1.Sleep Traits and Malignant Risk of Pulmonary Nodules: Evidence Triangulation From Questionnaire, Cohort, and Mendelian Randomization
Xiangyu CHEN ; Yiqiao XUE ; Mengqing LIU ; Yile HU ; Weizuo LIANG ; Hanqing LIU ; Yizheng WANG ; Mingfang ZHAO
Medical Journal of Peking Union Medical College Hospital 2026;17(3):663-676
To investigate the association between sleep-related phenotypes and the risk of malignancy in pulmonary nodules, and to provide complementary evidence from a general population cohort and genetic analyses. This study comprised three parts. Part 1 was a cross-sectional study that consecutively enrolled patients with imaging-confirmed pulmonary nodules at the First Hospital of China Medical University from November 2024 to December 2025. Nine sleep domains were constructed using items from the Pittsburgh sleep quality index (PSQI), with domain severity coded on a 0-6 scale according to the frequency of occurrence. Benign or malignant status of pulmonary nodules was determined based on pathological results or clinical follow-up. Multivariable Logistic regression models with progressive adjustment were constructed. Stratified, interaction, and dose-response analyses (including categorical grouping and restricted cubic splines) were performed focusing on the insomnia symptom domain to explore the association between sleep-related phenotypes and the risk of malignant pulmonary nodules. Part 2 was a prospective cohort study using the China Health and Retirement Longitudinal Study (CHARLS) to investigate the association between sleep duration and incident lung cancer risk in the general population. Part 3 comprised genetic causality analyses, including two-sample Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC), using data from the OpenGWAS database, to assess whether directionally consistent genetic association signals exist between sleep-related phenotypes and lung cancer risk. In the cross-sectional study, a total of 800 patients with pulmonary nodules were included, of whom 288 (36.0%) were in the malignant group. In the continuous-variable main model fully adjusted for baseline confounders, all nine sleep domains, imaging findings, and depression and anxiety status, the severity of the insomnia symptom domain showed a positive association signal with the risk of malignant pulmonary nodules (fully adjusted model: per 1-point increase, In patients with pulmonary nodules, an association signal exists between insomnia-related symptoms and the risk of malignancy, but the dose-response relationship remains unclear. The CHARLS cohort and genetic analyses provide supplementary directional clues for the above associations, albeit with limited statistical strength and result consistency. Definitive conclusions regarding the association between sleep phenotypes and the risk of malignant pulmonary nodules require further validation in prospective studies.
2.Analysis of Animal Models of Lumbar Spinal Stenosis Based on Clinical Characteristics of Traditional Chinese and Western Medicine
Miao HE ; Xuxing ZHANG ; Gang WU ; Yi ZHOU ; Hao RAO ; Xiangyu HU
Laboratory Animal and Comparative Medicine 2026;46(4):541-552
Lumbar spinal stenosis (LSS) is a common disabling condition in the elderly, and its clinical assessment relies not only on imaging and neurofunctional indicators but also on traditional Chinese medicine (TCM) syndrome differentiation. To evaluate the concordance between existing LSS animal models and clinical characteristics of TCM and Western medicine, clarify their advantages and limitations, and explore their translational potential, Chinese and English databases, including CNKI, Wanfang Data, PubMed, and Web of Science, are searched using combinations of the terms "lumbar spinal stenosis," "model," "guideline," "consensus," and "norm" from inception to the end of June 2025. After screening, a total of 21 publications are included, of which 15 report animal experimental studies, and 6 are guidelines, consensus statements, or normative documents. Based on these, the existing modeling methods are summarized, diagnostic indicators are extracted from clinical guidelines and expert consensus, and clinical concordance is evaluated using an assessment system proposed in the relevant literature. The results show that the existing animal models are categorized into three concordance levels: high (laminectomy/spinous process removal with filling; laminectomy/spinous process + ligament/muscle removal with filling; autologous bone backfilling), moderate (nylon tape dural binding method, adjustable screws, fixation combined with removal of ligament/muscle), and low (balloon compression method, adjustable balloon compression method, bipedal standing, ligament/muscle resection, steel wire cerclage method). Overall, current animal models of LSS generally perform well in terms of structural construction but show clear limitations in replicating clinical diagnostic logic and TCM syndromes. Future research should enhance syndrome phenotype collection and enrich TCM-based evaluation systems based on existing models. Additionally, multifactorial integrated modeling strategies should be introduced to extend the depth of syndrome-level simulation. This study aims to analyze LSS animal models that can faithfully recapitulate disease pathogenesis, conform to clinical realities of both Western medicine and TCM clinical practice, and have broad application potential, so as to narrow the translational gap between experimental findings and clinical practice.
3.Trends in prevalence of overweight and obesity among adult residents in Zhejiang Province from 2015 to 2023
CHEN Xiangyu ; WANG Meng ; HU Ruying ; GUAN Yunqi ; LIANG Mingbin ; HE Qingfang ; YAO Weiyuan ; ZHONG Jieming
Journal of Preventive Medicine 2025;37(11):1093-1098
Objective:
To investigate the prevalence levels and trends of overweight and obesity among adult residents in Zhejiang Province from 2015 to 2023, so as to provide a basis for developing regional weight management strategies.
Methods:
Permanent residents aged ≥18 years from Zhejiang Province who participated in the China Chronic Disease and Risk Factor Surveillance Project in 2015, 2018, and 2023 were selected as survey subjects. Data on sociodemographic information, height, weight and waist circumference were collected through questionnaire surveys and physical examinations. The prevalence of overweight, obesity, and central obesity were calculated and standardized using data from the Seventh National Population Census of Zhejiang Province in 2020. The Cochran-Armitage trend test was employed to analyze the trends in prevalence of overweight, obesity, and central obesity across different genders, ages and regions.
Results:
A total of 23 902 individuals were surveyed, comprising 10 985 males (45.96%) and 12 917 females (54.04%). Participants were aged ≥60 years, with 13 088 individuals accounting for 54.76%. There were 9 388 urban residents (39.28%) and 14 514 rural residents (60.72%). The standardized prevalence of overweight among residents increased from 30.05% in 2015 to 33.98% in 2023, the standardized prevalence of obesity increased from 7.67% to 15.22%, and the standardized prevalence of central obesity increased from 22.81% to 33.82%, all showed upward trends (all P<0.05). In 2015, 2018, and 2023, the standardized prevalence of overweight was higher in males than in females. In 2018 and 2023, the standardized prevalence of obesity and central obesity were higher in males than in females (all P<0.05). From 2015 to 2023, the standardized prevalence of overweight, obesity, and central obesity among both males and females showed upward trends (all P<0.05). In 2015, 2018 and 2023, the prevalence of central obesity showed an increasing trend with age (all P<0.05). From 2015 to 2023, upward trends were observed in the prevalence of overweight, obesity, and central obesity among residents aged 18-<45 years and aged ≥60 years, as well as in the prevalence of obesity and central obesity among residents aged 45-<60 years (all P<0.05). In 2015, 2018 and 2023, the standardized prevalence of overweight obesity were higher in urban areas than in rural areas, while the standardized prevalence of central obesity was lower in urban areas (all P<0.05). From 2015 to 2023, the standardized prevalence of overweight, obesity, and central obesity among both urban and rural areas showed upward trends (all P<0.05).
Conclusion
From 2015 to 2023, the prevalence of overweight, obesity, and central obesity among adult residents in Zhejiang Province showed increasing trends, with variations in prevalence levels and trends observed across genders, ages, and urban / rural areas.
4.Identification of novel pathogenic variants in genes related to pancreatic β cell function: A multi-center study in Chinese with young-onset diabetes.
Fan YU ; Yinfang TU ; Yanfang ZHANG ; Tianwei GU ; Haoyong YU ; Xiangyu MENG ; Si CHEN ; Fengjing LIU ; Ke HUANG ; Tianhao BA ; Siqian GONG ; Danfeng PENG ; Dandan YAN ; Xiangnan FANG ; Tongyu WANG ; Yang HUA ; Xianghui CHEN ; Hongli CHEN ; Jie XU ; Rong ZHANG ; Linong JI ; Yan BI ; Xueyao HAN ; Hong ZHANG ; Cheng HU
Chinese Medical Journal 2025;138(9):1129-1131
5.Professor Jin Shi Treats Vascular Intestinal Obstruction from the Perspective of Collaterals
Yufeng HU ; Xiaojin HE ; Feifei XI ; Xiangyu ZHANG ; Bin DU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(8):1100-1107
Ischemic obstruction is a dangerous condition with a high mortality rate.Professor Jin Shi proposed that vascular intesti-nal obstruction disease is based on the intestinal tract while the structure of mesenteric vascular structure in modern medicine is highly similar to the morphological description of"intestinal collateral"in traditional Chinese medicine.The"hypercoagulable state"of blood is highly consistent with the core of the pathogenesis of"intestinal stasis"in traditional Chinese medicine.Blood stasis is a key patho-logical product and pathogenic factor of vascular intestinal obstruction and it is necessary to pay attention to the combination of disease identification,clarification of urgency,and phased treatment.This study provides a theoretical basis and practical example for the treatment of vascular intestinal obstruction in traditional Chinese medicine.
6.Clinical efficacy of stellate ganglion block combined with intranasal dexmedetomidine spray in patients with insomnia disorders
Ziqi HUANG ; Xiaomin FAN ; Fang LIU ; Baojia LIN ; Shunqing HU ; Xiangyu LIU ; Shuangrui WANG ; Yongjia WANG ; Xinjian ZHANG
The Journal of Practical Medicine 2025;41(3):391-395
Objective To evaluate the clinical efficacy of stellate ganglion block(SGB)combined with intranasal dexmedetomidine for the treatment of insomnia.Methods A total of 64 patients aged 18 to 75 with insom-nia were randomly assigned to either the experimental group(DS group)or the control group(S group).The S group received SGB treatment for 14 consecutive days,whereas the DS group received an additional intranasal dexmedeto-midine spray at a dose of 100 μg,administered 30 minutes before bedtime on days 1 through 6,in conjunction with SGB.We measured and recorded the Pittsburgh Sleep Quality Index(PSQI),Self-Rating Depression Scale(SDS),Self-Rating Anxiety Scale(SAS)scores,and Psychomotor Vigilance Test(PVT)results for both groups at three time points:baseline(T1),the day after treatment(T2),and one month after treatment(T3).Results Intra-group Com-parison:In both the DS and S groups,PSQI scores and dimensionspecific scores at T2 and T3 were significantly lower compared to T1(P<0.05).SAS and SDS scores in both groups showed a significant reduction at T3 compared to T1 and T2(P<0.05),while PVT results exhibited no significant changes(P>0.05).Inter-group Comparison:The PSQI scores and dimensionspecific scores in the DS group at T2(8.44±2.99)and T3(8.22±2.60)were significantly lower than those in the S group at T2(10.88±2.56)and T3(10.88±2.84)(P<0.05).However,no significant differences were observed in SDS and SAS scores between the DS and S groups at T2 and T3(P>0.05).Conclusion Compared to standalone SGB,the combination of SGB with intranasal dexmedetomidine significantly enhances sleep quality in patients with insomnia,while not impacting their levels of anxiety,depression,or alertness.
7.Clinical efficacy of single channel split body endoscopic minimally invasive surgery for single segment thoracic ossification of the ligamentum flavum
Xiangyu LIN ; Wanlong XU ; Le LI ; Wencan ZHANG ; Chen LIU ; Kunpeng LI ; Bingtao HU ; Chongyi WANG ; Yunze FENG ; Kaibin WANG ; Haipeng SI
Chinese Journal of Orthopaedics 2025;45(17):1111-1118
Objective:To explore the efficacy and safety of one-hole split endoscope (OSE) minimally invasive surgery for the treatment of single-segment thoracic ossification of the ligamentum flavum (TOLF).Methods:This retrospective non-randomized controlled study included 41 patients with single-segment TOLF who underwent surgery at Qilu Hospital of Shandong University between July 2019 and July 2023. Patients were divided into two groups: the OSE group (19 cases) treated with one-hole split endoscope minimally invasive surgery and the open group (22 cases) treated with traditional laminectomy and pedicle screw fixation. There were no significant differences between the two groups on gender, age, disease duration, affected segment, presence or absence of dural ossification, and residual cross-sectional vertebral canal area on CT ( P>0.05). Additionally, perioperative surgical time, estimated blood loss (EBL), incision length, hospital stay duration, hospitalization costs and follow-up duration were compared. The Japanese Orthopaedic Association (JOA) score and Oswestry Disability Index (ODI) were compared preoperatively and at the last follow-up. Complications were also recorded. Results:All patients successfully completed the surgery with no significant differences at the last follow-up ( P>0.05). Compared with the open group, the OSE group had a significantly shorter operative time (133.1±16.8 vs. 160.5±22.6 min), lower EBL (91.2±15.0 vs. 192.5±43.8 ml), shorter incision length (2.6±0.5 vs. 7.9±1.9 cm), reduced hospital stay (3.9±0.8 vs. 5.6±0.8 days), and lower hospitalization costs (34,874.9±4,568.6 vs. 53,162.3±9,815.6 yuan) (all P<0.05). AAt the final follow-up, JOA scores (8.5±0.8 vs. 8.6±1.2) and ODI values (16.7%±2.1% vs. 17.7%±4.4%) showed no significant differences between the OSE and open groups ( P>0.05). During the perioperative period and follow-up, complications occurred in 2 patients in the OSE group (1 cerebrospinal fluid leak, 1 poor wound healing) and in 8 patients in the open group (5 cerebrospinal fluid leaks, 1 neurological deterioration, 2 poor wound healing). Conclusion:OSE minimally invasive surgery is an effective treatment for single-segment thoracic ossification of the ligamentum flavum. Compared with open surgery, it provides advantages such as minimal invasiveness and fewer complications.
8.Application progress of single-cell RNA sequencing technology in breast development and related diseases.
Shiyi WEN ; Yang HU ; Xiangyu CHEN ; Jianda ZHOU ; Ping LI
Journal of Central South University(Medical Sciences) 2025;50(6):1080-1087
The spatio-temporal heterogeneity of breast cell subsets forms the fundamental biological basis for physiological development and pathological progression, including tumorigenesis; however, its complex regulatory mechanisms are not yet fully elucidated. With its high-resolution capabilities, single-cell RNA sequencing (scRNA-seq) technology offers a powerful tool for dissecting this cellular heterogeneity. This technology enables the construction of high-precision breast cell atlases, the accurate identification of distinct cell subsets, and the reconstruction of differentiation trajectories from stem/progenitor cells to functional epithelial cells. By resolving the transcriptional regulatory networks that govern cell fate determination, intercellular communication patterns, and dynamic microenvironmental interactions, scRNA-seq has unveiled the molecular foundations of breast development and provided new perspectives on the pathogenesis of related diseases such as breast cancer and macromastia. Furthermore, scRNA-seq demonstrates significant potential for discovering early molecular markers of disease, deciphering tumor heterogeneity, and elucidating mechanisms of therapeutic resistance. The continued application of scRNA-seq for dissecting breast cell heterogeneity, combined with its integration with multi-modal data such as spatial omics, promises to provide critical evidence and new insights for revealing the molecular mechanisms of breast development-related diseases and for formulating precision therapeutic strategies.
Humans
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Single-Cell Analysis/methods*
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Female
;
Breast Neoplasms/pathology*
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Sequence Analysis, RNA/methods*
;
Breast/cytology*
9.PARylation promotes acute kidney injury via RACK1 dimerization-mediated HIF-1α degradation.
Xiangyu LI ; Xiaoyu SHEN ; Xinfei MAO ; Yuqing WANG ; Yuhang DONG ; Shuai SUN ; Mengmeng ZHANG ; Jie WEI ; Jianan WANG ; Chao LI ; Minglu JI ; Xiaowei HU ; Xinyu CHEN ; Juan JIN ; Jiagen WEN ; Yujie LIU ; Mingfei WU ; Jutao YU ; Xiaoming MENG
Acta Pharmaceutica Sinica B 2025;15(9):4673-4691
Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.
10.Chromatin landscape alteration uncovers multiple transcriptional circuits during memory CD8+ T-cell differentiation.
Qiao LIU ; Wei DONG ; Rong LIU ; Luming XU ; Ling RAN ; Ziying XIE ; Shun LEI ; Xingxing SU ; Zhengliang YUE ; Dan XIONG ; Lisha WANG ; Shuqiong WEN ; Yan ZHANG ; Jianjun HU ; Chenxi QIN ; Yongchang CHEN ; Bo ZHU ; Xiangyu CHEN ; Xia WU ; Lifan XU ; Qizhao HUANG ; Yingjiao CAO ; Lilin YE ; Zhonghui TANG
Protein & Cell 2025;16(7):575-601
Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism*
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Cell Differentiation
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Chromatin/immunology*
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Animals
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Mice
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Immunologic Memory
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Epigenesis, Genetic
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SOXC Transcription Factors/immunology*
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NF-E2-Related Factor 2/immunology*
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Mice, Inbred C57BL
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Gene Regulatory Networks
;
Enhancer Elements, Genetic


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