Objective:To investigate the clinicopathological and molecular genetic characteristics of the neuroepithelial tumor with PATZ1 fusion (NET-PATZ1).Methods:Five cases of NET-PATZ1 diagnosed at the Sanbo Brain Hospital of Capital Medical University, Beijing, China from January 2020 to October 2024 were collected. The clinical, prognostic, imaging, histological and immunohistochemical features and the results of next-generation sequencing (DNA and RNA) of these 5 patients were collected and analyzed. Relevant literature was also reviewed for discussion.Results:Among the 5 cases, there were 4 females and 1 male, with a median age of 9.0 (6.5, 15.5) years. The tumors all occurred in the supratentorial cerebral hemispheres, including the frontal lobe, parietal lobe, lateral ventricle, and thalamus. There were diverse histological features. Two cases exhibited the characteristics of high-grade neuroepithelial tumors, while 3 cases showed those of low-grade neuroepithelial tumors. The tumor cells were mostly arranged in a rosette-like pattern around small blood vessel. The background was rich in vascular components or microvascular hyperplasia. Immunohistochemistry showed that the tumor cells diffusely expressed MAP2 and Vimentin, and had various expression of S-100 protein, GFAP, Olig2, NG2 and CD99, and cytoplasmic and perinuclear expression of Syn. At the genomic level, all cases had PATZ1 gene fusion variants, and the gene breakpoints were all located in exon 1. Four cases had fusion with the EWSR1 gene, and 1 case had fusion with the MN1 gene. The 5 patients all underwent craniotomy for tumor resection. The pathological diagnosis was NET-PATZ1. All cases had no recurrence or metastasis at the end of follow-up except that Case 3 developed spinal cord metastasis 11 months after the surgery.Conclusions:NET-PATZ1 is commonly found in children and adolescents, with diverse histological features. The tumor cells typically arrange in rosette-like patterns, and the background is rich in vascular components or microvascular hyperplasia. Tumor cells express glial cell-related markers to varying degrees, and co-expression of NG2 and CD34 is suggestive of its diagnosis. The establishment of a pathological diagnosis relies on the detection of PATZ1 fusion variations through genetic testing or a DNA methylation profile of NET-PATZ1.

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.

Objective To develop a machine learning model integrating preoperative chest CT radiomic features with clinical data for predicting 5-year postoperative recurrence risk in stage Ⅰ non-small cell lung cancer(NSCLC)patients undergoing surgical resection.Methods A total of 217 patients with pathologically confirmed stage Ⅰ NSCLC(selected from 778 initially screened cases based on our inclusion and exclusion criteria)treated in Army Medical Center of PLA between January 2014 and December 2019 were retrospectively enrolled,including 53 recurrence cases and 164 non-recurrence cases within 5-year follow-up.They were randomly divided into a training set(n=173)and a validation set(n=44)in a ratio of 8:2.Radiomic models were established based on extracted features from tumor-dominant regions of interest(ROI)on CT images,while clinical models were developed using demographic characteristics and preoperative laboratory examinations.A combined model was further constructed by integrating both feature sets,and model performance was compared to identify the optimal predictive model.Results This study screened the features from non-contrast CT images and ultimately selected 7 radiomic features for constructing radiomic model.Among 6 machine learning algorithms,the adaptive boosting(Adaboost)model demonstrated the best overall predictive performance,with an area under the curve(AUC)of 0.866(95%CI:0.808～0.923;accuracy:0.832,specificity:0.884)in the training set and of 0.806(95%CI:0.630～0.983;accuracy:0.795,specificity:0.971)in the validation set.Univariate and multivariate logistic regression analyses identified 4 clinical features for clinical model construction.The clinical model achieved an AUC value of 0.874(95%CI:0.821～0.928;accuracy:0.827,specificity:0.891)in the training set and 0.813(95%CI:0.677～0.948;accuracy:0.636,specificity:0.600)in the validation set.By integrating the 7 radiomic features and 4 clinical features using a feature-level fusion strategy,the combined model exhibited further improved predictive performance,with an AUC value of 0.953(95%CI:0.924～0.983;accuracy:0.884,specificity:0.860)and 0.852(95%CI:0.729～0.976;accuracy:0.682,specificity:0.629),respectively in the training set and the validation set.Conclusion The combined model integrating preoperative CT radiomic features with clinical risk factors may provide an evidence-based framework for evaluating 5-year postoperative recurrence risk in stage Ⅰ NSCLC patients.

Objective:To investigate the clinicopathological and molecular genetic characteristics of the neuroepithelial tumor with PATZ1 fusion (NET-PATZ1).Methods:Five cases of NET-PATZ1 diagnosed at the Sanbo Brain Hospital of Capital Medical University, Beijing, China from January 2020 to October 2024 were collected. The clinical, prognostic, imaging, histological and immunohistochemical features and the results of next-generation sequencing (DNA and RNA) of these 5 patients were collected and analyzed. Relevant literature was also reviewed for discussion.Results:Among the 5 cases, there were 4 females and 1 male, with a median age of 9.0 (6.5, 15.5) years. The tumors all occurred in the supratentorial cerebral hemispheres, including the frontal lobe, parietal lobe, lateral ventricle, and thalamus. There were diverse histological features. Two cases exhibited the characteristics of high-grade neuroepithelial tumors, while 3 cases showed those of low-grade neuroepithelial tumors. The tumor cells were mostly arranged in a rosette-like pattern around small blood vessel. The background was rich in vascular components or microvascular hyperplasia. Immunohistochemistry showed that the tumor cells diffusely expressed MAP2 and Vimentin, and had various expression of S-100 protein, GFAP, Olig2, NG2 and CD99, and cytoplasmic and perinuclear expression of Syn. At the genomic level, all cases had PATZ1 gene fusion variants, and the gene breakpoints were all located in exon 1. Four cases had fusion with the EWSR1 gene, and 1 case had fusion with the MN1 gene. The 5 patients all underwent craniotomy for tumor resection. The pathological diagnosis was NET-PATZ1. All cases had no recurrence or metastasis at the end of follow-up except that Case 3 developed spinal cord metastasis 11 months after the surgery.Conclusions:NET-PATZ1 is commonly found in children and adolescents, with diverse histological features. The tumor cells typically arrange in rosette-like patterns, and the background is rich in vascular components or microvascular hyperplasia. Tumor cells express glial cell-related markers to varying degrees, and co-expression of NG2 and CD34 is suggestive of its diagnosis. The establishment of a pathological diagnosis relies on the detection of PATZ1 fusion variations through genetic testing or a DNA methylation profile of NET-PATZ1.

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.

[Objective]To investigate the implication of modified Duanggui Buxue Decoction on the immune function of normal mice.[Methods]A total of 120 BALB/c mice were stochastically divided into three groups,immunization group Ⅰ,immunization group Ⅱ and immunization group Ⅲ.According to body weight,each immune group was randomly divided into 4 groups:normal control group,modified Duanggui Buxue Decoction 1.4 g·kg-1 group,modified Duanggui Buxue Decoction 1.9 g·kg-1 group,modified Duanggui Buxue Decoction 2.3 g·kg-1 group.After being gavaged for 30 d,for immune group Ⅰ:test the behaviors,spleen index,thymus index,the proliferative capacity of splenic T lymphocytes,NK cell activities,blood indices,serum levels of immunoglobulin M(IgM)and immunoglobulin G(IgG),the ratios of T and B lymphocytes in the peripheral blood and spleen.Immune group Ⅱ:number of hemolytic vacant spots and 50%haemolysis requirement for complement(HC50).Immune group Ⅲ:phagocytosis of phagocytic chicken erythrocytes in mice peritoneal macrophages and expression of CD4 and CD8 in spleen.[Results]Compared with the normal control group,all three doses of modified Duanggui Buxue Decoction significantly elevated the number of voluntary activities and grip strength,spleen index and thymus index of mice(P<0.05,P<0.01);enhanced the proliferative capacity of splenic lymphocytes and the activity of NK cells(P<0.01);increased the number of hemolytic vacant spots,HC50,the phagocytosis rate of chicken erythrocytes and phagocytosis index of the peritoneal macrophage(P<0.01);elevated whole blood lymphocyte(LYMPH),white blood cell(WBC)and red blood cell(RBC)counts,and serum IgM and IgG content(P<0.05,P<0.01);and decreased the proportions of CD3+T and CD8+T cells in blood and spleen,and decreased the amount of CD8 positive expression(P<0.05,P<0.01).Elevated peripheral blood CD19+B cell percentage,peripheral blood and spleen CD4+/CD8+ratio and spleen CD4/CD8 positive expression ratio(P<0.05,P<0.01).[Conclusion]The modified Duanggui Buxue Decoction has the function of enhancing specific immunity and non-specific immunity,which contributes to enhancing immunity.

Objective To explore the potential value of coagulation indicators and their combinations for metastasis and postoperative recurrence in renal cell carcinoma(RCC)patients.Methods A total of 39 RCC patients with metastasis and postoperative recurrence were enrolled,and the controls groups included 64 RCC patients without metastasis,15 patients with renal vascular leiomyoma/oncocy-toma and 118 patients with renal cysts.All the patients were diagnosed and hospitalized in the Department of Urology of Nanjing Hospi-tal of Chinese Medicine affiliated with Nanjing University of Chinese Medicine and Jinling Hospital affiliated with Nanjing University School of Medicine from January 2018 to June 2024.The coagulation indicators in the blood samples were measured.The levels of plas-ma prothrombin time(PT),activated partial thromboplastin time(APTT),thrombin time(TT)and fibrinogen(Fib)were analyzed by clotting method.The levels of fibrinogen degradation products(FDP)and D-Dimer(DD)were analyzed by immunological turbidim-etry assay,and the levels of antithrombin Ⅲ(AT3)were analyzed by chromogenic substrate method,respectively.The differences of coagulation indicators between RCC patients with metastasis and postoperative recurrence and the controls were assessed by Mann-Whit-ney U test.The potential value of coagulation indicators and their combinations for predicating metastasis and postoperative recurrence in RCC patients was evaluated through Logistic regression and ROC curve analysis.Results The plasma levels of the seven coagulation indicators showed significant differences between the patients with RCC metastatic/recurrent and the controls(all with P＜0.05).The results of ROC curve analysis showed that the plasma levels of all the 7 coagulation index could distinguish the metastatic/recurrent RCC patients from the controls,and the DD level showed the highest value with the AUCROC=0.913(95％CI:0.859 to 0.967).Multi-ple logistic regression analysis revealed that the plasma levels of Fib,FDP,DD,and AT3 were associated with RCC metastasis/recur-rence.Logistic regression analysis combined with ROC curve analysis revealed that the panel of Fib,FDP,DD and AT3 had the best performance for discriminating RCC metastasis/recurrence along with the AUCROC of 0.920(95％CI:0.865 to 0.974).Conclusion Alterations of the levels of plasma Fib,DD,FDP and AT3 may be closely related to postoperative recurrence and metastasis in RCC patients,and the panel of Fib,FDP,DD and AT3 has the potential to serve as the monitoring and evaluation indicators for RCC recur-rence and metastasis.

ObjectiveTo investigate the effect of Yunkang oral liquid on postpartum kidney deficiency in mice. MethodPostpartum mice were randomized into model and low-dose （6 mL·kg^-1）， medium-dose （9 mL·kg^-1）， and high-dose （12 mL·kg^-1） Yunkang oral liquid groups. The mouse model of postpartum kidney deficiency was established by sleep deprivation combined with forced swimming. Another 9 female ICR mice were selected as the normal control group. The mice were administrated with Yunkang oral liquid during the period of modeling. The levels of estradiol （E₂）， progesterone （P）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH） in the serum were measured by the enzyme-linked immunosorbent assay. The morphological changes of ovaries and uterus were observed by hematoxylin-eosin （HE） staining， and the expression of transforming growth factor （TGF）-β and Smad2/3 was determined by immunohistochemistry and Western blotting. ResultThe mice in the model group showed prolonged estrous cycle， reduced voluntary activity， dorsal temperature， grip strength， and bone strength， and whitening tongue coating. Compared with the model group， Yunkang oral liquid shortened the estrous cycle， increased the voluntary activity， dorsal temperature， grip strength， and bone strength， and alleviated the whitening of tongue coating. Moreover， it elevated the E₂ and P levels and lowered the FSH and LH levels in the serum， decreased ovarian follicular atresia rate， promoted uterine repair， and down-regulated the expression of TGF-β and Smad2/3 in the ovarian and uterine tissues. ConclusionYunkang oral liquid can ameliorate postpartum kidney deficiency in mice by regulating the TGF-β/Smads signaling pathway.

Objective To explore the potential value of coagulation indicators and their combinations for metastasis and postoperative recurrence in renal cell carcinoma(RCC)patients.Methods A total of 39 RCC patients with metastasis and postoperative recurrence were enrolled,and the controls groups included 64 RCC patients without metastasis,15 patients with renal vascular leiomyoma/oncocy-toma and 118 patients with renal cysts.All the patients were diagnosed and hospitalized in the Department of Urology of Nanjing Hospi-tal of Chinese Medicine affiliated with Nanjing University of Chinese Medicine and Jinling Hospital affiliated with Nanjing University School of Medicine from January 2018 to June 2024.The coagulation indicators in the blood samples were measured.The levels of plas-ma prothrombin time(PT),activated partial thromboplastin time(APTT),thrombin time(TT)and fibrinogen(Fib)were analyzed by clotting method.The levels of fibrinogen degradation products(FDP)and D-Dimer(DD)were analyzed by immunological turbidim-etry assay,and the levels of antithrombin Ⅲ(AT3)were analyzed by chromogenic substrate method,respectively.The differences of coagulation indicators between RCC patients with metastasis and postoperative recurrence and the controls were assessed by Mann-Whit-ney U test.The potential value of coagulation indicators and their combinations for predicating metastasis and postoperative recurrence in RCC patients was evaluated through Logistic regression and ROC curve analysis.Results The plasma levels of the seven coagulation indicators showed significant differences between the patients with RCC metastatic/recurrent and the controls(all with P＜0.05).The results of ROC curve analysis showed that the plasma levels of all the 7 coagulation index could distinguish the metastatic/recurrent RCC patients from the controls,and the DD level showed the highest value with the AUCROC=0.913(95％CI:0.859 to 0.967).Multi-ple logistic regression analysis revealed that the plasma levels of Fib,FDP,DD,and AT3 were associated with RCC metastasis/recur-rence.Logistic regression analysis combined with ROC curve analysis revealed that the panel of Fib,FDP,DD and AT3 had the best performance for discriminating RCC metastasis/recurrence along with the AUCROC of 0.920(95％CI:0.865 to 0.974).Conclusion Alterations of the levels of plasma Fib,DD,FDP and AT3 may be closely related to postoperative recurrence and metastasis in RCC patients,and the panel of Fib,FDP,DD and AT3 has the potential to serve as the monitoring and evaluation indicators for RCC recur-rence and metastasis.

OBJECTIVES: Hyperhomocysteinaemia (Hcy) is an independent risk factor for cardiovascular and cerebrovascular diseases. MicroRNA (miR)-18a-5p is closely related to cardiovascular diseases. This study aims to investigate the effects of miR-18a-5p on homocysteine (Hcy)-induced myocardial cells injury. METHODS: H9c2 cells were transfected with miR-18a-5p mimic/miR-18a-5p mimic negative control (NC) or combined with Hcy for intervention, and untreated cells were set as a control group. The transfection efficiency was verified by real-time RT-PCR, and cell counting kit-8 (CCK-8) assay was used to determine cell viability. Flow cytometry was used to detect apoptosis and reactive oxygen species (ROS) levels. Western blotting was performed to measure the protein levels of microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, Beclin1, p62, Bax, Bcl-2, and Notch2. Dual luciferase reporter assay was used to detect the interaction of miR-18a-5p with Notch2. RESULTS: Compared with the control, treatment with Hcy or transfection with miR-18a-5p mimic alone, or combined treatment with Hcy and miR-18a-5p mimic/miR-18a-5p mimic NC significantly reduced the H9c2 cell viability, promoted apoptosis and ROS production, up-regulated the expressions of Bax and Beclin, down-regulated the expressions of Bcl-2, p62, and Notch2, and increased the ratio of LC3-II/LC3-I (all P<0.05). Compared with the combined intervention of miR-18a-5p mimic NC and Hcy group, the above indexes were more significantly changed in the combined intervention of miR-18a-5p mimic and Hcy group, and the difference between the 2 groups was statistically significant (all P<0.05). There is a targeted binding between Notch2 and miR-18a-5p. CONCLUSIONS MiR-18a-5p could induce autophagy and apoptosis via increasing ROS production in cardiomyocytes, and aggravate Hcy-induced myocardial injury. Notch2 is a target of miR-18a-5p.
Apoptosis/genetics* ; Autophagy/genetics* ; bcl-2-Associated X Protein ; MicroRNAs/metabolism* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Reactive Oxygen Species ; Rats ; Animals ; Myocytes, Cardiac/drug effects* ; Homocysteine/adverse effects* ; Hyperhomocysteinemia