Objective:To investigate the clinicopathological and genetic characteristics of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).Methods:The forty-two MEITL cases diagnosed in the Department of Pathology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China from 2016 to 2022 was retrospectively analyzed. Clinical data were collected, and follow-up was performed. Morphological characteristics were observed. Immunohistochemistry, Epstein-Barr virus (EBV) in situ hybridization, clonal rearrangement analysis of T-cell receptor (TCR) genes, and targeted next-generation sequencing (NGS) were performed.Results:Among the 42 patients (male/female ratio of 2.8∶1.0), the age range was 32-77 years with a median age of 59.5 (52.0-65.0) years. Grossly, the tumors were presented as ulcerative or exophytic lesions, with a maximum diameter of 2-18 cm. There were 34 cases with a single lesion and 8 cases with more than 1 lesion. The tumor cells in all 42 cases were relatively monotonous in histology and small or medium in size. They had round or oval nuclei, moderately pale or clear cytoplasm, evenly distributed nuclear chromatin, inconspicuous nucleoli, and frequent mitotic figures. In one of the cases, there were moderately large cells, vacuolated nuclei, and clear nucleoli. Lymphoepithelial lesions were observed in 36 (85.7%) of the 42 cases, tumor necrosis in 4 (9.5%) cases, scattered eosinophils and/or plasma cell infiltration in the background in 9 (21.4%) cases, and a "starry sky" phenomenon in 1 (2.4%) case. The tumor cells in all cases exhibited high expression of CD3, CD2, CD7, CD8, CD56, TIA1, Granzyme B, and Perforin, while some also expressed CD4 (5/41, 12.2%), CD5 (3/41, 7.3%), CD20 (4/41, 11.9%), CD79α (2/37, 5.4%), and CD30 (1/34, 2.9%). The Ki-67 proliferation index ranged from 40% to 90%. EBER in situ hybridization tests were negative in all cases. TCR gene clonal rearrangement was detected in 96.4% (27/28) of the tested cases. Targeted NGS revealed commonly mutated genes including SETD2, STAT5B, JAK3, TP53, and CREBBP. The primary treatment was chemotherapy, with 2 cases undergoing autologous hematopoietic stem cell transplantation. Follow-up information was obtained for 29 cases, with a follow-up period of 1-73 months. The mortality was 93.1% (27/29).Conclusions:MEITL is a rare and highly aggressive peripheral T-cell lymphoma. Its clinical manifestations are diverse, and diagnosis primarily relies on a comprehensive assessment of pathological morphology, immunohistochemical profiles, and EBV infection status, supplemented by genetic testing if necessary. At present, there is no effective treatment, and its overall prognosis is poor.

Objective:To investigate the clinicopathological and genetic characteristics of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).Methods:The forty-two MEITL cases diagnosed in the Department of Pathology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China from 2016 to 2022 was retrospectively analyzed. Clinical data were collected, and follow-up was performed. Morphological characteristics were observed. Immunohistochemistry, Epstein-Barr virus (EBV) in situ hybridization, clonal rearrangement analysis of T-cell receptor (TCR) genes, and targeted next-generation sequencing (NGS) were performed.Results:Among the 42 patients (male/female ratio of 2.8∶1.0), the age range was 32-77 years with a median age of 59.5 (52.0-65.0) years. Grossly, the tumors were presented as ulcerative or exophytic lesions, with a maximum diameter of 2-18 cm. There were 34 cases with a single lesion and 8 cases with more than 1 lesion. The tumor cells in all 42 cases were relatively monotonous in histology and small or medium in size. They had round or oval nuclei, moderately pale or clear cytoplasm, evenly distributed nuclear chromatin, inconspicuous nucleoli, and frequent mitotic figures. In one of the cases, there were moderately large cells, vacuolated nuclei, and clear nucleoli. Lymphoepithelial lesions were observed in 36 (85.7%) of the 42 cases, tumor necrosis in 4 (9.5%) cases, scattered eosinophils and/or plasma cell infiltration in the background in 9 (21.4%) cases, and a "starry sky" phenomenon in 1 (2.4%) case. The tumor cells in all cases exhibited high expression of CD3, CD2, CD7, CD8, CD56, TIA1, Granzyme B, and Perforin, while some also expressed CD4 (5/41, 12.2%), CD5 (3/41, 7.3%), CD20 (4/41, 11.9%), CD79α (2/37, 5.4%), and CD30 (1/34, 2.9%). The Ki-67 proliferation index ranged from 40% to 90%. EBER in situ hybridization tests were negative in all cases. TCR gene clonal rearrangement was detected in 96.4% (27/28) of the tested cases. Targeted NGS revealed commonly mutated genes including SETD2, STAT5B, JAK3, TP53, and CREBBP. The primary treatment was chemotherapy, with 2 cases undergoing autologous hematopoietic stem cell transplantation. Follow-up information was obtained for 29 cases, with a follow-up period of 1-73 months. The mortality was 93.1% (27/29).Conclusions:MEITL is a rare and highly aggressive peripheral T-cell lymphoma. Its clinical manifestations are diverse, and diagnosis primarily relies on a comprehensive assessment of pathological morphology, immunohistochemical profiles, and EBV infection status, supplemented by genetic testing if necessary. At present, there is no effective treatment, and its overall prognosis is poor.

OBJECTIVE To observe the clinical efficacy and effect on serum thymic stromal lymphopoietin(TSLP)levels of pa-tients with advanced liver cancer of qi deficiency and toxic stasis type by Jiawei Yupingfeng San.METHODS Using random double blind method,120 patients with advanced liver cancer of qi deficiency and toxic stasis type were randomly divided into 3 groups:Jiawei Yupingfeng San group,Yupingfeng San group,and placebo group,each consisting of 40 cases.All patients in the 3 groups were given conventional treatment such as radiotherapy,chemotherapy,interventional or targeted therapy;Jiawei Yupingfeng San group was given Jiawei Yupingfeng San granules,Yupingfeng San group was given Yupingfeng San granules,and placebo group was given placebo.The course of treatment was 2 months.The changes of Karnofsky functional status score(KPS score),TCM syndrome score,tumor size and serum TSLP level in the 3 groups were observed before and after treatment,and the correlation between the changes of tumor size and TSLP was analyzed.RESULTS After treatment,the KPS scores of Yupingfeng San group and Jiawei Yupingfeng San group were sig-nificantly increased(P<0.05,P<0.01),TCM syndrome score were decreased(P<0.01),tumor growth(P<0.05,P<0.01)was de-layed,and serum TSLP levels(P<0.05,P<0.01)were decreased.Furthermore,there was a slight positive correlation between chan-ges in tumor size and changes in TSLP(P<0.05).In terms of improving tumor size,the curative effect of Jiawei Yupingfeng San group was better than that of Yupingfeng San group(P<0.05).During the treatment period,no obvious adverse reactions were observed in the 3 groups of patients.CONCLUSION Combined with conventional treatment,Jiawei Yupingfeng San can significantly delay tumor growth in patients with advanced liver cancer of qi deficiency and toxic stasis type and improve patients'TCM syndromes and their qual-ity of survival.The therapeutic mechanism is related to reducing the expression of serum TSLP and improving the immune status of pa-tients,thereby delaying the growth of tumors.

Objective : To the effects and potential mechanisms of ST3GAL5 on biological behaviors of Bladder Urothelial Carcinoma(BLCA) . Methods : Differentially expressed genes related to bladder cancer were identified using microarray analysis . Suitable bladder cancer cell lines were then screened . In vitro experimental measurements , including CCK8 , EdU , colony formation assays , transwell migration , flow cytometry apoptosis experiments , scratch assay , were used to evaluate the effects of ST3GAL5 on biological behaviors of BLCA . ST3GAL5 gene Kyoto Encyclopedia of Genes and Genomes ( KEGG) , gene set enrichment analysis ( GSEA) were analyzed using The Cancer Genome Atlas (TCGA) database . Finally , Western blot technology was used to verify the classical proliferation and metastasis related pathway factors . Results : The combination of bioinformatics analyses and experimental measurements demonstrate that ST3GAL5 expression is aberrantly down⁃regulated in human cell lines of BLCA . Through Cancer Cell Line Encyclopedia (CCLE) database , HT⁃1376 cell lines were successfully screened for vitro test . Upregulation of ST3GAL5 was found to suppress the malignant biological behaviour of bladder cancer. GSEA enrichment analyses exhibited that ST3GAL5 and its co⁃expressed genes inhibited cell proliferation , invasion and metastasis of bladder urothelial carcinoma by activation of the PPAR pathway and inhibition of the PI3K/AKT pathway . The results of Western blot experiments verified that the key proteins of the PPAR signaling pathway showed a significant increase and the key proteins of the PI3K/AKT signaling pathway showed a significant decrease ( P <0. 05) after ST3GAL5 overexpression in bladder cancer. Conclusion ST3GAL5 gene might act as an oncogenic suppressor gene in bladder cancer , possibly inhibit the proliferation , invasion and metastasis of bladder cancer cells by activating the PPAR signaling pathway and inhibiting related molecules in the PI3K/AKT signaling pathway .

Objective : To investigation of the interaction between interstitial cells of Cajal (ICCs) and connexin 43 ( Cx43) in bladder contraction and its significance． Methods : Eighty male guinea pigs were randomly divided into blank control group，Glivec group，Gap27 group and Glivec + Gap27 group．Four groups of guinea pigs were per- fused with saline，Glivec，Gap 27，and Glivec + Gap 27 every morning for 2 months．Success of urodynamic testing model after 2 months．Bladder tissue was collected for an in vitro muscle strip test to detect muscle contraction in each group．Correlation between c-Kit and Cx43 was detected by immunofluorescence．The interaction between c- Kit and Cx43 in the bladder was further validated by qRT-PCR and Western blot．Ultrastructural changes in the muscle layer of the bladder were observed by electron microscopy. Results : Urodynamics revealed increased blad- der compliance in the experimental group compared to the blank control group (P＜0. 05) ; bladder compliance increased in the Glivec + Gap27 group compared to the Glivec and Gap27 groups (P＜0. 01) ．In vitro muscle strip experiments revealed that the frequency and tone of bladder muscle strip contractions were lower in the experimental group compared to the blank control group (P＜0. 05) ，and that muscle strip contractions were weaker in the ex- perimental group after administration of acetylcholine (ACH) compared to the control group(P＜0. 05) ．Immuno- fluorescence showed that c-Kit was co-expressed with Cx43 on ICCs cells．qRT-PCR and Western blot suggested that the protein expression level and gene expression level of Cx43 in bladder tissues were lower after inhibition of c-Kit than in the blank control (P＜0. 05) ; after inhibition of Cx43，the protein expression level and gene expres- sion level of c-Kit in bladder tissues the levels of c-Kit protein expression and gene expression in bladder tissues were lower than those in the blank control group (P＜0. 05) ．Electron microscopy revealed that the mitochondrial structure of bladder smooth muscle was disrupted after simultaneous inhibition of c-Kit and Cx43． Conclusion Cx43 is expressed on bladder ICCs and the two may be jointly involved in regulating bladder contractile function ; the joint reduction of Cx43 and c-Kit may have disrupted the mitochondria of bladder smooth muscle，affecting its function and consequently bladder contractile function.

Objective : To investigate the effect of the combination of stem cell leukemia(SCL)recombinant lentivirus and connexin 43 ( Cx43 ) recombinant lentivirus on the function of diabetic cystipathy ( DCP) in guinea pigs. Methods : After 90 healthy guinea pigs were fed normally for 1 week, streptozotocin(STZ)was injected intraperito⁃ neally at 200 mg/kg in a single dose, and random blood glucose was monitored weekly. After 12 weeks of normal feeding, 40 guinea pigs meeting the criteria were screened by urodynamic examination and randomly divided into 4 groups: diabetic group, SCL group, Cx43 group, and SCL + Cx43 group. In the diabetic group, 0. 2 ml of empty lentivirus without gene was instilled into the bladder through the urethra, in the SCL and Cx43 groups, 0. 2 ml of SCL lentivirus and Cx43 lentivirus were instilled using the same method, in the SCL + Cx43 lentivirus group, 0. 2 ml of each SCL and Cx43 lentivirus was instilled through the urethra. After 14 days of transfection, urodynamic examination was performed, and then the guinea pigs were executed after the examination, and the bladders were quickly removed for frozen bladder sections and fluorescent double staining. Results : There were no differences in urodynamic examinations between the SCL and Cx43 groups compared to the diabetic group( P > 0. 05 ) . Urodynamic examination in the SCL + Cx43 group showed improvement in detrusor pressure, abdominal pressure and bladder pressure compared to the diabetic group(P < 0. 05) . In laser confocal experiments, the number of interstitial cells of Cajal (ICC) was reduced in the diabetic group, and the spindle structure and cell protrusions were obviously destroyed and appeared in a state of cell lysis. In the SCL and Cx43 groups, there was an improvement in the spindle structure and cell protrusion of ICC⁃like cells, and there was no significant change in the number of cells. In the SCL + Cx43 group, there was an increase in the number of ICC⁃like cells, a significant improvement in the spindle structure and cell protrusion, and the formation of ICC⁃dimers. Conclusion Transurethral co⁃infusion of SCL and Cx43 gene recombinant lentivirus can be successfully transfected in guinea pig DCP bladder, which can restore the number and structure of damaged ICC cells and form ICC dimer structure, improve the pressure of diabetic bladder forced urinary muscle, improve the weakness of urination, ventral pressure voiding and other characteristics. It provides a new direction for the treatment of DCP.

Objective To explore the safety and efficacy of Solitaire AB double stents in acute occlusions in bifurcation of cerebral artery (including the ends of internal carotid artery and middle cerebral artery M1 segment).Methods The clinical and imaging data of six cases treated with the double stent retriever technique using the Solitaire AB system in Wuhan No.1 Hospital from January to November 2017 were retrospectively analyzed.And the therapeutic effect and postoperative complications of them were analyzed.Results One patient took the double stents directly,whereas five patients were treated with double stent-retriever thrombectomy after the failure of single stent thrombectomy.All of the six patients achieved recanalization successfully (modified thrombolysis in cerebral infarction (mTICI) 3 in five patients,mTICI 2b in one).All patients had no intracranial hemorrhage immediately after thrombectomy.In the 24 hours,7 days and 2 weeks,the median NIHSS score was 10 (3-17),3 (1-15) and 1 (0-15),respectively.During perioperative period,one patient had asymptomatic cerebral hemorrhage,one died of symptomatic cerebral hemorrhage within 48 hours,and one was complicated with pulmonary infection.Five patients were followed up by outpatient visit,and four patients showed good outcome (modified Rankin Scale score ≤2).Conclusion In the emergency revascularization of acute cerebral artery occlusion at arterial bifurcation,double stent-retriever is better at increasing the efficacy of thrombectomy and is safe compared with single stent mechanical thrombectomy.

Objective: To deepen the knowledge of HIV-negative plasmablastic lymphoma (PBL) . Methods: Medical records from 8 HIV-negative PBL patients diagnosed in Peking Union Medical College Hospital from January 1997 to May 2015 were collected, and the clinical features and prognosis of these patients were analyzed. Results: All of these 8 patients were diagnosed as HIV-negative PBL, 3 of 8 patients were males, and others were female. The median age was 60 (43-80) year. Among these patients, 4 cases had underlying immunosuppressive state. These patients all had extra-nodular involvement, and 6 cases of them were at stage Ⅳ according to Ann Arbor Staging, 5 patients had bone marrow involvement. CD38 and CD138 were diffusely positive for all patients, while the positive rate of B cell marker including PAX-5 and Bcl-6 were relative low. 5 of 8 patients had been detected for EBV-DNA, and all of them were negative. The median follow-up for the 7 patients receiving chemotherapy and regular follow-ups was 36 (11-57) months, the median progression-free survival (PFS) was 15 (6-52) months, and the median overall survival was 36 (2-52) months. Among these patients, 4 cases had received chemotherapy combined with Bortezomib, showing 3 cases of effective, but it seems to be difficult to keep the long term efficacy, and disease progression occurred in 2, 9, and 21 months after treatment. 2 patients at stageⅠ-Ⅱ were treated effectively, without disease progression and survival, 5 patients at stage Ⅳacquired the efficacy unsustainably, with a median PFS of 10 (2-21) months and a median overall survival of 12 (6-52) months. Conclusion HIV-negative PBL is relatively prevalent in elderly patients, and presenting with high invasiveness in clinical, extremely prone to extra-nodular involvement, especially the bone marrow. The immunophenotype of PBL is more resemble to that of plasmacytoma. Patients who were in late stage at diagnosis show poor prognosis.

Objective: To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm. Method: Clinical records of 6 patients diagnosed with blastic plasmacytoid dendritic cell neoplasm in our hospital from January 2008 to May 2016 were collected and retrospectively analyzed. Results: Six patients manifested with initial symptoms of skin lesions, other common symptoms included bone marrow involvement (5/6) , lymphadenectasis (4/6) , splenomegaly (4/6) , and hepatomegaly (3/6) . In addition, extra-nodal involvement except skin was also observed, including breast (1/6) , maxillary sinus (1/6) , vertebrae (1/6) , and central nervous system (1/6) . Characteristic immunophenotype, CD4, CD56, and CD123 were all positive. All these patients were treated with acute lymphoblastic leukemia type (ALL-type) chemotherapy and complete remission (CR) were reached in 4 patients. The median follow-up was 9.5 (7-37) months, median progression free survival was 7 months; while median overall survival was 9 months. A total of 3 patients died during the follow-up, which were all happened in the first year after diagnosis, and all resulted from the relapse or disease progression. Conclusion Blastic plasmacytoid dendritic cell neoplasm is highly aggressive, in which the skin lesions are always manifested as initial symptoms, and bone marrow involvement, lymphadenectasis, splenomegaly, and hepatomegaly is also common. Characteristic immunophenotype include the positivity of CD4, CD56, and CD123. Effective and standard therapy is limited in this disease, which indicates the poor prognosis.

Objectives To explore the prognostic factors of patients with pancreatic ductal adenocarcinoma and synchronous liver metastases ( PALM ) receiving palliative treatment .Methods The clinical characteristics , therapeutic approaches and survival outcomes of 108 consecutive patients with PALM who were pathologically diagnosed and received only palliative treatment at Tianjin Medical University Cancer Hospital from January 2001 to December 2015 .were retrospectively analyzed .Survival rates were calculated by Kaplan-Meier method, and factors influencing the survival were analyzed by univariate and multivariate Cox proportional hazard regression model .Results Of these patients, 68 were male and 40 were female, with an average age of 58 years old.Seventy-seven (71.3%) cases or their relatives refused to receive anticancer therapies.Palliative treatments included choledochojejunostomy and /or gastrojejunostomy after exploratory laparotomy for 5 (4.6%) cases, percutaneous transhepatic biliary drainage (n=22, 19.4%), drug analgesia (n=79, 73.1%), drug analgesia combined with percutaneous neurolytic coeliac plexus block (n=17, 15.7%).The median survival time (MS)was 94 days in all patients.Karnofsky performance score (KPS)<80, lymph node metastases, ascites, fasting blood glucose ≥6.1 mmol/L and lactate dehydrogenase ( LDH ) ≥250 U/L were independent risk factors influencing prognosis of PALM . Three groups were categorized according to the number of the above 5 risk factors for 0~1 in low risk group, 2~3 in middle risk group and 4~5 in high risk group, and the MS of 3 groups was 137, 95 and 48 days, respectively, with an extremely statistical significance (P<0.0001).Conclusions KPS, lymph node metastases, ascites, fasting blood glucose and LDH were the risk factors for prognosis of PALM .Patient stratification according to the above factors is more advantageous for judging individualized prognosis and can provide reference for making clinical decision .