apixaban, their tmax values were both significantly prolonged (P<0.05). However, there were no statistically significant differences in the other pharmacokinetic parameters between the two groups (P>0.05). CONCLUSIONS The combination of Shugan jieyu capsules can decrease the exposure, increase the clearance, and delay the peak concentration of oral voriconazole. However, it does not affect the exposure levels of rivaroxaban and apixaban, but it does delay the time to reach peak concentration for both drugs.
7.Non-suicidal self-injury behavior in adolescents: the impact of mobile phone social media dependence and related factors
Honghui WEI ; Ying ZHANG ; Ningning SUN ; Yue WANG ; Yang LI
Sichuan Mental Health 2025;38(3):211-216
BackgroundNon-suicidal self-injury (NSSI) behaviors are prevalent among adolescents, significantly affecting their physical and mental well-being. Understanding the risk factors associated with adolescent NSSI is crucial for prevention. Previous studies have identified mobile phone dependence as a risk factor for NSSI in adolescents. However, as a key form of mobile phone dependence, the evidence regarding the impact of mobile phone social media dependence on adolescent NSSI behavior remains insufficient. ObjectiveTo explore the impact of mobile phone social media dependence and its associated factors on adolescent NSSI behavior, so as to provide references for intervention strategies targeting NSSI in adolescents. MethodsA total of 100 adolescents diagnosed with NSSI according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), and receiving treatment at Tongde Hospital of Zhejiang Province from January 2022 to December 2023 were included in the study group. Concurrently, 100 age- and sex-matched students from Hangzhou were recruited as the control group. Assessments were conducted using Ottawa Self-injury Inventory(OSI) Function Subscale and Addiction Features Subscale, Adolescents Self-Harm Scale(ASHS), and Mobile Phone Social Media Dependence Questionnaire. Multiple linear regression was used to analyze the factors influencing NSSI behaviors. ResultsThe research group had a total of 99 patients (99.00%) who completed the study, while the control group consisted of 97 (97.00%) adolescents who finished this research.The study group had statistically significantly higher total scores on the Mobile Phone Social Media Dependence Questionnaire, as well as higher scores on the conflict and withdrawal dimensions, compared with control group(t=-3.061, -2.874, -2.368, P<0.05 or 0.01). The study group also scored significantly higher on the OSI Function Subscale for internal emotion regulation, social influence, external emotion regulation, and sensation-seeking factors, as well as on the OSI Addiction Features Subscale scores, compared to the control group(t=-22.249, -8.854, -17.968, -10.591, -20.157, P<0.01). OSI Function Subscale scores were positively correlated with Mobile Phone Social Media Dependence Questionnaire scores (r=0.321, P<0.01), and OSI Addiction Features Subscale scores were positively correlated with Mobile Phone Social Media Dependence Questionnaire scores (r=0.282, P<0.01). ASHS scores were positively correlated with Mobile Phone Social Media Dependence Questionnaire scores (r=0.145, P<0.05). Multiple linear regression analysis showed that compulsivity (β=0.416, P<0.01) and conflict (β=0.256, P<0.05) were significant predictors for adolescent NSSI behaviors. ConclusionAdolescent NSSI behaviors are associated with mobile phone social media dependence. The compulsivity and conflict dimension of mobile phone social media dependence are influencing factors for adolescent NSSI behaviors. The higher level of the compulsivity and conflict are associated with an increased risk of the NSSI behaviors in adolescents. [Funde by Zhejiang Medical and Health Science and Technology Plan Project in 2022 (number, 2022KY704]
8.Effects of music assisted drug treatment on behavioral and psychological symptoms and cognitive function in the elderly with moderate to severe dementia
Cairun LUO ; Hongyan MI ; Ying YANG ; Jiaqi LI ; Xiaobin YANG
Sichuan Mental Health 2025;38(3):235-240
BackgroundWith the acceleration of population aging in China, studies have documented an increased prevalence of dementia in the elderly. Behavioral and psychological symptoms and impaired cognitive function are important problems affecting the quality of life in the elderly with dementia. It has been noted that there are certain limitations on the management of problems mentioned above by drug treatment alone, while its combination with music intervention is emerging as an effective approach. However, the application of this approach in the elderly with moderate to severe dementia is still in its relative infancy. ObjectiveTo investigate the effect of music assisted drug treatment on behavioral and psychological symptoms and cognitive function in the elderly with moderate to severe dementia, so as to provide insights for the development of effective intervention. MethodsA randomized controlled study was utilized to enroll a coherent of 43 elderly patients with moderate to severe dementia who were hospitalized in Geriatric Psychiatry of Deyang Mental Health Center from January to July 2023 and met the International Classification of Diseases, tenth edition (ICD-10) diagnostic criteria for dementia. Eligible subjects were divided into study group (n=22) and control group (n=21) based on random allocation using SPSS 26.0. Both groups received routine drug treatment and nursing care, while the study group added music intervention, which consisted of two 30-minute sessions per week for 8 weeks. Neuro Psychiatric Inventory (NPI) and Mini-Mental State Examination (MMSE) were administered to all patients before and after intervention. ResultsA total of 36 patients completed the study, including 20 case in study group and 16 case in control group. No statistical difference was noted in baseline NPI score and MMSE score between two groups (P>0.05). After intervention, study group reported a statistical reduction in NPI total score [58.00 (49.00, 79.25) vs. 78.50 (55.00, 95.50), Z=-3.902, P<0.01)] along with a clinically unremarkable increase in MMSE score (P>0.05) compared with baseline data. After intervention, NPI total score and scores on sub-domains including agitation/aggression, depression/dysphoria, anxiety and aberrant motor behavior were all significantly lower in study group than those in control group (Z=-2.183, -2.438, -2.691, -3.716, -2.250, P<0.05 or 0.01), while there was no significant difference in MMSE score between two groups (P>0.05). ConclusionMusic assisted drugintervention may ameliorate behavioral and psychological symptoms in the elderly with moderate to severe dementia, while no significant improvement is documented on cognitive function. [Fund by the "14th Five Year Plan" for Philosophy and Social Sciences Research in Deyang (number, DY232C002)]
9.Impact of prenatal triclosan exposure on ADHD-like symptoms in school-aged children
Jingjing LI ; Xiaomeng CHENG ; Yan ZHANG ; Luanluan LI ; Xiaodan YU ; Ying TIAN ; Yu GAO
Journal of Environmental and Occupational Medicine 2025;42(6):645-651
Background Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental and behavioral disorder in children, often diagnosed during school age. The etiology of ADHD remains unclear; however, existing studies suggest that environmental factors, such as exposure to triclosan (TCS), may be associated with the occurrence of ADHD-like symptoms in offspring. Nevertheless, relevant research in China remains limited. Objective To investigate the impact of early pregnancy TCS exposure on ADHD-like symptoms in 7-year-old children. Methods This study was based on the Shanghai Birth Cohort (SBC) and included 662 mother-child pairs. TCS concentrations in early pregnancy urine samples were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Demographic information was collected via questionnaires and medical record abstraction. ADHD-like symptoms in 7-year-old children were first assessed using the Strengths and Difficulties Questionnaire (SDQ). Further differentiation of ADHD-like symptom subtypes (inattentive and hyperactive/impulsive) was conducted using the SNAP-IV, a clinically validated ADHD screening tool. Negative binomial regression models were applied to evaluate the associations between prenatal TCS exposure and hyperactive behavior (SDQ assessment) as well as ADHD-like symptom subtypes (SNAP-IV assessment) in 7-year-old children. Results The positive rate of TCS in early pregnancy urine samples was 91.39%, with median concentrations of 0.69 μg·L−1 and 0.63 μg·g−1 before and after the creatinine adjustment, respectively. The modeling results indicated that prenatal TCS exposure was associated with an increased risk of hyperactive symptoms (SDQ assessment) in 7-year-old children (RR=1.04, 95%CI: 1.02, 1.06); the stratified analyses by children sex revealed similar effects for both boys (RR=1.04, 95%CI: 1.02, 1.07) and girls (RR=1.04, 95%CI: 1.01, 1.07). Further analysis of ADHD-like symptom subtypes showed that prenatal TCS exposure increased the risk of inattentive symptoms (RR=1.03, 95%CI: 1.00, 1.05); the sex-stratified analyses indicated associations between TCS exposure and inattentive symptoms (RR=1.03, 95%CI: 1.00, 1.07) as well as hyperactive/impulsive symptoms (RR=1.04, 95%CI: 1.01, 1.08) in girls. Conclusion Prenatal TCS exposure is associated with an increased risk of ADHD-like symptoms in 7-year-old children, primarily contributing to the risk of the inattention subtype. The impact is more pronounced in girls.
10.Analysis of the nonlinear relationship between hypothermic machine perfusion parameters and delayed graft function and construction of an optimized predictive model based on sampling algorithms
Boqing DONG ; Chongfeng WANG ; Yuting ZHAO ; Huanjing BI ; Ying WANG ; Jingwen WANG ; Zuhan CHEN ; Ruiyang MA ; Wujun XUE ; Yang LI ; Xiaoming DING
Organ Transplantation 2025;16(4):582-590
Objective To analyze the nonlinear relationship between hypothermic machine perfusion (HMP) parameters and delayed graft function (DGF) and optimize the construction of a predictive model for DGF. Methods The data of 923 recipients who underwent kidney transplantation from deceased donors were retrospectively analyzed. According to the occurrence of DGF, the recipients were divided into DGF group (n=823) and non-DGF group (n=100). Donor data, HMP parameters and recipient data were analyzed for both groups. The nonlinear relationship between HMP parameters and the occurrence of DGF was explored based on restricted cubic splines (RCS). Over-sampling, under-sampling and balanced sampling were used to address the imbalance in the proportion of DGF to construct logistic regression predictive models. The area under the curve (AUC) of each model was compared in the validation set, and a nomogram model was constructed. Results Donor BMI, cold ischemia time of the donor kidney, and HMP parameters (initial and final pressures, resistance, and perfusion time) were significantly different between the DGF and non-DGF groups (all P<0.05). The RCS analysis revealed a threshold-like nonlinear relationship between HMP parameters and the risk of DGF. Among the models constructed using different sampling methods, the balanced sampling model had the highest AUC. Using this model, a nomogram was constructed to stratify recipients based on risk scores. Recipients in the high-risk group had higher serum creatinine levels at 1, 6, and 12 months after kidney transplantation compared to those in the low-risk group (all P<0.05). Conclusions There is a nonlinear relationship between HMP parameters and the risk of DGF, and the threshold is helpful for organ quality assessment and monitoring of graft function after transplantation. The predictive model for DGF constructed on the base of balanced sampling algorithms helps perioperative decision-making and postoperative graft function monitoring of kidney transplantation.

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