1.Management of Cutaneous Immune-Related Adverse Events of Malignant Tumors Induced by Immune Checkpoint Inhibitors Based on Theory of "Fire and Original Qi are Restricted"
Shiliang SHAO ; Lijing JIAO ; Yichao WANG ; Decai WANG ; Qishan HUA ; Yabin GONG ; Ling XU
Journal of Traditional Chinese Medicine 2025;66(16):1656-1661
Guided by the theory of "fire and original qi are restricted", it is believed that original qi depletion is the root of the cutaneous immune-related adverse events (cirAEs) related to immune checkpoint inhibitors (ICIs), and the yin fire exuberance is the branch. Among them, original qi depletion is the internal foundation of the disease, while the drug toxicity of ICIs harming original qi is the initiating factor, and exuberant yin fire is the key pathogenesis. In clinical practice, the general treatment principle advocates banking up original qi to consolidate the root and draining fire to raise yang. Buzhong Yiqi Decoction (补中益气汤) can be used to activate transportation of middle jiao (焦) and promote ascent and dispersion of clear yang, thereby restoring the balance of qi and fire, and medicinals such as Huangqin (Radix Scutellariae), Huanglian (Rhizoma Coptidis) and Huangbai (Cortex Phellodendri Chinensis) can be supplementetd to clear and drain yin fire. At the same time, considering the accompanying symptoms such as dampness-stasis and fluids depletion, the methods of removing dampness and dispelling stasis, supplementing blood and nourishing yin should be added flexibly. This approach can provide a new perspective and treatment strategy for reducing ICIs-related cirAEs in malignant tumors.
2.Treatment Strategies for Postoperative Complications of Lung Cancer from Protecting Healthy Qi and Treating Qi
Jiajun SONG ; Yichao WANG ; Xueqi TIAN ; Yi LIU ; Lijing JIAO ; Ling XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):94-105
Pulmonary complications, the most common postoperative complications of lung cancer, not only affect the quality of life of the patients after surgery but also increase the prognostic risks of postoperative recurrence and metastasis, threatening the life safety. At present, a multidisciplinary model of diagnosis and rehabilitation with integrated traditional Chinese medicine (TCM) and Western medicine has been initially formed under the guidance of the concept of rapid rehabilitation post operation for lung cancer. However, the treatment that only aims at shortening hospital stay and reducing the incidence of postoperative complications does not pay enough attention to the postoperative functional rehabilitation of the lung and the impact of follow-up adjuvant therapy, which affects the completeness of rehabilitation. This paper classifies the typical postoperative symptoms and manifestations of lung cancer into five groups: Lung system, emotion, digestive tract, pain, and nerve. On this basis, this paper summarizes the three core pathogeneses of postoperative complications of lung cancer as failure of Qi to ascend and descend leading to insecurity of defensive exterior, vessel block leading to Qi stagnation and fluid retention, and lung Qi deficiency leading to spleen and kidney deficiency. Accordingly, this paper proposes the treatment principle of protecting healthy Qi and treating Qi with the core of descending-tonifying-ascending-dispersing Qi and puts forward three treatment methods. The first is replenishing Qi and consolidating exterior, and expelling phlegm and regulating lung. The second is replenishing Qi and promoting blood flow to resolve stasis and relieving pain. The third is replenishing Qi and tonifying lung, and invigorating spleen and tonifying kidney. Furthermore, this paper elaborates on the pathogenesis and treatment principles of four common postoperative complications: Lung infection, pleural effusion, atelectasis, and bronchopleural fistula. On the basis of Western medical treatment, the TCM treatment characteristics of treating symptoms in the acute phase and eradicating the root cause in the chronic phase should be played. While dispelling the pathogen, measures should be taken to protect the healthy Qi, including tonifying lung Qi, regulating spleen Qi, and replenishing kidney Qi. This study summarizes the pathogenesis and treatment strategy of common postoperative complications of lung cancer according to the principle of protecting healthy Qi and treating Qi, aiming to provide guidance for the future treatment of postoperative complications of lung cancer.
3.Deep learning-based radiomics allows for a more accurate assessment of sarcopenia as a prognostic factor in hepatocellular carcinoma.
Zhikun LIU ; Yichao WU ; Abid Ali KHAN ; L U LUN ; Jianguo WANG ; Jun CHEN ; Ningyang JIA ; Shusen ZHENG ; Xiao XU
Journal of Zhejiang University. Science. B 2024;25(1):83-90
Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).
Humans
;
Aged
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Sarcopenia/diagnostic imaging*
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Carcinoma, Hepatocellular/diagnostic imaging*
;
Muscle, Skeletal/diagnostic imaging*
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Deep Learning
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Prognosis
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Radiomics
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Liver Neoplasms/diagnostic imaging*
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Retrospective Studies
4.Construction of Raji-Luc CD19 KO Lymphoma Cell Line Using CRISPR/Cas9 Technology
Jingjing LIU ; Xiuying LIU ; Yaru FENG ; Yichao FENG ; Mengyuan YU ; Jianxun WANG
Journal of Modern Laboratory Medicine 2024;39(1):10-15,99
Objective To construct Raji-Luc lymphoma cells with CD19 knockout using CRISPR/Cas9 technology and preliminarily validate their immune escape ability.Methods PB-CRISPR-CD19 small guide RNA(sgRNA)plasmids was constructed,the optimal sgRNA sequence was screened,and Raji-Luc cells with pCAG-PBase,PB-CD19 sgRNA,and PB-CRISPR-Cas9 were co-transfected.Stable knockout monoclonal cell lines were screened by flow sorting and limit dilution method and the knockout effect was verified through gene sequence testing.The expression of luciferase on the surface of the cell line was detected by microplate reader,CD19 CAR-T and CD38 CAR-T previously constructed in the laboratory were used as effector cells,and the immune escape ability of Raji-Luc CD19 KO cell line was verified by universal luciferase chemiluminescence method.Results The transfection efficiency of Raji-Luc CD19 KO cells prepared by electro transfection was high,and the knockout efficiency of the two monoclonal cells was more than 99%.There was no significant difference in luciferase expression compared to the original Raji-Luc cells,and CD19 CAR-T cells could not be activated to the kill them.Conclusion Successfully constructed Raji-Luc CD19 KO lymphoma cell line.
5.Radiomics combined with CT features for distinguishing mycoplasma and non-mycoplasma pneumonia in children
Chao WANG ; Peng XU ; Guoqiang HUANG ; Xiaohui QIU ; Yichao LIU
Chinese Journal of Interventional Imaging and Therapy 2024;21(3):155-159
Objective To observe the value of radiomics combined with CT features for distinguishing mycoplasma pneumonia(MP)and non-MP in children.Methods Data of 153 children with pneumonia were retrospectively analyzed.The children were divided into MP group(n=101)and non-MP group(n=52)according to mycoplasma RNA detection,and also were divided into training set(n=107,including 71 MP and 36 non-MP)and validation set(n=46,including 30 MP and 16 non-MP)at the ratio of 7∶3.CT findings were compared between groups.Six best CT features were selected in training set using F test algorithm,and a CT model was constructed using logistic regression(LR)method.The best radiomics features were extracted and screened in training set,and machine learning(ML)models were constructed using LR,support vector machine(SVM),random forest(RF),linear discriminant analysis(LDA)and stochastic gradient descent(SGD)classifiers,respectively.Based on the best CT features and radiomics features,CT-ML models were constructed using the above classifiers.Receiver operating characteristic curves were drawn,and the areas under the curve(AUC)were calculated,the efficacy of each model for distinguishing MP and non-MP was evaluated.Results Lesions involved the upper,middle and lower lobe of right lung,thickened bronchial wall,tree bud sign and edge retract sign were the best CT features.AUC of CTLR was 0.710,of MLLR,MLSVM,MLRF,MLLDA and MLSGD in validation set was 0.715,0.663,0.623,0.706 and 0.494,respectively,and MLLR was the optimal radiomics model.AUC of CT-MLLR,CT-MLSVM,CT-MLRF,CT-MLLDA and CT-MLSGD in validation set was 0.813,0.823,0.649,0.796 and 0.665,respectively,and CT-MLSVM was the optimal CT-ML model.In training set,AUC of CT-MLSVM(0.840)was higher than that of CTLR and MLLR model(AUC=0.713,0.740,both P<0.05).In validation set,no significant difference of AUC was found among CTLR,MLLR and CT-MLSVM(AUC=0.710,0.715 and 0.823,all P>0.05).Conclusion Radiomics combined with CT features could effectively distinguish MP and non-MP in children.
6.Comparative study of 18F-PSMA-1007, 18F-FDG PET/CT and mpMRI in the diagnosis of prostate cancer
Yiyi JIANG ; Fucen LIU ; Boliang LI ; Yichao WANG ; Minshan JIN ; Jun ZHANG ; Hui DAI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(3):147-152
Objective:To compare the diagnostic efficacy of 18F-prostate specific membrane antigen (PSMA)-1007 PET/CT, 18F-FDG PET/CT and multi-parameter MRI (mpMRI) in prostate cancer (PCa). Methods:Retrospective analysis was conducted on data from 22 patients ((72.6±6.2) years) with pathologically confirmed PCa in the Affiliated Taizhou People′s Hospital of Nanjing Medical University between April 2021 and September 2022. All patients underwent 18F-PSMA-1007 PET/CT, 18F-FDG PET/CT, and mpMRI examination within 30 d, and the imaging parameters were collected, including PSMA-SUV max, FDG-SUV max, minimum apparent diffusion coefficient (ADC min), mean apparent diffusion coefficient (ADC mean), PSMA-SUV max/ADC min, PSMA-SUV max/ADC mean, FDG-SUV max/ADC min, FDG-SUV max/ADC mean. Patients were divided into groups based on the International Society of Urological Pathology (ISUP) grading (≤3 vs >3) and serum total prostate specific antigen (TPSA; ≤20 μg/L vs >20 μg/L), and differences of imaging parameters between groups were compared (Mann-Whitney U test or independent-sample t test). ROC curves were generated to evaluate the diagnostic ability of each parameter for different levels of PCa. χ2 test and ROC curve analysis were used to compare the detection rate and diagnostic efficiency of three imaging methods for primary focus, lymph node metastasis, and bone metastasis in PCa. Results:Differences were found between ISUP≤3 ( n=6) and >3 ( n=16) groups in PSMA-SUV max/ADC min, PSMA-SUV max/ADC mean, PSMA-SUV max, and ADC min ( z values: from -2.65 to -2.36, t=3.60, P values: 0.002-0.018). But there was no significant difference found between TPSA≤20 μg/L ( n=5) and >20 μg/L ( n=17) groups in all indices ( z values: from -1.76 to -1.45, t values: -1.19 and 1.28, all P>0.05). The optimal cut-off value for PSMA-SUV max/ADC min in differentiating high-grade and low-grade PCa was determined to be 22.628×10 3. In the patient-based analysis, no statistical difference was found in the detection rate of PCa primary tumors among 18F-PSMA-1007 PET/CT, 18F-FDG PET/CT, and mpMRI ( χ2=1.91, P=0.767). However, the detection rates of lymph node and bone metastasis among three imaging methods were significantly different (72.73%(16/22), 59.09%(13/22), 36.36%(8/22) and 81.82%(18/22), 63.64%(14/22), 45.45%(10/22); χ2 values: 6.03, 6.29; P values: 0.049, 0.043). 18F-PSMA-1007 PET/CT resulted in a 36.36%(8/22) increase in N stage and the 40.91%(9/22) increase in M stage compared to mpMRI. Conclusions:PSMA-SUV max/ADC min is a valuable parameter for differentiating high-grade and low-grade PCa. 18F-PSMA-1007 PET/CT demonstrates superior detection rate of PCa lymph node and bone metastasis compared to 18F-FDG PET/CT and mpMRI, and exhibits higher diagnostic efficiency, so it can be recommended for NM staging in patients with PCa.
7.Xuebijing enhances antitumor efficacy of anti-CD19 CAR-T cells
Jingjing Zhu ; Jing Zhang ; Ping Wang ; Xiuying Liu ; Jingjing Liu ; Yichao Feng ; Mary Yue Jiang ; Zhiqiao Feng ; Xiaoqing Yao ; Jianxun Wang
Journal of Traditional Chinese Medical Sciences 2024;11(4):466-475
Objective:
To investigate the effects and mechanisms of Xuebijing injection (XBJ) on Chimeric antigen receptor-T (CAR-T) cell function and its therapeutic potential against CAR-T therapy-associated cytokine storms (CRS).
Methods:
Anti-CD19 CAR-T cells were established based on FMC63 antibodies. Different doses of XBJ (1 and 10 mg/mL) were added to the culture system. Untreated anti-CD19 CAR-T cells served as negative controls. After 48-h co-culture, the effects of XBJ on CAR-T cell function were assessed. Carboxyfluorescein diacetate succinimidyl ester staining was used to assess the effect of XBJ on CAR-T cell proliferation. Flow cytometry, luciferase reporter gene assays, and real time cellular analysis were employed to evaluate the effects of XBJ on CAR-T cell cytotoxicity in vitro. RNA-sequencing was performed to analyze the effects of XBJ on CAR-T cell gene expression. Network pharmacology predicted potential XBJ therapeutic targets for CRS, which were verified in a THP-1 macrophage inflammation model.
Results:
XBJ enhanced both the proliferation and tumor killing capacities of CAR-T cells. Transcriptome analysis showed that XBJ treatment affects multiple genes and pathways in CAR-T cells, with differential gene enrichment in multiple cell proliferation and growth factor pathways. Potential targets for CRS control by XBJ were predicted using network pharmacology, and the inhibitory effect of XBJ on the expression of relevant genes was verified using a macrophage model.
Conclusion
The results of this study indicate that XBJ can enhance the killing effect of CAR-T cells on tumor cells and that the mechanism is related to the regulation of T cell proliferation and activation. Moreover, XBJ inhibited excessive inflammation associated with CAR-T therapy. However, the current findings remain to be further validated through in vivo experiments.
8.Evaluation of clinical application of automatic coagulation detection assembly line in high-throughput specimen detection
Hui WU ; Lin SUN ; Meixiu GU ; Yichao GUO ; Chong WANG ; Beili WANG ; Baishen PAN ; Wei GUO
International Journal of Laboratory Medicine 2024;45(12):1416-1418,1424
Objective To evaluate the clinical application of automatic coagulation detection assembly line in high-throughput specimen detection.Methods The relevant information of sodium citrate anticoagulation samples in Zhongshan Hospital Affiliated to Fudan University from June to August 2021 was collected,inclu-ding sample collection time,receiving time,instrument sucking time,test completion time,and whether it pas-sed autoverification or not.The sample pretreatment time,testing time and turnaround time(TAT)of the au-tomatic coagulation detection assembly line were compared before and after installation,and the detection speed of the automatic coagulation detection assembly line was evaluated.Results The automatic coagulation detection line was expected to detect 650-900 samples per hour.The increase in the number of turbidimetric tests would slow down the detection speed of the instrument.Automatic coagulation detection assembly line test specimen to clinic and ward of pretreatment time and testing time were shorter than single detection,the differences were statistically significant(P<0.05).The automatic coagulation detection assembly line could shorten TAT(P<0.05).After the application of automatic coagulation detection assembly line,the autoveri-fication rate was 25.6%.Conclusion The automatic coagulation detection assembly line is suitable for high-throughput specimen detection in laboratory.Compared with stand-alone coagulation detection,the automatic coagulation detection assembly line could shorten TAT and testing time,and help to reduce the work pressure of laboratory personnel.
9.Evaluation of human cognitive performance using heart rate variability under sustained near-high temperature exposure
Hui ZHU ; Yufei WANG ; Yichao WANG ; Kun GAO ; Hua SU
Space Medicine & Medical Engineering 2024;35(2):84-90
Objective To explore the influence of continuous thermal exposure on human cognitive performance.It provides solutions for the reduction of cognitive performance caused by high temperature emergency,and reduces the misoperation problems or even safety accidents of astronauts in high temperature emergency.Methods 14 right-handed male subjects were recruited and continuously exposed to four thermal environments of 32℃,35℃,38℃,and 41℃for 150 minutes,during which 5 different cognitive tasks(Posner Cueing Task,Deary-liewald Task,N-back Task,Wisconsin Card Task,Visual Search Task)were continuously performed to obtain relative cognitive performance.At the same time,a portable 2-lead holter was used to continuously capture ECG R signals during the cognitive test.Thereafter,the heart rate variability(HRV)analysis was conducted based on the ECG data,to explore the correlations between nonlinear indices(SD1,Shannon entropy,α2,D2)and the cognitive performance.Results Tresults showed that all nonlinear indexes changed with the exposure time and exposure temperature with certain patterns.In addition,through the correlation analysis between relative cognitive performance and nonlinear indicators,the most relevant indicator is α2(correlation coefficient 0.7).The correlation analysis results showed that the nonlinear index α2 had a U-shaped relationship with relative cognitive performance(correlation coefficient was 0.7).Based on that,a quantitative relationship between α2 and relative cognitive performance was obtained.It is found that when α2 was equal to 0.98,the worst relative cognitive performance was observed.Conclusion This study showed that the HRV nonlinear index α2 could serve as a reliable indicator of the cognitive performance of human during hot exposure,which provided a potential solution for the productivity and health evaluation of astronauts.
10.Application of serum AST/ALT ratio and imaging features in predicting the prognosis of patients with hepatocellular carcinoma after receiving transarterial chemoembolization
Dawei LI ; Zhenyan ZHOU ; Changyou ZHOU ; Ningping ZHANG ; Hailong SHANG ; Yichao WANG
Journal of Interventional Radiology 2024;33(8):849-854
Objective To explore the relationship of the preoperative serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST)ratio and imaging features to the prognosis of patients with hepatocellular carcinoma(HCC)after receiving transarterial chemoembolization(TACE),and to develop a nomogram model used for predicting the patient's overall survival(OS).Methods A total of 211 patients,who were diagnosed as HCC and were treated with TACE as the initial therapy at the Guangci Branch of the First Affiliated Hospital of Soochow University of China between July 2016 and July 2020,were enrolled in this study.The patients were randomly divided into the modeling group(n=139)and validation group(n=72).The receiver operating characteristic(ROC)curve was used to determine the optimal cutoff value of AST/ALT ratio.The univariate and multivariate Cox regression analyses were conducted in the modeling group to screen out the independent predictors affecting HCC patient's OS and to establish a prognostic model.Harrell consistency index(C-index)was used to evaluate the predictive ability of the nomogram model for OS in HCC patients,and the calibration curves were plotted to assess the predictive accuracy of the nomogram model.Results No statistically significant difference in the baseline feature distribution existed between the modeling group and validation group(P>0.05).The median OS of the modeling group and validation group was 28.5 months(95%CI:22.1-34.9)and 25.1 months(95%CI:19.2-29.0)respectively,the difference was not statistically significant(x2=1.395,P=0.322).The optimal cutoff value of AST/ALT ratio for predicting OS was 1.10,and the area under curve(AUC)value was 0.674(95%CI:0.604-0.753).The Cox regression analysis indicated that the tumor number(HR=2.080,95%CI=1.245-3.475,P=0.005),tumor capsule(HR=1.771,95%CI=1.128-2.780,P=0.013),irregular marginal enhancement(HR=1.884,95%CI=1.190-2.984,P=0.007),and AST/ALT ratio(HR=2.450,95%CI=1.506-3.987,P<0.01)were the independent prognostic factors for HCC patients receiving TACE treatment.Based on the above variables,a nomogram model for predicting OS was established,and the C-index values in the modeling group and validation group were 0.733(95%CI:0.650-0.826)and 0.770(95%CI:0.688-0.862)respectively.The calibration curves showed that no significant deviations existed between the predictive curves of the prognostic model and the ideal reference curves for one-,2-and 3-year OS.Conclusion The nomogram model,which is established based on the tumor number,imaging features and preoperative AST/ALT ratio,has an excellent value in predicting the prognosis of HCC patients treated with TACE.


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