Abstract:With the development of economy and the improvement of medical level in China，individual differences in drug response have become increasingly attractive. To enhance the rational use of drug and promote the safety and effectiveness of medication，personalized medicine turns into a hot spot in precision medicine. So far，there is still an obvious gap in personalized medicine research between China and the developed countries. This review provides an overview of the research status of personalized medicine in China，aiming to reveal its own weakness and suggest its future potential.

Abstract:Objective：This study aims to identify the role of AIM2（absent in melanoma 2）in the development of obesity in mice，explore the functioning cells and the regulation mechanism of obesity. Methods：AIM2 knockout mice and AIM2fl/fl Cx3cr1-Cre mice were given 60% high-fat food to induce obesity. The body weight changes of mice was monitored every week. HE staining was used to analyze the adipose tissue structure. Glucose tolerance and insulin sensitivity test was used to analyze the role of AIM2 in insulin resistance. Flow cytometry analysis was used to detect the changes of macrophage typing，and fluorescence quantitative PCR method was used to detect the expression of pro-inflammatory cytokines and anti-inflammatory cytokines. Results：In high-fat-induced obese mice，AIM2 was significantly down-regulated. The body weight of AIM2 knockout mice exhibit much higher than WT mice，and AIM2 knockout mice were less sensitive to insulin. What is more，the results of specific AIM2 knockout mice in macrophages AIM2fl/fl Cx3cr1-Cre were consistent with the full AIM2 knockout mice. In addition，bone marrow derived macrophages stimulated results in vitro confirmed that AIM2 promoted the polarization of macrophages into M1 type macrophages. Conclusion： AIM2 plays a protective role in the development of obesity in mice. It mainly regulates the occurrence of obesity by regulating the polarization of macrophages.

Abstract:Objective：This study aims to investigate the roles of Toll like receptor（TLR）-Pellino 1（Peli1） axis in methamphetamine（Meth）-mediated microglial inflammation and pathway in BV2 cells. Methods：Western blot was used to observe the expression of Toll like receptors（TLR），the downstream adaptor proteins of myeloid differentiation factor 88（MyD88）and TIR-domain-containing adaptor inducing interferon-β（TRIF）. In parallel，the expression of Peli1 protein was detected by Western blot. The downstream inflammatory factors and signal pathway regulated by Peli1 were observed by ELISA，real-time PCR and Western blot. Results：The expression of TLR3，TLR4，TLR7，TLR8 and TLR11 was significantly up-regulated after Meth treatment in BV2 cells. Meanwhile，the expression of MyD88 and TRIF was significantly increased，and TRIF level exhibited a concentration-dependent effect. Meanwhile，Meth obviously induced the expression of ubiquitin protein Peli1. Noteworthily，after Peli1 was down-regulated by RNA interference，the expression of inflammatory factors including inducible nitric oxide synthase（iNOS），tumor necrosis factor（TNF）-α and interleukin（IL）-6 were dramatically decreased，accompanied by the significant attenuation of nuclear factor（NF）-κB activation. Conclusion：The TLRs-mediated inflammatory signal plays an important role in the process of microglial inflammatory response induced by Meth. Therefore，the TLRs-Peli1 signal axis may be a promising target for the intervention of Meth neurotoxicity，which displays significant application.

Abstract:Objective：This study aims to explore influences of recombinant chromodomain helicase DNA binding protein 4（CHD4）gene expression on proliferation and apoptosis of acute T lymphoblastic leukemia cells and to identify its promoter. Methods：siRNA-CHD4 was used to transiently transfect Jurkat cells to knock down the expression of CHD4. The qRT-PCR and Western blot were used to detect the expression of CHD4. The apoptosis rate and cell cycle were measured by flow cytometry. The effect of CHD4 gene on the proliferation of Jurkat cells was analyzed by CCK-8. According to bioinformatics analysis，a 2 091 bp fragment of CHD4 gene candidate promoter region was amplified by PCR using the whole genome DNA extracted from Jurkat cells as template. The sequence containing candidate promoter region of CHD4 gene was cloned with pGL3 basic as vector，and a series of plasmids containing truncated 5′ flanking region of CHD4 gene candidate promoter were constructed. The plasmids containing CHD4 promoter and truncated sequence were transfected into Jurkat and HEK293T cells. The promoter activity of each fragment was detected by double luciferase reporter gene，and the minimal active region of CHD4 gene promoter was determined. The effect of binding site on the transcription of CHD4 was analyzed by double luciferase reporter gene detection. Results：Flow cytometry showed that，compared with the control group，CHD4 inhibited the apoptosis of Jurkat cells，the Jurkat cells transfected siRNA-CHD4 were significantly increased in the G0/G1 phase and decreased in the S phase（P < 0.01）. CCK-8 essay identified that CHD4 gene promoted the proliferation of Jurkat cells（P < 0.05）. Plasmids containing CHD4 gene candidate promoter and truncated sequence plasmids were successfully constructed. Compared with empty vector，plasmids containing CHD4 gene candidate promoter sequences were significantly more active（P < 0.05）. The core promoter of CHD4 gene located in 233 bp to 13 bp relative to transcription start site，which contained transcription factor binding sites NF-κB and MZF1. NF-κB had a positive function to the CHD4 promoter activity. Conclusion：Our results suggested that CHD4 inhibited apoptosis and induced proliferation in Jurkat cells. The core promoter of CHD4 located in -233/-13 bp relative to TSS. NF-κB bound to the core promoter of CHD4 in vivo and it had positive function to the promoter activity of CHD4.

Abstract:Objective：This study aims to investigate the expression of CD109 in oral squamous cell carcinoma（OSCC）and its influence on clinical characteristics and prognosis. Methods：The expression of CD109 mRNA and protein in OSCC tissues were detected by real-time quantitative PCR and immunohistochemistry respectively. The relationships between CD109 expression and clinical characteristics and prognosis were analyzed according to clinicopathological data. Results：The mRNA and protein expression levels of CD109 in OSCC tissues were significantly higher than those in paracancerous oral tissues. CD109 expression was associated with lymph node metastasis（P=0.019），distant metastasis（P=0.007）and cancer stage according to American Joint Committee（P=0.031）. Multivariate analysis confirmed that CD109 expression was an independent prognostic factor for OSCC patients（P < 0.001）.OSCC patients with high CD109 expression had a poor overall survival compared with patients with low or none CD109 expression（P=0.004）. Conclusion：CD109 is an independent risk factor affecting the prognosis of OSCC patients，and may be an important marker to predict the prognosis of OSCC.

Abstract:Objective：This study aims to investigate the role of aquaporin 3（AQP3） in the chemoresistance of colorectal carcinoma mediated by hypoxia. Methods：Real-time quantitative PCR and Western blot were performed to detect the expression of AQP3 under hypoxic condition in colorectal carcinoma HCT116 cells and HT29 cells. CCK-8 was used to detect the influence of hypoxia on the sensitivity of HCT116 cells to 5-fluorouracil（5-Fu）under hypoxic condition. CCK-8 and colony formation assay were also used to detect the effect of AQP3 on the sensitivity of HCT116 cells to 5-Fu under hypoxic condition. Results：Under hypoxic condition，the expression levels of AQP3 mRNA and protein were significantly up-regulated in both HCT116 and HT29 cells. After hypoxia inducible factor（HIF-1α）was inhibited，and the expression levels of AQP3 mRNA and protein in HCT116 cells under hypoxic condition were not significantly increased. Under hypoxic condition，the sensitivity of HCT116 cells to 5-Fu was lower than that in normal oxygen condition，which was reversed by inhibiting AQP3. Colony formation assay also demonstrated that the effect of 5-Fu on the proliferation ability of HCT116 cells was smaller under hypoxic condition，which was reversed by inhibiting AQP3. Conclusion：Under hypoxic condition，colorectal carcinoma up-regulated AQP3 expression by HIF-1α，which lead to 5-Fu chemoresistance.

Abstract:Objective：This study aims to explore the molecular mechanism of the interaction between hepatocellular carcinoma（HCC） markers of glypican-3（GPC3）and miR-202. Methods：Total 126 cases of clinical HCC tissue samples and serum samples were collected. The expression of GPC3 was detected by immunohistochemistry，and the level of circulating miR-202 was detected by qRT-PCR. The HepG2 cells were cultured and transfected with miR-202 mimics，the expression of miR-202 was detected by qRT-PCR，and the expression of GPC3 protein was detected by Western blot. The effect of miR-202 mimics on the proliferation activity of HepG2 cells was detected by CCK8 assay. Luciferase reporter gene was used to determine the regulation of miR-202 on GPC3. Results：The total positive rate of GPC3 in 126 cases of HCC was 77.78%. Its expression level was not related to the patient’s gender，age，tumor size and clinical stage，but was highly correlated with the type of histological differentiation and microvascular invasion. The circulating miR-202 in HCC patients was at a low level，and was inversely correlated with the expression level of GPC3 in cancer tissues. The expression of miR-202 was up-regulated in HepG2 cells，and the expression of GPC3 was down-regulated accordingly，and the proliferation activity of cancer cells was thus inhibited. Luciferase experiment confirmed that miR-202 could directly and negatively regulate the expression of GPC3. Conclusion：This study demonstrates that GPC3 is directly regulated by miR-202，and high expression of GPC3 is a sign of malignant biological feature of HCC. Any targeted GPC3 therapeutic strategy，if it can assist to improve the function of miR-202，may produce a synergistic anti-tumor effect for HCC.

Abstract:Objective：This study aims to systematically compare the methods for detecting the proliferation and cytotoxic function of immune effector cells. Methods：CCK- 8 assay，EdU labeling assay and CFSE labeling assay were used to detect the proliferation of NK92 cells in vitro under different culture conditions（group 1：100 U/mL IL-2；group 2：100 U/mL IL-2+10 U/mL IL-15），and the killing effect of NK92 on K562 cells was detected by lactate dehydrogenase（LDH）release assay，double living cell dye labeling assay and luciferase assay. The principles，characteristics and effectiveness of the various methods were compared. Results：The results of CCK-8 assay showed that the proliferation ability of group 2 was stronger than that of group 1，but there was no significant difference between group 2 and group 1（P > 0.05），but both EdU and CFSE labeling assay showed that there were significant differences in proliferation ability between the two groups. Double living cell dye labeling flow assay and luciferase assay could detect the differences in cytotoxic function of NK92 between the two groups under different effector-target ratio（P < 0.05），but there was no difference in cytotoxicity between the two groups under low effector-target ratio detected by LDH release assay（P > 0.05）. When double living cell dye labeling flow assay was as standard method，results of luciferase assay and LDH release assay were significantly correlated with the results of living cell dye labeling flow assay（rS < 0.979 4，P < 0.001；rS=0.973 2，P < 0.001）. Conclusion：CCK-8 assay is more focused on the detection of metabolic activity，EdU and CFSE labeling assay are more suitable for detecting the proliferation of suspended immune cells. The three kinds of cytotoxic function assay are consistent. Double living cell dye labeling assay is suitable for detecting the killing of suspended target cells，and luciferase assay is more suitable than LDH release method for the killing of adherent cells.

Abstract:Objective：This study aims to establish a genotyping method based on the iPLEX analysis of MassARRAY platform to detect human platelet antigen （HPA）. Methods：The information of single nucleotide polymorphism mutation or base deletion in HPA1-29W system was searched by literature，and 29 gene mutations were identified. According to MassARRAY mutation site labeling method，primer design fixed format and primer design software，a total of 90 primers（30 forward，30 reverse amplification primers and 30 extension primers）were designed online. The sensitivity，specificity and repeatability were analyzed using 12 synthetic plasmids which were inserted into HPA1-29W wild-type or mutant sequences and 50 samples with known HPA typing. The results of 15 randomly selected samples were screened by the first generation sequencing and mass spectrometry typing to establish the detection method. Results：The results of mass spectrometry based on MassARRY platform were consistent with that of the sequencing method. The sensitivity，specificity and repeatability rate of the mass spectrum method were 100%，100% and 100%，respectively. Conclusion：The method of HPA1-29W gene mass spectrometry based on MassARRAY platform is successfully established，which is suitable for HPA typing in Chinese population，and has clinical application prospect.

Abstract:Objective：The objective of the study was to investigate the association between thyroid stimulating hormone（TSH） and incident non-alcoholic fatty liver disease（NAFLD） in middle-aged and elderly population in a 3-year follow-up study. Methods：Total 222 subclinically hypothyroid（TSH>4.50 mU/L）and 727 euthyroid people aged 40~75 years who were free of fatty liver disease at baseline in a community were included in the current study. The study population was screened initially in 2011 and re-evaluated in 2014. On both occasions they were assessed by structured interview via a questionnaire on general information，anthropometric measurements，thyroid hormones，biochemical and serological tests，liver ultrasound. Results：Among 222 baseline subclinical hypothyroidism patients，62（27.93%） reverted to euthyroidism at a 3-year follow-up. The 3-year incidence of subclinical hypothyroidism was 16.64%（121/727）. Higher TSH levels at baseline were associated with higher total cholesterol（TC），triglyceride（TG），low density lipoprotein cholesterol（LDL-C） and aspartate aminotransferase（AST） levels（P < 0.05）. The incidence rate of NAFLD increased with increasing baseline TSH levels in female（P < 0.05）. Logistic regression analyses showed，higher baseline TSH levels were associated with the diagnosis of NAFLD by unadjusted in model 1 in female. After adjustment for age，baseline BMI，baseline TG，baseline HbA1c in model 2，this association remained significant. When data were adjusted for the changes in BMI and changes in HbA1c in model 3，the association was no longer significant. Conclusion：Among middle-aged and elderly population，baseline TSH was an influencing factor，but not an independent risk factors，for 3-year incidence of NAFLD in female.

Abstract:Objective：This study aims to estimate the burden of diseases from high total cholesterol（TC）among population in Nanjing between 2011 and 2017. Methods：Population attributable fraction（PAF） of high TC were calculated by using data related to TC levels from chronic disease risk factor surveillance in Nanjing，2011 and 2017. By using the PAFs，data related to death and demographics of people in Nanjing were used to estimate the burden of diseases from high TC. Results：The level of TC in Nanjing population aged 25 and above was（4.57±1.86）mmol/L in 2011，（4.58±2.16）mmol/L for males and（4.55±1.58）mmol/L for females respectively，while appeared as （4.66±1.10）mmol/L in 2017，higher in females （4.71±1.11）mmol/L than that in males （4.61±1.09）mmol/L. In 2017，the level of TC was higher than that in 2011 among total population and women. As total of 4.77% of all deaths were attributed to high TC，while appeared as 5.78% in 2017 by increased of 21.17%. The mortality rate attributed to high TC in Nanjing population was 36.24/100 000 in 2011，which decreased to 30.08/100 000 in 2017，with a decrease of 17.00% in total，21.82% in males and 11.29% in females respectively. Compared with 2011（631.07/100 000），the rate of years of life lost（YLL） due to high TC in 2017（495.35/100 000） decreased by 21.51%. The loss of life expectancy caused by high TC in 2011 for Nanjing population was 0.45 years，higher in females（0.49 years）than that in males（0.41 years），and the loss of life expectancy in 2017 was 0.66 years，higher in females（0.78 years） than in males（0.54 years）. Conclusion：High TC is a major risk factor for the burden of diseases and death. Deaths and loss of life expectancy caused by high TC increased from 2011 to 2017 in Nanjing.

Abstract:Objective：This study aims to study the risk factors of living habits and behaviors related to poor eyesight and refractive index in middle school students，so as to provide evidence for the prevention and control of myopia. Methods：A total of 1 430 students were investigated by cluster sampling from two schools in the district. Visual acuity and refractive examination and questionnaire survey were conducted. According to the results of visual acuity examination and computer optometry examination，the risk behaviors affecting poor visual acuity of middle school students in Xuhui district of Shanghai were analyzed. Results：The detection rate of visual acuity impairment in Xuhui district was 84.0%. Mild visual acuity impairment was 6.8%，moderate visual acuity impairment was 22.0%，and severe visual acuity impairment was 55.2%. The abnormal detection rate of refractive spherical mirror value was 82.7%，mild myopia was 48.0%，moderate myopia was 31.7%，and severe myopia was 3.0%. The detection rate of refraction（astigmatism） was 82.2%，including 51.2% low astigmatism and 31.0% high astigmatism. After chi-square test and logistic regression analysis，the influencing factors of visual acuity examination results were not completely consistent with the results of computerized optometry. After one-way factor analysis，lights in the classroom，parental myopia，gender，grade，sleep time，sweet drinks in a week，sitting time in a day，exercise time reduced，native place，eating egg per day，time of close eyes，reading with lamp，rest area，reading book or looking electronic screens in walking，and reading book or looking electronic screens in the sun are influence factors. After the multi-factor analysis，gender，grade，frequency of eating vegetables every day，classroom light，PE classes a week，parental myopia，native place，nationality，and the rest area are the influencing factors. Conclusion：There is poor visual acuity and high detection rate of ametropia among middle school students in Xuhui district of Shanghai，which may be influenced by their living habits.

Abstract:Objective：A visual analysis system based on R Shiny was designed to analyze the prevalence of notifiable infectious diseases from 2004 to 2017，providing reference for disease control and prevention. Methods：Using R shiny and a variety of R packages，distribution was described and the visualized system was built based on four perspectives：population，time，space，and spatial-temporal interaction. Results：This system depicted spatial-temporal distribution maps of 39 notifiable diseases from 2004 to 2017，as well as disease clustering and age stratified heat maps. Meanwhile，it also performed time series analysis and spatial autoregression analysis on various notifiable infectious diseases. Conclusion：The R shiny visual analysis system has many advantages including simple operation and diverse analysis methods compared to other similar systems. And it is helpful to describe the epidemic characteristics of infectious diseases and facilitate the research of public health.

Abstract:With the development of China’s medical and health undertakings，it puts forward higher requirements on the indicators of in-vitro diagnostic technique such as sensitivity，limit of detection and analysis speed. However，traditional in-vitro diagnostic techniques are increasingly unable to meet this certain requirement. In the meanwhile，nanomaterial-based in-vitro diagnostic techniques with high sensitivity and analysis speed has increasingly attracted the attention from researchers. In this review，we will introduce this area by summarizing commonly used nanomaterials and the basic principles of the nanomaterial-based methods including gold-nanoparticle-labeling techniques，nanoPCR，nanopore sequencing，bio-barcode assay，etc，as well as their applications in protein or nucleic acid in-vitro analysis.

Abstract:Bone metabolic dynamic balance plays an important role in maintaining normal bone tissue function，and the disruption of this balance can lead to bone metabolic diseases. The mechanism of bone metabolism is still unclear，and the signaling pathway is complex. Canonical Wnt signaling plays multiple roles in bone development and bone metabolism，which is closely related to osteogenic differentiation of mesenchymal stem cells，proliferation and differentiation of osteoblasts and osteoclasts. This review summarizes the mechanism of Wnt/β-catenin signaling pathway in bone metabolism and its research progress in bone metabolic diseases，in order to explore new ideas and approaches in the prevention and treatment of bone metabolic diseases.

Abstract:Type 2 diabetes（T2DM）is a common metabolic disorder-related disease. Insulin resistance，one of the significant pathogenesis factors of T2DM，is tightly related to the insulin signaling pathway. MicroRNA（miRNA），is a small non-coding RNA，modulates protein expression at the post-transcriptional level through binding with target genes，which participates in avariety of pathophysiological processes. Previous studies reported that miRNA palys important roles in the regulation of insulin signaling pathway. This article reviewed some miRNAs affecting key proteins in insulin signaling pathway and the regulation mechanism of the miRNAs in T2DM-associated insulin resistance to provide a new direction for the pathogenesis and treatment of T2DM.