1.Standards for the Application of Hemodynamic Monitoring Technology in Critical Care
Hua ZHAO ; Hongmin ZHANG ; Xin DING ; Huan CHEN ; Jun DUAN ; Wei DU ; Bo TANG ; Yuankai ZHOU ; Dongkai LI ; Xinchen WANG ; Cui WANG ; Gaosheng ZHOU ; Xiaoting WANG
Medical Journal of Peking Union Medical College Hospital 2026;17(1):73-85
With the rapid advancement of hemodynamic indices and monitoring technologies, their classification methods and application processes have become increasingly complex. Currently, no unified standard hasbeen established, making it difficult to fully meet the clinical requirements for hemodynamic management. To assist in hemodynamic monitoring assessment and therapeutic decision-making in critically ill patients, the Critical Hemodynamic Therapy Collaborative Group, in conjunction with the Critical Ultrasound Study Group, has jointly developed the Standard for the Application of Hemodynamic Monitoring Techniques in Critical Care. The first part of this standard systematically categorizes hemodynamic indicators into flow indicators, pressure and its derivative indicators, and tissue perfusion indicators, while elaborating on the clinical application of each. The second part establishes a standardized clinical implementation pathway for hemodynamic monitoring. It proposes a tiered monitoring strategy-comprising basic, advanced, indication-specific, and special scenario monitoring-tailored to different clinical settings. It emphasizes the central role of critical care ultrasound across all levels of monitoring and establishes hemodynamic assessment standards for organs such as the brain, kidneys, and gastrointestinal tract. This standard aims to provide a unified framework for clinical practice, teaching, training, and research in critical care medicine, thereby promoting standardized development within the discipline.
2.Expert consensus on the diagnosis and treatment of cemental tear.
Ye LIANG ; Hongrui LIU ; Chengjia XIE ; Yang YU ; Jinlong SHAO ; Chunxu LV ; Wenyan KANG ; Fuhua YAN ; Yaping PAN ; Faming CHEN ; Yan XU ; Zuomin WANG ; Yao SUN ; Ang LI ; Lili CHEN ; Qingxian LUAN ; Chuanjiang ZHAO ; Zhengguo CAO ; Yi LIU ; Jiang SUN ; Zhongchen SONG ; Lei ZHAO ; Li LIN ; Peihui DING ; Weilian SUN ; Jun WANG ; Jiang LIN ; Guangxun ZHU ; Qi ZHANG ; Lijun LUO ; Jiayin DENG ; Yihuai PAN ; Jin ZHAO ; Aimei SONG ; Hongmei GUO ; Jin ZHANG ; Pingping CUI ; Song GE ; Rui ZHANG ; Xiuyun REN ; Shengbin HUANG ; Xi WEI ; Lihong QIU ; Jing DENG ; Keqing PAN ; Dandan MA ; Hongyu ZHAO ; Dong CHEN ; Liangjun ZHONG ; Gang DING ; Wu CHEN ; Quanchen XU ; Xiaoyu SUN ; Lingqian DU ; Ling LI ; Yijia WANG ; Xiaoyuan LI ; Qiang CHEN ; Hui WANG ; Zheng ZHANG ; Mengmeng LIU ; Chengfei ZHANG ; Xuedong ZHOU ; Shaohua GE
International Journal of Oral Science 2025;17(1):61-61
Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans
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Dental Cementum/injuries*
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Consensus
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Diagnosis, Differential
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Cone-Beam Computed Tomography
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Tooth Fractures/therapy*
3.Mediation analysis of plasma phosphorylated tau217 in the association between periodontitis and mild cognitive impairment.
Yanbiao ZHANG ; Meirong WEI ; Xuejuan ZHAO ; Xiaolei QI ; Shanshan ZUO ; Shumei MAO ; Jun WANG ; Gang DING
West China Journal of Stomatology 2025;43(6):845-859
OBJECTIVES:
This study aimed to investigate the potential mediating role of plasma phosphorylated tau217 (p-tau217) in the association between periodontitis and mild cognitive impairment (MCI).
METHODS:
In this case-control study, patients diagnosed with MCI in the Neurology Department of the First Affiliated Hospital of Shandong Second Medical University from November 2023 to May 2024 were selected as the case group (MCI group). Cognitively normal (CN) volunteers, matched for age and education level and recruited from the physical examination center during the same period, served as the control group (CN group). The general demographic data of the study participants were collected. The Beijing versions of the Montreal Cognitive Assessment (MoCA), clinical dementia rating (CDR), and activities of daily living scale (ADL) were used to assess neuropsychological functions. Clinical periodontal examinations were conducted, the periodontal inflamed surface area (PISA) was calculated, and the periodontitis stage was determined in accordance with the 2018 classification. Fasting elbow venous blood samples were collected in the morning, and blood biochemical indicators were measured. Plasma p-tau217 levels were detected using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using t-test, Mann-Whitney U test, chi-square test, partial correlation analysis, multivariate Logistic regression analysis, multiple linear regression analysis, restricted cubic spline (RCS) regression analysis, and mediation effect analysis.
RESULTS:
Among the 192 participants, 96 belong to the MCI group and 96 to the CN group. The prevalence of periodontitis was 63.5% in the MCI group and 43.8% in the CN group, with a statistically significant difference (χ²=7.561, P=0.006). The plasma p-tau217 levels in the MCI group were significantly higher than those in the CN group [7.00 (4.27-9.65) ng/mL versus 2.02 (0.80-3.81) ng/mL, Z=-8.108, P<0.001]. Partial correlation analysis revealed that plasma p-tau217 levels were positively correlated with all the clinical periodontal indices (all P<0.001). After adjustments for baseline covariates, multivariate Logistic regression indicated that periodontitis was an independent risk factor for MCI. Patients with periodontitis had a 1.977-fold higher MCI risk than those without periodontitis (OR=1.977, 95%CI: 1.088-3.594, P=0.025). Moreover, the MCI risk for stage Ⅰ/Ⅱ periodontitis and stage Ⅲ/Ⅳ periodontitis was 1.878 times (OR=1.878, 95%CI: 1.029-3.425, P=0.040) and 2.625 times (OR=2.625, 95%CI: 1.073-6.246, P=0.035) higher than that for patients without periodontitis, respectively. Trend test showed that the MCI risk increased with periodontitis severity (Ptrend=0.016). After adjustments for baseline covariates, multiple linear regression analysis showed that periodontitis was an independent risk factor for increased plasma p-tau217 levels (β=3.309, 95%CI: 2.363-4.254, P<0.001). Compared with patients without periodontitis, those with stage Ⅰ/Ⅱ periodontitis (β=1.838, 95%CI: 0.869-2.806, P<0.001) and stage Ⅲ/Ⅳ periodontitis (β=5.539, 95%CI: 4.442-6.636, P<0.001) had significantly higher plasma p-tau217 levels. In addition, trend test indicated that plasma p-tau217 levels increased with periodontitis severity (Ptrend<0.001). After adjustments for baseline covariates, RCS regression analysis further revealed that PISA had a positive linear dose-response relationship with MCI risk (Poverall=0.002, Pnonlinear=0.344) and plasma p-tau217 levels (Poverall<0.001, Pnonlinear=0.140). After adjustments for baseline covariates, mediation analysis showed that plasma p-tau217 mediated the association between periodontitis and MCI, with a mediation proportion of 13.99% (95% Bootstrap CI: 0.38%-49.39%, P=0.038).
CONCLUSIONS
Periodontitis was independently positively associated with MCI risk, and plasma p-tau217 plays a mediating role in this association.
Humans
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Cognitive Dysfunction/complications*
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tau Proteins/blood*
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Periodontitis/complications*
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Case-Control Studies
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Male
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Female
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Phosphorylation
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Aged
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Middle Aged
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Activities of Daily Living
4.Effects and mechanisms of total flavones of Abelmoschus manihot combined with empagliflozin in attenuating diabetic tubulopathy through multiple targets based on mitochondrial homeostasis and ZBP1-mediated PANoptosis.
Si-Yu CHA ; Meng WANG ; Yi-Gang WAN ; Si-Ping DING ; Yu WANG ; Shi-Yu SHEN ; Wei WU ; Ying-Lu LIU ; Qi-Jun FANG ; Yue TU ; Hai-Tao TANG
China Journal of Chinese Materia Medica 2025;50(13):3738-3753
This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals
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Rats
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Mitochondria/metabolism*
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Benzhydryl Compounds/administration & dosage*
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Glucosides/administration & dosage*
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Abelmoschus/chemistry*
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Male
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Homeostasis/drug effects*
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Flavones/administration & dosage*
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Rats, Sprague-Dawley
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Diabetic Nephropathies/physiopathology*
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Drugs, Chinese Herbal/administration & dosage*
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DNA-Binding Proteins/genetics*
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Humans
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Apoptosis/drug effects*
5.Expert consensus on visualized tele-round and quality control management based on the improvement of clinical practice ability
Wanhong YIN ; Xiaoting WANG ; Ran ZHOU ; Dawei LIU ; Yan KANG ; Yaoqing TANG ; Xiaochun MA ; Jianguo LI ; Zhenjie HU ; Haitao ZHANG ; Wei HE ; Lixia LIU ; Wenjin CHEN ; Ran ZHU ; Jun WU ; Hongmin ZHANG ; Lina ZHANG ; Wenzhao CHAI ; Shihong ZHU ; Wangbin XU ; Rongqing SUN ; Xiangyou YU ; Tianjiao SONG ; Ying ZHU ; Hong REN ; Ai SHANMU ; Qing ZHANG ; Wei FANG ; Xiuling SHANG ; Liwen LYU ; Shuhan CAI ; Xin DING ; Heng ZHANG ; Guang FENG ; Lipeng ZHANG ; Bo HU ; Dong ZHANG ; Weidong WU ; Feng SHEN ; Xiaojun YANG ; Zhenguo ZENG ; Qibing HUANG ; Xueying ZENG ; Tongjuan ZOU ; Milin PENG ; Yulong YAO ; Mingming CHEN ; Hui LIAN ; Jingmei WANG ; Yong LI ; Feng QU ; Gang YE ; Rongli YANG ; Xiukai CHEN ; Suwei LI ; Juxiang WANG ; Yangong CHAO
Chinese Journal of Internal Medicine 2025;64(2):101-109
Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.
6.Effects of Wenfei Jiangzhuo Formula on mitochondrial function of Aβ25-35-induced BV-2 cells based on PGAM5-Drp1 axis
Ding ZHANG ; Zhi-han HU ; Ke-qing ZHOU ; Wei CHEN ; Hong-ling QING ; Jun-jun XIANG ; Yue-qiang HU
Chinese Traditional Patent Medicine 2025;47(8):2558-2565
AIM To investigate the effects of Wenfei Jiangzhuo Formula on mitochondrial function of Aβ25-35-induced BV-2 cells.METHODS In the establishment of cell model of Alzheimer's disease(AD)using Aβ25-35 on the BV-2 cells,the optimal concentration and time point of Aβ25-35 intervention were determined;and the groups for the intervention of LFHP-1c group(inhibitor)or the serum containing Wenfei Jiangzhuo Formula were set up.The detection of the optimal intervention concentration and time point by CCK-8 assay;the observation of cell migration and apoptosis by Transwell assay and Hoechst 33342 staining;the detection of the positive expressions of PGAM5 and Drp1 by immunofluorescence;and the detection of cellular PGAM5,Drp1,OPA1,and Mfn1/2 mRNA and protein expressions by RT-qPCR and Western blot were conducted.RESULTS The best AD cell model was established by 48 h exposure to 5 μmol/L of Aβ25-35,and most active cell viability was achieved with the 48 h use of serum containing 20%Wenfei Jiangzhuo Formula.Compared with the control group,the model group displayed decreased number of cell migration,more bright blue positive apoptotic cells,increased number of PGAM5 and Drp1 positive cells and their mRNA and protein expressions(P<0.05);and decreased mRNA and protein expressions of OPA1 and Mfn1/2(P<0.05).Compared with the model group,the groups intervened with the medicines shared increased number of cell migration,less bright blue positive apoptotic cells,decreased number of PGAM5 and Drp1 positive cells and their mRNA and protein expressions(P<0.05);and elevated OPA1 and Mfn1/2 mRNA and protein expressions(P<0.05).CONCLUSION Wenfei Jiangzhuo Formula exerts cerebroprotective effects to improve cognition by reducing cell damage and improving the balance of mitochondrial homeostasis through PGAM5-Drp1 axis in AD model.
7.A Randomized Controlled Clinical Study on the Treatment of Knee Osteoarthritis with Cold-Dampness Arthralgia Obstruc-tion by Shangke Lengtong Patch
Li ZHANG ; Liang DING ; Zhengquan HUANG ; Wei MEI ; Runlin XING ; Songjiang YIN ; Peng WU ; Xi-aochen LI ; Zhenyuan MA ; Nongshan ZHANG ; Jun MAO ; Peimin WANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(3):393-398
OBJECTIVE To explore the effectiveness and possible mechanism of Shangke Lengtong Patch in treating knee osteo-arthritis with cold-dampness arthralgia obstruction.METHODS A total of 70 patients who met the inclusion criteria of knee osteoar-thritis with cold-dampness arthralgia obstruction in the Orthopedics Department of Affiliated Hospital of Nanjing University of Chinese Medicine from November to December 2024 were randomly divided into an experimental group and a control group,with 35 cases in each group.During the treatment,1 case dropped out of the experimental group,3 cases dropped out of the control group,and 1 case was discontinued.The experimental group was treated with Shangke Lengtong Patch,and the control group was treated with Compound Nanxing Zhitong Ointment.The WOMAC scores and TCM syndrome scores of the two groups before and after treatment were compared to comprehensively evaluate the clinical efficacy.The changes in the expression levels of CGRP,substance P,HMGB1,IL-1β,CX-CL12,and CXCR4 in the serum of the two groups were detected by ELISA.RESULTS After 3,7,and 14 d of treatment,the WOMAC scores and TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score of aggrava-ted cold in the experimental group was better than that in the control group at 7 d of treatment(P<0.05);after 14 d of treatment,the expression levels of CGRP,substance P,HMGB1,IL-1β,CXCL12,and CXCR4 in the serum of the two groups were significantly re-duced(P<0.05),and there was no statistical difference between the two groups.CONCLUSION Shangke Lengtong Patch can sig-nificantly relieve the pain symptoms of knee osteoarthritis patients with cold-dampness arthralgia obstruction and improve the joint func-tion of patients.It may improve synovial inflammation by inhibiting the HMGB1/CXCL12/CXCR4 pathway,thereby exerting a thera-peutic effect.
8.Deep learning model based on fundus images for detection of coronary artery disease with mild cognitive impairment
Yi YE ; Wei FENG ; Yao-dong DING ; Qing CHEN ; Yang ZHANG ; Li LIN ; Tong MA ; Bin WANG ; Xian-gang CHANG ; Zong-yuan GE ; Xiao-yi WANG ; Long-jun CAI ; Yong ZENG
Chinese Journal of Interventional Cardiology 2025;33(6):303-311
Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50% stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE<27 or MoCA<26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95%CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95%CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95%CI 0.714-0.802),corresponding to a validated AUC of 0.710(95%CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95%CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95%CI 0.719-0.778)and the specificity was 0.561(95%CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95%CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.
9.Measurement method based on EBT3 film technology for quality control detection of INTRABEAM PRS500 intraoperative radiotherapy equipment
Yi-kun LI ; Wei DING ; Xia-yu HANG ; Jun HU ; Xiang-dong SUN ; Ai-jun XU
Chinese Medical Equipment Journal 2025;46(6):47-53
Objective To propose an EBT3 film technology-based quality control measurement method for the INTRABEAM PRS500 intraoperative radiotherapy equipment to solve the problems of the traditional methods in cumbersome operation and setup error.Methods According to HJ 1198-2021 Requirements of radiation safety and protection for radiotherapy and GBZ 121-2020 Requirements for radiological protection in radiotherapy,the environmental radiation testing of the INTRABEAM PRS500 intraoperative radiotherapy equipment was carried out point by point by means of the radiation inspection instrument.The INTRABEAM PRS500 intraoperative radiotherapy equipment was characterized by a point X-ray source(XRS),and the XRS was detected in terms of the probe linearity,radiation dose,dynamic deviation,isotropy and dose rate.The EBT3 film technology was used to verify the symmetry and isotropy of the XRS planar dose of INTRABEAM PRS500 intraoperative radiotherapy equipment.Results The X-γ dose equivalent rate of each monitoring site of the INTRABEAM PRS500 intraoperative radiotherapy device was lower than the method detection limit(MDL).The results of SQA quality control showed that the INTRABEAM PRS500 intraoperative radiotherapy equipment XRS met the quality control requirements in terms of the probe linearity,radiation dose,dynamic deviation and etc,and the isotropy differences in the+X,-X,+Y,and-Y axis directions ranged from-1.40%to 1.79%,which were all within the allowable range of measurement tolerance(5.60%to 5.65%).The results of measuring the isotropy of the INTRABEAM PRS500 intraoperative radiotherapy equipment based on the EBT3 film technology showed that the dose distribution of the XRS in the directions of the+X,-X,+Y,and-Y axes at the same plane was well isotropic,and that the doses in the directions of the X and Y axes were symmetrically distributed,and that the maximum skewness value for the isotropy of the XRS in the XY plane was-1.581%,which met the requirements of AAPM TG61 report on the reference dosimetry of low-energy and medium-energy X-rays for radiotherapy and radiobiology of≤±5.3%.Conclusion The EBT3 film technology-based measurement method gains high simplicity and feasibility for the isotropy of the INTRABEAM PRS500 intraoperative radiotherapy equipment in the directions of the+X,-X,+Y,and-Y axes at the same planet,which realizes the dynamic monitoring of the dosimetric changes and facilitates the whole-process quality control management of the intraoperative radiotherapy equipment.[Chinese Medical Equipment Journal,2025,46(6):47-53]
10.Studies on the Design and Activity of Anticancer Peptides Based on the Weak Acidic Microenvironment of Tumors
Yue-Qi NIE ; Miao JIANG ; Hui-Yan WU ; Chang-Hao DING ; Wei REN ; Jun-Yi CHANG ; Ke CHEN ; Shao-Long DU ; Peng ZHANG ; Zhong-Hua LIU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(10):1380-1391
Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38%)and primary myocardial cells(the inhibition rate was 49.7%,with P<0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P<0.01),decreasing the hy-drated particle size(P<0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

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