Objective To evaluate the role of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation in relapsed/refractory marginal zone lymphomas. Methods The transplant database was reviewed retrospectively from Tianjin Medical University Cancer Hospital identified 12 patients who underwent high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation. Results Among the twelve patients who underwent autologous hematopoietic stem cell transplantation, the median duration of progression-free survival (PFS) was 104 months and the median duration overall survival (OS) was 117 months; 6 patients were still alive with disease-free. Conclusion High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation is feasible to patients with relapsed/refractory marginal zone lymphomas, particularly to those insensitive to rituximabincluded combined chemotherapy.

0.05).Conclusion:The lymphoid tissues can not only express the ACTH-R?5-HT_ 1A-R protein but also synthesize their mRNA.ACTH and 5-HT can regulate the functions of the immune system through their receptors on the membrane of the immunocytes.

Objective:Clinicopathological features, treatment and prognosis of urinary and male reproductive system soft tissue sarcoma (STS) and sarcomatoid carcinoma in adults were compared.Methods:A retrospective analysis was performed on the clinical data of 73 patients with STS and 15 patients with sarcomatoid carcinoma in adult urinary and male reproductive system in the First Affiliated Hospital of Zhengzhou University. There were 59 males and 14 females in STS group, with a median age of 41 (18-78)years old. The maximum tumor diameter ranged from 0.5 to 19.0 cm. The primary tumors were located in testis and peritesticular (23 cases), kidney (23 cases), prostate (15 cases), bladder (8 cases), ureter(3 cases), other parts(1 case). There were 18 cases of lymph node metastasis and 8 cases of distant metastasis. Among 73 patients with STS, 66 patients underwent surgical resection, of which 31 patients underwent radical resection. Among the 66 patients who underwent surgery, 3 patients received neoadjuvant chemotherapy; 22 patients received adjuvant chemotherapy; 5 patients were treated with adjuvant radiotherapy. Among 7 patients with STS did not receive surgical treatment, 2 patients received radiotherapy combined with chemotherapy, 2 patients received chemotherapy alone, and 3 patients received symptomatic support treatment.There were 11 males and 4 females in sarcomatoid carcinoma group, with a median age of 65 (23 - 84)years old. The measurable tumor diameter ranged from 0.4 to 16.9 cm. The primary tumors were located in kidney (6 cases), bladder (5 cases), ureter(2 cases) and prostate(2 cases). There were 2 patients of lymph node metastasis and 4 patients of distant metastasis. Of the 15 patients with sarcomatoid carcinoma, 12 patients underwent surgical resection, of which 5 patients underwent radical resection. 2 patients were treated with adjuvant therapy after operation. Among the 12 patients who received surgical treatment, 2 patients had distant metastasis before operation, all of which originated from the kidney. Among the 3 patients without surgical treatment, 1 patients received systemic chemotherapy and 2 patients received symptomatic supportive treatment. There was no significant difference in gender, tumor maximum diameter, distant metastasis and operation, chemotherapy, radiotherapy and operation combined with chemotherapy ( P>0.05) and there were significant differences in age, tumor primary location and lymph node metastasis ( P<0.05) between STS and sarcomatoid carcinoma patients.The categorical variables of the two groups were compared by χ2.With Kaplan-Meier method for univariate survival analysis, the Cox was used for multivariate analysis. Results:The median follow-up time was 18.3(0.3-90.4) months.In STS group, there were 14 patients of synovial sarcoma, 11 patients of liposarcoma, 15 patients of rhabdomyosarcoma, 16 patients of leiomyosarcoma, 10 patients of other types, and 7 patients of spindle cell sarcoma without specific classification. Among 66 patients with STS, 8 patients recurred, 14 patients metastasized after operation, 4 patients recurred and metastasized after operation. The 7 patients without surgical treatment all progressed. Among the 10 patients of sarcomatoid carcinoma without distant metastasis before operation, 3 patients recurred and 3 patients metastasized after operation. Two patients of renal sarcomatoid carcinoma with distant metastasis were treated with nephrectomy and chemotherapy. One of them had overall survival (OS) up to 2 years, and one recurred 2 months after operation. The 3 patients without surgical treatment all progressed without remission. The median OS of STS patients were 59.3 (95% CI 24.1-94.5) months and that of sarcomatoid carcinoma patients were 8.7 (95% CI 6.1-11.2) months. The OS of STS patients were better than those of sarcomatoid carcinoma patients ( HR=2.874, 95% CI 1.118-7.386, P=0.022). Conclusions:The onset age of STS in adult urinary and male reproductive system was lower than that in sarcomatoid carcinoma. The primary lesions of STS were mainly in testis, peritesticular and kidney. The primary lesions of sarcomatoid carcinoma were mainly in kidney. Among STS, leiomyosarcoma was the most common type.STS and sarcomatoid carcinoma should be diagnosed and treated with surgery quickly, and systemic therapy should be performed for patients who cannot be treated with surgery.

Objective:To investigate the expression of MACC1 in Klatskin tumor and the relationship between the clinicopathological features and prognosis and the expression of MACC1.Methods:Immunohistochemistry staining was employed to assess the expression of MACC1 protein in Klatskin tumor tissues and matched adjacent non-tumor bile duct tissues.Quantitative real-time PCR was performed to examine MACC1 mRNA expression in Klatskin tumor tissues and the adjacent non-tumor bile duct tissues and normal bile duct tissues.The correlation between MACC1 expression and the clinicopathological features and prognosis was analyzed.Results:The positive rate of MACC1 in Klatskin tumor tissues was significantly higher than that in matched adjacent non-tumor bile duct tissues(P＜0.05).MACC1 mRNA expression in carcinoma tissues was significantly higher than that in the non-tumor bile duct tissues and normal bile duct tissues(P＜0.05).MACC1 expression in Klatskin tumor tissues was related to tumor size,recurrence and lymphatic metastasis(P＜0.05).Survival analysis indicated that the 1-year,3-year,5-year survival rate were with significantly differences between the two groups (P＜0.05).Conclusion:MACC1 expression was significantly higher in Klatskin tumor and it was related to the tumor size,recurrence and lymphatic metastasis.It would affect the prognosis of patients.

Objective:To study the relationship between rs 2228314 polymorphism in sterol regulatory element binding protein 2 gene (SREBP2) and obesity, serum lipid levels in children and adolescents . Methods:In our study , 2 030 children and adolescents aged from 7 to 18 years participated .Anthropo-metric measurements, including height and weight, were performed.Their serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol ( HDL-C) were detected .The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS ) was used to detect rs2228314 genotypes.Results: The GC/CC genotypes of rs2228314 polymorphisms had lower HDL-C levels than GG genotype [(0.10 ±0.35) mmol/L vs. (0.14 ±0.36) mmol/L, P=0.020].The rs2228314 polymorphism was associated with the abnormal HDL-C level under the dominant model after adjustment for study samples , sex and age ( OR=1.400, 95%CI:1.027-1.907, P=0.033).The rs2228314 polymorphism was not associated with obesity un-der the dominant model after adjustment for study samples , sex, age and HDL-C level ( OR=1.178, 95%CI: 0 .971 -1 .430 , P =0 .096 ) . Conclusion: The GC/CC genotype carriers of SREBP2 rs2228314 polymorphism have higher risk of abnormal HDL-C level than the individuals with GG geno-type among children and adolescents .

Monoclonal antibody drugs that inhibit programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) have been widely used in esophageal cancer (EC) and yielded significant therapeutic responses. However, only a few patients obtain lasting clinical benefits due to primary or acquired drug resistance, and new treatment schemes are urgently needed. The tumor immune microenvironment is the main factor that affects patients' response to immunosuppressive agents. This article will discuss the role of immunosuppressive cells and non-cellular components in the immune process to provide ideas for the next research direction of EC.

Objective To establishing an immortal cell line of familial papillary thyroid carcinoma (FPTC), and explore a new approach for studying familial non-medullary thyroid carcinoma (FNMTC). Methods The specimen from a patient with FPTC was selected, separated, and the primary cells were cultured using DMEM/F12 medium (with TSH, T3, EGF and hydrocortisone). To inducing cell immortalization, the exogenous genes SV40T/TERT were transfected into cells by two ways. RT-PCR was used to detect the expressions of thyroid peroxidase (TPO), thyroid globulin (TG), thyroid stimulating hormone receptor (TSHR) and sodium/iodide co-transporter (NIS). Immunofluorescence method was used to detect the expressions of TPO and GPC3. In order to detect the genomic mutations, the peripheral blood DNA of the patient was extracted. The cell genome was detected. Results The FPTC cells adhered to the plate and showed an irregular polygon shape. The cells can stably grow for six months, FPTC-S (with SV40T transfected) passaged to p26, FPTC cells passaged to p23 and FPTC-ST (with SV40T/TERT transfected) passaged to p19. Both FPTC-S and FPTC-ST can stably express TPO, TG and TSHR in mRNA level. MLH1 R217C mutation existed in the peripheral blood of the patient, and BRAF V600E mutation existed in the primary cultured cells. Either the primary or the immortal cells showed MLH1 R217C mutation. Conclusion This study preliminarily established an immortal cell line of familial papillary thyroid carcinoma with MLH 1 R217C and BRAF V600E mutations. This cell line provides a research model for studying these mutations in FPTC.

Objective:To investigate the effect and mechanism of longikaurin A (LK-A) on glioma proliferation.Methods:Resuscitated frozen human glioma cell lines U87 and SNB19 were in vitro sub-cultured; CCK-8 assay was used to detect the cell activity changes 24 and 48 h after 0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0 μmol/L LK-A. Edu proliferation assay was used to detect the changes in number of Edu positive cells after 0, 1, 2 and 3 μmol/L LK-A, and cell clonal formation assay was used to detect the changes in number of cell colony formation after 0, 0.1, 0.2 and 0.3 μmol/L LK-A. Flow cytometry was used to detect the changes in cell cycle proportion after 0, 1, 2 and 3 μmol/L LK-A. Expression changes of proliferation-related proteins (Ki-67 and c-Myc) and cell cycle-related proteins (Cyclin B1, Cyclin D1, cyclin dependent kinase 1 [CDKl]) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway-related proteins were detected by Western blotting after 0, 1, 2, and 3 μmol/L LK-A. Results:U87 and SNB19 cell viabilities decreased gradually after being treated with 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, and 8.0 μmol/L LK-A for 24 and 48 h compared with those with 0 μmol/L LK-A, with significant differences ( P<0.05); cell viability was dose-dependent. The number of Edu positive cells in U87 and SNB19 after being treated with 2, and 3 μmol/L LK-A was significantly decreased compared with that with 0 μmol/L LK-A ( P<0.05). The colony formation number of U87 and SNB19 cells after being treated with 0.1, 0.2 and 0.3 μmol/L LK-A decreased significantly compared with that with 0 μmol/L LK-A ( P<0.05). The proportion of U87 and SNB19 cells at G2/M phase after being treated with 2 and 3 μmol/L LK-A were increased significantly compared with that with 0 μmol/L LK-A ( P<0.05). The Ki-67, c-Myc, Cyclin B1, CDK1, p-PI3K and p-AKT expressions were significantly decreased, while Cyclin D1 expression was significantly increased in U87 and SNB19 cells after being treated with 2 and 3 μmol/L LK-A compared with those with 0 μmol/L LK-A ( P<0.05). Conclusion:LK-A can inhibit the glioma proliferation and arrest glioma at G2/M phase, with dose-dependent manner; the mechanism is related to inhibition of PI3K/AKT signaling pathway by LK-A.

Objective: To explore the expression of microRNA-17-5p (miR-17-5p) in esophageal squamous cell carcinoma (ESCC) and its effects on cell proliferation and invasion ability. Methods: Real-time quantitative PCR (RT-qPCR) was used to detect the miR-17-5p level in ESCC tissues and cells. MiR-17-5p inhibitor and negative control (NC) were transfected into EC9706 and TE1 cells, and miR-17-5p expression was examined by using RT-qPCR. Cell counting kit-8 (CCK-8) and EdU were conducted to detect cell proliferation and Transwell chamber was used to investigate cell invasion ability. Dual-luciferase reporter assay was used to detect the direct interaction of miR-17-5p and retinoblastoma-like protein-2 (RBL2). Western blot and RT-qPCR were used to detect the expression of RBL2 in ESCC tissues, respectively. Finally, the correlation between RBL2 and miR-17-5p was analyzed. Results: The miR-17-5p level in ESCC tissues was 4.222±0.392, significantly higher than 1.081±0.046 in normal esophageal epithelial tissues (P<0.001). The expressions of miR-17-5p in ESCC cells, including EC9706, Eca109, TE1, KYSE450, KYSE70 and KYSE520, were 13.84±1.266, 6.453±0.293, 11.41±0.520, 2.613±0.548, 5.251±0.239 and 4.251±0.195, respectively, all obviously higher than (1.007±0.079) in normal esophageal epithelial cell Het-1A (P<0.05). The miR-17-5p level in patients with ESCC Ⅲ~Ⅳ was 5.094±0.562, markedly higher than 2.934±0.364 in patients with ESCCⅠ~Ⅱ(P<0.01). Moreover, the miR-17-5p level in ESCC patients with lymph node metastasis was 5.523±0.634, markedly higher than 3.533±0.461 in ESCC patients without lymph node metastasis (P<0.05). The survival ratio of ESCC patients with higher miR-17-5p level was evidently lower than that of ESCC patients with lower miR-17-5p level (P<0.05). MiR-17-5p inhibitor significantly downregulated the miR-17-5p expression in EC9706 and TE1, which suppressed cell proliferation and invasion ability. Dual-luciferase reporter assay revealed that co-transfection of 3′ untranslated region-wild type (3′UTR-WT) of RBL2 and miR-17-5p mimic significantly reduced luciferase activity in EC9706 and TE1 cells (P<0.01), which implicated that RBL2 was the direct target of miR-17-5p. The result of western blot revealed that RBL2 protein expressions in miR-17-5p group of EC9706 and TE1 cells were 0.936±0.055 and 0.923±0.048, obviously higher than 0.087±0.019 and 0.102±0.010 in control group (P<0.001). The expression of RBL2 in ESCC tissues was 0.219±0.510, markedly lower than 0.983±0.324 in normal esophageal epithelial tissues (P<0.001). The miR-17-5p level exhibited a negative correlation with RBL2 level in ESCC tissues (r=-0.462, P<0.001). Downregulation of RBL2 reversed the miR-17-5p inhibitor induced suppression of cell proliferation and invasion ability. Conclusion MiR-17-5p participates in the carcinogenesis and development of ESCC, thus may be a potential therapeutic target for ESCC patients.

The outbreak and spread of coronavirus disease 2019 (COVID-19) highlighted the importance and urgency of the research and development of therapeutic drugs. Very early into the COVID-19 pandemic, China has begun developing drugs, with some notable progress. Herein, we summarizes the anti-COVID-19 drugs and promising drug candidates originally developed and researched in China. Furthermore, we discussed the developmental prospects, mechanisms of action, and advantages and disadvantages of the anti-COVID-19 drugs in development, with the aim to contribute to the rational use of drugs in COVID-19 treatment and more effective development of new drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the variants. Neutralizing antibody is an effective approach to overcome COVID-19. However, drug resistance induced by rapid virus mutation will likely to challenge neutralizing antibodies. Taking into account current epidemic trends, small molecule drugs have a crucial role in fighting COVID-19 due to their significant advantage of convenient administration and affordable and broad-spectrum. Traditional Chinese medicines, including natural products and traditional Chinese medicine prescriptions, contribute to the treatment of COVID-19 due to their unique mechanism of action. Currently, the research and development of Chinese anti-COVID-19 drugs have led to some promising achievements, thus prompting us to expect even more rapidly available solutions.