1.Application of assisted reproductive technology in fertility pre-servation and promotion for women with malignant tumors.
Chunmei MA ; Xiaoling HU ; Shanshan ZHANG ; Lanfeng XING ; Yingwei ZHANG ; Yimin ZHU
Journal of Zhejiang University. Medical sciences 2025;():1-10
OBJECTIVES:
To evaluate the strategies and outcomes of assisted reproductive technology (ART) for fertility preservation and promotion in women with malignant tumors, and to analyze ART outcomes across different tumor types.
METHODS:
We conducted a retrospective analysis of female patients who underwent ART for fertility preservation or treatment at the Reproductive Center of the Women's Hospital, Zhejiang University School of Medicine, between January 1, 2018, and December 31, 2023. A total of 163 ART-aided pregnancy patients with malignant tumors were included in the case group, among which 6 patients underwent embryo cryopreservation for fertility preservation before radiotherapy or chemotherapy. Additionally, 11 unmarried women underwent oocyte cryopreservation due to borderline ovarian tumors, ovarian cancer, breast cancer, or hematological malignancies. The control group was selected from women without a history of malignant tumors who received ART treatment during the same period, using propensity score matching at a ratio of 1∶2, resulting in 326 cases. Data were collected through the reproductive medical record system and telephone follow-up (as of October 31, 2024). Baseline characteristics, controlled ovarian hyperstimulation parameters, laboratory indicators, and pregnancy outcomes were compared between case and control groups and among patients with different tumor types, and the tumor recurrence of the patients was followed up.
RESULTS:
Patients in the case group had significantly lower ovarian reserve (AMH, AFC) and a higher proportion of diminished ovarian reserve compared to the control group (all P<0.01). Regarding the ovulation induction protocol, the proportion of patients using the minimal stimulation protocol in the case group was significantly higher than that in the control group (29.45% vs. 12.88%, P<0.01), and the total dosage of gonadotropins used was lower (P<0.01). In terms of assisted reproductive outcomes, there were no statistically significant differences between the two groups in the number of retrieved oocytes, number of high-quality embryos, fertilization rate, cumulative pregnancy rate, cumulative live birth rate, or miscarriage rate (all P>0.05). However, the number of oocyte retrieval cycles and embryo transfer cycles required to achieve a live birth outcome in the case group were significantly higher than those in the control group (both P<0.05). Subgroup analysis showed that there were no significant differences in cumulative pregnancy rate and live birth rate among patients with different tumor types (thyroid cancer, reproductive system tumors, breast cancer, lung cancer). Nevertheless, lung cancer patients had the lowest ovarian reserve and required the most oocyte retrieval cycles due to their older age; breast cancer patients had a relatively lower fertilization rate partially because some of them were complicated with male factors. A follow-up of 154 tumor patients (with a follow-up rate of 88.5%) revealed that 6 patients (4.20%) had tumor recurrence, and 1 breast cancer patient died due to tumor recurrence. None of the 11 unmarried patients who had undergone oocyte cryopreservation had used the cryopreserved oocytes for assisted pregnancy yet, and 1 patient who had undergone fertility preservation died due to tumor recurrence.
CONCLUSIONS
Women of reproductive age with malignant tumors are at risk of diminished fertility. ART can effectively preserve and promote fertility, enabling favorable pregnancy and live birth outcomes. It is recommended to initiate a multidisciplinary assessment promptly prior to radiotherapy/chemotherapy and formulate an individualized ART regimen for fertility preservation or promotion, so as to achieve reproductive goals or safeguard future fertility potential.
2.Association of metabolic syndrome status change and risk of carotid plaque
Shuang LIU ; Xinlei MIAO ; Ziping SONG ; Xiaoling XIE ; Manling HU ; Yuting SUN ; Fei XU ; Song LENG
Chinese Journal of Endocrinology and Metabolism 2025;41(3):204-211
Objective:To investigate the effect of changes in metabolic syndrome status and persistence on carotid plaque risk.Methods:This retrospective cohort study analyzed individuals who underwent routine health check-ups at the health management center of the Second Affiliated Hospital of Dalian Medical University from 2014 to 2023. Participants with at least three carotid ultrasound records meeting the inclusion criteria were classified into 4 groups based on changes in metabolic status: persistently metabolic health, transitioning from metabolic health to unhealth, transitioning from metabolic unhealth to health, and persistently metabolic unhealth. The cumulative incidence of carotid plaque in these groups was compared. A Cox proportional risk model was used to evaluate the relationship between changes in metabolic syndrome status, the number of metabolic syndrome components, and the risk of carotid plaque development. Restricted cubic spline analysis was applied to explore the association between changes in individual metabolic syndrome components and carotid plaque risk.Results:Compared to the persistently metabolic health group, the persistent unhealth group had the highest risk of developing carotid plaque( HR=1.35, 95% CI 1.05-1.74, P=0.021), followed by those who transitioned from metabolic health to unhealth and those who improved from metabolic unhealth to health. Furthermore, the risk of carotid plaque increased progressively with the number of metabolic syndrome components. Restricted cubic spline analysis revealed a nonlinear relationship between fasting blood glucose change and carotid plaque risk, while systolic blood pressure, diastolic blood pressure, waist circumference, triglycerides, and high-density lipoprotein-cholesterol showed a linear dose-response relationship with carotid plaque. Conclusions:The change of metabolic syndrome is associated with the risk of developing carotid plaque, and maintaining metabolic health, recovering from metabolic syndrome, or minimizing the number of metabolic syndrome components may be effective strategies to prevent carotid plaque formation.
3.Association between thyroid hormone sensitivity indices and metabolic dysfunction-associated steatotic liver disease in euthyroid population
Manling HU ; Xinlei MIAO ; Qianqian WANG ; Shuang LIU ; Xiaoling XIE ; Ziping SONG ; Yuting SUN ; Yangxuan HE ; Song LENG
Chinese Journal of Endocrinology and Metabolism 2025;41(9):747-754
Objective:To explore the relationship between thyroid hormone sensitivity and metabolic dysfunction-associated steatotic liver disease(MASLD) in a population with normal thyroid function, with a particular focus on sex-specific differences.Methods:This retrospective study included 41 355 euthyroid cases who underwent routine health examinations at the Health Management Centre of the Second Affiliated Hospital of Dalian Medical University from January 2014 to December 2023 were included. The free triiodothyronine(FT 3) to free thyroxine(FT 4) ratio(FT 3/FT 4) was calculated in order to reflect the peripheral sensitivity of the thyroid gland. Similarly, thyroid feedback quantile-based index(TFQI), thyrotrophic thyroxine resistance index(TT 4RI), and the FT 3-based TFQI-derived index(TFQI-FT 3) were calculated in order to reflect the central sensitivity of the thyroid gland. A Logistic regression was employed to analyse the effect of sex-specific thyroid hormone sensitivity indices on the prevalence of MASLD. The restricted cubic spline was used to analyse the non-linear relationship between the thyroid sensitivity hormone indices and MASLD. Furthermore, the correlation between the thyroid hormone sensitivity indices and MASLD in different subgroups was also analysed. Results:The prevalence of MASLD in the study population was 28.8%. After adjusting the model for confounders, the risk of MASLD increased by 7%, 3%, 10%, and 5% for each standard deviation increase in FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI in the total population, respectively. The risk of MASLD increased by 6% and 5% for each standard deviation increase in FT 3/FT 4 and TFQI-FT 3 in men, respectively. For each standard deviation increase in FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI in women, the risk of MASLD increased by 6%, 5%, 11%, and 5%, respectively. Higher FT 3/FT 4 and TFQI-FT 3 were positively associated with the risk of developing MASLD in men, and higher FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI were positively associated with the risk of developing MASLD in women. There was a non-linear, inverted U-shaped relationship between TFQI and risk of MASLD in women. Subgroup analyses showed positive associations between FT 3/FT 4, TFQI, TFQI-FT 3, and MASLD. Conclusions:The thyroid hormone sensitivity indices may provide a basis for clinical prevention and management of MASLD in individuals with normal thyroid function. Additionally, FT 3/FT 4 and TFQI-FT 3 may indicate the risk of MASLD in the general population, while TFQI and TT 4RI are more suitable for assessing the risk of MASLD in women.
4.Analysis of T cell and natural killer cell characteristics in cerebrospinal fluid of multiple sclerosis patients based on single-cell transcriptome sequencing
Xue YANG ; Fanju LI ; Zhenzhen HU ; Jingtian ZHE ; Zhimian ZHANG ; Manxia WANG ; Xiaoling LI
Chinese Journal of Neurology 2025;58(7):757-767
Objective:To explore the characteristics of T cells and natural killer (NK) cells in cerebrospinal fluid of patients with multiple sclerosis (MS).Methods:Cerebrospinal fluids from patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls attending the Second Hospital of Lanzhou University from January 2023 to October 2024 were collected and analyzed by single-cell RNA sequencing (scRNA-seq) and flow cytometry, and T and NK cell characteristics were summarized and compared in the two groups. The proposed time-series analysis was used to explore the differentiation trajectories of T cells and NK cells.Results:A total of 3 patients with RRMS and 3 healthy controls underwent scRNA-seq, and 6 patients with RRMS and 4 healthy controls underwent flow cytometry. The composition of cerebrospinal fluid T and NK cell subtypes was similar in the RRMS group and the healthy control group, but the proportion of the cell subtypes differed. The RRMS group exhibited significantly higher frequencies of CD4 +Naive T- IL7R [1 529/9 055(16.89%) vs 1 423/9 910(14.36%), χ2=22.980, P<0.001], CD4 +Naive T- CCR7 [1 573/9 055(17.37%) vs 948/9 910(9.57%), χ2=250.114, P<0.001], and CD4 +Naive T- LTB [1 369/9 055(15.12%) vs 1 079/9 910(10.89%), χ2=75.336, P<0.001] subsets compared to controls. Conversely, the control group demonstrated greater proportions of CD4 +Th1- GZMA [1 255/9 910(12.66%) vs 719/9 055(7.94%), χ2=113.213, P<0.001] and CD8 +Tem- GZMK cells [1 607/9 910(16.22%) vs 1 232/9 055(13.61%), χ2=25.326, P<0.001] than the RRMS group. The transcription factors and gene expression of each T cell subtype were also different between the 2 groups, and CD4 initial T cells and CD8 effector T cells were located at the beginning and the end of the differentiation trajectory, respectively. Conclusions:The cerebrospinal fluid of MS patients is characterized by increased expression of genes involved in T cell differentiation and over-activation of immune cells.
5.Association between daily physical activity patterns and dyslipidemia among people receiving physical examination aged 40-65 years
Guangyan MAO ; Juzhen JIN ; Li ZHENG ; Jin HU ; Xiaoling SONG ; Yuanhao SHANG ; Junhua WANG ; Ziyun WANG
Chinese Journal of Health Management 2025;19(11):908-914
Objective:To analyze the association between daily physical activity patterns and dyslipidemia among people receiving physical examination aged 40-65 years.Methods:This cross-sectional study consecutively enrolled 864 participants aged 40-65 years and met the inclusion and exclusion criteria who underwent health check-ups at the Physical Examination Center of Fuquan First People′s Hospital from March to November in 2022. The data of general characteristics, physical activity, physical examination findings, and lipid profiles were collected. The daily physical activity patterns were identified using K-means clustering analysis. The unconditional binary logistic regression was employed to explore the associations between these activity patterns and dyslipidemia, followed by subgroup analyses.Results:The physical activity of the 864 study participants (517 males and 347 females) included in the analysis was divided into 4 patterns (G1: low physical activity; G2: active commuting; G3: housework; G4: leisure exercise). Using G1 as a reference, after adjusting for confounders, G4 was negatively associated with low high density lipoprotein cholesterol (HDL-C) ( OR=0.37, 95% CI: 0.14-1.00) ( P=0.05). In the male, G3 was negatively associated with dyslipidemia ( OR=0.44, 95% CI: 0.21-0.93) and low HDL-C ( OR=0.25, 95% CI: 0.10-0.68) (both P<0.05). In the subjects aged 50 years and above, G2 was negatively associated with dyslipidemia ( OR=0.52, 95% CI: 0.30-0.90), hypertriglyceridemia ( OR=0.50, 95% CI: 0.28-0.90) and low HDL-C ( OR=0.47, 95% CI: 0.24-0.91) (all P<0.05). In those who never or occasionally stayed up late, G2 was negatively associated with hypertriglyceridemia ( OR=0.31, 95% CI: 0.13-0.75) ( P<0.05); in those who stayed up late often, G4 was negatively associated with dyslipidemia ( OR=0.33, 95% CI: 0.13-0.85) and low HDL-C ( OR=0.19, 95% CI: 0.04-0.84) (both P<0.05). In the centrally obese population, G2 was negatively associated with dyslipidemia ( OR=0.55, 95% CI: 0.35-0.88) and hypertriglyceridemia ( OR=0.54, 95% CI: 0.33-0.86) (both P<0.05). Conclusions:Association between different physical activity patterns and dyslipidemia varied among adults aged 40-65 years undergoing health check-ups. Leisure-time exercise is associated with a reduced risk of dyslipidemia, while household activities also emerges as a beneficial factor linked to lower dyslipidemia risk particularly in the male population.
6.Horticultural Therapy Combined with Intradermal Needling for Patients with Generalized Anxiety Disorder of Liver Depression Transforming into Fire Syndrome Under Transcranial Magnetic Stimulation and Psychological Therapy:Clinical Observation of 60 Cases
Wanyun ZHANG ; Jiayi YAN ; Qingyi QIU ; Yumei PENG ; Xiaoling ZHONG ; Jinwen ZHANG ; Rundong TANG ; Miao WU ; Dan HU ; Guang SU
Journal of Traditional Chinese Medicine 2025;66(1):50-58
ObjectiveTo observe the clinical effectiveness of horticultural therapy involving the planting of Chinese medicinal herbs (mint and lily potted plants) combined with intradermal needling therapy for generalized anxiety disorder (GAD) of liver depression transforming into fire syndrome under transcranial magnetic stimulation and basic psychological therapy, and to explore the possible mechanisms of action. MethodsA total of 180 patients with GAD of liver depression transforming into fire syndrome were randomly divided into three groups, horticultural therapy group, intradermal needling group, and horticultural therapy+intradermal needling group, with 60 patients in each. All groups received basic treatment including basic psychological therapy and transcranial magnetic stimulation. The horticultural therapy group received horticultural therapy in addition to the basic treatment; the intradermal needling group received intradermal needling therapy once a week for 8 weeks in addition to the basic treatment; the horticultural therapy+intradermal needling group received both horticultural therapy and intradermal needling therapy, following the same procedures and duration. Hamilton Anxiety Rating Scale (HAMA), Self-Rating Anxiety Scale (SAS), and Pittsburgh Sleep Quality Index (PSQI) scores were assessed at baseline and after 2, 4, 6, and 8 weeks of treatment. Serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured before treatment and after 8 weeks of treatment. Motor-evoked potential (MEP) baseline levels were recorded before treatment, and MEP amplitude ratios were compared after 1 week and 8 weeks of treatment. Clinical effectiveness and safety were evaluated after 8 weeks of treatment. Pearson correlation analysis was used to examine the relationships between serum ACTH and CORT levels, MEP amplitude, and anxiety. ResultsIn the horticultural therapy group and intradermal needling group, HAMA, SAS and PSQI scores after 4, 6, and 8 weeks treatment were lower than baseline scores (P<0.05). In the horticultural therapy+intradermal needling group, these scores showed a significant decline starting after 2 weeks treatment and continuing through 8 weeks after treatment (P<0.05). The HAMA, SAS, and PSQI scores in the horticultural therapy+intradermal needling group were significantly lower than those in the other two groups after 2, 4, 6, and 8 weeks treatment (P<0.05). After 8 weeks of treatment, serum CORT and ACTH levels in the horticultural therapy+intradermal needling group were significantly lower than baseline levels (P<0.05) and were also lower than those in the horticultural therapy group and intradermal needling group at the same time point (P<0.01). When comparing the level after 8 weeks treatment to that after 1 week treatment, under PAS10 stimulation, the MEP amplitude ratio in the intradermal needling group decreased at 30 minutes, while in the horticultural therapy+intradermal needling group, the MEP amplitude ratio decreased at all time points (P<0.05 or P<0.001); under PAS25 stimulation, the MEP amplitude ratio in the horticultural therapy group increased at 20 minutes, and in the intradermal needle group at 10 minutes (P<0.05). In the horticultural therapy+intradermal needling group, the MEP amplitude ratio increased significantly at all time points after treatment (P<0.001). The cure rate in the horticultural therapy+intradermal needling group (74.14%, 43/58) was significantly higher than that in the horticultural therapy group (30.00%, 18/60) and the intradermal needling group (48.28%, 28/58, P<0.05). Correlation analysis revealed that serum ACTH and CORT levels were positively correlated with HAMA scores (r = 0.488, P<0.01; r = 0.428, P<0.01). Following PAS10 intervention, the MEP amplitude ratio was positively correlated with HAMA scores (r = 0.458, P<0.01), whereas after PAS25 intervention, the MEP amplitude ratio was negatively correlated with HAMA scores (r = -0.562, P<0.01). ConclusionHorticultural therapy combined with intradermal needling treatment, under transcranial magnetic stimulation and basic psychological therapy, demonstrates significant clinical effectiveness in patients with GAD of liver depression transforming into fire syndrome. Its mechanism of action may be related to the regulation of hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis and the reduction of cortical excitability.
7.Association between ambient ozone exposure during pregnancy and risk of preterm birth in Guangdong Province
Peng HU ; Shanshan RAN ; Qingmei LIN ; Yin YANG ; Zilong ZHANG ; Xiaoling GUO ; Yonggui GAO ; Jinde ZHAO ; Hualiang LIN
Journal of Environmental and Occupational Medicine 2025;42(4):379-384
Background Air pollution exposure has a significant impact on maternal and child health. However, the research on the association between ambient ozone (O3) exposure during pregnancy and the risk of premature birth in newborns is limited, and the conclusions are inconsistent. Objective To investigate the association of ambient O3 exposure during pregnancy with the risk of preterm birth in Guangdong Province. Methods Data of pregnant women in Guangzhou from 2013 to 2019 and Foshan from 2018 to 2023 were collected, and O3 concentrations during different trimesters were assessed according to maternal residential addresses. Bilinear interpolation was used to evaluate the concentrations of air pollution. A cohort study design was adopted in our study. Restricted cubic spline curves were used to evaluate the exposure-response relationship between O3 exposure and preterm birth risk and explore potential exposure threshold of O3. Logistic regression models were used to evaluate the association of O3 exposure with preterm birth. Results A total of 702 924 pregnant women were included in this study, of whom 43 051 (6.12%) were preterm. The average O3 exposure concentrations of pregnant women during the first, second, third, and whole trimesters were 95.51, 97.51, 100.60, and 97.87 μg·m−3, respectively. We observed J-shaped associations between O3 exposure and preterm birth risk during the second, third, and whole trimesters of pregnancy using restricted cubic spline curves. This study found that there were threshold concentrations between O3 exposure and preterm birth risk during different gestational periods, and the threshold concentrations in the first, second, third, and whole trimesters were 112.32, 99.83, 111.74, and 112.46 μg·m−3, respectively. During the second, third, and whole trimesters of pregnancy, after adjusting for maternal age, baby sex, pre-pregnancy body mass index, mode of delivery, baby birth weight, gestational diabetes, and gestational hypertension, the odds ratios (OR) of preterm birth were 1.02 (95%CI: 1.01, 1.04), 1.02 (95%CI: 1.00, 1.03), and 1.17 (95%CI: 1.13, 1.21) for each 10 μg·m−3 increase in O3 concentration above the O3 threshold. No significant association was found between O3 exposure and the risk of preterm birth during the first trimester. Conclusion There is a nonlinear association between the risk of preterm birth and O3 exposure during pregnancy, and higher concentrations of O3 exposure during pregnancy are associated with the risk of preterm birth. Above the O3 threshold concentration during pregnancy, especially during the second, third, and whole trimesters, the risk of preterm birth elevates with the increase of O3 exposure concentrations.
8.Shenqi Dihuang Decoction Improves Renal Function in Mouse Model of Diabetic Kidney Disease by Inhibiting Arachidonic Acid-related Ferroptosis Via ACSL4/LPCAT3/ALOX15 Axis
Yuantao WU ; Zhibin WANG ; Xinying FU ; Xiaoling ZOU ; Wenxiao HU ; Yixian ZOU ; Jun FENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):140-149
ObjectiveTo investigate the therapeutic effects and mechanism of Shenqi Dihuang decoction (SQDHD) on diabetic kidney disease (DKD), with a focus on its impact on arachidonic acid-related ferroptosis. MethodsSixty C57BL/6 mice were allocated into a normal group (n=10) and a modeling group (n=50), with 43 mice successfully modeled. The successfully modeled mice were further allocated into model, low-, medium-, and high-dose (4.68, 9.36, and 18.72 g·kg-1, respectively) SQDHD, and dapagliflozin (0.13 mg·kg-1) groups. The drug treatment groups were administrated with corresponding agents by gavage, and the normal and model groups were administrated with equal volumes of normal saline by gavage. An electronic balance and a glucometer were used to monitor the body weight and fasting blood glucose level from the tail tip, respectively. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were measured by enzyme-linked immunosorbent assay (ELISA). Histopathological changes in the renal tissue were assessed by hematoxylin-eosin staining, Masson staining, and periodic acid-Schiff (PAS) staining. The fluorescence intensity of reactive oxygen species (ROS) in frozen sections was observed by an inverted fluorescence microscope to evaluate the levels of ferrous ions (Fe2+) and lipid peroxidation in the renal tissue. Immunofluorescence staining of glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) in the renal tissue was performed to detect their localization and expression. Western blot was employed to assess the expression levels of key ferroptosis proteins such as GPX4 and cystine/glutamate antiporter (xCT), as well as the arachidonic acid metabolic pathway-related proteins, including ACSL4, lysophosphatidylcholine acyltransferase 3 (LPCAT3), and arachidonate 15-lipoxygenase (ALOX15). Real-time PCR was employed to measure the mRNA levels of key ferroptosis proteins, including solute carrier family 7 member 11 (SLC7A11) and GPX4, as well as arachidonic acid metabolism-related factors (ACSL4, LPCAT3, and ALOX15) in the renal tissue. ResultsCompared with the normal group, DKD model mice exhibited a decrease in body weight (P<0.01), increases in levels of blood glucose (P<0.01), 24-hour urinary protein, Scr, and BUN (P<0.01), along with severe pathological changes, such as mesangial cell proliferation, basement membrane thickening, tubular atrophy, and interstitial inflammatory cell infiltration. In addition, the modeling elevated the levels of Fe2+, MDA, LPO, and ROS (P<0.01), lowered the GPX4 and xCT levels (P<0.01), raised the ACSL4, LPCAT3, and ALOX15 levels (P<0.01), down-regulated the mRNA levels of GPX4 and SLC7A11 (P<0.01), and up-regulated the mRNA levels of ACSL4, LPCAT3, and ALOX15 (P<0.01) in the renal tissue. Compared with the model group, low-, medium-, and high-dose SQDHD groups and the dapagliflozin group showed an increase in body weight (P<0.01), decreases in levels of blood glucose (P<0.01), 24-hour urinary protein, and Scr (P<0.01), alleviated pathological changes in glomeruli and tubules, and reduced degree of glomerular and tubular fibrosis. The high-dose SQDHD group and the dapagliflozin group showed reductions in Fe2+, MDA, LPO, and ROS levels (P<0.01). The medium- and high-dose SQDHD groups and the dapagliflozin group exhibited increased levels of GPX4 and xCT (P<0.01), decreased levels of ACSL4, LPCAT3, and ALOX15 (P<0.05, P<0.01), and down-regulated mRNA levels of ACSL4, LPCAT3, and ALOX15 (P<0.01). ConclusionSQDHD ameliorates DKD by inhibiting ferroptosis potentially by reducing iron ion levels, inhibiting lipid peroxidation, up-regulating GPX4 expression, and down-regulating ACSL4 expression. This study provides new insights and a theoretical basis for the treatment of DKD with traditional Chinese medicine and identifies potential targets for developing novel therapeutics for DKD.
9.Shenqi Dihuang Decoction Improves Renal Function in Mouse Model of Diabetic Kidney Disease by Inhibiting Arachidonic Acid-related Ferroptosis Via ACSL4/LPCAT3/ALOX15 Axis
Yuantao WU ; Zhibin WANG ; Xinying FU ; Xiaoling ZOU ; Wenxiao HU ; Yixian ZOU ; Jun FENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):140-149
ObjectiveTo investigate the therapeutic effects and mechanism of Shenqi Dihuang decoction (SQDHD) on diabetic kidney disease (DKD), with a focus on its impact on arachidonic acid-related ferroptosis. MethodsSixty C57BL/6 mice were allocated into a normal group (n=10) and a modeling group (n=50), with 43 mice successfully modeled. The successfully modeled mice were further allocated into model, low-, medium-, and high-dose (4.68, 9.36, and 18.72 g·kg-1, respectively) SQDHD, and dapagliflozin (0.13 mg·kg-1) groups. The drug treatment groups were administrated with corresponding agents by gavage, and the normal and model groups were administrated with equal volumes of normal saline by gavage. An electronic balance and a glucometer were used to monitor the body weight and fasting blood glucose level from the tail tip, respectively. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were measured by enzyme-linked immunosorbent assay (ELISA). Histopathological changes in the renal tissue were assessed by hematoxylin-eosin staining, Masson staining, and periodic acid-Schiff (PAS) staining. The fluorescence intensity of reactive oxygen species (ROS) in frozen sections was observed by an inverted fluorescence microscope to evaluate the levels of ferrous ions (Fe2+) and lipid peroxidation in the renal tissue. Immunofluorescence staining of glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) in the renal tissue was performed to detect their localization and expression. Western blot was employed to assess the expression levels of key ferroptosis proteins such as GPX4 and cystine/glutamate antiporter (xCT), as well as the arachidonic acid metabolic pathway-related proteins, including ACSL4, lysophosphatidylcholine acyltransferase 3 (LPCAT3), and arachidonate 15-lipoxygenase (ALOX15). Real-time PCR was employed to measure the mRNA levels of key ferroptosis proteins, including solute carrier family 7 member 11 (SLC7A11) and GPX4, as well as arachidonic acid metabolism-related factors (ACSL4, LPCAT3, and ALOX15) in the renal tissue. ResultsCompared with the normal group, DKD model mice exhibited a decrease in body weight (P<0.01), increases in levels of blood glucose (P<0.01), 24-hour urinary protein, Scr, and BUN (P<0.01), along with severe pathological changes, such as mesangial cell proliferation, basement membrane thickening, tubular atrophy, and interstitial inflammatory cell infiltration. In addition, the modeling elevated the levels of Fe2+, MDA, LPO, and ROS (P<0.01), lowered the GPX4 and xCT levels (P<0.01), raised the ACSL4, LPCAT3, and ALOX15 levels (P<0.01), down-regulated the mRNA levels of GPX4 and SLC7A11 (P<0.01), and up-regulated the mRNA levels of ACSL4, LPCAT3, and ALOX15 (P<0.01) in the renal tissue. Compared with the model group, low-, medium-, and high-dose SQDHD groups and the dapagliflozin group showed an increase in body weight (P<0.01), decreases in levels of blood glucose (P<0.01), 24-hour urinary protein, and Scr (P<0.01), alleviated pathological changes in glomeruli and tubules, and reduced degree of glomerular and tubular fibrosis. The high-dose SQDHD group and the dapagliflozin group showed reductions in Fe2+, MDA, LPO, and ROS levels (P<0.01). The medium- and high-dose SQDHD groups and the dapagliflozin group exhibited increased levels of GPX4 and xCT (P<0.01), decreased levels of ACSL4, LPCAT3, and ALOX15 (P<0.05, P<0.01), and down-regulated mRNA levels of ACSL4, LPCAT3, and ALOX15 (P<0.01). ConclusionSQDHD ameliorates DKD by inhibiting ferroptosis potentially by reducing iron ion levels, inhibiting lipid peroxidation, up-regulating GPX4 expression, and down-regulating ACSL4 expression. This study provides new insights and a theoretical basis for the treatment of DKD with traditional Chinese medicine and identifies potential targets for developing novel therapeutics for DKD.
10.Temporal trend in mortality due to congenital heart disease in China from 2008 to 2021.
Youping TIAN ; Xiaojing HU ; Qing GU ; Miao YANG ; Pin JIA ; Xiaojing MA ; Xiaoling GE ; Quming ZHAO ; Fang LIU ; Ming YE ; Weili YAN ; Guoying HUANG
Chinese Medical Journal 2025;138(6):693-701
BACKGROUND:
Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China.
METHODS:
We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model.
RESULTS:
From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%).
CONCLUSIONS
CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans
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Heart Defects, Congenital/mortality*
;
Male
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Female
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China/epidemiology*
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Infant
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Child, Preschool
;
Adult
;
Child
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Adolescent
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Infant, Newborn
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Middle Aged
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Young Adult
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Aged
;
Rural Population

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