Abstract:Objective：To evaluate the relationship between the nuclear factor-κB（NF-κB）family member RelB and tumor metastasis，we established a RelB knockout mouse model by CRISPR/Cas9 system. Methods：The RelB specific single-guide RNAs targeted exon4 were designed for CRISPR/Cas9 system. The Cas9 and sgRNAs were transcribed by T7 RNA polymerase and microinjected into the mouse zygote. C57BL/6 mouse fertilized eggs injected with sgRNA and Cas9 mRNA in vitro were transplanted into mouse uterus. F1 generation was obtained by mating F0 generation with wild type. PCR and gene sequencing were performed to identify the RelB phenotype of F0 and F1 generation mice. The expression of RelB in F0 and F1 generation mice was evaluated in gene level and protein level. Results：We obtained four RelB-/+ F0 mice and stable inherited RelB-/- offspring. The results of genome sequencing showed that there was a nonsense mutation in the mRNA of RelB in the knockout group，which caused the mRNA translation to terminate. Compared with the control group，the expression of Relb protein was not detected in the knockout group. Meanwhile，the results of Western blot showed that there was no significant difference between knockout group and control group in the expression of NF-κB family members（RelA，p50 and p52）. Conclusion：The RelB knockout C57BL/6 mouse model was successfully established，which provided an important tool for the study of RelB in tumor metastasis and drug resistance.

Abstract:Objective：To construct and identify the recombinant adenovirus AdNICD1 carrying Notch1 intracellular domain（NICD1）and observe the influence of the overexpression of AdNICD1 on the activation of Notch signaling pathway. Methods：NICD1 coding area was amplified by high fidelity PCR（Hi-Fi PCR）and then subcloned to recombinant adenovirus vector by Gibson assembly. Bacteria screening and gene sequencing were used to make sure NICD1 was subcloned to recombinant adenovirus vector accurately. And then the plasmid was transfected into BJ5183 to complete homogenous recombination and generate recombinant adenovirus plasmid pAdNICD1. pAdNICD1 was identified by plasmid screening and linearized by PacⅠ enzyme，and then transfected to human embryo kidney 293 cell line（HEK293）for packaging. The packaged AdNICD1 were collected and amplified stepwisely. Immortalized multipotent adipose-derived mesenchymal stem cells（iMAD）were infected by AdNICD1，and the infection efficiency was tested. QPCR and Western blot were used to detect the expression of NICD1，and the downstream gene expression of Notch signaling pathway was determinated by QPCR. Results：NICD1 was successfully subcloned to the recombinant adenovirus vector，and AdNICD1 was successfully packaged and amplified in HEK293 cell line. The overexpression of NICD1 was confirmed by QPCR and Western blot in MSCs. Notch signaling pathway downstream gene expressions were also upregulated by AdNICD1. Conclusion：The recombinant adenovirus AdNICD1 was successfully constructed，and overexpression of NICD1 can exogenously activate Notch signaling pathway.

Abstract:Objective：To study the therapeutic properties and possible mechanism of Ganoderma lucidum polysaccharides（GL-PS）on diabetic nephropathy in streptozotocin（STZ）-induced mice. Methods：STZ［100 mg/（kg·d）］ was administered by intraperitoneal injection to induce diabetic nephropathy model in mice. The mice were randomly divided into 6 groups（n=10 in each group）：the normal group，model group，GL-PS groups with GL-PS dose of 50，100 and 200 mg/kg，and the telmisartan（TMS）group（5 mg/kg）. After 8 continuous weeks of intragastric administration，the mice uric，blood and renal were collected，and some physiological and biochemical indexes were determined by kits. Renal pathology was examined by hematoxylin-eosin（HE）staining. Protein expressions of NOD-like receptor 3（NLRP3），nuclear factor（NF）-κB and interleukin（IL）-1β in renal tissues were also analyzed by Western blot. Results：Compared with the model group，GL-PS and TMS obviously decreased the levels of blood urea nitrogen（BUN），serum creatinine（SCr），serum uric acid（SUA），glucose（GLU），total cholesterol（TC），triglyceride（TG），and interleukin（IL）-1β，IL-18，IL-6，as well as tumor necrosis factor（TNF）-α and urinary protein contents excreted during 24 h；significantly increased the high-density lipoprotein cholesterol（HDLC）level in STZ-induced diabetic nephropathy mice. HE and Western blot results indicated that GL-PS and TMS also obviously alleviated renal inflammatory reaction，inhibited NLRP3/NF-κB inflammasome activation，and down-regulated the protein expression of IL-1β. Conclusion：GL-PS has remarkable therapeutic properties on diabetic nephropathy in mice. The possible mechanism may be related to suppressing of inflammasome activation and improving of renal function.

Abstract:Objective：To investigate changes of long non-coding RNA expression in papillary thyroid carcinoma（PTC）and the role of lncRNA in occurrence and development of PTC. Methods：The microarray chip technique was used to detect the lncRNA expression profile in cancer tissues and paracancerous tissues after PTC resection. Five randomly expressed lncRNAs were randomly selected（fold change≥2，P < 0.05）. The real-time PCR method was used to verify expression microarray results. The different expression levels of lncRNA with the clinical features and stage of disease were compared in PTC patients. Results：Gene chip results showed that the expressions of lncRNAs in PTC tissues and paracancerous tissues were significantly different. There were 429 up-regulated lncRNAs and 1 449 down-regulated lncRNAs. In the tumor tissues and paracancerous tissues of 41 patients with PTC，real-time PCR results showed that expression levels of lncRNA TCONS-00020455 and TCONS-00020457（annotated：lncRNA TCONS-00020455 and TCONS-00020457 are abbreviated as lncRNA TCON-455 and TCON-457，and the short names for these two lncRNAs are used in the article.）in PTC tissues were significantly higher than those in adjacent tissues（P < 0.05）. Further analysis found that the expression levels of lncRNA TCON-455 and lncRNA TCON-457 were associated with lymph node metastasis，multiple lesions，and TNM stage in PTC patients（P < 0.05），but not correlated with age and gender（P > 0.05）. Conclusion：There is abnormal expression of lncRNAs in cancerous tissues of PTC patients. High expression of lncRNA TCON-455 and TCON-457 may be associated with metastasis and progression of PTC.

Abstract:Objective：To compare different proportions of rabbit allogeneic bone mixed with cancellous bone，cortical bone and demineralized bone matrix（DBM）in preservation of tooth extraction sites. Methods：A total of 24 New Zealand white rabbits were randomly assigned into A，B，C and D groups. The mandibular incisors were extracted on one side randomly. Group A was the blank control with tooth extraction healed naturally after treatment. Extraction sockets of group B，C，D were respectively filled with allograft bone 1（the weight ratio of cancellous bone：cortical bone：DBM=0∶9∶1），allograft bone 2（cancellous bone：cortical bone：DBM=3∶6∶1）and deproteinized bovine bone mineral（DBBM）. The morphological changes of the extraction sockets were evaluated. Micro-CT was taken 1 or 3 months after surgery to analyze the healing of sockets. The effect of different bone materials on the morphological preservation of alveolar ridge and the formation of new bone were compared. Results：The height reduction of alveolar ridge at 1 and 3 months after tooth extraction was D

Abstract:Objective：To assess the changes of ocular parameters and to evaluate the therapeutic effect after pulse treatment of glucocorticoid in patients with thyroid-associated ophthalmopathy（TAO） based on quantitative ocular muscle structure measurement of MRI. Methods：Eighteen TAO patients were enrolled for 3.0 T MRI orbit scan before and after methylprednisolone treatment. Quantitative measurement of orbital structures including exophthalmos values，fatty tissue thickness of inner side in eye balls，thickness of extraocular muscles with maximum signal intensity and signal intensity ratios（SIR）of extraocular muscles to ipsilateral temporal muscles were compared before and after treatment. Paired t test was used to compare changes of parameters before and after methylprednisolone pulse treatment. Results：After treatment of classical methylprednisolone，exophthalmos values and fatty tissue thickness of inner side in eye balls didin’t obviously changed，while SIR of extraocular muscles to ipsilateral temporal muscles，thickness of extraocular muscles with maximum signal intensity and CAS score decreased significantly. Conclusion：Glucocorticoid therapy can reduce SIR of extraocular muscles to ipsilateral temporal muscles，thickness of extraocular muscles with maximum signal intensity in TAO patients. MRI quantitative ocular muscle measurement can evaluate glucocorticoid treatment on TAO.

Abstract:Objective：To investigate the relationship between polymorphisms of matrix metalloproteinases（MMP）-9（rs3918242 and rs17576）and silicosis susceptibility of male workers who exposed to industrial dust with silicosis in Hongzhou，Hunan province. Methods：This case-control study included 186 silicosis patients and 186 individuals exposed to industrial dust but without silicosis（the control group），who were strictly matched with the case group for age，gender，work type and cumulative length of dust exposure. The rs3918242 and rs17576 polymorphisms of MMP-9 were detected in all participants using polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）. Meanwhile，plasma levels of total MMP-9 were analyzed by ELISA. Results：Frequencies of C/C，C/T and T/T genotypes of MMP-9 rs3918242 locus were 38.7%，34.4%，and 26.9% in the case group，significantly different from frequencies of 57.5%，25.8%，and 16.7% in the control group，respectively（P < 0.05）. Frequencies of C and T alleles were 55.9% and 44.1% in the case group，significantly different from frequencies of 70.4% and 29.6% in the control group，respectively（P < 0.05）. Frequencies of C/T，T/T genotype and T allele in the case group were significantly higher than those in the control group. There was no significant difference in the distribution of rs17576 loci genotype and allele frequency between two groups（P > 0.05）. Furthermore，frequencies of T allele of silicosis patients in theⅡand Ⅲ stages were significantly higher than those of the control group，and circulating levels of total MMP-9 were also significantly higher in subjects with T allele than those in subjects with CC genotype. Conclusion：MMP-9 rs3918242 polymorphism is significantly associated with silicosis and the severity of pulmonary fibrosis，and the polymorphism of rs17576 loci may not be related to silicosis susceptibility.

Abstract:Objective：To study the diagnostic value of apparent diffusion coefficient（ADC）in different grades of cerebral gliomas. Methods：A total of 83 cases of glioma were collected from January 2016 to December 2017 in the Department of Neurosurgery of Jiangsu Provincial People’s Hospital. The clinical data of diagnosis and treatment were analyzed retrospectively. All patients were divided into two groups：the low-grade group（Ⅰand Ⅱ grade，23 cases）and the high-grade group（Ⅲ and Ⅳ grade，60 cases）. The difference of ADC values between two groups was compared. Spearman rank correlation test was used to analyze the correlation between ADC values and pathological grades of gliomas. ROC curve was drawn to analyze the diagnostic value of ADC value for high and low grade gliomas. Results：The ADC values in the high-grade cerebral glioma group were significantly lower than those in the low-grade cerebral glioma group（P < 0.05）. There was a negative correlation between ADC values and histopathological grading of cerebral gliomas（r=-0.811，P <0.001）. ROC analysis showed that the area under the ROC curve was 0.976，and the optimal cut-off point of ADC values was 1.19×10-3 mm2 in diagnosing low-grade cerebral gliomas，and the corresponding sensitivity and specificity were 94.80% and 95.70%，respectively；the area under the ROC curve was 0.941，and the optimal cut-off point of ADC values was 1.02×10-3 mm2 in diagnosing high-grade cerebral gliomas，and the corresponding sensitivity and specificity were 94.25% and 95.10%，respectively. Conclusion：ADC values have good diagnostic value for predicting histopathological grade in cerebral gliomas.

Abstract:Objective：Alimentary tract hemorrhage is the most frequent complication after colonoscopic polypectomy. The aim of this study was to identify the risk factors for postpolypectomy bleeding（PPB）after endoscopic mucosal resection（EMR）. Methods：We retrospectively reviewed the clinical data of 111 patients who experienced PPB after EMR and 176 patients who did not. Results：Univariate logistic regression analysis showed that gender（male，P=0.008），numbers of polyps removed（≥3 polyps，P=0.001），polyp’ diameter（≥10 mm，P < 0.001），location（right colon，P=0.036），use of antithrombotic drug（P=0.015）were significantly correlated with PPB. Above factors，hypertension（P < 0.1）and pathological type（adenoma，P < 0.1）were analyzed by multivariate logistic regression，and only gender（male），polyps’ diameter（≥10 mm）and numbers of polyps removed（≥3 polyps）were significantly associated with PPB after EMR. Conclusion：Gender（male），polyps’ diameter（≥10 mm）and polyp number（≥3 polyps）are significantly associated with PPB after EMR，and we should pay more attention to these factors for preventing PPB

Abstract:Objective：To compare the visual acuity，contrast sensitivity and visual quality of patients with high myopia after the implantation of AT LISA tri 839 MP multifocal intraocular lens and CT SPHERIS 209M monofocal intraocular 1ens. Methods：Forty-four patients（44 eyes）were involved and divided into two groups in this study. The trail group（22 patients，22 eyes）received AT LISA tri 839MP multifocal intraocular lens implantation and the control group（22 patients，22 eyes）received CT SPHERIS 209M monofocal intraocular lens implantation after phacoemulsification. Parameters including visual acuity，contrast sensitivity at different spatial frequencies（3，6，12，18 cpd）in bright and dark circumstances，independent spectacles ratio，satisfaction and photic phenomena were observed. The post-operative visual acuity included the information of uncorrected distance visual acuity（UCDVA），uncorrected intermediate visual acuity（UCIVA），uncorrected near visual acuity（UCNVA），best corrected distance visual acuity（BCDVA），distance corrected intermediate visual acuity（DCIVA），and distance corrected near visual acuity（DCNVA）. The SPSS 16.0 statistic software was used to analyze the data. Results：The UCIVA，UCNVA，DCIVA，DCNVA，independent spectacles ratio and satisfaction of the trail group were better than those of the control group（all P < 0.05）. The mean contrast sensitivity at spatial frequency of 18 cpd in bright and dark circumstances of the control group was higher than that of the control group（P < 0.05）. The incidence of glare and halo showed no significantly statistical difference between two groups（P=0.50）. Conclusion：AT LISA tri 839MP multifocal intraocular lens provided better intermediate and near vision，higher independent spectacles ratio and more satisfaction of patients than CT SPHERIS 209M monofocal intraocular lens.

Abstract:Objective：To investigate the association between vitamin D（VitD）deficiency and the incidence and severity of bronchiolitis in infants and young children，and the relationship between VitD level and response of alveolar epithelial cells in vitro. Methods：A total of 80 children with bronchiolitis diagnosed during the period from January 2016 to December 2017 in Jiangning Hospital Affiliated to NMU were selected. Severity scores were given according to the standard. Forty healthy infants were selected as the control group. The level of 25-（OH）D was explored in relation to the severity score of bronchiolitis，and the levels of histamine and TNF-α in the two groups of children were examined to investigate the relationship between the level of VitD and in vivo VitD levels. Human alveolar epithelial cells A549 were cultured in groups A，B，and C. Group A served as the control group and were cultured in the original culture medium. Group B/C were infected with respiratory syncytial virus（RSV）for 24 hours. Group C was treated with calcitriol at the same time for 24 h. The levels of histamine and TNF-α in the culture supernatant and the differences of VitD receptor（VDR）and CYP27B1 mRNA expression in the cells of three groups were measured separately after 24 h. Results：The 25-（OH）D level in the bronchiolitis group was significantly lower than that in the healthy control group（P < 0.001）. The severity score of bronchiolitis was negatively correlated with the 25-（OH）D level in vivo（R2=0.5398）. The levels of serum histamine（P < 0.01）and TNF-α（P < 0.05）in the bronchiolitis group were significantly higher than those in the control group. After RSV infected cells in vitro，the levels of histamine and TNF-α in the culture supernatant of group B increased significantly（both P < 0.001）. The expression of VDR and CYP27B1 mRNA in group C increased significantly（both P < 0.001）. Conclusion：Increasing the VitD level in infants and young children can reduce the incidence and severity of bronchiolitis，which may be related to inhibiting inflammatory mediators released by type Ⅱ alveolar epithelial cells and promoting VitD activation and utilization.

Abstract:Objective：To investigate sensitive biological indicators for early diagnosis of bronchopulmonary dysplasia（BPD）by testing the expressions of 5-lipoxygenase activating protein（FLAP），leukotriene C4 synthase（LTC4S）and cysteinyl leukotriene receptor 1（CysLTR1） in serum of premature infants with BPD. Methods：Patients of the newborn less than 37 weeks of gestational age and less than 2 500 g of birth weight from the First Affilated Hospital of NMU were divided into 3 groups based on completed hospitalization information after discharge：premature infants without pulmonary diseases（the control group，n=65），premature infants with neonatal respiratory distress syndrome（NRDS）but without BPD（the NRDS group，n=60）and premature infants with BPD（the BPD group，n=49）. Serum levels of FLAP，LTC4S，CysLTR1 of the premature infants were tested by using enzyme-linked immunosorbent assay（ELISA）respectively at 3，7 and 14 days after birth. Statistical analysis was performed by variance analysis，t-verification and chi-square test etc. to compare the concentrations of 3 groups at different time points. Results：Serum levels of FLAP and CysLTR1 of infants with BPD at 3 days after birth were statistically significantly higher than that of NRDS and controls（P < 0.05）. Serum levels of FLAP，LTC4S and CysLTR1 of infants with BPD at 7 days after birth were significantly higher than that of controls（P < 0.05）. Serum levels of FLAP and CysLTR1 of infants with BPD at 7 days after birth were significantly higher than that of NRDS（P < 0.05）. Serum level of LTC4S in infants with BPD at 14 days after birth was higher than that of controls（P < 0.05）. Conclusion：Levels of serum FLAP and CysLTR1 of 3 days after birth，levels of FLAP，CysLTR1 and LTC4S of 7 days after birth，and LTC4S level of 14 days after birth may be useful biomarkers for early diagnosis of BPD.

Abstract:Objective：To compare the diagnostic efficacy of sonographic pattern from American Thyroid Association（ATA）Management Guidelines，thyroid imaging reporting and data system from Korean Society of Thyroid Radiology（K-TIRADS）and American College of Radiology（ACR-TIRADS）in diagnosis of thyroid nodules. Methods：From January 2012 to October 2017，756 patients with 1 065 thyroid nodules underwent preoperatively thyroid ultrasonographic examination and operation in Jiangsu Province Hospital on Integration of Chinese and Western Hospital. The general information of patients and ultrasound features of their thyroid nodules were collected. All nodules were categorized based on ATA sonographic pattern，K-TTIRADS and ACR-TIRADS. The receiver operating characteristic curve（ROC）curve was constructed，and the best diagnostic cut-off was selected according to the Youden index to compare their diagnostic performance. Results：Among 1 065 thyroid nodules，388 cases（36.43%）and 677 cases（63.57%）were confirmed to be benign and malignant by postoperative pathology，respectively. Ultrasound features including hypoechogenicity，solidity，microcalcification，irregular margin and aspect ratio＞1 had a higher rate of malignancy. The malignancy rates of each ATA sonographic pattern from low to high suspicious were 2.99%，23.53%，69.23% and 93.37%，respectively（P < 0.001）. The malignancy rates of category 3，4 and 5 nodules made by K-TIRADS were 13.33%，48.64% and 95.91%，respectively（P < 0.001）. The malignant rates of category 2，3，4 and 5 nodules made by ACR-TIRADS were 3.36%，13.22%，56.09% and 91.16%，respectively（P < 0.001）. Surprisingly，18.4% of thyroid nodules could not be categorized into any ATA pattern，of which 44.9% were ultimately found to be malignant. The ACR-TIRADS had a higher sensitivity and negative predictive value compared to K-TIRADS and ATA sonographic pattern. Conclusion：Three ultrasound reporting systems have certain clinical application value for diagnosis of thyroid nodules. Due to a small proportion of thyroid nodules can’t be classified by ATA sonographic pattern，TIRADS is worthy of further clinical research and application.

Abstract:Nanoparticles（NPs） have potential application in the field of biomedicine due to their unusual physicochemical，optical，and antibacterial properties. However，as particle size decreases，small size particles show increased toxicity. Meanwhile，their biosafety have attracted the attention of researchers. NPs interact with mammalian cells，and they can interfere with subcellular components，such as nuclei，mitochondria，endoplasmic reticulum and lysosomes，then causing apoptosis or necrosis. This brief review tries to summarize the toxicity effect of NPs on subcellular level，combining with the characteristics NPs.

Abstract:Cervical cancer is one of the three gynecological malignancies. Its high incidence，recurrence rate and transfer rate make it as a focus of lots of research. Previous research has clearly confirmed that infection of persistent human papilloma virus（HPV），especially the high-risk HPV infection，is the major cause of cervical cancer. The most commonly used treatments include surgery，radiotherapy，chemotherapy，immunotherapy，etc. The HPV gene vaccine，particularly in the target of E7 gene，can induce an specific immune response to control tumor growth，and it has been a research hot spot on the treatment of cervical cancer. But there is a common problem of reduced immunogenicity of gene vaccine when it is applied to the human body. Interleukin-15（IL-15）gene as a vaccine adjuvant used to promote antigen-specific immune responses can significantly improve immunogenicity. The prospect of IL-15 combined with HPV gene vaccine in the treatment of cervical cancer is reviewed，and the feasibility of its application and the value of immunotherapy in treatment of cervical cancer are discussed after consulting literature.

Abstract:Endometriosis is a common condition in women of reproductive age. According to several epidemiological studies，endometriosis may be associated with various malignancies，but the frequency of malignancy arising in endometriosis is always supposed lower than 1%. About 80% of endometriosis-associated malignancy（EAM） have been found in the ovary，whereas 20% are localized in extragonadal sites like intestine，rectovaginal septum，abdominal wall，pleura and others. Once the endometriosis is malignant，it will pose a great threat to the health of patients. Currently，exploring effective methods for diagnosis and treatment of EAM is the major clinical challenge. The article reviews the studies of the risk factors，clinicopathological characteristics and pathogenesis of EAM.

Abstract:Despite considerable progress has made in the clinical treatment of atrial fibrillation currently，it still represents one of the major causes of cardiovascular morbidity and mortality worldwide. It has a great prevalence particularly in the elderly population and in patients with basic diseases. And with the aging of our society，the problem of atrial fibrillation has also increased the social and economic burden. Cardiologists and surgeons are gradually understanding the pathogenesis of it and ameliorating the therapeutic methods of it. And through strengthening cooperation，we can improve the cure rate of atrial fibrillation and reduce operation-related complications. In the treatment of non-paroxysmal atrial fibrillation，hybrid ablation which combined with respective advantages of endocardial and epicardial ablation seems to have a better clinical effect. Therefore，we searched relevant literature and summarized the progress of hybrid ablation in the treatment of atrial fibrillation according to the clinical findings.

Abstract:Objective：Cysteine，a key component in the one-carbon metabolism，is of great importance in methylation. Many epidemiologic studies have assessed the association between cysteine and risk of cancer，but results are inconsistent. The objective of our meta-analysis is was to assess the association between plasma cysteine and cancer risk. Methods：Comprehensive searches were performed on PubMed and Embase databases up to November 1，2017 to identify relevant studies. Eight separate studies containing 11 comparisons were included in the meta-analysis. Relative risk（RR）and their corresponding 95% confidence intervals（95% CIs）were used to estimate the strength of relationship between cysteine and cancer risk. Results：The pooled RR of cancer risk for the highest versus lowest categories of blood cysteine level was 0.72（95%CI：0.62~0.83）with no significant heterogeneity observed（P=0.052，I2=45.1%）. Dose-response analysis showed that when plasma cysteine concentration was higher than 275 μmol/L，the higher cysteine level，the lower risk of cancer. Conclusion：Generally，our results indicated that higher concenteation of cysteine may decrease the risk of cancer.