1.High-dose estrogen impairs demethylation of H3K27me3 by decreasing Kdm6b expression during ovarian hyperstimulation in mice.
Quanmin KANG ; Fang LE ; Xiayuan XU ; Lifang CHEN ; Shi ZHENG ; Lijun LOU ; Nan JIANG ; Ruimin ZHAO ; Yuanyuan ZHOU ; Juan SHEN ; Minhao HU ; Ning WANG ; Qiongxiao HUANG ; Fan JIN
Journal of Zhejiang University. Science. B 2025;26(3):269-285
Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female
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Mice
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Demethylation/drug effects*
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Embryonic Stem Cells
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Estrogens/administration & dosage*
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Gene Expression/drug effects*
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Histones/metabolism*
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Jumonji Domain-Containing Histone Demethylases/metabolism*
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Mice, Inbred C57BL
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Oocytes
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Ovary/drug effects*
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Reproductive Techniques, Assisted
;
Animals
2.The management of infantile laryngeal cysts.
Fan LOU ; Cheng MING ; Yan GAO ; Jinyan ZU ; Jing MA
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(2):120-123
Objective:To explore the therapeutic strategy for laryngeal cysts in infants. Methods:A retrospective analysis of the clinical data of 19 children with laryngeal cysts treated in Kunming Children's Hospital from January 2020 to January 2023. All patients were diagnosed through electronic laryngoscopy examination. Twelve neonates were admitted to the neonatal intensive care unit. Five of them received mechanical ventilation with tracheal intubation before surgery due to severe respiratory distress, and seven received oxygen therapy with a head mask. The remaining seven children were admitted to Department of Otolaryngology Head and Neck Surgery, of which three cases were treated with oxygen therapy through a mask during sleep due to frequent shortness of breath during sleep. All patients underwent low-temperature plasma radiofrequency ablation under general anesthesia to remove the cysts. Results:Three newborns were unable to have their tracheal tubes removed due to complications with pneumonia after surgery, while the rest of the children were able to have their tubes successfully removed after complete anesthesia, and no gastric tubes were placed. All postoperative respiratory difficulties in the children disappeared, and there were no complications such as bleeding, hoarseness, or laryngeal stenosis. Five pediatric patients had incomplete relief of laryngeal ringing symptoms one month after surgery, and electronic laryngoscopy diagnosed laryngeal softening. Regular follow-up is recommended. One child relapsed 4 months after surgery and underwent a follow-up surgery six months later without recurrence. Conclusion:Endoscopic low-temperature plasma radiofrequency ablation is an effective surgical method for treating laryngeal cysts, with a low postoperative recurrence rate. Laryngeal cysts may be accompanied by laryngeal softening, which may be a possible reason for the postoperative symptoms not improving.
Humans
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Retrospective Studies
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Cysts/surgery*
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Laryngeal Diseases/surgery*
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Infant
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Laryngoscopy
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Infant, Newborn
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Male
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Female
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Radiofrequency Ablation
3.Diagnostic value of MRI radiomics analysis in mild carpal tunnel syndrome
Fan ZHAO ; Hongda LOU ; Weina WU ; Yingwei CHANG ; Hua GENG ; Yuping LI
Journal of Practical Radiology 2025;41(1):85-88,137
Objective To explore the diagnostic value of MRI radiomics analysis in mild carpal tunnel syndrome(CTS).Methods Seventy patients with mild CTS and 86 healthy volunteers who underwent wrist MRI examination were retrospectively selected.MRI fat-suppressed proton density weighted imaging(PDWI)were imported into 3D Slicer software,and the region of interest(ROI)delineation was performed by two radiologists independently.The 830 radiomics parameters were extracted,including first-order fea-tures,shape features,texture features,and wavelet-transform features.Radiomics parameter selection was performed through observer intraclass correlation coefficient(ICC),correlation analysis,and multivariate logistic regression.Five diagnostic models were estab-lished,including logistic regression,support vector machine,naive Bayes,decision tree,and random forest.Receiver operating charac-teristic(ROC)curve was used to analyze the diagnostic efficiency of the models.Results Seven radiomics features were selected for inclusion in the diagnostic models.The logistic regression model demonstrated the best performance,with an area under the curve(AUC)of 0.91[95%confidence interval(CI)0.86-0.96],a sensitivity of 88.63%,and a specificity of 89.00%in the training group.In the test group,the AUC was 0.92(95%CI 0.85-0.97),with a sensitivity of 90.48%and a specificity of 84.62%.Conclusion MRI radiomics analysis can be used to diagnose mild CTS,and the logistic regression model demonstrates superior diagnostic per-formance.
4.Mechanism of Huayu jiedu formula in alleviating inflammatory injury in chronic kidney disease based on AIM2 pyroptosis pathway
Jinhuan XUE ; Ziwen WU ; Fan YANG ; Yunyun LOU ; Yingjun DING ; Yupeng XIAO ; Xianhui LIU ; Wenjie LIANG
China Pharmacy 2025;36(21):2638-2644
OBJECTIVE To explore the mechanism of Huayu jiedu formula in regulating inflammatory injury in chronic kidney disease (CKD). METHODS Fifty male SD rats were randomly divided into a sham surgery group (10 rats) and a modeling group (40 rats). The CKD model was replicated in the modeling group by unilateral ureteral obstruction surgery. After successful modeling, the rats were randomly divided into model group, esaxerenone group (positive control), and TCM low- and high-dose groups, with 10 rats in each group. The Esaxerenone group was given 1 mg/kg of esaxerenone, while the TCM low- and high-dose groups were given 13.7 and 27.4 g/kg of Huayu jiedu formula respectively, the sham surgery group and model group were given an equal volume of physiological saline, all groups were intervened continuously for 14 days. Hematoxylin eosin and Masson staining were used to observe the pathological changes in rat kidney tissue. Conventional biochemical methods were used to detect serum urea (SUr), serum creatinine (SCr), malondialdehyde (MDA), and superoxide dismutase (SOD) levels; enzyme-linked immunosorbent assay was used to detect the levels of serum interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α(TNF-α); immunohistochemistry and Western blot were used to detect the protein expression of peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α) , mitochondrial transcription factor A (TFAM), absent in melanoma 2(AIM2), caspase-1, gasdermin D (GSDMD), IL-1β and IL-18 in renal tissue; real-time fluorescence quantitative PCR was used to detect the mRNA expression of AIM2. RESULTS Compared with the sham surgery group, the renal tissue of the model group showed pathological changes such as glomerular deformation and destruction, severe tubular dilation, and increased deposition of blue fibrin; the levels of SUr, SCr, MDA, IL-1β, IL-6, TNF-α,the protein expression of AIM2, GSDMD, caspase-1, IL-1β, IL-18 , and the mRNA expression of AIM2 were significantly increased or up-regulated (P<0.01); the levels of SOD, the protein expression of PGC-1α, TFAM were significantly reduced or down-regulated (P<0.01). Compared with the model group, all treatment groups showed improvement in the above symptoms and most indicators in rats. CONCLUSIONS Huayu jiedu formula may improve renal function, alleviate renal inflammatory damage and pyroptosis, and exert renal protective effects by regulating the AIM2 pyroptosis pathway.
5.Huanglian Jiedu Decoction prevents and treats acute liver injury in septic mice via AMPK/SIRT1 autophagy pathway.
Rui-Zhu ZHAO ; Xin-Yue REN ; Yu-Hang WANG ; Ding-Xing FAN ; Shi-Lei LOU ; Hui YAN ; Cong SUN
China Journal of Chinese Materia Medica 2025;50(2):507-514
This study aims to explore the mechanism of Huanglian Jiedu Decoction(HJD) in treating acute liver injury(ALI) in the mouse model of sepsis induced by lipopolysaccharide(LPS). Fifty-four male C57BL/6 mice were randomized into six groups: blank group, model group, low-, medium-, and high-dose group HJD, and dexamethasone group. The mouse model of sepsis was established by intraperitoneal injection of LPS after 7 days of gavage with HJD, and dexamethasone(0.2 mL) was injected intraperitoneally 1.5 h after modeling. The murine sepsis score(MSS) was recorded 12 h after modeling. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver tissue and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the serum were measured by ELISA. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of the mouse liver. The content of light chain 3 of microtubule-associated protein 1(LC3) was detected by immunofluorescence, and that of sirtuin 1(SIRT1) was detected by immunohistochemistry. The mRNA levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), LC3, and P62 were detected by RT-PCR. Western blot was employed to determine the protein levels of AMPK, p-AMPK, and SIRT1 in the liver tissue. The results showed that compared with model group, drug interventions decreased the MSS and liver injury indicators, lowered the levels of inflammatory cytokines, improved the liver tissue structure, upregulated the protein levels of of p-AMPK/AMPK and SIRT1 and the mRNA levels of AMPK and LC3, and downregulated the mRNA level of P62. To sum up, HJD can regulate the autophagy level and reduce inflammation to ameliorate acute liver injury in septic mice by activating the AMPK/SIRT1 autophagy pathway.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Sirtuin 1/genetics*
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Male
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Mice
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Sepsis/metabolism*
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Mice, Inbred C57BL
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Autophagy/drug effects*
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AMP-Activated Protein Kinases/genetics*
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Liver/metabolism*
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Humans
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Signal Transduction/drug effects*
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Disease Models, Animal
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Tumor Necrosis Factor-alpha/genetics*
6.Mechanism of SOS1-IT1 promoting EZH2 expression in human endometrial cancer cells by regulating acetylation modification
Hong-Yang LIU ; Xue-Ling LOU ; Rong-Jing ZHANG ; Quan-Ling FENG ; Kai-Ge GUO ; Hao-Fan WANG ; Ying-Ying LI ; Jun-Hu WAN ; Lin-Dong ZHANG
Acta Anatomica Sinica 2025;56(4):444-451
Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.
7.Research progress of mitochondrial quality control in diabetic retinopathy
Junfang FAN ; Jiangning YIN ; Shihan LOU
Chinese Journal of Diabetes 2025;33(5):392-395
[Summary]Diabetic retinopathy is the most common diabetic microvascular complication and the leading cause of vision loss in adults.Mitochondrial quality control regulates the quality and quantity of mitochondria through a series of processes to maintain mitochondrial function and homeostasis.These processes include mitochondrial biogenesis,mitochondrial dynamics and mitochondrial autophagy,abnormalities of which can lead to mitochondrial dysfunction.Current studies have shown that mitochondrial dysfunction is associated with a variety of diseases,including neurodegenerative diseases,tumors,cardiovascular diseases and diabetes.At present,there are few studies on mitochondrial dysfunction and DR.This paper reviews the literature on mitochondrial quality control and DR,discusses the possible role of mitochondrial dysfunction in the occurrence and development of DR in order to seek possible molecular therapeutic targets.
8.MRI radiomics model for predicting postoperative prognosis of moderate carpal tunnel syndrome
Fan ZHAO ; Hongda LOU ; Weina WU ; Yingwei CHANG ; Hua GENG ; Limei JIA ; Guiping LI ; Yuping LI
Chinese Journal of Medical Imaging Technology 2025;41(6):963-966
Objective To observe the value of MRI radiomics model for predicting postoperative prognosis of moderate carpal tunnel syndrome(CTS).Methods A total of 126 patients with moderate CTS who underwent endoscopic release and fat-suppressed proton density weighted imaging(PDWI)before operation were retrospectively enrolled.The patients were divided into good prognosis group(n=80)and poor prognosis group(n=46)based on postoperative functional evaluation,also randomly divided into training set and validation set at a ratio of 7∶3.Volume of interest(VOI)of the median nerve was obtained through delineating ROI of the affected wrist on fat suppressed PDWI.Radiomics features were extracted,and those associated with postoperative prognosis of CTS were screened in training set.Clinical prediction model,radiomics model and combined model of these two were established,and the predictive efficacy of the models were evaluated and compared according to the area under the curve(AUC)of receiver operating characteristic(ROC)curve.Results Patients in poor prognosis group were older than in good prognosis group(P<0.05).A clinical model was constructed based on age.The radiomics model was constructed based on 6 radiomics features associated with postoperative prognosis of CTS,with predictive efficacy(AUC=0.872)higher than that of clinical model(AUC=0.604,P<0.05)but not significantly different with that of the combined model(AUC=0.905,P>0.05).Conclusion MRI radiomics model could be used to effectively predict postoperative prognosis of moderate CTS.
9.Analysis of ACTH level heterogeneity and the diagnostic value of serum dehydroepiandrosterone sulfate in patients with subclinical Cushing′s syndrome
Wenji ZHAO ; Jiawei YANG ; Yuxing LOU ; Wei ZHANG ; Shiman LI ; Ziwei ZHANG ; Fan YANG ; Ping LI
Chinese Journal of Endocrinology and Metabolism 2025;41(10):830-836
Objective:To investigate the clinical characteristics and hormonal changes in patients with adrenocorticotropic hormone(ACTH)-suppressed and non-suppressed subclinical Cushing′s syndrome(SCS), to evaluate the influencing factors of ACTH suppression, and to assess the diagnostic efficiency of serum dehydroepiandrosterone sulfate(DHEAS) levels in distinguishing these two groups of SCS patients.Methods:Clinical data of patients diagnosed with SCS in the Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical College, between June 2014 and October 2023 were retrospectively collected. A total of 194 cases were included. According to morning(8: 00 AM) plasma ACTH levels, patients were divided into an ACTH-suppressed group(ACTH<2.2 pmol/L) and a non-suppressed group(ACTH≥2.2 pmol/L). Additionally, 194 gender-, age-, and BMI-matched patients with non-functional adrenal tumors(NFA) were enrolled as controls. Clinical characteristics and hormone levels were compared between groups. Logistic regression analysis was performed to identify factors influencing ACTH suppression in SCS patients. Furthermore, receiver operating characteristic(ROC) curve analysis was conducted to evaluate the diagnostic performance of serum DHEAS levels in distinguishing ACTH-suppressed and non-suppressed SCS patients. Results:There were no significant differences in the prevalence of overweight/obesity, hypertension, abnormal glucose metabolism, or bone metabolism disorders between the ACTH-suppressed and non-suppressed groups. The serum cortisol level after the 1 mg-dexamethasone suppression test(DST) was significantly lower in the ACTH non-suppressed group than that in the suppressed group, while the serum DHEAS level was significantly higher in the non-suppressed group(both P<0.01). The area under the curve(AUCs) of serum DHEAS for diagnosing ACTH non-suppressed SCS patients and ACTH-suppressed SCS patients was 0.779(95% CI 0.721-0.837) and 0.874(95% CI 0.831-0.918), respectively. Using a serum DHEAS cutoff of 60.0 μg/dL, the sensitivity and specificity for diagnosing ACTH non-suppressed SCS patients were 66.7% and 76.1%, respectively, while for ACTH-suppressed SCS patients, the sensitivity and specificity were 84.9% and 75.5%, respectively. Conclusion:There were no significant differences in metabolic characteristics between ACTH-suppressed and non-suppressed SCS patients. Serum cortisol level after 1 mg-DST is an independent influencing factor for ACTH suppression status. Low serum DHEAS level serves as a sensitive diagnostic marker for SCS and also demonstrates diagnostic value in ACTH non-suppressed SCS patients.
10.Analysis of the Influencing Factors and Short-Term Prognosis of Early Onset Coronary Heart Disease in Women in Wansheng District of Chongqing
Xiu-ping LOU ; Shi-cai LAN ; Hai-na FAN ; Yan WANG ; Sheng ZHANG ; Nong-hao WEN ; Rui-peng WEI
Progress in Modern Biomedicine 2025;25(20):3247-3253
Objective:To explore the incidence status,influencing factors and short-term prognosis characteristics of early onset coronary heart disease in women in Wansheng District of Chongqing,and to provide scientific basis for formulating regional prevention and treatment strategies.Methods:This study was a single-center retrospective study,100 coronary heart disease in women from January 2022 to December 2023 at Chongqing Wansheng Economic and Technological Development Zone People's Hospital were prospective selected,and they were divided into early onset group of 40 cases(≤ 65 years old)and late onset group of 60 cases(>65 years old)based on their age of onset.Another 60 healthy women who underwent physical examinations during the same period to exclude coronary heart disease were selected as the control group.Univariate factor and multiple factor logistic regression analysis were used to identify independent risk factors for early onset coronary heart disease in women.Draw receiver operating characteristic(ROC)curve for the subjects,the efficacy of risk factors in predicting early onset coronary heart disease based on the area under the curve(AUC)of ROC curve were evaluated.Patients were followed up for 1 year to observe the occurrence of major adverse cardiovascular events(MACE).Result:Among 100 fcoronary heart disease in women,the early onset group accounted for 40.00%(40/100).Univariate analysis showed that age,hyperlipidemia history,smoking history,hypertension history,family history,diabetes history,total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)were related to the early onset coronary heart disease.Multivariate analysis showed that,hyperlipidemia history(OR=4.124,95%CI:2.343-7.217),smoking history(OR=3.564),hypertension(OR=3.253),family history(OR=2.981),diabetes history(OR=2.873)were independent risk factors.ROC curve analysis results showed that joint evaluation had the best predictive value,with AUC of 0.829,which was higher than the AUC of individual evaluation for each factor.The incidence of MACE in the early onset group(45.00%)was significantly higher than that in the late onset group(P<0.05).Conclusion:Early onset coronary heart disease in women in Wansheng District of Chongqing is related to the hyperlipidemia history,smoking,hypertension history,family history and diabetes history.The incidence of MACE in early-onset patients followed up for 1 year is higher than that in late-onset patients.

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