Abstract:The wildly use of immunological checkpoint inhibitors（ICPI） in clinical practice and the indications expanding make endocrinologists and oncologists focused on the diagnose and treat the endocrine side effects of ICPI. The French Society of Endocrinol－ogy drafted guidance on Immunotherapy-related endocrine side effects. The guidance introduced research on endocrine side effects of ICPI，and provided consensus on the screening，management and monitoring of endocrine side effects which caused by ICPI. Here we provide an interpretation of this guidance.

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Abstract:MicroRNA（miRNA) is a sort of non-coding RNAs with regulatory functions，which plays important roles in the growth and development of individual organism，and disease development. In recent years，studies on the role of miRNAs in nonalcoholic fatty liver disease（NAFLD） have attracted more attention. The miRNA can involve in the occurrence and development of NAFLD by regulat－ing liver glucose and lipid metabolism，inflammatory response and fibrosis. The identification of miRNA profiles with abnormal expres－sion in tissues or circulation will serve as a novel biomarker for the diagnosis of NAFLD and is expected to be a new target for the treatment of NAFLD.

Abstract:Breast cancer is the most common malignant tumor of women in the world，which greatly threatens patients' health. Neoad－juvant therapy can not only increase the proportion of breast conserving surgery，but also can test internal sensitivity of treatments' efficacy. Especially in triple negative and Her-2 overexpression subtypes，pathological complete response is an important predictor of long-term prognosis. However，the overall prognosis of most patients with estrogen receptor（ER） positive breast cancer is good，but clinicians lack reliable evidence for decision-making between neoadjuvant endocrine therapy and neoadjuvant chemotherapy due to the lack of accurate and convenient predictors. In order to reduce side effects caused by unnecessary chemotherapy，it is urgent to find new predictive markers for neoadjuvant endocrine therapy. This paper reviewed applications and limitations of prognostic markers in current neoadjuvant endocrine therapy to treat ER+ breast cancer，and the current status of new biomarkers.

Abstract:Hepatocellular carcinoma（HCC） has become one of the most common and deadly malignancies. In recent years，the third phase of drugs based on target and immunity has obtained better results，more drugs focusing on specific tumor metabolic pathways and immune checkpoints are under clinical development，and some drugs have been identified that can improve the prognosis of liver cancer patients. Treatments of HCC changes rapidly. This article reviewed the mechanism，side effects，efficacy and ongoing research of targeted therapy and immunotherapy drugs for HCC.

Abstract:Nowadays，diabetes mellitus and bladder cancer are major public health problems in the world，which have a great impact on human health. Additionally，there are more and more patients with diabetes mellitus complicated with different cancers. A large number of studies have shown that there are some connections between bladder cancer and diabetes mellitus. Diabetes mellitus not only has many common risk factors with bladder cancer，but also may increase the incidence of bladder cancer and have a certain impact on its prognosis. Without doubt，there have been some studies holding different views. In addition，some antidiabetic drugs has certain correlation with bladder cancer. This article reviewed the relationship among diabetes mellitus，hypoglycemic drugs and bladder cancer，as well as the effect of diabetes mellitus on prognosis of bladder cancer.

Abstract:Objective：TACI is an important receptor of BAFF/APRIL pathway system. To investigate the level of serum soluble TACI （sTACI） in patients with different types of autoimmune thyroid diseases（AITD），to analyze its relationship with thyroid function and autoimmune antibody，and to explore the role of sTACI in AITD. Methods：Patients who were newly diagnosed with Graves disease （GD） and Hashimoto thyroiditis（HT） in our department and healthy people who had physical examination in physical examination center of our hospital were recruited. Venous blood samples were collected and serum was separated. Expression levels of thyroid function and autoimmune antibody were measured by electrochemical immunoluminescence and expression levels of serum sTACI were measured by enzyme linked immunosorbent assay（ELISA）. Results：Age and gender in the GD group and the HT group had no statistical difference when compared with that in the normal control（NC） group（both P>0.05）. The level of serum sTACI in the GD group，the HT group and the NC group were 13.24（10.40-18.60） pg/mL，12.75（11.17-16.14） pg/mL and 13.05（10.30-18.75） pg/mL，respectively. The level of serum sTACI in the GD group and the HT group had no significant difference when compared with that in the NC group（P=0.812，0.873）. The level of serum sTACI had no statistical difference between the GD group and the HT group（P=0.584）. In the GD group，the level of serum sTACI was not correlated with FT4，FT3，TSH，TPOAb，TgAb and TRAb level（all P>0.05）. In the HT group，the level of serum sTACI was not correlated with FT4，FT3，TSH，TPOAb and TgAb level（all P>0.05）. Conclusion：Compared with the NC group，the level of serum sTACI in AITD patients has no significant change and it has no correlation with thyroid function and autoimmune antibody level，suggesting that TACI receptor of BAFF/APRIL pathway system may not play a crucial role in the pathogenesis of AITD.

Abstract:Objective：To investigate the effect of gemcitabine on hepatitis B virus（HBV） pregenomic RNA（pgRNA） transcription and HBV replication in HepG2.2.15 cells and its possible mechanisms. Methods：HepG2.2.15 cells were treated with different concentra－tions of gemcitabine，and cell viability，apoptosis，cell cycle，intracellular HBV pgRNA，and HBsAg，HBeAg，HBV DNA in the cell culture supernatant were measured by CCK8 assay，flow cytometry，qRT-PCR，and ELISA respectively. The mRNA expression levels of pgRNA transcription-related regulatory genes，hepatocyte nuclear factor 4α（HNF4α），P38 mitogen-activated protein kinase（P38MAPK），CAMP responsive element binding protein 1（CREB1），nuclear factor-kappa B p65（NF-?资b p65），histone deacetylase 1（HDAC1），per－oxisome proliferator-activated receptor γ coactivator 1α（PGC-1α），forkhead box protein O1（FOXO1），sirtuin1（SIRT1），and P53，and pgRNA in HepG2.2.15 cells treated with gemcitabine were determined by real-time quantitative PCR. The correlations between these genes and pgRNA with changes in gemcitabine concentration were analyzed to identify the gene with the highest correlation with pgRNA，and the effect of gemcitabine on the protein ex－pression of the gene was verified at the protein level using Western blot. Results：Gemcitabine showed a concentration- and dose-de－pendent inhibitory effect on HepG2.2.15 cell growth；gemcitabine increased apoptosis；gemcitabine caused more cells to arrest in G0G1 phase，and the proportion of cells in S phase decreased. Gemcitabine significantly increased HBV pgRNA in hepG2.2.15 cells in a significant time- and dose-dependent manner within 72 h；treatment of cells with gemcitabine for 24 hours increased HBeAg in the cell culture supernatant；gemcitabine promoted the mRNA and protein expression of HNF4α，and among all the genes involved in the regulation of HBV transcription we detected，the changing trend of HNF4α mRNA expression was the most correlated with that of HBV pgRNA. Conclusion：Gemcitabine can increase HBV pgRNA transcription and HBV replication at the cellular level by promoting the expression of the HBV transcription factor HNF4α.

Abstract:Objective：To investigate the mechanism of action of nerve growth factor （NGF） and its receptor in regulating Warburg ef－fect and promoting metastasis of glioma cells. Methods：Western blot and RT-qPCR were used to measure the protein and mRNA ex－pression of NGF and TrkA in three glioma cell lines. U251 cells were divided into control group and NGF group（treated with 50 μg/L NGF）. CCK-8 assay was used to measure cell viability；flow cytometry after PI staining was used to observe the change in cell cycle；Transwell chamber was used to measure cell invasion ability；Western blot was used to measure the expression of TrkA，AKT，PI3K，phosphofructokinase（PFK），and pyruvate kinase M2（PKM2）. The levels of glucose uptake，lactic acid，and cell oxygen consumption were measured. U251 cells were divided into control group，AKT inhibitor group，and NGF group. The cells in the control group were given routine treatment，those in the AKT inhibitor group were pretreated with AKT inhibitor and then treated with 50 μg/L NGF，and those in the NGF group were treated with 50 μg/L NGF. The above tests were also performed. Results：Glioma cells had significantly higher levels of NGF and TrkA than glial cells，and U251 glioma cells had the highest levels. U251 cells showed a significant increase in cell viability after NGF intervention. Compared with the control group，the NGF group had a signifi－cantly higher number of cells in G2 phase，a significantly higher number of invasive cells，and significantly higher protein expression of TrkA，AKT，and PI3K，as well as significantly lower expression of the metabolic enzymes PFK and PKM2. There were significant differences between the NGF group and the control group in the levels of glucose uptake，lactic acid，and oxygen consumption. After AKT signal suppression，the NGF group had significantly higher cell viability and number of cells in G2 phase than the control group and the AKT inhibitor group. Compared with the control group and the AKT inhibitor group，the NGF group had significantly higher number of invasive cells and protein expression of TrkA，AKT，and PI3K，as well as significantly lower expression of the metabolic enzymes PFK and PKM2. There were significant differences in the levels of glucose uptake，lactic acid，and oxygen consumption between the NGF group and the control group/AKT inhibitor group. Conclusion：NGF can promote Warburg effect and metastasis of glioma cells through the TrkA-PI3K/AKT signaling pathway.

Abstract:Objective：To investigate the role of long non-coding RNA LINC00152 in papillary thyroid carcinoma（PTC）. Methods：A total of 32 patients with PTC were enrolled. Tumor tissue and adjacent normal tissue samples were collected during surgery，and qRT-PCR was used to measure the expression of LINC00152 in these samples. Knockdown of LINC00152 was performed to establish a PTC cell line with low expression of LINC00152，and Transwell migration and invasion experiments，cell cloning experiments，growth experiments，and wound healing assay were used to investigate the role of LINC00152 in the development and progression of PTC. Results：In 64 of all patients with PTC，the expression of LINC00152 in tumor tissue was higher than that in adjacent normal tissue（P<0.01）. In vitro cell experiments demonstrated that knockdown of LINC00152 reduced the growth，proliferation，invasion，and mi－gration abilities of PTC cells. Conclusion：Long non-coding RNA-LINC00152 has high expression in PTC and reduction in LINC00152 can significantly reduce the malignant ability of PTC cells.

Abstract:Objective：To construct the adenovirus vector of proteasome subunit alpha type 3（PSMA3） gene and investigate whether the adenovirus vector carrying PSMA3 gene affecting the proliferation，cell cycle，apoptosis and the growth of nude mice bearing tumors of human hepatocellular carcinoma cell line SMMC7721. Methods：cDNA fragment encoding human PSMA3 gene was amplified by re－verse transcriptase-polymerase chain reaction（RT-PCR）. The PCR amplified fragment was first cloned into pTG19-T vector，and then subcloned PSMA3 gene into the shuttle vector pAd－Track-CMV for constructing the recombinant plasmid pAd－Track/PSMA3，which homologously recombinated with the ade－noviral backbone vectors Adeasy-1 to generate recombinant adenoviral plasmids Ad/PSMA3. The recombinant adenoviruses Ad/PSMA3 were generated by transfecting the recombinant adenoviral DNA into 293 cells and then employed to infect SMMC7721 cells. The expression of enhanced green fluorescent protein（EGFP） in transfected SMMC7721 cells were observed by fluorescence microscope. The proliferation of transfected SMMC7721 cells were tested via Cell count kit-8（CCK-8），and the expreesion levels of PSMA3，proliferating cell nuclear antigen（PCNA） and caspase-3 mRNAs proteins in transfected SMMC7721 cells were detected by RT-PCR and Western blot，respectively. The cell cycle distribution and apoptosis rate of transfected SMMC7721 cells were analyzed by flow cytometry（FCM）. SMMC7721 cells infected with pAd/PSMA3 virus were transplanted subcutaneously into nude mice to gen－erate tumors，and the growth of the tumors was observed day by day. Results：PSMA3 gene was successfully cloned. Adenoviral virus particles which possess infectious competent were produced from Ad/PSMA3. The results of CCK-8 revealed that the proliferation of SMMC7721 cells，which overexpressed PSMA3，were slower than the control cells，especially from 48 h after transfection（P<0.01）. The results of RT-PCR and Western blot demonstrated that SMMC7721 cells transfected with pAd/PSMA3 recombinant virus can effectively overexpressed PSMA3，and the expression of PSMA3，caspase-3 mRNA and protein were up-regulated，while the expression of PCNA mRNA and protein were down-regulated in the cells. FCM detection confirmed that SMMC7721 cells transfected with pAd/PSMA3 were blocked in the G1 phase of cell cycle，and promoted apoptosis，and the difference of the apoptosis rate between trans－fected and control cells were statistically significant（P<0.01）. Conclusion：PSMA3 gene was successfully cloned. The proliferation of SMMC7721 cells，which overexpressed PSMA3，can be effectively suppressed，and their apoptosis be promoted. The growth of nude mice bearing tumors of SMMC7721 cells overexpressed PSMA3 can be also inhibited. These effects may be related to the down-regu－lattion of the PCNA expression and the up-regulation of the caspase-3 expression in the cells.

Abstract:Objective：To investigate the effect of radiotherapy on ovarian function in patients with cervical carcinoma after ovarian transposition. Methods：Data of 51 patients with stage Ⅰ-Ⅲ cervical carcinoma undergoing ovarian transposition and radiotherapy in our hospital from 2015 to 2019 were collected. Among those patients，5 patients showed progression and 5 patients lost follow-up. The postoperative condition were followed up，the modified Perimenopausal Syndrome Scale（modified Kupperman scale） was used to give score，and ovarian dysfunction and sexual life were observed. Results：Grouping based on age（≥ 40 years old and < 40 years old），operative way（radical laparotomy，laparoscopic radical operation and laparoscopic staging） and postoperative time（≥1 year and < 1 year） showed there was no statistical significance between ovarian dysfunction and age，as well as postoperative time. There were no significant differences in postoperative ovarian dysfunction between radical laparotomy and laparoscopic radical operation，as well as laparoscopic radical operation and laparoscopic staging（P<0.05）. A few patients（18%） had sexual life，and a very few patients（6%） were satisfied with sexual life. Conclusion：The change of ovarian function after ovarian transposition is not related with age and post－operative time，but may be related with operative ways. The preservation of ovarian function after ovarian transposition is very impor－tant for the life quality of young patients.

Abstract:Objective：To investigate the role of group 2 innate lymphoid cells（ILC2） and its transcription factors and products in the breast cancer（BC）. Methods：The peripheral blood from healthy subjects and BC patients（at early and advanced stage） was collect－ed. The peripheral blood mononuclear cell（PBMC） was isolated and the level of ILC2 in PBMC was detected by flow cytometry. Total RNA was extracted from PBMC. The gene expression level of specific transcription factor（GATA3 and RORα） and ILC2 production （IL-13 and IL-4），which regulated ILC2 development，was detected. The protein expression of T-helper 2 cytokine in serum（IL-13，IL-4，IL-33 and IL-10） were detected. Exogenous IL-13 and IL-4 were used to stimulate MCF-7 and MDA-MB 231 cancer cells，so as to simulate the polarization effect of ILC2 in BC patients：detecting the proliferation activity of cancer cells，detecting changes of protein expression of proliferation and autophagy signal factors；observing cell apoptosis via flow cytometry and fluorescence micro－scope. Results：ILC2 level in peripheral circulation of BC patients was increased（normal group vs. early stage group，0.019 6% vs. 0.028 9%，P=0.008；normal group vs. advanced stage group，0.019 6% vs. 0.027 3%，P=0.032）. Estrogen/progesterone expression status was an important factor influencing ILC2 level（HR=0.436，P=0.038）. The expression of GATA3，RORα，IL-13，IL-4，IL-33 and IL-10 was increased with tumor burden aggravation（P<0.05）. Com－bined stimulation of exogenous IL-13 and IL-4 was able to en－hance the proliferation viability of BC cells by up-regulating ERK1/2 and pERK1/2（P=0.000）. Combined stimulation was able to induce the expression of autophagy signaling molecules of MCF-7 and MDA-MB 231 cells（P=0.000） and to induce the apoptosis of MDA-MB 231 cells（P=0.000），but it had no obvious induction for the apoptosis of MCF-7 cells（P>0.05）. Conclusion：The increased proportion of ILC2 in peripheral circulation and the increased expression of up-and-down-stream factors of ILC2 is re－lated to the oncogenesis and development of BC.

Abstract:Objective：To investigate the clinical feature，diagnosis，treatment and prognosis of primary thyroid lymphoma（PTL）. Methods：The general information of 17 patients with PTL from January 2013 to September 2019 in our hospital was retrospectively analyzed. Results：Among those patients，9 patients had hypothyroidism，16 patients complicated with Hashimoto’s thyroiditis（HT），7 patients were finally diagnosed via core-needle biopsy（CNB） of thyroid，while the other 10 patients were diagnosed via partial thyroidectomy. The pathological types of these patients included diffuse large B cell lymphoma（DLBCL）（n=11），mucosa-associated lymphoid tissue lymphoma（MALT）（n=2），DLBCL and MALT transformation（n=2） and follicular lymphoma（FL）（n=2）. The average age of patients in the DLBCL group was （61.7±13.0） years old，in the DLBCL and MALT transformation group was （59.0±2.8） years old，in the MALT group was （61.5±3.5） years old，which all were significantly older than that in the FL group of （31.0±14.1） years old. The LDH level of patients in the DLBCL group was （380.3±197.9）U/L，which was higher than that in the MALT group and the FL group. The international prognostic index（IPI） in the FL group was 0，which was lower than that in the other three groups. The Ki-67 index in the DLBCL group was （70.0±16.1）%，which was higher than that in the MALT group of （16.25±8.80）%. Conclusion：PTL is closely related with the HT and diagnosis of PTL depends on histopathology. DLBCL is the most common pathological type，and the treatment protocol should be decided in accordance with the pathological type and clinical stage.

Abstract:Objective：To explore the differentially expressed genes in patients with prolactinoma（PRL） from the molecular level of genes，for studying the core driving gene of disease development；to provide potential targets for clinical diagnosis，treatment and prog－nosis in patients with RPL and predict molecular targeted drugs for treating patients with RPL by focusing on core driving genes. Methods：Gene expression profile data of PRL patients were obtained from the gene expression omnibus（GEO） database，and the differentially expressed genes（DEG） of PRL tissues and normal tissues were screened. At the same time，weighted gene co-expression network analysis（WGCNA） and protein-interaction analysis（PPI） were used to determine the core driver genes of PRL development. At the same time，gene ontology（GO） analysis，Kyoto Encyclopedia of Genes and Genomes（KEGG ） analysis and gene set enrichment analysis（GSEA） were conducted to explore the altered biological functions and signaling pathways in PRL patients，and to explore the molecular mechanism of tumor development. In addition，in vitro wound-healing test，clone formation assays，CCK-8 assays and flow cytometry experiments were performed to validate potential therapeutic effects of molecular-targeted drugs. Results：A total of 1 201 differentially expressed genes were identified，of which EGR1，MAPK1，MYC，BCL2 and CALM1 were important. The results of GO and KEGG analysis indicated that the formation of PRL was mainly related with changes of spindle pole and influenced oocyte meiosis. PRL was likely to have some homology with Parkinson’s disease. Simultaneously，CCK-8 assay，clone formation assay and in vitro wound-healing test confirmed that EGR1 agonist of Genipin had potential effect on anti-prolactinoma. Results of flow cytometry analysis showed that the apoptosis percentage of tumor cells was increased as the dose of Genipin increased. Conclusion：EGR1，MAPK1，MYC，BCL2 and CALM1 are core driving genes of PRL，which have important impacts on the PRL development. Genipin，an agonist of EGR1，inhibiting the proliferation and migration of PRL cells in vitro，shows a potential therapeutic effect on PRL. At the same time，this study screened a high-risk signal－ing pathway for the PRL development，providing a new target for clinical diagnosis and treatment，with great significance.

Abstract:Objective：To investigate the value of expression levels of serum miR-148a-3p and miR-139-5p on postoperative recur－rence and metastasis in prostate cancer（PCa） patients. Methods：A total of 142 patients with PCa admitted to our hospital from January 1st，2015 to December 31st，2017 were selected and divided into the non-recurrence and metastasis group（n=84） and the recurrence and metastasis group（n=58） according to their postoperative condition. The expression level of preoperative miR-148a-3p，miR-139-5p and prostate specific antigen（PSA） in two groups were detected，and their relationship with clinicopathological characteristics was analyzed. ROC curve was used to analyze the value of miR-148a-3p，miR-139-5p and PSA in predicting postoperative recurrence and metastasis of PCa. Pearson correlation analysis was used to analyze the correlation among miR-148a-3p，miR-139-5p and PSA. Results：Levels of serum miR-148a-3p，miR-139-5p and PSA in the recurrence and metastasis group were （4.80±0.75） ng/mL，（7.64±2.38） ng/mL，（63.75±14.92） ng/mL，respectively，which were significantly higher than those in the non-recurrence and metas－tasis group of （2.15±0.36） ng/mL，（3.50±0.62） ng/mL，（18.72±8.60） ng/mL，with statistically significant differences（t=10.648，14.715，and 9.804，P=0.000）. Expressions levels of serum miR-148a-3p and miR-139-5p in patients with recurrence and metastasis were correlated with tumor stage（t=5.117，P=0.024；t=5.304，P=0.018），Gleason score（t=5.512，P=0.006；t=6.218，P=0.000） and PSA level（t=10.208，P=0.000；t=13.620，P=0.000）. ROC curve analysis showed that the best cut-off values of serum miR-148a-3p，miR-139-5p and PSA for predicting postoperative recurrence and metastasis of PCa were 3.40，5.38 and 36.80 ng/mL，respectively. The area under curve（AUC）（0.914，95%CI=0.858 to 0.972） of postoperative recurrence and metastasis predicted by the three combinations was the highest，with the sensitivity of 92.0% and the specificity of 83.6%. Correlation analysis showed that expres－sion levels of serum miR-148a-3p and miR-139-5p were positively correlated with PSA in patients with recurrence and metastasis（r=0.774，P<0.001；r=0.806，P<0.001）. Conclusion：The up-regulated expression of serum miR-148a-3p and miR-139-5p before surgery is related to the recurrence and metastasis after PCa surgery，and the test combined with PSA has a high value in predicting the recurrence and metastasis after PCa surgery.

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Abstract:Objective：To determine the neuroprotective effect and mechanism of the stress-induced protein Sestrin2 in focal ischemic cerebral injury in rats. Methods：A clinically relevant Sprague-Dawley rat model of focal ischemic brain injury was established by photochemical embolization. Rats were divided into control group，model group，negative virus group，and Sesn2 overexpression group. Sestrin2 expression was upregulated using gene overexpression technique. The neurological deficits of each group were scored accord－ing to the modified Longa’s neurological scoring system. Cerebral infarction volume and neuronal injury were measured by TTC and Nissl staining，respectively. Sesn2 and VEGF protein expression was measured by Western blot. Results：Neurological function scores were significantly decreased in the Sesn2 overexpression group（2.100±0.738） than in the model group（3.200±0.789） and negative virus group（3.200±0.632）（both P<0.05）. TTC staining showed that cerebral infarction volume was significantly smaller in the Sesn2 overexpression group（0.034±0.004） than in the model group（0.072±0.003） and negative virus group（0.069±0.003）（both P<0.05）. In addition，Nissl staining showed that the number of intact neurons was significantly higher in the Sesn2 overexpression group（334.300±21.550） than in the model group（122.000±17.000） and negative virus group（137.700±16.070）（both P<0.05）. Western blot analysis indicated that Sesn2 and VEGF protein expression was significantly upregulated in the Sesn2 overexpression group than in the model group（0.542±0.035 and 1.074±0.094，respectively） and negative virus group（0.578±0.052 and 1.196±0.167，respectively）（all P<0.05）. Conclusion：Sesn2 overex－pression improves neurological deficit，decreases cerebral in－farction，and reduces neuronal damage. This protective effect may be mediated by upregulating VEGF and promoting mi－crovascular regeneration in areas of cerebral ischemia.

Abstract:Objective：To investigate the effect of specific inhibition of PI3Kγ by IPI549 on hepatic ischemia-reperfusion injury in mice. Methods：C57BL/6J mice were used to establish a model of hepatic ischemia-reperfusion injury，and RAW264.7 macrophages were used to establish a model of hypoxia and reoxygenation. The mice and RAW264.7 macrophages were treated with the PI3Kγ in－hibitor IPI549，and alanine aminotransferase，HE staining，and terminal deoxynucleotidyl transferase-mediated dUTP nick-end label－ing were used to evaluate hepatic injury. Western blot was used to measure the changes in the protein expression of p110γ （PI3Kγ） in tissue and primary cells and the protein expression of tumor necrosis factor-α（TNF-α），c-Jun N-terminal kinase（JNK），and phos－phorylated JNK （p-JNK） in RAW264.7 cells during hypoxia and reoxygenation. ELISA was used to measure the level of TNF-α in cell supernatant. Results：Kupffer cells had significantly higher expression of p110γ than primary hepatocytes. Compared with the sham group，the ischemia-reperfusion injury group had a significant reduction in the protein expression of p110γ in liver tissue. The mice treated with the PI3Kγ inhibitor IPI549 showed aggravation of liver injury and cell apoptosis after hepatic ischemia-reperfusion，and GdCl3 pretreatment to block Kupffer cells alleviated the aggravation of cell injury and apoptosis in liver tissue caused by IPI549. In vitro experiments showed that IPI549 intervention of RAW264.7 cells increased the phosphorylation level of JNK，the protein expres－sion of TNF-α，and the secretion of TNF-α in cell supernatant. Conclusion：Intervention with the PI3Kγ inhibitor IPI549 can aggra－vate hepatic ischemia-reperfusion injury in mice，possibly by inhibiting PI3Kγ in Kupffer cells to affect activation of the JNK signaling pathway and exerting a pro-inflammatory effect

Abstract:Objective：To establish a real-time fluorescent quantitative RT-PCR method to survey murine Norovirus（MNV） infection in laboratory mice in Chongqing，and explore the effect on immune function. Methods：①A pair of specific primers were designed targeting MNV GenBank genomic sequence，the specificity，sensitivity，repeatability and stability of the assay were evaluated，and comparison test of 123 clinical samples were carried out with two laboratory animal testing institutions to establish reliable real-time RT-PCR assay for MNV detection. ②The detection of MNV in different intestinal excretions（caecum contents，fresh feces，and excreted feces for 24 hours） was compared by real-time quan－titative RT-PCR. ③Real-time quantitative RT-PCR was used to investigate the infection of MNV in laboratory mice in Chongqing. ④Six to eight week-old BABL/c-nu mice were randomly di－vided into 3 groups（n=3 for each group）：control，MNV natural infection for 30 d，MNV infection for 60 d. Serum，liver lung，spleen，and colon were collected，the pathological changes of various organs were observed by HE staining；and tumor necrosis factor alpha（TNF-α） and interferon gamma（IFN-γ） levels in serum，tissue homogenates of spleen and colon were detected by enzyme linked immunosorbent assay（ELISA）. Results：①To established real-time RT-PCR assay could specifically detect MNV and had no cross reactions with mouse other virus. The sensitivity and repeatability were also excellent and the coincidence degree of comparison test in 123 clinical samples is as high as 98%. ②The detection results of MNV in fresh feces and caecum contents were completely consistent，excrement for 24 h in vitro can also accurately reflect MNV infection of mice in the cage. ③MNV infection rate in Chongqing is 65% to 85%，and no strain differences（68.3% vs. 70.6%， χ2=0.116，P=0.733），but genetically modified mice were more susceptible to MNV than normal mice（78% vs. 64%， χ2=6.434，P=0.011）. ④Compared with Control group，BABL/c-nu mice showed that inflam－matory cell infiltration and the obvious pathological changes in liver，lung，spleen and colon after natural infection with MNV，and the levels of TNF-α，IFN-γ in colon were significantly increased（F=21.682，P=0.002；F=77.223，P=0.000，respectively）. Conclusion：The established real-time fluorescent quantitative RT-PCR method is reliable and can monitor the infection of MNV through the stool samples of mice，MNV infection rate of mice in Chongqing is high and the infection in BABL/c-nu mice has interfered with the exper－imental results. Therefore，it is necessary to enhance the animal breeding management to reduce the risk of MNV infection in mice.

Abstract:Objective：To investigate the effect of ten-eleven translocation 2 protein（TET2） on expression of interleukin-1 receptor-related kinase-M（IRAK-M） in macrophage，and to investigate the upstream signaling pathway for TET2 expression induced by bacte－rial endotoxin/lipopolysaccharide（LPS）. Methods：LPS was used to stimulate macrophage cell line RAW264.7 in mice to induce endotoxin tolerance；qPCR and Western blot were used to detect the expression of IRAK-M and TET2 at different time points of LPS stimulation and endotoxin tolerance. After interference of siRNA toTET2 expression，qPCR and Western blot were used to detect the effect on IRAK-M expression. Cells were pretreated with mitogen-activated protein kinase（MAPK） signaling pathway inhibitors，and stimulated with LPS；qPCR and Western blot were used to detect the effect on TET2 expression. Results：TET2 and IRAK-M pro－tein continued to express after endotoxin tolerance in RAW264.7 cells，and its expression pattern was opposite to cytokines expression pattern. Expression of IRAK-M mRNA（P=0.000） and protein level was inhibited by interfering TET2 expression. Inhibition of MAPK signaling pathway was able to inhibit TET2 expression. Conclusion：MAPK signaling pathway up-regulates TET2 expression during macrophage inflammatory response，and TET2 promotes endotoxin tolerance by promoting IRAK-M expression.

Abstract:Confirmatory tests are of vital importance in the diagnosis of primary aldosteronism（PA）. Currently，the guideline does not explicitly recommend which confirmatory test is the most optimal one，and the classical ones commonly used in clinical practice still have their own shortcomings，which need to be further improved. Many studies have proposed modified or other new confirmatory tests，such as seated saline suppression test，losarton suppression test，furosemide upright test，fludrocortisone-dexamethasone suppres－sion test，dexamethasone-captopril-valsartan test. The progress in these new confirmatory tests is reviewed in this paper.

Abstract:Objective：Breast cancer is the most common cancer in women，and its incidence is the highest among all female cancers worldwide. About 5%-10% of women were newly diagnosed with distant metastatic breast cancer at the time of their initial diagnosis. Stage Ⅳ breast cancer is an incurable disease，and its treatment is mainly aimed at improving the quality of life and prolonging the life of patients. At present，stage Ⅳ breast cancer is still treated by an individualized treatment program based on systemic therapy. There is no clear conclusion on whether the primary lesion of stage Ⅳ breast cancer needs local surgical treatment. This article will review the local treatment of stage Ⅳ breast cancer.

Abstract:Objective：To study the effect of different amniotic fluid index on pregnancy outcome in full-term pregnancy. Methods：Five hundred and seventy two full-term pregnant women whose amniotic fluid index（AFI） were less than 80mm were selected as the experimental group，and 599 full-term pregnant women whose AFI was more than 81mm but less than 250 mm were selected as the control group. All the experimental subjects were chosen from Chongqing Medical University Affiliated University Town Hospital since 2014 to 2018. The two groups excluded high-risk obstetric factors，such as cephalopelvic disproportion，scarred uterus，previa placenta，abnormal placenta orientation and twin pregnancy，etc.. Groups were divided according to the AFI（mm） of 0-30，31-50，51-65，66-80. Then the cesarean section rates due to abnormal NST or OCT positive in each group were calculated and analyzed combined with the data of the group of 81-250. Results：The cesarean section rates of the group 0-30，31-50，51-65，66-80 and 81-250 were 79%，55%，47%，44%，44%，respectively. All pregnant women in the groups have a smooth delivery，and no newborn baby has been stifled to death. Comparative analyses of the Chi-square test and group to group comparison by using SPSS 20.0 showed that：the cesarean section rate was not all the same among the five groups（P<0.05）；there was no significant difference between 0-30 and 31-50 groups（P=0.05）；there were significant differences between 0-30 and 51-65 groups（P<0.05），0-30 and 66-80 groups（P<0.05），0-30 and 81-250 groups（P<0.05）；there was no significant difference between 31-50 and 51-65 groups（P>0.05）；there were signifi－cant differences between 31-50 and 66-80 groups（P<0.05），31-50 and 81-250 groups（P<0.05），31-50 and 66-80 groups（P<0.05），31-50 and 81-250 groups（P<0.05）. There was no significant difference between 51-65 and 66-80 groups（P>0.05），51-65 and 81-250 groups（P>0.05），66-80 and 81-250 groups（P>0.05）. Conclusion：The amniotic fluid index of 80 mm and 50 mm has definite guiding significance，while more detailed grouping of amniotic fluid volume has no obvious guiding significance for clinical work in this study.

Abstract:Objective：To investigate the relationship between axis length/corneal radius of curvature ratio（AL/CR ratio） and myopia degree in children of 7-12years old. Methods：Data of spherical equivalent refraction，axial length and corneal refractive power from 402 children（804 eyes） of 7-12 years old were obtained by cycloplegic optometry and IOL-Master and AL/CR ratio was calculated. According to the spherical equivalent refraction，402 children were divided into three groups：mild myopia group，moderate myopia group and high myopia group. Statistics were analyzed by SPSS 22.0 software. Results：AL/CR ratio among high myopia group（3.47±0.13），moderate myopia group（3.26±0.09） and mild myopia group（3.12±0.07） was significantly different（F=972.220，P=0.000）. Correlation between spherical equivalent refraction and AL/CR ratio was higher than that between axial length and corneal radius of curvature（r=-0.886，r=-0.752，r=0.243，P=0.000）. According to the linear regression，spherical equivalent refraction was changed about-15.2D with each increase of AL/CR ratio（r2=78.4%，P=0.000）. Among those three groups，difference of linear regression line between axial length and corneal radius of curvature had no statistical significance（r2=48.1%，r2=50.9%，r2=16.7%，P=0.000），but dif－ference of the linear regression line between AL/CR ratio and spherical equivalent refraction had statistical significance（r2=20.5%，r2=19.5%，r2=84.0%，P=0.000）. Conclusion：AL/CR ratio is an objective index in the diagnosis of myopia and can be used to clas－sify different degrees of myopia.