1.Analysis of the efficacy of glucocorticoid treatment in advanced thymoma
Xingguo YANG ; Lei YU ; Tao YU ; Zhen YU ; Xin DU ; Xiang GAO ; Xintao YU
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(1):24-27
Objective:To explore the clinical efficacy and safety of moderate-dose glucocorticoid treatment in patients with advanced thymoma.Methods:A retrospective analysis was conducted on clinical data of 56 patients with thymoma who received glucocorticoid treatment at Beijing Tongren Hospital, Capital Medical University, from January 2018 to March 2023. Among them, there were 33 males and 23 females; aged from 28 to 72 years old, with a median age of(43.8±11.2)years old. There were 16 cases of type B1 thymoma, 23 cases of type B2, and 17 cases of type B3. There were 17 cases with myasthenia gravis and 1 case with pure red blood cell aplasia. All patients had received radiotherapy or chemotherapy. Patients received moderate-dose glucocorticoid treatment(50 mg/day), and tumor response was evaluated by CT scan after 2 weeks of treatment. The tumor treatment effect and adverse reactions were recorded.Results:Among the patients, 22 cases achieved partial remission, and 3 cases achieved complete remission, resulting in an overall objective response rate (ORR) of 44.6%. Among them, 23 patients had type B2 thymoma, with 17 achieving partial remission and 3 achieving complete remission, resulting in an ORR of 87.0%. Among the 16 patients with type B1 thymoma, 5 achieved partial remission. No efficacy was observed in 17 patients with type B3 thymoma. The follow-up period ranged from 2 to 26 months, and 2 patients experienced thymoma recurrence.Conclusion:Moderate-dose glucocorticoid treatment demonstrates effective and safe outcomes in advanced or invasive thymoma, particularly for the treatment of type B2 thymoma.
2.Mechanism of extracts of Rhizoma Sparganii and Rhizoma Curcumae on cartilage damage and NOX2/ROS/NF-κB signaling pathway in osteoarthritis rats
Jinchao MA ; Minghao CHEN ; Chunqian JIANG ; Yang WANG ; Xingguo LIU ; Yongquan LI
International Journal of Biomedical Engineering 2024;47(3):242-246
Objective:To investigate the effects of extracts of Rhizoma Sparganii and Rhizoma Curcumae on cartilage damage in osteoarthritis rats and NADPH oxidase 2 (NOX2)/reactive oxygen species (ROS)/nuclear factor-κB (NF-κB) signaling pathways. Methods:Rats (50 cases) were divided into the sham group, and model group, as well as the low, medium, and high dose groups of extracts of Rhizoma Sparganii and Rhizoma Curcumae, with 10 rats in each group. Except for sham group, the rat model of cartilage damage in knee osteoarthritis was established. On the second day after modeling, the rats in the low, medium, and high dose groups received intragastric extracts perfusion of Rhizoma Sparganii and Rhizoma Curcumae at the doses of 5, 10, and 20 g/kg respectively. The rats in the sham and model groups received intragastric equivalent 0.9% sodium chloride solution perfusion, once daily, for 20 days by continuous administration. The knee joint behavior, bone metabolism indicators, serum superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) levels, inflammatory factors, NOX2, and NF-κB levels of each group were observed. Results:Compared with the model group, the behavioral abnormality scores, cartilage oligomeric matrix protein (COMP), MDA, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), NOX2, and NF-κB levels in the low, medium, and high dose groups were all gradually decreased (all P < 0.05), while proteoglycan, SOD, GSH, and interleukin-10 (IL-10) levels in the low, medium, and high dose groups were all gradually increased (all P < 0.05), and it was dose-dependent. Conclusions:Rhizoma Sparganii and Rhizoma Curcumae extracts can effectively improve cartilage damage in osteoarthritis rats, and it may be related to the inhibition of the NOX2/ROS/NF-κB signaling pathway.
3.Role of Oxidative Stress in Osteoporosis and Treatment by Traditional Chinese Medicine: A Review
Jian YUAN ; Lingjun KONG ; Jun ZHAO ; Yuquan WANG ; Zhaohui LIU ; Xingguo LI ; Delong YANG ; Chenliang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(6):268-274
Osteoporosis (OP) is a systemic metabolic bone disease. Amid population aging, OP has become a major health problem for the middle-aged and the elderly in China. Aging, iron load, and estrogen deficiency break the balance between oxidation and antioxidant systems, and the increase of reactive oxygen species mediates oxidative stress to damage DNA, lipids, proteins and other macromolecules, thus accelerating cell apoptosis and inducing OP, obesity, and neurodegenerative disorders. It has been found that oxidative stress is of great significance in the pathogenesis of OP. Oxidative stress regulates the signaling pathways, cytokines, and proteins related to the mesenchymal stem cells, osteoblasts, and osteoclasts, thereby weakening the osteogenic differentiation of mesenchymal stem cells, inhibiting osteoblast mineralization, and promoting the activation, proliferation, and maturation of osteoclasts. As a result, the dynamic imbalance between bone resorption and bone formation occurs, influencing bone remodeling and promoting the progression of OP. At the moment, anti-bone resorption drugs, bone formation-promoting drugs, and hormones are mainly used in clinical settings in western medicine. However, due to the long treatment cycle and the occurrence of serious gastrointestinal reactions, hypocalcemia, osteonecrosis, and others, patients show poor compliance and thus the effect is not as expected. Traditional Chinese medicine (TCM) demonstrates remarkable effect on OP attributing to the multi-pathway and multi-target characteristics. With low price and few adverse reactions, TCM is widely applied in clinical practice in comparison with western medicine. TCM has unique advantages in the treatment of OP by regulating oxidative stress. It exerts the therapeutic effect on OP by modulating different signaling pathways, providing new mindset for the treatment of this disease. Therefore, through literature research, this study summarized the research on mechanism of oxidative stress in OP and the treatment by TCM, which is expected to lay a foundation for further research.
4.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.
5.Establishment and validation of a nomogram to predict progression free survival of patients with thymoma
Xin DU ; Lei YU ; Tao YU ; Yunfeng ZHANG ; Baoxun ZHANG ; Ji KE ; Zhen YU ; Xingguo YANG ; Fei LI ; Xintao YU ; Jian CUI
Chinese Journal of Thoracic and Cardiovascular Surgery 2023;39(4):228-233
Objective:To explore the prognostic risk factors of thymoma patients after resection, and establish a novel nomogram to predict progression free survival(PFS) of patients with thymoma.Methods:A retrospectively analysis was performed on clinicopathological datas of 267 cases of thymoma patients underwent thymoma resection in Beijing Tongren Hospital from January 2010 to December 2019. The univariate and multivariate Cox risk ratio models were used to analyze the related factors that might affect PFS, and the prediction nomogram of PFS after thymoma resection was established using the screened independent risk factors. Then the predictive ability of the model was evaluated. Results:The univariate analysis showed that age, type of surgery, completeness of resection, WHO histologic classification, TNM stage and postoperative adjuvant therapy were significantly correlated with PFS after thymoma resection( P<0.05). The multivariate analysis showed that only age and TNM stage were independent prognostic factors affecting PFS after thymoma resection( P<0.05). The concordance index( C- index) of the prediction model for the prognosis of thymoma patients established by this method was 0.866(95% CI: 0.809-0.923), which had remarkable predictive efficiency. Conclusion:The nomogram model is constructed and verified based on age and TNM stage, excluding the interference of other clinicopathological factors on prognosis assessment, and which is convenient for clinicians to quickly and individually evaluate the prognosis of patients after thymoma resection.
6.Single-versus Two-port Video-assisted Thoracic Surgery in Thymoma: A Propensity-matched Study.
Xingguo YANG ; Lei YU ; Zhen YU ; Xiang GAO ; Xin DU
Chinese Journal of Lung Cancer 2022;25(4):253-258
BACKGROUND:
In recent years, with the advancement of minimally invasive techniques, thoracoscopic thymoma resection has experienced a development process from three-port video-assisted thoracic surgery (VATS) to two-port (TP) and single-port (SP) variants. However, the feasibility and safety of SP-VATS have not been generally recognized. This study intends to explore the safety and feasibility of SP-VATS in thymoma resection, in order to provide a reference for clinical surgicalselection.
METHODS:
The clinical data of 197 patients who underwent thoracoscopic thymoma resection in Beijing Tongren Hospital from January 2018 to September 2021 were retrospectively analyzed. The patients were divided into SP-VATS group (n=42) and TP-VATS group (n=155). After matching propensity scores, there is no statistically significant difference in preoperative baseline data between SP-VATS group and TP-VATS group. Among them, there were 17 males and 25 females with an average age of 28-72 (48.00±9.43) years in the SP-VATS group, and 20 males and 22 females with an average age of 30-75 (50.38±9.83) years in TP-VATS group. The clinical effects of the two groups were compared.
RESULTS:
The operation was successfully completed in both groups, and there was no conversion to thoracotomy or increased surgical incisions. Compared with the TP-VATS group, the chest drainage time and hospital stay in the SP-VATS group were shorter [(2.95±0.76) d vs (3.33±0.85) d; (4.57±0.83) d vs (5.07±1.13) d], and the visual pain score at 24 h and 72 h after surgery were lower [(3.64±0.85) points vs (4.05±0.66) points; (2.33±0.75) points vs (3.07±0.68) points] (P<0.05). There was no statistically significant difference between the two groups in operation time [(130.00±26.23) min vs (135.24±27.03) min], intraoperative blood loss [(69.52±22.73) mL vs (82.38±49.23) mL] (P>0.05).
CONCLUSIONS
SP-VATS in thymoma is a safe, feasible, and less invasive procedure, with less postoperative pain and faster recovery than multi-port VATS.
Adult
;
Aged
;
Female
;
Humans
;
Lung Neoplasms/surgery*
;
Male
;
Middle Aged
;
Retrospective Studies
;
Thoracic Surgery, Video-Assisted/methods*
;
Thymoma/surgery*
;
Thymus Neoplasms/surgery*
7.Comprehensive Analysis of the Relationship between m6A Methylation Patterns and Immune Microenvironment in Lung Adenocarcinoma.
Ji KE ; Jian CUI ; Xingguo YANG ; Xin DU ; Bobo MA ; Lei YU
Chinese Journal of Lung Cancer 2022;25(5):311-322
BACKGROUND:
m6A RNA methylation modification plays an important role in the occurrence and progression of lung cancer and regulates tumor immunity. Current studies mostly focus on the differential expression of some specific m6A effectors and infiltrating immune cell. m6A methylation modification is the result of mutual adjustment and balance between effectors, and changes in the expression of one or two effectors are far from enough to reflect the panorama of m6A methylation. The role of m6A in the immune microenvironment of lung adenocarcinoma (LUAD) is still poorly understood. The aim of this study is to investigate the effect of different m6A modification patterns in immune microenvironment of LUAD.
METHODS:
LUAD data was obtained from The Cancer Genome Atlas (TCGA), University of California Santa Cruz Xena (UCSC Xena) and Gene Expression Omnibus (GEO) databases. Gene mutation, differential expression and survival analysis were performed for 24 m6A effectors. The m6A modification pattern was constructed by unsupervised clustering method, and the m6A clusters survival analysis, gene set variation analysis, immune score and immune cell infiltration analysis were performed. The association between LRPPRC protein expression levels and infiltration of CD8+ cytotoxic T lymphocytes and CD68+ macrophages in the tumor microenvironment was validated by immunohistochemistry in LUAD tissue microarray with 68 cases.
RESULTS:
The mutations of m6A effector were found in 150 of 567 LUAD cases with a frequency of 26.46%. 6 readers and 3 writers were significantly up regulated in LUAD tissues compared with normal tissues. IGF2BP1 and HNRNPC are the independent risk factors for prognosis of LUAD. Abundant cross-talks among writers, erasers and readers were demonstrated. Three m6A modification patterns with different immune cell infiltration characteristics and clinical prognosis were established. Among m6A effectors, LRPPRC was found to be inversely associated with the infiltration of CD8+ cytotoxic T lymphocytes and CD68+ macrophages, and was validated in 68 LUAD tissues.
CONCLUSIONS
m6A modification patterns play non-negligible roles in regulating the immune microenvironment. LRPPRC has potential to be a new biomarker for checkpoint inhibitor immunotherapy.
Adenocarcinoma/genetics*
;
Adenocarcinoma of Lung/pathology*
;
Adenosine/metabolism*
;
Gene Expression Regulation, Neoplastic
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Humans
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Lung Neoplasms/pathology*
;
Methylation
;
Tumor Microenvironment/genetics*
8.Prognosis and risk factor analysis of cases underwent thymoma resection in single center
Xin DU ; Lei YU ; Fei LI ; Baoxun ZHANG ; Zhen YU ; Xingguo YANG ; Yuxuan JIANG ; Xintao YU
Chinese Journal of Thoracic and Cardiovascular Surgery 2021;37(10):615-617
Objective:To explore the prognosis and clinical risk factor of thymoma patients after resection.Methods:A retrospectively analysis of 154 cases of thymoma patients underwent thymoma resection in Beijing Tongren Hospital (Myasthenia Gravis & Thymoma Diagnosis and Treatment Center, Capital Medical University) from January 2005 to December 2015, and then the progress-free survival was calculated by Kaplan- Meier method, the differences between curves were analyzed by log- rank test. There were 74 males and 80 females; the median age was 52(22-77)years. 121 cases(78.6%)complicated with myashenia gravis. Thymoma cases were classfied into 5 cases A, 35 cases AB, 27 cases B1, 56 cases B2 and 31 cases B3 respectively. There were 80, 16, 45 and 13 patients with Masaoka-Koga type Ⅰ-Ⅳ, respectively. 122 cases were treated by thoracoscopic assisted operation, 32 cases were treated by median sternum. The risk factors about group of gender, age, thymoma-associated MG (Myasthenia Gravis), completeness of resection, histologic type and Masaoka-Koga stage were calculated by Cox regression analysis. Results:The overall 1-, 5- 10-year progress-free survival rate of 154 cases were 98.7%, 88.3%, and 78.7%, respectively. The adverse prognostic factors for progress-free survival were age, completeness of resection, WHO histologic classification and Masaoka-Koga stage at univariate analysis. The age, WHO histologic classification and Masaoka-Koga stage were the independent risk factors at multivariate analysis.Conclusion:For thymoma, we suggest early discovery and early treatment. For the thymoma patients who are available for surgical treatment, all the tumor, thymus and surrounding adipose tissue should be resected. For the thymoma patients whose tumors cannot excise completely, adjuvant radiotherapy can reduce the risk for tumor recurrence after resection. For patients with thymoma after surgery, MG treatment is particularly critical for prognosis.
9.Non-thymoma thymic morphology in patients with Myasthenia Gravis
Zhen YU ; Lei YU ; Xingguo YANG ; Xin DU
Chinese Journal of Thoracic and Cardiovascular Surgery 2021;37(5):278-280
Objective:To investigate the non-thymoma thymic morphology in patients with Myasthenia Gravis(MG), and provide the theoretical basis for extended thymectomy.Methods:From September 2008 to March 2018, extended thymectomy had been performed for 150 patients with MG in our department. In order to achieve maximal benefit, combined thoracoscopic and mediastinoscopic approach had been adopted to completely remove both thymus and ectopic thymic tissue in the neck and the anterior mediastinum. Cervical and mediastinal tissue including fat from the thyroid isthmus to the diaphragm was swept away from above the phrenic nerve. The regions containing mediastinal fat were divided into 12 stations.Results:There was no mortality. Pathology reports revealed 126(84.0%) patients with MG had hyperplastic thymus, 17(11.3%)cases with involuted thymus and 7 (4.7%)cases with normal thymus. 98 (65.3%)cases had more than two superior horns, and 59(39.3%) patients had ectopic thymic tissue in the mediastinum and in the neck. Positive rates of ectopic thymic tissue in the 12 cervical-mediastinal fat stations were 7.8%, 10.0%, 8.8%, 3.8%, 3.0%, 2.5%, 0, 0, 0.7%, 13.3%, 12.3% and 9.1%, respectively. After a follow-up period of 2-12 years, the rate of complete stable remission was 44.7%(59/132), and the effective rate was 89.4%(118/132).Conclusion:It is very meaningful to study non-thymoma thymic morphology in patients with MG in order to guide the performance of extended thymectomy and improve its outcome. For the purpose of minimally invasion, one side of mediastinal pleural should be carefully protected.
10.Analysis of Influencing Factors for Postoperative Venous Thromboembolism of Thymic Malignancies.
Xingguo YANG ; Hui LI ; Lei YU ; Tao YU ; Fei LI ; Zhen YU ; Baoxun ZHANG ; Xin DU
Chinese Journal of Lung Cancer 2021;24(7):497-502
BACKGROUND:
The previous study has indicated that the incidence of venous thromboembolism (VTE) after thoracic surgery is high. The purpose of this study was to analyze the incidence and risk factors of postoperative VTE in thymic malignancy patients.
METHODS:
This was a single-center study. Patients undergoing resection for thymic malignancy between December 2017 and February 2021 in Department of Thoracic Surgery, Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled in this study. In addition to the routine examination, all patients were screened for deep venous thrombosis (DVT) by using noninvasive duplex lower extremity ultrasound before and after surgery. Patients did not receive any prophylactic anticoagulant therapy before and after surgery. All patients received modified caprini risk assessment. According to whether VTE occurred after operation, patients were divided into VTE group and control group. The clinical data of the two groups were compared. The occurrence time and possible high risk factors of VTE after operation were analyzed.
RESULTS:
A total of 169 patients with thymic malignant tumor were enrolled, including 94 males and 75 females, aging from 22 to 76 years. A total of 95 patients underwent thoracoscopic surgery and 74 patients underwent median sternotomy. The total incidence of VTE was 12.4%. The median time for diagnosis of VTE was 4 days (2 days-15 days) after operation. According to the modified caprini score, the incidence of VTE in low risk patients (Caprini score≤4 points), moderate risk patients (Caprini score 5 to 8 points) and high risk patients (Caprini score≥9 points) were 0% (0/7), 7.0% (8/115) and 27.7% (13/47), respectively (Z=1.670, P=0.008). Univariate analysis showed that there were significant differences between VTE group and control group in age, operation method, operation time, indwelling central venous catheter, postoperative bed rest time more than 72 hours (P<0.05). Multivariate analysis showed that over 60 years old, operation method and operation time were independent risk factors for VTE after resection for thymic malignancies.
CONCLUSIONS
Over 60 years old, operation method and operation time are independent risk factors for VTE. Modified caprini assessment can effectively screen high-risk patients.

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