Objective To explore the CT diagnosis and differential diagnosis of perivascular epithelioid cell neoplasms (PEComa), improve the accuracy of PEComa diagnosis, and reduce misdiagnosis. Methods CT findings of 8 cases of PEComa confirmed by pathology in Jining First People’s Hospital from January 2020 to April 2024 were retrospectively analyzed for the location, shape, size, boundary, plain scan density, and enhancement characteristics of the lesions. Results All 8 tumors were solitary, with 5 located in the kidney, 1 in the liver, 1 in the extraperitoneal space, and 1 in the retroperitoneal space. The tumors were round in 3 cases, oval in 1 case, and irregular in 4 cases. Seven cases were benign with clear boundaries and 1 case was malignant with unclear boundaries. On plain CT, 2 cases showed slightly low density, 3 cases showed slightly high density, and 3 cases showed low density. One tumor had uniform density, and 7 tumors had nonuniform density with internal necrosis and cystic changes. Contrast-enhanced CT revealed diverse enhancement patterns. Four cases showed a “fast in and fast out” enhancement pattern, with significant arterial-phase enhancement and reduced portal venous-phase enhancement. Three cases showed a “fast-in and slow-out” enhancement pattern, with significant enhancement in the arterial phase, persistent enhancement in the portal venous phase, and slightly reduced density in the delayed phase. One case showed mild enhancement in the arterial phase and significant enhancement in the portal venous phase. In 3 cases, multiple tortuous and thickened blood vessels were observed around the tumors, while 3 cases showed tortuous vascular shadows within the tumors. Conclusion PEComa demonstrates characteristic CT features, predominantly with “fast in and fast out” or “fast in and slow out” enhancement patterns. When thickened and tortuous blood vessels are observed within or around the tumor, PEComa should be considered in combination with clinical findings.

Background China is a major coal producer and consumer country in the world. Coal workers' pneumoconiosis (CWP) is a primary factor endangering the occupational health of coal miners. Research on the disease burden of CWP and its changing trend is significant for disease prevention & control and associated policies. Objective To analyze the disease burden of CWP in China from 1990 to 2021 and its changing trend, and predict the disease burden from 2022 to 2035. Methods Using the Global Burden of Disease Study (GBD) database of 2021, numbers ofincident cases, prevalent cases, deaths, and disability-adjusted life years (DALYs) as well as crude and age-standardized rates of CWP in China were retrieved. Linear regression model was used to calculate the estimated annual percentage change (EAPC) of the age-standardized rates. Joinpoint regression model was used to analyze the temporal trend of disease burden and the disease burden of different sexes and age groups, and Bayesian age-period-cohort (BAPC) model was used to forecast the trend of CWP disease burden. Results In 1990, the incident, prevalent, and deaths cases of CWP in China were 3266, 18872, and 1561, respectively, and the DALYs of CWP were 44614.718 person-years. In 2021, the incident, prevalent, and deaths cases of CWP were 3446, 23975, and 1229, respectively, and the DALYs of CWP were 29610.754 person-years. From 1990 to 2021, the age-standardized incidence, prevalence, mortality, and DALYs rates of CWP in China all showed a downward trend, with the EAPCs of −3.121%, −2.532%, −4.018%, and −4.268%, respectively. The disease burden of CWP in China was mainly concentrated in the male population. The annual average percent change analysis indicated that each standardized rate showed a fluctuating downward trend in different periods. The BAPC model showed that from 2022 to 2035, the age-standardized rates of CWP in China would continue to decline steadily. In 2035, the age-standardized incidence, prevalence, mortality, and DALYs rates of CWP would be reduced to 0.10 per 100000, 0.74 per 100000, 0.03 per 100000, and 0.74 per 100000, respectively. Conclusion The disease burden contributed by CWP in China generally show a downward trend from 1990 to 2021, and it is expected that the age-standardized rates will continue to decline steadily from 2022 to 2035.

Cardiotoxicity is a critical issue in drug development that poses serious health risks, including potentially fatal arrhythmias. The human ether-à-go-go related gene (hERG) potassium channel, as one of the primary targets of cardiotoxicity, has garnered widespread attention. Traditional cardiotoxicity testing methods are expensive and time-consuming, making computational virtual screening a suitable alternative. In this study, we employed machine learning techniques utilizing molecular fingerprints and descriptors to predict the cardiotoxicity of compounds, with the aim of improving prediction accuracy and efficiency. We used four types of molecular fingerprints and descriptors combined with machine learning and deep learning algorithms, including Gaussian naive Bayes (NB), random forest (RF), support vector machine (SVM), K-nearest neighbors (KNN), eXtreme gradient boosting (XGBoost), and Transformer models, to build predictive models. Our models demonstrated advanced predictive performance. The best machine learning model, XGBoost Morgan, achieved an accuracy (ACC) value of 0.84, and the deep learning model, Transformer_Morgan, achieved the best ACC value of 0.85, showing a high ability to distinguish between toxic and non-toxic compounds. On an external independent validation set, it achieved the best area under the curve (AUC) value of 0.93, surpassing ADMETlab3.0, Cardpred, and CardioDPi. In addition, we explored the integration of molecular descriptors and fingerprints to enhance model performance and found that ensemble methods, such as voting and stacking, provided slight improvements in model stability. Furthermore, the SHapley Additive exPlanations (SHAP) explanations revealed the relationship between benzene rings, fluorine-containing groups, NH groups, oxygen in ether groups, and cardiotoxicity, highlighting the importance of these features. This study not only improved the predictive accuracy of cardiotoxicity models but also promoted a more reliable and scientifically interpretable method for drug safety assessment. Using computational methods, this study facilitates a more efficient drug development process, reduces costs, and improves the safety of new drug candidates, ultimately benefiting medical and public health.

Objective To investigate the effects of scoparone(Sco)on proliferation and invasion of colon cancer cell line HCT116,and its effect on the expression of epidermal growth factor receptor(EGFR).Methods 1)HCT116 cells were divided into control group,50Sco group,100Sco group and 200Sco group.The cells in con-trol group were incubated with culture medium for 48 hrs.The 50Sco group,100Sco group and 200Sco group were incubated with 50,100 and 200 μmol/L scoparone for 48 hrs respectively.2)HCT116 cells were divided into con-trol group,NC-200Sco group,NC-LV+200Sco group and EGFR-LV+200Sco group.The control group was incuba-ted with normal culture medium for 48 hrs.NC-200Sco group was incubated with 200 μmol/L scoparone for 48 hrs.NC-LV and EGFR-LV were infected into HCT116 cells in NC-LV+200Sco group and EGFR-LV+200Sco group,then incubated with 200 μmol/L scoparone for 48 hrs.Cell proliferation was detected by MTT assay and EdU stai-ning,cell apoptosis was detected by flow cytometry and cell invasion was detected by Transwell assay.EGFR mRNA was detected by RT-qPCR,the level of EGFR,Bcl-2,Bax,matrix metalloproteinase(MMP)-2 and MMP-9 protein was detected by Western blot.Results Compared to the control group,the cell viability,proportion of EdU positive cells and counting number of invasive cells in 50Sco group,100Sco group and 200Sco group all decreased(P＜0.05).Cell apoptosis rate and Bax protein expression increased(P＜0.05),the protein expression of Bcl-2,MMP-2 and MMP-9 decreased(P＜0.05).mRNA and protein expression of EGFR were de-creased(P＜0.05).Compared with NC-200 Sco group and NC-LV+200Sco group,the expression level of mRNA and protein of EGFR in EGFR-LV+200Sco group was increased(P＜0.05).Cell viability,proportion of EdU posi-tive cells and counting number of invasive cells all increased(P＜0.05).The cell apoptosis rate and Bax protein expression level were decreased(P＜0.05).The protein expression of Bcl-2,MMP-2 and MMP-9 was increased(P＜0.05).Conclusions Scoparone has anti-colon cancer cell activity and inhibits proliferation as well as invasion of colon cancer cells through inhibition of EGFR.

Cardiotoxicity is a critical issue in drug development that poses serious health risks,including potentially fatal arrhythmias.The human ether-à-go-go related gene(hERG)potassium channel,as one of the pri-mary targets of cardiotoxicity,has garnered widespread attention.Traditional cardiotoxicity testing methods are expensive and time-consuming,making computational virtual screening a suitable alter-native.In this study,we employed machine learning techniques utilizing molecular fingerprints and descriptors to predict the cardiotoxicity of compounds,with the aim of improving prediction accuracy and efficiency.We used four types of molecular fingerprints and descriptors combined with machine learning and deep learning algorithms,including Gaussian naive Bayes(NB),random forest(RF),support vector machine(SVM),K-nearest neighbors(KNN),eXtreme gradient boosting(XGBoost),and Trans-former models,to build predictive models.Our models demonstrated advanced predictive performance.The best machine learning model,XGBoost Morgan,achieved an accuracy(ACC)value of 0.84,and the deep learning model,Transformer_Morgan,achieved the best ACC value of 0.85,showing a high ability to distinguish between toxic and non-toxic compounds.On an external independent validation set,it achieved the best area under the curve(AUC)value of 0.93,surpassing ADMETlab3.0,Cardpred,and CardioDPi.In addition,we explored the integration of molecular descriptors and fingerprints to enhance model performance and found that ensemble methods,such as voting and stacking,provided slight improvements in model stability.Furthermore,the SHapley Additive exPlanations(SHAP)explanations revealed the relationship between benzene rings,fluorine-containing groups,NH groups,oxygen in ether groups,and cardiotoxicity,highlighting the importance of these features.This study not only improved the predictive accuracy of cardiotoxicity models but also promoted a more reliable and scientifically interpretable method for drug safety assessment.Using computational methods,this study facilitates a more efficient drug development process,reduces costs,and improves the safety of new drug candidates,ultimately benefiting medical and public health.

Objective:To explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring (TDM) in patients with gastrointestinal stromal tumors (GISTs) who are receiving adjuvant therapy after complete resection of their tumors.Methods:This was a descriptive study. Inclusion criteria were (1) complete surgical resection with a pathological diagnosis of GIST, (2) postoperative adjuvant therapy with imatinib and dosage adjustment, (3) multiple TDM of imatinib, and (4) complete clinical, pathological, and follow-up data. The data of 70 patients with GISTs treated at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively. The study cohort comprised 15 (21.4%) men and 55 (78.6%) women of median age 60 years (range: 25–82). Of the eligible patients, 49 (70.0%) were at high-risk, 14 (20.0%) at intermediate-risk, six (8.6%) at low-risk, and one (1.4%) at very low risk. Patients were followed up by the gastrointestinal stromal tumor clinic every 2–3 months and their plasma concentrations of imatinib were checked. The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had ≥ grade III adverse reactions, and whether the first plasma concentration of imatinib was ≥ 1,500 μg/L or between the expected range of 760 μg/L–1,100 μg/L. Studied indicators included adverse reactions, quality of life before and after dose adjustment, and overall survival and recurrence-free survival (RFS) after dose adjustment.Results:Before dose adjustment, all 70 patients received 400 mg of imatinib daily, with initial TDM values of 1,900 ± 568 μg/L, for a median duration of 8.3 months. After dose adjustment, 60 patients received 300 mg daily, with a TDM of 1,216 ± 350 μg/L, whereas 10 received 200 mg daily, with a TDM of 1,023 ± 269 μg/L. The median duration of treatment after dose adjustment was 23.4 months. Compared with those whose dosages were not adjusted, the incidence of bone marrow suppression was significantly lower (74.3% [52/70] vs. 51.4% [36/70], χ 2=9.202, P=0.010); as were the incidences of edema (95.7% [67/70] vs. 50.0% [35/70], χ 2=40.526, P<0.001); skin reactions (70.0% [49/70] vs. 32.9% [23/70), χ 2=22.495, P<0.001); and gastrointestinal reactions (38.6% [27/70] vs. 10.0% [7/70], χ 2=15.899, P<0.001) in those whose dosages were adjusted. The average total scores for physical health before and after dose adjustment were 76 ± 5 and 88 ± 4, respectively; whereas the mental health scores were 75 ± 6 and 89 ± 4, respectively. The median follow-up period was 36 months (range 6–126). During the first 3 years of follow-up, five high-risk patients with non-gastric GISTs developed recurrences. The 3-year overall survival rate was 100%, and the 3-year RFS rate was 92.8%, high-risk patients having a 3-year RFS rate of 89.8%. Conclusion:The adverse reactions and quality of life of GIST patients with severe adverse reactions to adjuvant imatinib therapy after complete resection can be mitigated by appropriately reducing the dosage of imatinib under the guidance of TDM.

Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.

Objective:To explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring (TDM) in patients with gastrointestinal stromal tumors (GISTs) who are receiving adjuvant therapy after complete resection of their tumors.Methods:This was a descriptive study. Inclusion criteria were (1) complete surgical resection with a pathological diagnosis of GIST, (2) postoperative adjuvant therapy with imatinib and dosage adjustment, (3) multiple TDM of imatinib, and (4) complete clinical, pathological, and follow-up data. The data of 70 patients with GISTs treated at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively. The study cohort comprised 15 (21.4%) men and 55 (78.6%) women of median age 60 years (range: 25–82). Of the eligible patients, 49 (70.0%) were at high-risk, 14 (20.0%) at intermediate-risk, six (8.6%) at low-risk, and one (1.4%) at very low risk. Patients were followed up by the gastrointestinal stromal tumor clinic every 2–3 months and their plasma concentrations of imatinib were checked. The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had ≥ grade III adverse reactions, and whether the first plasma concentration of imatinib was ≥ 1,500 μg/L or between the expected range of 760 μg/L–1,100 μg/L. Studied indicators included adverse reactions, quality of life before and after dose adjustment, and overall survival and recurrence-free survival (RFS) after dose adjustment.Results:Before dose adjustment, all 70 patients received 400 mg of imatinib daily, with initial TDM values of 1,900 ± 568 μg/L, for a median duration of 8.3 months. After dose adjustment, 60 patients received 300 mg daily, with a TDM of 1,216 ± 350 μg/L, whereas 10 received 200 mg daily, with a TDM of 1,023 ± 269 μg/L. The median duration of treatment after dose adjustment was 23.4 months. Compared with those whose dosages were not adjusted, the incidence of bone marrow suppression was significantly lower (74.3% [52/70] vs. 51.4% [36/70], χ 2=9.202, P=0.010); as were the incidences of edema (95.7% [67/70] vs. 50.0% [35/70], χ 2=40.526, P<0.001); skin reactions (70.0% [49/70] vs. 32.9% [23/70), χ 2=22.495, P<0.001); and gastrointestinal reactions (38.6% [27/70] vs. 10.0% [7/70], χ 2=15.899, P<0.001) in those whose dosages were adjusted. The average total scores for physical health before and after dose adjustment were 76 ± 5 and 88 ± 4, respectively; whereas the mental health scores were 75 ± 6 and 89 ± 4, respectively. The median follow-up period was 36 months (range 6–126). During the first 3 years of follow-up, five high-risk patients with non-gastric GISTs developed recurrences. The 3-year overall survival rate was 100%, and the 3-year RFS rate was 92.8%, high-risk patients having a 3-year RFS rate of 89.8%. Conclusion:The adverse reactions and quality of life of GIST patients with severe adverse reactions to adjuvant imatinib therapy after complete resection can be mitigated by appropriately reducing the dosage of imatinib under the guidance of TDM.

Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.