Objective:To analyze the survival and prognostic factors of adult acute lymphoblastic leukemia (ALL) with different consolidation regimens after complete remission by induction therapy.Methods:A total of 93 adult patients with ALL were enrolled from January 2012 to June 2019 in Peking University Shenzhen Hospital. All the patients achieved complete remission induced by VDLCP regimen, and were divided into the standard group, intensive group and transplantation group according to the consolidation treatment. Thirty-four patients in the standard group received an ALL-like chemotherapy regimen based on VDLCP or Hyper-CVAD consolidation for 4-6 courses. Twenty-nine patients in the intensive group received BFM90/95 consolidation treatment for 2 years. Thirty patients in the transplantation group received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after 2-3 courses of consolidation with the original induction regimen. The median follow-up was 18 (3-96) months, and the main follow-up indicators were overall survival (OS) and disease free survival (DFS). Prognostic factors of adult ALL patients and treatment-related deaths in each group were analyzed.Results:The 3-year OS rates of the standard group, intensive group and transplantation group were 54.0% (95% CI: 35.3%-72.6%), 71.8% (95% CI: 41.0%-94.5%), 62.3% (95% CI: 43.6%-80.9%), with a statistically significant difference ( χ2=6.110, P=0.047). The 3-year DFS rates of the three groups were 31.4% (95% CI: 12.9%-49.8%), 72.1% (95% CI: 52.3%-91.9%), 65.7% (95% CI: 45.3%-86.1%), with a statistically significant difference ( χ2=13.831, P=0.001). There were no significant differences in OS and DFS between the intensive group and the transplantation group ( χ2=0.709, P=0.400; χ2=0.046, P=0.830). OS and DFS of the intensive group were better than those of the standard group ( χ2=5.346, P=0.021; χ2=10.326, P=0.010). Multivariate analysis suggested that bone marrow minimal residual disease (MRD) negative on day 14-21 of chemotherapy was an independent prognostic factor affecting adult ALL ( HR=0.114, 95% CI: 0.015-0.841, P=0.033). The 3-year OS rates of Ph + ALL patients who received and did not receive allo-HSCT were 53.5% (95% CI: 23.1%-83.8%), 52.4% (95% CI: 23.8%-81.0%), the 3-year DFS rates were 77.1% (95% CI: 54.2%-100.0%), 35.0% (95% CI: 4.8%-65.2%), and there were no significant differences between the two groups ( χ2=3.600, P=0.223; χ2=3.824, P=0.050). The treatment-related mortalities of the non-transplantation group (standard group + intensive group) and the transplantation group were 3.2% (2/63) and 20.0% (6/30), and the treatment-related mortality of the non-transplantation group was significantly lower than that of the transplantation group ( χ2=7.318, P=0.007). Conclusion:Adult ALL has a poor prognosis. The 3-year OS rate and 3-year DFS rate of BFM intensive consolidation therapy are better than those of standard consolidation therapy, achieving a similar effect to allo-HSCT, but treatment-related mortality does not increase significantly. Patients with bone marrow MRD negative on the day 14-21 of chemotherapy have the better OS and DFS.

In recent years,immunotherapy has become an important part of the treatment for advanced non-small cell lung cancer (NSCLC).Tumor cells can escape from the body's immune system by mediating various immune escape mechanisms,among which programmed death-1/programmed death ligand-1 (PD-1/ PD-L1) mediated immune escape plays an important role.Currently,chemotherapy,radiotherapy and molecular targeted therapy have certain limitations in the treatment of advanced NSCLC.Recent studies have found that the combined application of PD-1/PD-L1 inhibitor and other treatment methods has certain synergistic effect,thus enhances the anti-tumor effect and further prolongs the survival of patients.Immunotherapy brings not only changes in the treatment patterns of NSCLC,but also challenges in the screening of target population and the management of treatment-related adverse reactions.Summarizing the research progress on immune checkpoint inhibitors in the comprehensive treatment of advanced NSCLC can provide reference for the best treatment of NSCLC.

Objective To compare the clinical value of different electroencephalogram (EEG) in the diagnosis of temporal lobe epilepsy.Methods A total of 123 patients in Taizhou Central Hospital received routine EEG , dynamic EEG,routine sphenoidal electrode examination ,and long sphenoidal electrode examination.The the detection rate of epileptic waves in EEG , awake and sleep phases of patients with temporal lobe epilepsy were compared . Results The detection rate of epileptiform wave by the routine EEG was 52.63%,which by the dynamic EEG was 61.11%,and there was no statistically significant difference (P＞0.05).The detection rate of epileptiform wave by the long range sphenoidal electrode EEG was 63.64%,which was higher than that by the conventional sphenoidal electrode EEG(22.22%)(χ2＝8.776,P＜0.05).The detection rate of epileptiform wave in the sleep period EEG in temporal lobe epilepsy was 51.35%,which was higher than that in the awake period (29.73%),and the difference was statistically significant ( χ2＝5.739, P ＜0.05).Conclusion Different types of EEG have their respective advantages in diagnosis of temporal lobe epilepsy ,sphenoidal electrodes and sleep induced temporal lobe epilepsy can significantly improve the detection rate of abnormal EEG ,has important clinical value in the diagnosis of temporal lobe epilepsy.

Objective:To investigate the icariin on cognitive function and astrocytic pyroptosis in hemorrhagic shock resuscitation model mice.Methods:Forty-eight SPF grade C57BL/6 mice (male) were randomly divided into four groups ( n=12 in each group): Sham operation control group (Group C), hemorrhagic shock and resuscitation group (Group H), hemorrhagic shock and resuscitation plus icariin group (Group HI) and hemorrhagic shock resuscitation plus icariin and SSK1 group (Group HIS, SSK1 was a phosphorylation agonist of mitogen-activated protein kinase p38(p38MAPK). The mice in Group H, HI and HIS were subjected to hemorrhagic shock and resuscitation model by bleeding and retransfusion via left femoral vein; the mice in Group HI and HIS were administered with icariin (10 mg/kg) intragastrically for 7 days; the mice in Group C and H were administered with the same amount of normal saline containing dimethyl sulfoxide(DMSO). The mice in Group HIS were administered with SSK1 (0.5 mg/kg) intraperitoneally, but the mice in Group C, H and HI were only administered with the same amount of normal saline containing DMSO.At 15 days after resuscitation, novel objective recognition test and fear conditioning test were used to assess cognitive dysfunction of mice.Microtubule-associated protein 2(MAP2), a specific marker protein of neurons reflecting astrocytic pyroptosis in the hippocampus of mice, were detected by immunofluorescence assay so as to assess neuronal injury and astrocytic pyroptosis.The levels of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the hippocampus were evaluated by Western blot.SPSS 21.0 software was used for data analysis, multiple samples among groups were compared by one-way ANOVA, and SNK- q test was used for further pairwise comparison. Results:The results of new object recognition test showed that the difference of new object recognition index among the four groups was statistically significant ( F=50.75, P<0.05). The new object recognition indexes in H group(22.7±6.9), HI group(40.1±7.0) and HIS group (22.5±7.5) were significantly lower than that in C group (58.5±11.2). The index in HI group was higher than that in H group, while the index in HIS group was lower than that in HI group (all P<0.05). The results of the fear conditioning test showed that there was a statistically significant difference in the percentage of freezing time among the four groups of mice ( F=60.54, P<0.05). And the percentage of freezing time in H group((21.8±5.0)%), HI group ((38.4±7.4) %)and HIS group((21.3±4.2)%)were lower than that in C group((49.1±7.0)%), which in HI group was higher than that in H group ( P<0.05)and which in HIS group was lower than that in HI group(all P<0.05). The results of immunofluorescence showed that there were significant decreases of MAP2 intensity ((35.3±9.3)%, (63.3±6.1)%, (28.7±10.3)%) but increases of pyroptotic astrocytes ((24.5±4.2)%, (9.3±1.5)%, (22.1±3.3)%) in the H, HI and HIS groups compared with those of C group ((106.7±19.7) %, (3.4±2.0)%). There was an increase of MAP2 intensity but a decrease of pyroptotic astrocytes in the HI group compared with those in H group, and there was a decrease of MAP2 intensity but an increase of pyroptotic astrocytes in the HIS group compared with those of HI group (all P<0.05). The Western blot results showed that there were significant increases of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the H, HI and HIS groups compared with C group, there were decreases of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the HI group compared with H group, and there were increases of IL-1β, IL-18, the ratio of phosphorylated p38MAPK to total p38MAPK in the HIS group compared with those in HI group (all P<0.05). Conclusion:Icariin alleviates hemorrhage shock and resuscitation-induced cognitive dysfunction and astrocytic pyroptosis in mice, and the mechanism may be associated with inhibition of phosphorylated p38MAPK.

Objective:To explore the effect of Toll-like receptor 9 (TLR9) signaling pathway activation on the transcriptome in the renal tubular cells.Methods:Mouse primary renal tubular epithelial cells were extracted and cultured. When the degree of cell fusion reached 80%, they were divided into two groups, which were added with 10 μL phosphate buffered saline (PBS, PBS control group) and TLR9 activator cytosine phosphate guanidine oligodeoxynucleotide (CpG-ODN) with a final concentration of 5 μmol/L (CpG-ODN treatment group). The RNA sequencing was performed on the Illumina platform after extraction. DEGseq software was used to analyze the differential expression of genes between the two groups. Goatools and KOBAS online software were used to analyze the differential genes involved signal pathways. Homer software was used to predict transcription factors.Results:Compared with the PBS control group, there were a total of 584 differentially expressed genes in the CpG-ODN treatment group, of which 102 were up-regulated and 482 were down-regulated. The most significantly enriched gene ontology (GO) terms of differentially expressed genes included response to interferon-β, defense response to virus and other inflammatory pathway. The most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways included 2'-5'-oligoadenylate synthase activity, regulation of ribonuclease activity, negative regulation of virus life cycle, cellular response to interferon-βand defense response to protozoan. The results of transcription factor prediction showed that interferon regulatory factor 3 (IRF3) was the most significantly enriched transcription factor in the promoter sequence of differential genes; the most significant transcription factor downstream of TLR9 was IRF3, and other predicted transcription factors such as transcription factor 21 (TCF21), zinc finger protein 135 (ZNF135), and PR domain containing 4 (PRDM4) might be new candidates for TLR9 signaling pathway.Conclusion:CpG-ODN activates TLR9 signaling pathway, and primary renal tubular epithelial cells can directly respond to CpG-ODN stimulation and undergo transcriptome changes, which provides a basis for further research on the molecular mechanism of TLR9 pathway in sepsis induced acute kidney injury.