1.DICER1-mutant primary intracranial sarcoma: analysis of five cases
Zejun DUAN ; Jing FENG ; Junping ZHANG ; Changxiang YAN ; Fangjun LIU ; Zhong MA ; Lei XIANG ; Zejuan HU ; Junjie YANG ; Xueling QI
Chinese Journal of Pathology 2025;54(6):632-639
Objective:To investigate the clinicopathological characteristics and differential diagnosis of DICER1-mutant primary intracranial sarcoma.Methods:Five cases of DICER1-mutant primary intracranial sarcoma at Sanbo Brain Hospital, Capital Medical University, Beijing, China during May 2013 to November 2024 were collected. The clinical and imaging data were retrieved. Histological evaluation, immunohistochemical staining and next generation sequencing were performed. Additionally, a literature review was conducted.Results:All five DICER1-mutant primary intracranial sarcomas were located in the supratentorial region, with one case involving the basal ganglia. There were two males and three females. The median age at diagnosis was 25 (14.0, 30.5) years. Morphologically, they were characterized by high-grade spindle cell sarcoma, with brisk mitotic activity and cytoplasmic eosinophilic globules. Myxoid degeneration, necrosis, and invasion into surrounding brain tissue were observed in some cases. The tumor cells showed diffuse staining of vimentin and variable expression of myogenic marker (desmin), with or without focal MyoD1 and/or Myogenin expression. Four tumors exhibited diffuse, strong expression of TLE1 and p53, while only three tumors showed loss of ATRX (nuclear) expression. Two cases showed mosaic loss of H3K27me3 expression in neoplastic cells. The Ki-67 proliferation index was high (40%-80%). Various neuronal markers, such as synaptophysin, NF, SOX2 and MAP2, were expressed in all tumor samples. Genetically, all tumors samples harbored biallelic abnormalities of DICER1. One was a hotspot missense mutation in the RNase Ⅲb domain within exon 25 on one allele (p.E1813 or p.D1810), while the other allele had mutations including a germline mutation in one case, a somatic mutation in two cases, and a copy number deletion in two cases. In addition, these sarcomas showed alterations in TP53 (4/5), ATRX (3/5), and the genes of the mitogen-activated protein kinase pathway (3/5). Finally, all five cases were diagnosed as DICER1-mutant primary intracranial sarcoma. All patients underwent craniotomy that led to complete tumor resection. Three patients received adjuvant radiotherapy and chemotherapy, with progression-free survival time of 28, 48, and 50 months, respectively. Patient 2 succumbed to the tumor after 3 months post-surgery due to rapid progression and tumor dissemination. Patient 5 was lost to follow-up 3 months after the surgery.Conclusions:DICER1-mutant primary intracranial sarcoma is a newly defined tumor entity in the fifth edition of the World Health Organization Classification of Central Nervous System Tumors, and commonly occurs in children and young adults. High-grade malignant spindle cells are their typical morphological feature. Eosinophilic cytoplasmic globules and myogenic differentiation can help establish the diagnosis. This study suggests that DICER1-mutant primary intracranial sarcomas exhibit immunophenotypic neuronal differentiation. Rendering the diagnosis of DICER1-mutant primary intracranial sarcoma largely relies on detecting DICER1 pathogenic alterations or DNA methylation profiling.
2.DICER1-mutant primary intracranial sarcoma: analysis of five cases
Zejun DUAN ; Jing FENG ; Junping ZHANG ; Changxiang YAN ; Fangjun LIU ; Zhong MA ; Lei XIANG ; Zejuan HU ; Junjie YANG ; Xueling QI
Chinese Journal of Pathology 2025;54(6):632-639
Objective:To investigate the clinicopathological characteristics and differential diagnosis of DICER1-mutant primary intracranial sarcoma.Methods:Five cases of DICER1-mutant primary intracranial sarcoma at Sanbo Brain Hospital, Capital Medical University, Beijing, China during May 2013 to November 2024 were collected. The clinical and imaging data were retrieved. Histological evaluation, immunohistochemical staining and next generation sequencing were performed. Additionally, a literature review was conducted.Results:All five DICER1-mutant primary intracranial sarcomas were located in the supratentorial region, with one case involving the basal ganglia. There were two males and three females. The median age at diagnosis was 25 (14.0, 30.5) years. Morphologically, they were characterized by high-grade spindle cell sarcoma, with brisk mitotic activity and cytoplasmic eosinophilic globules. Myxoid degeneration, necrosis, and invasion into surrounding brain tissue were observed in some cases. The tumor cells showed diffuse staining of vimentin and variable expression of myogenic marker (desmin), with or without focal MyoD1 and/or Myogenin expression. Four tumors exhibited diffuse, strong expression of TLE1 and p53, while only three tumors showed loss of ATRX (nuclear) expression. Two cases showed mosaic loss of H3K27me3 expression in neoplastic cells. The Ki-67 proliferation index was high (40%-80%). Various neuronal markers, such as synaptophysin, NF, SOX2 and MAP2, were expressed in all tumor samples. Genetically, all tumors samples harbored biallelic abnormalities of DICER1. One was a hotspot missense mutation in the RNase Ⅲb domain within exon 25 on one allele (p.E1813 or p.D1810), while the other allele had mutations including a germline mutation in one case, a somatic mutation in two cases, and a copy number deletion in two cases. In addition, these sarcomas showed alterations in TP53 (4/5), ATRX (3/5), and the genes of the mitogen-activated protein kinase pathway (3/5). Finally, all five cases were diagnosed as DICER1-mutant primary intracranial sarcoma. All patients underwent craniotomy that led to complete tumor resection. Three patients received adjuvant radiotherapy and chemotherapy, with progression-free survival time of 28, 48, and 50 months, respectively. Patient 2 succumbed to the tumor after 3 months post-surgery due to rapid progression and tumor dissemination. Patient 5 was lost to follow-up 3 months after the surgery.Conclusions:DICER1-mutant primary intracranial sarcoma is a newly defined tumor entity in the fifth edition of the World Health Organization Classification of Central Nervous System Tumors, and commonly occurs in children and young adults. High-grade malignant spindle cells are their typical morphological feature. Eosinophilic cytoplasmic globules and myogenic differentiation can help establish the diagnosis. This study suggests that DICER1-mutant primary intracranial sarcomas exhibit immunophenotypic neuronal differentiation. Rendering the diagnosis of DICER1-mutant primary intracranial sarcoma largely relies on detecting DICER1 pathogenic alterations or DNA methylation profiling.
3.Finite element analysis of intramedullary nail and locking plate fixation for proximal humeral fractures
Fangjun YANG ; Fuyang WANG ; Yun SU ; Yongze WANG ; Cunheng YANG ; Tienan WANG
Chinese Journal of Tissue Engineering Research 2024;28(21):3313-3318
BACKGROUND:Intramedullary nails and locking plates are widely used in the treatment of proximal humeral fractures,but there is no consensus on the choice of internal fixation. OBJECTIVE:To compare the biomechanical stability of intramedullary nails and locking plates in the treatment of two-part and three-part proximal humeral fractures by finite element analysis. METHODS:CT data of the humerus of a volunteer were collected and imported into Minics 21.0,Geomagic Wrap,Soildwork 2017,and Abaqus 2021 to establish finite element models of two-part and three-part fractures treated with two internal fixation methods,respectively.Group A:two-part fracture fixed with intramedullary nail model;group B:two-part fracture fixed with locking plate model;group C:three-part fracture fixed with intramedullary nail model;group D:three-part fracture fixed with locking plate model.The stress distribution,displacement degree,and maximum value of the humerus and internal fixation were compared and analyzed. RESULTS AND CONCLUSION:(1)The maximum stress and maximum displacement of the humerus were the smallest in the model of group A,and the maximum stress and maximum displacement of the humerus were the largest in the model of group D.The stress of the locking plate group was mainly concentrated in the medial inferior part of the humeral head and the screw hole area,while the stress of the intramedullary nail group was mainly concentrated around the fracture line and the lateral inferior part of the surgical neck of the humerus.There is no significant difference in displacement distribution between the two.It is mainly concentrated in the distal humerus.(2)The maximum stress value of the intramedullary nail was the lowest in the model of group A,and the maximum stress value of the locking plate was the highest in the model of group D.The maximum stress of the two internal fixations was mainly concentrated in the talar screw and the connection with the internal fixation.The stress cloud distribution of the locking steel plate was concentrated,while the stress cloud distribution of the intramedullary nail was more uniform.(3)The results showed that compared with the locking plate,the intramedullary nail had more biomechanical advantages,and this advantage was more obvious in three-part fractures.
4.Clinical characteristics of acute renal infarction: an analysis of 15 cases
Yinyin XIE ; Zhanwu LI ; Xiaozhou WANG ; Lei JIANG ; Qiang LIU ; Hao QIN ; Fangjun YANG
Chinese Journal of General Practitioners 2023;22(7):728-731
Clinical data of 15 patients diagnosed with acute renal infarction (ARI) in Affiliated Zhongshan Hospital of Dalian University from Jan 2011 to Dec 2021 were retrospectively analyzed. Of the included 15 patients, there were 14 cases of cardiac origin and 1 case of antiphospholipid syndrome. We found that there were 12 cases of atrial fibrillation, 2 cases of atrial premature beats, 12 cases of elevated level of D-dimer, 15 cases of elevated level of LDH, 11 cases of positive urine occult blood and positive urine protein. Among the 15 patients, catheter-directed thrombolysis was performed in 4 cases, of which 3 cases were revascularized successfully, intravenous thrombolysis in 2 cases and alone anticoagulation therapy in 9 cases. It is suggested that CECT or CTA can assist the early diagnosis of ARI especially in patients with acute onset and persistent abdominal pain with high risk factors of thromboembolism, high levels of LDH, microscopic hematuria and/or proteinuria. Despite prolonged embolic ischemia, try to reconstruct blood flow to save the kidney as much as possible. Late standardized anticoagulant therapy is of critical importance to prevent recurrent embolic episodes.
5.Application of ultrasound monitoring optic nerve sheath diameter in diagnosis and treatment of adult patients with intracranial hypertension
Chengyin LIU ; Xiang′en SHI ; Youquan WANG ; Jinju YANG ; Yuming SUN ; Fangjun LIU ; Hui SHEN ; Fuzheng ZHANG
Chinese Journal of Postgraduates of Medicine 2022;45(5):403-406
Objective:To investigate the effect of ultrasound measurement of optic nerve sheath diameter (ONSD) in adult patients with elevated intracranial pressure (ICP).Method:From June 2017 to March 2020, A total of 64 patients (32 patients with elevated ICP and 32 patients with normal ICP) were placed with invasive intracranial pressure monitoring probe in Beijing Pinggu Hospital. Their ICP and ONSD were continuously monitored. Thirty-two healthy volunteers were recruited as control group to check ONSD. The correlation between ONSD and ICP, and the changes of ICP and ONSD after osmotic therapy were observed.Results:The ONSD in ICP increased group was significantly higher than that in normal ICP group: (5.77 ± 0.3) mm vs. (5.01 ± 0.1) mm, with statistical difference ( P<0.05), and there was a positive correlation between ONSD and ICP. There was no significant difference in ONSD between normal ICP group and control group ( P>0.05). Conclusions:Ultrasound monitoring ONSD can reflect the level of ICP and evaluate the effect of osmotic therapy and the prognosis of patients. Bedside ultrasound examination of optic nerve sheath diameter could be used to judge ICP and to evaluate the curative effect of osmotic therapy, with high clinical application value.
6.Differential diagnostic value of intravoxel incoherent motion diffusion-weighted imaging combined with serum indicators for prostate cancer
Liguang YANG ; Yuzhu JIA ; Fangjun LUO ; Jianju FENG
Chinese Journal of Primary Medicine and Pharmacy 2022;29(3):387-391
Objective:To investigate the differential diagnostic value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) combined with serum indicators for prostate cancer.Methods:We recruited 97 patients with prostate diseases who received treatment in Zhuji People's Hospital from March 2018 to September 2020 for this study. Patients with prostate cancer were included in the study group ( n = 46) and patients with benign prostatic hyperplasia in the control group ( n = 51). All patients were subject to IVIM-DWI and serum early prostate cancer antigen-2 level detection alone or in combination. The sensitivity, specificity, accuracy, and diagnostic efficacy of IVIM-DWI and serum early prostate cancer antigen-2 level detection alone or in combination were compared between the two groups. Results:D and f values in the study group were (0.50 ± 0.14) × 10 -3 mm 2/s and (0.35 ± 0.11), respectively, which were significantly lower than those in the control group [(0.71 ± 0.12) × 10 -3 mm 2/s, (0.59 ± 0.08), t = 7.95, 12.37, both P < 0.001]. D* value and serum early prostate cancer antigen-2 level in the study group were (6.24 ± 1.90) × 10 -3 mm 2/s and (62.5 ± 18.3) μg/L, which were significantly higher than those in the control group [(4.08 ± 1.34) × 10 -3 mm 2/s, (17.3 ± 6.8) μg/L, t = -6.52, -16.43, both P < 0.001]. The overall detection rate, sensitivity, specificity, and accuracy of IVIM-DWI combined with serum early prostate cancer antigen-2 level detection for prostate cancer were 53.6% (52/97), 97.8% (45/46), 74.5% (38/51), and 85.6% (83/97), respectively. A receiver operating characteristic curve analysis showed that the sensitivity of IVIM-DWI combined with serum indicators in the diagnosis of prostate cancer and the area under the curve were greater than those produced by IVIM-DWI and serum early prostate cancer antigen-2 level detection alone (both P < 0.05). Conclusion:IVIM-DWI combined with serum early prostate cancer antigen-2 level detection has a higher sensitivity in the diagnosis of prostate cancer than monotherapy. The combined therapy provides a new perspective for the differential diagnosis of prostate cancer and has a certain clinical value.
7.Application of anterior clinoid grinding in sellar region tumors and ophthalmic/superior clinoid process aneurysms of internal carotid artery
Jie ZHANG ; Zhongqing ZHOU ; Xiang′en SHI ; Yang YANG ; Weimin NI ; Zaitao YU ; Yuming SUN ; Fangjun LIU ; Hai QIAN
Chinese Journal of Postgraduates of Medicine 2022;45(8):681-685
Objective:To evaluate the clinical effect of anterior clinoid process grinding in the treatment of ophthalmic / superior clinoid process aneurysms and sellar tumors.Methods:The clinical data of 16 patients who underwent anterior clinoid process grinding in Sanbo Brain Hospital, Capital Medical University from January 2015 to July 2021 were analyzed retrospectively. There were 1 patient with recurrent craniopharyngioma, 1 patient with recurrent pituitary adenoma, 13 patients with aneurysms, and 1 patient with suprasellar granulosa cell tumor combined with ophthalmic aneurysm of right internal carotid artery. The Modified Rankin Scale (mRS) score was used to evaluate the situation at discharge and in the medium-and-long term.Results:Sixteen patients underwent anterior clinoidprocess grinding. At discharge and the latest follow-up, the mRS scores of the patients were 0-2. A total of 15 aneurysms were treated, and there were no symptoms of visual loss or visual field defect after operation. No cerebrospinal fluid leakage occurred in all patients.Conclusions:The grinding of anterior clinoid process can effectively and fully stretch the optic nerve and internal carotid artery, and can observe the tumor neck at the lower end of pituitary stalk and the ocular segment/superior clinoid process of internal carotid artery under direct vision. It is one of the important auxiliary methods for the treatment of sellar lesions.
8.Effects of isoflurane and pentobarbital on the establishment of subarachnoid block model in rats
Fangjun WANG ; Jianhua HU ; Yujiao YANG ; Yong WAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2017;38(3):462-465
Objective To compare the effects of isoflurane and pentobarbital on the establishment of subarachnoid block model in rats.Methods 60 SD rats aged 4 months were randomly divided into Group A (n =30) and Group B (n=30).Rats in Group A received intraperitoncal injection of 10 g/L pentobarbital sodium solution 30 mg/kg and 1/4 of the initial dosage was added according to the operation effect.The induction and maintenance of anesthesia were achieved by isoflurane inhalation in Group B during operation.We recorded the time of anesthesia induction,quality of anesthesia,time of anesthesia,time of operation,and recovery time.The heart rate,respiration frequency,temperature,and saturation of blood oxygen were recorded during operation.We compared death from anesthesia and success of modeling in the two groups.Results There was no significant difference between the groups with regard to age,weight,body temperature or saturation of blood oxygen (P> 0.05).Compared to Group B,heart rate decreased 1-60 minutes after anesthesia and respiration frequency decreased 5 minutes after anesthesia in Group A (P<0.05).The time of anesthesia induction,time of anesthesia,time of operation,and recovery time were shorter in Group B (P<0.05).The quality of anesthesia was better in Group B (P<0.05).The success rate of modeling was higher but mortality rate of anesthesia was lower in Group B than in Group A (P<0.05).Conclusion Compared with intraperitoneal injection of pentobarbital sodium,isoflurane inhalation can provide a better anesthetic effect during the operation to establish a rat model of subarachnoid block.
9.Minimum effective local anesthetic dose of intra-articular ropivacaine with dexmedetomidine for analgesia in patients undergoing knee arthroscopy
Fangjun WANG ; Yan HE ; Shuang YANG ; Hongqiong LI
The Journal of Clinical Anesthesiology 2016;32(9):873-876
Objective To observe the minimum effective local anesthetic dose of intra-articular ropivacaine with dexmedetomidine for analgesia after knee arthroscopy in patients.Methods Seventy-two patients (35 males,37 females,aged 60-75 years,ASA grade Ⅰ or Ⅱ)undergoing knee arthro-scopy under total intravenous anesthesia were randomly divided into two groups (n =36 each):ropiv-acaine group (group R)and ropivacaine with dexmedetomidine group (group DR);Ropivacaine was injected intra-articularly in group C,and dexmedetomidine 1 μg/kg with ropivacaine was injected intra-articularly in group DR.ED50 of ropivacaine was determined by the sequence method.VAS score3 two hours after operation was rated as effective.The initial dose was 3 mg and according to the effective or ineffective results in previous patient,a dose of ropivacaine was decreased or increased 1.1 times to the previous patient.BP,HR,VAS Score,and OAA/S score were recorded five minutes preoperatively(T0 ),1 h (T1 ),2 h (T2 ),3 h (T3 ),6 h (T4 ),12 h (T5 ),24 h (T6 ),and 48 h (T7 ) after operation in two groups.Results There was no significant difference between the two groups with regard to the BP,HR,VAS Score,and OAA/S score.ED50 of ropivacaine for analgesia after knee arthroscopy was 0.31% (95%CI 0.30%-0.32%),and ED50 of ropivacaine with dexmedetomi-dine for analgesia after knee arthroscopy was 0.14% (95% CI 0.14%-0.1 5%). Conclusion Intra-articular administration of ropivacaine with dexmedetomidine could provide superior postoperative analgesia.The dose of ropivacaine for analgesia after knee arthroscopy should be reduced when combined with dexmedetomidine in patients.
10.Dynamic changes of rat cartilage ultrastructure in the early process of papain-induced knee osteoarthritis
Wenxiu DUAN ; Zongbao WANG ; Hao ZHANG ; Zhiwei YANG ; Zhilun HU ; Fangjun XU ; Yalin XU ; Dan LIU ; Yan XIE
Chinese Journal of Tissue Engineering Research 2015;(18):2789-2793
BACKGROUND:Papain-induced rat knee osteoarthritis is a common modeling method, which can obtain a stable osteoarthritis model.
OBJECTIVE:To observe the change of ultrastructure of chondrocytes in the early process of papain-induced rat knee osteoarthritis under transmission electron microscope.
METHODS:A total of 18 Sprague-Dawley rats were randomly divided into three groups. Two rats were considered as a normal control group, without intervention. The mixture of papain and L-cysteine was injected in right knee joint cavity of 16 rats to induce osteoarthritis models (osteoarthritis model group). Physiological saline was injected in the left side (physiological saline control group). At 1, 2, 4 and 6 weeks after injection, samples were col ected. Transmission electron microscope was used to observe the change of cartilage ultrastructure of the medial femoral condyle joint.
RESULTS AND CONCLUSION:For the normal control group and physiological saline control group, their cytoplasm contained abundant rough endoplasmic reticulum and mitochondria. After 1 week of injection,
mitochondria vacuoles and light expanded rough endoplasmic reticulum were visible. Two weeks later, lipid droplets appeared, mitochondria degeneration was distinct, vacuolization was serious and its number was reduced, and rough endoplasmic reticulum expansion was obvious. Four weeks later, lipid droplets became increased, and the number of mitochondria decreased significantly. Most of the rough endoplasmic reticula were highly expanded, and part of the rough endoplasmic reticula were dissolved and fractured. Six weeks later, a number of lipid droplets were visible in cytoplasm, most of the mitochondria disappeared, only a smal number of mitochondria existed, and most of the rough endoplasmic reticula were dissolved and fractured. These results confirmed that cartilage ultrastructure changes gradual y in the early process of papain-induced rat knee osteoarthritis under transmission electron microscope.

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