Abstract:The analysis of forensic DNA plays an irreplaceable role in criminal investigation. Forensic DNA identification is facing challenges while dealing with complex cases. The discovery of novel genetic markers for multiple forensic purposes exhibits important application value and scientific significance. Microhaplotype is a type of novel genetic marker，which is defined by two or more closely linked single nucleotide polymorphisms（SNPs）within a short length of DNA fragment. Thus，the multiple allelic combination of SNPs leads to high polymorphism of microhaplotype. It combines strengths of short tandem repeat（STR）and SNP，with relatively high polymorphism and extremely low mutation rate，while applied in forensic identification. Recent researches reveal that microhaplotype possesses unique advantages in ancestry inference，personal identification and paternity testing，as well as great potential in unbalanced DNA mixture analysis and degraded or trace DNA detection. This review summarized the concepts and characteristics，retrospected the research achievements and discussed the challenges in the application of microhaplotype，aiming at exploring a brighter future of microhaplotype in forensic application.

Abstract:Objective：To investigate the effect and the molecular mechanism of DJ-1/PARK7 on migration and invasion with irradiation of esophageal squamous cell carcinoma. Methods：Short hairpin RNA（shRNA）was used to stably transfect esophageal squamous cell carcinoma cells kyse150 and kyse450 and knockdown the expression of DJ-1 gene. Western blot was used to detect the transfection efficiency of cells. Transwell assay was used to detect the migration ability of esophageal squamous cell carcinoma cells under gradient irradiation（0，4，6，8 Gy）. The control group cells transfected with empty virus and the DJ-1 knockdown group cells were irradiated by 6 Gy X-ray. Cell healing assay and Transwell assay were used to analyze the migration and invasion ability of esophageal squamous cell carcinoma cells. Western blot was used to detect the expression changes of epithelial-mesenchymal transition（EMT）pathway related proteins E-cadherin，N-cadherin and matrix metalloproteinase 2（MMP2）. Results：After DJ-1 was knocked down，DJ-1 protein expression levels in esophageal squamous cell carcinoma cells kyse150 and kyse450 were significantly decreased. Transwell assay showed that，induced by 6 Gy radiation，esophageal squamous cell carcinoma cells kyse150 and kyse450 had the strongest migration ability. According to the cell healing assay and Transwell assay，the migration and invasion of kyse150 and kyse450 cells were reduced after DJ-1 was knocked down. Western blot analysis showed that E-cadherin expression increased，N-cadherin expression and MMP2 expression decreased after DJ-1 was knocked down. Conclusion：Knockdown of DJ-1 expression can reduce the irradiation-induced migration and invasion ability of esophageal squamous cell carcinoma cells kyse150 and kyse450，and the mechanism may be related to the inhibition of EMT process by up-regulating E-cadherin，down-regulating N-cadherin and MMP2 protein expression.

Abstract:Objective：To establish an osimertinib-resistant non-small cell lung cancer cell line H1975AR，identify parental and drug-resistant cells，and explore the mechanism of drug resistance. Methods：Induction of H1975 by increasing the concentration of osimertinib in vitro was performed to establish osimertinib-resistant cell line H1975AR. The morphological differences between the two cells were compared by light microscopy and Giemsa staining. Next generation sequencing（NGS）was used to detect epidermal growth factor receptor（EGFR）mutations. Cell proliferation was determined by SRB assay to access sensitivity to EGFR-tyrosine kinase inhibitor（TKI） and chemotherapeutic drugs. Western blot detected the changes of EGFR and downstream proliferation signaling pathway after treating with 0、10、100、 1 000 nmol/L osimertinib for 6 h. Results：①The resistance index of H1975AR measured by SRB assay was 3 634.75，which indicated that H1975AR was an osimertinib-resistant cell line. ②The morphology of drug-resistant cell line changed and the nuclear-to-cytoplasmic ratio increased. ③Compared with H1975，the inhibitory effected on p-EGFR and p-ERK in H1975AR were not obvious，and the same dose concentration had a weak inhibitory effect on p-AKT in H1975AR，and the expression of c-Met was down-regulated. ④H1975 and H1975AR were resistant to the first-generation EGFR-TKI and sensitive to cisplatin and paclitaxel. Conclusion：The EGFR mutation of cis-C797S in H1975AR cells is the main mechanism of osimertinib resistance and H1975AR is sensitive to cisplatin and paclitaxel.

Abstract:Objective：To observe the neuroprotective mechanism of astrocytes after oxidative stress injury by up-regulating endogenous gap junction protein alpha 1 truncated monomer- 20k（GJA1-20k）of neurons. Methods：Neurons and astrocytes were obtained from C57BL/6 fetal mice by primary culture method，and co-culture model was established. Neurons were injured by hydrogen peroxide（H2O2），insulin-like growth factor-1（IGF-1）receptor blocker AG1024 was given to astrocytes，respectively. Thus，Neuron+Astrocyte+Stress group and Neuron+Astrocyte+Stress+AG1024 group were established. Meanwhile，Neuron（Neuron alone without treatment）group and Neuron+Stress group（separately cultured Neuron given with H2O2）were also set up as control groups. The changes of GJA1-20k，non-phosphorylated（NP）-Cx43，glutamate transporter-1（GLT-1），mitochondrial function-related proteins（PGC-1α，mtTFA，Tom20，CoxⅣ），apoptosis-related proteins（Bcl-2，Bax，Caspases-9）were measured by Western blot. The oxidative stress factor NAPDH oxidase activity，inflammatory factors interleukin（IL）-1β，IL-6 and tumor necrosis factor-α（TNF-α）were detected by ELFA and ELISA，apoptosis of neurons was measured by Annexin V-FITC/PI assay，respectively. Results：Astrocytes co-culture significantly up-regulated the expression of endogenous GJA1-20k and NP-Cx43，reversed the down-regulation of PGC-1α，mtTFA，Tom20 and CoxⅣ，up-regulated apoptotic inhibitor Bcl-2，down-regulated apoptotic promoter Bax，Caspase-9，and reduced the expression of NAPDH oxidase activity and inflammatory products IL-1β，IL-6 and TNF-α（P < 0.05）. The protective effect of astrocytes on neurons was significantly inhibited by AG1024（P < 0.05）. Conclusion：The protective mechanism of astrocyte on neuron associated with IGF-1 may be related to the increase of endogenous GJA1-20k and protection of mitochondria function in neurons.

Abstract:Objective：To explore the effect and mechanism of macrophage scavenger receptor 1（MSR1）on osteogenic differentiation of bone marrow mesenchymal stem cells（BMSCs）. Methods：In vivo，MSR1 wild type（WT）and knock out（KO）mice were used to perform tibial monocortical defect model. Further，the three-dimensional reconstruction and parameter analysis after micro-CT scan were carried out on day 10 post-injury. In vitro，BMSCs were first stimulated by conditioned medium from MSR1 WT or KO primary macrophages. Then，CCK-8，Transwell，alizarin red staining，alkaline phosphatase staining and real-time quantitative reverse transcription polymerase chain reaction were performed to explore the effect of MSR1 on proliferation，migration and osteogenic differentiation of BMSCs. Western blot and ELISA were used to investigate the specific mechanism of MSR1 on osteogenic differentiation of BMSCs. Results：The loss of MSR1 significantly reduced the ability of bone regeneration in vivo. In addition，knockout of MSR1 in macrophages significantly affected the osteogenic differentiation ability of BMSCs，but not the proliferation and migration ability in vitro. We also identified MSR1 could increase the secretion of bone morphogenetic protein 2（BMP2）through JAK/STAT3 signaling pathway，thus exerting its regulatory effect on BMSCs osteogenic differentiation. Conclusion：MSR1 is one of the key molecules that macrophages play a role in regulating osteogenic differentiation of BMSCs，which provides a solid theoretical basis for targeting macrophages MSR1 to promote bone healing in the future.

Abstract:Objective：To observe the inhibitory effects of proanthocyanidin on activation of nucleotide-binding oligomerization domain-like receptor protein 3（NLRP3）inflammasome and phosphorylation of nuclear factor（NF）-κBp65 induced by lipopolysaccharide（LPS）and adenine nucleoside triphosphate（ATP）in mouse microglia（BV2）. Methods：BV2 cells were stimulated with 1.0 μg/mL LPS and 2.5 μmol/L ATP，and treated with different concentrations of proanthocyanidin（0.1，1.0，2.5，5.0 μg/mL）. Cell viability was determined by thiazolyl blue tetrazolium bromide（MTT）assay. Nitric oxide（NO）release was detected by colorimetry. The activity of lactate dehydrogenase（LDH）was measured by microenzyme labeling method. The secretion of interleukin（IL）-1β and IL-18 were determined by ELISA. Expression of NLRP3，apoptosis-associated speck-like protein containing a CARD（ASC），caspase-1，pro-caspase-1，p-NF-κBp65，NF-κBp65 were detected by Western blot. Results：The effect of different concentrations of proanthocyanidin on the survival rate of BV2 cells was not statistically significant compared with the control group（P > 0.05）. Compared with the control group，LPS/ATP increased the secretions of NO，IL-1β，IL-18 and LDH activity（P < 0.05），and the expressions of NLRP3，ASC，pro-caspase-1，caspase-1，p-NF-κBp65（P < 0.05）. Compared with the LPS/ATP group，proanthocyanidin reduced the secretions of NO，IL-1β，IL-18 and LDH activity of BV2 cells（P < 0.05）. In addition，proanthocyanidin（1.0，2.5，5.0 μg/mL） decreased the expressions of NLRP3，ASC，pro-caspase-1 and caspase-1（P < 0.05）. Similarly，NF-κB inhibitor BAY11-7082（5.0 μmol/L）reduced NF-κBp65 phosphorylation and the expressions of NLRP3，ASC，pro-caspase-1，and caspase-1（P < 0.05）. Conclusion：Proanthocyanidin can inhibit secretion of inflammatory factor and activation of NLRP3 inflammasome induced by LPS/ATP，which is closely related to the inhibition of phosphorylation of NF-κBp65 by proanthocyanidin in LPS/ATP induced status.

Abstract:Objective：To investigate the inhibitory effect of artemisinin on human skin keloid fibroblasts and its related mechanism. Methods：Primary isolation，culture and passage of human keloid fibroblasts were performed. Human keloid fibroblasts were pretreated with different concentrations of artemisinin，and cell proliferation was measured by CCK-8 method every 24 hours for 5 consecutive days to observe the optimal concentration of drug treatment. The following experiments were divided into four groups：blank group，artemisinin group，artemisinin+IL-6 group and artemisinin+AG490 group. Flow cytometry was used to detect the apoptosis rate in the early stage of each group，real-time PCR was used to detect the mRNA expression levels of matrix metalloproteinase（MMP）2，MMP9 and STAT3 in each group，and Western blot was used to detect the protein expression levels of MMP2，MMP9，STAT3 and p-STAT3 in each group. Results：According to the results of CCK-8，150 μg/mL artemisinin cells for 48 hours were selected as the concentration and time of follow-up intervention. Flow cytometry results showed that the percentage of early apoptotic cells in artemisinin group，artemisinin+IL-6 group and artemisinin+AG490 group was significantly higher than that in the blank group，and the percentage of early apoptotic cells in artemisinin+IL-6 group was lower than that in artemisinin group and artemisinin+AG490 group（P < 0.01）. Real - time PCR showed that compared with the blank group，the expression of MMP2 and MMP9 mRNA in artemisinin，artemisinin+IL-6 groups，artemisinin+AG490 group were significantly lower（P < 0.01）. The expressions of MMP2，MMP9 mRNA in artemisinin，artemisinin+AG490 group were lower than in artemisinin+IL-6 group（P < 0.01）. Western blot showed that compared with the blank group，the expressions of STAT3，p-STAT3，MMP2，MMP9 protein in artemisinin，artemisinin+IL-6 groups，artemisinin+ AG490 group were significantly lower（P < 0.01）. The expressions of p-STAT3，MMP2，MMP9 protein in artemisinin，artemisinin+AG490 group were lower than in artemisinin+IL-6 group（P < 0.01）. Conclusion：Artemisinin has an inhibitory effect on keloid，and its mechanism may inhibit the experession of MMP2，MMP9 by inhibiting the excessive activation of p-STAT3.

Abstract:Objective：To observe the effects of 3D-printed poly lactic-co-glycolic acid（PLGA）scaffold on the repair of rat palate bone defect. Methods：The PLGA was dissolved in acetone，and disc-shaped mesh scaffolds having pores with diameters of 100 μm and a single layer thickness of 60 μm were printed using a 3D printer. Twelve rats were randomly divided into two groups（n=6）to create round palate bone defects with a diameter of 3 mm. The bone defect in the experimental group was implanted with a 3D-printed PLGA scaffold and sutured to close the defect，while in the control group the defect was sutured to close only. The rats were sacrificed after 8 weeks，and the bone defect repair was evaluated by using micro-CT and histological analysis. Results：3D-printed PLGA scaffolds were successfully fabricated. Eight weeks after the establishment of the palate defects model in rats，the bone-volume/total-volume（BV/TV）of the experimental group implanted with the 3D-printed PLGA scaffold was significantly higher than the control group（P < 0.05），and the unhealed area of the bone defect was also smaller than that of the control group（P < 0.05）. HE staining of the palate bone tissue showed that a large amount of new bone was formed at the edge of the defect in the experimental group，while the control group had only a small amount of new bone. Conclusion：3D-printed PLGA scaffold can promote the bone regeneration in palate bone defect.

Abstract:Objective：To treat the rabbit model of bone tuberculosis through preparation of calcium sulphate/nano hydroxyapatite immune artificial bone，and discuss the actual effect of nanometer hydroxyapatite immune artificial bone application. Methods：Calcium sulfate/nanometer hydroxyapatite was prepared by gelatine and polyhexyl ester composite coating，the rabbit model of the right femoral immune bone tuberculosis was established by injecting tuberculosis factor. After the lesion in the bone tuberculosis model was removed，the calcium sulfate/nanometer hydroxyapatite artificial bone was plated into the defect site. The blood drug concentration of the treated group was detected at 7，14，28 days after surgery. At 4 weeks and 12 weeks after surgery，bone repair was observed under a microscope. Results：The anti-tuberculous bone of calcium sulfate/nanometer hydroxyapatite was successfully prepared，and the immune artificial bone space was basically uniform under the electron microscope，and the anti-tuberculosis drugs were dispersed between the spaces. The model of rabbit femoral tuberculosis was successfully established and the tuberculosis of bone tuberculosis was formed. In the treatment group，the blood drug concentration was maintained within 28 days after operation. Chondrocyte proliferation and the occurrence of bone healing of treatment group were active in 4 weeks after operation. At 12 weeks after surgery，the bone defect of treatment group was healed completely，and the defect was repaired by bone tissue induced by anti-tuberculous bone. The bone loss in the control group was also healed，but the bone healing was weak. Tartrate resistant acid phosphatase（TRAP）staining showed that the volume and number of osteoclasts formed decreased at 12 weeks after surgery，and the number of osteoclasts in the control group was greater than that in the treatment group. The ELISA results showed that serum C-reactive protein（CRP），interleukin-8（IL-8），interleukin-6（IL-6），tumor necrosis factor-α（TNF-α） levels decreased after treatment. Conclusion：The sulphate/nanometer hydroxyapatite immune anti-tuberculous bone can effectively treat rabbit immune bone tuberculosis，maintain the blood drug concentration for a period of time，and has a good osteogenic effect.

Abstract:Objective：To investigate the DNA methylation sites related to the prognosis of patients with pancreatic ductal adenocarcinoma（PDAC）at the whole-genome level by utilizing The Cancer Genome Atlas（TCGA）database. Methods：The clinical data，DNA methylation data detected on Illumina Humanmethylation450k beadchip and transcriptome data produced by Illumina Hiseq of PDAC patients were downloaded from TCGA database（version 2016_01_28）. We finally chose 179 cases containing both of clinical data and methylation expression profiles to analyze the effect of methylation level on survival by Cox’s proportional hazards model. Five factors including age，sex，location，histological grade and pathological stage were used to correct hazard ratio and P value. Next we chose 173 cases containing both of gene expression and methylation expression profiles to explore correlation between methylation level and mRNA expression level. Furthermore，we also evaluated the expression level of mRNAs with the prognosis. Results：The age of 179 patients was 64.64±10.96 years and that of 173 patients was 64.46 ± 10.91 years. The median survival times were both 20.1 months. Among the top 20 methylation sites，hypermethylation of 11 sites and hypomethylation of other 9 sites were associated with worse prognosis. The strongest site influencing the survival for PDAC in this study was cg01656216，which was located in the 5′UTR region of ZNF438（P=4.11×10-6，HR=0.37，95%CI：0.24-0.56）. The methylation levels of 8 sites showed significant inverse correlation with mRNA expression levels（r<-0.3，P < 0.05）. In addition，the mRNA expression level of PKP3（cg20268054）and EFNB2（cg22179913）were also related to the survival of PDAC（HR=1.66，95%CI：1.06-2.61，P=0.027；HR=1.86，95%CI：1.21-2.88，P=0.005）. Conclusion：Based on the analysis of TCGA database，methylation sites in PKP3 and EFNB2 genes regions are significantly associated with PDAC prognosis，whose potential for predicting prognosis of PDAC can be further studied.

Abstract:Objective：To find more differentially expressed circRNAs in thyroid cancer and explore their mechanisms through microarray analysis. Methods：R software was used to obtain differential expressed circRNAs from the microarray datasets GSE93522. CircRNA-miRNA-mRNA regulatory networks were constructed by Cytoscape software according to the relevant miRNAs and mRNAs predicted by miRDB，miRTarBase and TargetScan，combining with differential expressed miRNAs and mRNAs from The Cancer Genome Atlas（TCGA）. The important circRNA-miRNA-mRNA networks were obtained by using gene ontology（GO）analysis，Kyoto encyclopedia of genes and genomes（KEGG）analysis，survival curve analysis and so on. Furthermore，the vital regulatory networks were verified by GSE40807，GSE3467，GSE33630 and clinical data from TCGA. Results：The circRNA-miRNA-mRNA regulatory networks included 18 circRNAs，8 miRNAs and 26 mRNAs. GO analysis showed that some of the mRNAs were involved in cell metabolism，migration，and other functions，as well as the composition of cyclin-dependent protein kinase complex. KEGG analysis showed that some mRNAs were correlated with the PI3K-AKT pathway，MAPK pathway，and P53 signaling pathway. Important circRNA-miRNA-mRNA regulatory networks were constructed according to the circRNA score and function analysis，which based on 6 circRNAs，8 miRNAs and 16 mRNAs. Hsa_circ_0001658-hsa-mir-183-AKAP12 was considered to the vital regulatory network according to the expression verification and clinical data analysis from TCGA. Conclusion：Many circRNA-miRNA-mRNA networks are related to the development of thyroid cancer. Hsa_circ_0001658-hsa-mir-183-AKAP12 is considered to a vital regulatory network. These findings may be helpful to find more diagnostic or prognostic markers and therapeutic targets of thyroid cancer.

Abstract:Objective：To analyze the role of long no-codding RNA（lncRNA）MIR4713HG in the progression and prognosis of colorectal cancer（CRC）by bioinformatics methods，and further predict the possible molecular mechanisms. Methods：The gene expression data and clinical data of CRC were downloaded from The Cancer Genome Atlas（TCGA）database. The data were analyzed by Perl and R software，and the differentially expressed genes were screened. Further，the differential gene survival，independent prognosis and clinicopathological correlation analysis were performed. The most relevant differential gene was selected as the target gene. The correlation between the expression of the target gene and the different clinicopathological features of CRC and its influence on the prognosis of CRC patients were analyzed. The independent prognosis analysis was performed on different clinicopathological features by R software. Gene set enrichment analysis（GSEA）enrichment analysis of the target gene was used to predict the possible mechanism by which the target gene regulated the progression and prognosis of CRC. Results：By analyzing the gene expression data，we obtained 7 866 differentially expressed genes. The correlation analysis of differential gene survival，independent prognosis and clinicopathological features found that MIR4713HG was significantly associated with survival prognosis and clinicopathological features of CRC. MIR4713HG was used as the target gene. MIR4713HG was found to be highly expressed in CRC tissues by TCGA database（P < 0.001）. MIR4713HG was associated with CRC grade and TNM stage（P < 0.05），but no age correlation with patients（P=0.999）. Independent prognostic analysis suggested that the prognosis was associated with MIR4713HG，age，tumor grade，TNM stage（P < 0.05），MIR4713HG and age as independent risk factors for evaluating patient prognosis. GSEA enrichment analysis showed that MIR4713HG was enriched in the P53 signaling pathway. Conclusion：The gene of lncRNA MIR4713HG can be used as a target for evaluating the progression and prognosis of CRC，which may play a role through the P53 signaling pathway.

Abstract:Objective：To investigate the change of bacterial composition in the gut of Crohn’s disease（CD）patients in comparison with the healthy subjects and the effects of Bifidobacterium longum（B. longum） on differentiation of peripheral blood mononuclear cells（PBMCs） to CD25+Foxp3+Treg cells and secretion of interleukin（IL）-10，IL-12，and transforming growth factor（TGF）-β of PBMCs in patients with CD. Methods：Fecal samples were obtained from active CD patients（n=19）and healthy subjects（n = 20）. Bacterial microbiome was analyzed by high-throughput sequencing of 16S rRNA. PBMCs obtained from CD patients were co-cultured in vitro with B. longum，B. longum supernatant，B. longum medium and PBS. The proportion of CD25+Foxp3+Treg cells in the peripheral blood was determined by flow cytometry. Concentrations of IL-10，IL-12 and TGF-β in culture supernatant were measured by ELISA. Results：We observed that bacterial microbiota was skewed in CD，with an increased proportion of Proteobacteria and a decreased proportion of Firmicutes and Actinobacteria at the phylum level，and an increased proportion of Escherichia Shigella，Streptococcus，and Veillonella，while a decreased proportion of Faecalibacterium，Gemmiger，Bifidobacterium，Ruminococcus，Roseburia and Fusicatenibacter at the genus level. Compared with B. longum medium and PBS，B. longum and B. longum supernatant showed a significant higher induction capacity of the anti-inflammatory cytokine IL-10 and TGF-β，while did not remarkably elicit the production of pro-inflammatory cytokine IL-12. The B. longum supernatant induced the highest IL-10/IL-12 ratio and the frequency of peripheral blood CD25+Foxp3+Treg cells in PBMCs，followed by the B. longum. Conclusion：Both B. longum and B. longum supernatant display anti-inflammatory capacities and properties to induce the peripheral blood CD25+Foxp3+Treg cells differentiation. The metabolite of B. longum shows a promising role in treating the inflammatory bowel disease.

Abstract:Objective：To investigate the characteristics of 24-hour urinary electrolyte excretion in non-dialysis patients with chronic kidney disease（CKD）and its correlation with clinical parameters. Methods：A total of 752 patients with CKD from May 2017 to April 2019 were selected to retrospectively analyze the relationship between 24-hour urinary electrolytes and clinical indicators. Results：Our results showed that there was no significant difference in urinary sodium or urinary potassium excretion in patients with different stages of CKD1-4. However，urinary calcium and urinary phosphorus excretion decreased with the decline of glomerular filtration rate. Besides，24-hour urinary sodium and urinary potassium were positively correlated with 24-hour urine protein，regardless of the complication of high blood pressure or diabetes. Meanwhile，24-hour urinary calcium was negatively correlated with 24-hour urine protein and 24-hour urinary phosphorus was showed no correlation with 24-hour urine protein. The prevalence of hypertension and cardiovascular disease in the low urine phosphorus group was higher than that in the high urine phosphorus group，the prevalence of cardiovascular disease in the low urine calcium group was higher than that in the high urine calcium group，and the prevalence of diabetes in the high urine potassium group was higher than that in the low urine potassium group. Conclusion：The level of urine electrolyte in patients with CKD is associated with urine protein，the prevalence of hypertension，diabetes and cardiovascular diseases. Its management deserves more attention.

Abstract:Objective：To evaluate the value of the difference between peripheral venous and arterial lactate level for the prognosis of patients with septic shock after early resuscitation. Methods：Patients with septic shock in the Department of Critical Care Medicine，Affiliated Hospital of Integration of Chinese and Western Medicine，Nanjing University of Chinese Medicine from May 2017 to May 2018 were enrolled in this prospective observational study. Patients were divided into two groups according to the 28-day mortality. Peripheral venous and arterial blood samples were withdrawn simultaneously and analyzed immediately at the bedside on admission and after 6 h-bundles of treatments. Peripheral venous lactate concentration（V-Lac）and arterial lactate concentration（A-Lac）were recorded，while the difference between V-Lac and A-Lac（ΔLac） was calculated. Multivariate logistic regression analysis was performed to select possible risk factors for 28-day mortality，and the receiver operating characteristic curve（ROC） was plotted to assess the prognostic value for 28-day mortality. Results：Fifty-nine patients were enrolled. Thirty-four patients survived and twenty-five patients died during the 28-day period. Compared with the survivor group，acute physiology and chronic health evaluation Ⅱ score（APACHE Ⅱ）and acute physiology and chronic health evaluation Ⅱ score（SOFA）were significantly higher in the non-survivor group（P < 0.05）. In the non-survivor group，A-Lac and V-Lac were significantly higher at admission（P < 0.05），and V-Lac and ΔLac were significantly higher after 6 h-bundles of treatments（P < 0.05）. Multivariate logistic regression analysis showed that ΔLac after 6 h-bundles of treatments（OR=74.107，P=0.005）was the independent risk factors for 28-day mortality. It was shown by ROC curve analysis that the maximum area under the ROC curve（AUC）of ΔLac was 0.838（P < 0.001）.When the best cut-off value was 0.65 mmol/L as a predictor of 28-day mortality，the sensitivity was 76.0% and the specificity was 85.3%. Conclusion：The presence of ΔLac after the early resuscitation of septic shock is associated with worse outcomes. It can be used to gauge the severity of tissue hypofusion and to estimate poor outcome of patients with septic shock.

Abstract:Objective：To investigate the clinical characteristics and outcomes of central nervous system（CNS） involvement in pediatric patients with hemophagocytic syndrome，also known as hemophagocytic lymphohistiocytosis（HLH）. Methods：A total of 112 pediatric patient who were newly diagnosed with HLH at the Children’s Hospital Affiliated to Nanjing Medical University during November 2008 to December 2017 were retrospectively evaluated for CNS involvement. Neurological symptoms，cerebrospinal fluid（CSF） findings，neuroradiological results and treatment outcome were analyzed. Results：About 84.1% patients（22/29）with CNS-HLH in our study had neurologic manifestation. The most two common symptoms were seizures and disturbance of consciousness. CSF analysis and neuroradiological studies were performed in 28 patients. The results showed that 18 patients（62.0%）had CSF abnormalities，9 patients（32.1%）presented nodular or diffuse signal abnormalities，while 17 patients（60.7%）had cerebral atrophy，mild ventriculomegaly or other signs of chronic changes. Five-year cumulative survival rate of 112 patients with HLH was 75.9%. Patients with CNS involvement showed poor overall survival compared to those without CNS involvement（χ2=3.936，P=0.047）. Overall survival of CNS-HLH who did not receive intrathecal therapy was inferior to those who received intrathecal therapy（χ2=6.003，P=0.014）. Cox multivariate analysis showed that absence of intrathecal therapy and severe anemia（Hb≤60 g/L）at diagnosis were independent risk factors in pediatric CNS-HLH. Conclusion：CNS involvement is associated with poor prognosis in pediatric patients with HLH. Children with HLH require overall assessment of neurological involvement and appropriate therapy. Lack of intrathecal therapy and severe anemia are related to poor prognosis.

Abstract:Objective：To analyze the correlation between the expression of forkhead box P1（FOXP1）and proliferative factor Ki67 protein，and investigate the effects on prognosis of advanced gastric carcinoma patients. Methods：Paraffin-embedded sections immunohistochemical SP method was used to detect the expression of FOXP1 and Ki67 in gastric sdenocarcinoma and paracancerous tissue. Pearson rank correlation analysis was used to analyze the relationship，and regression analysis was performed to estimate the effects of FOXP1 and Ki67 expression on the recurrence-free survival（RFS）. Results：The expressions of FOXP1 were lower in the gastric cancer tissues than in the corresponding adjacentnon-tumor tissues. There was negative correlation between the expression of FOXP1 and Ki67 in gastric cancer tissue. The results showed that the loss of FOXP1 expression and the higher Ki67 expression were influential factors of efficacy in the RFS. Conclusion：The expression of FOXP1 negatively correlates with the expression of Ki67 in gastric carcinoma. A loss of FOXP1 expression and a higher Ki67 expression affect the prognosis of gastric carcinoma patients together.

Abstract:Objective：To investigate the distribution of stereoacuity and the relationship between stereoacuity and ocular parameters in children aged 5to 6 years. Methods：Children aged 5 to 6 years from Yuhuatai District，Nanjing City were recruited in 2017 for relevant examinations，including visual acuity（VA），ocular alignment and movements，anterior segment and fundus examination，refraction，axial length（AL），interpupillary distance，randot stereotest，etc. The distribution of stereoacuity in children aged 5 to 6 years was analyzed，and the relationship between stereoacuity and ocular parameters was analyzed by using bivariate correlation analysis and multiple linear regression model analysis. Results：A total of 1 154 children were included in the study，with stereoacuity of 40 arc seconds（652 cases）accounting for 56.5% and 60 arc seconds（388 cases）for 33.6%. Multiple linear regression showed that interocular difference in AL（P < 0.001），VA（P < 0.001）and interocular difference in spherical refractive errors（P < 0.001）were all correlated with stereoscopic vision. Conclusion：The children aged 5 to 6 years with higher interocular difference in AL，worse VA and higher interocular difference in spherical refractive errors have worse stereoacuity score.

Abstract:Objective：To investigate the distribution of glucose metabolism in the brain of type 2 diabetes mellitus（T2DM）. Methods：Retrospective analysis was performed on 47 patients with T2DM who had been clinically confirmed and had no significant brain injury，62 healthy persons were selected as healthy control（HC）group. Statistical parametric mapping（SPM）was used to analyze 18Fluoro-2-deoxyglucosel（18F-FDG） positron emission tomography/computed tomography（PET/CT）imaging data in the brain of two groups，two independent sample t-test based on voxel level was performed. Talairach coordinate values and corresponding brain regions with different cerebral glucose metabolism were obtained. Results：Brain PET/CT imaging of T2DM patients showed regional abnormal patterns of cerebral glucose metabolism，decreased glucose metabolism in the cognitive cortex of the frontal and parietal lobes of the brain，and increased glucose metabolism in the extensive white matter region，all of which showed statistically significant differences compared with HC group（P < 0.001）. Conclusion：Increased white matter metabolism related to inflammatory response may aggravate white matter damage in T2DM patients，while hypermetabolism in the cognitive gray matters of the posterior cerebellum may have a negative feedback effect on the cerebral cognitive cortex. This specific regional differential pattern of cerebral glucose metabolism provides a material basis for the study of cognitive impairment in T2DM.

Abstract:Objective：To investigate the association between methylation of adenomatous polyposis coli（APC） gene and the risk of upper digestive tract tumor. Methods：Relevant articles were identified using PubMed，Web of Science，Embase and China National Knowledge Infrastructure（CNKI）database. We used the keywords “APC” and “methylation”，in conjunction with any of the following terms：“esophageal cancer”，“esophagus cancer”，“gastric cancer” or “stomach cancer”. References listed in the identified articles were further manually searched for additional studies. The search range was from January 2000 to February 2018. A random or fixed effect model was adopted to calculate pooled odd ratio with 95% confidence interval. Results：The current Meta-analysis included 17 studies with 1 201 cases and 959 controls. The significant heterogeneity was across studies. The pooled OR of APC methylation was 13.24（95% CI：6.42-27.33，P < 0.001）for upper digestive tract tumor. A significant association was found between the hypermethylation frequency and the increased TNM stages（pooled OR：3.95，95% CI：1.46-10.66，P=0.007）. Conclusion：The present Meta-analysis provides evidence that APC promoter methylation is associated with an increased risk in upper digestive tract tumor. Our findings underscore the clinical relevance of aberrant methylation as a promising biomarker for upper digestive tract tumor.