1.Performance comparison of domestic and imported CD3/CD28 activation beads for CAR-T cell manufacturing
Xianzheng WEI ; Shuyu ZHANG ; Yuhang JIN ; Pu WANG ; Xu WANG ; Junnian ZHENG ; Dan LIU ; Ming SHI
Chinese Journal of Cancer Biotherapy 2025;32(5):492-497
Objective:To compare the performance differences of domestic and imported CD3/CD28 activation beads for manufacturing CAR-T cells,providing a backup or alternative for domestic CAR-T cell research and manufacture.Methods:A mature protocol using imported CD3/CD28 activation beads with a 1∶1 ratio for CD3+T cells was implemented as research control.Domestic beads were used with gradient ratios of 1∶2,1∶1,and 2∶1 to activate T cells.72 h after T cell activation,CAR-T cells were manufactured by CAR lentiviral infection and cell proliferation was monitored at 2-,4-,and 7-days post-infection.Flow Cytometry was used to detect CAR-T cell positivity 5 days after infection and to detectCD4/CD8 phenotype of CAR-T cells and PD1+TIM3+cell exhaustion ratio 8 days after infection.Results:CAR-T cells manufactured by domestic CD3/CD28 activation beads exhibited similar phenotype compared with those manufactured by imported CD4/CD8 beads.The positive rate of CAR-T cells prepared with domestic beads was slightly lower than that of imported beads(53.7%vs 57.9%).However,the proliferation of CAR-T cells manufactured by domestic beads was about twice that of cells manufactured by imported beads,and the exhaustion level was only half that of imported beads(4.21%vs 7.91%).Moreover,the use of domestic magnetic beads was lower than that of imported magnetic beads,which was advantageous for cutting the costs of CAR-T cells research and manufacture.Conclusion:Domestic CD3/CD28 activation beads used for CAR-T cells manufacturing demonstrate comparable overall performance to their imported counterparts,showing potential as a backup or alternative for imported beads.
2.Clinicopathological features of primary thoracic synovial sarcoma: a study of 42 cases
Jing HAN ; Xianzheng GAO ; Qian DU ; Ke CHEN ; Huaying ZHAO ; Jingmiao ZHANG ; Minjing SUN ; Hui LI ; Shichang WANG ; Shenglei LI
Chinese Journal of Pathology 2025;54(5):488-493
Objective:To investigate the clinical and pathological characteristics of primary thoracic synovial sarcoma (PTSS).Methods:Forty-two PTSS cases diagnosed at the Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from October 2011 to April 2024 were analyzed. All cases were retrospectively studied using hematoxylin-eosin staining and immunohistochemistry. Their clinicopathological features were also reviewed. SS18 rearrangement was assessed in 28 cases using fluorescence in situ hybridization (FISH). Next generation sequencing (NGS) was performed on 8 cases.Results:Among the 42 cases, there were 23 biopsies and 19 surgically-removed specimens. One case was a specimen resected after neoadjuvant chemotherapy. There were 22 males and 20 females, with an age ranging from 6 to 68 years. Twenty-nine cases occured in the lung, 6 in mediastinum, 4 in pericardium, 1 in visceral pleura, and 1 in right atrium. One case did not show any unequivocal primary site. Computed tomography showed the tumors were manifested as a cystic mass, a solid mass, or thickening of the pleura and pericardium. Thirty-two cases had respiratory symptoms, while 19 had pleural effusion. One case had a history of radiotherapy for papillary thyroid carcinoma. Nineteen patients were treated with surgery, while 19 were treated with chemotherapy without surgery. Four patients were diagnosed and discharged, without specific treatment on the record. Morphologically, 1 case was biphasic type, 39 cases were monophasic type, and 2 cases were poorly differentiated type. In addition to the typical morphology of synovial sarcoma, tumors also showed pulmonary bullous changes, stromal collagen hyalinization, hemangiopericytoma-like vasculature, stromal edematous myxoid changes, and microcystic structure. Immunohistochemically, all cases were diffusely positive for TRPS1 (22/22), TLE1 (21/22), CD99 (26/26), SS18-SSX (25/25) and INI1 (12/12), including 3 cases with decreased expression of INI1. Twenty-one cases were focally positive for EMA (21/30), 4 cases for SMA (4/23), 2 cases for S-100 (2/28), and 2 cases (2/35) for CKpan. Twenty-eight cases (28/28) had SS18 rearrangement displaying a split signal on FISH analysis. Eight cases were found to have mutations in SMC1A, NOTCH2, CDK12, SPRY4, BRCA1, STK11, NF2, and PDGFRα genes using NGS. Eighteen of the 29 patients survived and 16 showed disease progression.Conclusions:PTSS is more commonly found in the lungs than other sites and has non-classical morphological features of various types, which need to be differentiated from other tumors. TRPS1 is highly expressed in PTSS and has certain diagnostic values. The diagnosis of PTSS also requires combination of patient′s medical history with thorough imaging studies.
3.Clinicopathological features of primary thoracic synovial sarcoma: a study of 42 cases
Jing HAN ; Xianzheng GAO ; Qian DU ; Ke CHEN ; Huaying ZHAO ; Jingmiao ZHANG ; Minjing SUN ; Hui LI ; Shichang WANG ; Shenglei LI
Chinese Journal of Pathology 2025;54(5):488-493
Objective:To investigate the clinical and pathological characteristics of primary thoracic synovial sarcoma (PTSS).Methods:Forty-two PTSS cases diagnosed at the Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from October 2011 to April 2024 were analyzed. All cases were retrospectively studied using hematoxylin-eosin staining and immunohistochemistry. Their clinicopathological features were also reviewed. SS18 rearrangement was assessed in 28 cases using fluorescence in situ hybridization (FISH). Next generation sequencing (NGS) was performed on 8 cases.Results:Among the 42 cases, there were 23 biopsies and 19 surgically-removed specimens. One case was a specimen resected after neoadjuvant chemotherapy. There were 22 males and 20 females, with an age ranging from 6 to 68 years. Twenty-nine cases occured in the lung, 6 in mediastinum, 4 in pericardium, 1 in visceral pleura, and 1 in right atrium. One case did not show any unequivocal primary site. Computed tomography showed the tumors were manifested as a cystic mass, a solid mass, or thickening of the pleura and pericardium. Thirty-two cases had respiratory symptoms, while 19 had pleural effusion. One case had a history of radiotherapy for papillary thyroid carcinoma. Nineteen patients were treated with surgery, while 19 were treated with chemotherapy without surgery. Four patients were diagnosed and discharged, without specific treatment on the record. Morphologically, 1 case was biphasic type, 39 cases were monophasic type, and 2 cases were poorly differentiated type. In addition to the typical morphology of synovial sarcoma, tumors also showed pulmonary bullous changes, stromal collagen hyalinization, hemangiopericytoma-like vasculature, stromal edematous myxoid changes, and microcystic structure. Immunohistochemically, all cases were diffusely positive for TRPS1 (22/22), TLE1 (21/22), CD99 (26/26), SS18-SSX (25/25) and INI1 (12/12), including 3 cases with decreased expression of INI1. Twenty-one cases were focally positive for EMA (21/30), 4 cases for SMA (4/23), 2 cases for S-100 (2/28), and 2 cases (2/35) for CKpan. Twenty-eight cases (28/28) had SS18 rearrangement displaying a split signal on FISH analysis. Eight cases were found to have mutations in SMC1A, NOTCH2, CDK12, SPRY4, BRCA1, STK11, NF2, and PDGFRα genes using NGS. Eighteen of the 29 patients survived and 16 showed disease progression.Conclusions:PTSS is more commonly found in the lungs than other sites and has non-classical morphological features of various types, which need to be differentiated from other tumors. TRPS1 is highly expressed in PTSS and has certain diagnostic values. The diagnosis of PTSS also requires combination of patient′s medical history with thorough imaging studies.
4.Histopathological diagnosis of pulmonary sclerosing pneumocytoma in needle biopsy specimens
Qianqian SI ; Jing HAN ; Xianzheng GAO ; Yuanyuan ZANG ; Tielin WANG ; Shenglei LI
Chinese Journal of Pathology 2024;53(11):1105-1110
Objective:To investigate the diagnostic features of pulmonary sclerosing pneumocytoma (PSP) in needle biopsy specimens so as to improve the preoperative diagnostic accuracy and to prevent misdiagnoses.Methods:A total of 79 needle biopsy cases confirmed as PSP in surgical resection specimens were collected in the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from January 2015 to January 2023. A retrospective analysis was conducted to investigate the clinical, pathological, and immunohistochemical characteristics of PSP.Results:Among the 79 cases, there were 8 males and 71 females, with an age range of 14 to 67 years (median 47 years). Among the 79 needle biopsy cases of PSP, 5 cases were initially misdiagnosed as adenocarcinoma and 1 as carcinoid preoperatively, while the remaining 73 cases were correctly diagnosed. 84.8% (67/79) of the PSP presented with well-defined, homogeneous, solitary solid tumors on chest imaging. Morphologically, 26.6% (21/79) of the PSP mainly showed a single histological component, 67.1% (53/79) contained two histological components, and 6.3% (5/79) contained three histological components. There were no cases containing all four histological components simultaneously. The tumor was composed of cuboidal cells on the surface and round cells in the stroma and lacked significant cytological atypia and mitotic figures. Some cases exhibited variations in histology and cellular morphology, such as glandular spaces (58.2%, 46/79), sclerotic papillae (46.8%, 37/79), hypercellularity (16.5%, 13/79), and cytological atypia (24.1%, 19/79). Immunophenotyping indicated that both tumor cell types expressed TTF1, EMA and β-catenin, while surface cells expressed pan-cytokeratin and Napsin A, and stromal cells expressed vimentin. In some cases, ER and PR were also expressed.Conclusions:When diagnosing PSP in needle biopsy specimens, the key to avoiding misdiagnosis is recognizing the presence of dual-cell populations within the tumor. The useful clues include presence of cellular papillae, mild cellular atypia, morphological diversity, interstitial foam-like cell aggregates, and prominent background hemorrhage and sclerosis. The characteristic immunophenotype and middle-aged female predilection are also helpful for the diagnosis of PSP.
5.Comparison of the diagnostic efficacy between fine needle aspiration needles and end-cutting fine needle biopsy needles in endoscopic ultrasound-guided tissue acquisition for solid pancreatic lesions
Yundi PAN ; Chunhua ZHOU ; Minmin ZHANG ; Taojing RAN ; Xianzheng QIN ; Kui WANG ; Yao ZHANG ; Tingting GONG ; Ling ZHANG ; Dong WANG ; Xiangyi HE ; Wei WU ; Benyan ZHANG ; Lili GAO ; Duowu ZOU
Chinese Journal of Digestive Endoscopy 2024;41(11):864-870
Objective:To compare the diagnostic efficacy of 22 G fine needle aspiration (FNA) needles and 22 G end-cutting fine needle biopsy (FNB) needles for solid pancreatic lesion using both cytological and histological examination.Methods:Clinical data of 116 patients who underwent endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/FNB) at the Digestive Endoscopy Center of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from June 2022 to March 2023 were retrospectively analyzed. Sixty-three patients sampled with 22 G FNA needles were the FNA group, and 53 sampled with 22 G FNB needles were the FNB group. The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and cytological and histological diagnostic yield of FNA needles and FNB needles for solid pancreatic lesions were compared.Results:There were no significant differences in age, gender, lesion location, lesion size, or the number of passes between the FNA group and the FNB group ( P>0.05). There were no significant differences in the diagnostic accuracy [93.7% (59/63) VS 90.6% (48/53), P=0.730], sensitivity [93.0% (53/57) VS 90.2% (46/51), P=0.732], specificity [100.0% (6/6) VS 100.0% (2/2), P=1.000], positive predictive value [100.0% (53/53) VS 100.0% (46/46), P=1.000] and negative predictive value [60.0% (6/10) VS 28.6% (2/7), P=0.335] of combined cytology and histology in distinguishing benign and malignant lesions between the two groups. In the FNA group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [93.7% (59/63) VS 81.0% (51/63), P=0.008], and was higher than histology alone without statistical significance [93.7% (59/63) VS 87.3% (55/63), P=0.125]. In the FNB group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [90.6% (48/53) VS 69.8% (37/53), P=0.001], but not than histology alone [90.6% (48/53) VS 90.6% (48/53), P=1.000]. For solid masses located in pancreatic body/tail, the diagnostic accuracy for malignancy by histology using FNB needles tended to be higher than that of FNA needles [100.0% (17/17) VS 81.3% (26/32), P=0.080]. Conclusion:Both FNA needles and FNB needles exhibit adequate diagnostic yield for solid pancreatic masses when combining cytology and histology. FNB needles may offer a higher histological diagnostic yield.
6.Research progress in influencing factors and pathogenesis of dementia after traumatic brain injury
Xianzheng SANG ; Chengqing WANG ; Lijun HOU
Chinese Journal of Trauma 2023;39(2):185-192
Traumatic brain injury (TBI) has been recognized as a risk factor for developing dementia. Currently, around 69 million people worldwide suffer from TBI each year, while the overall incidence of TBI among Chinese residents is on a rapid rise. Such a large population of TBI patients may lead to a future surge in the number of dementia patients, bringing heavy burdens on families and societies. However, it seems to be suggested by numerous studies that not all TBI patients are associated with an increased risk of dementia. Dementia can result in disability as well as interfere with caregivers ′ normal lives. Therefore, it will be significant to clarify the relationship between TBI and dementia as well as explain the process of onset and development of post-TBI dementia. In this study, the authors summarize post-TBI dementia from aspects of influencing factors and pathogenic mechanisms, so as to provide relevant references for related studies, therapy, and prophylaxis of post-TBI dementia.
7.Mediastinal T lymphoblastic lymphoma/leukemia: clinicopathological and prognostic analyses of 61 cases
Xianzheng GAO ; Jianguo WEI ; Shenglei LI ; Jing HAN ; Guannan WANG ; Wencai LI
Chinese Journal of Pathology 2020;49(6):601-606
Objective:To investigate the clinicopathologic features and prognosis of mediastinal T lymphoblastic lymphoma/leukemia (T-LBL/ALL).Methods:Sixty-one patients with mediastinal T-LBL/ALL diagnosed at First Affiliated Hospital of Zhengzhou University from August 1, 2011 to December 31, 2018 were enrolled. Their clinical, pathological, imaging features and prognosis were retrospectively analyzed.Results:Of the 61 patients with mediastinal T-LBL/ALL, 46 were male and 15 were female, with a male to female ratio of approximately 3∶1, aged 5 to 71 years (median 24 years, average of 24.5 years). Radiological findings were mediastinal soft tissue masses (58 cases) or mediastinal multiple enlarged lymph nodes (1 case). The tumor had a diameter of 4.9 to 18.3?cm in size, and data of 2 cases was unavailable. The patient′s main symptoms were superior vena cava syndrome (cough, dyspnea, facial or neck edema), shortness of breath and chest pain, while about 1/3 of patients developed B symptoms (high fever, night sweats or significant weight loss). All 61 cases were biopsy specimens, and 2 of the tumors were later resected. Histopathologic examination showed that the thymic tissue epithelial network structure was destroyed or completely disappeared. A large number of lymphocytoid tumor cells were diffusely infiltrative, with infiltration into adipose tissue, starry sky phenomenon, linear-like arrangement, interstitial collagen hyperplasia and tumor cell extrusion. Focal tumor necrosis was present in some cases. Tumor cells were overall small to medium in size. They had little cytoplasm, slightly distorted, round or oval-shaped nuclei, fine chromatin, and innocuous/small nucleoli. Immunohistochemical studies showed that the tumor cells expressed CD7 (100%, 33/33), TDT (93.4%, 57/61), CD99 (83.3%, 25/30), CD1a (4/7), CD10 (8/18), CD34 (13.2%, 5/38), but did not express B cell markers (CD20 and PAX5) or granulocyte monocyte marker (MPO). The Ki-67 proliferation index was usually greater than 50%. One case was tested for TCR clonal rearrangement, which was positive. Several hemotherapy regiments were used. Hyper-CVAD (cyclophosphamide, vindesine, dexamethasone, and epirubicin) were most frequently administrated (60.4%, 32/53), followed by BFM-90 (50.9%, 27/53). Some patients were treated with the above two and other treatment options. Follow-up data were available in 55 of the 61 patients, and 26 patients (47.3%) survived. The average five-year survival rate was 50.6%. The patient′s prognosis was not significantly related to the International Prognostic Index, age of onset, gender, or tumor size.Conclusions:The mediastinal T-LBL/ALL is rare, and most of its specimens are needle biopsies. The histological morphology is often difficult to interpret, while the addition of clinical features and immunohistochemistry may help. The combination of CKpan, TDT, CD99, CD7, CD3, PAX5, CD34, CD10, and Ki-67 immunohistochemicl studies may assist in diagnosis of the most cases.
8. Pulmonary extranodal NK/T-cell lymphoma, nasal type: a clinicopathological analysis of eleven cases
Xianzheng GAO ; Jianguo WEI ; Shenglei LI ; Guannan WANG ; Jing HAN ; Wugan ZHAO ; Yilin XIE ; Wencai LI
Chinese Journal of Pathology 2019;48(6):433-437
Objective:
To investigate the clinicopathological features, diagnosis and differential diagnosis of pulmonary extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT).
Methods:
Eleven cases of newly diagnosed (10 puncture biopsies and 1 transbronchial biopsy), previously untreated pulmonary ENKTL-NT were collected at the First Affiliated Hospital of Zhengzhou University, from August 2013 to November 2018. The clinicopathological features including histomorphology, immunohistochemistry and in situ hybridization were collected and analyzed.
Results:
Among the 11 cases, 8 were males and 3 were females, with a male to female ratio of 8∶3.The age range was from 30 to 74 years, with an average of 48 years and a median of 43 years. Tumors involved bilateral lung lobes in 8 cases, the upper left lobe in 1 case, lower left lobe in 1 case, and upper right lobe in 1 case. Main clinical symptoms included fever, often accompanied by cough, and bloody sputum in most cases. All cases were stage Ⅳ E. Histological features included scattered or focal aggregates of marked pleomorphic tumor lymphocytes, accompanied by necrosis and heavy admixture of inflammatory cells. In a few cases, diffuse neoplastic lymphocytes or vascular central and destructive infiltrations were seen. Tumor cells in most cases expressed CD3ε, CD3, CD43, CD56, TIA-1, granzyme B, but did not express CD20, CD79a, and CD5. Ki-67 index ranged from 40%to 90%.All cases were positive for EBER by in situ hybridization. Four of five patients died during follow-up with a survival period of only 1 week to 13 months.
Conclusions
Pulmonary ENKTL-NT is rare, high grade malignancy with a poor prognosis. Misdiagnosis is common due to lesional necrosis and heterogeneous cell components. Immunohistochemistry and EBER in situ hybridization are essential for accurate diagnosis.
9. A comparison study of two channels during MIS-TLIF in degenerative lumbar spinal stenosis treatment
Shixue LI ; Wei ZHANG ; Yapeng SUN ; Fei ZHANG ; Hao CUI ; Yuan GAO ; Jiaqi LI ; Zeyang LI ; Xianzheng WANG
Chinese Journal of Orthopaedics 2019;39(20):1275-1284
Objective:
To compare the clinical effects between minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) assisted by Microendoscopic discectomy (MED) and Quadrant for the treatment of degenerative lumbar spinal stenosis (DLSS).
Methods:
All of 59 patients suffered from DLSS treated surgically from May 2015 to October 2017 were reviewed. According to the surgery method, all cases were divided into MED group (27 cases) and Quadrant channel group (32 cases). All patients were followed up for an average of 18.5 months (11-29 months). Comparison was made on the operative time, intraoperative blood loss, postoperative drainage, postoperative time in bed, postoperative creatine kinase (CK), fusion rate and the degree of muscle fibrosis shown in MRI, as well as visual analogue scale (VAS)score and Oswestry dysfunction index (ODI) score in two groups.
Results:
The duration of operation in MED group was significantly longer than that in Quadrant group (161.7±22.4 min
10.Pulmonary extranodal NK/T?cell lymphoma, nasal type: a clinicopathological analysis of eleven cases
Xianzheng GAO ; Jianguo WEI ; Shenglei LI ; Guannan WANG ; Jing HAN ; Wugan ZHAO ; Yilin XIE ; Wencai LI
Chinese Journal of Pathology 2019;48(6):433-437
Objective To investigate the clinicopathological features, diagnosis and differential diagnosis of pulmonary extranodal NK/T‐cell lymphoma,nasal type (ENKTL‐NT).Methods Eleven cases of newly diagnosed (10 puncture biopsies and 1 transbronchial biopsy), previously untreated pulmonary ENKTL‐NT were collected at the First Affiliated Hospital of Zhengzhou University, from August 2013 to November 2018. The clinicopathological features including histomorphology, immunohistochemistry and in situ hybridization were collected and analyzed. Results Among the 11 cases, 8 were males and 3 were females, with a male to female ratio of 8∶3.The age range was from 30 to 74 years, with an average of 48 years and a median of 43 years. Tumors involved bilateral lung lobes in 8 cases, the upper left lobe in 1 case, lower left lobe in 1 case, and upper right lobe in 1 case. Main clinical symptoms included fever, often accompanied by cough, and bloody sputum in most cases. All cases were stage ⅣE. Histological features included scattered or focal aggregates of marked pleomorphic tumor lymphocytes, accompanied by necrosis and heavy admixture of inflammatory cells. In a few cases, diffuse neoplastic lymphocytes or vascular central and destructive infiltrations were seen. Tumor cells in most cases expressed CD3ε, CD3, CD43, CD56, TIA‐1, granzyme B, but did not express CD20, CD79a, and CD5. Ki‐67 index ranged from 40%to 90%.All cases were positive for EBER by in situ hybridization. Four of five patients died during follow‐up with a survival period of only 1 week to 13 months. Conclusions Pulmonary ENKTL‐NT is rare, high grade malignancy with a poor prognosis. Misdiagnosis is common due to lesional necrosis and heterogeneous cell components. Immunohistochemistry and EBER in situ hybridization are essential for accurate diagnosis.

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