[Clinical analyses of 24 patients with primary pulmonary NK/T-cell lymphoma].

Objective: To explore the clinical characteristics, the best treatment and prognostic factors of primary pulmonary NK/T-cell lymphoma. Methods: A total of 24 cases with primary pulmonary NK/T-cell lymphoma from April 2011 to May 2019 were analyzed retrospectively. Survival analysis was performed using the Kaplan-Meier method and groups were compared using the log-rank test. Multivariate analysis using Cox proportional hazard regression model was conducted to confirm independent prognostic factors for overall survival (OS) and progression-free survival (PFS) . Results: ①The cohort of 24 patients included 16 male and 8 female with a median age of 49 years (range, 4-76 years) old. ②Most patients initially presented with a fever (66.7%) , cough and dyspnea. Chest imaging manifestations were primarily unilateral (45.8%) or bilateral (54.2%) pulmonary consolidation, nodules or mass. ③20 patients received chemotherapy, radiotherapy or hematopoietic stem cell transplantation, the rest 4 cases palliative treatment. Median OS was 9.5 months (range, 0.1-26.0 months) . The estimated 1-year OS rate was 45.8%. Overall response rate of patients treated with asparaginase-based regimen was 88.2%. ④In univariate survival analysis, age≤60 was prognostic for longer OS and PFS, compared with age>60 (P=0.002 and 0.004, respectively) ; ECOG≤2 was prognostic for longer OS and PFS, compared with ECOG>2 (P=0.042 and 0.004, respectively) . In multivariate survival analysis, age>60 and ECOG>2 were significantly correlated with inferior OS and PFS (OS: P=0.024 and 0.024, respectively; PFS: P=0.035 and 0.024, respectively) . Conclusions: Primary pulmonary NK/T-cell lymphoma was a rare disease with poor prognosis. Asparaginase-based regimens appeared to be effective. Age and ECOG served as independent prognostic factors for primary pulmonary NK/T-cell lymphoma patients.

A novel bio-active adhesive monomer induces odontoblast differentiation: a comparative study.

AIM: To evaluate the in vitro effect of the novel adhesive monomer CMET, a calcium salt of 4-methacryloxyethyl trimellitate (4-MET), on the proliferation, mineralization and differentiation of odontoblast-like cells, comparing with 4-MET, calcium hydroxide (CH) and mineral trioxide aggregate (MTA). METHODOLOGY: Rat odontoblast-like MDPC-23 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 5% foetal bovine serum. The powder of four tested materials (CMET, 4-MET, CH and MTA) was first dissolved in distilled water (dH2O) and then was diluted by DMEM to yield final concentrations. Solvent (dH2O) was used as a control. Cell viability was assessed using CCK-8 assay. Real-time RT-PCR was used to quantify the mRNA expression of odontogenic markers, cytokines and integrins. Mineralization inducing capacity was evaluated by alkaline phosphatase (ALPase) activity and alizarin red S staining. Statistical analyses were performed using one-way anova and post hoc Tukey's HSD test, with the significance level at 1%. RESULTS: Cell viability was significantly greater in the CMET- (83 to 828 mmol L-1), CH- and MTA-treated (low concentrations) groups than that in the control group (P < 0.01). Higher concentrations of each material decreased the viable cells to different extents (P < 0.01). CMET treatment augmented the expression of several integrin subunits and exhibited the highest mRNA expression levels of odontogenic markers among all groups (P < 0.01). CH and MTA treatment caused significantly greater upregulation of pro-inflammatory cytokines expression than the other groups (P < 0.01). The calcific deposition of MDPC-23 cells was dose-dependently accelerated by the addition of CMET (P < 0.01); the enhancement of mineralization was also found in the fresh prepared CH and MTA treatments. Besides, CMET showed consistency in mineralization induction after 8 weeks storage. Exposure to SB202190, a specific p38 mitogen-activated protein kinases inhibitor, significantly decreased the ALPase activity as well as the mineral deposition which was enhanced by CMET treatment (P < 0.01). CONCLUSIONS: The novel bio-active monomer had the lowest cytotoxicity among all groups and it induced the proliferation, mineralization and differentiation of odontoblast-like cells under appropriate concentrations. This adhesive monomer possesses excellent biocompatibility and hence exhibits great potential in dentine regeneration.

[14-3-3ζ protein mediates gemcitabine resistance in NK/T-cell lymphoma].

Objective: To explore the molecular mechanisms of 14-3-3ζ in gemcitabine resistance in extranodal NK/T-cell lymphoma, nasal type (ENKTL) . Methods: The effects of cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and transwell assay. YTS cells were exposed to gradually increased concentrations of gemcitabine to establish gemcitabine-resistant YTS cells (YTS-gem) in vitro. 14-3-3ζ specific siRNA lentiviral vector was transfected into YTS and YTS-gem cells to downregulate 14-3-3ζ expression, and stable transfected cell clones were screened. The protein expression was determined by Western blot. Results: ①14-3-3ζ expression was significantly up-regulated in gemcitabine resistant YTS-gem cells, comparing with that of YTS cells (P<0.05) . ②The results of CCK-8 and transwell assay showed that downregulation of 14-3-3ζ significantly reduced the cell proliferation and invasion abilities (P<0.05) . ③Downregulation of 14-3-3ζ could restore gemcitabine sensitivity in gemcitabine resistant YTS-gem cells (P<0.05) . ④Western blotting results showed that knockdown of 14-3-3ζ significantly upregulated pro-apoptotic Bax, and downregulated anti-apoptotic Bcl-2, Caspase-3, cleaved caspase-3, Cyclin D1 in gemcitabine-resistant YTS-gem cells (P<0.05) . There was no significant difference in p53 ang P-gp expression levels. Conclusions: 14-3-3ζ was upregulated in gemcitabine resistant YTS cells. Overexpression of 14-3-3ζ promoted cell proliferation and enhanced cell migration. 14-3-3ζ contributed to gemcitabine resistance to ENKTL through anti-apoptosis.

[Clinical characteristics of lung NK/T cell lymphoma misdiagnosed as pneumonia].

Objective: To investigate the clinical features of lung natural killer (NK)/T cell lymphoma. Methods: The clinical data of patients with lung NK/T-cell lymphoma confirmed by pathology who were hospitalized due to lung shadow and initially treated as pneumonia from the First Affiliated Hospital of Zhengzhou University was collected from June 2013 to January 2019. The clinical manifestations, laboratory tests, chest CT findings, treatment procedures, outcomes, and misdiagnosis were retrospectively analyzed. Results: Among the 15 enrolled patients with lung NK/T-cell lymphoma, 5 were primary and the other 10 were secondary. There were 8 males and 7 females, aged 20-76 years. Fever presented in 14 cases, dyspnea was observed in 4 cases and 2 cases had cough. A total of 12 cases had leukopenia, 10 cases had mononuclear cell increase, 10 cases had liver dysfunction, 13 cases had elevated serum lactate dehydrogenase (LDH), and 2 cases of primary lung NK/T-cell lymphoma had increased pleural LDH and adenosine deaminase. Five cases of primary lung NK/T-cell lymphoma had multiple lung lesions, with diffuse multiple solid shadows, ground glass and patchy shadows, some with nodules; 10 cases of secondary lung NK/T-cell lymphoma showed nodular masses, some were accompanied by patchy shadows, and most patients had multiple lesions scattering in the lung. All the fifteen patients were misdiagnosed as pneumonia in the early stage, and then were diagnosed by percutaneous lung biopsy or transbronchial biopsy. Six patients underwent chemotherapy, of which 1 achieved complete response, 4 were in follow-up and 1 died of respiratory failure; 5 patients died of respiratory failure after diagnosis and 4 patients discharged and died within half a year. Conclusions: The lung NK/T-cell lymphoma are rare. The clinical manifestations and pulmonary imaging findings are indistinguishable from pulmonary inflammatory lesions. They are easily misdiagnosed as pneumonia. Early CT-guided percutaneous lung biopsy or transbronchial biopsy can improve the diagnostic accuracy.

[PD-L1 expression is related with prognosis of small cell lung cancer].

Objective: To explore the correlation between programmed death ligand 1 (PD-L1) expression and clinicopathological features and prognosis of small cell lung cancer (SCLC). Methods: The clinicopathological data of 64 patients with small cell lung cancer from January 2013 to December 2016 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed in this study. The correlation between PD-L1 expression and the clinicopathological features and prognosis of SCLC was analyzed. Results: Immunohistochemical staining revealed that PD-L1 expression was observed in 60.9% (39/64) of patients with small cell lung cancer. PD-L1 expression was significantly related to stages (P<0.001). Univariate analysis showed that the median overall survival of PD-L1 negative group was longer than PD-L1 positive group (16 months vs 14 months, P<0.001). Median progression-free survival of PD-L1 negative group was longer than PD-L1 positive group(15 months vs 9 months, P<0.000 1). In multivariate analysis, PD-L1 positive was significantly correlated with inferior progression-free survival (P=0.006). Conclusions: PD-L1 expression rate was high in small cell lung cancer. PD-L1 expression was an independent predictor for poor prognosis of patients with small cell lung cancer.

[Different care models and symptom progression of Alzheimer's disease in China].

Objective: To compare the differences of cognitive function, daily living ability and neuropsychiatric symptoms in patients with sporadic type of Alzheimer's disease (AD) under different care modes, and find the most favorable care mode for delaying the progress of disease. Methods: One hundred and twenty cases of AD patients were divided into three groups: Spouse Care Group, Adult Child Care Group and Nursing Home Group. Medical history collection and scale evaluation were carried out by trained specialists on 3 groups of patients and caregivers. Assessment included socio-demographic data, including name, gender, age, course of the disease, the year of education and the way of care, Mini mental state examination (MMSE), Activity of Daily Living (ADL), Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog), Neuropsychiatric Inventory (NPI), and the Relevant Outcome Scale for Alzheimer's disease (ROSA). All the evaluations were completed upon enrollment. The differences in cognitive function, daily living ability and neuropsychiatric symptoms were compared among the three groups. Results: There was no significant difference in age, gender, education duration and course of disease between the three groups (P>0.05). The MMSE average scores of Spouse Care Group, Adult Child Care Group and Nursing Home Group were 19±7, 15±6, 13±7 respectively. The ADAS-Cog median scores of Spouse Care Group, Adult Child Care Group and Nursing Home Group were 17.32(9.78, 26.50), 30.00(16.10, 38.55), 33.15 (16.28, 50.68). The NPI median total scores of Spouse Care Group, Adult Child Care Group and Nursing Home Group were 5.00(1.00, 13.00), 9.00(4.00, 20.00), 19.50(8.50, 28.50) respectively. The ADL average scores of Spouse Care Group, Adult Child Care Group and Nursing Home Group were 21±9, 25±9, 35±11. The difference of MMSE, ADAS-Cog, ADL and NPI was statistically significant among the three groups (P<0.05). No significant difference was found in care burden among the three groups (P>0.05). Conclusions: The AD patients with spouse care tend to suffer from mild diseases severitys, no matter in terms of cognitive function, daily living ability or neuropsychiatric symptoms. Close, familiar and comprehensive care plays an important role in delaying the progress of AD.

Opa interacting protein 5 promotes metastasis of nasopharyngeal carcinoma cells by promoting EMT via modulation of JAK2/STAT3 signal.

OBJECTIVE: Opa interacting protein 5 (OIP5), as a tumor promoter gene, has emerged as a regulator in several types of tumors. However, the role of OIP5 in nasopharyngeal carcinoma (NPC) has not been reported. In this study, we aimed to explore the expression and biological function of OIP5 in NPC. PATIENTS AND METHODS: The lung cancer datasets GSE12452 and GSE53819 were downloaded from the Gene Expression Omnibus (GEO) repository. Real-time-Polymerase Chain Reaction (RT-PCR) was performed to detect the expression levels of OIP5 mRNA. Cell Counting Kit-8 (CCK-8), colony-formation assay, wound healing assay and transwell assay were conducted to measure cells' proliferation, migration and invasion. Flow cytometry was used for analysis of apoptosis. Western blot assays were used to assess the effects of OIP5 on EMT and JAK2/STAT3 pathway. RESULTS: The up-regulation of OIP5 mRNA was observed in NPC tissues from both GSE12452 and GSE53819. The results of RT-PCR also showed that the expression of OIP5 mRNA was significantly up-regulated in several NPC cell lines compared to normal nasopharyngeal cells. Furthermore, lost-function assay revealed that the knockdown of OIP5 markedly suppressed NPC cells proliferation, migration and invasion, and promoted cell apoptosis. In addition, the results of Western blot showed that silencing of OIP5 suppressed the EMT in NPC cell line. Meanwhile, the knockdown of OIP5 remarkably decreased the expression of p-JAK2 and p-STAT3 protein in both CNE1 and SUNE1 cells. CONCLUSIONS: Our data indicated that OIP5 was highly expressed in NPC and promoted NPC progression by modulating JAK2/STAT3; our results shed light on utilizing OIP5 as a potential novel therapeutic target for the treatment of NPC.

[Efficacy and tolerance of Memantine monotherapy and combination therapy with Reinhartdt And Sea Cucumber Capsule on agitation in moderate to severe Alzheimer disease].

Objective: To explore the efficacy and tolerance of Memantine combined Reinhartdt And Sea Cucumber Capsule (R.S.C) on treating agitation in patients with moderate-severe Alzheimer disease (AD). Methods: One hundred and fifty-eight moderate-sever AD patients from Sep.2013 to Sep.2014 in Zhejiang Provincial People's Hospital were randomly divided into two groups: group of Memantine combined R. S.C and group of single Memantine. Then Mini-Mental Sate Examination (MMSE) and Neuropsychiatric Inventory (NPI) were used to evaluate cognition symptom, behavioral and psychological symptoms of dementia (BPSD) and agitation symptom at the baseline and the end of 24 weeks.The Treatment Emergent Symptom Scale (TESS) was used to assess adverse reaction and tolerance.At last, the data was analyzed by chi-square test, t-test and covariance test. Result: At the terminal of experience, the total NPI scores and agitation factor decreased markedly in both of the two groups (P<0.05). Among the patients who had agitation symptom at the baseline, the total NPI scores and agitation factor (18±5, 3.7±2.6) in group of Memantine combined R. S.C were notably lower than those in the group of single Memantine (21±6, 5.3±2.5) (P<0.05). The incidence of adverse reaction between the two groups had no significant difference (combined treatment group was 27.7%, single treatment group was 23.2%). One patient dropped out because of skin allergy, and most adverse reactions were tolerant. Conclusions: Both two groups are effective in agitation and BPSD, and Memantine combined R. S.C is better than single treatment.R.S.C dose not aggravate adverse reaction and can be well tolerated.

Experimental test and life estimation of the OLED at normal working stress based on the luminance degradation model.

In order to accurately acquire the life time information for the organic light emitting diode (OLED), an experiment based on the normal stress life test was carried out to gain the data for the luminance degradation tests. The luminance degradation model of OLED was established based on the Weibull function and the least square method. Combined with luminance degradation data, Weibull parameters were estimated, the qualitative and the quantitative relationship between the initial luminance and the OLED life was obtained, and the life estimation of the product was achieved. Numerical results show that the test scheme is feasible, the luminance degradation model proves to be reliable for the OLED life estimation, and the fitting accuracy is very high by comparison with the test data fluctuation. Moreover, the real life time of the OLED is measured, which can verify the validity of the assumptions used in accelerated life test methods and provide manufacturers and customers with significant guidelines.

Efficacy of a pegaspargase-based regimen in the treatment of newly-diagnosed extranodal natural killer/T-cell lymphoma.

Extranodal natural killer (NK)/T-cell lymphoma (ENKL) is an aggressive neoplasm with poor prognosis. Currently, there is no consensus on the optimal treatment of this disease. In this study, we report the efficacy of a pegaspargase (PEG-Asp)-based chemotherapy, a DDGP regimen (PEG-Asp, dexamethasone, cisplatin, gemcitabine), for the treatment of newly-diagnosed ENKL. From August 2010 to May 2012, 12 patients with newly-diagnosed stage II - IV ENKL were initially treated with a DDGP regimen in our center. Ten patients (10/12, 83.3%) achieved complete response (CR) and two (2/12, 16.7%) achieved partial response (PR). The objective overall response rate (ORR) was 100%. Three patients (3/12, 25.0%) relapsed, and as a result, two died of disease. Eight patients (8/12, 66.7%) were alive with no evidence of disease (NOD) after a median follow-up of 19 months (range 16 - 31 months). Hematologic toxicity was the most frequent toxicity reported in this study. Grade 3/4 leukopenia and neutropenia were common and both occurred in eight patients (8/12, 66.7%), respectively. Additionally, six patients (6/12, 50.0%) experienced grade 3/4 thrombocytopenia and three (3/12, 25.0%) experienced grade 3/4 anemia. However, no patient died of hematologic toxicity. Our results demonstrate the significant efficacy and safety profile of a DDGP regimen in the treatment of newly-diagnosed ENKL, and indicate the potential of this regimen as a first-line therapy against this disease.