1.ESCRT Mechanism-mediated Repair of Plasma Membrane Damage Induced by Regulatory Cell Death
Tian-Yang FENG ; Le DENG ; Gou XU ; Li LI ; Miao-Miao GUO
Progress in Biochemistry and Biophysics 2025;52(5):1099-1112
The plasma membrane (PM) plays an essential role in maintaining cell homeostasis, therefore, timely and effective repair of damage caused by factors such as mechanical rupture, pore-forming toxins, or pore-forming proteins is crucial for cell survival. PM damage induces membrane rupture and stimulates an immune response. However, damage resulting from regulated cell death processes, including pyroptosis, ferroptosis, and necroptosis, cannot be repaired by simple sealing mechanisms and thus, requires specialized repair machinery. Recent research has identified a PM repair mechanism of regulated cell death-related injury, mediated by the endosomal sorting complexes required for transport (ESCRT) machinery. Here, we review recent progress in elucidating the ESCRT machinery-mediated repair mechanism of PM injury, with particular focus on processes related to regulated cell death. This overview, along with continued research in this field, may provide novel insights into therapeutic targets for diseases associated with dysregulation of regulated cell death pathways.
2.Monitoring and analysis of eye lens dose of interventional radiology workers
Qiuqiu PAN ; Jun DENG ; Mengxue LI ; Xiaohua MIAO ; Lingling ZHENG ; Yajuan FENG ; Senxing ZHENG
Chinese Journal of Radiological Health 2025;34(3):384-389
Objective To investigate the levels and influencing factors for eye lens dose of interventional radiology workers, and to provide a basis for reasonable and scientific radiation protection. Methods Thermoluminescent eye lens dosimeters were used to monitor the left and right eye lens doses of interventional radiology workers in real time during different surgical positions and varying eye protection conditions. The annual eye lens doses for the operators were estimated based on their yearly workload. The differences in eye lens doses under different conditions were analyzed and the influencing factors were identified. Results For individual interventional operations, the range of personal dose equivalent Hp(3) of the left eye of interventional radiology workers was ( < MDL ~ 418.33) μSv, the median (Q1, Q3) was 9.29 ( < MDL, 40.79) μSv, and the mean was 40.79 ± 70.36 μSv. The estimated annual eye lens doses were 4.05 mSv and 17.80 mSv based on the median and mean values of the eye lens dose of a single operation multiplied by average annual frequency of operations per person, respectively. The left eye lens dose was higher than the right eye lens dose of the same operator (Z = −4.24, P < 0.05), and the dose of the right eye lens was strongly positively correlated with that of the left eye lens. The left eye lens dose of the first surgeon was higher than that of the second surgeon in the same operation (Z = −3.10, P < 0.05). The eye lens dose was influenced by operator position (χ2 = 9.149, P = 0.002, OR = 8.343), eye protection (χ2 = 4.619, P = 0.032, OR = 4.352), and air kerma area product (χ2 = 8.032, P = 0.005, OR = 5.488). Conclusion According to the results of this study, a significant portion of interventional operators have eye lens doses that approach or exceed international occupational dose limits. It is recommended to pay attention to the operation frequency of the first operator and the air kerma area product of interventional operation, and strengthen radiation protection and dose monitoring for the eye lens of interventional radiology workers.
3.Analysis of anatomical characteristics of proximal humerus measured based on three-dimensional reconstruction technique and its clinical significance.
Jun WANG ; Jun DENG ; Shuo LI ; Facan LI ; Yanlin LI ; Miao CHEN
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(10):1296-1303
OBJECTIVE:
To conduct a comprehensive analysis of proximal humeral anatomical characteristics in the Chinese population utilizing three-dimensional reconstruction technology, thereby establishing an evidence base for the enhancement of shoulder hemiarthroplasty procedures and the development of domestically manufactured prostheses.
METHODS:
The study cohort comprised 30 patients (60 shoulders) presenting with cervicoscapular pain between July 2023 and June 2025, with equal gender distribution (15 males and 15 females); age distribution ranged from 20 to 75 years (mean, 53.7 years). Data acquisition was performed via high-resolution CT imaging (technical parameters: slice thickness 0.625 mm, voltage 120 kV, current 150 mA, matrix 512×512). Subsequently, CT datasets were processed in DICOM format using Mimics17.0 software for three-dimensional reconstruction, followed by quantitative assessment via Imageware12.0 software to evaluate key proximal humeral parameters: humeral head dimensions (coronal diameter, sagittal diameter, surface curvature diameter, thickness), angular measurements [neck-shaft angle, retroversion angle (retroversion angle 1 was the angle between the humeral head axis and the line connecting the medial and lateral condyles, and retroversion angle 2 was the angle between the humeral head axis and the tangent of the trochlea)], and positional metrics (medial offset, posterior offset). Statistical analysis incorporated Pearson correlation coefficients to determine parameter relationships, with comparative evaluations conducted across demographic variables including gender, height, body mass, and age.
RESULTS:
Quantitative analysis yielded the following measurements: humeral head coronal diameter (41.8±3.6) mm, sagittal diameter (39.1±4.1) mm, surface curvature diameter (44.9±4.6) mm, thickness (17.2±1.8) mm, neck-shaft angle (128.4±4.2)°, retroversion angle 1 (16.9±8.9)°, retroversion angle 2 (21.4±11.3)°, medial offset (3.8±1.7) mm, and posterior offset (5.1±1.6) mm. Correlation analysis demonstrated the most pronounced positive relationship between humeral head surface curvature diameter and thickness ( r=0.966, P=0.001), with additional significant positive correlations observed between surface curvature diameter and coronal diameter ( r=0.842, P=0.001), posterior offset and retroversion angle 1 ( r=0.766, P=0.001), and coronal diameter and thickness ( r=0.727, P=0.001). Demographic analysis revealed significantly greater dimensions in males compared to females for humeral head surface curvature diameter, coronal diameter, sagittal diameter, and thickness ( P<0.05), with these parameters demonstrating progressive increases corresponding to height ( P<0.05). With the exception of neck-shaft angle, all parameters exhibited a positive correlation with body mass. No significant age-related differences were detected across parameters ( P>0.05).
CONCLUSION
The proximal humeral morphology in the Chinese population exhibits substantial variability, necessitating optimization of prosthetic designs based on population-specific anatomical metrics to enhance the efficacy of personalized clinical interventions.
Humans
;
Middle Aged
;
Male
;
Female
;
Aged
;
Imaging, Three-Dimensional/methods*
;
Adult
;
Tomography, X-Ray Computed/methods*
;
Humerus/diagnostic imaging*
;
Shoulder Joint/surgery*
;
Hemiarthroplasty/methods*
;
Humeral Head/anatomy & histology*
;
Young Adult
;
Clinical Relevance
4.Additional role of low-density lipoprotein cholesterol on the risk of osteoporosis in men with or without coronary heart disease: a real-world longitudinal study.
Jing ZENG ; Zi-Mo PAN ; Ting LI ; Ze-Yu CHEN ; Xiao-Yan CAI ; Mei-Liang GONG ; Xin-Li DENG ; Sheng-Shu WANG ; Nan LI ; Miao LIU ; Chun-Lin LI
Journal of Geriatric Cardiology 2025;22(2):219-228
BACKGROUND:
Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China.
METHODS:
The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model.
RESULTS:
During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437).
CONCLUSIONS
Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.
5.Progress and prospects of anti-IL-4/IL-13 monoclonal antibody treatment in chronic rhinosinusitis with nasal polyps.
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(12):1197-1202
Chronic rhinosinusitis(CRS) is a chronic inflammation of the nasal cavity and sinus mucosa, which is mainly characterized by nasal obstruction, runny nose, headache and hyposmia. Due to complex mechanisms, CRS can be divided into different clinical phenotypes and inflammatory endotypes. Approximately 80% of chronic rhinosinusitis with nasal polyps(CRSwNP) patients present with type Ⅱ inflammation. IL-4 and IL-13 are the key factors in the process of type Ⅱ inflammation, and drugs targeting IL-4/IL-13 provide new options for the treatment of CRSwNP. Therefore, this article mainly reviews the application of anti-IL-4 /IL-13 monoclonal antibody in CRSwNP.
Humans
;
Nasal Polyps/therapy*
;
Sinusitis/therapy*
;
Chronic Disease
;
Interleukin-13/antagonists & inhibitors*
;
Antibodies, Monoclonal/therapeutic use*
;
Interleukin-4/antagonists & inhibitors*
;
Rhinitis/drug therapy*
;
Rhinosinusitis
6.Prognositic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma
Dong WANG ; Qing DENG ; Yi PENG ; Zhaochen TONG ; Zixin LI ; Liping HUANG ; Jin ZENG ; Jinsong LI ; Jinglei MIAO ; Shijie CHEN
Journal of Central South University(Medical Sciences) 2024;49(5):758-774
Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor prognosis.Anchorage-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary site.However,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune microenvironment.This study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma. Methods:Anoikis-related genes(ANRGs)were obtained from GeneCards.Clinical information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)databases.ANRGs highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)algorithm.Machine learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO cohort.Finally,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor microenvironment. Results:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic model.Significant differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all P<0.05).Additionally,characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling pathway. Conclusion:The prognostic model based on ANRGs and tumor microenvironment demonstrate good predictive power and provide more personalized treatment options for patients with osteosarcoma.
7.Diagnostic performance of PI-RADS v2.1 for clinically significant prostate cancer in the peripheral,transitional and multiple zones
Xiao-Jun DENG ; Hao-Cheng ZHANG ; Jiong ZHANG ; Yu-Hang QIAN ; Mei-Mei TAO ; Chun-Mei LIAO ; Miao-Wen LIN ; Gen-Qiang LANG
National Journal of Andrology 2024;30(11):982-986
Objective:To evaluate the diagnostic performance of the Prostate Imaging Reporting and Data System version 2.1(PI-RADS v2.1)for clinically significant prostate cancer(CSPCa)in the peripheral zone(PZ),transitional zone(TZ)and multiple zones(MZs).Methods:We retrospectively studied the clinical data on 108 patients undergoing multiparametric magnetic resonance imaging(mpMRI)and transperineal prostate biopsy in our hospital from January 2021 to January 2023.Using PI-RADS v2.1,we ex-amined the MR images of the patients with suspected PCa,compared the PI-RADS v2.1 scores with the results of prostate biopsy,and analyzed the correlation of the PI-RADS v2.1 scores with CSPCa.We calculated the area under the receiver operating characteristic(ROC)curve(AUC),and described the diagnostic performance of PI-RADS v2.1 for CSPCa in the PZ,TZ and MZs.Results:Transperineal prostate puncture biopsy was successfully completed in all the patients,which revealed 66(61.11%)cases of CSPCa with Gleason score(GS)7-10.Suspected CSPCa was observed in 45(95.74%)of the 47 PZ lesions,8(47.06%)of the 17 TZ le-sions,and 40(90.91%)of the 44 MZ lesions.The PZ,TZ and MZ lesions diagnosed by PI-RADS v2.1 were significantly correlated with CSPCa(r=0.492,P<0.001).The AUCs of PI-RADS v2.1 for PZ,TZ and MZs were 0.644,0.732 and 0.811,with specificities of 66.8%,57.6%and 62.1%,and sensitivities of 57.2%,78.4%and 93.2%,respectively.The negative predictive values were 46.5%,85.7%and 79.2%,and the positive predictive values 76.2%,43.4%and 84.8%,respectively.Conclusion:The PI-RADS v2.1 score has a high diagnostic value for CSPCa in the PZ,TZ and MZs,with the best performance for that in the MZs.
8.Effect of irregular follow-up during normalized prevention and control of epidemic on viral load upon BK virus reactivation and prognosis of kidney transplant recipients
Zhouting WU ; Yuchen WANG ; Wenli ZENG ; Renfei XIA ; Wenfeng DENG ; Jian XU ; Yun MIAO
Organ Transplantation 2024;15(3):429-434
Objective To evaluate the effect of irregular follow-up during normalized prevention and control of novel coronavirus pneumonia (COVID-19) epidemic on BK virus (BKV) reactivation and clinical prognosis of kidney transplant recipients. Methods Clinical data of 363 kidney transplant recipients were retrospectively analyzed, and they were divided into the pre-epidemic follow-up group and during-epidemic follow-up group according to the follow-up time. All patients were followed up for 1 year. The follow-up interval was compared between two groups. The infection of BKV and the correlation between the infection process of BKV and renal graft function were analyzed in two groups. Results A total of 1 790 preson-times were followed up before COVID-19 epidemic and 2 680 during COVID-19 epidemic. Compared with the during-epidemic follow-up group, the follow-up intervals within 3, 3-6 and 7-12 months after kidney transplantation were shorter in the pre-epidemic follow-up group, and the differences were statistically significant (all P<0.05). Within 1 year after kidney transplantation, 35 cases(32%) were diagnosed with BKV viruria, 3 cases(3%) of BKV viremia and 1 case(1%) of BKV-associated nephropathy (BKVAN) in the pre-epidemic follow-up group, and 53(25%), 3(1%) and 1(1%) in the during-epidemic follow-up group, with no statistical significance (all P>0.05). In the pre-epidemic follow-up group, the time for the initial diagnosis of BKV viruria was longer and the viral load of the first urinary BKV reactivation was smaller than those in the during-epidemic follow-up group, with statistical significance (both P<0.05). The load of the first urinary BKV reactivation was positively correlated with the peak load of urinary BKV, and the differences between the baseline and serum creatinine levels at 1 and 3 months after BKV reactivation (all P<0.05). Conclusions Irregular follow-up after kidney transplantation may lead to early BKV reactivation and higher detection value of the first viral load of urinary BKV, delay diagnosis and interventions, and lead to poor prognosis. It is urgent to establish a remote follow-up system to meet the follow-up requirements of kidney transplant recipients when public health incidents occur.
9.Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis.
Shuran FAN ; Ming QI ; Qi QI ; Qun MIAO ; Lijuan DENG ; Jinghua PAN ; Shenghui QIU ; Jiashuai HE ; Maohua HUANG ; Xiaobo LI ; Jie HUANG ; Jiapeng LIN ; Wenyu LYU ; Weiqing DENG ; Yingyin HE ; Xuesong LIU ; Lvfen GAO ; Dongmei ZHANG ; Wencai YE ; Minfeng CHEN
Acta Pharmaceutica Sinica B 2024;14(2):682-697
Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.
10.Relationship between perioperative nutrition risk and venous thromboembolism in patients with hip fracture
Miao HE ; Rong PENG ; Jinshan TIAN ; Xuan LIU ; Lei DENG ; Qian WU
Tianjin Medical Journal 2024;52(1):97-101
Objective To investigate the relationship between perioperative nutritional risk and venous thromboembolism(VTE)in patients with hip fracture.Methods A total of 379 patients with unilateral hip fracture due to fall or sprain who underwent elective surgery were selected and divided into the non-VTE group(246 cases)and the VTE group(133 cases)according to whether or not VTE occurred during perioperative period.Basic information,surgical and anesthesia records,nutritional risk related indicators,inflammatory indicators and outcome indicators of patients were collected.Multiple Logistic regression was used to analyze the independent influencing factors of perioperative VTE.Receiver operating characteristics(ROC)curves were used to assess the ability to discriminate independent factors,and DeLong test was used to compare area under the curve(AUC).Results Compared with the non-VTE group,the proportion of patients in the VTE group was older,complicated with hypertension,the time to visit hospital more than 2 days,received(hollow/intramedullary nail)internal fixation,perioperative blood transfusion,ASA gradeⅢtoⅣ,and higher nutritional risk screening Table(NRS)-2002 scores on admission and higher postoperative neutrophil/lymphocyte ratio(NLR).Nutritional prognosis index(PNI),hemoglobin(Hb)and prealbumin(PA)at admission and after operation were lower in the VTE group than those in the non-VTE group(P<0.01).Multivariate Logistic regression analysis showed that PNI was decreased,NRS-2002 scores and PA were increased,and the time of visit hospital was>2 days after internal fixation.American College of Anesthesiologists(ASA)gradesⅢ-Ⅳwere independent risk factors for perioperative VTE of hip fracture(P<0.05).ROC curve analysis showed that the AUC(95%CI)of NRS-2002 at admission was 0.739(0.692-0.783),and that of PNI at admission was 0.720(0.672-0.765),both of which were better than other influencing factors(P<0.01).Conclusion NRS-2002 and PNI are good predictors of perioperative VTE in patients with hip fracture.

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