Abstract:Objective：Isolate and identify a new strain of lytic phage and study its biological characteristics，so as to provide an alternative treatment for clinical infection caused by multi-drug resistant bacterial in the future. Methods：The new phage named vB_EcoM_RZ was isolated and purified by double layer agar method. The morphology of the new phage was observed by electron microscope. The incubation period and burst size of the new phage were determined by one-step growth curve，the genomic characteristics and encoded proteins of phage vB_EcoM_RZ were studied through the whole genome sequencing and mass spectrometry analysis combined with bioinformatics analysis. Results：A new type of Escherichia coli virulent bacteriophage was successfully isolated；biological experiments showed that it had fast lytic speed，wide host range，and good temperature stability；genomics studies showed that it did not encode genes related to toxins or other virulence factors；43 known proteins and some hypothetical proteins with unknown functions were isolated and identified by mass spectrometry. Phylogenetic analysis showed that it was a new type of bacteriophage. Conclusion：A new type of Escherichia coli virulent bacteriophage named vB_EcoM_RZ has been isolated and identified. It has excellent properties and the potential to be further used in the treatment of infection caused by drug-resistant bacteria.

Abstract:Objective：This stndy aims to investigate the effect of CAMK4-EGR3 signaling axis on neuronal dendritic development in the hippocampus of congenital hypothyroidism（CH） rats. Methods：The CH models were established in 1-day-old，7-day-old and 21-day-old SD rats，and were divided into CH group and control group. Transcriptome sequencing，q-PCR and Western blot were used to detect the expression of CAMK4 and EGR3，and immunofluorescence was used to observe the growth of neuronal dendrites. Results：①The protein expressions of CAMK4 and EGR3 in the hippocampus of the control group increased in a time dependent manner，and the expression of CH group was significantly lower than that of the control group（P < 0.05）；②After CAMK4 was knocked down in the primary hippocampal neurons，the expression of Egr3 was decreased correspondently，and the mean length of dendrites of hippocampal neurons was decreased compared with the control group；③After T3 stimulation on CH primary hippocampal neurons，the protein expression level of CAMK4 increased in a time dependent manner. Conclusion：Thyroid hormone deficiency can decrease the expression of CAMK4 and EGR3 in the hippocampus of rats，and inhibit the development of neuronal dendrites，suggesting that the CAMK4-EGR3 signaling axis plays an important role in the neurodevelopmental abnormalities in the hippocampus of CH rats.

Abstract:Objective：This stndy aims to evaluate the efficacy of palbociclib alone or in combination with the epidermal growth factor receptor inhibitor erlotinib in the treatment of colorectal cancer（CRC）. Methods：Alamar bule method and clone formation assay were used to detect the effects of palbociclib alone or in combination with erlotinib on the proliferation of CRC cell lines. Cell cycle distribution was determined by DNA content. Cell senescence and reactive oxygen species （ROS） accumulation were detected by β-galactosidase and DCFH-DA staining. The expression levels of related proteins were analyzed by Western blot and their clinical efficacies were evaluated in CRC patient-derived xenograft models. Results：Palbociclib inhibits CRC cell proliferation，induce G1 cell arrest，cell senescence and intracellular ROS accumulation effectively. Combination of palbociclib and erlotinib exhibits synergistic effects on CRC，and erlotinib further enhances the multiple inhibitory effects and multi-signaling pathway inhibition of palbociclib on CRC. Synergistic inhibition was also shown in CRC patient-derived xenograft models. Conclusion：Palbociclib combined with erlotinib synergistically inhibits the growth activity of colorectal cancer in vitro and in vivo.

Abstract:Objective：This stndy aims to investigate whether the inhibition of protein phosphatase 2A catalytic subunit Cα（PP2Acα） affects the malignant phenotype of gastric cancer cells and the expression of Wilms tumor 1 related protein（WTAP） in this progression. Methods：The Cancer Genome Atlas（TCGA）database was used to compare the expression of PP2Acα coding gene（PPP2CA）and WTAP in gastric cancer and normal tissues adjacent to the cancer；the KM-plot website was used to analyze the relationship between PPP2CA，WTAP and the prognosis of gastric cancer；lentivirus-mediated short hair Card RNA（shRNA）was used to inhibit the expression of PP2Acα in gastric cancer cells，and then RNA and protein for PCR and WB were extracted to detect the mRNA and protein levels of PPP2CA/PP2Acα and WTAP，respecfively；finally，the influences of PP2Acα inhibition on gastric cancer cells phenotype were detected in vitro and in vivo. Results：After inhibiting PP2Acα，it was found that the proliferation，migration and invasion capabilities of gastric cancer cells were enhanced with epithelial-mesenchymal transition（EMT），accompanied by a significant increase in the protein levels of WTAP. Conclusion：Inhibition of PP2Acɑ promotes the malignant phenotype of gastric cancer cells，which may be achieved by upregulating the levels of WTAP.

Abstract:Objective：This study aims to investigate the effects and potential mechanisms of metformin on the inflammatory cytokine interferon （IFN）-γ induced cell damage in human ovarian granulosa cells KGN. Methods：The effects of metformin alone and with IFN-γ on the viability of KGN cells were detected using CCK-8 kit，and the cell growth status of KGN cells were observed under microscope. The apoptotic cells and the cell cycle in KGN cells were analyzed using flow cytometry. The mRNA expression levels of cyclin dependent kinase inhibitor 1A（CDKN1A），a gene related to cell cycle regulation，were analyzed using q-PCR. Results：IFN-γ treatment inhibited the vitality of KGN cells through blocking these cells from G0-G1 phase to S phase and promoting into apoptosis. Although metformin treatment alone had no obvious effects on the KGN cells， it alleviated the apoptosis in KGN cells and reversed the cell cycle which induced by IFN-γ. Moreover，metformin significantly inhibited the expression levels of CDKN1A in IFN-γ treated KGN cells. Conclusion：Metformin had a protective role on the IFN-γ induced cell injury in KGN cells by down-regulating the abnormal expression of the negative cell cycle regulator CDKN1A in these cells．

Abstract:Objective：The weighted gene co-expression network（WGCNA）and least absolute shrinkage and selection operator（LASSO）were used to investigate the prognostic value of transcription factor SOX12 in the occurrence and development of hepatocellular carcinoma（HCC）. Methods：Using Gene Expression Omnibus（GEO）and The Cancer Genome Atlas（TCGA）corresponding information，Kaplan-Meier（K-M）survival curve and single factor，multivariate Cox regression were used to analyze the clinical value of SOX12 gene expression in HCC. ESTIMATE and CIBERSORT algorithms were used to study the correlation between SOX12 gene expression and tumor immune microenvironment. The WGCNA and LASSO algorithms were used to establish a risk prognosis model to further evaluate the effect of SOX12 gene expression in the high and low risk groups on the mutations of HCC genes. Results：In HCC tumor tissues，the expression of SOX12 was significantly increased，which was related to age，gender，tumor grade，disease stage，and was significantly related to the survival and prognosis of patients. In the risk prognosis model of immune-related genes（IRGs） showed that the overall survival rate of the high-risk group was worse than that of the low-risk group. The risk prognosis model had a significant prognostic prediction effect，and its 1-year，3-year and 5-year AUCs were 0.823，0.811 and 0.824，respectively. The proportion of TP53 gene mutations in the high SOX12 expression group（40%）was significantly higher than that in the low SOX12 expression group（25%）. The results indicated that the high and low SOX12 expression in the high and low risk groups affects the frequency of HCC genetic mutations. Conclusion：The expression of SOX12 is associated with HCC immune infiltration and disease gene mutations，suggesting that it may become a potential target for prognostic evaluation of HCC patients.

Abstract:Objective：This study aims to identify the peptide with different expression in preeclamptic placenta by liquid chromatography-tandem mass spectrometry（LC-MS/MS），and to study the bio-active function of the differentially expressed peptides. Methods：Placental tissues were collected from 4 normal pregnant women and 4 pregnant women with preeclampsia. All participants underwent planned cesarean section in the Department of Obstetrics，the First Affiliated Hospital of Nanjing Medical University from May 2019 to September 2019. The effects of the differential peptide 405SPLFMGKVVNPTQK418 on the proliferation and migration of trophoblast cells（HTR-8/SVneo） were studied by CCK-8 assay，clone formation assay and transwell assay. And the matrigel assay was used to study the effect of this peptide on the angiogenesis ability of human umbilical vein endothelial cells（HUVECs）. Western blot was used to detect the metalloproteinase 2 （MMP2） and metalloproteinase tissue inhibitor 1 （TIMP1） in peptide-treated group and control group. Results：A total of 3 582 peptides were screened out and 48 differentially expressed peptides were identified. In vitro functional assays showed that the differential peptide 405SPLFMGKVVNPTQK418 could promote the proliferation and migration of trophoblast cells and the tube formation ability of endothelial cells. After peptide treatment，the expression of MMP2 was up-regulated and the expression of TIMP1 was down-regulated. Conclusion：A series of differentially expressed peptides were detected in preeclamptic placenta，and the differential peptide 405SPLFMGKVVNPTQK418 exhibited a promotive role in the behaviour of trophoblast cells and endothelial cells，which provides support for the study of pathogenesis and treatment of preeclampsia.

Abstract:Objective：This study aims to observe the changes of miRNA-199a-5p expression in human skin fibroblasts with thermal injury and its effects on the proliferation，migration and invasion of skin fibroblasts. Methods：Cell models of thermal injury were established using human skin fibroblast cell line by bathing in water at 52℃ for 30 s and 60 s，respectively，and the thermal injury of cells was observed and compared. The proliferation rate of cells 24 h and 48 h after thermal injury was detected by MTT assay. The changes of miRNA-199a-5p expression in the cells 24 and 48 h after thermal injury were determined through qRT-PCR. Cell migration and invasion were detected using wound-healing assay and Transwell assay. The expression of miRNA-199a-5p in thermally injured cells was increased using mimics，and the proliferation and invasion of thermally injured cells were detected. Results：Bathing in water at 52 ℃ for 30 s could successfully establish a thermal injury model in human skin fibroblasts. After thermal injury，miRNA-199a-5p expression was down-regulated［24 h，（2.67±0.35）%，P＜0.001；48 h，（18.42±0.44）%，P＜0.001］，cell proliferation was significantly inhibited［24 h，（17.10±3.21）%，P＜0.002；48 h，（25.93±1.74）%，P＜0.001］，cell migration decreased significantly［（35.35±7.07）%，P＜0.001］，and cell invasion was also significantly inhibited［（57.14±9.52）%，P＜0.007］. After enhancing miRNA-199a-5p expression in the thermally injured cells using mimics，the proliferation of the cells increased significantly［（136.55±6.14）%，P＜0.003］，and the invasion ability of the cells was enhanced［（136.55±6.14）%，P＜0.003］. Conclusion：The expression level of miRNA-199a-5p in human skin fibroblasts with thermal injury is positively correlated with cell proliferation，migration and invasion. Increasing the expression level of miRNA-199a-5p in thermally injured cells can help it rapid return.

Abstract:Objective：This stndy aims to investigate the application prospect of lawsone in the treatment of triple negative breast cancer（TNBC）. Methods：Two TNBC cell lines，MDA-MB-231 and SUM1315，were selected as the research subjects. The effects of lawsone on breast cancer cells were investigated by CCK-8 assay，wound-healing assay，cellular invasion assay，colony formation assay，EdU assay and cell cycle assay. Results：The 72-hour IC50 values of MDA-MB-231 and SUM1315 were 249.87 μmol/L and 158.34 μmol/L，respectively. Lawsone could significantly inhibit the migration，invasion and proliferation of breast cancer cells，and prolong the G1 phase of breast cancer cell cycle. Conclusion：Lawsone may affect the occurrence and development of breast cancer by inhibiting the migration，invasion and proliferation of breast cancer cells.

Abstract:Objective：To investigate the predictive value of galectin-3（Gal-3）on carotid atherosclerosis（CAS）in middle-aged and elderly people. Methods：The general data and clinical biochemical indexes of 95 subjects who underwent physical examination in the community health service center of Nanchan temple in Wuxi from September 2017 to March 2018 were collected，and their Gal-3 level was detected. In December 2020，carotid artery ultrasound was used to assess carotid intima media thickness（cIMT）. The subjects were divided into 4 groups by the quartile method of Gal -3 level，and the characteristics of different groups were analyzed. The correlation between cIMT and clinical characteristics in all subjects and then particularly in patients who diagnosed with type 2 diabetes（T2DM）was explored，respectively. Finally，multiple linear regression analysis was used to explore the affecting factors of cIMT in T2DM patients. Results：Subjects with low Gal-3 level had corresponding lower fasting blood glucose（FBG）and glycated hemoglobin（HbA1c），as well as lower cIMT. Gal-3 was related with bilateral cIMT and found as affecting factor of CAS in patients with T2DM（P < 0.05）. Conclusion：Gal-3 is correlated with cIMT and has predictive value for the development of CAS in patients with T2DM.

Abstract:Objective：This study aims to detect the differential expression profile of platelet miRNAs（miRNA）in patients with coronary artery disease（CAD）and clopidogrel low response（CLR）. Methods：A total of 78 CAD patients with clopidogrel treatment（loading dose 300 mg and maintenance dose 75 mg/d）at least 5 days were consecutively enrolled. Adenosine diphosphate（ADP）induced platelet aggregation（PLADP）was tested by light transmittance aggregation（LTA）. Nineteen patients whose PLADP were at upper quartile were defined as CLR group，while another nineteen patients at lower quartile were selected as control. The total RNA of leukocyte depleted platelet（LDP）were extracted from each of the selected patients，and the extracted total RNA from the two groups were mixed into two RNA pools respectively. After two RNA pools were qualified by RNA denaturation electrophoresis，the differential expression profiles of platelet miRNAs were screened by high-throughput sequencing. The target gene predicting software including TargetScan，miRanda，PITA and miRWalk were adopted to explore the miRNAs that modulate the key protein in the process of platelet aggregation. Results：Baseline clinical characteristics of the two groups showed no significant difference. The PLADP level of the CLR group was significantly higher than that of the control group（P < 0.000 1）. The total RNA pools of the two groups were detected by RNA denaturation electrophoresis and no significant degradation was found. 95 platelet miRNAs were differently expressed by high-throughput sequencing between the two groups，among which 20 miRNAs（hsa-miR-300，hsa-miR-151b，hsa-miR-1299，et al）were 2-fold down-regulated in CLR patients，and 8 miRNAs（hsa-miR-188-5p、hsa-miR-6874-3p、hsa-miR-218-5p、hsa-miR-3150b-3p、hsa-miR-1288-3p、hsa-miR-1299、hsa-miR-6862-5p、hsa-miR-4421）were identified by at least two target gene predicting software as having regulatory effects on key proteins associated with platelet aggregation. Conclusion：There is a significant downregulation of platelet miRNAs in CLR patients. We successfully screen 8 miRNAs that could modulate the key protein in the process of platelet aggregation，which is warrant to be investigated in future study.

Abstract:Objective：The clinical manifestations of patients with anti-N-methyl-D-aspartate receptor（anti-NMDAR） encephalitis in East China and factors associated with prognosis were analyzed. Methods：A retrospective study of 106 patients（58 females，48 males）with anti-NMDAR encephalitis in East China was carried out from June 2015 to February 2020. Clinical features and factors influencing outcomes were reviewed. Results：Behavioral changes were observed in 74.5%（79/106）of patients，and comprised the initial symptoms in 61.3%（65/106）. Seizures were observed in 67%（71/106） of patients，and served as initial symptoms in 31.1%（33/106）. A total of 54.9%（39/71）of seizures were focal seizures. The patients with high cerebrospinal fluid（CSF）antibody titers experienced more clinical symptoms than those with low CSF antibody titers. One hundred and fourteen electroencephalography（EEG） or video EEG recordings were obtained from 92 patients. EEG background activity（BA） was significantly aggravated at 12 days. A total of 72.5%（74/102）of patients showed normal magnetic resonance imagings（MRIs）. Brain lesions were observed in 27.45% of patients（28/102）. During the peak stage of the disease，focal high blood flow with normal MRIs were observed from 56.52%（13/23） arterial spin labeling（ASL）of anti-NMDAR encephalitis patients. Focal high blood flow with brain lesions were observed in 39.13%（9/23）ASL of patients. The binary logistic regression analyses revealed the factors associated with poor outcomes included consciousness disturbance，EEG BA，number of symptoms and CSF antibody titer. Conclusion：EEG BA and number of symptoms are associated with CSF antibody titers. Consciousness disturbances，EEG BA，number of symptoms and increasing CSF antibody titers served as predictors of poor outcomes.

Abstract:Objective：This study aimed to analyze the safety and short-term efficacy of pulmonary subsegmentectomy in the treatment of early-stage of small nodule lung cancer，comparing to pulmonary segmentectomy. Methods：We retrospectively analyzed 367 patients with small lung nodules who underwent pulmonary subsegmentectomy or segmentectomy in the First Affiliated Hospital of Nanjing Medical University from April 2020 to December 2020. All these subjects were divided into two groups according to surgical types：pulmonary subsegmentectomy（107 cases） and pulmonary segmentectomy（260 cases）. Perioperative clinical characteristics and short-term prognosis between these two groups were compared. Results：The mean surgical margin of the subsegmentectomy group was （2.58 ± 0.94）cm，the removal catheter time was（2.56 ± 0.85）days，and the hospital stay was（3.50 ± 1.07）days. Compared to pulmonary segmentectomy，subsegmentectomy had a similar surgical margin（P=0.446），removal catheter time（P=0.639），hospital stay（P=0.267）and pathological diagnosis（P=0.337），as well as postoperative complications，such as air leak，hoarseness，fever，arrhythmia and so on. The operative time of subsegmentectomy was（147.21 ± 37.97）min，which was longer than that of segmentectomy（134.66 ± 40.70）min（P=0.007）. Besides，the hemorrhage of subsegmentectomy was （50.42 ± 38.59）mL，more than that in pulmonary segmentectomy （41.95 ± 28.16）mL（P=0.027）. However，the number of lymph node sampling in subsegmentectomy（3.46 ± 2.40）was less than that in pulmonary segmentectomy（4.18 ± 2.49）（P=0.011）. At the end of follow-up，there was no metastasis or recurrence in both groups. Conclusion：Pulmonary subsegmentectomy is safe and reliable. It can be applied to treat early-stage small nodules lung cancer. However，the long-term oncological efficiency of pulmonary subsegmentectomy needs further follow-up studies.

Abstract:Objective：This study compared prognoses of advanced non-small cell lung cancer patients with epidermal growth factor receptor exon 19 or 21 mutations after two types of first-line treatment：Icotinib hydrochloride alone or icotinib combined with chemotherapy. Methods：The clinical data of 174 patients admitted to the First Affiliated Hospital of Nanjing Medical University from August 2012 to October 2020 were retrospectively analyzed. Totally，82 cases carried EGFR 21 exon mutation，38 cases received first-line Icotinib therapy，while 44 cases received icotinib combined with the chemotherapy. 92 cases were with the presence of EGFR19 exon mutation，43 cases received first-line icotinib therapy，and 49 cases received iotinib combined with chemotherapy. We compared differences in objective response rate，disease control rate，progression-free survival，and overall survival between EGFR 21 and 19 exon mutation patients after receiving different treatment regimens. Results：Among the patients receiving icotinib treatment，the patients with EGFR21 mutation had a median PFS that was 3.5 months shorter than those with 19 mutation（9.5 months vs. 13.0 months，P=0.046）. There were no significant differences in the median OS，ORR and DCR after 1 cycle of treatment（P > 0.05）. Among patients receiving icotinib combined with chemotherapy，there was no significant difference in PFS，OS，ORR and DCR after 1 cycle of treatment in patients with EGFR exon 21 mutation compared to patients with EGFR exon 19 mutation（P > 0.05）. Among patients with EGFR 21 exon mutations，the median PFS was 5.8 months longer in the combination group compared to the single-agent group（15.3 months vs. 9.5 months，P=0.002）and the median OS was 20.2 months longer than in the single-agent group（46.0 months vs. 25.8 months，P=0.004）. There was no significant difference in ORR or DCR between the two groups after one cycle of treatment（P > 0.05）. Among patients with EGFR 19 exon mutations，median PFS was 9.1 months longer in the combination group compared to the single-agent group（22.1 months vs. 13.0 months，P < 0.001）and median OS was 35 months longer in the combination group compared to the single-agent group（61.0 months vs. 26.0 months，P < 0.001）. There was no significant difference in ORR and DCR between the two groups after one cycle of treatment（P > 0.05）. Conclusion：For patients with advanced NSCLC with EGFR-sensitive mutations，first-line treatment with icotinib combined with chemotherapy significantly improved PFS and OS compared with icotinib monotherapy. In particular，the PFS and OS in patients with EGFR 21 exon mutations were comparable to those in patients with EGFR 19 exon mutations.

Abstract:Objective：To comparethe therapeutic efficiency and risk of intraoperative cryoablation therapy（IOCT）and intraoperative combined cryoablation and hyperthermia（ICCH）in the treatment of unresectable pancreatic cancer. Methods：Patients with unresectable pancreatic cancer admitted to the Pancreatic Center of the Second Affiliated Hospital of Nanjing Medical University were divided into two groups：IOCT group（101 cases）and ICCH group（35 cases）. The clinical data of patients were analyzed and surgical methods were compared. The incidence of postoperative complications，survival rate，tumor indexes and pain scores were compared in groups. Results：Compared with IOCT group，the intraoperative blood loss was less in ICCH group（P < 0.01）. The postoperative fasting time in ICCH group was shorter than that in IOCT group（P < 0.01）. The incidence and severity of postoperative complications in ICCH group were lower than those in IOCT group（P < 0.05）. The 1-year survival rate of patients with pancreatic head carcinoma was significantly higher in ICCH group than in IOCT group（P=0.034）. Conclusion：ICCH is more effective in the treatment of unresectable pancreatic cancer，with lower risk and lower complication rate than IOCT.

Abstract:Objective：This study aims to explore the risk factors that affect the frequent occurrence of convulsions（>3 times）in benign infantile convulsions associated with mild gastroenteritis（BICE），establish a nomogram prediction model，and test its predictive ability. Methods：A retrospective analysis of the clinical data of 91 cases of BICE admitted to the Department of Pediatrics of Affiliated Hospital of Jiangnan University from October 2013 to December 2017 was conducted. According to the number of convulsions，they were divided into frequent convulsions group（>3 times）and control group（≤3 times）. Logistic regression analysis was used to determine the independent risk factors affecting the frequency of convulsions，and construct a nomogram. The receiver operating curve（ROC）and area under the curve（AUC），consistency index（C-index），calibration curve and decision curve analysis（DCA）were used to test the predictive ability of the nomogram. Results：A total of 91 cases with BICE who met the criteria were enrolled，including 29 in the frequent convulsions group and 62 in the control group. The content of CD4 + and CD8 + T cells in the frequent convulsions group was significantly lower than that in the control group. The positive rate of rotavirus，IL-6，IL-10 and TNF-α levels were significantly higher than those in the control group，and the differences were statistically significant（all P < 0.05）. Multivariate logistic regression analysis showed that rotavirus，CD4+ T cell content，IL-10 and TNF-α levels were independent risk factors affecting the frequency of convulsions in cases with BICE（P < 0.05）. These four independent risk factors were incorporated and a nomogram was successfully constructed. AUC，C-index，calibration curve and DCA analysis showed that the nomogram has good prediction effect，and the actual observation has good consistency. Conclusion：The reconstructed nomogram based on rotavirus，CD4+ T cell content，IL-10 and TNF-α levels can more accurately predict the frequency of convulsions in children with BICE，which can provide references for clinical management and treatment of convulsions.

Abstract:Objective：To investigate the clinical efficacy of vitamin D in the adjuvant treatment of bronchial asthma in children. To investigate the correlation between vitamin D levels and various biological indicators of asthma in children with bronchial asthma. Methods：279 children with initial diagnosis of bronchial asthma were recruited as study subjects. Various clinical and biological indicators were detected at the first visit of children. All subjects were grouped and compared according to the initial vitamin D level. Then，children with low serum vitamin D level were randomly divided into the treatment group and the control group. On the basis of the conventional treatment for asthma，the treatment group was given vitamin D supplementation of 400-800 IU/ day orally，and the differences between the two groups in the proportion of patients with acute asthma attacks，the level of asthma control and the number of unsuccessful step-down treatment were compared. Results：The mean proportion of eosinophil in the low vitamin D group was significantly higher than that of the normal group［（4.46±3.92）% vs. （3.46±2.61）%，P < 0.05）］. During the 1-year follow-up，the proportion of acute asthma attacks，the level of asthma control and the number of unsuccessful step-down treatments in the experimental group were not significantly improved compared with those in the control group. Even within 3 months of treatment，the proportion of children in the experimental group with acute asthma attacks was significantly higher than that in the control group［37.3% vs. 12.5%，P < 0.05］. Conclusion：Among children with bronchial asthma，children with low vitamin D levels may be more susceptible to allergies. Vitamin D supplementation in children with bronchial asthma has no significant effect on asthma symptom control and may even increase the risk of acute asthma attacks.

Abstract:Objective：This study aims to clarify the evolution and space-time clusters of the coronavirus disease 2019（COVID-19）epidemic of Jiangsu，providing evidences for rapid detecting and responding to potential outbreaks. Methods：Epidemic curves and dot maps based on coordinates were applied to display the temporal the spatial evolution process. The nearest neighbor indicator（NNI） was used to estimate the global spatial aggregation of indigenous cases，and Kulldorff space-time scan statistic was performed to detect the space-time clusters at the county level. These analysis were performed by Excel 2010，SatScan 9.6.1 and ArcGIS 10.2. Results：A total of 684 confirmed cases were reported during 2020 in Jiangsu. There were 631 indigenous cases，involving 79.44% counties. The NNI of the indigenous cases was 0.27（P < 0.01），indicating global spatial aggregation. The most likely cluster covered four cities in north Jiangsu，including 21 counties，which emerged between January 26 and February 1（LLR=74.92，RR=5.06，P < 0.01）. Three secondary clusters were detected in south Jiangsu，including 27 counties. In particular，secondary cluster-2 happened in early February. 53 Imported cases involved 28 counties in 11 cities，23 of which were admitted in Nanjing and 9 in Lianyungang. Conclusion：COVID-19 cases concentrated in the south and north Jiangsu，but scattered in middle area. More efforts should be put into precise containments to contain potential local multipoint outbreaks in early stage，especially in the Yangtze River Delta core cities in south area and transport hubs in north area.

Abstract:Objective：This study aims to explore the related factors of chronic obstructive pulmonary disease（COPD） in non-smokers，and provide a basis for the development of early screening indicators. Methods：A total of 2 440 non-smokers above 30 years old without history of COPD were recruited from the Health Management Center and Department of Respiratory Medicine of the First Affiliated Hospital with Nanjing Medical University. Questionnaires were used to collect related factors. Symptoms combined with lung function test were used to diagnose COPD. The independent-sample t test was used to compare continuous variables between groups，and the chi-square test or Kruskal-Wallis H test was used for categorical variables，and the correlation strength was estimated by logistic regression model and expressed by OR（95% CI）. Results：After adjusting for age and gender by single factor logistic regression analysis，low education level，low income，living in rural or suburban areas，long-term exposure to dust or chemical poisons，long-term exposure to indoor air pollution such as bio-fuels or oil fume，history of chronic respiratory diseases in childhood，frequent coughing，wheezing and shortness of breath after activities were significantly associated with COPD. Multivariate stepwise regression analysis showed that age of 60 and above，low BMI，history of chronic respiratory disease in childhood，long-term exposure to dust or chemical toxins，frequent coughing when not having a cold，wheezing，and shortness of breath after activities were significantly associated with COPD. Conclusion：Age of 60 and above，low BMI，history of chronic respiratory diseases in childhood，long-term exposure to dust or chemical poisons，frequent coughing when not having a cold，wheezing，shortness of breath after activities are related to COPD in non-smokers. Early screening and intervention should be carried out for people with such characteristics.

Abstract:Advance in research of pyroptosis

Abstract:Allergic conjunctivitis is a common ocular surface disease in children，but the research reports on allergic conjunctivitis in children are relatively scarce. The prevalence of allergic conjunctivitis in children in various countries is increasing year by year and the disease course is long and easy to recur，which seriously affects the quality of life of children. Understanding the epidemiological characteristics of children’s allergic conjunctivitis and the latest research progress of related risk factors can help clinicians to improve their understanding and attention to children’s allergic conjunctivitis. Therefore，it is necessary to review the current epidemiological characteristics and related risk factors of children with allergic conjunctivitis.

Abstract:Thiopurine drugs 6-mercaptopurine（6-MP），thioguanine（TG）and azathioprine（AZA）are widely used immunosuppressive treatment in pediatric patients with inflammatory bowel disease（IBD）and acute lymphoblastic leukemia（ALL）. However，the incidence of adverse reactions especially myelosuppression and hepatotoxicity is high. The metabolism and transformation of thiopurine drugs are mediated by thiopurine S-methyltransferase（TPMT），nudix hydrolase 15（NUDT15），inosine triphosphate pyrophosphohydrolase（ITPA）and multidrug resistance-associated protein（MRP4）. Genetic polymorphisms in genes encoding above-mentioned drug-metabolizing enzymes and transporter proteins can significantly in-uence the pharmacokinetics and pharmacological effects of thiopurines and can be significant determinants of the efficacy and toxicity of therapy. There is still a gap between the current drug treatment strategy and precise clinical application of thiopurines. In this article，we review the studies of pharmacogenetics of thiopurines and therapeutic drug monitoring of active metabolites to provide a new insight into the precise clinical application to thiopurines.