1.Influenza A virus infection activates TLR3-mediated necroptosis
Weijie LI ; Congying HUANG ; Ziling ZENG ; Xiang LI ; Jia XU ; Tian GONG ; Hao ZHANG ; Xinyan ZHANG ; Ping WANG ; Yuanjia HU ; Haiyu XU ; Lijuan SONG
Science of Traditional Chinese Medicine 2026;4(1):40-49
Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 −10; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 −7). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.
2.Preliminary exploration of differentiating and treating multiple system atrophy from the perspective of the eight extraordinary meridians
Di ZHAO ; Zhigang CHEN ; Nannan LI ; Lu CHEN ; Yao WANG ; Jing XUE ; Xinning ZHANG ; Chengru JIA ; Xuan XU ; Kaige ZHANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):392-397
Multiple system atrophy (MSA) is a rare neurodegenerative disease with complex clinical manifestations, presenting substantial challenges in clinical diagnosis and treatment. Its symptoms and the eight extraordinary meridians are potentially correlated; therefore, this article explores the association between MSA symptom clusters and the eight extraordinary meridians based on their circulation and physiological functions, as well as their treatment strategies. The progression from deficiency to damage in the eight extraordinary meridians aligns with the core pathogenesis of MSA, which is characterized by "the continuous accumulation of impacts from the vital qi deficiency leading to eventual damage". Liver and kidney deficiency and the emptiness of the eight extraordinary meridians are required for the onset of MSA; the stagnation of qi deficiency and the gradual damage to the eight extraordinary meridians are the key stages in the prolonged progression of MSA. The disease often begins with the involvement of the yin and yang qiao mai, governor vessel, thoroughfare vessel, and conception vessel before progressing to multiple meridian involvements, ultimately affecting all eight extraordinary meridians simultaneously. The treatment approach emphasizes that "the direct method may be used for joining battle, but indirect method will be needed in order to secure victory" and focuses on "eliminate pathogenic factors and reinforce healthy qi". Distinguishing the extraordinary meridians and focusing on the primary symptoms are pivotal to improving efficacy. Clinical treatment is aimed at the target, and tailored treatment based on careful clinical observation ensures precision in targeting the disease using the eight extraordinary meridians as the framework and core symptoms as the specific focus. Additionally, combining acupuncture, daoyin therapy, and other method may help prolong survival. This article classifies clinical manifestations based on the theory of the eight extraordinary meridians and explores treatment.
3.Association between pubertal timing and depressive symptoms among high school students in Suzhou City
HU Jiale, ZHANG Liye, LING Ruizhe, HAN Di, WANG Xi, HU Jia, SHEN Hui
Chinese Journal of School Health 2025;46(10):1469-1473
Objective:
To investigate the relationship between pubertal timing and depressive symptoms among high school students in Suzhou, so as to provide scientific evidence for promoting adolescents mental health.
Methods:
From October 2023 to January 2024, 3 369 students were selected from 20 high schools in Suzhou using stratified cluster random sampling method. Physical examinations and questionnaire surveys were conducted. The Preece & Baines growth Model 1 was used to calculate the age at take off of height velocity (ATO) and age at peak height velocity (APHV), categorizing students into three groups: early pubertal timing group (< P 15 ), ontime group ( P 15 - P 85 ), and delayed group (> P 85 ). Binary Logistic regression was used to analyze its association with depressive symptoms.
Results:
The ATO for male and female high school students in Suzhou was (9.35±1.23) and ( 8.12 ±1.52) years old, respectively. The mean APHV was (12.35±0.74) years old for boys and (10.91±0.82) years old for girls. The overall prevalence of depressive symptoms was 34.22%, with no statistically significant gender difference ( χ 2=0.42, P =0.52). Significant differences in depressive symptom prevalence were observed across grade levels, breakfast frequency, weekly days of moderate to vigorous physical activity, daily sleep duration, history of school bullying, and the presence of Internet addiction ( χ 2=5.03-69.21, all P < 0.05 ). After adjusting for age, body mass index, region, boarding status, breakfast frequency, weekly moderate to vigorous physical activity days, sleep duration, campus bullying, and presence of Internet addiction, Logistic regression analysis revealed that when ATO was used to evaluate pubertal timing, the risk of depressive symptoms in the delayed group of boys was 1.65 times that of the on time group (95% CI =1.24-2.19); when APHV was used to evaluate pubertal timing, the risks of depressive symptoms in the early pubertal timing group and delayed group of boys were 1.43 times (95% CI =1.07-1.91) and 1.41 times (95% CI =1.05-1.88) of that of the on time group, respectively (all P <0.05). No statistically significant associations were found among females (all P > 0.05 ).
Conclusion
The prevalence of depressive symptoms among high school students in Suzhou is relatively high, and both early and delayed puberty timing in boys are associated with depressive symptoms.
4.Relationship between changes in classroom lighting environment and refractive progression among primary and secondary school students
HAN Di, LING Ruizhe, ZHANG Liye, WANG Yuehong, BAO Xinyu, SHEN Hui, HU Jia
Chinese Journal of School Health 2025;46(11):1549-1553
Objective:
To analyze the changes in classroom lighting environment of schools in Suzhou and their impact on refractive progression among primary and secondary school students, so as to provide the basis for accurate provention and control of myopia.
Methods:
A baseline investigation was conducted in October 2022 by using a stratified cluster random sampling method to recruit primary and secondary school students from Suzhou. A follow up visit was performed in October 2023. A total of 12 302 students and 360 classrooms that participated in both surveys were included analysis. The visual acuity progression over one year and classroom lighting conditions were assessed. Group comparisons were performed by using the Wilcoxon or Kruskal-Wallis rank-sum, and Chi-square tests. Multivariate Logistic regression was employed to identify the major factors influencing refractive changes.
Results:
The compliance rate of average illuminance on classroom blackboard surface increased from 72.22% to 75.28%, while the compliance rate of average illuminance on desks decreased from 89.44% to 87.22%, the overall myopia rate among students rose from 59.63% to 66.99% from 2022 to 2023. The average annual progression of equivalent spherical power(SE) in the right eye of students was -0.25(-0.75,0.06)D. Significant statistical differences were observed in the annual mean changes across different school levels, regions, baseline refractive statuses, and classroom lighting environment change groups ( Z/H =316.59, -8.27, 38.80 , 51.01, all P <0.05). Multivariate Logistic regression analysis showed that pre myopia, low myopia, junior high school, senior high school, vocational high school, and improved classroom lighting environment were protective factors of reducing the risk of rapid progression in refractive error ( OR =0.58, 0.69, 0.81, 0.50, 0.28, 0.82, all P <0.05). Conversely, female students and rural students had higher risks of rapid myopia progression ( OR =1.09, 1.42, both P <0.05).
Conclusions
Over one year follow up, the complance rate of classroom lighting indicators in Suzhou remaines stable, while students refractive status shows a trend toward myopia. Improving classroom lighting environment can reduce the risk of rapid myopia progression.
5.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
6.Genome-wide investigation of transcription factor footprints and dynamics using cFOOT-seq.
Heng WANG ; Ang WU ; Meng-Chen YANG ; Di ZHOU ; Xiyang CHEN ; Zhifei SHI ; Yiqun ZHANG ; Yu-Xin LIU ; Kai CHEN ; Xiaosong WANG ; Xiao-Fang CHENG ; Baodan HE ; Yutao FU ; Lan KANG ; Yujun HOU ; Kun CHEN ; Shan BIAN ; Juan TANG ; Jianhuang XUE ; Chenfei WANG ; Xiaoyu LIU ; Jiejun SHI ; Shaorong GAO ; Jia-Min ZHANG
Protein & Cell 2025;16(11):932-952
Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics*
;
Humans
;
Chromatin/genetics*
;
Animals
;
Binding Sites
;
Mice
;
DNA Footprinting/methods*
7.From pioneering to innovation: A comprehensive review of acupuncture anesthesia in cardiothoracic surgeries.
Xin-di WU ; Xu-Qiang WEI ; Tong-Yu CHEN ; Wen-Xiong ZHOU ; Ke WANG ; Jia ZHOU
Journal of Integrative Medicine 2025;23(6):623-629
The evolution of acupuncture anesthesia (AA) has spanned six decades. Cardiothoracic surgery serves as a representative case study to illustrate this evolution. Reflecting on its historical development, the use of AA in cardiothoracic surgery has advanced from basic AA procedures in the 1960s to combined acupuncture and drug anesthesia techniques in the early 1980s. Since 2005, the innovative use of non-intubation AA combined anesthesia has been implemented extensively in cardiothoracic surgery. As the medical industry continues to evolve, the techniques applied in AA have expanded to encompass the entire perioperative period in cardiothoracic surgery, leading to the introduction of the concept of modern AA. The use of AA in cardiothoracic surgery exemplifies the ongoing advances and integration of traditional Chinese and Western medicine. Moving forward, it is imperative to enhance the theoretical framework of AA through the execution of rigorous multicenter clinical trials, to further strengthen the body of evidence supporting evidence-based medicine, and to finally explore the underlying mechanisms of AA. Please cite this article as: Wu XD, Wei XQ, Chen TY, Zhou WX, Wang K, Zhou J. From pioneering to innovation: A comprehensive review of acupuncture anesthesia in cardiothoracic surgeries. J Integr Med. 2025; 23(6):623-629.
Humans
;
Acupuncture Analgesia/methods*
;
Acupuncture Therapy/methods*
;
Cardiac Surgical Procedures
;
Anesthesia/methods*
;
Thoracic Surgical Procedures
8.Development and Initial Validation of the Multi-Dimensional Attention Rating Scale in Highly Educated Adults.
Xin-Yang ZHANG ; Karen SPRUYT ; Jia-Yue SI ; Lin-Lin ZHANG ; Ting-Ting WU ; Yan-Nan LIU ; Di-Ga GAN ; Yu-Xin HU ; Si-Yu LIU ; Teng GAO ; Yi ZHONG ; Yao GE ; Zhe LI ; Zi-Yan LIN ; Yan-Ping BAO ; Xue-Qin WANG ; Yu-Feng WANG ; Lin LU
Chinese Medical Sciences Journal 2025;40(2):100-110
OBJECTIVES:
To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels.
METHODS:
The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT).
RESULTS:
The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049).
CONCLUSIONS
The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans
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Adult
;
Male
;
Attention/physiology*
;
Female
;
Middle Aged
;
Reproducibility of Results
;
Young Adult
;
Psychometrics
9.Effectiveness analysis of arthroscopic outside-in release for gluteal muscle contracture in supine position.
Di JIA ; Qiguo RAN ; Fei SUN ; Kun ZHANG ; Yanlin LI
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(7):848-854
OBJECTIVE:
To compare the effectiveness of arthroscopic outside-in release for gluteal muscle contracture (GMC) in supine position versus lateral decubitus position.
METHODS:
The clinical data of 34 GMC patients meeting selection criteria between January 2022 and May 2023 were retrospectively analyzed. Arthroscopic contracture band release was performed in the lateral decubitus position (lateral group, n=14) or the supine position (supine group, n=20). No significant difference ( P>0.05) was observed between groups in baseline data, including gender, age, body mass index, preoperative GMC functional quantitative score, modified Harris hip score (mHHS), visual analogue scale (VAS) pain score, and hip flexion/adduction range of motion (ROM). The total operation time, release procedure time, non-release procedure time, intraoperative blood loss, hospital stay, and postoperative complications were recorded and compared. Functional outcomes (GMC functional quantitative score, mHHS score, VAS score, hip flexion/adduction ROM) were evaluated preoperatively and at 3, 12, and 24 months postoperatively.
RESULTS:
All incisions healed by first intention without major vascular or neurological complications. In the lateral group, 3 patients developed patchy bruising on bilateral buttocks and posterior thighs at 3 days after operation, which resolved after 2 weeks of ice packs and ultrasonic therapy. The supine group demonstrated significantly shorter total operation time, non-release procedure time, hospital stay, and reduced intraoperative blood loss versus the lateral group ( P<0.05). No significant difference was found in release procedure time ( P>0.05). All patients were followed up 24 months. Both groups showed significant improvements ( P<0.05) in mHHS score, GMC functional quantitative score, VAS score, and hip adduction/flexion ROM at all postoperative timepoints compared to preoperative values, with no significant intergroup differences ( P>0.05).
CONCLUSION
Both surgical positions effectively improve hip function in GMC patients. However, the supine position offers significant advantages over the lateral decubitus position in operation time, anesthesia management, intraoperative blood loss control, and reduced hospital stay.
Humans
;
Male
;
Female
;
Arthroscopy/methods*
;
Retrospective Studies
;
Buttocks/surgery*
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Adult
;
Range of Motion, Articular
;
Supine Position
;
Treatment Outcome
;
Middle Aged
;
Contracture/surgery*
;
Muscle, Skeletal/surgery*
;
Young Adult
;
Operative Time
;
Hip Contracture/surgery*
;
Patient Positioning/methods*
10.Effectiveness of arthroscopic treatment for femoroacetabular impingement syndrome combined with ligamentum teres injury.
Siyu HAN ; Song LI ; Di JIA ; Yanlin LI ; Guofeng CAI
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(12):1551-1555
OBJECTIVE:
To investigate the effectiveness of hip arthroscopy in the treatment of patients with femoroacetabular impingement (FAI) syndrome combined with ligamentum teres injury.
METHODS:
A retrospective analysis was conducted on 23 patients (23 hips) with Cam-type FAI syndrome combined with ligamentum teres injury who met the selection criteria between April 2022 and May 2024. The cohort included 12 males and 11 females, with a mean age of 29.16 years (range, 16-57 years). According to Tönnis classification, there were 5 cases of grade 0, 10 cases of grade Ⅰ, and 8 cases of grade Ⅱ in hip osteoarthritis. The disease duration ranged from 6 to 24 months, with an average of 12 months. Under hip arthroscopy, hypertrophic synovium and the damaged ligamentum teres were debrided, while the torn labrum and cartilage were repaired, and femoral head-neck osteoplasty was performed to eliminate impingement, restore the normal morphology of the acetabulum and femoral head-neck, and suture the joint capsule. Acetabular lateral center-edge angle (LCEA) and α angle (reflecting the degree of non-sphericity at the femoral head-neck junction) were measured before and after operation, and the modified Harris hip score (mHHS), the International Hip Outcome Tool-12 (IHOT-12), and the visual analogue scale (VAS) score for pain were evaluated.
RESULTS:
The operation was successfully completed in all patients. The incisions healed by first intention after operation, and there was no perioperative complications such as iatrogenic cartilage injury, fracture, infection, neurovascular traction injury, or lower extremity venous thrombosis. All the 23 patients were followed up 12-24 months, with an average of 14.6 months. The pain of hip joint significantly relieved, and the function of hip joint improved; no complication such as joint stiffness, joint instability, and osteonecrosis of the femoral head occurred. The α angle, VAS score, mHHS score, and IHOT-12 score at last follow-up were significantly better than those before operation ( P<0.05); there was no significant difference in LCEA compared to preoperative value ( P>0.05).
CONCLUSION
Hip arthroscopy is a safe and effective treatment for patients with FAI syndrome combined with ligamentum teres injury, which can achieve satisfactory effectiveness.
Humans
;
Femoracetabular Impingement/complications*
;
Arthroscopy/methods*
;
Adult
;
Male
;
Female
;
Retrospective Studies
;
Middle Aged
;
Adolescent
;
Treatment Outcome
;
Young Adult
;
Hip Joint/surgery*
;
Acetabulum/surgery*
;
Round Ligaments/surgery*
;
Range of Motion, Articular


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