Purpose To study the clinicopathologic features, diagnosis and differential diagnosis of extranodal NK/T-cell lymphoma, nasal type ( EN-NK/TCL) . Methods Twenty-eight cases of EN-NK/TCL were analyzed according to WHO classification of tumors of haematopoietic and lymphoid tissues, the cases were studied by microscopy, immunohistochemistry and in situ hybridization. Results In 28 cases, the male to female ratio was 1 ∶ 1. 2. The mean age was 46 years, with the median of 44. 5. Eighteen cases involved nasal cavity, 5 cases of skin, and 1 case of tonsil, upper palate, root of tongue, adrenal glands and gastric, respectively. The main presentation was nasal obstruction in cases with nasal involvement, and the cases with skin involvement present with rash, ulcer, plaque or nodular mass. Patients might be accompanied by B-type symptoms, lymphoadenopathy or with multiple sites involvement. The tumor cells were small, medium, large-sized, or mixed, and angiocentric and angiodestructive growth pattern was frequently pres-ent. Most cases were mixed with inflammatory cells infiltration. The typical immunophenotype was T-cell ( the most sensitive, CD3ε) , CD56 and cytotoxic markers. In situ hybridization for EBER was positive. Ten cases were followed up, and 1 case died. Conclusions The most common site of EN-NK/TCL is nasal cavity, followed by skin. EN-NK/TCL can be definitely diagnosed by integration of pathological morphology, immunophenotype and in situ hybridization of EBER.

Objective To investigate the mechanism of brain derived neurotrophic factor (BDNF) regulated by differ-ent isoforms of tyrosine kinase receptor B (TrkB) in epileptic hippocampal neurons. Methods Primary hippocampal neu-rons were cultured in vitro for 7 days, and divided into two groups, ALLN (calcineurin inhibitor) group and Anisomycin (trans-lation inhibitor) group. ALLN group included control group, control+BDNF group, epilepsy group, epilepsy+BDNF group, control+ALLN group, epilepsy+ALLN group and epilepsy+ALLN+BDNF group. Anisomycin group was sub-divided into con-trol group, control+BDNF group, epilepsy group, epilepsy+BDNF group, control+Anisomycin group, epilepsy+Anisomycin group and epilepsy+Anisomycin+BDNF group. The immunofluorescent technique was used to identificate the hippocampal neurons. Epileptiform discharges were detected by electrophysiological techniques. Western blot assay was used to deter-mine the protein expression of TrkB and phosphorylated TrkB (p-TrkB) in all cell groups. Results (1) In ALLN group, the gray value of p-TrkB/TrkB was higher in control+BDNF group compared with that of control group, the value was higher in epilepsy+BDNF group than that of epilepsy group but was lower than that of control+BDNF group. The gray value of p-TrkB/TrkB was lower in epilepsy+ALLN+BDNF group than that of epilepsy+BDNF group, but no significant difference compared with that of epilepsy+ALLN group. (2) In Anisomycin group:the gray value of p-TrkB/TrkB was higher in control+BDNF group than that of control group. The gray value of p-TrkB/TrkB was higher in epilepsy+BDNF group than that of epilepsy group, but which was lower than that of control+BDNF group. The gray value of p-TrkB/TrkB was higher in epilepsy+Aniso-mycin+BDNF group than that of epilepsy+BDNF group and epilepsy+Anisomycin group. Conclusion The decreased ex-pression of TrkB.T can improve the inhibition of BDNF/TrkB signaling, and BDNF can activate BDNF/TrkB signal pathway in epileptic hippocampal neurons. The increased TrkB.FL protein level by ALLN can’t improve the inhibition of BDNF/TrkB signal pathway.

Objective To study the effect of miR-204 on BDNF/TrkB signaling and pathogenesis on the neuron model of epilepsy. Methods Primary hippocampal neurons were cultured in vitro for 7 days, and were divided into control group, control+BDNF group, epilepsy group, epilepsy+BDNF group , control+miR204 group, epilepsy+miR204 group and ep-ilepsy+miR204+BDNF group. The epilepsy model of hippocampal neurons was established by being exposed to Mg2+free me-dia for 3 hours. The miR-204 lentivirus vector was constructed. The effect of miR-204 on BDNF/TrkB expression was detect-ed by immunohistochemistry, patch clamp and Western blot technique. Results Compared with the control group, the TrkB phosphorylation level was higher in control+BDNF group. The TrkB phosphorylation level was lower in epilepsy+BDNF group than that of control+BDNF group, but it was higher than that of epilepsy group. The TrkB phosphorylation level was higher in epilepsy+miR204+BDNF group than that of epilepsy+BDNF group and epilepsy+ miR204 group. Conclusion BDNF and miR-204 can improve the inhibitory condition of BDNF/TrkB signaling and may play an important role in alleviat-ing epilepsy disease.

Objective To establish a multiplex real-time PCR mothed for rapid detection of seven species of intracranial bacteria after surgery. Methods Firstly ,the Gram′s identification was deter mined. Secondly , according to the results of Gram identification ,the bacterium was typed by the specific primers and probes to deter mine the distribution of bacteria. Simul taneously ,the sensitivity and specificity of this method were verified by making intracranial infected sim ulated samples and contrasting national standard method. Results The method established could complete detention within 4 hours with a good specificity. Staphylococcus aureus,Streptococcus pneumoniae ,Escherichia coli ,Pseudomonas aeruginosa pseudomonas ,Klebsiella pneumoniae and Acinetobacter baumannii could be detected at concentrations of ≥102 CFU/mL. Enterococcus faecalis could be detected at concen-trations of≥103 CFU/mL. The lowest detection limita of this method is higher than culture method for Streptococcus pneumoniae. Conclusions Real-time Multiplex PCR method was with high sensitivity and specificity. It reduced the detection time greatly and has great value in early diagnosis of bacteria in intracranial infection. It should be of great significance for guiding clinical treatment.

Objective To explore the protein expression of PLAC1/CP1 ( cancer-placenta 1 ) and its correlation with clinicopathological characteristics in patients of colorectal carcinoma. Methods The expression of PLAC1/CP1 gene was studied by using tissue chip and immunochemistry in 125 cases CRC tissue specimens. Data were analyzed with the x2-test or Fisher's x2 test statistic by SPSS 16. 0 software.Results The protein expression of PLAC1/CP1 gene was 57.6% (72/125) in 125 cases of CRC and 56. 7% (55/97)in 97 primary adenocarcinoma cases. That was 78. 9% (15/19)in poor differentiated colorectal primary adenocarcinoma, those were significantly higher than that of 35.3% (6/17) in well and 55.7% (34/61) in moderately differentiated adenocarcinoma ( P ＜ 0.05 ); PLAC1/CP1 protein expression was significantly higher in stage TNM Ⅲ + Ⅳ 71.2% (37/52) than in stage TNM Ⅰ + Ⅱ 40% (18/45)(P ＜ 0.05 ); PLAC1/CP1 genes expression rate was 69.6% (32/46) in these with lymphoid node metastasis and 45.1% (23/51)in patients without lymphoid node metastasis (P ＜ 0.05 ). The positive expression rate of PLAC1/CP1 increased in colorectal carcinoma with the increasing of the numbers of lymphoid node involved with metastasis( x2 = 13. 353, P = 0.001 ). Conclusions The protein expression of PLAC1/CP1 is associated with tumor differentiation, TNM stage and lymphoid node metastasis.

Objective To explore protein expression and significance of MAGE genes in colorectal carcinoma(CRC)tissues.Methods The expression of MAGE genes were studied by using tissue chip and immunochemistry methods in primary CRC tissue and paired adjacent tissue samples in 97 cases.Data were analyzed with x2-test by SPSS 16.0 software.Results The protein expression of MAGE-A3,MAGE-A4 and MAGE-A10 genes were 57％(56/97),63％(61/97)and 28％(27/97)respectively in 97 cases of primary adenocarcinoma.The protein expression frequency of MAGE-A3 in poor colorectal adenocarcinomas was significantly higher than in well-and moderately disfferentiated adenocarcinomas(x2 =9.133,P =0.010).MAGE-A10 in poor colorectal primary adenocarcinomas was significantly higher than in well and moderately adenocarcinomas(x2 =15.280,P =0.000); MAGE-A10 protein expression was significantly higher in stage TNM Ⅲ + Ⅳ than in stage TNM Ⅰ + Ⅱ(x2 =4.227,P=0.040); MAGE-A10 gene expression was higher in metastasis lymphoid node than in no metastasis lymphoid node(x2 =5.557,P =0.018),and the expression level was higher in primary lesion with the increasing of the numbers of lymphoid node metastasis(x2 =7.296,P =0.026).Conclusions The protein expression of MAGE genes is associated with the tumor differentiation,TNM stage and lymphoid node metastasis.MAGE-A3 and MAGE-A10 genes are the possible prognosis marker and potential target of immunotherapy of CRC.

Objective: To study the clinicopathologic features, diagnosis and differential diagnosis of the tumors of lymphoidand hematopoietic tissue of the spleen(TLTS). Methods: Fifty-three cases of TLTS were selected from the pathologic files from Peking University People′s Hospital from April 2002 to April 2017. According to WHO classification of tumors of hematopoietic and lymphoid tissues (2008) and its updated classification (2016), the cases were studied by microscopy, immunohistochemistry and in situ hybridization, combined with the bone marrow biopsy and clinical examination. Results: In 53 cases of TLTS, the male to female ratio was 3.4∶1.0; the mean age was 55.4 years (range 21-76 years), and all patients presented with variable degree of splenomegaly. Laboratory examination showed increased percentage of lymphocyte in peripheral blood in 22 cases, and elevated serum LDH level in 24 cases. Abnormal blood counts were seen in 26 cases pre-operatively, in which 22 cases showed complete or partial correction of these abnormalities post-operatively (84.6%, 22/26). The clinical symptoms included abdominal pain or distension, fatigue, fever, and weight loss, etc. Seventeen cases presented with lymphadenopathy of abdomen or other sites. Bone marrow biopsy was performed in 30 cases, and 19 cases were involved by tumor (63.3%). Of all 53 cases, 43 were diagnosed as primary splenic lymphoma (PSL), and the remaining 10 cases as secondary TLTS. According to Ann Arbor staging, 14 cases were stages Ⅰ or Ⅱ, 6 were stage Ⅲ and 28 were stage Ⅳ. By histopathologic classification, 43 cases of PSL were splenic B-cell marginal zone lymphoma (SMZL; 48.8%, 21/43), diffuse large B cell lymphoma (DLBCL; 23.3%, 10/43), splenic diffuse red pulp small B-cell lymphoma (11.6%, 5/43), mantle cell lymphoma (9.3%, 4/43), follicular lymphoma (4.7%, 2/43), and composite lymphoma (CL, DLBCL and classical Hodgkin lymphoma; 2.3%, 1/43). The remaining 10 cases were chronic lymphocytic leukaemia/small lymphocytic lymphoma (4 cases), hairy cell leukaemia (1 case), hepatosplenic T-cell lymphoma (HSTL; 5 cases), with lesions in other sites. Of the 53 cases of TLTS, 47 were B cell neoplasm (88.7%, 47/53), and the T cell neoplasms were all HSTL(5 cases, 9.4%, 5/53), 1 case was composite lymphoma. In 11 cases of TLTS, EBER in situ hybridization was performed and all cases were negative. Forty eight cases had follow-up data, and the median survival period was 17.0 months(range: 1-96 months). The survival of patients with SMZL and DLBCL were 25.7 and 18.6 months respectively. Thirteen patients died (27.1%, 13/48). The prognosis of those with elevated LDH level, high clinical stage, B symptoms and older than 60 years of age was worse. And the prognosis of DLBCL was worse than that of SMZL. There was no statistically significant difference between these factors and prognosis (P>0.05). Conclusions Most TLTS cases present with splenomegaly and abnormal blood counts, and complete or partial remission of blood counts isseen after splenectomy. The most common pathologic types of TLTS are SMZL and DLBCL. Definite diagnosis of TLTS could be made by combining clinical features, histopathology, immunophenotype, genetics, bone marrow biopsy and laboratory examination.

Objective To study the clinicopathologic features,diagnosis and differential diagnosis of tumors of haematopoietic and lymphoid tissue in the female productive tract. Methods Eleven cases of myeloid sarcoma and leukemia, 9 of non Hodgkin lymphoma(NHL),13 of cervical lymphoma-like lesions were selected from Peking University People′s Hospital from January 2006 to August 2017. According to WHO classification of tumors of haematopoietic and lymphoid tissues(2008)and updated classification(2016),the cases were studied by microscopy,immunohistochemistry and in situ hybridization.Results In 20 cases of tumors of haematopoietic and lymphoid tissue,the mean and median age was 48.5 and 56 years old(range:16-77 years old).In cases of lymphoma-like lesion of uterine cervix,the mean and median age was 45.9 and 48 years old(range:23-62 years old).The patients with neoplasm present as fever,fatigue, hypogastralgia, colporrhagia and mass etc. Eight cases had history of acute myeloid leukemia, and 3 had myeloid leukemia while pregnancy. One case of chronic lymphocytic leukaemia/small lymphocytic lymphoma(CLL/SLL)had history of ovary small cell carcinoma and high grade serous carcinoma resected with chemotherapy.One case of diffuse large B cell lymphoma(DLBCL)had history of renal transplantation. Lactic dehydrogenase(LDH)was elevated in 9 cases(9/18).The cases of lymphoma-like lesion present as contact bleeding in most cases and all located in cervix. Four cases of neoplasm located in vulva, 1 in vagina,4 in cervix, 4 in uterine corpus, 8 in ovary and 2 in placenta.Clinical staging of NHL: 4 case was stageⅠ,1 case of stageⅢ,and 4 cases of stageⅣ.Pathological morphology:9 cases were myeloid sarcoma, 2 cases were placenta invaded by myeloid leukemia. Six cases were DLBCL, and 1 case was CLL/SLL, 1 case was mucosa associated lymphoid tissuse lymphoma(MALToma), and 1 case was anaplastic large cell lymphoma. Resected mass, chemotherapy was performed in tumors of haematopoietic and lymphoid tissue. Five cases of myeloid sarcoma and 2 of NHL died. In 13 cases of lymphoma-like lesion of uterine cervix, the general condition was good as following up. Conclusions The clinical history, pathological morphology and immunohistochemistry are very important for diagnosing tumors of haematopoietic and lymphoid tissue in the female productive tract.Resection with chemotherapy is recommended in treatment. The prognosis of lymphoma-like lesion of uterine cervix is good,and should be differentiated from lymphoma.

Metronomic chemotherapy is a brand-new and multi-target chemotherapy strategy.Totally different from the traditional chemotherapy,metronomic chemotherapy can exert synergistic and durable anti-tumor effects via multiple mechanisms,including cytotoxic effect,anti-angiogenesis,immune regulation and so on.Single and combined therapy modes of metronomic oral vinorelbine have good curative effects and safeties for the treatment of advanced non-small cell lung cancer.With the in-depth understanding of metronomic chemotherapy,it will certainly become an important treatment mode for advanced non-small cell lung cancer.

Objective:To investigate the clinicopathological characteristics of non-Hodgkin lymphoma (NHL) in Shandong province.Methods:The clinicopathological data of 2 886 NHL cases in Shandong Cancer Hospital from January 2002 to December 2017 were retrospectively analyzed, the clinicopathological characteristics of patients were summarized and compared with other regions in China and abroad.Results:The median age of all NHL cases was 52 years old (4-90 years old), and the ratio of male to female was 1.57∶1. The subtypes distribution analysis revealed that B-cell NHL (B-NHL) accounted for 66.7% (1 925 cases) of all cases and T-cell NHL (T-NHL) accounted for 27.3% (788 cases) of all cases. The common subtypes were diffuse large B-cell lymphoma (36.0%, 1 039/2 886), NK/T-cell lymphoma (8.8%, 254/2 886), follicular lymphoma (8.2%, 237/2 886) and peripheral T-cell lymphoma (7.4%, 214/2 886). Of all the cases, the nodal lymphomas accounted for 45.8% (1 322 cases) and the extra nodal lymphomas accounted for 54.2% (1 564 cases); there were 389 patients (13.5%) with stage Ⅰ, 678 patients (23.5%) with stage Ⅱ, 975 patients (33.8%) with stage Ⅲ, and 722 patients (25.0%) with stage Ⅳ. The distribution of NHL subtypes in Shandong province was consistent with the domestic multicenter study. However, T-NHL subtype ratio was significantly higher than the foreign studies.Conclusions:The overall incidence of NHL in Shandong province of China is dominated by middle-aged people, and the proportion of B-NHL is higher than that of T-NHL. The distribution of NHL subtypes in Shandong province of China are different from those in the European and American countries, but are roughly consistent with the domestic multicenter study.