Lymphoma is a malignancy of mature lymphocytes. Signalling through the B cell receptor ( BCR ) is central to the development and maintenance of B cells. In light of the numer-ous proliferative and survival pathways activated downstream of the BCR, it comes as no surprise that malignant B cells would co-opt this receptor to promote their own growth and survival. Compounds that inhibit various components of this pathway, in-cluding spleen tyrosine kinase(Syk), Bruton’s tyrosine kinase (Btk), and phosphoinositol-3 kinase(PI3K), have been devel-oped. In this paper,the B-cell receptor signaling and its targeted inhibitors of lymphoid malignancies are reviewed.

Objective To express and detect the antigenicity of human laminin alpha4 LG3-4 module (hLN?4LG3-4) protein by gene engineering techniques. Methods The cDNA encoding hLN?4LG3-4 was amplified by RT-PCR from human placenta, then inserted into pMD-18T vector by T/A cloning and sequenced. Prokaryotic expression vector pET-28a-LG3-4 was constructed by recombinant DNA technique. The hLN?4LG3-4 fusion protein expressed in BL21(DE3)/pET system was identified by SDS-PAGE, purified by Ni-NTA resin, and assayed by Western blotting. Results The cDNA fragment of hLN?4LG3-4 was cloned successfully. While BL21 (DE3)/pET28a-LG3-4 bacterium was induced with IPTG, a new protein band with a relative molecular weight of 44 000 was shown on SDS-PAGE profile. hLN?4LG3-4 fusion protein of high purity (95%) was obtained and specific protein band was detected by Western blotting. Conclusion The hLN?4LG3-4 fusion protein was successfully expressed.

Objective To study the characteristics and regularities of somatotype growth of Yugu adolescents.Methods The somato-type growth of 989 Yugu adolescents(male:512,female:477)in Sunan was evaluated by the Heath-Carter method.Results The average somatotype of YuGu adolescents in males was mesomorphic ectomorph(3.0-3.6-3.7),and in females,the average somatotype was ectomorphic endomorph(3.8-2.9-3.6).The somatotypes develop from central,endomorphic ectomorph to mesomorphic ectomorph in the male,however,in the female from central,ectomorphic endomorph,endomorphic ectomorph,to mesomorphic endomorph.Conclusion The somatotypes of Yugu adolescents are very different between males and females.In the male group,the somatotypes of the 7-12 year-old group of Yugu adolescents are similar to the Mongolia,Han ethnic,Zhuang ethnic and Hungary.The somatotypes of 13-17 year-old group are similar to Tibetan,Zhuang ethnic,Han ethnic and Daur.However for the female group,the somatotypes of the 7-9 year-old group are similar to Hungary,and the 10-17 year-old group are similar to Tibetan,Zhuang ethnic,Han ethnic and Finn.

Objective To explore the molecular genetic characteristics of primary and recurrent glioblastomas (GBMs) from the same patient in vivo, primary glioma stem cells cultured in vitro, and patient-derived xenograft (PDX). Methods (1) The primary and recurrent GBM specimens from one patient during surgical resection were collected; and the expressions of glial fibrillary acidic protein (GFAP), nestin and Ki-67 were detected by immunohistochemical staining; the methylation of O6-methylguanine DNA methyltransferase (MGMT) gene, mutation of isocitrate dehydrogenase (IDH) gene and amplification of epidermal growth factor receptor (EGFR) gene were analyzed. (2) The primary and recurrent GBM stem cells were cultured in vitro and named as SU5-1 and SU5-2 cells, respectively; the expressions of nestin and CD133 were detected by immunohistochemical staining; GFAP expression was detected by immunohistochemical staining after induced differentiation, and the growth curve was detected by CCK-8 assay; Transwell invasion assay was used to detect the invasion ability; cell resistance to temozolomide (TMZ), carboplatin (CBP), cisplatin (DDP) and adriamycin (ADM) was detected by CCK-8 assay; the protein expression of programmed death receptor-ligand 1 (PD-L1) was detected by Western blotting. The rate of PD-L1 positive cells was detected by flow cytometry; genetic testing analysis was as above. (3) The primary and recurrent in situ PDX models in nude mice were established, and the expressions of nestin, GFAP and Ki-67 were detected by immunohistochemical staining. Results (1) As compared with the primary GBM, the recurrent GBM had significantly higher percentages of Ki-67 and nestin positive cells, while statistically lower percentage of GFAP positive cells (P<0.05); genetic analysis showed that there was no mutation in IDH gene in the primary GBM tissues and recurrent GBM tissues; the MGMT gene in the primary GBM tissues was methylated and EGFR gene was not amplified, while the MGMT gene in recurrent GBM tissues was demethylated and EGFR gene amplification was positive. (2) Both SU5-1 and SU5-2 cells expressed nestin and CD133, and GFAP was expressed after induced differentiation; the growth curve showed that the proliferation of SU5-2 cells started earlier than that of SU5-1 cells, the two were equal on the 3rd, 4th, and 5th d, and the proliferation of SU5-1 cells was faster than that of SU5-2 cells from the 6th d; the invasion ability of SU5-2 cells was statistically stronger than that of SU5-1 cells (P<0.05); the inhibition rates of SU5-2 cells treated with 5, 10, and 15 mmol/L CBP, 0.3125, 1.25, and 5 mmol/L DDP, 0.5 and 2 mmol/L ADM, and 125 and 500 mmol/L TMZ were significantly lower than those of SU5-1 cells treated with the same concentrations and same drugs (P<0.05); the protein expression of PD-L1 in SU5-2 cells was higher than that in SU5-1 cells; the positive rate of PD-L1 in SU5-2 cells was statistically higher than that in SU5-1 cells (P<0.05); the results of genetic analysis were consistent with those of the primary and recurrent GBM samples. (3) As compared with those in the primary PDX model, the nestin and Ki-67 expressions were significantly higher and GFAP expression was significantly lower in the recurrent PDX model (P<0.05); the results of genetic analysis were consistent with those of the primary and recurrent GBM samples. Conclusions Genetic differences are detected between primary and recurrent GBMs; recurrent GBM has stronger invasive capacity and multi-drug resistance. The primary stem cells derived from surgical specimens and corresponding PDX models could replicate the molecular genetic characteristics of original tumors, which provide a reliable experimental platform for both tumor translation researches and screening of molecular therapeutic targets.

Objective:To investigate the prognostic effect of polymorphnuclear neutrophil (PMN) in cervical cancer. Methods:Patients (n=92) who underwent curative surgery for the treatment of stage Ib and IIa cervical cancer according to the International Federation of Gynecology and Obstetrics (FIGO) were assessed to determine their tumor-infiltrating CD66b-positive neutrophils through immuno-histochemistry. Assessment results were then analyzed to identify their correlation with recurrence-free survival (RFS) as an end point. Kaplan-Meier method was used for survival curve analysis, and a Cox proportional hazard model was utilized for univariate and multi-variate analyses. Results:The RFS of the group with a density of CD66b-positive neutrophils above the median in cervical cancer tis-sues was significantly shorter than that of the group with a density of CD66b-positive neutrophils below the median (P=0.001). Univari-ate and multivariate analyses revealed adenocarcinoma (HR=3.020;95%CI=1.340-6.805;P=0.008), lymph node metastasis (HR=2.450;95%CI=1.065-5.637;P=0.035), and high neutrophil density (HR=2.866;95%CI=1.274-46.447;P=0.011) as independent prognostic fac-tors of short RFS. Conclusion:The increasing number of tumor-infiltrating neutrophils in cervical cancer tissues was correlated with short RFS of patients with cervical cancer.

Objective:To investigate the clinicopathological characteristics of the T cell lymphomas with CD20 expression, and to better understand this rare entity.Methods:Two-hundred cases of T-cell lymphoma diagnosed in the Department of Pathology of the Affiliated Hospital of Qingdao University from November 2016 to February 2020 were examined, and 5 cases of CD20-positive T-cell lymphomas were identified and included. Combined with clinical data and review of the literature, the clinicopathological characteristics of the disease were analyzed.Results:The five patients were all male, and had an average age of 56 years (range, 47 to 64 years). There were 2 cases of monomorphic epitheliotropic intestinal T-cell lymphoma, 2 cases of mycosis fungoides (1 case was plaque stage and the other was tumor stage) and 1 case of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Immunohistochemistry showed that all 5 cases expressed multiple T cell markers (CD3/CD4/CD5/CD7/CD8) and only one of B cell markers (CD20). Three of the 5 cases were negative for CD20 at the first diagnosis, while CD20 was diffusely positive on the second biopsy from the recurrence or progression of the disease, without expression of CD79a or PAX5. Epstein-Barr encoding region (EBER) in situ hybridization was negative in all 5 cases. T-cell receptor gene analysis showed monoclonal rearrangement of β or/and δ chains;Ig rearrangements were all polyclonal. None of the five patients were treated with rituximab, and 4 patients survived with disease and 1 patient survived without disease at the end of follow-up. Among them, the patient with mycosis fungoides at the cancerous stage has progressed rapidly and had poor quality of life.Conclusions:CD20-positive T-cell lymphoma is extremely rare. Its prognosis is closely related to the type of T-cell lymphoma, clinical stage and initial therapeutic effect. However, the expression of CD20 indicates the recurrence or progression of the disease, and the prognosis is relatively poor. When CD3 expression is absent in T-cell lymphoma, it is easy to be misdiagnosed as B-cell lymphoma. The combination of multiple immunohistochemical antibodies and molecular detection can improve the accuracy of diagnosis.

Objective:To investigate the association of plasma EBV-DNA copy number, serum cytokines and B symptoms in patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), unravel the mechanism and assess the prognostic value of clinical indicators.Methods:Clinical data of 173 newly-diagnosed ENKTL patients (116 male, 57 female; median age: 43, 4 to 71 years)were retrospectively analyzed. According to Ann Arbor stage, 126 cases were classified as stage I-II and 47 cases of stage Ⅲ-IV. The primary sites of tumors included nasal cavity (n=100), extranasal upper aerodigestive tract (extranasal UADT, n=34), and extra-upper aerodigestive tract (extra-UADT, n=39). Prior to treatment, 91 patients had B symptoms and 82 cases of without B symptoms. According to plasma EBV-DNA copy levels, all patients were divided into the negative group (n=36), low load group (<10 4 copies/ml, n=73) and high load group (≥10 4 copies/ml, n=64). Serum cytokines including IFN-γ, IL-2, IL-4, IL-6, IL-10 and TNF-α were detected. Correlation analysis was performed by Cochran-Armitage trend test and Spearman correlation analysis. Survival analysis was conducted using univariate and multivariate Cox regression hazard analysis and survival curves were derived from Kaplan-Meier survival analysis. Results:The incidence of B symptoms and fever showed a significant upward trend with the increasing plasma EBV-DNA copy levels. In addition, serum levels of IFN-γ, IL-6 and IL-10 cytokines were higher in patients with B symptoms than those without B symptoms (all P<0.05). Serum IFN-γ, IL-6, and IL-10 levels were also positively correlated with plasma EBV-DNA copy number. The occurrence of B symptoms was associated with high-risk clinical features including advanced stage, primary tumor invasion, regional lymph node involvement, and elevated pre-treatment LDH. Survival analysis showed that stage, B symptoms, plasma EBV-DNA, and the above serum cytokines affected the prognosis of overall survival (OS) and progression-free survival (PFS) (all P<0.05). However, multivariate analysis showed that the occurrence of B symptoms was not an independent prognostic factor of ENKTL patients. Conclusion:This exploratory study suggests that the incidence of B symptoms is associated with increasing levels of EBV-DNA copies and cytokines, and these indicators are also important factors influencing the prognosis of ENKTL patients.

Cancer genomics has led to the discovery of numerous oncogenes and tumor suppressor genes that play critical roles in cancer development and progression.Oncogenes promote cell growth and proliferation,whereas tumor suppressor genes inhibit cell growth and division.The dysregulation of these genes can lead to the development of cancer.Recent studies have focused on non-coding RNAs(ncRNAs),including circular RNA(circRNA),long non-coding RNA(lncRNA),and microRNA(miRNA),as therapeutic targets for cancer.In this article,we discuss the oncogenes and tumor suppressor genes of ncRNAs associated with different types of cancer and their potential as therapeutic targets.Here,we highlight the mechanisms of action of these genes and their clinical applications in cancer treatment.Understanding the molecular mechanisms underlying cancer development and identifying specific therapeutic targets are essential steps towards the development of effective cancer treatments.

Purpose To investigate the expression and po-tential clinical value of heat shock protein 90α(Hsp90α)in co-lon adenocarcinoma.Methods The expression level of Hsp90αin colon adenocarcinoma and its relationship with clinicopatho-logical features,prognosis and immune cell infiltration were ana-lyzed by bioinformatics and immunohistochemistry.The prolifer-ation ability of colon cancer cells before and after Hsp90AA1 knockout was detected by CCK-8 cell proliferation assay and plate cloning assay.Results The bioinformatics tools showed that Hsp90AA1 was abnormally higher in colon cancer tissues than adjacent tissues,and the higher the expression level,the worse the prognosis of patients.The expression of Hsp90AA1 was positively correlated with the infiltration levels of CD4+T cells(Th2),CD8+T cells,myeloid inhibitory cells,Tregs cells,neutrophils,macrophages,M1 macrophages and M2 macropha-ges.Immunohistochemical results showed that the expression of Hsp90α in colon cancer tissues was significantly higher than in its adjacent tissues.The expression of Hsp90α was related to age(P＜0.05),not related to gender,tumor size,location,clini-cal classification,differentiation degree,tumor node metastasis,lympho-vascular invasion,perineural invasion(P＞0.05).The high expression of Hsp90α was an independent risk factor for the prognosis of colon cancer patients.The results of cell experi-ments showed that Hsp90AA1 knockout inhibited the growth and proliferation of colon cancer cells.Conclusion Hsp90α is highly expressed in colon adenocarcinoma,which may be a po-tential molecular marker for poor prognosis of colon adenocarci-noma.

Objective: To investigate the expression of metastasis-associated protein 2 (MTA2) in human bladder cancer tissues and its effect on the malignant biological behaviors of bladder cancer T24 cells, as well as to explore the effect of MTA2 on the progression of bladder cancer. Methods: Sixty-two cases of human bladder cancer tissues and 28 cases of normal bladder tissues (from patients with cystitis, and pathologically confirmed as normal tissue) were collected at People’s Hospital of Hebei Province during December 2012 and December 2014. The expression of MTA2 in bladder cancer tissues and normal bladder tissues was detected by immunohistochemical staining, and the correlation between MTA2 expression and clinicopathological characteristics of patients was also analyzed. The bladder cancer T24 cell line stably expressing MTA2 was constructed. The effects of MTA2 on the proliferation, colony formation, migration and invasion of bladder cancer T24 cells were detected by MTS, clone formation, scratch healing and Transwell assay, respectively. Results: Immunohistochemical staining showed that MTA2 expression was significantly up-regulated in bladder cancer tissues as compared with normal bladder tissues (P<0.01). The high expression of MTA2 in bladder cancer tissues was not related to gender, age and tumor volume (P>0.05), but was associated with higher TNM stage, histological grade, and lymphatic infiltration and metastasis (all P<0.05). After over-expression of MTA2 in bladder cancer T24 cell line, the proliferation activity of the cells was significantly increased (P<0.05), and the colony formation, scratch healing, migration and invasion ability were significantly increased (all P<0.01). Conclusions: MTA2 is up-regulated in human bladder cancer tissues and can promote the proliferation, tumor formation, migration and invasion of T24 cells.