Analysis of correlation between the number of circulating DLBCL cells and marrow tumor burden by FCM and its clinical significance / 中华检验医学杂志

Objective:To investigate the correlation between the number of circulating DLBCL cell and the marrow tumor cell burden and the prognostic indicators in patients with DLBCL, and to evaluate the feasibility of circulating DLBCL cell reflecting the marrow tumor burden and disease progression. Optimization of FCM for screening circulating DLBCL cell was done to monitor MRD and recurrence.Methods:We conducted a retrospective study in 75 diagnosed DLBCL patients in the First Affiliated Hospital of Zhengzhou University from June 2020 to February 2021, including 43 males and 32 females aged 61 (37-85) years. According to the diagnosis and treatment criteria, the patients were divided into initial and recurrence group ( n = 53), partial response(PR)group ( n=14) and complete response(CR)group ( n=8). According to the positive criteria of circulating DLBCL cells, 48 cases were divided into circulating DLBCL positive group and 27 cases were negative group. 30 anemia patients with non-B-cell tumor-related diseases were selected as the control group, including 16 males and 14 females, aged 52 (30-79) years. 70 healthy subjects, including 36 males and 34 females, aged 39 (25-57), were selected for methodology optimization. FCM was used to detect the ratio of marrow and circulating DLBCL cells in each group, and analyze the connection between circulating DLBCL cells and clinical indicators. Statistical analysis was performed using t test, χ 2 test, Kruskal-Wallis H test, Spearman rank correlation, and Logistic regression. Results:(1) Bone marrow and circulating DLBCL cells were not detected in CR group and control group; The positive rate of circulating DLBCL cells in the initial/recurrent group and PR groups was 75.47% and 57.14%, respectively. The proportion of bone marrow and circulating DLBCL cells was positively correlated in the two groups ( P value was <0.001 and 0.020, respectively). (2) The proportion of bone marrow and circulating DLBCL cells in the initial and recurrent groups, PR group, CR group and control group decreased successively ( P<0.05). The proportion of DLBCL cells was 27.72% (initial and recurrent bone marrow group), 26.92% (initial and recurrent circulating group), 3.23% (bone marrow PR group) and 1.67% (circulating PR group), respectively. (3) Compared with the negative group, the circulating DLBCL cell positive group had increased LDH, β 2-MG, and CMYC expression(≥80%), with decreased LYM, HGB<100 g/L, B symptoms, PD-L1 expression, and age ≥60 years, showing higher ECOG, aaIPI/IPI scores and Ann staging ( P<0.05). Age ≥60, B symptoms, and PD-L1 expression were independent risk factors for circulating DLBCL cells ( P<0.05). Conclusions:The detectable rate of circulating DLBCL cell could be improved by optimizing the preoperative treatment conditions of FCM. Circulating DLBCL cells can reflect the tumor burden and disease progression. Detecting circulating DLBCL cells may improve patients′ compliance.

The effect of rapamycin and underlying mechanism on hepatic ischemia-reperfusion injury in Sprague Dawley rats / 中华肝胆外科杂志

Objective:To investigate the effect of rapamycin on hepatic ischemia-reperfusion injury (HIRI) in Sprague Dawley (SD) rats and its underlying mechanism.Methods:Forty-eight specific pathogen-free SD male rats with the body weight of 180-200 g and the age of 4-8 weeks were randomly divided into 3 groups, 16 rats each group. In the rapamycin group, the rats were injected with rapamycin intraperitoneally everyday lasting for 3 days before the surgery, and in the model group and the sham group, the rats were injected with normal saline intraperitoneally. The HIRI model was performed in the rapamycin group and the model group. Serum of 8 rats was randomly harvested from each group at 2 h and 24 h after the surgery and was used to detect level of alanine aminotransferase(ALT), total bilirubin, and lactate dehydrogenase. At the meantime, liver tissues were collected for HE staining, and enzyme-linked immunosorbent assay of superoxide dismutase(SOD), glutathione, hexokinase 2, phosphofructokinase 1(PFK1), and adenosine triphosphate. Polymerase chain reaction and Western blots were used to determine the levels of mammalian target of rapamycin(mTOR), ribosomal protein S6 kinase 1(S6K1), and protein kinase B and their phosphorylation levels respectively.Results:Two hours post the surgery, the serum level of ALT(150.9±18.7) U/L, total bilirubin(5.15±0.69) μmol/L, and lactate dehydrogenase(9 547±365) U/L were higher in the model group than sham group (42.4±10.7) U/L, (2.48±0.24) μmol/L, (4 424±376) U/L and rapamycin group (87.7±11.2) U/L, (3.09±0.12) μmol/L, (8 268±264) U/L, and all differences were statistically significant (all P<0.05). HE staining and serum assay showed that the lesion of liver tissuesand of liver function were damaged in the model group, and mitigated in the rapamycin group at 2h and 24h after the surgery. At 2h and 24h after the surgery, liver SOD, glutathione, hexokinase 2, PFK1, and adenosine triphosphate in the model group were lower than those in the sham group and the rapamycin group, and all differences were statistically significant (all P<0.05). The relative levels of mTOR, S6K1, and their phosphorylation level in the model group were higher than those in the sham group and the rapamycin group at 2 h and 24 h after the surgery, but the relative levels of protein kinase B and phosphorylated protein kinase B were lower than those in the sham group and the rapamycin group, and all differences were statistically significant (all P<0.05). Conclusions:Rapamycin improves glucose metabolism and reduces oxidative stress via upregulating the phosphorylated protein kinase B through inhibition of mTOR signaling pathway, thus alleviates HIRI in rats.

Inhibitory effect of PI3Kδ inhibitor idelalisib on proliferation of human myeloid leukemia cells and the reversal effect on drug resistance to adriamycin / 中南大学学报(医学版)

OBJECTIVES@#To investigate the effect of adriamycin (ADM), idelalisib or ADM and their combination on cell proliferation and intracellular concentration of ADM, and to explore the reversal effect of idelalisib on drug resistance to ADM.@*METHODS@#The K562 and K562/ADM cells were respectively treated with ADM and idelalisib at different concentrations. The 50% inhibitory concentration (IC@*RESULTS@#The cell survival rates were significantly decreased in a dose-dependent manner when the cells were treated with different doses of ADM (0.001-10.000 mg/L ). The IC@*CONCLUSIONS@#Idelalisib exerts effect on inhibition of the proliferation in myeloid leukemia K562 and K562/ADM cells, which may partially reverse the drug resistance of K562/ADM cells to ADM. The mechanisms for the effect of idelalisib may be related to increasing the accumulation of ADM and inducing the cell apoptosis in the K562 and K562/ADM cells.

Effect of rapamycin on hepatic ischemia reperfusion injury in rats and its possible mechanism / 中华肝胆外科杂志

Objective To analyze the effects of different doses of rapamycin on hepatic ischemia reperfusion injury in rats and the possible mechanism.Methods 48 Sprague-Dawley rats were randomly divided into four groups(n=12),low dose group (preoperative injection of low dose of rapamycin+ischemia),high dose group (preoperative high dose of rapamycin injection + ischemia),model group (preoperative injection of 0.9％ sodium chloride solution + ischemia),sham group (preoperative injection of 0.9％ sodium chloride solution,only dissected the first hepatic portal).Serum was collected 24 and 72 hours after surgery,ALT,AST,TNF-α and IL-6 concentrations were detected,Western blotting and PCR were performed to detect the expression of autophagy proteins,and HE staining was performed.Results 24 h after the operation,the liver tissue of the sham group was almost normal,the hepatic lobule structure of the model group disappeared,the liver cells were edema,vacuolar degeneration and necrosis,and the damage was reduced in the low dose and high dose group.24 h after surgery,levels of ALT,AST,TNF-α and IL-6 was on a declining curve in all groups,with statistically significant differences (P＜0.05).24 h after surgery,the relative expression levels of ULK1 (1.00±0 vs.4.76±2.62 vs.8.26±3.46 vs.12.95±6.45),microtubuleassociated protein 1 light chain 3(LC3,1.00±0 vs.2.88±0.59 vs.4.66± 1.22 vs.7.10±0.85) mRNA in sham group,model group,low dose group and high dose group were increased.While the relative mRNA expression levels of mammalian target of rapamycin (mTOR,1.00±0 vs.0.31 ±0.09 vs.0.18±0.04 vs.0.02± 0.01),P70 ribosomal protein kinase (S6K1,1.00±0 vs.0.57±0.34 vs.0.27±0.14 vs.0.03±0.01) showed a decreasing trend,and the differences were statistically significant (P＜0.05).24 h after surgery,the relative expressions of ULK1 and LC3 proteins in sham group,model group,low dose group and high dose group increased,while the phosphorylation of mTOR,S6K1 and ULK1 decreased,with statistically significant differences (P＜0.05).72 h after the operation,the results were agreed with those at 24 h after the operation.Conclusion Rapamycin activates autophagy through mTORC1-ULK1 signaling pathway to reduce HIRI,and the protective effect of high dose is better than that of low dose.

Advances of treatment for early stage extranodal nature killer/T-cell lymphoma, nasal type / 中国医师杂志

Extranodal natural killer/T-cell lymphoma (ENKTL) (nasal type) is a special type of non-Hodgkin's lymphoma.This disease is highly aggressive with rapid progression and poor prognosis.It appears mostly in nasal cavity,most patients are in early stage,and the treatment outcome and prognosis are poor.There is no standard treatment scheme.Recently,L-asparaginase based chemotherapy shows good short-term effect and long-term survival in the treatment of localized extranodal natural killer/T-cell lymphoma.This review will explore the advances of treatment for localized extranodal nature killer/T-cell lymphoma.

Research progress of primary breast diffuse large B cell lymphoma / 中国医师杂志

Primary breast lymphoma (PBL) is a rare form of extranodal non-Hodgkin lymphoma,with breast mass as the main symptom,with or without local lymphadenpathy,and it shows metastatic features and poor prognosis.Diffuse large B-cell lymphoma is the most common pathological pattern,other forms like follicular lymphoma is less common.There is no consensus on prognostic factor and first-line treatment plan at present.In this review,we describe the pathogenesis,staging,risk stratification,prognosis,and treatment advances of primary breast diffuse large B cell lymphoma (PB-DLBCL).

Silencing of Long Non-Coding RNA MALAT1 Promotes Apoptosis of Glioma Cells

The metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) is a highly conserved long non-coding RNA (lncRNA) gene. However, little is known about the pathological role of lncRNA MALAT1 in glioma. In the present study, we explored the expression level of lncRNA MALAT1 in primary glioma tissues as well as in U87 and U251 glioma cell lines. Using qRT-PCR, we found that the expression of lncRNA MALAT1 was significantly increased in glioma tissues compared with that of paracancerous tissues. Meanwhile, the expression of MALAT1 was highly expressed in U98 and U251 cells. In order to explore the function of MALAT1, the expression of MALAT1 was greatly reduced in U87 and U251 cells transfected with siRNA specifically targeting MALAT1. Consequently, cell viability of U87 and U251 cells were drastically decreased after the knockdown of MALAT1. Concomitantly, the apoptosis rate of the two cell lines was dramatically increased. Furthermore, the expression levels of some tumor markers were reduced after the knockdown of MALAT1, such as CCND1 and MYC. In summary, the current study indicated a promoting role of MALAT1 in the development of glioma cell.