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    21 August 2026, Volume 47 Issue 4
    Interpretation of the guidelines for the prevention, treatment and clinical management of iatrogenic premature ovarian insufficiency in clinical practice
    Zhang Mingzhen, Ruan Xiangyan, Gu Muqing, Du Juan, Cheng Jiaojiao, Alfred O. Mueck
    2026, 47(4):  637-642.  doi:10.3969/j.issn.1006-7795.2026.04.001
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    With continuous progress a comprehensive analysis in the diagnosis and treatment of malignancies and refractory diseases, long-term survival rates have improved significantly. However, iatrogenic premature ovarian insufficiency (POI) induced by chemotherapy, radiotherapy, and pelvic surgery has become a critical issue affecting the whole-life-cycle health of female survivors. Based on the latest evidence-based medical data, this article presents a comprehensive analysis of the Practice Guideline for the Treatment and Management of Iatrogenic Premature Ovarian Insufficiency (2025) and the Practice Guideline on Ovarian Tissue Cryopreservation and Transplantation in the Prevention and Treatment of Iatrogenic Premature Ovarian Insufficiency. Both guidelines emphasize that the prevention and management of iatrogenic POI should be integrated throughout the entire course of  diagnosis and treatment. Ovarian tissue cryopreservation has emerged as a promising fertility preservation strategy and is currently the only option for preserving ovarian function and fertility in prepubertal girls and reproductive-aged women who cannot delay chemotherapy or radiotherapy. Gonadotropin-releasing hormone agonists (GnRHa) cannot replace established fertility preservation techniques. International guidelines currently endorse slow freezing as the standard method for ovarian tissue cryopreservation, while vitrification is still regarded as an experimental clinical procedure. Clinicians should inform patients or their guardians of the risks of infertility and ovarian insufficiency as early as possible before initiating cancer treatment, recommend consultation on fertility preservation, and arrange timely referrals. Once POI occurs, early diagnosis, hormone-based comprehensive treatment, and long-term management are essential to reduce long-term all-cause mortality in affected patients.


    Study on the correlation between the expression of key regulatory molecules and metabolic disorders in patients with polycystic ovary syndrome
    Zhao Yue, Ruan Xiangyan, Wang Yuejiao, Xie Dan, Jin Jing, Tian Xuanxuan, Zhang Xu, Zhang E, Zhu Jianguo, Zhang Zheng
    2026, 47(4):  643-649.  doi:10.3969/j.issn.1006-7795.2026.04.002
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    Objective  To investigate the expression level of progesterone receptor membrane component 1 (PGRMC1) in the serum of patients with polycystic ovary syndrome (PCOS) and its association with hyperandrogenemia (HA), insulin resistance (IR), and dyslipidemia. Methods  A cross-sectional study design was adopted, enrolling 80 PCOS patients from Beijing Obstetrics and Gynecology Hospital, Capital Medical University, plus 80 healthy controls with matched age and body mass index (BMI). Serum PGRMC1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Androgen indicators—total testosterone (TT), free testosterone (fT), and bioavailable testosterone (Bio-T)—were quantified via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The  chemiluminescence was used to test fasting insulin [FINS(OH)] and lipid profiles. Multiple linear regression and Logistic regression analyses were utilized to assess the relationship between PGRMC1 and metabolic parameters. Results  Serum PGRMC1 concentrations in the PCOS group were significantly higher than that in the control group [115.23 (67.18, 144.36) vs 26.45 (16.94, 40.63) ng/L, P<0.001], and is was positively correlated with TT (r=0.693), fT (r=0.612), Bio-T (r=0.573), HOMA-IR (r=0.964), TG (r=0.401), and LDL-C (r=0.559), while showing a negatively association with HDL-C (r=-0.228) (all P<0.05). The results of multiple linear stepwise regression analysis indicated that HOMA-IR had a positive effect on PGRMC1 (B=11.495, P=0.002). The model explained 11.4% of the variance in PGRMC1 (R2=0.114) and was statistically significant overall (F=10.029, P=0.002). Multivariate Logistic regression analysis confirmed that PGRMC1 (OR=1.039, 95% CI: 1.025-1.053, P<0.001) and TG (OR=4.080, 95% CI: 1.770-9.406, P=0.001) were independent risk factors for PCOS. Conclusion  PGRMC1 might participate in the pathogenesis of metabolic disorders in PCOS by modulating androgen synthesis and insulin signaling pathways, and together with TG, it serves as an independent risk factor for PCOS. PGRMC1 is closely associated with IR, and is expected to be a molecular marker for PCOS diagnosis and metabolic abnormality assessment, providing a novel target for precision diagnosis and treatment.
    Mechanisms of follicle loss after ovarian tissue cryopreservation and transplantation and the protective effect of N-acetylcysteine
    Li Yanglu, Ruan Xiangyan, Cheng Jiaojiao, Du Juan, Gu Muqing, Jin Fengyu, Li Yanqiu, Wang Zecheng, Zhang Mingzhen, Alfred O. Mueck,
    2026, 47(4):  650-657.  doi:10.3969/j.issn.1006-7795.2026.04.003
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    Objective  To investigate the mechanisms underlying follicle loss after ovarian tissue transplantation and evaluate the protective effects of N-acetylcysteine (NAC) on primordial follicles.Methods  Frozen-thawed human ovarian tissue was transplanted onto the chorioallantoic membrane (CAM) of chick embryos. Four groups were established: fresh ovarian tissue (fresh group), standardized cryopreservation and transplantation (control group), PI3K inhibitor treatment (PI3Ki group), and NAC treatment (NAC group). Follicle counts were assessed by hematoxylin-eosin staining (HE) staining, mitochondrial membrane potential (ΔΨm) was measured by JC-1 staining using flow cytometry, and the expression of phosphorylated protein kinase B (p-Akt) and phospholated forhead box o3a (p-Foxo3a) in the PI3K-Akt-Foxo3a pathway was detected by Western blotting.Results  Compared with the fresh group, all transplantation groups showed significantly reduced follicle counts (P<0.008 3) and increased mitochondrial depolarization (P<0.001). Compared with PI3Ki group, the control group exhibited activation of the PI3K-Akt-Foxo3a pathway, as indicated by elevated p-Akt and p-Foxo3a levels. This activation was suppressed in the PI3Ki group. In the NAC group, the expression of p-Akt and p-Foxo3a was significantly lower than in the control group (P<0.008 3), and the mitochondrial depolarization was the lowest among all transplanted groups(P<0.008 3).Conclusion  NAC protects primordial follicles during ovarian tissue transplantation by downregulating the PI3K-Akt-Foxo3a signaling pathway, thereby inhibiting excessive follicle activation and reducing mitochondrial damage.
    Effects of estrogen replacement therapy on the recovery of endocrine function after xenotransplantation of human ovarian tissue in nude mice
    Jiang Lingling, Ruan Xiangyan, Du Juan, Liu Anming, Cheng Jiaojiao, Gu Muqing, Li Yanglu, Zhang Mingzhen, Wang Zecheng, Li Yanqiu , Alfred O.Mueck,
    2026, 47(4):  658-664.  doi:10.3969/j.issn.1006-7795.2026.04.004
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    Objective  To investigate the effects of estrogen replacement therapy (ERT) on the recovery of ovarian endocrine function after human ovarian tissue xenotransplantation in nude mice. Methods  Female BALB/c nude mice aged 6-8 weeks were subjected to bilateral ovariectomy to establish a castrated model. Except for the control group, all mice underwent xenotransplantation of human ovarian cortical tissue under the renal capsule. ERT was administered via subcutaneous implantation of 17β-estradiol slow-release pellets (0.72 mg/pellet). Animals were divided into four groups according to the timing of estrogen intervention: pre-transplant estrogen pretreatment (Pre-ERT), continuous estrogen treatment (C-ERT), no estrogen treatment (No-ERT), and control group. Serum samples were collected at days 7 and 21 after transplantation, and levels of follicle-stimulating hormone (FSH), estradiol (E2), and anti-Müllerian hormone (AMH) were measured using ELISA. Results  At day 7, serum FSH levels in the control group were significantly higher than those in all transplantation groups, while the Pre-ERT group showed lower FSH levels than the No-ERT group. The C-ERT group exhibited the highest E2 levels, with all transplantation groups showing elevated E2 levels compared to the control group. AMH levels in the C-ERT group were higher than those in the No-ERT group, with all transplantation groups showed higher AMH levels than the control group (all P < 0.05). At day 21, FSH levels in the control group remained higher than those in all transplantation groups. Both Pre-ERT and C-ERT groups showed higher E2 levels than the No-ERT and control groups. AMH levels in the C-ERT group were higher than those in the No-ERT group, and all transplantation groups showing higher AMH levels relative to the control group (all P < 0.05). Conclusion  ERT improves the recovery of endocrine function after ovarian tissue xenotransplantation. Continuous estrogen treatment appears to be more effective than pre-transplant pretreatment in maintaining E2 and AMH levels, possibly by improving the local microenvironment and supporting graft function.
    Effect of ethinylestradiol /drospirenone and dydrogesterone on body composition and lipid metabolism in overweight polycystic ovary syndrome patients
    Li Yanqiu , Ruan Xiangyan, Gu Muqing , Jiang Lingling , Zhang Mingzhen , Alfred O. Mueck
    2026, 47(4):  665-672.  doi:10.3969/j.issn.1006-7795.2026.04.005
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    Objective  To compare the effects of ethinyl estradiol/drospirenone(EE/DRSP) and dydrogesterone on body composition and lipid metabolism in overweight patients with polycystic ovary syndrome (PCOS). Methods  A total of 160 overweight (24≤body mass index (BMI)< 28 kg/m2) women of reproductive age (18-40 years) who were  diagnosed with PCOS and treated at the Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, were recruited. The patients were randomly divided into two groups, with 80 patients in each group (EE/DRSP group, n=80; dydrogesterone group, n=80). Each group underwent three treatment cycles. The following parameters were observed before treatment and on days 2-5 of menstrual cycle after completing three cycles of treatment: anthropometric measurements (BMI, waist circumference, hip circumference); blood lipid parameters [triglycerides (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C)]; and body composition parameters (lower limb muscle distribution coefficient, fat percentage, fat distribution).Results  After three  treatment cycles, waist circumference, hip circumference, BMI, fat distribution, fat percentage, TC and LDL-C in the EE/DRSP group were significantly reduced compared to baseline (P all<0.05). While HDL-C was significantly increased (P < 0.05). In the dydrogesterone group, BMI, waist circumference, and hip circumference, fat percentage, TC and LDL-C were significantly decreased (P<0.05). When the groups were compared, EE/DRSP led to more significant reductions in waist circumference, hip circumference, BMI, fat distribution, and fat percentage. It also resulted in a more significant increase in HDL-C and a more significant reduction in LDL-C (P all < 0.05). Conclusion  While both EE/DRSP and dydrogesterone can improve the metabolic status of patients with polycystic ovary syndrome to some extent, EE/DRSP may offer more pronounced advantages in improving body composition and lipid metabolism.
    Efficacy of the natural cryoprotectant L-proline versus conventional cryoprotectants in human ovarian tissue cryopreservation and transplantation
    Liu Anming, Ruan Xiangyan, Du Juan, Jiang Lingling, Li Yanqiu, Gu Muqing, Cheng Jiaojiao, Zhang Mingzhen, Wang Zecheng, Alfred O. Mueck,
    2026, 47(4):  673-679.  doi:10.3969/j.issn.1006-7795.2026.04.006
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    Objective  To evaluate the efficacy of the natural cryoprotectant L-proline (L-pro) in human ovarian tissue cryopreservation and transplantation, and to compare it with the conventional cryoprotectant dimethyl sulfoxide (DMSO).Methods  Ovarian cortical tissues obtained from ten patients were cryopreserved using a slow-freezing protocol with either DMSO-based or L-pro-based cryoprotective solutions. After thawing, the tissues were xenotransplanted into ovariectomized female nude mice, while the control group underwent ovariectomy only. Twenty-one days after transplantation, grafts were retrieved for follicle counting, and serum levels of follicle-stimulating hormone (FSH), estradiol (E2), and anti-Müllerian hormone (AMH) were measured.Results  The number of quiescent (primordial) follicles was significantly higher in the L-pro group than in the DMSO group (P=0.042), whereas no significant differences were observed in the number of growing follicles or total follicle counts between the two groups (all P> 0.05). Serum hormone levels in both experimental groups were significantly improved compared with the control group (all P<0.05), with no significant differences between the L-pro and DMSO groups.Conclusion L-pro, as a cryoprotectant, demonstrates comparable efficacy to DMSO in preserving follicular integrity and restoring endocrine function following ovarian tissue cryopreservation and xenotransplantation. These findings provide a novel perspective for optimizing cryoprotective agents in ovarian tissue preservation, although further studies are needed to elucidate the underlying mechanisms and long-term functional outcomes.
    Study on the effect of body composition on bone mineral density in perimenopausal and postmenopausal women
    Li Kaiyin, Ruan Xiangyan, Wang Zecheng , Zhang Mingzhen, Liu Anming, Wang Yuejiao, Alfred O. Mueck,
    2026, 47(4):  680-685.  doi:10.3969/j.issn.1006-7795.2026.04.007
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    ObjectiveTo investigate the relationship between body weight, fat mass index (FMI), fat-free mass (FFM), and bone mineral density (BMD) in perimenopausal and postmenopausal women.MethodsA total of 153 perimenopausal and postmenopausal women aged 40–65 years, who visited our hospital between March 2024 and February 2026, were recruited. Height and body weight were measured. Body composition (including total body fat percentage and fat distribution) was assessed using bioelectrical impedance analysis to calculate FFM. BMD in the lumbar spine, femoral neck, and total hip was measured using dual-energy X-ray absorptiometry (DXA). Spearman correlation analysis, linear regression analysis, and mediation analysis were performed on the obtained BMD and body composition data.ResultsSpearman correlation analysis showed that body weight, body mass index (BMI), FFM, FMI, total body fat percentage, and fat distribution were significantly positively correlated with BMD in different areas (all P < 0.05). Multivariate linear regression analysis revealed that after including FFM in the model, the positive effect of body weight on BMD in different areas disappeared. Mediation analysis further confirmed that the effect of body weight on lumbar spine BMD was mediated by FFM.ConclusionIn perimenopausal and postmenopausal women, FFM, rather than total body mass, exerts a protective effect on bone mineral density. Therefore, maintaining a favorable body composition structure is beneficial for bone health.
    Study on the correlation between blood miR-181a and PGRMC1 levels and breast cancer characteristics
    Wang Yuejiao , Ruan Xiangyan, Gu Muqing, Wei Yun, Guan Yuwei, Alfred O.Mueck,
    2026, 47(4):  686-691.  doi:10.3969/j.issn.1006-7795.2026.04.008
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    ObjectiveTo investigate the correlation between the expression of microRNA-181a (miR-181a) in serum and the progesterone receptor membrane component 1 (PGRMC1) in whole blood, as well as the association with breast cancer characteristics, and to evaluate its potential as a biomarker for breast cancer risk.MethodsBlood samples were collected from 60 pre-operative breast cancer patients and 60 age-matched healthy women. The relative expression level of serum miR-181a and the concentration of PGRMC1 in whole blood were measured using real-time fluorescence polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The correlation between miR-181a and PGRMC1 levels was analyzed in both groups, with further comparisons made among subgroups based on clinicopathological characteristics.ResultsCompared with the healthy control group, the serum miR-181a expression level was significantly decreased in breast cancer patients (P < 0.001), while the PGRMC1 concentration was significantly increased (P < 0.001). Among breast cancer patients, serum miR-181a levels were significantly negatively correlated with PGRMC1 concentrations (P < 0.01). Intergroup comparisons showed that the T3-T4 tumor diameter group, clinical stage Ⅲ-Ⅳ group, and lymph node metastasis group had lower serum miR-181a relative expression and higher PGRMC1 concentrations compared to the T1-T2 tumor diameter group, clinical stage Ⅰ-Ⅱ group, and lymph node non-metastasis group, respectively (all P < 0.05).ConclusionThe expression of miR-181a in the serum of breast cancer patients is downregulated, and the protein level of PGRMC1 is upregulated. They are negatively correlated and closely related to the malignant characteristics of breast cancer, suggesting that the combined detection of serum miR-181a and PGRMC1 may provide a new perspective on risk assessment and prognosis of breast cancer.
    Fine particulate matter induces epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps via the C3a/C3aR axis
    Liang Shuang, Yan Bing, Li Ying , Wang Chengshuo, Zhang Luo
    2026, 47(4):  692-699.  doi:10.3969/j.issn.1006-7795.2026.04.009
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    Objective  To investigate the role of the complement C3a/C3aR axis in PM2.5-induced epithelial-mesenchymal transition (EMT) in chronic rihinosinusitis with nasal polyps (CRSwNP).Methods  The expression levels of the epithelial marker  E-cadherin and mesenchymal marker vimentin were detected by immunofluorescence staining in 50 μg/mL PM2.5-treated human primary nasal epithelial cells (HPNECs) from patients with CRSwNP. Public datasets (GSE220165 and GSE36830) were obtained to analyzed the expression of cadherin 1 and VIM, and Spearman' correlation analysis between the complement component 3a receptor (C3aR) and EMT-related molecules [cadherin 1, VIM, zinc finger E-box binding homeobox 2 (ZEB2), and matrix metallopeptidase 9 (MMP9)] were performed. Protein levels of C3a and C3aR in PM2.5-treated HPNECs were analyzed by Western blotting. EMT markers were examined in HPNECs after C3aR antagonist (C3aRA) treatment using immunofluorescence and Western blotting assays.Results  PM2.5 downregulated cadherin 1 and upregulated vimentin expression in HPNECs, in agreement with previously published transcriptomic data (GSE220165).  PM2.5 increased both C3a and its receptor C3aR levels in HPNECs. C3aR expression positively correlated with the EMT-related molecules ZEB2 (r=0.497, P=0.014 4) and MMP9 (r=0.409, P=0.048). Although its correlation with VIM exhibited a positive trend, it did not reach statistical significance (r=0.377, P=0.069 9). Blocking the C3a/C3aR axis with C3aRA partially alleviated PM2.5-induced downregulation of E-cadherin and upregulation of vimentin, ZEB2, and MMP9 in HPNECs.Conclusion  PM2.5 could induce EMT via activation of the C3a/C3aR axis in CRSwNP.
    Expression and significance of C6orf58/LEG1 in chronic rhinosinusitis with nasal polyps
    Wang Ping, Wang Xiangdong , Zhao Yan
    2026, 47(4):  700-706.  doi:10.3969/j.issn.1006-7795.2026.04.010
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    Objective  To investigate the expression profile of chromosome 6 open reading frame 58/liver-enriched gene 1(C6orf58/LEG1) in chronic rhinosinusitis with nasal polyps (CRSwNP) tissues and explore its potential clinical significance. Methods  Four CRSwNP-related transcriptomic datasets (GSE136825, GSE36830, GSE72713, and GSE23552) were downloaded from the gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using R software with criteria of |log2 FC| ≥ 1 and adjusted P < 0.05, and the intersecting DEGs across all four datasets were determined. Nasal polyp tissues from 44 CRSwNP patients and nasal mucosa from 21 healthy controls were collected, and real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was performed to detect C6orf58 mRNA expression. Publicly available single-cell RNA sequencing data were analyzed by uniform manifold approximation and projection(UMAP) clustering to define the cell-type-specific localization of C6orf58 and compare its expression between the two groups. Additionally, 4D label-free quantitative proteomics was performed on nasal polyp tissues from 3 CRSwNP patients and nasal mucosa from 3 healthy controls to validate LEG1 protein expression. Results  Bioinformatic analysis revealed that C6orf58 exhibited the most pronounced and consistent downregulation across all four GEO datasets. RT-qPCR confirmed that C6orf58 mRNA expression was significantly lower in CRSwNP tissues than that in healthy controls (P<0.01). Single-cell RNA sequencing analysis demonstrated that C6orf58 was predominantly enriched in glandular cells,  where its expression was significantly downregulated in  CRSwNP patients compared to healthy controls. No significant inter-group differences were observed in other cell types. Proteomic analysis further corroborated that LEG1 protein levels were significantly decreased in CRSwNP tissues, aligning with findings at the gene and mRNA levels. Conclusion  Reduced C6orf58/LEG1 expression in CRSwNP nasal polyps, particularly in glandular cells, points to a possible role in disease pathogenesis linked to glandular secretory dysfunction. It may represent a candidate biomarker meriting further study.
    Establishment of nasal mucosal epithelial organoids and assessment of their barrier function
    Wang Jingwen, Zhang Yuan, Zhang Xu, , Zhang Luo, Li Jingyun
    2026, 47(4):  707-714.  doi:10.3969/j.issn.1006-7795.2026.04.011
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    Objective  To establish, characterize and validate nasal epithelial organoids derived from surgical specimens of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and to comprehensively evaluate their growth, cellular composition, and functional epithelial barrier properties. Methods  Cell clusters isolated from CRSwNP specimens were encapsulated in 3D Matrigel and serially passaged. Organoid growth was quantified by organoid quantity, average area of organoids, and organoid forming efficiency (OFE). Cellular composition was assessed using flow cytometry, immunohistochemistry(IHC), and immunofluorescence(IF) for canonical epithelial markers. Barrier function was evaluated by transepithelial electrical resistance (TEER). Results  CRSwNP-derived clusters developed into compact, well-defined 3D organoids that remained at least five generation (P5). At day 7 post-seeding (D7)—a time point representing structural maturation—organoid quantity and OFE increased significantly compared with day 1 (D1) (P < 0.05), whereas organoid area remained statistically invariant (P > 0.05), indicating preserved clonogenic efficiency and proliferative fidelity across passages.  KRT5-positive basal cells accounted for >90% of undifferentiated organoids with stable distribution across passages. TEER increased progressively during differentiation, indicating establishment of epithelial barrier function. Differentiated organoids expressed β-tubulin (ciliated cells) and MUC5AC (goblet cells). Conclusion  We  established patient-derived, CRSwNP-origin nasal epithelial organoids that retain key structural, cellular, and functional features. Organoid quantity, area, and OFE are effective indicators for quantifying growth, and combined with TEER and differentiation markers, they are used to evaluated barrier function. This model offers a robust in vitro platform for investigating nasal inflammatory disease mechanisms and for the preclinical evaluation of novel therapeutics, including biologics.
    Construction of the IL-10rb genes mouse model with allergic asthma disease based on CRISPR/Cas9 technology
    Zhang Xu, Li Jingyun, Tan Juan, Yu Boyang, Zhang Yuan, Zhang Luo
    2026, 47(4):  715-721.  doi:10.3969/j.issn.1006-7795.2026.04.012
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    Objective  To generate IL-10rb gene knockout mice (IL-10rb-/-) using CRISPR/Cas9 gene editing technology and to evaluate the impact of this knockout on the pathological manifestations of an ovalbumin (OVA)-induced allergic asthma mouse model.Methods  A targeting gRNA was designed against exons 1-2 of the IL-10rb gene. The CRISPR/Cas9 system was microinjected into fertilized eggs of C57BL/6J mice.  F0 positive mice with the IL-10rb-/- genotype were identified and selected by polymerase chain reaction (PCR) at 7 day after birth. The mice were divided into four groups: wild-type (WT) group, IL-10rb-/- group, WT-OVA asthma group, and IL-10rb-/--OVA asthma group. Lung function testing as well as hematoxylin-eosin(H&E), periodic acid Schiff(PAS), and Masson staining of lung tissues were performed to assess airway inflammatory infiltration, goblet cell metaplasia, and collagen deposition.Results  PCR identification confirmed the successful generation of a stably heritable IL-10rb homozygous knockout mouse strain. Lung function tests showed that compared with the WT group, the IL-10rb-/- group, WT-OVA asthma group, and IL-10rb-/--OVA asthma group all exhibited significantly decreased respiratory system compliance (P<0.05). Compared with the WT-OVA group, the IL-10rb-/--OVA group showed a further decrease in respiratory system compliance (P<0.05). In terms of main airway resistance, compared with the WT group, airway resistance and tissue elasticity in the WT-OVA group and the IL-10rb-/--OVA group were significantly increased  (P<0.05). Lung histopathology revealed that compared with the WT group, the inflammatory cell infiltration in  the IL-10rb-/- group, WT-OVA group, and IL-10rb-/--OVA group was significantly increased. Airway goblet cell metaplasia was more pronounced in the IL-10rb-/--OVA group  than that in the WT-OVA group. Collagen deposition was markedly enhanced in the OVA-sensitized groups (WT-OVA and IL-10rb-/--OVA) compared with the WT and IL-10rb-/- groups.Conclusion IL-10rb gene knockout mice can be successfully generated using CRISPR/Cas9 gene editing technology. These mice can recapitulate the typical pathological features of allergic asthma and  serve as an animal model for further investigating the pathogenesis of allergic asthma and developing targeted intervention strategies.
    GDE1 contributes to lipid metabolic pathway dysregulation in type 2 chronic rhinosinusitis with nasal polyps
    Wang Qiqi, Guo Yushi, Li Yan
    2026, 47(4):  722-729.  doi:10.3969/j.issn.1006-7795.2026.04.013
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    Objective  To elucidate the immune cell infiltration characteristics and lipid metabolic activation in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods  Eight datasets from the Gene Expression Omnibus(GEO) database containing bulk-RNA sequencing results of normal nasal mucosa and CRSwNP tissues were selected. After batch effect correction, Weighted Gene Co-expression Network Analysis (WGCNA) was performed to identify key modules associated with CRSwNP. Additionally, differentially expressed genes (DEGs) between CRSwNP tissues and the control group were analyzed, followed by functional enrichment analysis of the DEGs within the key modules. XCell analysis was used to characterize immune cell infiltration in CRSwNP tissues. The impact of varying Th2 cell infiltration levels on activation of lipid metabolic pathway  in CRSwNP was investigated, and key genes were screened for validation using real-time fluorescence polymerase chain reaction (RT-PCR). Results  Compared to the controls, DEGs in the midnight blue module of CRSwNP tissues were primarily involved in the regulation of metabolic processes. Immune infiltration analysis revealed more prominent Th2 cell infiltration in CRSwNP tissues, and lipid metabolic pathways were significantly enriched in high-type 2 CRSwNP tissues. The expression of the  key gene GDE1  was upregulated in type 2 CRSwNP tissues as measured by RT-PCR.Conclusion  GDE1 may influence disease progression by modulating the activation level of lipid metabolic pathways in type 2 CRSwNP.
    Climate change, oxidative stress, allergic rhinitis: mechanisms and management strategies
    Niu Xinlei, Yang Xiaozhe, Cai Chao, Wang Xiangdong, Zhang Luo
    2026, 47(4):  730-737.  doi:10.3969/j.issn.1006-7795.2026.04.014
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    The global prevalence of allergic rhinitis (AR) continues to rise at an accelerating pace, imposing a substantial public health burden that currently affects more than 500 million individuals worldwide. Increasing evidence highlights global climate change and oxidative stress (OS) as pivotal drivers of both susceptibility  and severity of AR. This article analyzes the mechanistic pathways through which climatic warming, elevated concentrations of airborne pollutants, and more frequent extreme weather events contribute to prolonged pollen exposure, heightened allergic sensitization, and impairment of the nasal epithelial barrier. These interrelated processes induce cellular dysfunction and trigger excessive generation of reactive oxygen species (ROS), which in turn aggravates the development and progression of AR. We further provide a systematic review of the complex interrelationships between climate change, OS, and AR pathogenesis. We propose the following measures: advancing the construction of “healthy cities” that adapt to climate change; integrating meteorological and air pollution data; optimizing the configuration of urban vegetation and environmental controls; enhancing public awareness of allergic diseases; and emphasizing a prevention measure for AR. A three-dimensional strategy encompassing “policy and public health — health education — integration of prevention and treatment” should be developed to address the challenges posed by climate-related and OS-associated AR, thereby optimizing strategies for disease prevention, control, and clinical management.
    Effect of HDAC3 on promoting the epithelial-mesenchymal transition in triple-negative breast cancer
    Li Qing#, Wang Siqi#, Ma Tianyu, Ma Xiaoqi, Sun Yuting, Teng Xu, Yu Hefen, Zhang Jingyao△, Huang Wei△
    2026, 47(4):  738-753.  doi:10.3969/j.issn.1006-7795.2026.04.015
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    Objective  To investigate the role of histone deacetylase 3 (HDAC3) in the epithelial-mesenchymal transition (EMT) of triple-negative breast cancer (TNBC) cells and elucidate its underlying mechanisms. Methods  The expression level of HDAC3 in breast cancer tissues was analyzed based on Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and immunohistochemical (IHC) staining. The prognostic potential of HDAC3 expression in TNBC patients was analyzed by using Kaplan-Meier Plotter. Cell proliferation was assessed via growth curve and colony formation assays; Transwell assays were performed to evaluate cell migration and invasion. Western blotting analysis was applied to determine the expression of EMT-related markers. RNA-sequencing (RNA-seq) was performed on MDA-MB-231 cells with HDAC3 knockdown to identify target genes and signaling pathways regulated by HDAC3. Key candidate genes were validated by using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Chromatin immunoprecipitation polymerase chain reaction (ChIP-PCR) was used to verify HDAC3 binding to the promoters of target genes. Finally, the expression correlation between HDAC3 and target genes, along with their clinical prognostic significance, were analyzed by using GEO, TCGA databases and Kaplan-Meier Plotter. Results  HDAC3 was significantly upregulated in TNBC tissues, and its elevated expression was closely correlated with poor overall survival (OS) and recurrence-free survival (RFS) in patients. Growth curve, colony formation, and Transwell assays demonstrated that HDAC3 overexpression significantly promoted the proliferation, migration, and invasion of TNBC cells. HDAC3 overexpression downregulated the expression of epithelial markers α-catenin and γ-catenin, while upregulating the expression of mesenchymal markers Fibronectin and Vimentin in MDA-MB-231 and SUM 159 cells, whereas HDAC3 knockdown resulted in the opposite effects. RNA-seq analysis identified 693 differentially expressed genes after HDAC3 knockdown, which were enriched in signaling pathways related to malignant tumor progression, such as the PI3K-Akt and NF-κB pathways. RT-qPCR validation confirmed that the expression of genes including acyl-CoA synthetase short-chain family member 1 (ACSS1) and epidermal growth factor (EGF) was downregulated, while that of genes including E-cadherin (CDH1) and superoxide dismutase 2 (SOD2) was upregulated. ChIP-PCR assays confirmed that HDAC3 could specifically bind to the promoter regions of CDH1 and SOD2. Analysis of the GSE31519 dataset showed that HDAC3 expression was significantly negatively correlated with CDH1 and SOD2 expression. Furthermore, Kaplan-Meier survival analysis revealed that low expression of CDH1 and SOD2 was associated with poor prognosis in TNBC patients. Conclusion  HDAC3 promotes the proliferation, migration, invasion, and EMT progression of TNBC cells by through transcriptionally repressing the expression of CDH1 and SOD2. These findings suggest that HDAC3 is a potential therapeutic target for TNBC.
    Retinal ganglion cells echo the temporal pattern of periodic stimulation
    Li Xuexia, Shao Pan, Li Dapeng
    2026, 47(4):  754-765.  doi:10.3969/j.issn.1006-7795.2026.04.016
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    Objective  To develop a method for long-term recording of retinal ganglion cells (RGCs) in rats and to examine their responses to periodic light stimulation patterns. Methods  In vivo single-unit recordings were performed in the optic chiasm (OC) or optic tract (OPT) of rats during periodic temporal light stimulation. Results  This method enabled stable single-unit recording for at least 2 h. The spontaneous firing pattern after stimulation was more similar to the firing pattern during stimulation than that before stimulation, indicating that RGCs could transiently retain and represent the temporal pattern of periodic light stimulation. Spontaneous activity before stimulation showed rhythmicity, and the strength of this rhythmic activity influenced this representation. Conclusion  Rat RGCs can represent exogenous temporal patterns over timescales ranging from tens of milliseconds to minutes and respond to periodic light stimulation.
    Effects of zinc ions on RIPK3-mediated necroptosis and caspase-8-dependent apoptosis following cerebral ischemia-reperfusion in rats
    Zhu Yuequan, Liu He, Zhou Yingnan, Li Yakun, Zhao Haiping, Zhao Yongmei
    2026, 47(4):  766-774.  doi:10.3969/j.issn.1006-7795.2026.04.017
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    Objective  To establish a rat middle cerebral artery occlusion (MCAO) model and investigate the protein expression and cellular localization of receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and cleaved caspase-8, as well as the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in the ischemic brain tissue 6 h and 24 h following reperfusion. Additionally, zinc chelator N,N,N′,N′-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) was administered to investigate the effects of zinc ions on the expression of RIPK3, cleaved caspase-8 and Bcl-2/Bax at 6 h and 24 h after reperfusion, providing novel theoretical insights into the mechanisms of zinc ion-mediated cerebral ischemia-reperfusion injury.Methods  Adult male Sprague-Dawley rats were randomly allocated to Sham, MCAO, and TPEN + MCAO groups. MCAO model was established by intraluminal filament technique, with 90 min of occlusion followed by reperfusion for 6 h and 24 h. The ischemic brain tissue was separated and Western blotting was used to quantify the protein expression of RIPK3, cleaved caspase-8, Bcl-2 and Bax in the ischemic hemisphere. The co-localization of RIPK3 and cleaved caspase-8 with neuronal marker NeuN was observed through immunofluorescence staining.Results  ① Compared with the Sham group, the expression of RIPK3 was increased significantly in the ischemic brain tissues of MCAO group rats at 6 h and 24 h after reperfusion (P<0.05), and RIPK3 was co-localized with the neuronal marker NeuN. Compared with the MCAO group, TPEN treatment markedly decreased the expression of RIPK3 at 6 h (P<0.05) and 24 h after reperfusion. ② Compared with the Sham group, the expression of cleaved caspase-8 in the ischemic brain tissues of MCAO group rats was increased at 6 h and 24 h after reperfusion and co-localized with NeuN. Compared with the MCAO group, TPEN treatment markedly downregulated the expression of cleaved caspase-8 at 6 h (P<0.05) and 24 h after reperfusion. ③ Compared with the Sham group, the ratio of Bcl-2/Bax was decreased significantly in the ischemic brain tissues of MCAO group rats at 6 h and 24 h after reperfusion (P<0.05). Compared with the MCAO group, the Bcl-2/Bax ratio was increased significantly in the TPEN + MCAO group at 6 h and 24 h after reperfusion (P<0.05).Conclusion  This study demonstrates that zinc upregulates the expression of RIPK3 and cleaved caspase-8 and downregulates the Bcl-2/Bax ratio within the ischemic brain tissue following cerebral ischemia-reperfusion in rats, indicating that zinc ions may exacerbate cerebral ischemia-reperfusion injury by promoting RIPK3-mediated necroptosis and cleaved caspase-8-dependent apoptosis. This study provides novel insights into the role of zinc ions in the mechanisms underlying cerebral ischemia-reperfusion injury.
    Association of loneliness with transition risks of major non-communicable chronic diseases and healthy life expectancy among middle-aged populations in China
    Xia Xue, Tian Xue, Zhou Quan, Xu Qin, Zhang Yijun, Zhang Xiaoli, Li Jing, Wang Anxin
    2026, 47(4):  775-782.  doi:10.3969/j.issn.1006-7795.2026.04.018
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    Objective  To explore the association between loneliness and the whole transition course of non-communicable chronic diseases (NCDs), and to quantify its impact on life expectancy (LE) and healthy life expectancy (HLE) among middle-aged population.Methods  Based on the 2011—2020 follow-up data of individuals aged ≥45 years from the China Health and Retirement Longitudinal Study (CHARLS), a multi-state Markov model (MSM) was fitted to analyze the association of loneliness with the occurrence and progression of NCDs. Further, microsimulation was used to quantify its impact on both LE and HLE.Results  Of 12 316 participants included in the study, 47.99% were males and the median age was 59 (52,66) years-old. The transition course of NCDs mainly involved three pathways: from health to NCDs, from health to death, and from NCDs to death. During the follow-up period, 3 616 new cases of NCDs and 1 858 deaths were recorded. Compared with those who rarely felt lonely, healthy individuals with loneliness had a 20% increased risk of NCDs (OR=1.20, 95%CI: 1.10-1.30) and a 38% increased risk of death (OR=1.38, 95%CI: 1.15-1.66). Loneliness was significantly associated with an increased risk of transition from health to NCDs regardless of gender, whereas its impacts on transitions from health or NCDs to death seemed different between males and females (P forinteraction< 0.05). In addition, middle-aged individuals with loneliness had shorter LE, and the proportion of healthy survival time was also smaller. For individuals who were initially healthy, the HLE at the age of 45 years and its proportion was 12.8 years (32.8%) for lonely participants and 14.4 years (34.5%) for those without loneliness, respectively.Conclusion  Loneliness was significantly associated with increased risks of NCDs and death, which led to shortened LE and reduced proportion of HLE for middle-aged population.
    Predictors of pulmonary infection during hospitalization in patients with chronic heart failure and development of a predictive model
    Sun Yao, Hao Jingjing, Liu Yufeng, Guo Hebing, Zhong Xiaoxi, Liu Jingyuan
    2026, 47(4):  783-791.  doi:10.3969/j.issn.1006-7795.2026.04.019
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    ObjectiveTo investigate the risk factors for pulmonary infection (PI) during hospitalization in patients with chronic heart failure (CHF) and to develop a predictive model based on these findings, thereby providing a reference for early identification of high-risk individuals and formulation of personalized intervention strategies. MethodsA retrospective study was conducted enrolling 181 CHF patients admitted from March 2022 to March 2025. Patients were grouped based on whether they developed PI during hospitalization, forming a PI group and a non-PI group. Baseline characteristics and relevant examination data were compared between groups. Variables showing significant differences were subjected to least absolute shrinkage and selection operator (LASSO) regression for variable selection. A multivariate Logistic regression model analyzed factors influencing PI occurrence during hospitalization. The SHAP-interpreted CatBoost model ranked variable importance, and a receiver operating characteristic (ROC) curve risk prediction model was constructed based on the finalized key variables. ResultsAmong 181 CHF patients hospitalized, 51 (28.18%) developed PI. The PI group exhibited statistically significant differences compared to the non-PI group in smoking history, comorbid pulmonary diseases, invasive procedures, heart function classification, and mechanical ventilation (P < 0.05). The PI group exhibited higher white blood cell  (WBC), N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), and procalcitonin (PCT) levels compared to the non-PI group, while the left ventricular ejection fraction (LVEF) was lower in the PI group (P < 0.05). Seven important influencing factors were obtained by least absolute shrinkage and selection operator(LASSO) regression : pulmonary disease, mechanical ventilation, WBC, NT-proBNP, CRP, PCT, LVEF, and there was no collinearity problem, which were all important variables affecting the occurrence of PI in CHF patients during hospitalization. NT-proBNP (OR=1.044,95 % CI : 1.017-1.071), CRP (OR=1.386,95 % CI : 1.139-1.686), PCT (OR=29.223,95 % CI : 1.512-564.776) and LVEF (OR=0.814,95 % CI : 0.719-0.921) were independent influencing factors of PI in CHF patients during hospitalization (NT-proBNP>CRP > LVEF > PCT). The area under the ROC curve of combined prediction reached 0.937 (95 % CI : 0.894-0.979), which was significantly higher than that of single index (P<0.05). ConclusionThere is a risk of PI in CHF patients during hospitalization. The study suggests that it is related to NT-proBNP, CRP, PCT and LVEF. Based on this, it is feasible to construct a prediction model, which can help identify high-risk patients in the early stage of clinical practice and provide scientific guidance for individualized intervention. 
    Application of real-time Raman spectroscopy based on a high-throughput optical fiber probe for the in vivo and non-invasive diagnosis of bladder tumors
    Li Jiaxing, Wang Xiaotong, Tian Zhongqiu, Huang Shan, Gu Haihan, Yin Hang
    2026, 47(4):  792-798.  doi:10.3969/j.issn.1006-7795.2026.04.020
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    Objective  To collect Raman spectral data of bladder tumor tissues and normal mucosa in vivo by using a high-throughput fiber-optic Raman probe, construct a diagnostic model based on Principal Component Analysis Neural Network (PCANet), evaluate its performance, and explore its application in non-invasive real-time diagnosis of bladder tumors.Methods  During cystoscopy, patients undergoing random biopsy or transurethral resection of bladder tumors were included. In vivo Raman spectra were collected from suspicious tumor tissues and normal mucosa by using a high-throughput fiber-optic Raman probe, and tissue samples from corresponding sites were obtained. All sampling sites were confirmed by postoperative pathological examination. Based on pathological results, Raman spectral data were categorized into tumor and normal mucosa groups, and a PCANet-based diagnostic model for bladder tumors was constructed.Results  A total of 150 patients were enrolled, among whom 134 were pathologically diagnosed with bladder tumors postoperatively. In vivo Raman spectra were collected from 196 tumor tissue sites and 329 normal mucosa sites. Significant differences were observed at six characteristic peaks: 916, 1 094, 1 290, 1 346, 1 436, 1 672 cm-1. The PCANet-based diagnostic model demonstrated a sensitivity of 90.6% and a specificity of 91.3% in classifying in vivo bladder Raman spectra.Conclusion  This study demonstrates that the real-time Raman spectroscopy diagnosis technology based on high-throughput fiber Raman probes can achieve rapid and non-invasive in vivo diagnosis of bladder tumors, with excellent diagnostic performance and significant clinical application prospects.
    Research progress on the role of gut microbiota and its metabolites in the pathogenesis of multiple sclerosis
    Liu Tianyu, Zhang Xianan, Meng Qingtao, Chen Rui
    2026, 47(4):  799-806.  doi:10.3969/j.issn.1006-7795.2026.04.021
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    Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease of the central nervous system. The gut microbiota (GM) and its metabolites crucially regulate immune responses and inflammation in MS pathogenesis via the “gut-brain” axis. However, existing studies predominantly focus on compositional phenotypes and conventional immune pathways, highlighting an urgent need to systematically dissect the micro-level molecular networks mediated by core metabolites. This review summarizes recent advances in key metabolites—short-chain fatty acids, indole derivatives, and bile acids—and explores their networked regulatory roles bridging peripheral immunity and central neuropathology. By multidimensionally elucidating these mechanisms, we aim to provide a theoretical basis for developing novel clinical biomarkers and microbiota-targeted interventions.
    Analysis on the transforming dilemma and promotion measures of scientific research achievements in medical schools
    Zhang Jiahuai, Chen Rui, Ma Ning, Jia Xiaojuan, An Kui
    2026, 47(4):  807-817.  doi:10.3969/j.issn.1006-7795.2026.04.022
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    The transformation of medical research achievements is a crucial step in advancing medical technologies and improving people’s health. In recent years, China has vigorously implemented the strategy of innovation-driven development, promoted the transformation and application of research achievements, and fostered a favorable ecosystem for their transformation. However, medical schools encounter numerous challenges in transforming research achievements: the misalignment between the outputs of research achievements and market demands; the imperfect coordinative mechanisms among participating entities; the weak service capabilities of common technology platforms; the shortages of technology transfer personnel; and the rigidity of evaluation and assessment systems. To address these challenges, here several recommendations are proposed, including establishing a new multi-party transformation system; improving patent quality and refining evaluation systems; adjusting assessment mechanisms; strengthening the construction of common platforms; establishing and improving institutional frameworks for the transformation of scientific and technological achievements; and enhancing the development of professional talents.