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.

Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of patients with chronic myeloid leukemia (CML), and achieving treatment-free remission (TFR) has become a new goal for these patients. Various methods of discontinuing medication are continuously being explored, with successful cessation linked to factors such as the duration of TKI treatment, the sustainability of deep molecular response (DMR), transcript type, and immunological factors. Early switching of TKI, combining other therapies, and targeting leukemia stem cells may help increase the TFR rate. This article reviews the latest research developments on the exploration of TKI cessation, factors affecting TFR, selection of patients for discontinuation, strategies to enhance TFR, and monitoring after cessation, expecting to provide reference and guidance for achieving TFR in CML patients.
Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Protein Kinase Inhibitors/therapeutic use* ; Remission Induction ; Tyrosine Kinase Inhibitors

OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Mutation ; Adult ; Repressor Proteins/genetics* ; Adolescent ; Retrospective Studies ; Aged ; Nucleophosmin ; Young Adult ; Transplantation, Homologous ; Prognosis ; Survival Rate

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Ovulatory dysfunction (OD) is one of the main causes of infertility in women of childbearing age, which not only affects their reproductive ability, but also physical and mental health. Traditional treatment strategies have limited efficacies, and the emergence of biomedicines provides a promising alternative solution via the strategies of combining engineered design with modern advanced technology. This review explores the pathophysiological characteristics and related induction mechanisms of OD, and evaluates the current cutting-edge advances in its treatments. It emphasizes the potentials of biomedicines strategies such as hydrogels, nanoparticles and extracellular vesicles in improving therapeutic precision and efficacy. By mimicking natural physiological processes, and achieving controlled drug release, these advanced drug carriers are expected to address the challenges in ovarian microenvironment reprogramming, tissue repair, and metabolic and immune regulation. Despite the promising progress, there are still challenges in terms of biomedical complexity, differences between animal models and human physiology, and the demand for intelligent drug carriers in the therapy of OD. Future researches are mainly dedicated to developing precise personalized biomedicines in OD therapy through interdisciplinary collaboration, promoting the development of reproductive regenerative medicine.

Objective:To conduct bioinformatics analysis by detecting and screening differentially expressed miRNAs in urine exosomes of subjects with damp heat IgA nephropathy, non damp heat IgA nephropathy, and healthy individuals; To explore the role of miRNAs in renal tubulointerstitial fibrosis.Methods:A cross-sectional study was conducted to select 40 subjects with primary IgA nephropathy diagnosed by renal biopsy in the Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University from November 2021 to February 2023, who were divided into damp-heat group and non-damp-heat group according to TCM constitution, with 20 cases in each group; 10 healthy subjects were also recruited for control observation.High-speed centrifugation and Illumina high-throughput sequencing technology were used to isolate and detect the expression of miRNA in urine exosomes from three groups of people, and their differential expression profiles were constructed. Bioinformatics analysis was performed on differentially expressed genes to determine the main biological functions of differentially expressed miRNAs and the signaling pathways they may participate in.Results:Compared with the non-damp heat group, there were 231 miRNAs with abnormal expression in the urine exosomes of the damp heat group, including 119 up-regulated and 112 down-regulated. Through GO enrichment and KEGG analysis, differentially expressed miRNAs may participate in the occurrence and development of renal tubulointerstitial fibrosis through MAPK signaling pathway, PI3K Akt signaling pathway, Hippo signaling pathway, Ras signaling pathway, Wnt signaling pathway, mTOR signaling pathway, etc., involving biological processes such as cell proliferation, apoptosis, cell deformation (EMT), migration and invasion, and tissue and organ fibrosis. MiR-29c-3p expression levels in the urinary exosome miRNA expression profiles of subjects in the three groups were lower in the damp-heat group, but higher in the non-damp-heat group versus the healthy control group, of which, the damp-heat group was lower than the non-damp-heat group versus the healthy control group ( P<0.01); there was no significant difference between the healthy control group and the non-damp-heat group ( P>0.05）. Conclusion:The expression profile of miRNAs in the urine exosomes of subjects with damp heat IgA nephropathy showed significant changes,that the significant down-regulation of miR-29c-3p may be a key factor in exacerbating tubulointerstitial fibrosis in IgA nephropathy.

Objective To investigate the correlations of expression levels of serum transforming growth factor-β1(TGF-β1)and insulin-like growth factor-1(IGF-1)with clinicopathological features of patients with adenomyosis,and the clinical value of their prediction of postoperative recurrence.Methods Eighty-two patients with adenomyosis were selected as study subjects(study group).Patients were followed up for two years after surgery and divided into recurrence group(n=15)and non-recur-rence group(n=67)based on their postoperative status.An additional 85 healthy individuals who un-derwent physical examinations during the same period were selected as control group.Serum TGF-β1 and IGF-1 levels were compared between the study group and the control group.The correlations of se-rum TGF-β1 and IGF-1 levels with the clinicopathological characteristics of adenomyosis patients was analyzed.Serum TGF-β1 and IGF-1 levels were compared between the recurrence and non-recurrence groups.Receiver operating characteristic(ROC)curve analysis was used to evaluate the diagnostic efficacy of serum TGF-β1 and IGF-1 levels in predicting postoperative recurrence in adenomyosis pa-tients.Results Serum TGF-β1 and IGF-1 levels in the study group were significantly higher than those in the control group(P＜0.05).Serum TGF-β1 levels were correlated with menstrual vol-ume,history of curettage,uterine volume,pathological type,lesion volume,endometrial status and ectopic gland cycle(P＜0.05).Serum IGF-1 levels were correlated with menstrual volume,history of curettage,uterine volume,pathological type,endometrial status and ectopic gland cycle(P＜0.05).Postoperative serum TGF-β1 and IGF-1 levels in the recurrence group were significantly higher than those in the non-recurrence group(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)for predicting postoperative recurrence using serum TGF-β1,IGF-1 and their combination were 0.823,0.803 and 0.940,respectively.The clinical efficacy of TGF-β1 and IGF-1 in combination in predicting postoperative recurrence was superior to that of TGF-β1 alone(ZcombinedwithTGF-β1=2.001,ZcombinedwithIGF-1=2.318,P=0.045,0.021).Conclusion The serum levels of TGF-β1 and IGF-1 in patients with adenomyosis are significantly increased,which are closely related to the clinicopathological features of the patients.The combination of serum TGF-β1 and IGF-1 levels has high clinical efficacy in predicting postoperative recurrence.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective To explore the modal testing method for the three-axis manned centrifuge under elastic boundary conditions with considerations on its complicated structure and high rotational inertia.Methods Modal testing was carried out with a three-axis manned centrifuge under elastic boundary conditions as the subject and a force hammer as the excitation source according to GJB 2706A-2008 Modal tests method for spacecraft and GB/T 11349.3-1992 Experimental determination of mechnical mobility measurements using impact excitation.Four times of hammering were carried out at each excitation position,and the data of the four times of hammering underwent linear average computation.Data acquisition was implemented with a three-axis accelerometer and a 64-channel data collector,and the modal data were analyzed using a frequency response function based on the Test.Lab modal test and analysis software.Results The coherence coefficient of the excitation signal was not lower than 0.8 in the 30 Hz band;the first three orders of the system's intrinsic vibrations were all torsional vibrations,with the frequencies of 9.15,15.66 and 19.22 Hz,respectively;the first order frequency of the system was about 9.15 Hz for both Z18 and Z21 excitation positions,and each of the second and third order frequencies similar situations were observed for also had a roughly equal value for the two excitation positions.Conclusion The force hammer testing method is applicable for the modal testing of the three-axis manned centrifuge,ensuring equipment safety and subject comfort.Referen-ces are provided for the following structural optimization design.[Chinese Medical Equipment Journal,2024,45(8):38-43]