Objective To explore the role of mitogen-activated protein kinase(MAPK)in lipopolysaccharide(LPS)-induced iNOS expression and NO production in rat Schwann cells by the use of inhibitors PD98059 selective for extracellular signal-regulated kinase 1/2(EPK1/2), SB202190 for P38 MAPK and SP600125 for the c-Jun NH_2-terminal kinase (JNK). Methods Schwann cells were pretreated with PD98059 (30, 50, 70?mol/L), SB202190 (10, 20, 40?mol/L) and SP600125 (10, 30, 50?mol/L) at the indicated concentrations for 1 hour before the stimulation with LPS (10mg/L) for 4 hour. The estimation of iNOS mRNA, IL-6 mRNA and TNF-? mRNA was performed by RT-PCR; the changes of iNOS protein expression were investigated by Western blotting. The NO level was observed with measurement of nitrite in the cell culture medium. Results LPS could significantly activate MAPK signal pathway and lead to the expression of iNOS and NO production. The iNOS expression and NO production induced by LPS stimulation were significantly inhibited by the three highly specific inhibitors of MAPK. In addition, the inhibitors decreased LPS-induced the expression of IL-6 mRNA and TNF-? mRNA. Conclusion Activation of MAPK pathway is involved in iNOS expression and NO production in rat Schwann cells, and the inhibition of the signal transduction pathway can be effective to reduce the production of iNOS and NO, which may be a useful strategy against inflammatory and immune reaction after peripheral nerve injury.

ObjectiveTo explore the cause of early death (death within 3-12 months after hemodialysis) and the related influencing factors patients undergoing maintenance hemodialysis (MHD) as to provide a scientific basis for the prevention of early death.Methods A retrospective matched controlled study was conducted. Fifty-one patients who underwent MHD from January 2004 to April 2014 and died within 3-12 months after hemodialysis in hemodialysis center of the 174th Chinese People's Liberation Army Hospital were included in the case group by retrospective analysis method. According to 1∶2 matched controls, 102 patients underwent hemodialysis in the same period (±2 months) and survived over 12 months were selected as control group. All patients received regular hemodialysis (dialysis 2-3 times per week), with conventional limitation of water and sodium intake, routine treatments such as control of blood pressure, treatment of anemia and disorders of calcium and phosphorus contents. Causes of short-term death were analyzed. Clinical and biochemical parameters of two groups were collected when dialysis was started, and the single factor and multiple factors logistic regression was used to analyze the related risk factors when dialysis was started. Receiver operating characteristic curve (ROC) was plotted to evaluate the value of above parameters in predicting the early death in patents with MHD.Results The main causes of early death of 51 patients with MHD were mainly cardiovascular and cerebrovascular diseases (27 cases, 52.9%), and infections (15 cases, 29.4%). It was shown by single factor analysis that the age [odds ratio (OR) = 6.625, 95% confidence interval (95%CI) = 3.232-13.580,P = 0.000], diabetes (OR = 3.875, 95%CI = 0.654 - 10.622,P = 0.031), specialist intervention time before dialysis (OR = 0.349, 95%CI =0.287 - 0.572,P = 0.004), the emergence of cardiovascular and cerebrovascular events before dialysis (OR = 9.667, 95%CI = 4.632 - 20.174,P = 0.000), the first dialysis for emergency dialysis (OR = 3.875, 95%CI = 1.713 - 8.765, P = 0.005), blood albumin level (OR = 0.294, 95%CI = 0.068 - 0.550,P = 0.008), leukocyte count (OR = 6.286, 95%CI = 1.648 - 23.982,P = 0.026), neutrophil count (OR = 2.833, 95%CI = 1.630 - 4.923,P = 0.001) might be the factors correlating with early death. Eight independent factors were statistically significant, and their effect on the MHD patients was analyzed by logistic regression analysis inα = 0.05 level. The results showed that patients with old age (OR = 1.054, 95%CI = 1.019-1.090,P = 0.002), and the emergence of cardio-cerebrovascular events (OR = 7.469, 95%CI = 2.474 - 22.545,P = 0.000)were early death risk factors of MHD patients, and early specialist intervention before dialysis was a protective factor (OR = 0.286, 95%CI = 0.113-0.722,P = 0.008). ROC curve showed that age had moderate diagnostic value for early death of MHD [area under ROC curve (AUC) = 0.756], the cut-off value was 59.0 years old, the sensitivity was 66.7%, and the specificity was 77.5%. The diagnostic value of early specialist intervention before dialysis was relatively low (AUC = 0.367), the cut-off value was 0.875 years, the sensitivity was 39.2%, and the specificity was 33.3%.Conclusion Old age, the emergency of cardiovascular and cerebrovascular events before dialysis is associated with early death, and specialist intervention ahead of dialysis can reduce the risk of early death.

OBJECTIVETo investigate retrospectively the efficacy of cyclosporine A (CsA) in the treatment of membranous lupus nephropathy (MLN).

METHODSTwenty-four patients with systemic lupus erythematosus (SLE) and biopsy-proven MLN were treated with CsA in combination with prednisone. CsA was given at a starting dosage of 5 mg x kg(-1) x d(-1) for 3 months, with a 1 mg x kg(-1) x d(-1) reduction every month and then maintained at a dosage of 2 mg x kg(-1) x d(-1). The dosage of oral prednisone differed from person to person according to levels of extra-renal activity. Clinical efficacy and adverse reactions were retrospectively analyzed. Complete remission was defined as having a urinary proteinuria level (Upr) of < 0.4 g/d, and normal serum albumin and serum creatinine (SCr) levels, without SLE activity. Partial remission was defined as having a UPr decrement > 50% of baseline value and a serum albumin value of 30 - 35 g/L, without SLE activity. No response was defined as having a Upr decrement < 50% of baseline value and > 2.0 g/d, or as a deterioration of renal function, or as having active SLE.

RESULTSOne patient could no longer undergo follow-up, and the other 23 patients were treated with CsA and followed up for 6 - 36 months (mean 16.8 +/- 8.4 months). The mean starting dosage of CsA was 4.7 +/- 0.5) mg x kg(-1) x d(-1) and the trough level of the whole blood CsA was 248 +/- 110) micro g/L. Twelve patients (52.2%) achieved complete remission, 10 patients (43.3%) achieved partial remission after CsA treatment, and one patient showed no response. At different CsA treatment timepoint, the complete remission rates were 17.4% (3rd month), 21.7% (6th month), 40% (12th month), 88.9% (18th month) and 100% (24th month) respectively. SCr elevation, when within a normal limit was not observed in most patients during early CsA administration, and at the end of the follow-up all the patients had a normal SCr. Relapse occurred in 33.3% of the patients after withdrawing CsA for 4 - 24 months. No chronic CsA renal toxicity was observed in 4 patients who had a repeat renal biopsy after CsA treatment for 6 - 24 months.

CONCLUSIONSCsA could be regarded as an effective therapy for patients with membranous lupus nephropathy, but its adverse effects, especially its nephrotoxicity, should be carefully monitored during CsA treatment.

Adolescent ; Adult ; Cyclosporine ; administration & dosage ; therapeutic use ; Female ; Glomerulonephritis, Membranous ; drug therapy ; Humans ; Lupus Nephritis ; drug therapy ; Male ; Prednisone ; administration & dosage ; Retrospective Studies ; Treatment Outcome

Background: Aberrant Bcl-2 transcription is closely related with nodal diffuse large B-cell lymphoma (DLBCL), however, the relationship between Bcl-2 and primary gastrointestinal DLBCL (PGI-DLBCL) was not fully studied.Aims: To investigate the relationship between Bcl-2 gene amplification and protein expression and clinicopathological characteristics, immunophenotype and prognosis of PGI-DLBCL.Methods: Clinical data was collected from 136 PGI-DLBCL patients receiving surgical treatment, and a telephone interview was conducted for survival information.Bcl-2 gene amplification and protein expression in tumor tissue were determined by fluorescence in situ hybridization and immuno-histochemistry, respectively, and relationships between Bcl-2 and clinicopathological characteristics, immunophenotype and prognosis of PGI-DLBCL were analyzed.Results: Among 136 PGI-DLBCL patients, 33 (24.3%) showing gene amplification and 90 (66.2%) showing protein expression of Bcl-2;gene amplification was correlated with primary tumor location, Ann Arbor stage, serum lactate dehydrogenase level, B symptom and International Prognostic Index (IPI) score (P<0.05), while protein expression was correlated with primary tumor location and immunophenotype (P<0.05).5-year overall survival (OS) in patients positive for Bcl-2 gene amplification and patients with non-GCB immunophenotype and positive for Bcl-2 protein expression were inferior to those negative ones (41.5%vs.71.5%, P<0.05;54.6% vs.84.6%, P<0.05).In Bcl-2 gene amplification or protein expression positive patients, 5-year OS of CHOP chemotherapy was inferior to that of rituximab combined with CHOP chemotherapy (48.6%vs.80.3%, P<0.05;66.4%vs.83.4%, P<0.05).Conclusions: Detection of Bcl-2 gene amplification is useful for prediction of prognosis in PGI-DLBCL.Both patients with Bcl-2 gene amplification and non-GCB patients with Bcl-2 protein expression have a poorer prognosis.Rituximab may improve the prognosis in patients with Bcl-2 gene amplification or protein expression.

Objective:To summarize the clinical characteristics of children with Mycoplasma pneumoniae pneumonia(MPP) complicated with pleural effusion, and explore the effect of mixed adenovirus infection on children with MPP complicated with pleural effusion.Methods:The clinical data of children with MPP complicated with pleural effusion diagnosed in Children′s Medical Center at the First Affiliated Hospital of Hunan Normal University (Hunan Provincial People′s Hospital) from January 2013 to December 2019 were collected.MPP cases were divided into single infection group and mixed infection group according to whether mixing adenovirus infection.The clinical characteristics were compared between two groups.Results:A total of 180 children with MPP complicated with pleural effusion were included, the male to female ratio was 1.22∶1 (99/81), the age was 66.13 (44.35, 83.98) months, and the most common cases were children over 5 years old (55.56%). The length of hospitalization was 9.00 (7.00, 12.00) days.Fever (93.33%) and cough (98.33%) were the most common clinical manifestations, and mild increases in C-reactive protein, erythrocyte sedimentation rate and D-dimer were the most common laboratory results.Among included children, right pleural effusion was the most common (54.44%), bilateral pleural effusion accounted for 26.67%, and left pleural effusion accounted for 18.89%.Compared with single infection group, the mixed infection group had a longer hospital stay, a higher proportion of oxygen intake, a higher proportion of gamma globulin use, and a higher value of lactate dehydrogenase and aspartate aminotransferase.The results of multivariate Logistic regression analysis showed that compared with single infection group, although the mixed infection group had a higher proportion of gamma globulin use (36.54% vs.10.93%, P<0.05), the length of hospital stay, clinical manifestations, laboratory examination, chest CT and fiberoptic bronchoscopy showed no statistically significant difference between two groups. Conclusion:MPP complicated with pleural effusion is more common in children over 5 years old, especially in the right side.Mild increases of C-reactive protein, erythrocyte sedimentation rate, and D-dimer are more common.The clinical features of MPP complicated with pleural effusion are similar between mixed adenovirus infection group and single infection group.

The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8⁺PD1⁺TCF1⁺ progenitor exhausted T cells (TCF1⁺Tex^prog) and CD8⁺PD1⁺TCF1^- terminally exhausted T cells (TCF1^-Tex^term). Moreover, fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells (Tregs) in the tumor immune microenvironment (TIME). mIHC and flow cytometry analysis showed that TCF1^-Tex^term represented a greater proportion of CD8⁺PD1⁺Tex than TCF1⁺Tex^prog in most patients. TCF1⁺Tex^prog produced abundant TNFα, while TCF1^-Tex^term expressed higher levels of CD103, TIM-3, CTLA-4, and TIGIT. TCF1^-Tex^term exhibited a polyfunctional TNFα⁺GZMB⁺IFNγ⁺ phenotype; and were associated with better overall survival and recurrence-free survival. The results also indicated that larger proportions of TCF1^-Tex^term were accompanied by an increase in the proportion of Tregs. Therefore, it was concluded that TCF1^-Tex^term was the major CD8⁺PD1⁺Tex subset in the HNSCC TIME and that these cells favor patient survival. A high proportion of TCF1^-Tex^term was associated with greater Treg abundance.
CD8-Positive T-Lymphocytes ; Head and Neck Neoplasms/therapy* ; Humans ; Immunotherapy/methods* ; Prognosis ; Programmed Cell Death 1 Receptor ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Tumor Microenvironment ; Tumor Necrosis Factor-alpha