1.Feixin Decoction Treats Hypoxic Pulmonary Hypertension by Regulating Pyroptosis in PASMCs via PPARγ/NF-κB/NLRP3 Signaling Pathway
Junlan TAN ; Xianya CAO ; Runxiu ZHENG ; Wen ZHANG ; Chao ZHANG ; Jian YI ; Feiying WANG ; Xia LI ; Jianmin FAN ; Hui LIU ; Lan SONG ; Aiguo DAI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):1-9
ObjectiveTo investigate the mechanism by which Feixin decoction treats hypoxic pulmonary hypertension (HPH) by regulating the peroxisome proliferator-activated receptor gamma (PPARγ)/nuclear factor-kappa B (NF-κB)/NOD-like receptor pyrin domain containing 3 (NLRP3) signaling pathway. MethodsForty-eight male SD rats were randomly allocated into normal, hypoxia, and low-, medium- and high-dose (5.85, 11.7, 23.4 g·kg-1, respectively) Feixin decoction groups, with 8 rats in each group. Except the normal group, the remaining five groups were placed in a hypoxia chamber with an oxygen concentration of (10.0±0.5)% for 8 h per day, 28 days, and administrated with corresponding drugs during the modeling process. After 4 weeks of treatment, echocardiographic parameters [pulmonary artery acceleration time (PAT), pulmonary artery ejection time (PET), right ventricular anterior wall thickness (RVAWd), and tricuspid annular plane systolic excursion (TAPSE)] were measured for each group. The right ventricular systolic pressure (RVSP) was measured by the right heart catheterization method, and the right ventricular hypertrophy index (RVHI) was calculated by weighing the heart. The pathological changes in pulmonary arterioles were observed by hematoxylin-eosin staining. The co-localization of α-smooth muscle actin (α-SMA) with NLRP3, N-terminal gasdermin D (N-GSDMD), and cysteinyl aspartate-specific proteinase-1 (Caspase-1) in pulmonary arteries was detected by immunofluorescence. The protein levels of PPARγ, NF-κB, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), N-GSDMD, interleukin-1β (IL-1β), interleukin-18(IL-18), and cleaved Caspase-1 in the lung tissue was determined by Western blot. The ultrastructural changes in pulmonary artery smooth muscle cells (PASMCs) were observed by transmission electron microscopy. ResultsCompared with the normal group, the hypoxia group showed increased RVSP and RVHI (P<0.01), decreased right heart function (P<0.01), increased pulmonary vascular remodeling (P<0.01), increased co-localization of α-SMA with NLRP3, N-GSDMD, and Caspase-1 in pulmonary arterioles (P<0.01), up-regulated protein levels of NF-κB, NLRP3, ASC, N-GSDMD, IL-1β, IL-18, and cleaved Caspase-1 in the lung tissue (P<0.05, P<0.01), a down-regulated protein level of PPARγ (P<0.05, P<0.01), and pyroptosis in PASMCs. Compared with the hypoxia group, Feixin decoction reduced RVSP and RVHI, improved the right heart function and ameliorated pulmonary vascular remodeling (P<0.05, P<0.01), decreased the co-localization of α-SMA with NLRP3, N-GSDMD, and Caspase-1 (P<0.05, P<0.01), down-regulated the protein levels of NF-κB, NLRP3, ASC, N-GSDMD, IL-1β, IL-18, and cleaved Caspase-1 in the lung tissue (P<0.05, P<0.01), up-regulated the protein level of PPARγ (P<0.05, P<0.01), and alleviated pyroptosis in PASMCs. ConclusionFeixin decoction can ameliorate pulmonary vascular remodeling and right heart dysfunction in chronically induced HPH rats by regulating pyroptosis in PASMCs through the PPARγ/NF-κB/NLRP3 pathway.
2.Effects of imperatorin on malignant biological behavior of gastric cancer cells by regulating ThPOK expression
Lan CHEN ; Lingli XIA ; Ying CHEN ; Gang ZHANG ; Feng WEN
China Pharmacy 2025;36(2):191-196
OBJECTIVE To investigate the effects of imperatorin (IMP-SD) on malignant biological behavior of gastric cancer (GC) cells by regulating zinc finger and BTB domain 7B (ThPOK). METHODS Human GC cells MKN-7 were used as the research object and then divided into control group (no treatment), IMP-SD low-, medium- and high-concentration groups (40, 80 and 160 μmol/L IMP-SD), si-ThPOK and si-NC group [treated with 160 μmol/L IMP-SD and then transfected with ThPOK small interfering RNA (si-ThPOK) or its negative control (si-NC)]. After treatment, cell clone formation, migration and invasion abilities and apoptosis of MKN-7 cells were detected; the killing activity of NK cells, T cells classification, the protein expressions of ThPOK, programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) were all determined. RESULTS Compared with the control group, the number of cell clones, migration number, invasion number, and the protein expressions of PD-1 and PD-L1 were decreased or down-regulated significantly in IMP-SD groups, while the cell apoptotic rate, NK cell killing activity, CD4+ T proportion, the ratio of CD4+ T proportion and CD8+ T proportion (CD4+ T/CD8+ T), and the protein expression of ThPOK were increased or up-regulated significantly, in a concentration-dependent manner (P<0.05). Compared with IMP-SD high-concentration group and si-NC group, the number of cell clones, migration number, invasion number, and the protein expressions of PD-1 and PD-L1 were increased or up-regulated significantly in si-ThPOK group, while the cell apoptotic rate, NK cell killing activity, CD4+ T proportion, CD4+ T/CD8+ T, and the protein expression of ThPOK were decreased or down-regulated significantly (P<0.05). CONCLUSIONS IMP-SD may reduce the clonal formation, migration and invasion abilities of GC cells, promote their apoptosis and inhibit their immune escape by promoting ThPOK expression.
3.Effects of imperatorin on malignant biological behavior of gastric cancer cells by regulating ThPOK expression
Lan CHEN ; Lingli XIA ; Ying CHEN ; Gang ZHANG ; Feng WEN
China Pharmacy 2025;36(2):191-196
OBJECTIVE To investigate the effects of imperatorin (IMP-SD) on malignant biological behavior of gastric cancer (GC) cells by regulating zinc finger and BTB domain 7B (ThPOK). METHODS Human GC cells MKN-7 were used as the research object and then divided into control group (no treatment), IMP-SD low-, medium- and high-concentration groups (40, 80 and 160 μmol/L IMP-SD), si-ThPOK and si-NC group [treated with 160 μmol/L IMP-SD and then transfected with ThPOK small interfering RNA (si-ThPOK) or its negative control (si-NC)]. After treatment, cell clone formation, migration and invasion abilities and apoptosis of MKN-7 cells were detected; the killing activity of NK cells, T cells classification, the protein expressions of ThPOK, programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) were all determined. RESULTS Compared with the control group, the number of cell clones, migration number, invasion number, and the protein expressions of PD-1 and PD-L1 were decreased or down-regulated significantly in IMP-SD groups, while the cell apoptotic rate, NK cell killing activity, CD4+ T proportion, the ratio of CD4+ T proportion and CD8+ T proportion (CD4+ T/CD8+ T), and the protein expression of ThPOK were increased or up-regulated significantly, in a concentration-dependent manner (P<0.05). Compared with IMP-SD high-concentration group and si-NC group, the number of cell clones, migration number, invasion number, and the protein expressions of PD-1 and PD-L1 were increased or up-regulated significantly in si-ThPOK group, while the cell apoptotic rate, NK cell killing activity, CD4+ T proportion, CD4+ T/CD8+ T, and the protein expression of ThPOK were decreased or down-regulated significantly (P<0.05). CONCLUSIONS IMP-SD may reduce the clonal formation, migration and invasion abilities of GC cells, promote their apoptosis and inhibit their immune escape by promoting ThPOK expression.
4.Transzonal Projections and Follicular Development Abnormalities in Polycystic Ovary Syndrome
Di CHENG ; Yu-Hua CHEN ; Xia-Ping JIANG ; Lan-Yu LI ; Yi TAN ; Ming LI ; Zhong-Cheng MO
Progress in Biochemistry and Biophysics 2025;52(10):2499-2511
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting a substantial proportion of women of reproductive age. It is frequently associated with ovulatory dysfunction, infertility, and an increased risk of chronic metabolic diseases. A hallmark pathological feature of PCOS is the arrest of follicular development, closely linked to impaired intercellular communication between the oocyte and surrounding granulosa cells. Transzonal projections (TZPs) are specialized cytoplasmic extensions derived from granulosa cells that penetrate the zona pellucida to establish direct contact with the oocyte. These structures serve as essential conduits for the transfer of metabolites, signaling molecules (e.g., cAMP, cGMP), and regulatory factors (e.g., microRNAs, growth differentiation factors), thereby maintaining meiotic arrest, facilitating metabolic cooperation, and supporting gene expression regulation in the oocyte. The proper formation and maintenance of TZPs depend on the cytoskeletal integrity of granulosa cells and the regulated expression of key connexins, particularly CX37 and CX43. Recent studies have revealed that in PCOS, TZPs exhibit significant structural and functional abnormalities. Contributing factors—such as hyperandrogenism, insulin resistance, oxidative stress, chronic inflammation, and dysregulation of critical signaling pathways (including PI3K/Akt, Wnt/β‑catenin, and MAPK/ERK)—collectively impair TZP integrity and reduce their formation. This disruption in granulosa-oocyte communication compromises oocyte quality and contributes to follicular arrest and anovulation. This review provides a comprehensive overview of TZP biology, including their formation mechanisms, molecular composition, and stage-specific dynamics during folliculogenesis. We highlight the pathological alterations in TZPs observed in PCOS and elucidate how endocrine and metabolic disturbances—particularly androgen excess and hyperinsulinemia—downregulate CX43 expression and impair gap junction function, thereby exacerbating ovarian microenvironmental dysfunction. Furthermore, we explore emerging therapeutic strategies aimed at preserving or restoring TZP integrity. Anti-androgen therapies (e.g., spironolactone, flutamide), insulin sensitizers (e.g., metformin), and GLP-1 receptor agonists (e.g., liraglutide) have shown potential in modulating connexin expression and enhancing granulosa-oocyte communication. In addition, agents such as melatonin, AMPK activators, and GDF9/BMP15 analogs may promote TZP formation and improve oocyte competence. Advanced technologies, including ovarian organoid models and CRISPR-based gene editing, offer promising platforms for studying TZP regulation and developing targeted interventions. In summary, TZPs are indispensable for maintaining follicular homeostasis, and their disruption plays a pivotal role in the pathogenesis of PCOS-related folliculogenesis failure. Targeting TZP integrity represents a promising therapeutic avenue in PCOS management and warrants further mechanistic and translational investigation.
5.The moderating role of estradiol in the relationship between parenting styles and preschool children s behavioral problems
XIA Moyan, YAN Chao, DONG Suhua, TANG Jinhui, LIU Ying, SONG Xingxing, TAO Lan, YAO Rongying
Chinese Journal of School Health 2024;45(1):95-98
Objective:
To explore the moderating role of estradiol in the relationship between parenting styles and preschool children's behavioral problems, so as to provide a theoretical basis for improving the development of human s emotional health development in early life stage.
Methods:
During September to November in 2022, 354 children aged 3-6 years and their parents from two kindergartens in Bengbu City were chosen by using stratified cluster sampling method for the questionnaire survey. The Parenting Style Scale and the Child Behavior Checklist (CBCL) were used to collect information on parenting style and child behavioral problems. Salivary estradiol of children was collected and tested. Independent samples t test was applied to compare the scores of the scale for parental up bringing and children s behavioral problems, and Pearson correlation analysis was conducted to explore the relationship among parental upbringing, estradiol and children s behavioral problems.
Results:
Parents doting, laissez faire, autocratic, and inconsistent parenting styles were positive associated with child behavior problems( r =0.14-0.70); fathers democratic parenting style was negatively associated with child behavior problems( r =-0.14,-0.22,-0.21,-0.17,-0.27,-0.20); mothers democratic parenting styles was negatively correlated with scores on all five dimensions of child behavior problems except the withdrawal dimension ( r =-0.14,-0.12,-0.13,-0.21,-0.12)( P <0.05). Estradiol levels had significant moderating effects on maternal doting parenting style and children s withdrawal ( β =0.68) as well as social problems ( β =-1.00), also moderating laissez faire parenting styles and children s withdrawal problems ( β =0.75)( P <0.05). For children with low levels of estradiol, withdrawal problem scores were negatively associated with mother s doting parenting style and positively associated with laissez faire parenting style, and socialization problem scores were associated with mother s doting parenting style; for children with high levels of estradiol, withdrawal problem scores were positively associated with mother s doting parenting style, and socialization problem scores were associated with mother s doting parenting style ( t=2.84, 6.24, 3.16 , 2.37, 4.49, P <0.05).
Conclusions
Parenting styles are strongly associated with child behavioral problems; estradiol levels play a moderating role in mothers doting, laissez faire parenting styles and children s withdrawal problems and social problems.Parents should adopt more positive parenting styles and focus on the role of estradiol levels in maternal education to reduce the occurrence of behavioral problems in children.
6.Analysis of driver gene mutations in “Xuanwei” multi-nodular non-small cell lung cancer
WANG Xiaoxionga ; LI Quana ; SHEN Zhenghaib ; CAI Jingjinga ; LI Zhuoyinga ; SHEN Shaoconga ; LI Hongshenga ; LIU Xina ; LIU Xia ; LIU Junxia ; GUO Yinjina ; DU Yaxia ; LAN Yunyia ; MA Luyaoa ; YANG Ruijiaoa ; WU Shunxiana ; ZHOU Yongchuna ; HUANG Yunchaob
Chinese Journal of Cancer Biotherapy 2024;31(4):377-382
[摘 要] 目的:探讨多结节非小细胞肺癌(NSCLC)组织中的驱动基因突变情况与临床病理特征的关系,为多结节NSCLC患者治疗提供分子诊断依据。方法:本研究共纳入2018年1月至2023年10月间云南省肿瘤医院分子诊断中心检测的121例多结节NSCLC患者的253个肺结节肿瘤组织标本,以第二代测序(NGS)技术或扩增阻滞突变系统PCR(ARMS-PCR)技术检测多结节NSCLC 组织中驱动基因突变情况,分析其与患者临床病理特征的关系,比较不同结节间肺癌驱动基因的突变异质性。结果:与非“宣威”NSCLC相比,“宣威”多结节NSCLC患者驱动基因突变具有显著的地域特点,表现在“宣威”患者具有较低(20%)的EGFR敏感突变(L858R、19-del)及较高(27.26%)的EGFR少见突变(主要为G719/S768I、G719);“宣威”多结节NSCLC患者的KRAS突变率(27.27%)亦显著高于非“宣威”患者突变率(12.59%)(P<0.05)。此外,“宣威”多结节NSCLC患者驱动基因突变不一致率高达69.23%,远高于非“宣威”患者驱动基因突变不一致率(55.07%)(P<0.05)。结论:“宣威”多结节NSCLC患者具有较高的EGFR少见突变及KRAS突变率,同一患者不同病灶之间存在更高的驱动基因突变异质性,本研究将为“宣威”多结节NSCLC的诊疗策略提供更多的选择。
7.A multicenter retrospective cohort study on the attributable risk of patients with Acinetobacter baumannii sterile body fluid infection
Lei HE ; Dao-Bin JIANG ; Ding LIU ; Xiao-Fang ZHENG ; He-Yu QIU ; Shu-Mei WU ; Xiao-Ying WU ; Jin-Lan CUI ; Shou-Jia XIE ; Qin XIA ; Li HE ; Xi-Zhao LIU ; Chang-Hui SHU ; Rong-Qin LI ; Hong-Ying TAO ; Ze-Fen CHEN
Chinese Journal of Infection Control 2024;23(1):42-48
Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3%,and that of non-infected group was 23.1%,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2%(95%CI:-2.3%-22.8%).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P>0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P>0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.
8.Experience of National TCM Master Xiong Jibai in Treating Pulmonary Nodules Based on"Body Fluids and Blood Stasis Mixing"
Jiayu CHANG ; Xia HE ; Sifan ZHONG ; Jiayue LIN ; Songbo LAN ; Ting ZHANG ; Xu YAN ; Jibai XIONG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(4):175-178
This article summarized the experience of Professor Xiong Jibai,a national TCM master,in treating pulmonary nodules based on the theory of"body fluids and blood stasis mixing"in Huang Di Nei Jing.Professor Xiong Jibai believes that the basic pathogenesis of pulmonary nodules is that"body fluids and blood stasis mixing"accumulate in lung collaterals,and the fundamental pathological factor is phlegm and blood stasis.Xiong's treatment is based on dissipating phlegm and activating qi,activating blood circulation and resolving masses,paying attention to syndrome differentiation and treatment,examining syndromes and seeking causes,flexibly selecting prescriptions and treating both symptoms and root causes;attaching importance to maintaining healthy qi,preventing both illness and change,and preventing recovery after illness.Clinical medical records were attached to prove the clinical thinking and medication characteristics.
9.Prognostic value of 18F-FDG PET/CT combined with clinical staging/scoring system in nasal extranodal natural killer/T-cell lymphoma
Yuhu LYU ; Lianglan YIN ; Xiaotian XIA ; Yongxue ZHANG ; Xiaoli LAN ; Chunxia QIN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(3):134-140
Objective:To compare and choose the best method for measuring metabolic tumor volume (MTV) of nasal extranodal natural killer/T-cell lymphoma (ENKTL), evaluate the prognostic value of 18F-FDG PET/CT metabolic parameters and clinical staging/scoring systems for patients with nasal ENKTL, and explore the added value of the two combinations for prognostic prediction. Methods:From January 2016 to September 2022, 44 patients (26 males, 18 females; age (47.5±13.6) years) pathologically diagnosed with nasal ENKTL who underwent 18F-FDG PET/CT imaging before treatment in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively collected. SUV 2.5, SUV 4.0 and 41%SUV max were used as thresholds to measure MTV and total lesion glycolysis (TLG), and the consistency was analyzed by Bland-Altman analysis. The ROC curve analysis was used to compare the prognostic efficiency of different methods and determine the best method. The prognostic values of different clinical factors and clinical staging/scoring systems between groups were evaluated by corrected χ2 test. The independent factors were screened by Cox-regression model, and the combined diagnosis model was constructed by logistic regression. Results:Of 44 patients, 6(13.6%) were dead, with the overall survival (OS) of 32.05(11.77, 64.43) months, and the 2-year and 5-year OS rates of 86.6% and 82.5%, respectively. The mortality of different groups in age (≥60 and <60 years), prognostic index of natural killer cell lymphoma (PINK) score (low- and high-risk), and international prognostic index (IPI) score (low- and high-risk) were significantly different ( χ2 values: 5.02, 4.12, 3.88, all P<0.05). The consistency of MTV measured by different thresholds was good. Among them, the MTV measured by threshold of SUV 2.5 had the highest predictive efficiency with the AUC of 0.737. Multivariate analysis showed that MTV (hazard ratio ( HR)=10.488, 95% CI: 1.864-59.026, P=0.008) was the independent influencing factor of OS. By removing other factors, minimization model was obtained, including MTV and PINK score ( P values: 0.006, 0.048). The prediction model of MTV combined with PINK score improved prognostic efficacy with the AUCs of MTV, PINK score and the combination model of 0.781, 0.741 and 0.912, respectively. Conclusions:MTV measured by threshold of SUV 2.5 has better prognostic predictive value. MTV is the independent prognostic factor for OS in nasal ENKTL patients. MTV combined with PINK score has better prognostic value.
10.A preliminary exploration of a deep learning-based artificial intelligence model for automatic quantification of echocardiographic left ventricular ejection fraction
Lan HE ; Yang LU ; Zhigang XIA ; Xiaoyi XIE ; Lili DU ; Shulian GU ; Lan MA ; Yongming HE ; E SHEN
Journal of Clinical Medicine in Practice 2024;28(9):9-14
Objective To construct a deep learning-based artificial intelligence model to automatically quantify left ventricular ejection fraction (LVEF) using static views of echocardiography. Methods The study included data of 1, 902 adults with left ventricular multi-slice echocardiographic views at end-systole and end-diastole. The collected dataset was divided into development set (1, 610 cases, with 1, 252 cases for model training and 358 cases for parameter adjustment), internal test set (177 cases for internal validation), and external test set (115 cases for external validation and generalization testing). The model achieved left ventricular segmentation and automatic quantification of LVEF through precise identification of the left ventricular endocardial boundary and inspection of key points. The Dice coefficient was employed to evaluate the performance of the left ventricular segmentation model, while the Pearson correlation coefficient and the intraclass correlation coefficient were used to assess the correlation and consistency between the automatically measured LVEF and the reference standard. Results The left ventricular segmentation model performed well, with Dice coefficients ≥ 0.90 for both the internal and external independent test sets; the agreement between the automatically measured LVEF and the cardiologists' manual measurements was moderate, with Pearson correlation coefficients ranging from 0.46 to 0.71 and intragroup correlation analysis agreements from 0.39 to 0.57 for the internal test set; and Pearson correlation coefficients for the independent external test set were 0.26 to 0.54 and intra-group correlation analysis agreement of 0.23 to 0.50. Conclusion In this study, a left ventricular segmentation model with better performance is constructed, and initial application of the model for automatic quantification of LVEF for two-dimensional echocardiography has general performance, which requires further optimisation of the algorithm to improve the model generalisation.


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