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.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.
7.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.
8.Research on population pharmacokinetics of propofol injection in adult patients under general anesthesia
Jin-Xia LI ; An-Cheng GU ; Fu-Miao YUAN ; Cai LI ; Hai-Jun DENG ; Zhong-Yuan XU
The Chinese Journal of Clinical Pharmacology 2024;40(14):2124-2128
Objective To quantitatively assess the influence of various factors on the pharmacokinetic parameters of propofol and to develop a propofol population pharmacokinetic model tailored for Chinese patients.Methods Thirty patients scheduled for selective abdominal surgeries received an anesthesia dose of propofol at 2.0 mg·kg-1.The concentration of propofol in collected venous blood samples was measured using liquid chromatography-tandem mass spectrometry.Polymorphisms in metabolizing enzyme genes were detected through Sanger sequencing technology.Pharmacokinetic parameters were computed,and models were constructed and evaluated using Phoenix Winnonlin software.Results Through software analysis,the drug's in vivo process was best described by a three-compartment model.The population mean values for the central compartment clearance rate(CL),shallow peripheral compartment clearance rate(Q2),deep peripheral compartment clearance rate(Q3),central compartment volume of distribution(V),shallow peripheral compartment volume of distribution(V2),and deep peripheral compartment volume of distribution(V3)were 1.71 L·min-1,1.31 L·min-1,1.51 L·min-1,5.92 L,19.86 L and 99.06 L,respectively.Body weight was identified as a significant covariate affecting CL and V,and was incorporated into the model.Conclusion The evaluation of the final model demonstrates its substantial predictive capability,offering directional guidance for the clinical administration of propofol.
9.Clinical trial of cis-atracurium in the treatment of patients with hysteroscopic surgery
Miao JI ; Yong-Zhi ZHANG ; Yan WU ; Xue-Feng DENG
The Chinese Journal of Clinical Pharmacology 2024;40(18):2640-2644
Objective To explore the influence of intravenous injection of cis-atracurium during anesthesia induction on QT interval(QTc),hemodynamics and oxidative stress level in patients undergoing hysteroscopic surgery.Methods Patients undergoing hysteroscopic surgery were classified into control group and treatment group.The treatment group was given intravenous injection of 2 mg·kg-1 of propofol emulsion injection+3 μg·kg-1 of fentanyl+0.15 mg·kg-1 of cis-atracurium besylate for injection,while the control group was given intravenous injection of 2 mg·kg-1 of propofol emulsion injection+3 μg·kg-1 of fentanyl+the same amount of 0.9%NaCl as treatment group.Laryngeal mask was placed in the two groups after 3 min,and laryngeal mask ventilation was given for general anesthesia.QTc value and hemodynamics[mean arterial pressure(MAP)]were detected before entering the room(T0),after 1 min of propofol+fentanyl intravenous injection(T1),after 1 min of cis-atracurium besylate for injection/0.9%NaCl(T2),immediately after laryngeal mask insertion(T3)and after 3 min of laryngeal mask insertion(T4).The anesthetic effect,postoperative dynamic pain visual analogue scale(VAS)score and sore throat were counted.The levels of serum oxidative stress indicators[superoxide dismutase(SOD),malondialdehyde(MDA)]at T0 and at the end of surgery(T5)were detected,and the safety was assessed.Results Fifty-two cases in treatment group and forty-four cases in control group were included.There was no statistical difference in QTc value between treatment group and control group at T0-T4(all P>0.05).The MAP values in treatment group and control group at T3 were(84.22±5.96)and(86.78±6.11)mmHg,respectively,with a statistical difference(P<0.05).The laryngeal mask insertion times in treatment group and control group were(17.02±2.47)and(19.52±2.34)s;the spontaneous breathing recovery times were(8.51±1.84)and(6.18±1.15)min;the eye opening time were(10.49±2.42)and(9.53±2.17)min;the laryngeal mask removal time were(11.16±2.16)and(10.21±2.34)min;the incidence rates of postoperative sore throat were 13.46%and 31.82%,and the differences were statistically significant(all P<0.05).The levels of SOD in treatment group and control group at T5 were(36.63±4.17)and(33.26±4.86)nU·mL-1;the levels of MDA were(7.42±2.14)and(8.59±2.83)mmol·L-1(all P<0.05).The adverse drug reactions in treatment group were mainly nausea and vomiting,respiratory depression and hypotension,and the adverse drug reactions in control group were mainly nausea and vomiting and respiratory depression.The incidence rates of adverse reactions in treatment group and control group were 13.46%and 11.36%,respectively(P>0.05).Conclusion Cis-atracurium intravenous injection during anesthesia induction has no influence on QTc in patients undergoing hysteroscopic surgery,and has advantages in stabilizing intraoperative hemodynamics,reducing postoperative sore throat and improving serum oxidative stress indicators.
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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