1.Zuogui Wan Improve Ovarian Inflammatory Microenvironment and Stemness of Ovarian Germline Stem Cells in Ovarian Aging via cGAS/STING Signaling Pathway
Yunling ZHENG ; Xinyi PAN ; Zuang LI ; Yixuan WANG ; Junyi AN ; Yuxin ZOU ; Mengting XIAO ; Zheng CHEN ; Ling ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):1-10
ObjectiveTo investigate the mechanism of Zuogui Wan (ZGW) in improving ovarian inflammatory microenvironment and stemness of ovarian germline stem cells (OSCs) for treating ovarian aging via the cyclic guanosine monophosphate/adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. MethodsForty C57BL/6 female mice were randomly divided into a blank group, a model group, a low-dose ZGW group (2.7 g·kg-1), a high-dose ZGW group (5.4 g·kg-1), and an estradiol valerate group (0.15 mg·kg-1), with 8 mice in each group. Except the blank group, all other groups received a single intraperitoneal injection of cyclophosphamide at 120 mg·kg-1 to establish an ovarian aging mouse model. After successful modeling, each group was continuously administered for 4 weeks, once daily. The physiological status of the mice was observed, and the ovarian index was calculated. The estrus cycle of the mice was monitored. Hematoxylin-eosin (HE) staining was used to observe pathological changes in ovarian tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum sex hormone levels. Serum inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and mouse interleukin-6 (IL-6) levels were detected using kits. Western blot was used to detect the protein expression of ovarian cGAS, STING, p-STING, TANK-binding kinase 1 (TBK1), p-TBK1, interferon-induced transmembrane protein 3 (Fragilis), and Vasa homolog protein (MVH). Quantitative real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of inflammatory factors in ovarian tissue. Immunofluorescence double labeling was performed to locate OSCs in ovarian tissues, and fluorescence intensities of OSCs markers MVH and octamer binding transcription factor 4 (Oct4) were calculated. ResultsCompared with the blank group, the model group showed reduced body weight, ovarian wet weight, and ovarian index (P<0.01) and a disordered estrus cycle (P<0.01). In addition, the levels of serum follicle-stimulating hormone (FSH), TNF-α, IL-6, and IL-1β were increased (P<0.01), while anti-Müllerian hormone (AMH) and estradiol (E2) levels were decreased (P<0.01). The protein expression of cGAS, p-STING/STING, and p-TBK1/TBK1 in ovarian tissue was increased (P<0.05, P<0.01), while that of OSCs stemness factors MVH and Fragilis was reduced (P<0.01). Immunofluorescence indicated a reduction in MVH and Oct4 expression in OSCs (P<0.01). The mRNA expression of inflammatory factors TNF-α, IL-6, and IL-1β in ovarian tissue was increased (P<0.05, P<0.01). Compared with the model group, the treatment groups exhibited improved body weight, ovarian wet weight, and ovarian index (P<0.05) and a reduced rate of estrus cycle disorder (P<0.05, P<0.01). The levels of serum FSH, TNF-α, IL-6, and IL-1β were decreased (P<0.05, P<0.01), while AMH and E2 levels were increased (P<0.01). The protein expression levels of cGAS, p-STING/STING, and p-TBK1/TBK1 in ovarian tissue were decreased (P<0.05), while the protein expression of MVH and Fragilis was increased (P<0.05), and the fluorescence intensities of MVH and Oct4 were increased (P<0.05, P<0.01). The mRNA expression of inflammatory factors in ovarian tissue was decreased (P<0.05). ConclusionZGW alleviate ovarian inflammatory response, regulate ovarian microenvironment homeostasis, and maintain stemness of OSCs in ovarian aging mice probably by modulating the cGAS-STING signaling pathway, thereby improving ovarian function and delaying ovarian aging.
2.Network analysis of basic psychological needs and psychological behavioral problems among junior and senior high school students in Taizhou City
LIN Nan, LI Li, FU Chaowei, LIN Haijiang, YANG Yuting, LIU Yixuan, WANG Tingting, WANG Jingyi
Chinese Journal of School Health 2026;47(3):388-393
Objective:
To explore the network structure of middle school students basic psychological needs and psychological behavioral problems, and identify the core nodes within the network, as well as examine demographic subgroup differences, so as to provide support for targeted mental health interventions for adolescents.
Methods:
In September and October of 2023, a total of 2 000 junior and senior high school students were selected with multistage cluster random sampling from 8 schools in Jiaojiang District and Tiantai County, Taizhou City. An online self administered questionnaire was used to assess emotional and behavioral problems, perceived autonomy, self awareness, loneliness, and social support. The instruments included the Strengths and Difficulties Questionnaire (SDQ), Perceived Choice and Awareness of Self Scale (PCASS), Mental Health Literacy Questionnaire (MHLQ), University of California,Los Angeles Loneliness Scale (UCLA-LS), and the Multidimensional Scale of Perceived Social Support (MSPSS). A network analysis approach was employed to construct a network representing adolescents basic psychological needs and psychological behavioral problems, focusing on centrality measures and demographic subgroup differences.
Results:
A total of 418 students (20.9%) reported abnormal emotional and behavioral problems. Perceived autonomy and competence were negatively correlated with emotional problems (weights: 0.12, 0.14) and hyperactivity (weights: 0.10, 0.16). Social support showed negative correlation with peer relationship issues, hyperactivity, and conduct problems (weights: 0.16, 0.13, 0.10). Loneliness was positively correlated with emotional symptoms and peer relationship problems (weights: 0.28, 0.18). In the overall network, perceived relationships (social support and loneliness), emotional symptoms, and hyperactivity emerged as central nodes. Significant differences in network structure were observed between gender subgroups ( P =0.02). Girls internalizing issues were more influenced by loneliness and perceived autonomy frustration, while social support exhibited higher centrality in boys.
Conclusions
Perceived relationships, emotional problems, and hyperactivity are key nodes in the network of adolescents basic psychological needs and psychological behavioral problems. Loneliness demonstrates a prominent influence within the network, and the overall network exhibits gender differences.
3.Analysis of hepatitis B infection characteristics in HBsAg-/HBV DNA+ blood donors in Taiyuan
Zhiye LI ; Baifeng SHAN ; Liuming ZHANG ; Yixuan LI ; Aichun CHU ; Weiyu YUAN ; Lixia DOU ; Qiang ZHANG ; Yuan BAI ; Yuan ZHOU
Chinese Journal of Blood Transfusion 2026;39(3):373-378
Objective: To analyze characteristics of hepatitis B infection in HBsAg-/HBV DNA+ blood donors in Taiyuan, so as to provide evidence for adjusting blood screening strategies. Methods: Blood samples of HBsAg-/HBV DNA+ donors were tested using enzyme-linked immunosorbent assay (ELISA), chemiluminescence assay, nucleic acid qualitative test, and nucleic acid quantitative test. Data on HBsAg-/HBV DNA+ donors in Taiyuan region from January 1, 2016 to December 31, 2024 were statistically analyzed to evaluate the detection rate, demographic characteristics, influencing factors of detection rate, nucleic acid quantitative results, and serological patterns of HBsAg-/HBV DNA+ donors. Results: From January 1, 2016 to December 31, 2024, 991 565 donor samples underwent nucleic acid testing in Taiyuan. A total of 309 HBsAg-/HBV DNA+ samples were detected, resulting in an HBsAg-/HBV DNA+ detection rate of 3.12 per 10 000. The detection rate varied significantly across different years (P<0.05). Males had a significantly higher HBsAg-/HBV DNA+ detection rate than females, first-time donors had a higher rate than repeat donors, and whole blood donors had a higher rate than apheresis donors (P<0.05). The detection rate also differed significantly among age groups (P<0.05). Logistic regression analysis showed that gender, age, donation frequency, and donation type were all influencing factors for HBsAg-/HBV DNA+ detection (all P<0.05). The predominant serological patterns among HBsAg-/HBV DNA+ donors were HBsAb+/HBcAb+ (43.69%, 135/309) or HBcAb+ alone (24.27%, 75/309). Viral load was detectable in 53.40% (165/309) of the HBsAg-/HBV DNA+ donors. Among these, 61.21% (101/165) donors had a viral load<20 IU/mL, and 94.55% (156/165) had a viral load<200 IU/mL. Donors with viral load<200 IU/mL primarily exhibited HBsAb+/HBcAb+ (41.67%, 65/156) or HBcAb+alone (36.54%, 57/156) serological patterns. Conclusion: The prevalence of HBsAg-/HBV DNA+ is low among blood donors in Taiyuan. Higher detection rates were observed in the 46-55 years age group, males, first-time donors, and whole blood donors. HBsAg-/HBV DNA+ donors exhibit specific serological patterns and generally have low viral loads, indicating a potential residual transfusion risk. It is recommended to add HBcAb testing, together with high-sensitivity nucleic acid testing technologies and donor follow-up, to ensure blood safety and guide donor reentry.
4.Study on the safety and efficacy of micro-perfusion device for preserving isolated porcine limbs
Pengkai LI ; Zhaodi MI ; Shen LI ; Man YUAN ; Xiwei PENG ; Jia LÜ ; Sice WANG ; Zhibo JIA ; Xiangyu SONG ; Yixuan ZHU ; Chonghui LI ; Moling XIAO ; Wenjing XU ; Jiang PENG
Organ Transplantation 2026;17(3):422-431
Objective To evaluate the safety and efficacy of a self-developed micro-normothermic machine perfusion (NMP) system (micro-perfusion device) for preserving isolated porcine limbs. Methods Five healthy Landrace pigs were selected, and their left and right forelimbs were randomly divided into the NMP group and static cold storage (SCS) group. The NMP group was perfused with the self-developed micro-perfusion device and polymerized hemoglobin perfusate for 32 hours at normothermia, while the SCS group was preserved at 4 ℃. Hemodynamic parameters such as perfusion pressure and flow were monitored. The pH value, partial pressure of oxygen (PO2), lactic acid (Lac), creatine kinase (CK) and lactate dehydrogenase (LDH) in the perfusate were measured. Hematoxylin-eosin staining was used to assess the muscle tissue structure, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was employed to evaluate muscle cell apoptosis, and immunohistochemistry staining was applied to detect the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6. A mixed-effects model was used to analyze the effects of time and treatment methods on tissue structure, cell apoptosis and inflammatory factors. Results The device could stably maintain a perfusion pressure of (69±15) mmHg and a flow rate of (117±42) mL/min. The pH value and electrolytes of the perfusate were generally stable, with PO2 maintained at a high level. Lac was maintained at 5.38(3.81, 6.45) mmol/L, while CK and LDH increased over time. After 32 hours of perfusion in the NMP group, both the myocyte spacing and apoptosis rate were better than those in the SCS group. Mixed-effects model analysis showed that there were statistically significant differences in the effects of NMP treatment and SCS treatment on myocyte spacing and apoptosis rate per unit time (both P < 0.05). There were no statistically significant differences in TNF-α and IL-6 between the two groups, and mixed-effects model analysis showed no statistically significant differences in the effects of NMP treatment and SCS treatment on TNF-α and IL-6 per unit time (both P > 0.05). Conclusions The micro-perfusion device used in this study may achieve 32-hour normothermic preservation in a porcine limb amputation model, maintain basic metabolism and ionic homeostasis, reduce muscle structural damage and cell apoptosis without inducing additional inflammatory responses. This technology is expected to significantly extend the time window for replantation of amputated limbs in disaster rescue and long-distance transportation, providing an important technical basis for clinical translation and subsequent replantation research.
5.Development and Validation of a High-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Detecting Adrenocortical Hormones and Establishment of Age-Stratified Reference Intervals in Reproductive-Aged Women from Guangxi, China
Yixuan LIU ; Tingwei JIN ; Yushuang WEI ; Xuelian QIN ; Siyu DENG ; Jie ZHENG ; Boteng YAN ; Yuanyuan NONG ; Yu YE ; Shengzhu HUANG ; Yu LONG ; Jianmin LI ; Ganqin WANG ; Pei HUANG ; Jinghang JIANG ; Fan WU ; Zengnan MO ; Yonghua JIANG
Annals of Laboratory Medicine 2026;46(2):146-154
Background:
Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications.
Methods:
A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated.
Results:
The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels.
Conclusions
We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.
6.Fangji Fulingtang Attenuates Myocardial Fibrosis by Regulating Mitochondrial Function Through AMPK/PGC-1α/MFN2-PKM2 Signaling Pathway
Xuqin DU ; Yixuan LI ; Yuxia JIN ; Hongding LI ; Ruogu YANG ; Lipeng SHI ; Yi REN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):1-10
ObjectiveTo investigate the effects and mechanisms of Fangji Fulingtang (FFD) on mitochondrial function in the mouse model of myocardial fibrosis (MF). MethodsSixty SPF-grade male C57BL/6J mice were randomly allocated into six groups (n=10 per group): control, model, low-dose, medium-dose, and high-dose (3.315, 6.63, and 13.26 g·kg-1, respectively) FFD, and captopril (20 mg·kg-1). MF was induced by subcutaneous injection of isoproterenol (10 mg·kg-1·d-1) in other groups except the control group for 14 consecutive days, with simultaneous gavage of corresponding drugs. Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured by echocardiography. Serum levels of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-pro BNP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were measured by biochemical assays. Reactive oxygen species (ROS) were detected by dihydroethidium (DHE) fluorescence staining. Hematoxylin-eosin (HE), Masson's trichrome, and wheat germ agglutinin (WGA) staining were performed to evaluate myocardial structure and fibrosis. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy, adenosine triphosphate (ATP) colorimetric assay, and JC-1 fluorescence staining. The protein levels of phosphorylated adenosine monophosphate-activated protein kinase α subunit (p-AMPKα), AMPKα, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitofusin 2 (MFN2), pyruvate kinase M2 isoform (PKM2), lactate dehydrogenase A (LDHA), and hypoxia-inducible factor 1 alpha (HIF-1α) were analyzed by Western blot. ResultsCompared with the control group, the model group exhibited decreased LVEF and LVFS, increased heart weight index and heart weight-to-tibia length ratio (P<0.01), elevated levels of myocardial injury markers (CK-MB, cTnI, and NT-pro BNP), inflammatory cytokines (TNF-α, IL-1β, and IL-6), and MDA, along with reduced SOD and GSH levels (P<0.01). Enhanced interstitial collagen deposition and cardiomyocyte hypertrophy were observed in the model group (P<0.01). Transmission electron microscopy and JC-1 staining revealed mitochondrial swelling, crista disruption, decreased ATP content, and reduced red/green fluorescence ratio in the model group (P<0.01). Western blot analysis demonstrated downregulation of p-AMPKα, PGC-1α, and MFN2 and upregulation of PKM2, LDHA, and HIF-1α in the model group (P<0.01). Compared with the model group, treatment with FFD or captopril improved LVEF and LVFS, reduced heart weight index and heart weight-to-tibia length ratio (P<0.05, P<0.01), lowered the serum levels of CK-MB, cTnI, NT-pro BNP, TNF-α, IL-1β, IL-6, and MDA, increased the SOD and GSH levels (P<0.05, P<0.01), attenuated the myocardial fibrosis and cardiomyocyte hypertrophy (P<0.01), and restored the mitochondrial ultrastructure. The medium and high-dose FFD groups as well as the captopril group showed increased ATP production and red/green fluorescence ratio (P<0.05, P<0.01). Furthermore, FFD upregulated the expression of p-AMPKα and PGC-1α while downregulating the expression of LDHA and HIF-1α (P<0.05, P<0.01). ConclusionFFD activates the AMPK/PGC-1α/MFN2 signaling pathway and inhibits the PKM2/LDHA/HIF-1α axis to restore mitochondrial function and energy metabolic homeostasis, thereby attenuating isoproterenol-induced myocardial fibrosis.
7.Effect of Zhishi Daozhi Formula (枳实导滞方) on Intestinal Flora and TLR4/MyD88/NF-κB Signaling Pathway in Rats with Sepsis-Induced Gastrointestinal Dysfunction
Chenyu LIU ; Changhui LI ; Haoyang CHENG ; Zhiyang TIAN ; Yixuan LIU ; Jiuzhuo TIAN
Journal of Traditional Chinese Medicine 2026;67(18):2003-2010
ObjectiveTo investigate the effect and potential mechanism of Zhishi Daozhi Formula (枳实导滞方, ZDF) on inflammation in rats with sepsis-induced gastrointestinal dysfunction based on the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF‑κB) signaling pathway and intestinal flora. MethodsSixty SD rats were randomly divided into sham‑operation group, model group, ulinastatin group, and low‑, medium‑ and high‑dose ZDF groups, with 10 rats in each group. Except for the sham‑operation group, the rat model of sepsis‑induced gastrointestinal dysfunction was established by cecal ligation and puncture (CLP). Three days before modeling and 12 h after modeling, the low-, medium- and high-dose ZDF groups were intragastrically administered with ZDF solution at doses of 3.80, 7.60 and 15.20 g·kg⁻¹·d⁻¹, respectively. The ulinastatin group received intraperitoneal injection of ulinastatin at 100,000 U/kg, while the sham-operation and model groups were given normal saline at 1 ml/100 g by gavage. All interventions were performed once daily for 4 consecutive days. Tow hours after the last intervention, gastric emptying rate and small intestinal propulsion rate were detected. Gastrointestinal function indicators including D‑lactic acid (D‑LA) and intestinal fatty acid binding protein (i‑FABP), as well as inflammatory indicators including procalcitonin (PCT) and C‑reactive protein (CRP) were measured by ELISA 24 h after modeling. The counts of Escherichia coli, Bifidobacterium and Lactobacillus in the intestine were compared. The histopathological morphological changes of the rat intestinal mucosa were observed by HE staining. The protein and mRNA expressions of IκB kinase (Ikk), TLR4, MyD88 and NF‑κB in ileal tissues were detected by western blot and qRT‑PCR, respectively. ResultsCompared to the sham-operation group, the model group showed decreased gastric emptying rate and small intestinal propulsion rate, increased intestinal Escherichia coli count, elevated serum D‑LA, i‑FABP, PCT and CRP levels, increased protein and mRNA expressions of Ikk, TLR4, MyD88 and NF-κB in ileal tissue, decreased counts of Lactobacillus and Bifidobacterium (P<0.05), accompanied by obvious pathological injury of ileal mucosa. Compared to the model group, all medication groups exhibited significant improvements in the above mentioned indicators and alleviated intestinal mucosal injury (P<0.05). Compared to the ulinastatin group, except for D-LA in the medium-dose ZDF group, the differences in the above indicators between the low- and medium-dose ZDF groups were statistically significant (P<0.05), while the differences between the high-dose ZDF group and the ulinastatin group were not statistically significant (P>0.05). With increasing dosage, the gastric emptying rate, small intestinal propulsion rate, Lactobacillus and Bifidobacterium counts in the rats of all three ZDF groups increased, while the levels of serum D-LA, PCT, CRP, and i-FABP, the protein levels of Ikk, TLR4, MyD88, and NF-κB in intestinal tissue, and the Escherichia coli count decreased (P<0.05). ConclusionZDF can ameliorate intestinal mucosal injury, maintain intestinal flora balance and inhibit inflammatory response in rats with sepsis‑induced gastrointestinal dysfunction, with the high-dose group showing the best efficacy, which may be achieved by down‑regulating the TLR4/MyD88/NF-κB signaling pathway.
8.Fangji Fulingtang Attenuates Myocardial Fibrosis by Regulating Mitochondrial Function Through AMPK/PGC-1α/MFN2-PKM2 Signaling Pathway
Xuqin DU ; Yixuan LI ; Yuxia JIN ; Hongding LI ; Ruogu YANG ; Lipeng SHI ; Yi REN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):1-10
ObjectiveTo investigate the effects and mechanisms of Fangji Fulingtang (FFD) on mitochondrial function in the mouse model of myocardial fibrosis (MF). MethodsSixty SPF-grade male C57BL/6J mice were randomly allocated into six groups (n=10 per group): control, model, low-dose, medium-dose, and high-dose (3.315, 6.63, and 13.26 g·kg-1, respectively) FFD, and captopril (20 mg·kg-1). MF was induced by subcutaneous injection of isoproterenol (10 mg·kg-1·d-1) in other groups except the control group for 14 consecutive days, with simultaneous gavage of corresponding drugs. Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured by echocardiography. Serum levels of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-pro BNP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were measured by biochemical assays. Reactive oxygen species (ROS) were detected by dihydroethidium (DHE) fluorescence staining. Hematoxylin-eosin (HE), Masson's trichrome, and wheat germ agglutinin (WGA) staining were performed to evaluate myocardial structure and fibrosis. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy, adenosine triphosphate (ATP) colorimetric assay, and JC-1 fluorescence staining. The protein levels of phosphorylated adenosine monophosphate-activated protein kinase α subunit (p-AMPKα), AMPKα, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitofusin 2 (MFN2), pyruvate kinase M2 isoform (PKM2), lactate dehydrogenase A (LDHA), and hypoxia-inducible factor 1 alpha (HIF-1α) were analyzed by Western blot. ResultsCompared with the control group, the model group exhibited decreased LVEF and LVFS, increased heart weight index and heart weight-to-tibia length ratio (P<0.01), elevated levels of myocardial injury markers (CK-MB, cTnI, and NT-pro BNP), inflammatory cytokines (TNF-α, IL-1β, and IL-6), and MDA, along with reduced SOD and GSH levels (P<0.01). Enhanced interstitial collagen deposition and cardiomyocyte hypertrophy were observed in the model group (P<0.01). Transmission electron microscopy and JC-1 staining revealed mitochondrial swelling, crista disruption, decreased ATP content, and reduced red/green fluorescence ratio in the model group (P<0.01). Western blot analysis demonstrated downregulation of p-AMPKα, PGC-1α, and MFN2 and upregulation of PKM2, LDHA, and HIF-1α in the model group (P<0.01). Compared with the model group, treatment with FFD or captopril improved LVEF and LVFS, reduced heart weight index and heart weight-to-tibia length ratio (P<0.05, P<0.01), lowered the serum levels of CK-MB, cTnI, NT-pro BNP, TNF-α, IL-1β, IL-6, and MDA, increased the SOD and GSH levels (P<0.05, P<0.01), attenuated the myocardial fibrosis and cardiomyocyte hypertrophy (P<0.01), and restored the mitochondrial ultrastructure. The medium and high-dose FFD groups as well as the captopril group showed increased ATP production and red/green fluorescence ratio (P<0.05, P<0.01). Furthermore, FFD upregulated the expression of p-AMPKα and PGC-1α while downregulating the expression of LDHA and HIF-1α (P<0.05, P<0.01). ConclusionFFD activates the AMPK/PGC-1α/MFN2 signaling pathway and inhibits the PKM2/LDHA/HIF-1α axis to restore mitochondrial function and energy metabolic homeostasis, thereby attenuating isoproterenol-induced myocardial fibrosis.
9.Health literacy prediction models based on machine learning methods: a scoping review
PAN Xiang ; TONG Yingge ; LI Yixuan ; NI Ke ; CHENG Wenqian ; XIN Mengyu ; HU Yuying
Journal of Preventive Medicine 2025;37(2):148-153
Objective:
To conduct a scoping review on the types, construction methods and predictive performance of health literacy prediction models based on machine learning methods, so as to provide the reference for the improvement and application of such models.
Methods:
Publications on health literacy prediction models conducted using machine learning methods were retrieved from CNKI, Wanfang Data, VIP, PubMed and Web of Science from inception to May 1, 2024. The quality of literature was assessed using the Prediction Model Risk of Bias ASsessment Tool. Basic characteristics, modeling methods, data sources, missing value handling, predictors and predictive performance were reviewed.
Results:
A total of 524 publications were retrieved, and 22 publications between 2007 and 2024 were finally enrolled. Totally 48 health literacy prediction models were involved, and 25 had a high risk of bias (52.08%), with major issues focusing on missing value handling, predictor selection and model evaluation methods. Modeling methods included regression models, tree-based machine learning methods, support vector machines and neural network models. Predictors primarily encompassed factors at four aspects: individual, interpersonal, organizational and society/policy aspects, with age, educational level, economic status, health status and internet use appearing frequently. Internal validation was conducted in 14 publications, and external validation was conducted in 4 publications. Forty-two models reported the areas under the receiver operating characteristic curve, which ranged from 0.52 to 0.983, indicating good discrimination.
Conclusion
Health literacy prediction models based on machine learning methods perform well, but have deficiencies in risk of bias, data processing and validation.
10.Effect of miR-130a-3p targeting PPAR-γ on epithelial-mesenchymal transition in silica-induced pulmonary fibrosis
Xiaohui HAO ; Qian LI ; Yixuan JIN ; Qinxin ZHANG ; Yudi WANG ; Fang YANG
Journal of Environmental and Occupational Medicine 2025;42(2):188-195
Background At present, the treatment of silicosis is still limited, and no method is available to cure the disease. miRNAs are involved in the process of fibrosis at the transcriptional level by directly degrading target gene mRNA or inhibiting its translation. However, how miR-130a-3p regulates silicosis fibrosis has not been fully elucidated yet. Objective To investigate whether miR-130a-3p promotes epithelial-mesenchymal transition (EMT) by inhibiting peroxisome proliferators-activated receptors gamma (PPAR-γ), thereby pro-moting the process of silicotic fibrosis. To identify effective new targets for the treatment of silicotic fibrosis. Methods (1) Animal experiments: C57BL/6J mice were intratracheally injected with a one-time dose of 10 mg silica suspension (dissolved in 100 μL saline) as positive lung exposure. A silicosis model group was established 28 d after the exposure. A control group was injected with the same amount of normal saline into the trachea. Hematoxylin-eosin staining and Sirius red staining were used to observe the pathological changes and collagen deposition in lung tissues respectively. Realtime fluorescence-based quantitative polymerase chain reaction (RT-qPCR) was used to assay the expression of miR-130a-3p and PPAR-γ mRNA in lung tissues. Western blotting was used to detect the protein expression of PPAR-γ, transforming growth factor (TGF)-β1, E-cadherin, α-smooth muscle actin (α-SMA), and Collagen Ⅰ in lung tissues. (2) Cells experiments: Mouse lung epithelial cells (MLE-12) were induced with 5 µg·L−1 TGF-β1 for different time (0, 12, 24, 48 h). RT-qPCR was used to detect the expression of miR-130a-3p and PPAR-γ mRNA in cells. The binding relationship between miR-130a-3p and PPAR-γ mRNA was verified by dual luciferase reporter gene assay. MLE-12 cells were stimulated by 5 µg·L−1 TGF-β1 after transfection of miR-130a-3p inhibitor, and Western blotting was used to measure the protein expression of PPAR-γ, E-cadherin, and α-SMA in the TGF-β1-induced cells. Results In the silicosis model group, the alveolar septum was widened and the pulmonary nodules were formed. The Sirius red staining collagen deposition in pulmonary nodules indicated that a silicosis fibrosis model was successfully established. The expressions of TGF-β1, α-SMA, and Collagen Ⅰ proteins were increased, and the expressions of E-cadherin and PPAR-γ proteins were decreased in lung tissues of the silicosis group, compared with the control group (P<0.05 or P<0.01). The expression of miR-130a-3p was increased and the expression of PPAR-γ mRNA was decreased in lung tissues of the silicosis model (P<0.01). The expression of miR-130a-3p was significantly increased, while the expression of PPAR-γ mRNA was decreased in the TGF-β1 induced MLE-12 cells (P<0.05 or P<0.01). The dual luciferase reporter assay showed a direct relationship between miR-130a-3p and PPAR-γ mRNA in MLE-12 cells. The transfection of miR-130a-3p inhibitor in the TGF-β1 induced MLE-12 cells inhibited the decrease of PPAR-γ and E-cadherin proteins, and the increase of α-SMA protein in the MLE-12 cells induced by TGF-β1 (P<0.05 or P<0.01). Conclusion miR-130a-3p promotes the development of silicosis fibrosis by targeting PPAR-γ to increase pulmonary EMT.


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