NDRG2 mRNA levels and miR-28-5p and miR-650 activity in chronic lymphocytic leukemia.

BACKGROUND: NDRG2 is identified as a tumor suppressor gene in many tumors, and functions in cell proliferation, differentiation and apoptosis. Recent data indicate that NDRG2 expression is up-regulated by TP53. Moreover, proposed mechanisms of NDRG2 inactivation include epigenetic silencing of the NDRG2 promoter and down-regulation by microRNAs (miRNAs). However, few studies have ever been done on the role of NDRG2 and the NDRG2-regulating miRNAs interference in chronic lymphocytic leukemia (CLL). METHODS: NDRG2 and microRNAs mRNA levels in CLL subjects were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The dual-luciferase reporter assay was performed to determine NDRG2-related miRNAs. Low expression of mature exogenous miRNAs in CLL cells was established by transient transfection. NDRG2 protein levels in CLL cells were detected by western blot. In addition, flow cytometry was conducted to examine the apoptosis of CLL cells. RESULTS: Lower expression of NDRG2 was found in the B-cells from 102 CLL patients compared the 40 normal subjects (P < 0.001). Patients with advanced Binet stage (P = 0.001), high lactate dehydrogenase (LDH) level (P = 0.036), un-mutated immunoglobulin heavy chain variable region gene (IGHV) (P = 0.004) and those with p53 aberrations (P < 0.001) had a markedly lower levels of NDRG2 mRNA. This decrease was associated with briefer time-to-treatment (P = 0.001) and poorer survival (P < 0.001). High expression of miR-28-5p and miR-650 was associated with Binet B/C stage (P = 0.044) and IGHV un-mutated (P = 0.011), as well as Binet B/C stage (P = 0.013) and p53 aberrations (P = 0.037), respectively. Inhibition of miR-28-5p or miR-650 could induce more apoptosis in CLL cells with germline TP53. CONCLUSIONS: NDRG2 mRNA levels might be a useful prognostic variable for patients of CLL and up-regulating NDRG2 transcription may be a therapy approach in CLL without p53 aberrations.

[Clinical Characteristics of CD4-CD56+ Blastic Plasmacytoid Dendritic Cell Neoplasm].

OBJECTIVE: To explore the clinical manifestations, pathological features, immunophenotype, as well as diagnosis, treatment and prognosis of patients with CD4-CD56+ blastic plasmacytoid dendritic cell neoplasm (BPDCN), in order to further understand the rare disease. METHODS: The clinical data, laboratory examinations and treatment regimens of two patients with CD4-CD56+ BPDCN in the First Affiliated Hospital of Wannan Medical College were retrospectively analyzed. RESULTS: The two patients were both elderly males with tumor involved in skin, bone marrow, lymph nodes, etc. Immunohistochemical results of skin lesions showed that both CD56 and CD123 were positive, while CD4, CD34, TdT, CD3, CD20, MPO and EBER were negative. Flow cytometry of bone marrow demonstrated that CD56, CD123, and CD304 were all positive, while specific immune markers of myeloid and lymphoid were negative. Two patients were initially very sensitive to acute lymphoblastic leukemia or lymphomatoid chemotherapy regimens, but prone to rapid relapse. The overall survival of both patients was 36 months and 4 months, respectively. CONCLUSION: CD4-CD56+ BPDCN is very rare and easily misdiagnosed as other hematological tumors with poor prognosis. Acute lymphoblastic leukemia or lymphomatoid therapy should be used first to improve the poor prognosis.

[Clinical Anslysis of Primary Adrenal NK/T-Cell Lymphoma].

OBJECTIVE: To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma. METHODS: The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed. RESULTS: Combined with pathology, imaging, bone marrow examination， etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimen（gemcitabine 1 g/m2 d1 + oxaliplatin 100 mg/m2 d 1 + etoposide 60 mg/m2 d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5） was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later. CONCLUSION: PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.

Efficacy and Safety of Sevelamer Carbonate in Chinese Nondialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized, Double-Blind, Parallel-Group Study.

Introduction: Previous studies suggested that sevelamer carbonate is well tolerated with a favorable efficacy and safety profile in both dialysis and nondialysis patients in Europe; however, the efficacy remains controversial, and few studies have examined sevelamer carbonate therapy in other ethnic nondialysis CKD patients. This study assessed the efficacy and safety of sevelamer carbonate in Chinese nondialysis CKD patients with hyperphosphatemia. Methods: The multicenter, randomized, double-blind, parallel-group, placebo-controlled, and phase 3 clinical trial enrolled 202 Chinese nondialysis CKD patients with serum phosphorus ≥1.78 mmol/L. Patients were randomly assigned 1:1 to receive sevelamer carbonate (2.4-12 g per day) or placebo for 8 weeks. The primary outcome was the change in serum phosphorous between baseline and week 8. Results: Totally 482 Chinese patients were screened and 202 were randomized (sevelamer carbonate, n = 101; placebo, n = 101). The mean serum phosphorous decreased significantly in patients treated with sevelamer carbonate compared with placebo (-0.22 ± 0.47 vs. 0.05 ± 0.44 mmol/L, p < 0.0001). Significantly (p < 0.0001), decreases of serum total cholesterol, low-density lipoprotein cholesterol, and calcium-phosphorus (Ca × P) product levels from baseline to week 8 were shown in sevelamer carbonate group compared with placebo group. Serum intact parathyroid hormone was not significantly changed in the sevelamer carbonate group (p = 0.83). Patients in the sevelamer carbonate group experienced similar adverse events as the placebo group. Conclusion: Sevelamer carbonate is an effective and well-tolerated phosphate binder in advanced nondialysis CKD Chinese patients with hyperphosphatemia.

The clinical significance of neutrophil-lymphocyte ratio in patients treated with hemodialysis complicated with lung infection.

ABSTRACT: The goal of this work was to investigate the potential significance of neutrophil-lymphocyte ratio (NLR) in patients treated with maintenance hemodialysis (MHD).Herein, we retrospectively reviewed the electronic medical records of 100 patients with end-stage renal failure who were treated with MHD. All patients enrolled in this study met the inclusion criteria and were followed. The differences in each indicator between the two groups were compared using the Wilcoxon rank-sum test. On the other hand, Spearman correlation and logistic regression analysis were used to explore the correlation and risk factors for pulmonary infection between NLR and other indicators. Finally, we determined the optimal cut-off values for NLR, hypersensitive c-reactive protein (hs-CRP), and procalcitonin (PCT) diagnosis of pulmonary infection using the receiver operating characteristic curve.We found that NLR was positively correlated with age, PCT, hs-CRP, and hospital stay, but negatively correlated with hemoglobin, red blood cell, and Albumin. The expression levels of PCT, hs-CRP, and NLR in the infected group decreased significantly than those before treatment. Multiple regression analysis revealed that NLR is an important independent risk factor for MHD patients with pulmonary infection. Additionally, receiver operating characteristic curve analysis showed that the sensitivity, specificity, and area under the curve were 87.76%, 100%, and 0.920 when using NLR combined with hs-CRP to predict pulmonary infection in MHD patients, whereas that of NLR combined with PCT were 87.76%, 96.08%, and 0.944, respectively.Findings from this study suggested that NLR is an independent risk factor for MHD patients with pulmonary infection, which can effectively predict pulmonary infection. Moreover, sensitivity and specificity were greatly enhanced when using NLR combined with PCT/hs-CRP to predict pulmonary infection in MHD patients.

A brief review concerning Chimeric Antigen Receptors T cell therapy.

The understanding concerning the function of immune system in cancer has achieved considerable advance with time passes by. Manipulating genetically engineered immune cells were investigated as a novel strategy for treating cancer. Chimeric antigen receptors (CARs) are recombinant protein molecules by merging the exquisite targeting the potent cytotoxicity of T cells and specificity of monoclonal antibodies and, which could trigger serial cascades of signal transduction and thereby activate T cells to directly destroy the tumor cells. Manufacturing CAR-modified T lymphocytes were successfully implemented in treating cancer derived from they could specifically retarget tumor-associated antigens, causing effective elimination of tumor cells, which spurred the optimization and development of new CAR-T cell technology. The advancement of synthetic biology methodologies of cell therapy in CAR-T would ultimately provide us with a much safer, reliable and efficient modality to against cancer. This review primarily described the emergence, development and application of cell therapy in CAR-T, then discuss the side effects and the potential factors of tumor reccurrence caused by CAR-T cell therapy, in addition to the corresponding countermeasure concerning complications.

[Clinical Characteristics of Patients with Myeloid Sarcoma].

OBJECTIVE: To investigate the clinical characteristics, diagnosis and treatment methods of patients with myeloid sarcoma(MS)． Methods: The clinical data, laboratory examination, clinical pathology and treatment methods of 15 patients with MS treated in the First Affiliated Hospital of Wannan Medical College from June 2012 to January 2020 were retrospectively analyzed. RESULTS: Among the 15 cases of MS, including eight males and seven females, the middle age of patients were 53（19 to 72）. Among the 15 patients with MS, 4 showed solitary MS, while 11 showed secondary MS. Immunohistochemical results showed that MPO+（12/15）、CD68+（3/6）、Lys+（3/3）、CD34+（6/14）、TdT+（0/9）、CD43+（13/13）、CD117+（6/10）、CD15+（7/10）、CD3+（1/15）、CD20+（0/15）. 6 of 13 patients were survival till follow-up date．The median overall survival (OS) time was 16 months (1-88 months)．Conclusion: Myeloid sarcoma is rare and often secondary from acute myeloid leukemia(AML) and chronic myeogenous leukemia(CML). Isolated MS can easily be misdiagnosed as lymphoma. Treatment response should be evaluated in combination with bone marrow examination, PET/CT and other imagines．Systematic chemotherapy and hematopoietic stem cell transplantation are the main method to treat MS.

[Neutrophil-Lymphocyte Ratio as a Prognostic Predictor in Patients with Newly Diagnosed Angioimmunoblastic T Cell Lymphoma].

OBJECTIVE: To investigate the prognostic evaluation value of neutrophil-lymphocyte ratio (NLR) in patients with newly diagnosed angioimmunoblastic T cell lymphoma (AITL). METHODS: Clinical data of 39 patients with newly diagnosed AITL in our hospital from March 2010 to August 2018 were colleated and retrospective analyzied, and the relationship between NLR before treatment and the prognosis of AITL patients was analyzed. RESULTS: Among 39 AITL patients, the median value of NCR was 5.43. Based on the cut-off value (5.43), all the patients were divided into 2 groups: high NLR group (5.43, n=20) and a low NLR group (＜5.43, n=19). The total effective rate of treatment was lower in the high NLR group as compered with low NLR group (P=0.041). Univariate analysis showed that, age ＞60 years old, extranodal involvement＞1 as well as high NLR were the independent risk factors that affected overall survival (OS) in newly diagnosed AITL patients. Multivariate Cox analysis showed that extranodal involvement＞1 and high NLR were the independent risk factors that affected OS in newly diagnosed AITL patients. CONCLUSION: The NLR may be an independent prognostic factor in patients with newly diagnosed AITL. High NLR associated with poor prognosis.

[sCD40L, sP-selectin and sICAM-1 plasma levels in nasopharyngeal carcinoma].

OBJECTIVES: To analyze plasma levels of soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and soluble intercellular adhesion molecule-1 (sICAM-1) in the patients with nasopharyngeal carcinoma (NPC). METHODS: Plasma samples were obtained from 110 NPC patients and 55 age and sex matched healthy individuals as controls. Using commercially available enzyme-linked immunosorbent assay (ELISA) kits, plasma levels of sCD40L, sP-selectin and sICAM-1 were measured in all the samples. RESULTS: The plasma levels of sCD40L, sP-selectin and sICAM-1 in NPC patients were higher than those in the controls, while the levels of these three proteins in NPC patients with neck node metastasis were significantly higher than those in the patients without metastasis. Moreover, plasma sCD40L and sP-selectin levels in the patients were significantly decreased after treatment, and sICAM-1 levels decreased only in stage III + IV patients. CONCLUSIONS: The levels of sCD40L, sP-selectin and sICAM-1 increased in NPC patients, especially in those with neck node metastasis. Abnormal high plasma levels of these molecules may be related to metastasis, which might be used as therapeutic effect indicators in NPC patients.

[Response of mechanical composition of fractured soil to rainfall in shallow Karst slopes in central Guizhou, China]. / é»”ä¸­å–€æ–¯ç‰¹å¡åœ°æµ å±‚è£‚éš™åœŸå£¤æœºæ¢°ç»„æˆå¯¹é™é›¨çš„å“åº”.

Field sampling and indoor pipette method was used to analyze the variation of soil mechanical composition of shallow Karst fissures in response to rainfall under different land uses in Karst rocky desertification region in central Guizhou. Results would supply important scientific basis and direction for further research of soil leakage in the Karst areas. The results showed that silt was the dominant component in soil mechanical composition of shallow Karst fissures, with a content of 57%. In response to rainfall, the contents of silt and clay were increased and that of fine sand was reduced in slope cropland, while the content of fine sand was reduced and that of silt was increased in grassland. The changes of mechanical composition of shallow Karst fissures in forest and shrub land were irregular. Moreover, there was a positive correlation between rainfall and the sand content of shallow Karst fissures. The fissures of land use types had effects on the changes of silt and extremely coarse sand contents with the increase of soil depth, with a decreasing trend of silt.

[Influence of the dentin smear layer trait on the bond strength of the self-adhesive resin cements].

OBJECTIVE: This work aimed to evaluate the influence of smear layer on the bonding effectiveness and durability of the self-adhesive resin cements to dentin. METHODS: A total of 48 fresh caries-free third molars with exposed dentin surface were divided into two groups. The dentin surfaces were treated using a standard grit diamond bur (group A) or further polished using a fine grit diamond bur (group B) and then bonded with either of the two self-adhesive resin cements, namely, Clearfil SA Cement (CSA, Kuraray) and Multilink Speed (MS, Ivoclar Vivadent). After 24 h or 2-year water storage, a microtensile bond strength test was performed. RESULTS: In group A, the dentin surface was rough, the smear layer was thick, and the dentin tubule orifice detritus showed low embolism value. In group B, the dentin surface roughness decreased, the embolism proportion increased, and the smear layer became thin. The initial bonding strengths of CSA and MS in group A were significantly lower than those in group B (P<0.05). The bonding strengths of CSA and MS significantly decreased after two years of water storage (P<0.05). For CSA, the bond strength of group B was significantly lower than that of group A (P<0.05). For MS, the differences in the bonding strength between groups A and B were insignificant (P>0.05). CONCLUSIONS: The properties of the smear layer and the types of self-adhesive resin cement used affected the bond strength and durability.

[Analysis of Clinical Characteristics for Primary Adrenal Lymphoma].

OBJECTIVE: To explore clinical characteristics of the Primary Adrenal Lymphoma(PAL), so as to enhance the understanding of diagnosis, treatment and prognosis of PAL. METHODS: The clinical data of 2 patients with PAL retrospectively analyzed and the clinical characteristics were explored in combination with releted literalures. RESULTS: Adrenal gland neoplasm was found in 2 patients by imaging examination. The pathological type of one case was diffuse large B cell lymphoma, the other one was extranodal NK/T-cell lymphoma. The former refused to hosipitali3t and the other received to be admited in hospital after the definite diagnosis. She died at the 32th day after diagnosis, due to the complication with acute pancreatitis before chemotherapy. The latter accepted the scheme of"Gemox"combining with the scheme"VP-16+DXM"to control hemophagocytic lymphohistiocytosis. The patient's condition deteriorated rapidly after a short period of improvement, then died at the 40th day after chemotherapy because of multiple organ failure. CONCLUSION: PAL is a rare extra-nodal lymphoma with higher malignancy, the combination of chemotherapy and radiotherapy results in the best outcome among all the treatments. The prognosis of patients with different pathological types was diverse, thus it is very important to choose the appropriate treatment according to different pathological types.

Epidemiology and risk factors of retinoblastoma in Chongqing area.

AIM: To investigate the risk factors of retinoblastoma in Chongqing and offer the bases for scientific measures. METHODS: One hundred and thirty-three retinoblastoma patients were taken as case group, and 133 children were taken as control group in 1:1 ratio. The relevant factors were collected from a questionnaire survey which was made by our research group. First, Chi-square and t-test were used to discuss the various factors, and then the logistic regression analysis was made by statistics software SPSS17.0 based on the result of 266 people. RESULTS: Single factor analysis results showed the differences between the two groups were statistically significant (P<0.05) in 17 factors which were education level of their parents, occupation of their parents, exposure to harmful chemicals of their parents 6mo before pregnancy, the history of pelvic inflammatory disease of mother before pregnancy, childbearing history of their parents, pregnant age of their parents, the medication history of father 6 mo before pregnancy, living place of their parents, the pollution living place of mother, hobbies of their parents. Multivariate analysis showed that the living place of parents, mother who feed pets before pregnancy, and exposure to harmful chemicals of father before pregnancy were the independent risk factors of retinoblastoma (P<0.05). CONCLUSION: The living place of parents, mother who feed pets before pregnancy, exposure to harmful chemicals of father before pregnancy were the risk factors of retinoblastoma which affects the occurrence of retinoblastoma in a certain extent.

Exploring the role of bone marrow increased FDG uptake on PET/CT in patients with lymphoma-associated hemophagocytic lymphohistiocytosis: a reflection of bone marrow involvement or cytokine storm?

The role of 18F-2-fluoro-2-deoxy-D-glucose (FDG) uptake of bone marrow (BM) on positron emission tomography/computed tomography (PET/CT) in patients with lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH) remains uncertain. This retrospective study included 34 LA-HLH patients who underwent both PET/CT and comprehensive BM examinations prior to treatment. Comparison between PET/CT and BM examinations for the assessment of bone marrow involvement (BMI) indicated statistical difference (p = 0.039). The specificity of PET/CT in detecting BMI was 11.1% compared to BM examinations. However, a significant correlation was found between PET parameters of BM and laboratory parameters associated with HLH, such as C-reactive protein, ferritin, fibrinogen and soluble CD25. By multivariate analysis, PET parameters of marrow were significantly associated with overall survival. The findings suggest that FDG uptake of marrow might fail to detect lymphomatous BMI, but reflected the level of cytokine storm to a certain extent and might be a prognostic factor in patients with LA-HLH.

Elevated absolute monocyte count predicts unfavorable outcomes in patients with angioimmunoblastic T-cell lymphoma.

This study was aimed at investigating the prognostic significance of the absolute monocyte count (AMC) in peripheral blood in patients with newly diagnosed angioimmunoblastic T cell lymphoma (AITL). AMC was performed in 73 therapy-naive patients with AITL in 2 institutions during 2008-2015, and higher AMC was observed in those with extranodal sites >1, bone marrow involvement, high lactate dehydrogenase level, the EBV infection, no response to treatment and high IPI, PIT, PIAI score group. The best AMC cut-off level at diagnosis was 0.8 × 10(9)/L and the 3-year overall survival (OS) was 64% for patients with low AMC group (≤ 0.8 × 10(9)/L) compared to 10% in high AMC group (>0.8 × 10(9)/L) (P<0.001). Multivariate analysis showed that elevated AMC remained an adverse prognostic parameter. Our results suggest that AMC is an independent prognostic parameter for OS in patients with AITL, and AMC >0.8 × 10(9)/L can routinely be used to identify high-risk patients with unfavorable survival.

Prognostic impact of Epstein-Barr virus (EBV)-DNA copy number at diagnosis in chronic lymphocytic leukemia.

Epstein-Barr virus (EBV)-DNA is detected in the blood of some persons with chronic lymphocytic leukemia (CLL) at diagnosis. Whether this is important in the development or progression of CLL is controversial. We interrogated associations between blood EBV-DNA copy number and biological and clinical variables in 243 new-diagnosed consecutive subjects with CLL. Quantification of EBV-DNA copies was done by real-time quantitative PCR (RQ-PCR). All subjects had serological evidence of prior EBV-infection. However, only 24 subjects (10%) had a EBV-DNA-positive test at diagnosis. EBV-DNA-positive subjects at diagnosis had lower hemoglobin concentrations and platelet levels, higher thymidine kinase-1 and serum ferritin levels, un-mutated IGHV genes and a greater risk of Richter transformation compared with EBV-DNA-negative subjects. Percent CD20-, CD148- and ZAP70-positive cells and mean fluorescence intensity (MFI) of each cluster designation were also increased in EBV-DNA-positive subjects at diagnosis. EBV-DNA test positivity was associated with a briefer time-to-treatment interval (HR 1.85; [95% confidence interval, 1.13, 3.03]; P=0.014) and worse survival (HR 2.77; [1.18, 6.49]; P=0.019). Reduction in EBV copies was significantly associated with therapy-response. A positive blood EBV-DNA test at diagnosis and sequential testing of EBV copies during therapy were significantly associated with biological and clinical variables, time-to-treatment, therapy-response and survival. If validated these data may be added to CLL prognostic scoring systems.

Systemic lymphoma arising from hydroa vacciniforme-like lymphoma: report of two cases with review of literature.

Hydroa vacciniforme-like lymphoma (HVLL) is an extremely rare lymphoma described in children that occurs mainly in Asia and Latin American countries. It is an Epstein-Barr virus (EBV)-positive lymphoproliferative disease (LPD) characterized by a monoclonal proliferation of T or NK cells. In this study, we report the clinical and pathological features of two Chinese patients with HVLL showed T-cell phenotype expressing CD4. The two patients generally presented with similar clinical histories of waxing and waning ulcerative blistering lesions for ten years or more until progression to systemic lymphoma. One patient died two months after progression and another is alive with disease. In the two cases, persistence infection of EBV may be attributed to the disease progression, and systemic lymphoma arising from HVLL behaves in an aggressive fashion and is predisposing to chemotherapeutic agent resistance.