Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Purpose To investigate the clinicopathological features,diagnosis,differential diagnosis and molecular charac-teristics desmoid fibromatosis the breast(DFB).Methods The clinicopathological data and prognostic information of 26 pa-tients with desmoid fibromatosis of the breast were collected.Their clinical characteristics,histological morphologies,immu-nophenotypes and molecular characteristics were analyzed.Re-sults All the 26 patients were female,with a median age of 34.5 years and an average age of 36.8 years(range from 13 to 69 years).There were 10 cases in left breast,14 cases in right breast and 2 cases in bilateral breast.Isolated and painless breast masses were found in all patients,and 3 cases were ac-companied by nipple depression.Grossly,most of them showed a poorly circumscribed tan-white to gray mass with a trabeculated appearance.Microscopically,all the tumors were composed of mild spindle cells with varying intervals of collagen fiber bun-dles.The boundary between the tumor and the surrounding breast tissue was not clear,and the tumor cells infiltrated adja-cent tissues,such as breast ducts,lobules,adipose tissue,and skeletal muscle.Uniform spindle or oval cells formed in fascicles and interwoven,without atypical or polymorphism;the nuclear chromatin was sparse or vacuolar,with small nucleoli,but mito-ses were rare or absent.Nuclear accumulation of β-catenin was present in 20 of 26 tumors,SMA was variously positive in 20 of 26,desmin was focally positive in 6 of 26;CKpan,CK5/6,p63,CD34,CD10 and S-100 were all negative.The Ki67 index was 5％-10％.The gene mutations of CTNNB1 exon 3 were found in 18 of 26 by Sanger sequencing,including T41A(83.3％),S45P(11.1％)and S45F(5.6％).Two patients also had familial adenomatous polyposis.Local resection was performed in 23 cases,mastectomy was performed in 2 cases,and one case did not require any additional treatment after core needle biopsy.20 cases were followed up for 1-108 months,and no recurrence occurred.Conclusion Desmoid fibromatosis of the breast is rare,and can mimic breast cancer clinically,ra-diologically and histologically.It should be always considered in differential diagnosis for the spindle cell proliferations of the breast.A diagnosis of DFB can be achieved basing on the typi-cal histopathology,immunohistochemistry,history and gene se-quencing.

Objective:To explore the clinicopathological features, immunophenotype and molecular genetic characteristics of malignant solitary fibrous tumor (MSFT).Methods:Seven cases of MSFT were collected from the First Affiliated Hospital of Zhengzhou University from July 2018 to December 2020. Immunohistochemistry, RNA-based NGS and DNA-based NGS were performed. Results Among the 7 patients, there were 5 males and 2 females with a median age of 53 years (37-69 years). Two tumors located at skull base, and one in the tentorium of cerebellum, parietal occipital region, occipital area, chest and buttock respectively. The maximum diameter of the tumor was 2.5-20.0 cm. Microscopically, typical hemangiopericomatoid structures were noted; the tumor was cellular, fusiform or oval, very pleomorphic, with necrosis and high mitotic figures (>4/10 HPF). In some cases, classical solitary fibrous tumor morphology and dedifferentiated region were observed. Immunohistochemically, the tumor was positive for CD34 (6/7), STAT6 (7/7), bcl-2 (7/7), but negative for S-100 (7/7); CKpan or EMA was positive to varying degrees; mutated p53 was noted (3/7); Ki-67 positive index was more than 10%. NAB2-STAT6 gene fusion was typically detected in all the 7 cases. In 4 cases, ZNF415-FGFR1, COPG1-MET, IPO11-LRRC70_ncRNA-PLAG1 and Clorf198-CD274 (PD-L1) gene fusions were also detected. NOTCH1 mutation was found in 7 cases and TP53 mutation in 4 cases. TERT promoter mutations were not detected in all the cases. Conclusions:MSFT is rare and needs to be differentiated from many other spindle cell tumors. Especially when tumors express epithelial markers, they are easily misdiagnosed as sarcomatoid carcinoma and synovial sarcoma, etc. Immunohistochemistry and molecular detection of NAB2-STAT6 gene fusion have important diagnostic values. NOTCH1 and TP53 mutations may be associated with the progression of MSFT. Some patients have FGFR1 gene fusion and MET gene fusion, which may be potential therapeutic targets.

Objective:To study the clinicopathologic features and MYD88 L265P mutation status of intravascular large B cell lymphoma (IVLBCL).Methods:Fourteen cases of IVLBCLs were diagnosed from March 2014 to December 2019 at the First Affiliated Hospital of Zhengzhou University. The clinicopathologic features and prognosis were analyzed. Epstein-Barr virus encoded RNAs and MYD88 L265P mutation status were detected using in situ hybridization and Sanger sequencing, respectively. The follow-up data were obtained by telephone interview.Results:There were 6 males and 8 females with a median age of 62 years (range: 48-73 years). The involved anatomic locations were demonstrated by positron emission tomography-computed tomography, including adrenal gland (7/14), bone (6/14), central nerve system (4/14), skin (3/14), female reproductive system (3/14), local lymph nodes (3/14), prostate (2/14), liver and spleen (2/14), sphenoid sinus (1/14), penis (1/14), bladder (1/14), and right lung (1/14). Fever was the most common symptom (7/14), followed by neurologic symptoms and lower abdominal pain (2/14 each). The reminder symptoms included rash with edema, legs weakness and numbness, or postmenopausal bleeding (1/14 each). Eleven cases were at Lugano stage Ⅳ. Four cases were associated with the hemophagocytic syndrome, while 6 cases with bone marrow involved. Microscopically, the tumor cells were generally concentrated within the small-to-medium vascular lumens or sinusoids; they had centroblast-like appearance and showed large round or oval nuclei with slightly irregularities, coarse chromatin and 1-3 distinct nucleoli. One exception was the one case with an embryoid nuclei, reminiscent of anaplastic large cell lymphoma. The mitosis was not uncommon. Extravascular neoplastic cells were seen in two cases. The neutrophils could be appreciable in most of the cases (10/14). Immunophenotyping showed that CD20 and CD79α were diffusely and strongly positive in 14 cases; 12 cases were classified as the non-GCB subtype; 6 out of the 11 cases were double expressor lymphoma; 7 out of the 12 cases were CD5-positive. Twelve cases were EBER negative. The MYD88 L265P mutation was detected in 1 case (1/10). The duration of the follow-up ranged from 0.5 to 24.0 months, and 11 patients survived and 3 died.Conclusions:IVLBCL is rare. The most common type of IVLBCL in China is Asian type with scant tumor cells. Combination of clinical and immunohistochemical features can avoid most, if not all, misdiagnoses and missed diagnoses. Some IVLBCL cases may harbor the MYD88 L265P mutation, but the prevalence of MYD88 L265P mutation in the population still warrants additional studies.

Objective:To study the clinicopathological features and prognosis of nodal lymphoplasmacytic lymphoma/Waldenstrom′s macroglobulinemia (n-LPL/WM).Methods:A total of 19 cases of n-LPL/WM were collected from May 2009 to January 2020 at First Affiliated Hospital of Zhengzhou University. The clinicopathologic features, immunophenotype, Ig gene rearrangement (BIOMED-2), MYD88 L265P mutation status (by Sanger sequencing) and follow-up data (by telephone) were analyzed.Results:There were 15 males and 4 females with a median age of 61 years (range 43 to 82 years). There were 14 WM and five LPL. The most common symptoms were weakness, fatigue (9/19) and B symptoms (11/19). Majority of the patients (16/18) presented with systemic multiple lymphadenopathies. Eighteen patients presented at advanced stages (Ⅲ/Ⅳ stage). Serum M protein status was IgM (15 cases), IgG (1 case), IgA (1 case) and no-secretory type (2 cases). Seventeen patients had bone marrow involvement. Morphologically, all 19 cases were divided into two groups: typical group (9 cases) or atypical group (10 cases). In the typical group, the structures of the lymph nodes were preserved; the neoplastic cells were predominantly plasmacytoid lymphocytes or mixed small lymphocytes, plasmacytoid lymphocytes and plasma cells, without proliferation of FDC network and follicular implantation. In the atypical group, the tumor showed effaced nodal architecture (5 cases), mainly proliferation of small lymphocytes (6 cases), FDC proliferation and/or follicular implantation (6 cases), marginal zone B cell differentiation (4 cases) and diffuse amyloidosis (1 case). Hemosiderin deposition (19 cases), infiltration of fatty tissue (19 cases) and interstitial sclerosis (9 cases) were commonly seen in both groups. Immunohistochemically, the neoplastic B cells expressed CD20 and CD79α, and the neoplastic plasma cells were positive for CD38, CD138 and MUM-1; eight cases showed light chain restriction; of the seven detected cases, five expressed IgM and the other two expressed IgG and IgA respectively; four cases expressed CD23 weakly, Ki-67 index was 10%-30%. MYD88 L265P mutation was seen in 18/18 cases. There was no significant difference in clinicopathologic features and prognosis between the two groups ( P>0.05). The median follow-up time was 61 months, 11 patients were alive, while eight died; the 5-year survival rate was 21.1%. Conclusions:n-LPL/WM is rare, but patients usually present in advanced stages. It is easily confused with other small B-cell lymphomas with plasma cell differentiation, especially basing on morphologic features alone; thus the accurate diagnosis of n-LPL/WM requires a combination of clinical features, serum M protein, immunohistochemistry, bone marrow morphology,flow cytometry and MYD88 L265P mutation status etc. The prognosis of n-LPL/WM may be not very good, and further studies with more cases are needed.

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of gastrointestinal glomus tumors (GIGT). Methods: Totally 15 cases of GIGT were collected at the First Affiliated Hospital, Zhengzhou University, from January 2011 to June 2018. The clinicopathological features, immunophenotype, BRAF V600E mutation and prognosis were retrospectively analyzed. Results: The 15 patients′ age ranged from 37 to 59 years(median 49 years, mean 50 years). Eleven patients presented with intermittent abdominal pain and distention, three showed antral space-occupying lesions at physical examination, and one had abdominal pain accompanied by fecal blood. Fourteen tumors were located in the stomach, and one was in the ileum. Imaging showed the gastric glomus tumors were located in the submucosal layer with obvious enhancement in the arterial phase, and the ileum glomus tumor involved the whole layer of intestinal wall causing luminal obstruction. The maximum diameters of the tumors ranged from 1.5 to 3.0 cm (mean 2.3 cm). Grossly, the gastric glomus tumors were solid. Microscopically, the gastric glomus tumors were mostly located in the muscularispropria layer and were vascular. The tumor boundary was distinct but without capsule formation. The tumor cells were round or oval, and showed perivascular hemangiopericytoma-like or solid nest-like structures. The tumor cells were mildly pleomorphic, with rare mitosis and no necrosis. Two tumors had focal calcification, two showed mucosal invasion, two showed vascular invasion and five showed perineural invasion. The ileum glomus tumor was cellular, with prominent cellular atypia, and the mitotic count in hot spots was about 5-6/HPF. Immunohistochemistry showed that SMA and collage Ⅳ were strongly expressed in all the tumor cells; caldesmon and calponin were moderately expressed in some regions, and syn was weakly expressed in 12 cases. The Ki-67 proliferation index in the gastric glomus tumors ranged from 1% to 30% (mean 6%); and that in the ileum glomus tumor was about 70%. BRAF V600E mutations were not detected in any of 15 GIGTs. All patients did not receive radiotherapy or chemotherapy post operatively. Thirteen patients were followed up by telephone for 18-90 months (mean 42 months). Twelve patients with gastric glomus tumors survived without recurrence and metastasis, and the patient with ileum glomus tumor had liver metastasis 15 months after operation. Conclusions Glomus tumors is a rare mesenchymal tumor of the gastrointestinal tract. It should be differentiated from gastrointestinal stromal tumors, neuroendocrine tumor, leiomyoma, solitary fibrous tumor and paraganglioma. Most GIGTs are benign and have good prognosis. More experience is needed to understand the biologic behavior and prognostication of GIGTs.

Objective:To study the clinicopathologic and genetic features of Waldeyer′s ring peripheral T-cell lymphoma with follicular helper T cell immunophenotypes (wPTCL-TFH), with comparison to the nodal peripheral T-cell lymphoma with TFH immunophenotypes (nPTCL-TFH) and angioimmunoblastic T-cell lymphoma (AITL), as to know this rare tumor better.Methods:The clinical data, histopathology features, EBV positivity, T cell clonality and IDH2 R172 gene mutation in 8 cases of wPTCL-TFH were collected at the First Affiliated Hospital of Zhengzhou University from December 2015 to April 2019, and analyzed by immunohistochemistry, in situ hybridization, TCR gene rearrangement (BIOMED-2) and Sanger sequencing.Follow-up data were obtained by telephone. Results:There were 6 males and 2 females with a median age of 62.5 years (age ranging from 30 to 75 years). All patients had neither fever nor skin manifestations, but were all found mucosa thickened or mass of waldeyer′s ring with multiple lymph nodes enlarged by PET-CT/CT scans. Five of the 7 patients were at advanced stages (Ⅲ/Ⅳ stage). Microscopically, the mucosa was infiltrated diffusely and characteristically by numerous small-medium sized lymphocytes, lacking polymorphous inflammatory background and extra-follicular expansion of follicular dendritic cell networks (FDC networks). The clear T cells presented in 5 cases. Ulcers on mucosal surfaces (6 cases) and local-extensive loss of intramucosal glands (7 cases) were commonly noted. Granulomas composed of epithelioid histiocytes were observed in 2 cases. Immunohistochemically, all the tumor cells expressed CD4 and at least 2 types of follicular helper of T cell (TFH) markers: PD-1 (8/8), bcl-6 (8/8), CXCL13 (7/8) and CD10 (1/8). Most of the cases (6 cases) expressed CD30. EBV positive appeared in 4 cases. All 8 cases were T cell monoclonal. IDH2 R172 were wild-type in 6 cases. One patient died at the follow-up time on 18 months; the other 7 survived (the follow-up time varied from 3 to 10 months). Conclusions:wPTCL-TFH is rare, and its clinicopathological features are similar to nPTCL-TFH which may be the manifestation of the same disease at different stage, and partly overlapped with AITL. The differential diagnosis from PTCL-NOS is necessary and comprehensive analyses of clinical, morphological, immunohistochemical and genetic features can help make a correct diagnosis.

This paper explores the relationship between the cardiac volume and time, which is applied to control dynamic heart phantom. We selected 50 patients to collect their cardiac computed tomography angiography (CTA) images, which have 20 points in time series CTA images using retrospective electrocardiograph gating, and measure the volume of four chamber in 20-time points with cardiac function analysis software. Then we grouped patients by gender, age, weight, height, heartbeat, and utilize repeated measurement design to conduct statistical analyses. We proposed structured sparse learning to estimate the mathematic expression of cardiac volume variation. The research indicates that all patients' groups are statistically significant in time factor ( = 0.000); there are interactive effects between time and gender groups in left ventricle ( = 8.597, = 0.006) while no interactive effects in other chambers with the remaining groups; and the different weight groups' volume is statistically significant in right ventricle ( = 9.004, = 0.005) while no statistical significance in other chambers with remaining groups. The accuracy of cardiac volume and time relationship utilizing structured sparse learning is close to the least square method, but the former's expression is more concise and more robust. The number of nonzero basic function of the structured sparse model is just 2.2 percent of that of least square model. Hence, the work provides more the accurate and concise expression of the cardiac for cardiac motion simulation.

This study was aimed to improve the sensitivity of magnetic induction phase shift detection system for cerebral hemorrhage. In the study, a cerebral hemorrhage model with 13 rabbits was established by injection of autologous blood and the cerebral hemorrhage was detected by utilizing magnetic induction phase shift spectroscopy (MIPSS) detection method under the feature band. Sixty five groups of phase shift spectroscopy data were obtained. According to the characteristics of cerebral hemorrhage phase shift spectroscopy under the feature hand, an effective method, B-F distribution, to diagnose the severity of cerebral hemorrhage was designed. The results showed that using MIPSS detection method under feature band, the phase shift obviously growed with increase of injection volume of autologous blood, and the phase shift induced by a 3-mL injection reached -7.750 3 degrees ± 1.420 4 degrees. B-F distribution could effectively diagnose the severity of cerebral hemorrhage. It can be concluded that the sensitivity of the cerebral hemorrhage magnetic induction detection system is improved by one order of magnitude with the MIPSS detection method under the feature band.
Animals ; Cerebral Hemorrhage ; diagnosis ; Magnetic Phenomena ; Magnetics ; Rabbits ; Spectrum Analysis ; methods

The real-time monitoring of cerebral hemorrhage can reduce its disability and fatality rates greatly. On the basis of magnetic induction phase shift, we in this study used filter and amplifier hardware module, NI-PXI data-acquisition system and LabVIEW software to set up an experiment system. We used Band-pass sample method and correlation phase demodulation algorithm in the system. In order to test and evaluate the performance of the system, we carried out saline simulation experiments of brain hemorrhage. We also carried out rabbit cerebral hemorrhage experiments. The results of both saline simulation and animal experiments suggested that our monitoring system had a high phase detection precision, and it needed only about 0.030 4s to finish a single phase shift measurement, and the change of phase shift was directly proportional to the volume of saline or blood. The experimental results were consistent with theory. As a result, this system has the ability of real-time monitoring the progression of cerebral hemorrhage precisely, with many distinguished features, such as low cost, high phase detection precision, high sensitivity of response so that it has showed a good application prospect.
Algorithms ; Animals ; Cerebral Hemorrhage ; diagnosis ; Computer Systems ; Magnetics ; Rabbits ; Software