1.Molecular Mechanism Mediated by HIF-1α/HO-1 Signaling Pathway of Guizhi Fulingwan in Suppressing Ferroptosis in Endometriosis
Li TANG ; Yi ZHANG ; Lulu WU ; Yingying LIANG ; Wenying GONG ; Quanning TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):1-11
ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan (GFW) inhibits ferroptosis in endometriosis (EMT) through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 (HIF-1α/HO-1) signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT, including core targets. Functional enrichment analysis was conducted to explore the biological processes, molecular functions, cellular components, and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley (SD) rats were randomly divided into five groups: sham-operated, model, positive control (dienogest at 0.2 mg·kg-1), low-dose GFW (2.5 g·kg-1), and high-dose GFW (5 g·kg-1). After modeling, the rats received their respective treatment by oral gavage for 28 consecutive days, while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin (HE) staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction (Real-time PCR) and Western blot were conducted to assess mRNA and protein expression of HIF-1α, HO-1, glutathione peroxidase 4 (GPX4), spermidine/spermine N1-acetyltransferase (SAT1), and prostaglandin-endoperoxide synthase 2 (PTGS2). Tissue levels of malondialdehyde (MDA), glutathione (GSH), and ferrous iron (Fe²⁺) were quantified using commercial assay kits. Serum levels of interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) were measured via enzyme-linked immunosorbent assay (ELISA). ResultsFive ferroptosis-related biomarkers in EMT were identified: ALOX12, CHAC1, SAT1, AST1, and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment, with FOS, JUN, HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group, the model group exhibited significant increases in both mRNA and protein expression of HIF-1α, HO-1, and PTGS2, as well as elevated tissue levels of Fe²⁺ and MDA. Conversely, GSH levels and the expression of GPX4 and SAT1 were markedly reduced, and serum levels of IL-6 and TGF-β1 levels were significantly higher (P<0.01). Compared with the model group, all GFW-treated groups showed significant downregulation of HIF-1α and HO-1, reduced Fe²⁺ levels, and downregulated expression of MDA, PTGS2, IL-6, and TGF-β1. Meanwhile, GSH, GPX4, and SAT1 expression levels were significantly increased (P<0.05, P<0.01), effectively ameliorating iron overload and oxidative stress, thereby demonstrating therapeutic efficacy in EMT, with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation, providing a novel theoretical foundation for the clinical application of GFW in EMT treatment.
2.Experience of LI Diangui in Treating Gastroesophageal Reflux Disease Based on the Theory of Turbidity-Toxin in Liver
Shiyue LIANG ; Mengqi GAO ; Yansheng LIU ; Minan BAI ; Yingying LOU ;
Journal of Traditional Chinese Medicine 2025;66(16):1640-1644
This paper summarized the clinical experience of Prof. LI Diangui in treating gastroesophageal reflux disease (GERD) based on the theory of turbidity-toxin in liver. It is believed that internal accumulation of turbidity-toxin and liver depression with stomach counterflow are the main pathogenesis of GERD, and thus the therapeutic methods of resolving turbidity and resolving toxins, regulating the liver and harmonizing the stomach are proposed. In clinical practice, GERD is divided into the early stage, middle stage and late stage. For the early stage, the modified Huazhuo Shugan Hewei Formula (化浊疏肝和胃方) is used to regulate qi and remove turbidity, soothe the liver and harmonize the stomach; for the middle stage, the modified Huazhuo Qingre Zhisuan Formula (化浊清热制酸方) is applied to clear heat, direct the turbid downward, and resolve toxins; for the late stage, the modified Yiwei Decoction (益胃汤) is adopted to replenish qi, nourish yin and simultaneously resolve turbidity-toxin. Throughout the treatment process, attention should be paid to protecting the spleen and stomach, and the medication could be modified according to changes of individual condition.
3.Cytoplasmic and nuclear NFATc3 cooperatively contributes to vascular smooth muscle cell dysfunction and drives aortic aneurysm and dissection.
Xiu LIU ; Li ZHAO ; Deshen LIU ; Lingna ZHAO ; Yonghua TUO ; Qinbao PENG ; Fangze HUANG ; Zhengkun SONG ; Chuanjie NIU ; Xiaoxia HE ; Yu XU ; Jun WAN ; Peng ZHU ; Zhengyang JIAN ; Jiawei GUO ; Yingying LIU ; Jun LU ; Sijia LIANG ; Shaoyi ZHENG
Acta Pharmaceutica Sinica B 2025;15(7):3663-3684
This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.
4.Expression and Clinical Value of Serum miR-4429 and miR-19-3p in Patients with Pelvic Floor Dysfunctional Disease
Yingying ZHANG ; Chen LIANG ; Xiaoyan LI ; Yanling ZHANG ; Weili JIU
Journal of Modern Laboratory Medicine 2024;39(2):119-123
Objective To investigate the expression and significance of microRNA(miR)-4429 and microRNA(miR)-19-3p level in patients with pelvic floor dysfunctional(PFD)disease.Methods A total of 90 PFD patients admitted to the Second People's Hospital of Hengshui from June 2021 to June 2022 were selected as the PFD group.They were grouped into the pelvic organ prolapse(POP)group(n=50),the stress urinary incontinence(SUI)group(n=25),and the POP combined with SUI group(n=15).Meanwhile,80 healthy women who were examined in the Second People's Hospital of Hengshui were collected as the control group.The general data such as delivery mode,previous abortion history and family history were compared between the control group and the PFD group.The levels of serum miR-4429 and miR-19-3p in each group were compared.The diagnostic value of serum miR-4429 and miR-19-3p levels in PFD was analyzed by receiver operating characteristic(ROC)analysis.Logistic regression analysis was applied to analyze the factors affecting PFD.The paired sample t-test was applied to compare the changes in serum miR-4429 and miR-19-3p levels before and after PFD treatment.Results There were significant differences between the PFD group and the control group in terms of delivery mode,previous abortion history,and PFD family history,and the differences were statistically significant(t=4.415,6.444,4.707,all P<0.05).The serum miR-4429(0.71±0.19 vs 1.00±0.25)level in the PFD group was lower than that in the control group,while the miR-19-3p(1.44±0.35 vs 1.01±0.28)level was higher than that in the control group,and the differences was statistically significant(t=8.927,8.772,all P<0.05).The serum miR-4429(0.73±0.22,0.74±0.16 vs 0.59±0.16)level in the POP and SUI groups was higher than that in the POP combined SUI group,while the serum miR-19-3p(1.35±0.39,1.41±0.31 vs 1.77±0.56)level in the POP group and SUI group was lower than that in the POP combined with SUI group,with significant differences(t=3.531,3.411;5.003,3.865,all P<0.05).ROC analysis showed that the areas under curve(AUC)for miR-4429 and miR-19-3p to assist in assessing whether PFD occurs were 0.805 and 0.825,respectively.The AUC of the combined detection was 0.865.Multivariate logistic regression analysis showed that miR-19-3p was a risk factor affecting PFD,while miR-4429 was a protective factor.After treatment,serum miR-4429(0.93±0.23 vs 0.71±0.19)level in PFD patients increased,while the miR-19-3p(1.12±0.29 vs 1.44±0.35)level decreased,the diffences were statistically significant(t=6.996,6.679,all P<0.05).Conclusion The serum miR-4429 level in patients with PFD decreased,while the miR-19-3p level increased.The levels of miR-4429 and miR-19-3p in serum were closely related to the occurrence and development of PFD diseases,which can be used as evaluation indicators to predict PFD.
5.Pregnancy Outcome and Puerperal Follow-up of Cesarean Section with SARS-CoV-2 Omicron Variant in Different Periods of Pregnancy
Jieming LIANG ; Yingying LI ; Guocheng LIU
Journal of Practical Obstetrics and Gynecology 2024;40(5):392-397
Objective:To investigate the pregnancy outcome and the maternal and infant follow-up in the puer-peral period(42 days after delivery)of cesarean section with SARS-CoV-2 Omicron variant in different periods of pregnancy.Methods:330 pregnant women who were diagnosed with SARS-CoV-2 infection and delivered by ce-sarean section in Guangdong Women and Children Hospital from November 20,2022 to January 25,2023 were selected as the research subjects.They were divided into the early(80 cases),middle(151 cases)and late(99 cases)pregnancy group according to the gestational age of infection.The general information,pregnancy compli-cations and comorbidities,pregnancy outcomes,and postpartum maternal and infant follow-up of each group of pregnant women were compared.Results:The clinical classification of pregnant women was asymptomatic and mild,with 9 cases of asymptomatic and 321 cases of mild.The incidence of gestational diabetes mellitus(GDM)in the early and late group was higher than that in the middle group(P<0.05).There was no statistically significant difference in the incidence of placental abruption,fetal growth restriction,fetal distress,amniotic fluid contamina-tion,preterm labor,postpartum hemorrhage,macrosomia,low-birth-weight infants and the maternal intensive care unit(MICU)transfer rate,newborn birth weight,neonatal asphyxia rate and NICU transfer rate among the three groups(P>0.05).The incidence of preterm rupture of membranes in the middle group was higher than that in the late group(P<0.05).Puerperal follow-up results showed that there was no statistically significant difference in the incidence of poor maternal uterine incision healing,poor uterine involution,vaginal microecological imbal-ance and neonatal acute upper respiratory tract infection,pneumonia,digestive system disease,cardiovascular system disease among the three groups(P>0.05).Conclusions:The majority of pregnant women with Omicron infection during pregnancy are mild.Omicron infection in different periods of pregnancy has no significant effect on pregnancy outcome and puerperal follow-up of cesarean section.No evidence was found that GDM and prema-ture rupture of membranes are significantly associated with Omicron infection in different periods of pregnancy.
6.Pregnancy Outcome and Puerperal Follow-up of Cesarean Section with SARS-CoV-2 Omicron Variant in Different Periods of Pregnancy
Jieming LIANG ; Yingying LI ; Guocheng LIU
Journal of Practical Obstetrics and Gynecology 2024;40(5):392-397
Objective:To investigate the pregnancy outcome and the maternal and infant follow-up in the puer-peral period(42 days after delivery)of cesarean section with SARS-CoV-2 Omicron variant in different periods of pregnancy.Methods:330 pregnant women who were diagnosed with SARS-CoV-2 infection and delivered by ce-sarean section in Guangdong Women and Children Hospital from November 20,2022 to January 25,2023 were selected as the research subjects.They were divided into the early(80 cases),middle(151 cases)and late(99 cases)pregnancy group according to the gestational age of infection.The general information,pregnancy compli-cations and comorbidities,pregnancy outcomes,and postpartum maternal and infant follow-up of each group of pregnant women were compared.Results:The clinical classification of pregnant women was asymptomatic and mild,with 9 cases of asymptomatic and 321 cases of mild.The incidence of gestational diabetes mellitus(GDM)in the early and late group was higher than that in the middle group(P<0.05).There was no statistically significant difference in the incidence of placental abruption,fetal growth restriction,fetal distress,amniotic fluid contamina-tion,preterm labor,postpartum hemorrhage,macrosomia,low-birth-weight infants and the maternal intensive care unit(MICU)transfer rate,newborn birth weight,neonatal asphyxia rate and NICU transfer rate among the three groups(P>0.05).The incidence of preterm rupture of membranes in the middle group was higher than that in the late group(P<0.05).Puerperal follow-up results showed that there was no statistically significant difference in the incidence of poor maternal uterine incision healing,poor uterine involution,vaginal microecological imbal-ance and neonatal acute upper respiratory tract infection,pneumonia,digestive system disease,cardiovascular system disease among the three groups(P>0.05).Conclusions:The majority of pregnant women with Omicron infection during pregnancy are mild.Omicron infection in different periods of pregnancy has no significant effect on pregnancy outcome and puerperal follow-up of cesarean section.No evidence was found that GDM and prema-ture rupture of membranes are significantly associated with Omicron infection in different periods of pregnancy.
7.Pregnancy Outcome and Puerperal Follow-up of Cesarean Section with SARS-CoV-2 Omicron Variant in Different Periods of Pregnancy
Jieming LIANG ; Yingying LI ; Guocheng LIU
Journal of Practical Obstetrics and Gynecology 2024;40(5):392-397
Objective:To investigate the pregnancy outcome and the maternal and infant follow-up in the puer-peral period(42 days after delivery)of cesarean section with SARS-CoV-2 Omicron variant in different periods of pregnancy.Methods:330 pregnant women who were diagnosed with SARS-CoV-2 infection and delivered by ce-sarean section in Guangdong Women and Children Hospital from November 20,2022 to January 25,2023 were selected as the research subjects.They were divided into the early(80 cases),middle(151 cases)and late(99 cases)pregnancy group according to the gestational age of infection.The general information,pregnancy compli-cations and comorbidities,pregnancy outcomes,and postpartum maternal and infant follow-up of each group of pregnant women were compared.Results:The clinical classification of pregnant women was asymptomatic and mild,with 9 cases of asymptomatic and 321 cases of mild.The incidence of gestational diabetes mellitus(GDM)in the early and late group was higher than that in the middle group(P<0.05).There was no statistically significant difference in the incidence of placental abruption,fetal growth restriction,fetal distress,amniotic fluid contamina-tion,preterm labor,postpartum hemorrhage,macrosomia,low-birth-weight infants and the maternal intensive care unit(MICU)transfer rate,newborn birth weight,neonatal asphyxia rate and NICU transfer rate among the three groups(P>0.05).The incidence of preterm rupture of membranes in the middle group was higher than that in the late group(P<0.05).Puerperal follow-up results showed that there was no statistically significant difference in the incidence of poor maternal uterine incision healing,poor uterine involution,vaginal microecological imbal-ance and neonatal acute upper respiratory tract infection,pneumonia,digestive system disease,cardiovascular system disease among the three groups(P>0.05).Conclusions:The majority of pregnant women with Omicron infection during pregnancy are mild.Omicron infection in different periods of pregnancy has no significant effect on pregnancy outcome and puerperal follow-up of cesarean section.No evidence was found that GDM and prema-ture rupture of membranes are significantly associated with Omicron infection in different periods of pregnancy.
8.Pregnancy Outcome and Puerperal Follow-up of Cesarean Section with SARS-CoV-2 Omicron Variant in Different Periods of Pregnancy
Jieming LIANG ; Yingying LI ; Guocheng LIU
Journal of Practical Obstetrics and Gynecology 2024;40(5):392-397
Objective:To investigate the pregnancy outcome and the maternal and infant follow-up in the puer-peral period(42 days after delivery)of cesarean section with SARS-CoV-2 Omicron variant in different periods of pregnancy.Methods:330 pregnant women who were diagnosed with SARS-CoV-2 infection and delivered by ce-sarean section in Guangdong Women and Children Hospital from November 20,2022 to January 25,2023 were selected as the research subjects.They were divided into the early(80 cases),middle(151 cases)and late(99 cases)pregnancy group according to the gestational age of infection.The general information,pregnancy compli-cations and comorbidities,pregnancy outcomes,and postpartum maternal and infant follow-up of each group of pregnant women were compared.Results:The clinical classification of pregnant women was asymptomatic and mild,with 9 cases of asymptomatic and 321 cases of mild.The incidence of gestational diabetes mellitus(GDM)in the early and late group was higher than that in the middle group(P<0.05).There was no statistically significant difference in the incidence of placental abruption,fetal growth restriction,fetal distress,amniotic fluid contamina-tion,preterm labor,postpartum hemorrhage,macrosomia,low-birth-weight infants and the maternal intensive care unit(MICU)transfer rate,newborn birth weight,neonatal asphyxia rate and NICU transfer rate among the three groups(P>0.05).The incidence of preterm rupture of membranes in the middle group was higher than that in the late group(P<0.05).Puerperal follow-up results showed that there was no statistically significant difference in the incidence of poor maternal uterine incision healing,poor uterine involution,vaginal microecological imbal-ance and neonatal acute upper respiratory tract infection,pneumonia,digestive system disease,cardiovascular system disease among the three groups(P>0.05).Conclusions:The majority of pregnant women with Omicron infection during pregnancy are mild.Omicron infection in different periods of pregnancy has no significant effect on pregnancy outcome and puerperal follow-up of cesarean section.No evidence was found that GDM and prema-ture rupture of membranes are significantly associated with Omicron infection in different periods of pregnancy.
9.Pregnancy Outcome and Puerperal Follow-up of Cesarean Section with SARS-CoV-2 Omicron Variant in Different Periods of Pregnancy
Jieming LIANG ; Yingying LI ; Guocheng LIU
Journal of Practical Obstetrics and Gynecology 2024;40(5):392-397
Objective:To investigate the pregnancy outcome and the maternal and infant follow-up in the puer-peral period(42 days after delivery)of cesarean section with SARS-CoV-2 Omicron variant in different periods of pregnancy.Methods:330 pregnant women who were diagnosed with SARS-CoV-2 infection and delivered by ce-sarean section in Guangdong Women and Children Hospital from November 20,2022 to January 25,2023 were selected as the research subjects.They were divided into the early(80 cases),middle(151 cases)and late(99 cases)pregnancy group according to the gestational age of infection.The general information,pregnancy compli-cations and comorbidities,pregnancy outcomes,and postpartum maternal and infant follow-up of each group of pregnant women were compared.Results:The clinical classification of pregnant women was asymptomatic and mild,with 9 cases of asymptomatic and 321 cases of mild.The incidence of gestational diabetes mellitus(GDM)in the early and late group was higher than that in the middle group(P<0.05).There was no statistically significant difference in the incidence of placental abruption,fetal growth restriction,fetal distress,amniotic fluid contamina-tion,preterm labor,postpartum hemorrhage,macrosomia,low-birth-weight infants and the maternal intensive care unit(MICU)transfer rate,newborn birth weight,neonatal asphyxia rate and NICU transfer rate among the three groups(P>0.05).The incidence of preterm rupture of membranes in the middle group was higher than that in the late group(P<0.05).Puerperal follow-up results showed that there was no statistically significant difference in the incidence of poor maternal uterine incision healing,poor uterine involution,vaginal microecological imbal-ance and neonatal acute upper respiratory tract infection,pneumonia,digestive system disease,cardiovascular system disease among the three groups(P>0.05).Conclusions:The majority of pregnant women with Omicron infection during pregnancy are mild.Omicron infection in different periods of pregnancy has no significant effect on pregnancy outcome and puerperal follow-up of cesarean section.No evidence was found that GDM and prema-ture rupture of membranes are significantly associated with Omicron infection in different periods of pregnancy.
10.Pregnancy Outcome and Puerperal Follow-up of Cesarean Section with SARS-CoV-2 Omicron Variant in Different Periods of Pregnancy
Jieming LIANG ; Yingying LI ; Guocheng LIU
Journal of Practical Obstetrics and Gynecology 2024;40(5):392-397
Objective:To investigate the pregnancy outcome and the maternal and infant follow-up in the puer-peral period(42 days after delivery)of cesarean section with SARS-CoV-2 Omicron variant in different periods of pregnancy.Methods:330 pregnant women who were diagnosed with SARS-CoV-2 infection and delivered by ce-sarean section in Guangdong Women and Children Hospital from November 20,2022 to January 25,2023 were selected as the research subjects.They were divided into the early(80 cases),middle(151 cases)and late(99 cases)pregnancy group according to the gestational age of infection.The general information,pregnancy compli-cations and comorbidities,pregnancy outcomes,and postpartum maternal and infant follow-up of each group of pregnant women were compared.Results:The clinical classification of pregnant women was asymptomatic and mild,with 9 cases of asymptomatic and 321 cases of mild.The incidence of gestational diabetes mellitus(GDM)in the early and late group was higher than that in the middle group(P<0.05).There was no statistically significant difference in the incidence of placental abruption,fetal growth restriction,fetal distress,amniotic fluid contamina-tion,preterm labor,postpartum hemorrhage,macrosomia,low-birth-weight infants and the maternal intensive care unit(MICU)transfer rate,newborn birth weight,neonatal asphyxia rate and NICU transfer rate among the three groups(P>0.05).The incidence of preterm rupture of membranes in the middle group was higher than that in the late group(P<0.05).Puerperal follow-up results showed that there was no statistically significant difference in the incidence of poor maternal uterine incision healing,poor uterine involution,vaginal microecological imbal-ance and neonatal acute upper respiratory tract infection,pneumonia,digestive system disease,cardiovascular system disease among the three groups(P>0.05).Conclusions:The majority of pregnant women with Omicron infection during pregnancy are mild.Omicron infection in different periods of pregnancy has no significant effect on pregnancy outcome and puerperal follow-up of cesarean section.No evidence was found that GDM and prema-ture rupture of membranes are significantly associated with Omicron infection in different periods of pregnancy.

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