1.Preparation of a near-infrared photoresponsive biomimetic nanoprobe and its application in photothermal detection and treatment of breast cancer
Wenlan LI ; Wenyuan WANG ; Wenxiu REN ; Yupei ZHANG ; Xiaoyan YANG ; Zhigang WANG ; Jizhu XIA
Chinese Journal of Tissue Engineering Research 2024;28(5):669-675
BACKGROUND:Photothermal therapy is a novel tumor treatment strategy that uses photothermal agents to transform light energy into heat energy to accomplish non-invasive tumor ablation.The rise of photothermal therapy and nanotechnology has provided a new perspective on breast cancer treatment.OBJECTIVE:To prepare a new type of near-infrared biomimetic nanoprobe that has been modified by breast cancer cell membrane,to investigate the effect of near-infrared fluorescence/ultrasound imaging in vitro,and to observe its targeting ability and photothermal therapy effect on homologous tumor cells in vitro.METHODS:Organic small molecule ITIC-4CI with A-D-A structure was used as photothermal agents;polylactic acid/glycolic acid copolymer as nanocarrier;4T1 cell membrane of mouse breast cancer cells as a surface modifier of nanoparticles;perfluorohexane(PFH)was loaded.A novel near-infrared biomimetic nanoprobe(4T1m/ITIC-4CI/PFH)was prepared by the double emulsion evaporation method and sonication method.The basic characterization of the nanoprobe and the homologous targeting ability were detected.The photothermal properties and photothermal stability of the probe were investigated,and the near-infrared fluorescence/ultrasound imaging effect of the probe under laser irradiation was observed.The CCK-8 assay and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.RESULTS AND CONCLUSION:(1)The prepared 4T1m/ITIC-4CI/PFH nanoprobes had uniform size,high stability,and an average particle size of(92.7±2.3)nm.The probe's protein composition was identical to that of the 4T1 cell membrane.The nanoprobe's ability to target homologous 4T1 cells was validated by an in vitro cell uptake assay.(2)The nanoprobe had a red-shift absorption spectrum and tail emission extending to the near-infrared-Ⅱ,which emitted a bright near-infrared-Ⅱ fluorescence signal under laser irradiation.(3)After laser irradiation,the nanoprobe 4T1m/ITIC-4CI/PFH could be turned into microbubbles and enhanced ultrasound imaging.The results of CCK-8 assay and calcein/propidium iodide staining showed that the nanoprobe 4T1m/ITIC-4CI/PFH had an obvious photothermal killing effect on 4T1 cells.(4)The results show that the nanoprobe 4T1m/ITIC-4CI/PFH has the ability to target homologous tumors and enhance near-infrared-Ⅱ fluorescence imaging/ultrasound imaging and photothermal therapy effects.
2.Analysis of potential risks of clean government in public hospitals and research on preventive measures
Modern Hospital 2024;24(1):38-40,45
Clean governance risk management is one of the important tasks of the Party building in public hospitals in the new era.This article reviews and analyzes the corruption case judgments of public hospitals in 2020 and 2021 published on the China Judgment Document Network,summarizes the high incidence of potential corruption risks in public hospitals,and proposes risk prevention strategies based on the requirements of high-quality development of public hospitals in the new era,in order to provide new ideas and countermeasures for future anti-corruption risk management in public hospitals.
3.Standardized specialist training for developmental and behavioral pediatrics in China and the United States: current status and thoughts
Xiaoyang CHEN ; Lingling WU ; Wenhao LI ; Wenyuan JIN ; Yanyan WANG ; Xiaolin LIU ; Zhiwei ZHU
Chinese Journal of Medical Education Research 2024;23(3):314-320
The United States has established a perfect specialist training system for developmental and behavioral pediatrics (DBP), while the DBP specialist training system in China is still in the early stage of development and has been constantly improved. This article analyzes and compares the current status of DBP specialist training system between the United States and China from the aspects of training pattern, eligibility criteria, training plans and contents, assessment and evaluation, and certification. With reference to the training system in the United States, we can further improve the DBP specialist training system in China by perfecting the training system and related documents, constructing reasonable eligibility criteria, establishing a training pattern guided by post competency, improving the DBP assessment and evaluation system based on competency, and enhancing the certification of DBP physicians.
4.Effects of ZXDC Mediates CCL2 on Chronic Neuropathic Pain in Spinal Dorsal Root Ganglion
Wenyuan LI ; Xiaoyu WANG ; Zhongx-Iao LV
Journal of Medical Research 2024;53(1):56-62
Objective To explore the effect and mechanism of C-C motif chemokine ligand 2(CCL2)/C-C chemokine receptor type 2(CCR2)signaling pathway mediated by ZXDC in spinal dorsal root ganglion(DRG)on neuropathic pain after chronic compressive injury.Methods A chronic compressive injury(CCI)mouse model was established.The expression of ZXDC and CCL2 in DRG was detected by immunofluorescence,Western blot,and real-time fluorescent quantitative PCR(RT-qPCR).The animals were divided in-to sham group,CCI+AAV-NC group,and CCI+AAV-ZXDC siRNA group.Western blot and immunofluorescence were employed to measure the expression of ZXDC,CCL2,and CCR2 in DRG after CCI,and the expression of pro-inflammatory factor TNF-α and IL-1β mRNA was evaluated by RT-qPCR.At last,the paw withdrawal threshold was used to evaluate the changes in neuropathic pain be-havior.Results ZXDC was localized in large,medium,and small DRG neurons.The expression of ZXDC and CCL2 protein and mRNA were significantly increased 1-3 days after CCI,and decreased 7days after CCI in DRG.The expression of ZXDC and CCL2mRNA was positively correlated(P<0.05).3 days after CCI,compared with sham group,ZXDC,CCL2,CCR2 protein expression,TNF-α and IL-1 β mRNA in CCI+AAV-NC group and CCI+AAV-ZXDC siRNA group were significantly increased,and ZXDC,CCL2,CCR2 protein expression,TNF-α and IL-1 β mRNA in CCI+AAV-ZXDC siRNA group were significantly decreased than those in CCI+AAV-NC group(P<0.05).Compared with sham group,the paw withdrawal threshold of CCI+AAV-ZXDC siRNA group and CCI+AAV-NC group were significantly decreased at various time points after CCI,and the withdrawal threshold in CCI+AAV-ZXDC siRNA group was significantly increased than that in CCI+AAV-NC group at 7days after CCI(P<0.05).Conclusion Spinal dorsal root gan-glion ZXDC siRNA can inhibit neuropathic pain after CCI injury by downregulating CCL2/CCR2signaling axis.
5.Discussion on the pathogenesis and treatment of non-alcoholic fatty liver disease in postmenopausal women based on the theory of "deficient qi and stagnation"
Mingyao XU ; Wenyuan SU ; Jing WU ; Jiawen HE ; Haowei ZHANG ; Jinjuan LI ; Jia YUE ; Yan ZHANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(12):1745-1752
Non-alcoholic fatty liver disease is a common chronic liver disease in clinical practice. In recent years, with increasing social attention to the health of women and the elderly, the prevention and treatment of non-alcoholic fatty liver disease after menopause has increasingly become a research hotspot in metabolic diseases. This study explores the pathogenesis and treatment method of non-alcoholic fatty liver disease in postmenopausal women based on the theory of "deficient qi and stagnation" and combined with the physiological and pathological characteristics of postmenopausal women and the Western medicine understanding of non-alcoholic fatty liver disease. We believe that the pathogenesis of non-alcoholic fatty liver disease in postmenopausal women is rooted in the "deficient qi" caused by depletion of liver and kidney essence and blood. The imbalance between the physical and functional aspects of the liver due to this "deficient qi" is the primary factor, while the "stagnation" of phlegm and blood stasis is the manifestation. Furthermore, the "deficient qi" and "stagnation" reinforce each other, with the deficiency leading to stagnation and stagnation exacerbating the deficiency, thus accelerating the progression of the disease. The treatment approach should be one that combines nourishing deficiency and resolving stagnation, addressing both root cause and maifestations. Given the female characteristic of "the liver as the innate organ" and the post-menopausal physiological state of "gradual decline of kidney essence", it is important to focus on nourishing the liver and kidneys, nurturing the liver′s physical body while maintaining its function, and also promoting the circulation of qi, resolving phlegm, and invigorating blood circulation to remove blood stasis. This approach aims to reduce the accumulation of lipids in the liver, offering a new perspective and approach for the treatment of non-alcoholic fatty liver disease in post-menopausal women with traditional Chinese medicine.
6.Clinical Questions Construction in Clinical Practice Guidelines: Based on Case-guided Approach
Yicheng GAO ; Zijin YU ; Yaqi WANG ; Rui FANG ; Cheng WANG ; Yuanyuan LI ; Yingjie DENG ; Xue BAI ; Wenyuan XIANG ; Yutong FEI
Medical Journal of Peking Union Medical College Hospital 2024;16(1):198-203
Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.
7.Optimization of Adaptive Design in Clinical Research and Inspiration for Traditional Chinese Medicine Research and Development
Ruiting LYU ; Bingqing LU ; Wenyuan LI ; Jianyuan TANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):110-119
In recent years, adaptive design has gradually emerged in clinical trials, gaining widespread application and expansion. Compared with traditional randomized controlled trials, appropriate adaptive design can save time and resources to some extent, improve the validity of the trial results and strength of the evidence, align better with ethical requirements, and facilitate subsequent drug market research. However, due to the greater flexibility of adaptive design, controlling type Ⅰ error rates and truly enhancing research efficiency are challenging aspects of its application. Therefore, the normative application and optimization of adaptive design in research deserve early focus, including adhering to good adaptive design principles, conducting rigorous pre-design planning, scientifically applying various statistical methods such as Bayesian dynamic models and simulation methods, and utilizing monitoring tools like monitoring committees to ensure the scientific integrity of the research process. Moreover, the flexibility of adaptive design aligns well with the practical realities of traditional Chinese medicine (TCM) clinical practice. The main characteristics of TCM, such as the holistic concept and treatment based on syndrome differentiation, determine that TCM provides a dynamic and personalized treatment plan. In contrast, the traditional fixed development approach of western medicine limits the application of "human experience" in TCM. To address this bottleneck in TCM research and development, the innovative use of adaptive design, a modern scientific theory and methodology with multiplicity and variability, offers a feasible new approach for TCM clinical research and the innovation of Chinese herbal medicine. By learning from successful cases such as the first Food and Drug Administration (FDA)-approved oral botanical drug, Crofelemer, researchers can explore optimal solutions for adaptive design in clinical research protocols and its role in the "three-combination" evaluation system for Chinese herbal medicines, further refine trial design, clarify key trial points, and develop innovative research and development applications that adapt to the clinical positioning of TCM and highlight the characteristics and advantages of TCM, paving the way for the clinical efficacy, pharmacological mechanism exploration, and post-market efficacy evaluation of Chinese herbal compounds.
8.Entity Recognition in Famous Medical Records Based on BRL Neural Network Model
Hang YANG ; Yehui PENG ; Wei YANG ; Jiaheng WANG ; Zhiwei ZHAO ; Wenyuan XU ; Yuxin LI ; Yan ZHU ; Lihong LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):167-173
ObjectiveIn order to improve the recognition accuracy of named entities in medical record texts and realize the effective mining and utilization of medical record knowledge, a Bert-Radical-Lexicon(BRL) neural network model is constructed to recognize medical record entities with respect to the characteristics of medical record texts. MethodWe selected 408 medical records related to hypertension from the the Complete Library of Famous Medical Records of Chinese Dynasties and constructed a dataset consisting of 1 672 medical records by manually labeling. Then, we randomly divided the dataset into three subsets, including the training set(1 004 cases), the testing set (334 cases) and the validation set(334 cases). Based on this dataset, we built a BRL model that fused various text features of medical records, as well as its variants BRL-B, BRL-L and BRL-R, and a baseline model Base for experiments. During the model training phase, we trained the above models using the training set to reduce the risk of overfitting. We continuously monitored the performance of each model on the validation set during training and saved the model with the best performance. Finally, we evaluated the performance of these models on the testing set. ResultCompared with other models, the BRL model had the best performance in the medical records named entity recognition task, with an overall recognition precision of 90.09%, a recall of 90.61%, and the harmonic mean of the precision and recall(F1) of 90.35% for eight types of entities, including disease, symptom, tongue manifestation, pulse condition, syndrome, method of treatment, prescription and traditional Chinese medicine(TCM). Compared with the Base model, the BRL model improved the overall F1 value of entity recognition by 5.22%, and the F1 value of pulse condition entity increased by 6.92%, which was the largest increase. ConclusionBy incorporating a variety of medical record text features in the embedding layer, the BRL neural network model has stronger named entity recognition ability, and thus extracts more accurate and reliable TCM clinical information.
9.Epidemic characteristics of mycoplasma pneumoniae infection and drug-resistant gene mutations in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023
Bibo MAO ; Daina CHEN ; Wenbo LU ; Chunyan LIU ; Zhuoling LI ; Changshui CHEN ; Haiyan QIU ; Wenyuan LIU
Chinese Journal of Preventive Medicine 2024;58(7):1035-1040
To analyze the infection and drug-resistant gene 23S rRNA mutations of mycoplasma pneumoniae (Mp) in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023. Throat swabs were collected from hospitalized children with respiratory tract infections in Ningbo University Affiliated Women and Children′s Hospital from 2019 to 2023. They were subjected to real-time fluorescence quantitative polymerase chain reaction detection to analyze Mp infection and drug-resistant gene (23S rRNA) mutations. Intergroup comparisons were made by the Chi-square test or Fisher′s exact probability method. A total of 18 968 hospitalized children were included, with a total positive rate of 30.37% (5 760/18 968). The total positive rate of drug-resistant gene mutations was 82.45% (4 749/5 760). The positive rate of Mp in male children was 29.26%, which was lower than that in female children (31.67%, χ 2=12.948, P<0.001). The positive rate of Mp drug-resistant gene mutations in male children was 82.52%, which was higher than that in female children(82.37%, χ 2=0.021, P=0.885). The positive rates of Mp increased with age ( χ 2=1 722.21, P<0.001). The positive rates of Mp drug-resistant gene mutations also increased with age ( χ 2=13.152, P<0.001). In the four seasons, the total positive rate of Mp in summer and autumn was significantly higher than that in winter and spring ( χ 2=1 085.149, P<0.001). Among them, the Mp positive rates in the summer and autumn of 2019 were as high as 38.26% and 34.49%, while in the summer and autumn of 2020, the Mp positive rates were 2.55% and 1.65%, respectively, which were the lowest in previous years. In the summer and autumn of 2023, the Mp positive rates increased to 47.22% and 51.06%. There was no statistically significant difference in the detection rate of Mp drug-resistant gene mutations among the four seasons. In Conclusion, Mp infection was more prevalent in the summer and autumn in Ningbo city and females and children aged 7-17 were more susceptible. The epidemic of Mp infection in Ningbo occurred in the summer of 2019. After the COVID-19 pandemic in 2020, the positive rate of Mp rapidly decreased and later remained in a low incidence state. After the lifting of restrictive prevention and control measures in 2023, the Mp positive rate returned to an epidemic state. The positive rate of Mp drug-resistant gene (23S rRNA) mutations was relatively high.
10.Recent advance in application of blood biomarkers in early diagnosis and prognosis of mild traumatic brain injury
Lijuan AN ; Yifei DONG ; Zhiyan CHEN ; Simin CHEN ; Wenyuan WANG ; Hongyu QUAN ; Yufan WANG ; Yongmei LI
Chinese Journal of Neuromedicine 2024;23(10):1074-1080
Missed diagnosis can often be noted in mild traumatic brain injury (mTBI), resulting from atypical symptoms, diverse performances and subjectively dependent report. Blood biomarkers can not only reflect the pathophysiological process of mTBI to a certain extent, but also have important clinical value in assessing brain injury severity and predicting adverse outcomes. This article systematically describes the research progress of blood biomarkers that can assist mTBI diagnosis, distinguish CT manifestations and predict prognoses in recent years, aiming to provide references for clinical application of blood biomarkers in mTBI.


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