1.Comparison of Histopathological and Molecular Pathological Phenotypes in Mouse Models of Intrauterine Adhesions Induced by Two Concentrations of Ethanol Perfusion
Juan JIANG ; Ning SONG ; Wenbo LIAN ; Congcong SHAO ; Wenwen GU ; Yan SHI
Laboratory Animal and Comparative Medicine 2025;45(4):393-402
Objective To construct intrauterine adhesion (IUA) mouse models induced by two different concentrations of ethanol injury, compare the phenotypes, and optimize a more stable IUA modeling method. Methods Twenty 8-week-old female C57BL/6N mice were randomly divided into two groups: the 95% ethanol injury group and the 50% ethanol injury group. Using a self-control method, the left uterine horn was infused with ethanol to establish the IUA model, while the right uterine horn was infused with saline as the sham operation. Five mice from each group were euthanized on day 7 and 15 after modeling, and uterine tissues were collected. Hematoxylin-eosin (HE) staining was used to observe the endometrial pathology, and Masson staining was used to assess the degree of endometrial fibrosis. Quantitative real-time PCR was employed to detect the expression levels of fibrosis markers and pro-inflammatory factors in the uterine tissues. Results Compared to the sham operation, these two ethanol injury led to a significant reduction in elasticity of the uterus, an increase in inflammatory infiltration, and a marked increase in the degree of fibrosis on day 7 after modeling (P<0.05). The 95% ethanol injury group showed a significant decrease in endometrial thickness (P<0.05), whereas no significant change was observed in the 50% ethanol injury group when compared to the sham operation (P>0.05). The expression levels of fibrotic marker molecules collagen type Ⅳ alpha 1 chain (Col4A1), α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and pro-inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were significantly elevated in the 50% ethanol injury group when compared to the sham operation (P<0.05), although there was an increasing trend of the same markers in the 95% ethanol injury group, the differences were not statistically significant (P>0.05). On day 15 after modeling, the histopathological changes in both ethanol injury groups were not significant when compared to the sham operation, the expression levels of Col4A1, TGF-β, TNF-α and IL-1β remained significantly higher in the 50% ethanol injury group (P<0.05), while only IL-1β was significantly elevated in the 95% ethanol injury group (P<0.05). Conclusion Uterine infusion with 95% ethanol results in more marked histopathological changes in the IUA mouse model compared to the 50% ethanol injury group. The 95% ethanol injury model is suitable for histopathological studies. However, the 50% ethanol injury group shows higher expression levels of fibrosis markers and pro-inflammatory factors compared to the 95% ethanol injury group, suggesting that the 50% ethanol injury model is more suitable for molecular pathological study.
2.RXRα modulates hepatic stellate cell activation and liver fibrosis by targeting CaMKKβ-AMPKα axis.
Lijun CAI ; Meimei YIN ; Shuangzhou PENG ; Fen LIN ; Liangliang LAI ; Xindao ZHANG ; Lei XIE ; Chuanying WANG ; Huiying ZHOU ; Yunfeng ZHAN ; Gulimiran ALITONGBIEKE ; Baohuan LIAN ; Zhibin SU ; Tenghui LIU ; Yuqi ZHOU ; Zongxi LI ; Xiaohui CHEN ; Qi ZHAO ; Ting DENG ; Lulu CHEN ; Jingwei SU ; Luoyan SHENG ; Ying SU ; Ling-Juan ZHANG ; Fu-Quan JIANG ; Xiao-Kun ZHANG
Acta Pharmaceutica Sinica B 2025;15(7):3611-3631
Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl4 and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.
3.Predicting the potential suitable areas of Platycodon grandiflorum in China using the optimized Maxent model
Yu-jie ZHANG ; Han-wen YU ; Zhao-huan ZHENG ; Chao JIANG ; Juan LIU ; Liang-ping ZHA ; Xiu-lian CHI ; Shuang-ying GUI
Acta Pharmaceutica Sinica 2024;59(9):2625-2633
italic>Platycodon grandiflorum (Jacq.) A. DC is one of the most commonly used bulk medicinal herbs. It has important value in the fields of medicine, food and cosmetics, and its market demand is increasing year by year, and it has a good development prospect. In this study, based on 403 distribution records and 8 environmental variables, we used Maxent model to predict the potential distribution of
4. Effect of LncRNA p21 regulating Hippo-YAP signaling pathway on formation of abdominal aortic aneurysm in mice and its mechanism
Xiao CHEN ; Jin-Jun WANG ; Lin-Lin ZHANG ; Lian-Lian GUO ; Zhong-Wang ZHANG ; Juan-Zi ZHANG
Chinese Pharmacological Bulletin 2024;40(1):55-62
Aim To investigate the effect of long non- coding RNA p21 (LncRNA p21) regulating Hippo- Yes-associated protein (Hippo-YAP) signaling pathway on the formation of abdominal aortic aneurysm (AAA) in mice. Methods C57BL/6 ApoE
5.The use of bronchial occlusion test in a preterm infant with severe bronchopulmonary dysplasia complicated by severe lobar emphysema
Hui-Juan LIU ; Rui-Lian GUAN ; Xin QIN ; Huai-Zhen WANG ; Gao-Long ZHANG ; Jian-Bin LI ; Li MA ; Le LI ; Lian-Wei LU ; Yi SUN ; Hua-Yan ZHANG
Chinese Journal of Contemporary Pediatrics 2024;26(6):659-664
In infants with severe bronchopulmonary dysplasia(sBPD),severe pulmonary lobar emphysema may occur as a complication,contributing to significant impairment in ventilation.Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation.However,prior to the lobectomy,it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively.In addition,preoperative planning and perioperative management are also quite challenging in these patients.This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema.Since infants with sBPD already have poor lung development and significant lung injury,lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution.Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema.However,given the technical difficulty,successful application of this technique requires close collaboration of an experienced interdisciplinary team.
6.ZHANG Zhong-De's Experience in Treating Long-Term Symptoms After Novel Coronavirus Infection Using the Method of Harmonizing Five Zang-Organs
Li-Juan TANG ; Wei-Yan HE ; Lian-Shun JIN ; Tong ZHANG ; Zhong-De ZHANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(10):2591-2595
The multiple systemic symptoms appearing during the convalescence of novel coronavirus infection(COVID-19)are called long-term symptoms after COVID-19,also named as long COVID.Traditional Chinese medicine(TCM)has unique advantages in the treatment of long COVID.In the view of Professor ZHANG Zhong-De,the novel coronavirus infection belongs to the category of damp-toxin pestilence in TCM.During the convalescence of novel coronavirus infection,the damp-toxin pathogen causes the dysfunction of qi,blood,yin and yang of zang-fu organs,and then results in the consumption of yang qi or the depletion of fluid and blood.Damp-turbidity obstructing qi movement and entering collaterals and then developing into blood stasis is the key pathogenesis of long COVID.Therefore,the therapeutic principle of harmonizing yin,yang,qi and blood of the five zang-organs is proposed,and the methods for transporting and transforming damp-toxin and phlegm-turbidity,regulating qi,activating blood and removing stasis should be adopted.According to the exuberance or decline of qi,blood and body fluid,and yin and yang of the five zang-organs,the Fuzheng Series Formulas(series formulas for supporting healthy qi)were recommended for the specific syndrome types:Fuzheng Shengbai Formula can be used for the syndrome of deficiency of original qi;Fuzheng Yifei Formula can be used for lung-spleen-kidney deficiency syndrome;Fuzheng Anshen Formula can be used for the syndrome of liver qi stagnation and heart-spleen deficiency.During the treatment,Professor ZHANG Zhong-De makes the modification of drugs indicated for the retention sites of damp-toxin and turbid qi,and addresses the importance of spleen and stomach in the whole treatment process by protecting spleen and stomach,so as to promote the rehabilitation of patients after novel coronavirus infection and improve their quality of life.
7.Research progress on the role and mechanism of IRAK4 in hematological malignancies
Ying SHANG ; Li-Juan LI ; Lian-Sheng ZHANG
Medical Journal of Chinese People's Liberation Army 2024;49(9):1094-1098
Interleukin-1 receptor associated kinase 4(IRAK4)plays a crucial role in signal transduction and regulation in the TLRs/IL-1R signaling pathway,coordinating multiple inflammatory pathways involving immune system activation,cytokine production,and cell proliferation and differentiation.IRAK4 is associated with the pathogenesis and progression of hematological malignancies,including myelodysplastic syndrome,acute myeloid leukemia,chronic lymphocytic leukemia,and lymphoma.Therefore,IRAK4 may serve as an effective therapeutic target for hematologic malignancies.This review summarizes the research advances in the structure and function of IRAK4,as well as its mechanism of action and therapeutic implications in hematological malignancies,aiming to provide insights into pathogenesis of related diseases and targeted therapy research.
8.Association between delivery mode and exclusive breastfeeding during hospitalization and within six months after birth: a meta-analysis
Weining LIAN ; Tiantian XIONG ; Lintao NIE ; Juan DING
Chinese Journal of Perinatal Medicine 2023;26(7):533-545
Objective:To systematically review the association between delivery mode and exclusive breastfeeding rate during hospitalization and within the first six months of life.Methods:Observational studies on the association between delivery mode and feeding pattern were searched from PubMed, Web of Science, Cochrane Library, EBSCO, China Biomedical Literature Database, CNKI, Wanfang Database, and VIP Database from inception to October 2022. Two independent reviewers screened the literature, extracted data, and assessed the quality of included studies using Critical Appraisal Tools published by Joanna Briggs Institute or Newcastle-Ottawa Quality Scale (NOS). This meta-analysis was performed using R 4.1.0 software. Fixed-effect or random-effect models were used to pool data. Egger test and funnel plot were used to assess publication bias.Results:A total of 34 studies involving 597 203 subjects were included, including 22 cross-sectional studies and 12 cohort studies. All of the 22 cross-sectional studies were B-level quality, and eleven out of the 12 included cohort studies scored 7 points or above on the NOS scale with high quality. The results of meta-analysis showed that the likelihood of exclusive breastfeeding during hospitalization of women who had cesarean section was lower than those who delivered vaginally ( OR=0.33, 95% CI: 0.22-0.50, P<0.001); and so was the likelihood of exclusive breastfeeding at six months postpartum ( OR=0.61, 95% CI: 0.47-0.79, P<0.001). Conclusion:Current evidence suggests that cesarean section is a disadvantage to exclusive breastfeeding during hospitalization and within six months after delivery.
9.Status and influencing factors of delayed onset of lactogenesis Ⅱ in mothers of preterm infants
Weining LIAN ; Juan DING ; Xiao MA ; Lintao NIE
Chinese Journal of Perinatal Medicine 2023;26(7):554-560
Objective:To investigate the incidence of delayed onset of lactogenesis Ⅱ (DOL Ⅱ) in mothers of preterm infants and its influencing factors.Methods:This retrospective cohort study involved women who delivered prematurely at the Department of Obstetrics of the First Affiliated Hospital of Zhengzhou University from September 2021 to March 2022. Demographic and perinatal data of the subjects were collected. According to lactation outcome on the third day after delivery, these women were divided into DOL Ⅱ and non-DOL Ⅱ groups. The two groups' differences in general conditions were compared, and the potential factors influencing DOL Ⅱ were also analyzed. Chi-square test, two independent samples t-test, Mann-Whitney U test, and logistic regression analysis were used for statistical analysis. Results:There were 286 mothers of premature infants enrolled in this study, and 73 (25.5%) of them experienced DOL Ⅱ. The other 213 cases without DOL Ⅱwere included as the non-DOL Ⅱ group. Univariate analysis showed significant differences between the DOL Ⅱ and non-DOL Ⅱ groups in the following aspects: the proportion of women with adverse pregnancy history [28.8% (21/73) vs 41.8% (89/213), χ2=3.89], the proportion of primiparas [60.3% (44/73) vs 38.0% (81/213), χ2=10.93], the incidence of hypertensive disorders of pregnancy [35.6% (26/73) vs 16.4% (35/213), χ2=11.92], the time to initiate breastfeeding after birth[5.0 h (3.0-7.0 h) vs 4.0 h (2.0-5.0 h), Z=-4.27], and the frequency of breastfeeding or pumping within 48 h after delivery [7.0 times (6.0-9.0 times) vs 9.0 times (7.0-11.0 times), Z=-3.62] (all P<0.05). Multivariate logistic regression showed that primipara ( OR=2.720, 95% CI: 1.485-4.982), hypertensive disorders of pregnancy ( OR=3.178, 95% CI: 1.609-6.274), the time to initiate breastfeeding ( OR=1.394, 95% CI: 1.211-1.604) and the frequency of breastfeeding/pumping within 48 h after delivery ( OR=0.861, 95% CI: 0.772-0.962) were independent influencing factors for DOL Ⅱ (all P<0.05). Conclusions:?The factors that influence the occurrence of DOL Ⅱ in preterm mothers are primipara hypertensive disorders of pregnancy, breastfeeding initiation time after delivery, and the frequency of breastfeeding or pumping within 48 h postpartum.
10.Clinical Features and Prognosis of Patients with Castleman's Disease.
Xiu-Juan HUANG ; Xin-Lian ZHANG ; Xiao-Fang WEI ; Xiao-Qin LIANG ; Yuan FU ; Yang-Yang ZHAO ; Qing-Fen LI ; Qi-Ke ZHANG ; You-Fan FENG
Journal of Experimental Hematology 2023;31(1):135-140
OBJECTIVE:
To analyze the clinical features and prognosis of patients with Castleman's disease (CD) and improve the diagnosis and treatment of CD.
METHODS:
Clinical data of patients diagnosed with CD by pathological biopsy in Gansu Provincial Hospital from January 2009 to November 2020 were retrospectively analyzed. According to clinical classification, the patients were divided into two groups: UCD (unicentric CD) group (n=20) and MCD (multicentric CD) group (n=9). The clinical manifestations, laboratory examination, treatment regimens, pathological examination and follow-up data were statistically analyzed.
RESULTS:
There were no significant differences in average age and gender ratio between UCD group and MCD group. In UCD patients, 80.0% were hyaline vascular type, and 20.0% were plasma cell type. In MCD patients, 33.3% were hyaline vascular type, 55.6% were plasma cell type, and 11.1% were mixed type. There was significant difference in pathological classification between the two groups (P=0.039). The UCD patients usually presented asymptomatic single lymph node enlargement with mild clinical symptoms, while the MCD patients were characterized by multiple superficial and deep lymph node enlargement throughout the body. The incidences of asthenia, splenomegaly, serous effusion in MCD group were higher than those in UCD group (P<0.05). Meanwhile, the incidences of anemia, hypoproteinemia, increased ESR, elevated serum globulin and elevated β2-microglobulin were significantly higher than those in UCD group too (P<0.05). There was no significant difference in the incidences of abnormal WBC, PLT and elevated LDH between the two groups (P>0.05). Among 20 patients with UCD, 13 cases reached complete remission (CR), 1 case achieved partial remission (PR). Among 9 patients with MCD, 3 cases received CR and 4 cases received PR.
CONCLUSION
Patients with CD requires pathological examination for diagnosis. Patients with UCD show mild clinical symptoms, good surgical treatment effect and good prognosis. Patients with MCD have diversified clinical manifestations and relatively poor prognosis, and these patients require comprehensive treatment.
Humans
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Castleman Disease/therapy*
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Retrospective Studies
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Prognosis
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Splenomegaly
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Anemia

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