1.Metabolic reprogramming nanomedicine potentiates colon cancer sonodynamic immunotherapy by inhibiting the CD39/CD73/ADO pathway.
Yuanyuan ZHANG ; Weiwei JIN ; Zhichao DENG ; Bowen GAO ; Yuanyuan ZHU ; Junlong FU ; Chenxi XU ; Wenlong WANG ; Ting BAI ; Lianying JIAO ; Hao WU ; Mingxin ZHANG ; Mingzhen ZHANG
Acta Pharmaceutica Sinica B 2025;15(5):2655-2672
Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.
2.Dynamic prediction of clinical outcomes for critical trauma patients based on a recurrent neural network model
Geyao QI ; Jin XU ; Zhichao JIN
Academic Journal of Naval Medical University 2024;45(10):1241-1249
Objective To explore the value of dynamic prediction model based on recurrent neural network(RNN)algorithms for dynamic prediction of clinical outcomes in patients with critical trauma,and to study the feasible construction scheme and path of dynamic strategy and real-time prediction model.Methods The data of this study were derived from the US Medical Information Mart for Intensive Care(MIMIC)-IV 2.0.In order to predict the in-hospital outcomes of critical trauma patients,2 RNN algorithms,long short-term memory(LSTM)and gated recurrent unit(GRU)were used to train dynamic prediction models under the time windows of 4,6 and 8 h,respectively.The performance of the models was evaluated using the sensitivity,specificity,F1 value and area under curve(AUC)value;and the effects of different RNN algorithms and time windows on the performance of the models were analyzed.Hidden Markov model(HMM),random forest(RF)model and logistic model were trained under 8-h time window as the controls to compare the performances and the time trends horizontally with the 2 RNN algorithm models.Results There were significant differences in the 4 performance indexes of the RNN dynamic models including the sensitivity,specificity,F1 value and AUC value(all P<0.001),and the performance indexes at 8-h time window were higher than those at 6 h and 4 h;there was only significant difference in specificity between different RNN algorithms(LSTM & GRU)(P=0.036).The results of the horizontal comparison showed that there were significant differences in each performance index between the 2 RNN prediction models and other models(all P<0.001),and each index of the 2 RNN algorithm models was higher than those of the HMM,RF model and logistic model.The intraclass correlation coefficients(ICCs)of each algorithmic model were less than 0.400 for the sensitivity,specificity and F1 value(0 was not included in 95%confidence interval[CI]),while the ICCs for the AUC value were statistically under-evidenced(0 was included in 95%CI).Conclusion The dynamic models based on RNN algorithms have certain performance advantages over those based on other common algorithms,and the time window may have an impact on the model performance.
3.Comparative study of endoscopic spine surgery with and without assistance of an electromagnetic navigation surgical robot in the treatment of lumbar disc herniation
Zhichao CONG ; Zhiping YU ; Chengzhen JIN ; Xiaogeng SUN ; Wei XIONG ; Haitao WANG ; Haibo CONG
Chinese Journal of Microsurgery 2023;46(2):139-146
Objective:To compair the clinical effect of endoscopic spine surgery with and without assistance of an electromagnetic navigation surgical robot(ENSR) system in the treatment of lumbar disc herniations(LDH).Methods:From March 2021 to December 2021, 73 patients with LDH underwent endoscopic minimally invasive treatment in the Department of Spine Surgery, Limin Hospital of Weihai High District. Thirty-eight patients were treated with endoscopic spine surgery assisted by domestic ENSR system(ENSR group), and 35 patients were treated with endoscopic spine surgery alone(endoscopic group). The patients received follow up regularly by telephone or Wechat. The intraoperative fluoroscopy times, puncture times, upper facet arthroplasty times, operation time, preoperative and postoperative Visual Analogue Scale(VAS), Japanese Orthopaedic Association Scores(JOA), and the MOS item short from health survey(SF-36)were compared between the 2 groups. The early postoperative efficacy was evaluated by modified MacNab criteria at 1 week after surgery. SPSS 26.0 was used to analyse the data. P<0.05 was considered that the difference was statistically significant. Results:The age, gender, body mass index(BMI) and other general data of the 2 groups were basically the same, and there was no statistically significant difference( P>0.05). There was no significant difference in the excellent and good rate of postoperative treatment between ENSR group(97.37%) and endoscopic group(94.29%)( Z=0.90, P>0.05). In terms of operation time, intraoperative fluoroscopy times, puncture times, and plasty times, ENSR group[(67.00±17.00) min, (4±2) times, 1 time, 1 time, respectively] was compared with the endoscopic group[(82.00±16.00] min, (17±6) times, (9±5) times, (5±2) times], and the difference was statistically significant( t=3.87,12.62, 9.87, respectively, P<0.05). There were significant differences in VAS, JOA and SF-36 scores between the 2 groups between before and after surgery( F=106.42, 112.14, 26.88, respectively, P<0.05). There was no significant difference in VAS, JOA and SF-36 scores before and after surgery between the 2 groups( F=0.95, 3.54, 0.97, respectively, P>0.05). Conclusion:The endoscopic spine surgery assisted by the ENSR can achieve satisfactory clinical results and is a safe and effective surgical assistance system. For the endoscopic surgery, assisted by the ENSR has obvious advantages in reducing the times of fluoroscopy, puncture, and facet arthroplasty, and shortening the operation time.
4.Efficacy comparison of different machine learning models to predict adverse inhospital outcome in patients with severe trauma
Chi PENG ; Fan YANG ; Xiang GAO ; Shuogui XU ; Zhichao JIN
Chinese Journal of Trauma 2023;39(6):545-550
Objective:To compare the predictive performance of different machine learning models using pre-hospital data to predict adverse inhospital outcome in patients with severe trauma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 100 135 patients with severe trauma from the National Trauma Data Bank (NTDB) from January 2017 to December 2018. There were 69 644 males and 30 480 females apart from 11 patients with missing gender information, with the range age of 16-89 years [(50.1±21.1)years]. Clinical characteristics included demographic information (sex and age), trauma type (blunt or penetrating trauma), pre-hospital time [emergency medical services (EMS) response time, EMS scene time, and EMS transport time], pre-hospital vital signs (systolic blood pressure, pulse rate, respiratory rate, and oxygen saturation), trauma score [Glasgow coma score (GCS) and injury severity score (ISS)]. The original data were divided into the training set (in the year 2017) and the testing set (in the year 2018) according to the year of admission, including 50 429 patients in the training set and 49 706 patients in the testing set. The patients were classified into non-adverse outcome group ( n=94 526) and adverse outcome group ( n=5 609), according to whether they had an adverse outcome or not. There were 2 808 patients with adverse outcome in the training set and 2 801 patients with adverse outcome in the testing set. All models were built based on the training set. Eight machine learning algorithms consisting of neural network (NNET), naive Bayes (NB), gradient boosting machine (GBM), adaptive boosting (Ada), random forest (RF), bagging tree (BT), categorical boosting (CatBoost) and extreme gradient boosting (XGB) were used to construct prediction models for clinical outcomes among patients with severe trauma based on their clinical features. Models were evaluated according to the sensitivity, specificity, area under the receiver operating characteristic (ROC) curve (AUC) and Hosmer-Lemeshow goodness-of-fit test. Results:Of the NNET, NB, GBM, Ada, RF, BT, CatBoost and XGB models in the testing set, the sensitivity was 0.84, 0.83, 0.27, 0.79, 0.83, 0.81, 0.62 and 0.78, respectively; the specificity was 0.79, 0.76, 0.81, 0.79, 0.79, 0.74, 0.83 and 0.79, respectively; the AUC was 0.89 (95% CI 0.88, 0.90), 0.86 (95% CI 0.85, 0.87), 0.54 (95% CI 0.53, 0.55), 0.86 (95% CI 0.85, 0.87), 0.88 (95% CI 0.88, 0.90), 0.83 (95% CI 0.82, 0.85), 0.77 (95% CI 0.76, 0.79) and 0.86 (95% CI 0.85, 0.87), respectively. The NNET model had the best differentiation. In terms of calibration degree, both NNET and NB showed good performance ( P>0.05 for Hosmer-Lemeshow goodness-of-fit test). Conclusion:The NNET model has a favorable predictive performance for adverse inhospital outcome in patients with severe trauma, which may provide a reference for the rapid prediction of prognosis in patients with severe trauma.
5.Systematic review and meta-analysis in medical research
Shanghai Journal of Preventive Medicine 2023;35(7):724-727
In order to facilitate systematic reviews and meta-analyses by medical researchers, this paper provides a tutorial-style review of the relevant concepts, necessary steps, and some key considerations in conducting systematic reviews and meta-analyses. Specifically, it offers detailed explanations on literature search, evaluation of study bias, effect size selection, outcomes pooling, and testing and correction of publication bias. Additionally, the paper provides references to softwares and literature for implementing the methods, and concludes with a brief overview of the requirements for writing research papers.
6.A randomized controlled trial on sodium hyaluronate gel in prevention of postoperative intestinal adhesion
Wensheng HUANG ; Jiancong HU ; Chuanqing WU ; Liang SHANG ; Chengle ZHUANG ; Ke AN ; Zhichao ZHAI ; Changmin DING ; Zhaoya GAO ; Qingkun GAO ; Pengfei NIU ; Yanzhao WANG ; Qingmin ZENG ; Yuming HONG ; Wanshui RONG ; Fuming LEI ; Zhongchen LIU ; Leping LI ; Kaixiong TAO ; Xiaojian WU ; Jin GU
Chinese Journal of General Surgery 2023;38(11):809-813
Objective:To evaluate the efficacy and safety of sodium hyaluronate gel in preventing adhesion after prophylactic enterostomy.Methods:One hundred and twenty four patients from 6 hospitals were enrolled in this prospective multi-center randomized controlled trial. Patients were randomized into the study group ( n=59) or the control group ( n=65).All patients underwent prophylactic enterostomy. Patients of study group received odium hyaluronate gel for adhesion-prevention,while those in control group did not receive any adhesion-prevention treatment. The incidence of moderate to severe adhesion around the incision in the stoma area were evalutated during stoma reduction surgery. Results:The incidence of moderate to severe adhesion around the incision in the stoma area was 6.3% in the study group, the difference was statistically significant ( P<0.05) compared to that of the control group (32.6%). Conclusion:Sodium hyaluronate gel can safely and effectively reduce the incidence of moderate and severe adhesions after abdominal surgery.
7.Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood.
Shuzhen CHEN ; Yaping DONG ; Xinming QI ; Qiqi CAO ; Tao LUO ; Zhaofang BAI ; Huisi HE ; Zhecai FAN ; Lingyan XU ; Guozhen XING ; Chunyu WANG ; Zhichao JIN ; Zhixuan LI ; Lei CHEN ; Yishan ZHONG ; Jiao WANG ; Jia GE ; Xiaohe XIAO ; Xiuwu BIAN ; Wen WEN ; Jin REN ; Hongyang WANG
Acta Pharmaceutica Sinica B 2022;12(5):2252-2267
Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.
8. Targeted therapy for malignant peripheral nerve sheath tumor: translational research and clinical application
Zhichao LIAO ; Chao ZHANG ; Xinyue LIU ; Zhiwu REN ; Jin XU ; Chunzhi ZHANG ; Yun YANG ; Ze ZHU ; Jilong YANG
Chinese Journal of Oncology 2019;41(9):648-653
Malignant peripheral nerve sheath tumor (MPNST) is a rare invasive soft tissue sarcoma that originates from peripheral nerve branches and peripheral nerve sheaths. Early radical surgery is an effective treatment for MPNST. Since it is insensitive to radiotherapy and chemotherapy, the disease manifests a rapid progression, poor prognosis and high mortality. In recent years, the translational researches on the driving factors and therapeutic targets of MPNST have been rapidly developed, including the pathways of NF1-Ras, Raf-MEK-ERK, PI3K-AKT-mTOR, Wnt signaling, and abnormal expressions of apoptotic proteins, the general loss of polycomb repressive complex 2 (PRC2), upregulation of the HDAC family, abnormal expressions of receptor tyrosine kinases, expressions of programmed cell death ligand (PD-L1), aurora kinase and various microRNAs.This review summarizes the current translational researches on potential therapeutic targets of MPNST, and the clinical trials which provide helpful information for MPNST targeted therapy.
9.Investigation and Analysis of Pedi atric Medication Information of Microecological Preparations in China
Ting WEI ; Xiaoling WANG ; Yan JIN ; Zhichao ZHAO ; Yuncui YU
China Pharmacy 2019;30(22):3155-3159
OBJECTIVE: To provide suggestions for improving pediatric medication information in drug instructions of microecological preparations in China. METHODS: Using text analysis method, the pediatric medication information in the instructions of 36 approval number of microecological (29 varieties from 23 enterprises) is statistically analyzed. RESULTS: Among the 36 microecological preparations, there were 2 medicines for children (5.56%). There were 2 granules (5.56%), 9 dispersants (25.00%), 9 tablets (25.00%) and 16 capsules (44.44%); there were 6 national essential medicines (16.67%); there were 13 products in the list of national essential medical insurance (36.11%); there were 22 OTC products (61.11%). The proportion of children’s indications, children’s usage and dosage, child-related adverse reactions, taboos and matters needing attention in the drug instructions for children were 19.44%, 55.56%, 2.77%, 5.56% and 8.33%, respectively. The proportion of specific information about children’s drug use marked in the item of “children’s drug use” was 25.00%. CONCLUSIONS: There is a lack of information on pediatric medication in the instructions of microecologial preparations in China, and there are some problems such as unclear wording, scattered labeling position of the medication information for children, and the content is not practical. It is recommended that medical institutions should strengthen the rational use of medical guidance for medical personnel, implement the scientific management process of over-instruction medications; the relevant departments should introduce more incentive policies, encourage enterprises to improve the basis of children’s medications, and make standardized labeling of children’s medication information in drug specifications. In addition, a database of information on children’s medications can be established to provide a reference for rational use of pediatric drugs.
10. Comparison in preoperative evaluation effects of abdominal enhanced CT two-dimensional coronal imaging versus three-dimensional vascular reconstruction for critical blood vessels in right colon cancer
Yunjie SHI ; Shuai LI ; Zhichao JIN ; Xiaoshuang LIU ; Quanquan ZHAO ; Fu SHEN ; Hao WANG
Chinese Journal of Digestive Surgery 2019;18(10):992-997
Objective:
To compare the evaluation effects of abdominal enhanced computed tomography (CT) coronal imaging versus three-dimensional (3D) vascular reconstruction for critical blood vessels in right colon cancer.
Methods:
The retrospective and descriptive study was conducted. The clinicopathological data of 50 patients with right colon cancer who were admitted to Changhai Hospital Affiliated to Naval Medical University from January to September in 2018 were collected. There were 33 males and 17 females, aged from 33 to 86 years, with an average age of 63 years. All the 50 patients underwent abdominal multi-slice CT examination on the same CT equipment. The CT examination data were analyzed by two-dimensional (2D) coronal imaging and 3D vascular reconstruction. Observation indicators: (1) anatomical type of Henle trunk; (2) the length of Henle trunk and surgical trunk; (3) the positional relationship between ileocolic vein (ICV) and ileocolic artery (ICA). Measurement data with normal distribution were represented as

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