1.A Mouse Model of Polycystic Ovary Syndrome Established Through Subcutaneous Administration of Letrozole Sustained-Release Pellets and Hepatic Transcriptome Analysis
Qiuyu XU ; Guofeng YAN ; Li FU ; Wenhua FAN ; Jing ZHOU ; Lian ZHU ; Shuwen QIU ; Jie ZHANG ; Ling WU
Laboratory Animal and Comparative Medicine 2025;45(2):119-129
Objective Prepubertal mice are administered subcutaneously with letrozole sustained-release pellets behind the neck and treated with a high-fat diet to establish a mouse model of polycystic ovary syndrome(PCOS).The liver transcriptomes of the model mice are compared with those of the placebo control mice to investigate the underlying mechanisms of liver involvement in the pathogenesis of PCOS.Methods A customized 2 mg dose of letrozole sustained-release pellets with a 40-day release period was used.The control placebo and letrozole pellets were implanted subcutaneously in the dorsal cervical region of 3-4-week-old C57BL/6J mice(8 mice per group)to establish the control group and letrozole-induced PCOS model group.Both groups were treated with a high-fat diet starting the day after administration.The modeling period lasted for 5 weeks,during which body weight and 24-hour food intake were monitored in each group every week.When samples were collected,liver weight was recorded.Pathological changes in ovarian and hepatic tissues were examined by hematoxylin-eosin(HE)staining,while hepatic lipid deposition was observed by Oil Red O staining.The extent of macrophage infiltration in the liver was evaluated via F4/80 immunohistochemical staining,and hepatic fibrosis levels were observed by Masson's trichrome staining.Transcriptomic sequencing was performed to analyze differentially expressed genes(DEGs)in liver tissues between the control and model groups,followed by enrichment analysis of significant DEGs.Quantitative real-time fluorescent quantitative PCR(qPCR)was subsequently used to validate the expression of significant DEGs in liver tissues of both groups.Results Compared with the control group,the model group which received subcutaneous letrozole sustained-release pellets combined with a high-fat diet exhibited significantly increased body weight(P<0.001),prominent polycystic ovarian morphology,and significantly decreased liver-to-body weight ratio(P<0.05).However,no significant changes were observed in absolute liver weight(P>0.05),hepatic histomorphology,or lipid deposition.Transcriptome sequencing identified 119 upregulated and 217 downregulated DEGs in the liver tissues of letrozole-treated mice,which were predominantly enriched in pathways related to cholesterol and steroid biosynthesis,steroid hormone metabolism,and inflammatory responses.qPCR validation demonstrated that mRNA expression of HSD3B2 and HMGCR was significantly upregulated in liver(P<0.01),while mRNA expression of IL4,CCL2 and COL1A1 was downregulated(P<0.05)in the model group compared with the control group.However,Masson's trichrome staining and F4/80 immunohistochemical analysis showed no significant changes in hepatic fibrosis or macrophage infiltration.Conclusion Subcutaneous administration of letrozole sustained-release pellets combined with a high-fat diet successfully establishes a mouse model of PCOS.The model mice exhibited significant changes in hepatic gene expression.Liver may contribute to PCOS pathogenesis through regulating cholesterol and steroid metabolism.
2.A Mouse Model of Polycystic Ovary Syndrome Established Through Subcutaneous Administration of Letrozole Sustained-Release Pellets and Hepatic Transcriptome Analysis
Qiuyu XU ; Guofeng YAN ; Li FU ; Wenhua FAN ; Jing ZHOU ; Lian ZHU ; Shuwen QIU ; Jie ZHANG ; Ling WU
Laboratory Animal and Comparative Medicine 2025;45(2):119-129
Objective Prepubertal mice are administered subcutaneously with letrozole sustained-release pellets behind the neck and treated with a high-fat diet to establish a mouse model of polycystic ovary syndrome(PCOS).The liver transcriptomes of the model mice are compared with those of the placebo control mice to investigate the underlying mechanisms of liver involvement in the pathogenesis of PCOS.Methods A customized 2 mg dose of letrozole sustained-release pellets with a 40-day release period was used.The control placebo and letrozole pellets were implanted subcutaneously in the dorsal cervical region of 3-4-week-old C57BL/6J mice(8 mice per group)to establish the control group and letrozole-induced PCOS model group.Both groups were treated with a high-fat diet starting the day after administration.The modeling period lasted for 5 weeks,during which body weight and 24-hour food intake were monitored in each group every week.When samples were collected,liver weight was recorded.Pathological changes in ovarian and hepatic tissues were examined by hematoxylin-eosin(HE)staining,while hepatic lipid deposition was observed by Oil Red O staining.The extent of macrophage infiltration in the liver was evaluated via F4/80 immunohistochemical staining,and hepatic fibrosis levels were observed by Masson's trichrome staining.Transcriptomic sequencing was performed to analyze differentially expressed genes(DEGs)in liver tissues between the control and model groups,followed by enrichment analysis of significant DEGs.Quantitative real-time fluorescent quantitative PCR(qPCR)was subsequently used to validate the expression of significant DEGs in liver tissues of both groups.Results Compared with the control group,the model group which received subcutaneous letrozole sustained-release pellets combined with a high-fat diet exhibited significantly increased body weight(P<0.001),prominent polycystic ovarian morphology,and significantly decreased liver-to-body weight ratio(P<0.05).However,no significant changes were observed in absolute liver weight(P>0.05),hepatic histomorphology,or lipid deposition.Transcriptome sequencing identified 119 upregulated and 217 downregulated DEGs in the liver tissues of letrozole-treated mice,which were predominantly enriched in pathways related to cholesterol and steroid biosynthesis,steroid hormone metabolism,and inflammatory responses.qPCR validation demonstrated that mRNA expression of HSD3B2 and HMGCR was significantly upregulated in liver(P<0.01),while mRNA expression of IL4,CCL2 and COL1A1 was downregulated(P<0.05)in the model group compared with the control group.However,Masson's trichrome staining and F4/80 immunohistochemical analysis showed no significant changes in hepatic fibrosis or macrophage infiltration.Conclusion Subcutaneous administration of letrozole sustained-release pellets combined with a high-fat diet successfully establishes a mouse model of PCOS.The model mice exhibited significant changes in hepatic gene expression.Liver may contribute to PCOS pathogenesis through regulating cholesterol and steroid metabolism.
3.Clinicopathological and genetic characteristics of common lymphatic malformations in superficial soft tissues
Qiuyu LIU ; Chunxiao LI ; Dakan LIU ; Shuang XUE ; Fangfang FU ; Xiaoshuang ZHU ; Lingfei KONG ; Changxian DONG
Chinese Journal of Pathology 2024;53(3):230-236
Objective:To investigate the clinicopathological features, classification, and genetic characteristics of common lymphatic malformation (CLM) in superficial soft tissue.Methods:A retrospective study of 110 patients with the diagnosis of CLM at the Henan Province People′s Hospital, China from August 2019 to August 2022 was performed. The clinicopathological features, relevant immunohistochemical (IHC) staining results, and fluorescence quantitative PCR of PIK3CA mutation were analyzed, and patients were followed up.Results:Among the 110 CLM patients, there were 53 males and 57 females; 65 cases (65/110, 59.1%) were first detected when the patients were≤2 years old. The most common location was the head and neck in 41 cases (41/110, 37.3%). Clinically, 102 cases (102/110, 92.7%) were solitary, 83 cases (83/110, 75.5%) were skin-colored, 69 cases (69/110, 62.7%) had indistinct borders, and 10 cases (10/110, 9.1%) had diffuse and severe macroscopic manifestations. There were 52 macrocystic type (52/110, 47.3%), 23 microcystic type (23/110, 20.9%), and 35 combined type (35/110, 31.8%). The macrocystic CLM presented as soft, translucent masses with large cystic cavities on the cut surface, and histologically they were composed of large, irregularly dilated channels that were thicker with irregular smooth muscle and lymphocytic infiltration. Microcystic CLM showed wartlike projections or translucent blisters on the skin, with small honeycomb structures on the cut surface, and histologically consisted of round or angular dilated small lymphatic vessels with little or no smooth muscle. The combined CLM had both macrocystic and microcystic morphologies. IHC staining showed that the lymphatic endothelial cells were positive for LYVE-1, D2-40, PROX1, CD31, and VEGFR3 but negative for CD34; in the macrocystic and combined CLM vessel walls were positive for SMA. Eight of 13 CLM had PIK3CA mutation. All patients were followed up, and 24 (24/110, 21.8%) had relapses, which more frequently occurred in combined type, followed by microcystic type.Conclusions:CLM is a congenital vascular malformation composed of dilated, abnormal lymphatic channels, with PIK3CA mutation. There are significant differences in clinicopathological characteristics among the different types. Since microcystic and combined CLM are prone to recurrence, accurate pathological subtyping is necessary to guide treatment and to predict prognosis.
4.The clinical value of coronary artery calcification in early screening of coronary atherosclerotic heart disease in civil pilots
Lin ZHANG ; Qingqing JIN ; Qingqing DUAN ; Yan XU ; Qiuyu SHEN ; Shaojie ZHU ; Kai CHEN ; Jie GAO ; Yukai LI ; Yan CHEN ; Xuejun ZHAO ; Meng SONG ; Jinke ZHENG ; Bin REN
Chinese Journal of Aerospace Medicine 2023;34(4):210-214
Objective:To explore the clinical value of coronary artery calcification (CAC) detected by chest CT in early screening of coronary atherosclerotic heart disease (CAHD) in civil pilots.Methods:The physical examination data of 2 899 civil pilots were retrospectively analyzed. Pilots were divided into CAHD group and control group based on the results of coronary angiography (CAG). The health data were compared between 2 groups and the clinical value of CAC in the diagnosis of CAHD was analyzed by using binary Logistic regression model and receiver operating characteristic (ROC) curve.Results:Thirty-eight CAHD cases were diagnosed, and the remaining 2 861 were in the control group. Comparing to that of control group, the average age of the pilots in CAHD group was greater ( t=12.09, P<0.001), and the average total flying hours were longer ( Z=-7.68, P<0.001). The proportions of smoking, hyperlipidemia, diabetes, hypertension, fatty liver, obesity, carotid plaques, positive or suspiciously positive in submaximal treadmill exercise test, CAC, as well as the proportions of taking further requested coronary CT angiography and CAG were significantly higher in the CAHD group ( χ2=5.42-1 430.25, P<0.01 or <0.05). Logistic regression model showed that smoking ( OR=2.800, 95% CI: 1.074-7.301, P=0.035), obesity ( OR=3.336,95% CI:1.243-8.956, P=0.017), positive or suspiciously positive in submaximal treadmill exercise test ( OR=17.669, 95% CI: 2.923-106.756, P=0.002) and CAC ( OR=96.039, 95% CI: 11.439-806.396, P<0.001) were the independent risk factors for diagnosing CAHD. The ROC curve results suggested that the sensitivity and specificity of CAC for predicting CAHD was 97.4% and 93.1%, respectively, and the area under the ROC curve was 0.952 ( P<0.001). Conclusions:CAC detected by chest CT in physical examination is helpful for early screening of asymptomatic or atypical CAHD in civil pilots.
5.The clinical value of coronary artery calcification in early screening of coronary atherosclerotic heart disease in civil pilots
Lin ZHANG ; Qingqing JIN ; Qingqing DUAN ; Yan XU ; Qiuyu SHEN ; Shaojie ZHU ; Kai CHEN ; Jie GAO ; Yukai LI ; Yan CHEN ; Xuejun ZHAO ; Meng SONG ; Jinke ZHENG ; Bin REN
Chinese Journal of Aerospace Medicine 2023;34(4):210-214
Objective:To explore the clinical value of coronary artery calcification (CAC) detected by chest CT in early screening of coronary atherosclerotic heart disease (CAHD) in civil pilots.Methods:The physical examination data of 2 899 civil pilots were retrospectively analyzed. Pilots were divided into CAHD group and control group based on the results of coronary angiography (CAG). The health data were compared between 2 groups and the clinical value of CAC in the diagnosis of CAHD was analyzed by using binary Logistic regression model and receiver operating characteristic (ROC) curve.Results:Thirty-eight CAHD cases were diagnosed, and the remaining 2 861 were in the control group. Comparing to that of control group, the average age of the pilots in CAHD group was greater ( t=12.09, P<0.001), and the average total flying hours were longer ( Z=-7.68, P<0.001). The proportions of smoking, hyperlipidemia, diabetes, hypertension, fatty liver, obesity, carotid plaques, positive or suspiciously positive in submaximal treadmill exercise test, CAC, as well as the proportions of taking further requested coronary CT angiography and CAG were significantly higher in the CAHD group ( χ2=5.42-1 430.25, P<0.01 or <0.05). Logistic regression model showed that smoking ( OR=2.800, 95% CI: 1.074-7.301, P=0.035), obesity ( OR=3.336,95% CI:1.243-8.956, P=0.017), positive or suspiciously positive in submaximal treadmill exercise test ( OR=17.669, 95% CI: 2.923-106.756, P=0.002) and CAC ( OR=96.039, 95% CI: 11.439-806.396, P<0.001) were the independent risk factors for diagnosing CAHD. The ROC curve results suggested that the sensitivity and specificity of CAC for predicting CAHD was 97.4% and 93.1%, respectively, and the area under the ROC curve was 0.952 ( P<0.001). Conclusions:CAC detected by chest CT in physical examination is helpful for early screening of asymptomatic or atypical CAHD in civil pilots.
6.Establishment of a risk prediction model for postoperative constipation in patients with oral and maxillofacial malignant tumors
ZHU Huixuan ; HE Xingfang ; HUANG Qiuyu ; LIU Manfeng ; LIN Yantong
Journal of Prevention and Treatment for Stomatological Diseases 2022;30(8):564-570
Objective:
To understand the incidence and influencing factors of postoperative constipation in patients with malignant tumors who undergo oral and maxillofacial surgery and construct a constipation risk prediction model to provide a reference for the prevention and treatment of postoperative constipation.
Methods:
The data of 191 patients who underwent oral and maxillofacial malignant tumor surgery at the Affiliated Stomatological Hospital of Sun Yat sen University from June 2019 to June 2020 were analyzed retrospectively. The independent influencing factors were selected via univariate analysis and logistic multivariate regression analysis, a risk prediction nomogram was established, and the prediction model was evaluated by the area under the ROC curve. Both internal and external use the C index to verify the accuracy of the model.
Results :
Among 191 patients, 52 (27.23%) had postoperative constipation. Univariate analysis showed that a preoperative secret history of defecation, total energy intake, tracheotomy, smoking, drinking, operation duration, bleeding volume, bed time, eating homogenate diet, sex, surgical repair method, use of probiotics, T-stage of cancer and food intake may be the influencing factors of postoperative constipation in patients with oral and maxillofacial malignant tumors (P<0.05). Multivariate analysis showed that repair method, bed time and sex were independent risk factors for postoperative constipation in patients with oral and maxillofacial malignant tumors (P<0.05). The repair method was a fibular myocutaneous flap with a long bed time, and male patients were prone to constipation after surgery. The c-index values in the training group and the verification group were 0.882 and 0.953, respectively. The area under the ROC curve of the training group was 0.909 (95%CI: 0.850-0.968), and the area under the ROC curve of the verification group was 0.893 (95%CI: 0.787-0.999). The nomogram showed good discrimination ability.
Conclusion
The repair method, bed time and sex are independent risk factors for postoperative constipation in patients with oral and maxillofacial malignant tumors. The risk prediction model has good discrimination ability.
7.New definition of metabolic dysfunction-associated fatty liver disease with elevated brachial-ankle pulse wave velocity and albuminuria: a prospective cohort study.
Jialu WANG ; Shanshan LIU ; Qiuyu CAO ; Shujing WU ; Jingya NIU ; Ruizhi ZHENG ; Lizhan BIE ; Zhuojun XIN ; Yuanyue ZHU ; Shuangyuan WANG ; Hong LIN ; Tiange WANG ; Min XU ; Jieli LU ; Yuhong CHEN ; Yiping XU ; Weiqing WANG ; Guang NING ; Yu XU ; Mian LI ; Yufang BI ; Zhiyun ZHAO
Frontiers of Medicine 2022;16(5):714-722
A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans
;
Pulse Wave Analysis
;
Albuminuria
;
Ankle Brachial Index
;
Non-alcoholic Fatty Liver Disease/diagnosis*
;
Vascular Stiffness
;
Prospective Studies
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Risk Factors
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China/epidemiology*
8.Repair of tongue defect with submental artery island flap and free anterolateral thigh flap after resection of tongue cancer: A comparative analysis
Xinqiang LI ; Qiuyu ZHU ; Dandan ZHU ; Shuang WU ; Wenlu LI
Chinese Journal of Microsurgery 2021;44(2):161-165
Objective:To compare and analyse the clinical outcome, advantages and disadvantages of submental artery island flap (SAIF) and free anterolateral thigh flap (ALTF) in the repair and reconstruction of tongue after radical surgery of tongue cancer.Methods:From January, 2016 to December, 2018, a total of 40 patients received tongue repair and reconstruction with either SAIF or ALTF after radical resection of tongue cancer. There were 28 males and 12 females, with an average age of 51 years old. Eighteen patients received tongue repair and reconstruction with SAIF and 22 with ALTF. Postoperative follow-up were carried out and the clinical data were collected. Swallowing, speech and softness of the tongue between the 2 repair methods were compared and statistically analysed. P<0.05 indicated a significant statistical difference between 2 groups. Results:All flaps survived. One ALTF had a venous vascular crisis. The flap survived after the removal of thrombus at the anastomotic site. Functional recovery of tongue was analysed after the follow-up of 12-48 months. It was found that there was no significant difference in speech function between the 2 groups (SAIF vs ALTF: 13 vs 15, P=0.206). The swallowing dysfunction in SAIF group was significantly higher than that of the ALTF group (SAIF vs ALTF: 15 vs 7, P=0.014). Moreover, the average time of surgery in SAIF group (3.5 h) was significantly less than that of the ALTF group (6.8 h), which had statistically significance ( P<0.05). Conclusion:The SAIF and ALTF are ideal flaps for repairing the tongue defect caused by tongue cancer surgery. SAIF features a simple surgical procedure and a short time for flap taking. ALTF provides sufficient amount of tissue to cover the scars left by the surgery, reduce donor site complications, and benefit the recovery of swallowing and speech functions.
9.Levels of bisphenols in patients with chronic kidney disease and their correlation with renal function
Tingyan LIU ; Yuanyuan SHI ; Qiuyu ZHU ; Feng ZHUANG ; Jianxin LU ; Feng DING
Chinese Journal of Nephrology 2018;34(9):654-660
Objective To observe the levels of four bisphenols (bisphenol A,B,S and F) and their correlation with renal function in chronic kidney disease (CKD) patients.Methods Patients with CKD were identified according to Kidney Disease:Improving Global Outcomes (KDIGO) criteria.Sixty-three CKD patients and eleven healthy controls were enrolled.CKD patients were further classified as mild renal injury group (CKD stage 1 and 2,n=30),moderate renal injury group (CKD stage 3,n=19) and severe renal injury group (CKD stage 4 and 5,n=14).The levels of four bisphenols in serum were determined by high performance liquid chromatography (HPLC).The correlation between concentrations of four bisphenols and estimated glomerular filtration rate (eGFR) was assessed by Spearman's rank correlation analysis.The associations of four bisphenols with coronary heart disease,diabetes and hypertension in CKD patients were estimated by binary multivariate logistic regression.Results (1) Four bisphenols were not detected in serum of healthy control.In the mild renal injury group the bisphenol A and bisphenol S were not detected,and patients had 5.24 (5.24,9.38) μg/L bisphenol B and 0.74 (0.74,0.74) μg/L bisphenol F.In the moderate renal injury group bisphenol S was not detected,and patients had 2.79 (1.01,4.53) μg/L bisphenol A,5.24 (5.24,5.24) μg/L bisphenol B and 0.74 (0.74,0.74) μg/L bisphenol F.In severe renal injury group patients had 14.30 (7.97,18.17) μg/L bisphenol A,0 μg/L bisphenol B,23.73 (23.73,136.59) μg/L bisphenol S and 0.74 (0.74,1.42) μg/L bisphenol F.The levels of bisphenol A and bisphenol S in severe renal injury group were higher than those in the healthy control group,mild renal injury group and moderate renal injury group (all P < 0.05).Bisphenol B and bisphenol F were not statistically different among four groups.(2) Bisphenol A and bisphenol S were negatively correlated with eGFR (r=-0.779,P < 0.001;r=-0.546,P < 0.001).(3) Among CKD patients,bisphenol A was correlated with diabetes (OR=4.951,95%CI 1.603-15.294,P=0.005),and bisphenol S was correlated with hypertension (OR=4.466,95% CI 1.575-12.666,P=0.005).Conclusions CKD patients have a variety of bisphenol compounds,especially bisphenol A and bisphenol S.Bisphenol A and bisphenol S have high levels,and their exposures are correlated with renal function.
10.Application of sensitive index of nursing quality in nursing management of patients with cancer pain
Yuhua ZHU ; Qiuyu LI ; Weimei CAI ; Xiangqing LI
Journal of Xinxiang Medical College 2017;34(9):857-859
Objective To explore the application value of sensitive index of nursing quality in nursing management of patients with cancer pain.Methods One hundred and eight patients with cancer pain in the First Affiliated Hospital of Xinxiang Medical University from February 2014 to March 2015 were selected as the control group;one hundred and eight patients with cancer pain in the First Affiliated Hospital of Xinxiang Medical University from April 2015 to June 2016 were selected as the study group.The traditional cancer pain nursing quality evaluation criterion was taken in the control group,and the improved cancer pain nursing quality evaluation criterion was taken in the study group to evaluate the nursing quality.The accuracy of pain assessment,awareness rate of cancer pain knowledge,degree of satisfaction to the nursing work were compared between the two groups.Results The accuracy of pain assessment of patients in the study group (90.7%,98/108)was significandy higher than that in the control group (45.4%,49/108) (x2 =51.16,P < 0.05);the awareness rate of cancer pain knowledge of patients (98.1%,106/108) in the study group was significantly higher than that in the control group (72.2%,78/108) (x2 =28.83,P < 0.05);the satisfaction rate of the patients in the study group (100.0%,108/108) was significantly higher than that in the control group (85.2%,92/108) (x2 =17.38,P < 0.05).Conclusion The overall quality of cancer pain care can be improved by strengthening the quality evaluation of the pain assessment accuracy and the awareness rate of cancer pain knowledge in patients with cancer pain.


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