1.Prediction of recurrence risk in soft tissue sarcomas by MRI and digital pathology based omics nomogram
Tongyu WANG ; Hexiang WANG ; Xindi ZHAO ; Feng HOU ; Jiangfei YANG ; Mingyu HOU ; Guangyao WAN ; Bin YUE ; Dapeng HAO
Chinese Journal of Radiology 2024;58(2):216-224
Objective:To investigate the value of an MRI and digital pathology images based omics nomogram for the prediction of recurrence risk in soft tissue sarcoma (STS).Methods:This was a retrospective cohort study. From January 2016 to March 2021, 192 patients with STS confirmed by pathology in the Affiliated Hospital of Qingdao University were enrolled, among which 112 patients in the Laoshan campus were enrolled as training set, and 80 patients in the Shinan campus were enrolled as validation set. The patients were divided into recurrence group ( n=87) and no recurrence group ( n=105) during follow-up. The clinical and MRI features of patients were collected. The radiomics features based on fat saturated T 2WI images and pathomics features based on digital pathology images of the lesions were extracted respectively. The clinical model, radiomics model, pathomics model, radiomics-pathomics combined model, and omics nomogram which combined the optimal prediction model and the clinical model were established by multivariate Cox regression analysis. The concordance index (C index) and time-dependent area under the receiver operating characteristic curve (t-AUC) were used to evaluate the performance of each model in predicting STS postoperative recurrence. The DeLong test was used for comparison of t-AUC between every two models. The X-tile software was used to determine the cut-off value of the omics nomogram, then the patients were divided into low risk ( n=106), medium risk ( n=64), and high risk ( n=22) groups. Three groups′ cumulative recurrence-free survival (RFS) rates were calculated and compared by the Kaplan-Meier survival curve and log-rank test. Results:The performance of the radiomics-pathomics combined model was superior to the radiomics model and pathomics model, with C index of 0.727 (95% CI 0.632-0.823) and medium t-AUC value of 0.737 (95% CI0.584-0.891) in the validation set. The omics nomogram was established by combining the clinical model and the radiomics-pathomics combined model, with C index of 0.763 (95% CI 0.685-0.842) and medium t-AUC value of 0.783 (95% CI0.639-0.927) in the validation set. The t-AUC value of omics nomogram was significantly higher than that of clinical model, TNM model, radiomics model, and pathomics model in the validation set ( Z=3.33, 2.18, 2.08, 2.72, P=0.001, 0.029, 0.037, 0.007). There was no statistical difference in t-AUC between the omics nomogram and radiomics-pathomics combined model ( Z=0.70, P=0.487). In the validation set, the 1-year RFS rates of STS patients in the low, medium, and high recurrence risk groups were 92.0% (95% CI 81.5%-100%), 55.9% (95% CI 40.8%-76.6%), and 37.5% (95% CI 15.3%-91.7%). In the training and validation sets, there were statistically significant in cumulative RFS rates among the low, medium, and high groups of STS patients (training set χ2=73.90, P<0.001; validation set χ2=18.70, P<0.001). Conclusion:The omics nomogram based on MRI and digital pathology images has favorable performance for the prediction of STS recurrence risk.
2.Evaluation of tigecycline intraventricular injection regimens in extensively drug resistant Acinetobacter baumannii intracranial infection based on Monte Carlo simulation and pharmacokinetic/pharmacodynamic model
Changxiu LI ; Zhenshan LI ; Han ZHANG ; Fei GAO ; Jin LI ; Jing WANG ; Dapeng HOU ; Yanlin LIU
Chinese Journal of Neuromedicine 2024;23(4):379-386
Objective:To evaluate and screen the regimens of tigecycline intraventricular injection in extensively drug resistant Acinetobacter baumannii (XDRAB) intracranial infection based on Monte Carlo simulation and pharmacokinetic/pharmacodynamic (PK/PD) model.Methods:Nine patients with XDRAB intracranial infection confirmed as having susceptibility to tigecycline or polymyxin antimicrobials from January 1, 2018 to December 31, 2023 were screened from electronic medical record system in Second Affiliated Hospital of Shandong First Medical University. WHONET software was used to extract pathogen susceptibility data isolated from cerebrospinal fluid samples. Minimum inhibitory concentration (MIC) of tigecycline against XDRAB was analyzed by drug susceptibility test; different regimens for intraventricular tigecycline injection were designed based on MIC: 2 mg/12 h, 3 mg/12 h, 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h, with drug concentration of 0.5 mg/mL or 1.0 mg/mL once a day. Target value of PK/PD index was set as ?C max/MIC≥8; Monte Carlo was used to simulate the compliance of PK/PD index of tigecycline with different MIC against XDRAB for different dosed regimens (probability of target attainment [PTA] and cumulative fraction of response [CFR]); the best regiment was selected (screening basis: PTA≥90% or CFR≥90%). Results:(1) A total of 27 strains of pathogenic bacteria from 9 patients were extracted from drug susceptibility test, in which MIC of tigecycline against XDRAB was 55.56% for 2 mg/L, 25.93% for 4 mg/L, and 18.52% for 8 mg/L. (2) When the drug concentration was 0.5 mg/mL or 1.0 mg/mL, respectively, all 6 regimens had PTA>90% at 2 mg/L MIC; 5 regimens, except for 2 mg/12 h, had PTA>90% at 4 mg/L MIC; regimens of 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve PTA>90% at 8 mg/L MIC. (3) When the drug concentration was 0.5 mg/mL, regimens of 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve CFR>90%; when the drug concentration was 1 mg/mL, regimens of 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve CFR>92%.Conclusion:In intraventricular tigecycline injection for XDRAB intracranial infection, 2 mg/12 h regimen is available in 2 mg/L MIC, 3 mg/12 h regimen is available in 4 mg/L MIC, and 5 mg/12 h regimen is available in 8 mg/L MIC, with either 0.5 mg/mL or 1 mg/mL concentration.
3.Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors
Yan CHEN ; Xingguo HOU ; Dapeng LI ; Jin DING ; Jiayue LIU ; Zilei WANG ; Fei TENG ; Hongjun LI ; Fan ZHANG ; Yi GU ; Steven YU ; Xueming QIAN ; Zhi YANG ; Hua ZHU
Journal of Pharmaceutical Analysis 2023;13(4):367-375
Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,>99%)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5%human serum albumin,and phosphate buffer saline(>85%RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P>0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.
4.An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique (version 2023)
Jie SHEN ; Lin CHEN ; Shiwu DONG ; Jingshu FU ; Jianzhong GUAN ; Hongbo HE ; Chunli HOU ; Zhiyong HOU ; Gang LI ; Hang LI ; Fengxiang LIU ; Lei LIU ; Feng MA ; Tao NIE ; Chenghe QIN ; Jian SHI ; Hengsheng SHU ; Dong SUN ; Li SUN ; Guanglin WANG ; Xiaohua WANG ; Zhiqiang WANG ; Hongri WU ; Junchao XING ; Jianzhong XU ; Yongqing XU ; Dawei YANG ; Tengbo YU ; Zhi YUAN ; Wenming ZHANG ; Feng ZHAO ; Jiazhuang ZHENG ; Dapeng ZHOU ; Chen ZHU ; Yueliang ZHU ; Zhao XIE ; Xinbao WU ; Changqing ZHANG ; Peifu TANG ; Yingze ZHANG ; Fei LUO
Chinese Journal of Trauma 2023;39(2):107-120
Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.
5.Preoperative MRI-based deep learning radiomics machine learning model for prediction of the histopathological grade of soft tissue sarcomas
Hexiang WANG ; Shifeng YANG ; Tongyu WANG ; Hongwei GUO ; Haoyu LIANG ; Lisha DUAN ; Chencui HUANG ; Yan MO ; Feng HOU ; Dapeng HAO
Chinese Journal of Radiology 2022;56(7):792-799
Objective:To investigate the value of a preoperatively MRI-based deep learning (DL) radiomics machine learning model to distinguish low-grade and high-grade soft tissue sarcomas (STS).Methods:From November 2007 to May 2019, 151 patients with STS confirmed by pathology in the Affiliated Hospital of Qingdao University were enrolled as training sets, and 131 patients in the Affiliated Hospital of Shandong First Medical University and the Third Hospital of Hebei Medical University were enrolled as external validation sets. According to the French Federation Nationale des Centres de Lutte Contre le Cancer classification (FNCLCC) system, 161 patients with FNCLCC grades Ⅰ and Ⅱ were defined as low-grade and 121 patients with grade Ⅲ were defined as high-grade. The hand-crafted radiomic (HCR) and DL radiomic features of the lesions were extracted respectively. Based on HCR features, DL features, and HCR-DL combined features, respectively, three machine-learning models were established by decision tree, logistic regression, and support vector machine (SVM) classifiers. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each machine learning model and choose the best one. The univariate and multivariate logistic regression were used to establish a clinical-imaging factors model based on demographics and MRI findings. The nomogram was established by combining the optimal radiomics model and the clinical-imaging model. The AUC was used to evaluate the performance of each model and the DeLong test was used for comparison of AUC between every two models. The Kaplan-Meier survival curve and log-rank test were used to evaluate the performance of the optimal machine learning model in the risk stratification of progression free survival (PFS) in STS patients.Results:The SVM radiomics model based on HCR-DL combined features had the optimal predicting power with AUC values of 0.931(95%CI 0.889-0.973) in the training set and 0.951 (95%CI 0.904-0.997) in the validation set. The AUC values of the clinical-imaging model were 0.795 (95%CI 0.724-0.867) and 0.615 (95%CI 0.510-0.720), and of the nomogram was 0.875 (95%CI 0.818-0.932) and 0.786 (95%CI 0.701-0.872) in the training and validation sets, respectively. In validation set, the performance of SVM radiomics model was better than those of the nomogram and clinical-imaging models ( Z=3.16, 6.07; P=0.002,<0.001). Using the optimal radiomics model, there was statistically significant in PFS between the high and low risk groups of STS patients (training sets: χ2=43.50, P<0.001; validation sets: χ2=70.50, P<0.001). Conclusion:Preoperative MRI-based DL radiomics machine learning model has accurate prediction performance in differentiating the histopathological grading of STS. The SVM radiomics model based on HCR-DL combined features has the optimal predicting power and was expected to undergo risk stratification of prognosis in STS patients.
6.Bone pain, thyroid nodule and lymphadenectasis: a report of one case with literature review
Bo ZANG ; Hui HUA ; Feng HOU ; Xianqi FENG ; Dapeng HAO ; Zhenguang WANG ; Xu ZHANG ; Bin LIU
Chinese Journal of Rheumatology 2021;25(8):516-520,C8-1
Objective:By analyzing the clinical and pathologic manifestations of systemic mastocytosis (SM) to improve the recognition of the disease.Methods:Clinical manifestations, diagnosis and treatment of a middle-aged male patient with SM was reported with multidisciplinary discussions.Results:A middle-aged man with bone pain, thyroid nodules and lymphadenectasis came to our clinic. Thyroid cancer with lymph node and bone metastasis was suspected by imaging examination. The pathological results showed cell proliferation with transparent cytoplasm and irregular nuclear in the trabecular bone. Toluidine blue staining showed the proliferated cells were mast cells(+). Immunohistochemistry showed proliferating mast cells stained with CD117 and CD2. SM with extensive bone marrow involvement was diagnosed and treated with thalidomide and calcitriol.Conclusion:Knowing the characteristics of SM is helpful for accurate diagnosis and treatment.
7.Practice and discussion of integrating ideological and political elements into psychiatry
Ying CHEN ; Guoping HUANG ; Jiaming LUO ; Dapeng WU ; Yan ZHANG ; Ling YU ; Xuehua LI ; Xin HOU
Sichuan Mental Health 2021;34(1):79-82
The aim of this paper is to explore the practical measures of integrating “ideological and political course” into “Psychiatry”. “Ideological and political course” is a key measure to foster character and civic virtue in colleges and universities, and a crucial link of “three -full education”. Based on the characteristics of the course “Psychiatry” and the practical experience of the course “ideological and political work” in the faculty of mental health, North Sichuan Medical College, this paper puts forward the strategies of implementing “ideological and political course” from four aspects: improving teachers’ understanding and practical ability of “ideological and political course”, constructing the integration point of ideological and political course in “Psychiatry”, choosing the teaching methods of “ideological and political course” and evaluating the teaching effect, thus providing references for the implementation of “ideological and political course” in the follow-up professional courses.
8.Expression and clinical significance of MHC Ⅱ in medullary thyroid carcinoma
Xiukun HOU ; Xiangqian ZHENG ; Dapeng LI ; Jingzhu ZHAO ; Ming GAO
Chinese Journal of General Surgery 2020;35(6):480-483
Objective:To examine the expression of MHC class Ⅱ in medullary thyroid carcinoma(MTC) and analyze its clinical significance.Methods:98 MTC patients treated at Tumor Hospital of Tianjin Medical University from Jan 2010 to Dec 2018 were included for the study. Immunohistochemistry was used to detect the expression of MHC class Ⅱ molecule .Results:The high expression of MHC class Ⅱ was not correlated with age (χ 2=0.900, P=0.410), multifocal (χ 2=0.295, P=0.672), bilateral (χ 2=2.957, P=0.127), T stage (χ 2=0.554, P=0.457), but correlated with gender (χ 2=5.227, P=0.025), preoperative calcitonin level (χ 2=6.663, P=0.019), lymph node metastasis (χ 2=21.651, P<0.001) and AJCC stage (χ 2=19.522, P<0.001). Overall survival rate of patients with high expression of MHC class Ⅱ was 97.4%.It was significantly higher than that of patients with low expression 66.1% ( P=0.016 3). COX regression model showed that age >55 years old ( HR=4.129, P=0.009), T stage ( HR=3.265, P=0.024) were independent risk factors for the prognosis of MTC patients. High expression of MHC class Ⅱ molecules ( HR=0.103, P=0.030) was a protective factor for the prognosis of MTC patients. Conclusion:The MTC patients with high expression of MHC class Ⅱ have a better prognosis.
9.The imaging diagnosis of synovial chondromatosis of the temporomandibular joint
Lihua HOU ; Chan HOU ; Dapeng HAO ; Yang LI ; Jihua LIU ; Wenjian XU
Journal of Practical Radiology 2016;32(5):691-693,698
Objective To investigate X‐ray ,CT and MRI features of synovial chondromatosis of the temporomandibular joint (TMJ) .Methods X‐ray ,CT and MRI features of eight patients of synovial chondromatosis of TMJ with histo‐pathologically con‐firmed were analyzed retrospectively .X‐ray examination and CT scanning were performed in all eight patients .Routine MRI scanning was performed in six patients and contrast‐enhanced MRI scanning was performed in two patients synchronously .Results Tumors occured unilaterally in all eight cases ,which occured on the right TMJ in six cases and on the left side in two cases .On X‐ray films , widen joint space and calcificated loose bodies occured in all eight cases .On CT scanning ,cystic‐solid mixed mass around the joint and calcificated loose bodies occured in all eight cases .On MR scanning ,multiple nodular long T1 and short T2 signal occured in six cases . Arthroedema and synovial hyperplasia with iso T1 and iso or slightly long T2 signal in six cases .On contrast‐enhanced MR ,homoge‐neous enhancement occurred in svnovial tissue and the edge of loose bodies in two cases .Conclusion The synovial chondromatosis of TMJ owns typical imaging features .The imaging findings can serve as a reference to improve diagnosis of synovial chondromatosis of TMJ .
10.Antimicrobial stewardship and bacterial resistance in the intensive care unit
Jin LI ; Jing WANG ; Dapeng HOU
Chinese Journal of Clinical Infectious Diseases 2016;9(2):156-160,167
Objective To investigate the changes of antibiotic resistance and its correlations with antibiotics use density (AUD) in intensive care unit (ICU) after implementation of antimicrobial stewardship. Methods Data on AUDs and synchronous antibiotic resistance in ICU of the Affiliated Hospital of Taishan Medical University during 2010 and 2014 were retrospectively reviewed.Autoregressive integrated moving average ( ARIMA) model was used to identify the correlation between AUDs and antibiotic resistance.Results The total AUD which stood at 163.46 DDDs· 100 person-1 · d-1 in the year 2010 decreased to 68.20 DDDs · 100 person-1 · d-1 in 2014, and the most significant decreases were found in quinolones, imidazole, carbapenems, aminoglycosides, other beta lactam and macrolides. Synchronously, a wide range of improvements in antibiotic resistance of major pathogens were also observed from 2010 to 2014, and the improvements were positively correlated with the decrease of AUDs.However, antibiotic resistance in 2014 was not significantly improved compared with that in 2013. The rate of ciprofloxacin resistance in Pseudomonas aeruginosa and the resistant rates of amikacin, imipenem, and meropenem in Acinetobacter baumannii even increased in 2014.Conclusions With the implementation of antimicrobial stewardship, antibiotic consumption in ICU was decreasing, and antibiotic resistance rate in major pathogenic bacteria was decreasing.But the rebound in antibiotic resistance in some types of bacteria was also observed and should be put on enough caution.

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