Abstract:The first monoclonal antibody was approved by the Food and Drug Administration（FDA） in 1986. Over the past 30 years，the antibody field has developed rapidly. By December 2019，79 monoclonal antibodies have been approved by FDA for the treatment of cancer，autoimmune，infectious and other diseases. Antibodies have the advantages of high specificity and less side effects，and have become the mainstream of new drug development. Among the top ten biological drugs in the world，antibodies account for half of the total. This paper introduces the novel research technologies，including antibody humanization，phage display，transgenic mice，and single cell PCR，etc.

Abstract:Objective：This study aims to observe the effects of disulfiram（DSF） on the proliferation and cell cycle arrest in human pancreatic cancer cells，and to explore its mechanism. Methods：CCK-8 was used to detect the effects of DSF on the proliferation activity and the cycle distribution was detected by flow cytometry. Real-time PCR and Western blot were used to detect mRNA and protein expression of GADD45A，G2/M related CCNB1，CDC25C，and CDK1 genes and proteins. The phosphorylation of P38 and JNK in MAPK pathway were also detected. SiRNA assay was used to detect the changes of cell cycle and phosphorylation of proteins in MAPK pathway after growth arrest and DNA damage inducible 45A（GADD45A） genes were decreased. Results：DSF combined with Cu（DSF/Cu）inhibited the proliferation of pancreatic cancer cells in concentration-dependent trend. GADD45A was significantly increased in DSF treated groups（11.4 times of control group in PANC-1 cells and 7.99 times of control group in PATU8988T cells，P < 0.001，respectively）. The cells were mainly blocked in G2/M phase and CCNB1，CDC25C and CDK1 genes were significantly decreased（31%，35%，37% of control in PANC-1 cells and 48%，24%，29% of control in PATU8988T cells，P < 0.05，respectively）after treated 24 hours. The proteins showed the same results with the mRNA expression while the p-P38 and p-JNK were increased in dosage and time-dependent trend. Compared with the DSF treated groups，the groups of cells pretreated with siRNA-GADD45A showed an increasing relative viability and the percentage of G2/M phase cells was decreased. Meanwhile，the p-P38 and p-JNK were also decreased. Conclusion：DSF/Cu can significantly inhibit the proliferation and induce G2/M arrest in pancreatic cancer cells. Its anti-tumor effect may attribute to upregulating GADD45A and activating JNK/P38 MAPK signaling pathway.

Abstract:Objective：This study aims to investigate the effects of protein kinase C-α（PKC-α）over-expression on the phosphorylation level of nuclear factor-κB-p65（NF-κB-p65）in human embryonic kidney 293T（HEK-293T）cells，and examine the inhibitory effect of sinomenine（SIN）on PKC-α/NF-κB-p65 signaling pathway. Methods：To construct the rat wild type（WT）PKC-α over-expression plasmid（pIRES2-PKC-α WT，PKC-αWT），rat PKC-α complete sequence coding（CDS）was amplified by PCR and cloned into pIRES2-EGFP. Then，alanine（A） at the site of 25 and lysine（K） at the site of 368 were mutated to glutamic（E） and arginine（R），respectively based on PKC-αWT to construct PKC-α constitutively active（CA） mutant（pIRES2-PKC-α A25E，PKC-αCA）and PKC-α dominant negative（DN） mutant（pIRES2-PKC-αK368R，PKC-αDN）. The rat wild-type NF-κB-p65 over-expression plasmid，namely pIRES2-NF-κB-p65（p65WT），was constructed by our research group previously. The plasmid of p65WT was transfected into HEK-293T cells together with the above-mentioned different PKC-α over-expression plasmids respectively. The expression and phosphorylation levels of PKC-α and NF-κB-p65 were detected by Western blot. Next，HEK-293T cells were co-transfected with the above-mentioned plasmids in different groups，and after 46 h cells were continuously treated with SIN at the dose of 50 ng/mL for 2 h. Then，the effects of SIN on phosphorylation of PKC-α and NF-κB-p65 were determined by Western blot. Results：PCR analysis and nucleotide sequencing verified that the above-mentioned PKC-α over-expression plasmids were constructed successfully. The phosphorylation of NF-κB-p65 in HEK-293T cells was increased in response to PKC-αWT and PKC-αCA over-expression，especially PKC-αCA over-expression. However，there was no significant change of NF-κB-p65 phosphorylation after PKC-αDN over-expression. SIN treatment could inhibit the phosphorylation of PKC-α in HEK-293T cells transfected with PKC-αWT，PKC-αCA and PKC-αDN. SIN could also inhibit the phosphorylation of NF-κB-p65 in HEK-293T cells caused by PKC-αWT over-expression，but not by PKC-αCA or PKC-αDN over-expression. Conclusion：Over-expression of PKC-α can promote the phosphorylation of NF-κB-p65 in HEK-293T cells. SIN treatment can down-regulate NF-κB-p65 phosphorylation through inhibition of PKC-α phosphorylation in HEK-293T cells.

Abstract:Objective：This study aims to investigate the effects of sodium tanshinone type ⅡA sulphonate（STS）on lipopolysaccharide（LPS）-induced dysfunction and apoptosis of human umbilical vein endothelial cells（HUVEC）. Methods：Cultured HUVEC of 6-8 generation were grouped and stimulated as follows：DMEM group，LPS（1.0 μg/mL） group，high concentration（50.0 μg/mL）STS pre-treated group，medium concentration（25.0 μg/mL）STS pre-treated group，low concentration（12.5 μg/mL） STS pre-treated group. For STS pre-treated groups，HUVEC were pre-treated with corresponding concentrations of STS for 2 h，followed by the stimulation with 1 μg/mL LPS. After 24 h stimulation，cell viability was determined by CCK-8 method. Cell proliferation was detected by flow cytometry. Protein level of inflammatory cytokine interleukin-1 beta（IL-1β） in culture supernatant was determined by ELISA. Western blotting was employed for the detection of protein levels of intracellular IL-1β，cleaved caspase-3 and cleaved caspase-9，and nucleus-translocated nuclear factor-κB-p65（NF-κB-p65）. Then，migration ability of HUVEC was investigated by wound-healing test. The changes of cell and chromatin morphology in HUVEC were observed by microscopy，and the apoptosis of HUVEC was detected by Annexin V/PI staining. Results：Compared with DMEM，LPS treatment reduced viability and migration capacity of HUVEC，whereas promoted their proliferation. The protein levels of IL-1β，NF-κB-p65，cleaved caspase-3 and cleaved caspase-9 in HUVEC，as well as their apoptosis level were increased after LPS stimulation（P < 0.05）. However，STS can partially reverse the described effects of LPS in a dose-dependent manner（P < 0.05）. Conclusion：STS inhibits LPS-induced dysfunction and apoptosis in HUVEC，thus exerts protective effects on vascular endothelium.

Abstract:Objective：This study aims to investigate the possible mechanism by which vitamin D（VD） regulates the secretion of neurotransmitters in hippocampal neurons. Methods：The serum levels of 25 hydroxyvitamin D［25（OH）D］，5-hydroxytryptamine（5-HT）and norepinephrine（NE）were detected by chemiluminescence and enzyme immunoassay （ELISA） in 62 postpartum depression（PPD）patients and 31 healthy pregnant women. The proliferation of hippocampal neurons was determined by methylthiazolyltetrazolium（MTT）colorimetric method. Western blotting was used to detect the expression of total Akt（T-Akt）and phosphorylated Akt（p-Akt）. Results：The serum levels of 25（OH）D，5-HT and NE in the mild depressed group were lower than those in the healthy control group，and the differences were statistically significant（all P < 0.05）. The serum levels of 25（OH）D，5-HT and NE in the severe depression group were significantly lower than those in the mild depression group（all P < 0.05）. VD had a significant dose-dependent effect on the proliferation of hippocampal neurons and the levels of secreted 5-HT and NE in vitro. In addition，the proliferation and secreted 5-HT and NE levels of neurons were significantly different between VD+negative small interfering RNA（siRNA）group and control group（all P < 0.05）. In the VD+VD receptor（VDR）siRNA group，there was no statistically significant difference in proliferation of neurons and the levels of 5-HT and NE when compared with contrd group（all P > 0.05）. Western blot results showed that the expression of phosphorylated Akt in the VD+negative siRNA group was significantly increased when compared with control group，with statistical differences（P < 0.01）. There was no significant difference in the expression of phosphorylated Akt between the VD+VDR siRNA group and control group（all P > 0.05）. In the VD+DMSO group，the proliferation of neurons and the levels of 5-HT and NE were significantly different when compared with control group（all P < 0.05）. However，there was no significant difference in proliferation of neurons and the levels of 5-HT and NE between VD+LY294002（inhibitor of PI3k/Akt signaling pathway） group and control group（all P > 0.05）. Conclusion：VD promotes the activity of hippocampal neurons and secretion of 5-HT and NE，which may be related to the activation of PI3k/Akt signaling pathway. That plays an important role in the clinical prevention and treatment of PPD and postpartum care.

Abstract:Objective：This study aims to investigate the metabolic changes in bone marrow of female rabbits during the development of osteoporosis（OP）. Methods：The rabbit osteoporotic model was created by ovariectomy（OVX）. The loss of bone mineral density（BMD）was evaluated by dual-energy X-ray absorptiometer（DXA）. Metabolomic profiling of bone marrow was conducted through a multiplatform approach including in vivo proton magnetic resonance spectroscopy（1H-MRS）and in vitro liquid chromatography coupled to mass spectrometry（LC-MS/MS）-based analysis. The analysis was conducted before the surgery（baseline），2-month and 5-month after the surgery. Results：BMD in OVX group decreased gradually over time and was significantly lower than the Sham group at 5-month after OVX（2-month，P < 0.05；5-month，P < 0.01）. 1H-MRS analysis showed lactate and lipid in bone marrow were significantly increased in OVX group. Compared to Sham group，choline，creatine，glutamine and hydroxyproline in bone marrow of OVX qroup decreased dramatically. Similarly，in vitro metabolomic analysis of bone marrow showed dramatic metabolic changes as early as 2-month during the development of osteoporosis. In vivo 1H-MRS analysis showed that，compared to the Sham group，amino acids，acylcarnitines，nucleotides and ceramides were significantly altered. Correlation analysis identified a significant negative correlation between BMD and lactate（r=-0.842，P < 0.01）. Significant positive correlations were found between BMD and choline，creatine，glutamine and hydroxyproline. Conclusion：Some complex and diverse changes in bone marrow metabolism was discovered in this study during the development of OP. In vivo analysis of bone metabolism using 1H-MRS might be a potential non-invasive approach for the evaluation of OP.

Abstract:Objective：This study aims to investigate the inhibitory effect of miR-23a-5p on oxidative stress in rats with cerebral ischemia-reperfusion. Methods：The expression of miR-23a-5p in middle cerebral artery occlusion（MCAO） rat model was detected by qPCR assay. MCAO rats were injected with miR-23a-5p lentivirus and 3 groups were seted： Sham group，NC virus group and miR-23a-5p virus group. The nerve damage were evaluated by Berdron score and cerebral infarction volume were evaluated by 2，3，5-triphenyltetrazoliumchloride（TTC）staining. The total superoxide dismutase（SOD）and manganese superoxide dismutase（MnSOD）contents were determined by chemical colorimetry. The contents of 3-nitrotyrosine（3-NT）and nitric oxide（NO）were detected by ELISA. B35 cells，the central nerve cells of rats，were treated with H2O2 to establish oxidative damage mode and 4 groups were seted：control group，miR-23a group，H2O2 group and H2O2+miR-23a group. The total SOD and MnSOD contents were detected by chemical colorimetry，and the contents of 3-NT and NO were detected by ELISA. Results：After ischemia-reperfusion in MCAO rats，the expression of miR-23a-5p decreased rapidly and then gradually increased. In vivo，the overexpression of miR-23a-5p reduced the Berdron score and cerebral infarction volume，decreased the 3-NT and NO levels in serum，increased the total SOD and MnSOD levels. In B35 cells，the overexpression of miR-23a-5p decreased the intracellular levels of 3-NT and NO whereas increased the levels of total SOD and MnSOD. Conclusion：miR-23a-5p can inhibit oxidative damage induced by cerebral ischemia and reperfusion.

Abstract:Objective：This study aims to observe the effects of neutralizing interleukin-17（IL-17）on bleomycin（BLM） induced idiopathic pulmonary fibrosis and PI3K/Akt/mTOR signaling pathway. Methods：C57BL/6 mice were randomly divided into control group，BLM group，neutralizing antibody group and autophagy inhibition group，respectively. BLM group，neutralizing antibody group and autophagy inhibition group were administrated BLM（5 U/kg） through a single intratracheal injection to induce idiopathic pulmonary fibrosis，while the control group was received the equivalent sterile saline. Meanwhile，autophagy inhibition group was injected 3-methyl adenine（3-MA） via intraperitoneal injection 5 times a week for 4 weeks. Other groups were given the same amount of sterile saline. Neutralizing antibody group and autophagy inhibition group were administrated neutralizing IL-17 mAb via caudal vein every 3 days from day 3 after model made. All mice were sacrificed after 28 days. Lung tissues were used to evaluate pulmonary fibrosis by Masson staining and collagen expression changes by hydroxyproline contents measurement. Bronchoalveolar lavage fluid was collected for transform growth factor-β1（TGF-β1） measurement by ELISA. The expression of LC3Ⅱ/LC3Ⅰ，Beclin-1，p62，p-PI3K/PI3K，p-Akt/Akt and p-mTOR/mTOR proteins were all assayed by Western blot. Results：Compared with BLM group，hydroxyproline content，TGF-β1 concentration and pulmonary fibrosis in neutralizing antibody group were significantly decreased（P < 0.01），the ratio of LC3Ⅱ/LC3Ⅰ and Beclin 1 expression significantly raised（P < 0.01，P < 0.05），p62 expression reduced remarkably（P < 0.05），and the ratio of p-PI3K/PI3K，p-Akt/Akt and p-mTOR/mTOR decreased significantly（P < 0.05）. Conclusion：The mechanism of IL-17 in pulmonary fibrosis is related to inhibition of autophagy. Neutralization of endogenous IL-17 can significantly attenuate BLM-induced pulmonary fibrosis，reduce the production of TGF-β1，inhibit the PI3K/Akt/mTOR signaling pathway，and activate cell autophagy.

Abstract:Objective：This study aims to assess the utility of rapid on-site evaluation（ROSE） for transbronchial lung biopsy（TBLB）and endobronchial ultrasound-guided transbronchial needle aspiration（EBUS-TBNA） in cytological diagnosis of lung malignant tumor. Methods：Total 174 cases performed TBLB and EBUS-TBNA procedures prospectively collected between January 2018 to August 2019 at the Affiliated Nanjing Hospital of Nanjing Medical University. They were randomly divided into the two groups according to with or without ROSE. There were 106 cases in ROSE group，while there were 68 cases in non-ROSE group. Histological findings was the gold standard. The accuracy of TBLB or EBUS-TBNA with and without ROSE was compared. The sensitivity of the two methods in cytological diagnosis of lung malignant tumor was analyzed，and the differences between the two methods in cytological diagnosis of lung malignant tumor was compared. Results：Overall accuracy in ROSE group and non-ROSE group was 88.7%和77.9%，respectively. Sensitivity to detect malignant lesions in ROSE group and non-ROSE group was 90.1%和71.4%，respectively. The diagnostic accuracy rate and sensitivity rate in ROSE group were higher than those in non-ROSE group（P＜0.05），and the rate of secondary inspection in ROSE group was lower than that in non-ROSE group（P＜0.05）. The time of inspection in ROSE group was higher than that in non-ROSE group，but there were no siginificant differences between two groups. Specimen satisfaction（96.2%） of ROSE group was higher than that of non-ROSE group（86.8%），and there were significant differences between two groups（P＜0.05）. Conclusion：The combination of ROSE can improve the satisfaction of TBLB and EBUS-TBNA in the sampling process，improve the diagnostic accuracy rate of lung lesions，especially the sensitivity of cytological diagnosis for malignant tumor，which has certain application value in the diagnosis of lung tumors.

Abstract:Objective：This study aims to investigate enhanced CT combined with tumor markers （TM）in diagnosis and prognosis of hepatocellular carcinoma（HCC）. Methods：Total 62 HCC patients were selected and all of them had undergone hepatectomy. In addition，65 healthy subjects were selected as control. Blood samples were collected preoperatively from all subjects，and serum alpha fetoprotein（AFP），carbohydrate antigen 19-9（CA19-9）and carcinoembryonic antigen（CEA）levels were determined by radioimmunoassay. The correlation between serum TM levels and clinicopathological features was investigated by pathological examination. The imaging features of HCC were explored by spiral enhanced CT scanning. The diagnostic effiency of single TM，combined TMs，combined TMs and CT was analyzed by receiver operating characteristic（ROC） curves. Results：The levels of serum AFP，CA19-9 and CEA in HCC patients were significantly higher than those in controls（P < 0.05）. Patients with low differentiation and distant metastasis lesions had higher levels of AFP，CA19-9 and CEA（P < 0.05），compared with patients with high differentiation and no distant metastasis lesions. There were no significant differences in TM levels in HCC patients with different age，gender and clinical stages（P > 0.05）. The ROC analysis showed that the detection of single serum AFP，CEA or CA19-9 had lower specificity and sensitivity compared with the combined detection of three TMs（P < 0.05）. The combined detection of TMs and CT examination could achieve a specificity of 95.71% and a sensitivity of 87.47%，superior to the detection of the TMs（P < 0.05）. Eight HCC patients relapsed within 6 months after operation. Compared with those before operation，the levels of serum AFP，CA19-9 and CEA in the relapsed patients were increased significantly，and the TM levels were higher than those in patients without relapse（P < 0.05）. Conclusion：The detection of serum AFP，CA19-9 and CEA combined with CT can overcome the deficiency of single detection，avoid misdiagnosis，and significantly increase the positive detection rate of HCC。

Abstract:Objective：This study aims to investigate the correlation between serum 25-hydroxyvitamin D3［25（OH）D3］ level and carotid atherosclerosis（CAS） in patients with type 2 diabetes mellitus（T2DM）. Methods：The clinical information of 345 patients with T2DM were collected. According to carotid artery color Doppler ultrasound results，the patients were divided into two groups：T2DM with or without atherosclerosis（T2DM-CAS，T2DM-NCAS）. There were 131 normal samples without T2DM nor CAS enrolled as control group. The serum 25（OH）D3 and other biochemical parameters were measured. Results：There was no significant difference in the level of serum 25（OH）D3 between T2DM group and control group. In the male T2DM patients，the serum 25（OH）D3 was significantly lower in T2DM-CAS than in T2DM-NCAS and acted as an independent impact factor for CAS by binary logistic regression analysis. However，for female T2DM patients，CAS was only related to age and pulse pressure. There was no correlation between the level of serum 25（OH）D3 and age in T2DM patients. Conclusion：There was no significant difference in the serum 25（OH）D3 level between the T2DM patients and control. For the male T2DM patients，the serum 25（OH）D3 reduction is a risk factor for CAS.

Abstract:Objective：This study aims to explore the reliability and validity of the modified test for respiratory and asthma control in kids-Chinese version（TRACK-C） in the clinical application of children under 5 years old with asthma in China. Methods：A retrospective questionnaire was used to collect basic information related to asthma children under 5 years old. TARCK-C was used to evaluate symptoms and medication in children with asthma. The results of TRACK-C were compared with GINA guidelines to test the reliability and validity. Results：A total of 136 children were enrolled in the study. The median score of the TRACK-C questionnaire was 95 and Cronbach’s α was 0.704. The scores of children who had visited the emergency department last month were significantly lower than those of children who hadn’t，and the differences were statistically significant（P < 0.001）. There was no significant difference among the children who had or hadn’t used glucocorticoids in the last month（P > 0.05），but the score of children with wheezing was significantly lower than that of non-wheezing children（P < 0.001）. When the children were judged according to the GINA standard，the scores of children in the partially controlled group were significantly lower than those of children in the well controlled group，and the differences were statistically significant（P < 0.001）. When children were classified according to the criteria of clinicians，there were also significant differences among the uncontrolled group，the partially controlled group and the well control group（P < 0.001）. The cut-off of 90 points had the highest area under the ROC curve（0.943）. Conclusion：It was demonstrated that the TRACK-C has satisfactory clinical reliability（internal consistency）and validity（compared with GINA）. It can be used as a useful tool to distinguish children with different respiratory symptoms and different control levels，and suggested in asthma management of children under 5 years old in China.

Abstract:Objective：This study aims to evaluate effects of continuous subglottic suction and intermittent subglottic suction on prevention of ventilator-associated pneumonia（VAP）and damage to airway mucosa. Methods：Randomized controlled trials published in PubMed，Cochrane library，Web of Science，Science Direct，EMBASE，CNKI，WANFANG，VIP regarding comparison between continuous and intermittent subglottic secretion drainage were searched from database inception to March 31st，2019. Two reviewers independently screened literatures，extracted data，and evaluated the risk of bias in the included studies，then Review Manager 5.3 and Stata15.1 software were used for meta-analysis. Results：Nine studies enrolling a total of 865 patients were included. The results of meta-analysis showed there were no significant differences in the incidence of VAP［RR=1.06，95%CI（0.88-1.28），P=0.53］，incidence of early-onset VAP［RR=1.09，95%CI（0.66-1.79），P=0.74］，duration of mechanical ventilation［MD=0.12，95%CI（-0.49~0.72），P=0.70］，length of staying in intensive care unit［MD=-0.16，95%CI（-0.88~0.56），P=0.66］and mortality rate［RR=0.92，95%CI（0.69~1.23），P=0.58］ between continuous and intermittent subglottic secretion drainage. The incidence of testing for occult blood［RR=2.74，95%CI（1.72-4.37），P < 0.000 1］ of intermittent subglottic secretion drainage was lower than continuous subglottic secretion drainage. Conclusion：There were no apparent differences between continuous and intermittent subglottic secretion drainage for preventing VAP，but continuous subglottic secretion drainage was easy to damage tracheal mucosa.

Abstract:Objective：This study aims to analyze syphilis infection and its risk factors among men who have sex with men（MSM）. Methods：Altogether 3 043 MSMs aged 16 and above were recruited by respondent driven sampling and snowball sampling method. Multivariate unconditional logistic regression was used to analyze factors associated with syphilis infection. Results：The prevalence of syphilis infection was 14.7% among 3 043 MSMs，and increased with age. Those with lower educational level and divorce/widowhood had a higher prevalence，with significant differences（P < 0.05）. Logistic regression analysis showed age，educational level，and marriage status had significant relationship with syphilis infection. The risk for human immunodeficiency virus（HIV） infection increased in MSMs with syphilis infection（OR=2.48，95%CI：1.81-3.40）. Conclusion：The syphilis infection is high in MSMs，and the risk of HIV infection is higher in those with syphilis infection. Comprehensive strategies should be developed to further improve the effect of syphilis and HIV prevention and control in MSMs.

Abstract:Objective：This study aims to analyze the short-term effect of PM2.5 and PM10 concentration on daily outpatient visits of influenza-like illness（ILI）in Lianyungang. Methods：The daily mean concentration of air pollutants，meteorological parameters and daily outpatient visits of ILI in 8 monitoring hospitals in Lianyungang from 2014 to 2016 were collected. The effects of PM2.5 and PM10 on daily outpatient visits of ILI and exposure-response relations were analyzed by generalized additive model. Results：The single pollutant model showed that the daily outpatient visits of ILI increased by 2.3%（RR=1.023，95% CI=1.017-1.035）and 3.8%（RR=1.038，95% CI=1.025-1.051）respectively for each quartile interval of PM2.5 and PM10 under the optimal lag condition. Dual-pollutant and multi-pollutant models showed that PM2.5 and PM10 were positively correlated with daily outpatient visits of ILI after correction of confounding factors. Exposure-response relations showed that the risk of ILI increased gradually with the increase of PM2.5 and PM10 at low concentrations. However，when PM2.5 and PM10 increased to about 50 μg/m3 and 100 μg/m3 respectively，the risk of ILI tended to stabilize. Conclusion：The increase of PM2.5 and PM10 concentration can increase the daily outpatient visits of ILI，and there is exposure-response relation.

Abstract:Objective：According to the seasonal and trend epidemic phenomenon of hepatitis E，the multiple seasonal ARIMA model was established to predict the infectious incidence of hepatitis E in China. Methods：SPSS23.0 software was used to model the monthly data of the epidemic of hepatitis E infectious diseases in China from January 2004 to June 2018，so as to predict the incidence of hepatitis E in the second half of 2018 and to evaluate the prediction effect of the model through the epidemic data during the period. Results：The average values of the prediction of the two models，ARIMA（2，1，0）（0，1，1）12 and ARIMA（0，1，2）（0，1，1）12，were used as the prediction values，the average relative error of the prediction was 4.69% and the standard deviation was 3.27%. Conclusion：Results of fitting and prediction of the multiple seasonal ARIMA model are good. The model can better describe the incidence trend of hepatitis E in China during the period，and provide certain scientific basis for the formulation of preventive control measures against hepatitis E and reasonable allocation of health resources.

Abstract:Many ocular diseases and systemic diseases manifest with changes of optic disc and peripapillary blood flow. Optical coherence tomography angiography（OCTA），as a non-invasive，repeatable imaging technique can provide high-resolution images of peripapillary vascular network. Recent studies have reported its application and new findings in diseases such as glaucoma and Alzheimer’s disease. This article focuses on the features of peripapillary vascular anatomy，OCTA in detecting peripapillary vascular changes，and application value of OCTA in diagnosis and treatment of diseases.

Abstract:Lung cancer is one of the malignant tumors with high morbidity and mortality in the world. Lung cancer is divided into small cell lung cancer （SCLC） and non-small cell lung cancer （NSCLC），of which NSCLC accounts for about 85% of lung cancer. The traditional treatment of NSCLC mainly is surgery，chemotherapy，radiotherapy and targeted therapy. The emergence of immune checkpoint inhibitors takes the treatment of lung cancer into the era of immunotherapy. This article focused on the mechanism of immunotherapy，the new progress of immune checkpoints，the immunotherapy of advanced NSCLC and the latest research progress of immunotherapy in locally advanced NSCLC.