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.Trend analysis of malnutrition among primary and middle school students of Han nationality in Hainan Province from 2005 to 2019
ZUO Xin, LI Yingqi, ZHAO Yingying, GUAN Changrong, LIANG Qiqing, TIAN Ye, LIU Yumei
Chinese Journal of School Health 2024;45(7):950-954
Objective:
To understand the trends in malnutrition among primary and middle school students of Han nationality in Hainan Province from 2005 to 2019, so as to provide a basis for improving nutrition intervention measures for children and adolescents.
Methods:
A sample of 32 949 Han nationality primary and middle school students aged 7-18 years old in Hainan Province were investigated in 2005, 2010, 2014 and 2019 based on national survey on student physical fitness and health. The Malnutrition Screening Standard of Schoolage Children and Adolescents was used to screen malnutrition. Statistical analysis was performed using the χ2 test and the χ2trend test.
Results:
In the four surveys conducted during 2005 to 2019, the prevalence of malnutrition among primary and middle school students were 22.12%, 18.80%, 15.89% and 9.56%, respectively, with an increase of -12.56% and an average annual increase of -5.82%. The decreasing trend of malnutrition by year was statistically significant (χ2trend=600.72, P<0.01), and the proportion of emaciation type was the highest (8.87%-20.15%). The detection rates of malnutrition among all students aged 7 to 18 showed a decreasing trend from 2005 to 2019 (χ2trend=56.44, 60.04, 61.48, 42.49, 51.81, 50.81, 72.86, 101.34, 86.38, 24.81, 17.72, 10.38, P<0.01). From 2005 to 2019, the detection rates of malnutrition in boys were higher than that of girls (in 4 surveys), and that in rural students from 2005 to 2014 of 3 surveys were higher than that in towns (χ2=92.07, 35.16, 25.29, 29.98; 64.35, 4.26, 6.32, P<0.05).
Conclusions
The malnutrition of Han nationality primary and middle school students aged 7-18 years in Hainan Province show a trend of improvement year by year from 2005 to 2019, despite the overall high detection rate. Wasting is the most common type of malnutrition. The epidemic of malnutrition varies by age, sex and areas. Further targeted measures should be taken to strengthen intervention in the diet of primary and middle school students, to improve the nutritional status of children and adolescents.
5.Chinese Translation of the Stanford Expectations of Treatment Scale and Its Application Evaluation on Traditional Chinese Medicine for Diarrhea-Predominant Irritable Bowel Syndrome with Liver-Constraint and Spleen-Deficiency Syndrome
Shibing LIANG ; Yingying ZHANG ; Zhijie WANG ; Zeyu YU ; Mei HAN ; Huijuan CAO ; Guoyan YANG ; Shihuan CAO ; Hongjie CHENG ; Qiaoyan ZHANG ; Youzhu SU ; Yufei LI ; Jianping LIU
Journal of Traditional Chinese Medicine 2024;65(19):1994-2001
ObjectiveTo adapt the Stanford Expectations of Treatment Scale(SETS) into Chinese(C-SETS) and test the feasibility, validity and reliability of its application in patients with diarrhea-predominant irritable bowel syndrome(IBS-D) with liver-constraint and spleen-deficiency syndrome treated with traditional Chinese medicine(TCM). MethodsWe obtained authorisation from the developer of the SETS, and followed the principle of "two-way translation" to translate the SETS by literal translation and back translation to form the C-SETS. Ninety-six IBS-D patients with liver-constraint and spleen-deficiency syndrome were enrolled as respondents and filled out C-SETS before receiving treatment; the feasibility was assessed by the recall rate, completion rate and the duration of filling out the scale; the reliability was assessed by Cronbach's α; the structural validity was assessed by exploratory and confirmatory factor analysis, and the content validity was assessed by correlation analysis. ResultsThe C-SETS consists of 10 items, with the 1st, 3rd, and 5th rating items constituting the Positive Expectations subscale, and the 2nd, 4th, and 6th rating items constituting the Negative Expectations subscale, each of which is rated on a 7-point Likert Scale. The recall of C-SETS was 100%(96/96), the completion rate was 89.58%(86/96); Cronbach's α for the Positive and Negative Treatment Expectations subscales were 0.845 and 0.854, respectively; exploratory factor analysis showed that the coefficient of commonality for all six entries was larger than 0.4, and that the six entries could be used by both factors to explain 77.092% of the total variance; validation factor analysis showed that the goodness-of-fit index, comparative fit index, root mean square of approximation error, canonical fit coefficient, and chi-square degrees of freedom ratio took the values of 0.943, 1.003, 0, 0.943, and 0.626, respectively; and the results of Spearman's analysis suggested that the C-SETS had good content validity. ConclusionThe C-SETS has well feasibility, reliability, and validity, which initially proves that it can be used as a tool to assess the treatment expectation of patients with IBS-D with liver-constraint and spleen-deficiency syndrome before receiving TCM treatment.
6.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.
7.Analysis and prediction of disease burden of cirrhosis and other chronic liver diseases due to alcohol use in China from 1990 to 2030
Sui ZHU ; Shentong CHEN ; Yingying JIN ; Shangwen LU ; Fengjuan ZOU ; Wenjun MA ; Fangfang ZENG ; Xiaofeng LIANG
Chinese Journal of Epidemiology 2024;45(2):185-191
Objective:To comprehensively understand the disease burden of liver cirrhosis and other chronic liver diseases caused by alcohol use in China from 1990 to 2019, as well as to predict the trends in disease burden from 2020 to 2030.Methods:The analysis utilized data from the Global Burden of Disease study in 2019 (GBD2019). Key indicators such as incidence rate, mortality rate, disability-adjusted life years (DALY), years of life lost due to premature mortality, and years lived with disability were selected to describe the disease burden of alcohol-related liver cirrhosis and other chronic liver diseases in China from 1990 to 2019. The estimated annual percentage change (EAPC) was used to depict the temporal trends in disease burden. Furthermore, a Bayesian age-period-cohort (BAPC) model was constructed using R software to predict the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of alcohol-related liver cirrhosis and other chronic liver diseases in China from 2020 to 2030.Results:From 1990 to 2019, the incidence of alcohol-related liver cirrhosis and other chronic liver diseases in China showed an upward trend, with an EAPC of 0.31% (95% CI: 0.10%-0.52%). However, the DALY declined, with an EAPC of -2.81% (95% CI: -2.92% - -2.70%). The ASMR showed a downward trend, with an EAPC of -2.55% (95% CI: -2.66% - -2.45%). The highest incidence of cirrhosis of liver caused by alcohol and other chronic liver diseases was reported in the age group of 35-49 years, while the ASMR increased gradually with age, with a significant rise after the age of 30. The age-standardized DALY rate peaked between the ages of 55 and 64. The disease burden indicators for males were consistently higher than those for females during the same period. According to the predictions of the BAPC model, from 2020 to 2030, the ASIR for cirrhosis of liver caused by alcohol and other chronic liver diseases in the entire population of China was projected to increase from 3.45/100 000 in 2020 to 3.78/100 000 in 2030, a growth of 9.57%. Conversely, the ASMR was expected to decrease from 1.45/100 000 in 2020 to 1.24/100 000 in 2030, a reduction of 14.48%. Conclusions:The disease burden of cirrhosis of liver caused by alcohol and other chronic liver diseases remained serious in China, especially in men and the middle-aged to elderly population. There is a pressing need to prioritize attention and resources towards these groups. Despite the projected decrease in ASMR, the ASIR continued to rise and is expected to persist in its upward trend until 2030.
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.Drug resistance mutation analysis of HIV-1 among blood donors in Dalian:2011-2020
Xiaohan GUO ; Xuelian DENG ; Xiaochun LIU ; Yingying WANG ; Liang ZANG ; Jun ZHOU
Chinese Journal of Blood Transfusion 2024;37(8):902-907
Objective To study the distribution and trend of HIV-1 drug resistance mutation in Dalian blood donors be-tween 2011 and 2020.Methods The protease-reverse transcriptase(PR-RT)region was sequenced in Dalian blood donors tested HIV-1 positive between 2011 and 2020.Drug resistance mutation(DRM)rate and level of resistance to selected drugs were analyzed by the Stanford HIV Drug Resistance Database.Results DRM were detected in 17.2%(30/174)of samples,while transmitted drug resistance(TDR)was5.7%(10/174).Between2011 and2020,DRM and TDR rates in-creased significantly in 2019 and reached their highest levels in 2020(44.4%and 22.2%,respectively).DRM carriage was associated with people with college degree or above and with local residents(P<0.05).NNRTI DRMs were the most fre-quently detected(12.6%,22/174),followed by PIs(5.7%,10/174),with V179D/E/T and M46I being the main DRMs detected.Only one HIV-1strain(0.57%,1/174)carried a NRTI DRM(L74I).The overall rate of predicted high level re-sistance to antiretroviral drugs was 6.9%(12/174),with the highest proportion of NNRTI resistance(83.3%,10/12).Two samples were classified as highly resistant to EFV and NVP,accounting for 1.1%(2/174).CRF55_01B strains showed a significantly higher DRM rate than strains of other HIV-1 genotypes(P<0.05).Conclusion Between 2011 and 2020,the rate of HIV-1 DRMs in blood donors in Dalian showed a significant upward trend,particularly in 2019-2020,with NNRTI resistance being the most common.The combination of DRMs detection before and after implementation of ART un-der the latest national ART treatment plan would improve the effectiveness of HIV-1 prevention and control locally.
10.Grey-scale Reversed T1-weighted MRI for Detecting Structural Lesions of the Sacroiliac Joint in Patients with Axial Spondyloarthritis
Ximeng LI ; Wenjuan LI ; Ke ZHANG ; Chaoran LIU ; Yunfei ZHU ; Yingying ZHAN ; Mingzhu LIANG ; Guobin HONG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(3):412-419
[Objective]To analyze the value of grey-scale reversed T1-weighted(rT1)MRI in the detection of structur-al lesions of the sacroiliac joint(SIJ)in patients with axial spondyloarthritis(ax-SpA).[Methods]Fifty-two ax-SpA pa-tients who underwent both MRI and CT in our hospital within a week from February 2020 to December 2022 were retrospec-tively included.Both sacral and iliac side of each SIJ on oblique coronal images were divided into anterior,middle and pos-terior portion.Two radiologists reviewed independently three groups of MRI including T1-weighted imaging(T1WI),rT1 and T1WI+rT1 images to evaluate the structural lesions like erosions,sclerosis and joint space changes in each of the 6 re-gions of the SIJ.One of the radiologist did the evaluation again one month later.CT images were scored for lesions by a third radiologist and served as the reference standard.Intra-class correlation coefficients(ICC)were calculated to test the inter-and intra-reader agreement for the assessment of SIJ lesions.A Friedman test was performed to compare the lesion results of MRI and CT image findings.We examined the diagnostic performance[accuracy,sensitivity(SE)and specifici-ty]of different groups of MRI in the detection of lesions by using diagnostic test.A McNemar test was used to compare the differences of three groups of MRI findings.[Results]CT showed erosions in 71 joints,sclerosis in 65 and joint space changes in 53.Good inter-and intra-reader agreements were found in three groups of MRI images for the assessment of le-sions,with the best agreement in T1WI+rT1.There were no difference between T1WI+rT1 and CT for the assessment of all lesions,nor between rT1 and CT for the assessment of erosions and joint space changes(P>0.05).T1WI+rT1 yielded better accuracy and SE than T1WI in detection of all lesions(Accuracy erosions:90.3%vs 76.9%;SE erosions:91.6%vs 76.1%;Accu-racy sclerosis:89.4%vs 80.8%;SE sclerosis:84.6%vs 73.9%;Accuracy joint space changes:86.5%vs 73.1%;SE joint space changes:84.9%vs 60.4%;P<0.05).rT1 yielded better accuracy and SE than T1WI in detection of erosions and joint space changes(Accuracy erosions:87.5%vs 76.9%;SE erosions:88.7%vs 76.1%;Accuracy joint space changes:85.6%vs 73.1%;SE joint space changes:83.0%vs 60.4%;P<0.05).[Conclusions]In the detection of SIJ structural lesions in ax-SpA,rT1 improves the diagnostic perfor-mance and T1WI+rT1 is more superior to others.


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