Abstract:Objective：To construct nerve injury-inducing protein 2（Ninj2） knockout mice and study its role during mouse ovarian development. Methods：We generated Ninj2 knockout mice by CRISPR/Cas9 technology，and detected the role of Ninj2 in mouse ovarian development by HE staining，immunofluorescence，in vitro fertilization（IVF） and lipopolysaccharide（LPS） exposure. Results：Ninj2 knockout mouse model was successfully constructed. Body weight and detection of related biochemical indicators showed that there was no significant difference between Ninj2 homozygous knockout mice and wild-type mice；HE staining showed that there was no significant difference in follicular development between Ninj2 knockout mice and wild-type controls at all levels in newborn and adult ovaries；IVF results showed that the early embryos of Ninj2 knockout mice developed normally；LPS had no effect on ovarian development in Ninj2 knockout mice. Conclusion：Depletion of Ninj2 does not affect the mouse ovarian development in normal physiological or inflammatory condition.

Abstract:Objective：CRISPR/Cas9 gene editing technology was employed to knockout the PIN1 gene of adult neural stem cells（NSCs）and finally established a PIN1 gene knockout adult neural stem cell line. Methods：The tissue from the subventricular zone of 8-week-old C57BL/6 mice was dissected and cultured in vitro；single guide RNA（sgRNA）targeting PIN1 gene in mice was designed，and the PX330 plasmid was used as the skeleton to construct PIN1 Cas9 target vector. PIN-knockout monoclonal cells were obtained after transfection and puro screening. The expression level of PIN1 protein was verified by immunofluorescence and Western blot. The expression of nestin was used to identify the neural stem cell characteristics. The differentiation ability to neuronal lineage was determined by beta Ⅲ tubulin immunofluorescence. Results：Cas9/sgRNA expression vector of PIN1 gene was successfully constructed，and nine PIN1 knockout neural stem cells were cloned after transfection. Immunofluorescence and Western blot showed no expression of PIN1 protein，immunofluorescence showed positive expression of nestin in PIN1 knockout neural stem cells，and neural stem cells could differentiate into beta Ⅲ tubulin positive neurons in differentiation culture. Conclusion：CRISPR/Cas9 gene editing technology can realize the editing of PIN1 gene in mouse adult neural stem cells. After knock-out of PIN1 gene，PIN1 protein is not expressed，but neural stem cells still partially express the specific marker nestin and have the ability to differentiate toward neurons.

Abstract:Objective：We aimed to investigate the potential effects of low-intensity pulsed ultrasound（LIPUS）on the polarization and lipid droplet phagocytosis of macrophage，and further explore the underlying molecular mechanism. Methods：Murine tibial bone marrow was perfused to extract murine bone marrow-derived macrophage. Different intensities（4.825，19.300，43.425 mW/cm2）of LIPUS treatment were performed in macrophage. Then LPS was used to induce polarization of macrophage to the M1 phenotype. After that，we used flow cytometry and CCK-8 kit to determine the levels of apoptosis and viability of macrophage in different groups，respectively. Besides，the heating effects of LIPUS irradiation were measured by thermocouples. The mRNA expression of inflammatory-related genes was validated by q-PCR analysis. Western blot was conducted to explore the protein levels of NF-κB/MAPK pathway. Then，the phagocytosis of DiI-labeled OX-LDL was observed under inverted fluorescence microscope after 6 h co-culture with macrophage. Results：First，no significant difference of cell apoptosis in LIPUS group was shown in flow cytometry compared with that in the control group. The viability of macrophage examined in CCK-8 did not behave obvious difference. Besides，the results of temperature test demonstrated that the ultrasound conditions we set hardly changed the temperature of culture medium during LIPUS procedures. Then，results of q-PCR showed that mRNA levels of M1 phenotype genes were remarkedly up-regulated in LPS-induced macrophage compared with those in the control group，which was attenuated by LIPUS treatment（P < 0.05）. Moreover，LIPUS treatment down regulated LPS-induced phagocytosis of DiI-labeled OX-LDL（P < 0.05）. Results of western blot showed that LIPUS inhibited LPS-induced activation of NF-κB/MAPK pathways（P < 0.05）. Conclusion：Overall，our results demonstrated that LIPUS could reduce LPS-induced polarization of macrophage to the M1 phenotype，and phagocytosis of lipid droplet through inactivating NF-κB/MAPK pathway.

Abstract:Objective：To investigate the effects and mechanisms of netrin-1（NTN1）in antagonizing polychlorinated biphenyls（PCBs）toxicity in retinal ganglion cells RGC-5. Method：RT-qPCR and Western blot were used to detect the expression levels of NTN1 and ERK signaling molecules in RGC-5 cells after exposure to PCB1254；NTN1 small interfering RNA and NTN1 overexpression lentivirus were used to transfect RGC-5 cells，and control groups were set as negative control group and empty lentivirus group，and treated with or without PCB1254. Cell proliferation was detected by CCK-8 assay，cell cycle and apoptosis were detected by flow cytometry，and expression levels of ERK signal molecules were detected by RT-qPCR and Western blot. Results：①After exposure to PCB1254，the expression levels of NTN1 and p-ERK in RGC-5 cells were significantly reduced. ②NTN1 silencing reduced RGC-5 cell proliferation and led to S phase arrest；NTN1 silencing significantly inhibited the phosphorylation of ERK signaling molecules. ③NTN1 overexpression rescued the proliferation of RGC-5 cells after PCB1254 exposure，reduced the proportion of S phase cells，and increased the phosphorylation level of ERK. Conclusion：NTN1 can regulate the ERK signaling pathway to antagonize the decline in the proliferation of retinal ganglion cells caused by PCB1254 exposure，reduce the proportion of S-phase cells，and alleviate the toxic effects of PCB1254 on retinal development.

Abstract:Objective：To explore the effects and mechanisms of lobaplatin on antitumor immunity and programmed cell death 1（PD-1）expression in hepatocellular carcinoma（HCC）. Methods：①A total of 73 HCC patients were randomly divided into two groups：the lobaplatin group（50 mg lobaplatin in 100 ml sterile water was infused into abdominal cavity during liver cancer resection，n=40），and the control group（n=33）. The changes in peripheral blood lymphocyte subsets were analyzed before and after surgery. ②The effects of lobaplatin（16 μmol/L）on the expression of HLA-I，TAP-1，TAP-2 in Hep3B cells were analyzed by flow cytometry. ③Hep3B，HepG2，SMMC-7721 cells treated with lobaplatin（0，8，16 μmol/L）for 24 h，then the expressions of PD-L1，AKT，p-AKT protein were analyzed by Western blot and RT-qPCR. ④the expression of PD-L1 in Hep3B cells treated with lobaplatin，or lobaplatin and AKT-inhibitor MK2206 or PBS was analyzed by Western blot. Result：①After intraperitoneal infusion of lobaplatin，the rates of CD4+ and CD4+/CD8+ increased（P < 0.05），Treg decreased（P < 0.05）in the peripheral blood. ②Lobaplatin upregulated the expression of HLA-I，TAP1，and TAP2 in Hep3B cells. ③Lobaplatin upregulated the expression of PD-L1，p-AKT protein in HepG2，SMCC-7721，and Hep3B cells. ④AKT-inhibitor MK2206 reduced the effect of lobaplatin on the up-regulation of PD-L1 expression in Hep3B cells. Conclusion：Lobaplatin can enhance the anti-tumor immunity of HCC patients，induce antigen presentation of liver cancer cells and increase the expression of PD-L1 through AKT signal pathway，so that lobaplatin maybe combine with immune checkpoint inhibitor to treat HCC.

Abstract:Objective：To explore the clinical significance of the expression level of miR-182 in serum exosomes in the infiltration of oral squamous cell carcinoma. Methods：Combined with the TCGA database and related research in the literature，miRNAs highly expressed in exosomes of head and neck squamous cell carcinoma tissues and cell lines were screened. Exosomes were extracted using ExoQuick kit and ultracentrifugationfrom serum and culture supernatant of HEK293 cells，and identified with transmission electron microscopy，nanoparticle tracking analyzer and Western blot；the expression levels of miR-182 in two oral cancer cell lines，HN6，CAL27，and serum exosome were determined by real-time quantitative RT-PCR . The proliferation of CAL27 cells treated with miR-182 antagomir loaded HEK293 cell exosomeswas detected by CCK-8 experiment. Results：miR-182 was highly expressed in the exosomes of head and neck squamous cell carcinoma tissues，oral squamous cell carcinoma cell lines and head and neck squamous cell carcinoma cell lines. The expression levels of serum exosome miR-182 in patients with oral cancer increased，compared with those in the control group. However，the differences were statistically insignificant（P > 0.05）. The content of miR-182 in the serum exosomes of patients with tumor infiltration depth >5 mm was significantly higher than that of the control group（P < 0.05）. After CAL27 cells were treated with exosomes loaded with miR-182 antagomir，the proliferation ability of CAL27 cells decreased significantly（P < 0.05）. Conclusion：miR-182 is highly expressed in oral cancer and the expression level of serum exosome miR-182 is related to the depth of tumor infiltration of oral squamous cell carcinoma. The exosomes loaded with miR-182 antagomir significantly inhibit the proliferation of CAL27 cells.

Abstract:Objective：To explore the effects of histidine decarboxylase inhibitors on lipopolysaccharide（LPS）-induced inflammation and cognitive impairment in rats in vivo. Methods：Forty-eight SD male rats were randomly divided into 4 groups with 12 rats in each group：control group，α-FMH group，LPS group and α-FMH+LPS group. Catheters were placed in the right lateral ventricle of rats with a stereotactic instrument，and a week after recovery，they were placed in an escape fear experimental instrument to learn. Then α-FMH and the same volume of normal saline were directionally injected into the lateral ventricle of rats. Half an hour after administration，LPS（1 mg/kg）was injected intraperitoneally. A day later，the ability of rats to escape fear was evaluated by behavioral experiments. The activation of microglia in the hippocampus was detected by immunohistochemistry. The expression of interleukin 6 and tumor necrosis factor α was detected by ELISA method. Results：After intraperitoneal injection of LPS，the expression of histamine in hippocampus began to increase significantly at 6 h，and was higher than the basic level within 24 h. Compared with the control group，the activation of microglia and the expression of inflammatory factors mentioned above in the hippocampus of the LPS group were increased（P < 0.01），and the freezing time of the LPS group was significantly decreased（P < 0.01）. Compared with LPS group，the activation of microglia and the expression of the inflammatory factors in the hippocampus of α-FMH+LPS group were significantly decreased（P < 0.01），and the freezing time of α-FMH+LPS group was significantly increased（P < 0.01）. Conclusion：Histidine decarboxylase inhibitor α-FMH can alleviate LPS-induced inflammation and cognitive impairment in rats by inhibiting the activation of microglia.

Abstract:Objective：To explore the role of cardiopulmonary exercise testing（CPET）in noninvasive evaluation of chronic obstructive pulmonary disease（COPD）related pulmonary hypertension（PH）by comparing the differences of gas exchange and exercise tolerance in CPET between patients with COPD related PH and patients without PH. Method：A total of 94 stable COPD patients were divided into COPD-nonPH group，COPD-PH group，COPD-severe PH group according to mean pulmonary artery pressure measured by right heart catheterization. All patients underwent routine lung function testing and CPET. Result：Compared with COPD-nonPH，diffusing lung capacity for carbon monoxide（DLCO）decreased significantly after PH occurred［（46.5 ± 21.8）% vs.（64.6 ± 34.0）%，P < 0.05］. Peak load，peak VO2% pred，peak VO2/kg，peak O2 pulse，and oxygen uptake efficiency slop（OUES）in COPD-PH group were lower than those in COPD-nonPH group，and further decreased with PH severity，there were statistically significant differences（P < 0.05）. The ventilatory equivalents for CO2 nadir（VE/VCO2 nadir）in COPD-PH group was higher than that in COPD-nonPH group，and increased significantly in severe PH group（49.0 ± 24.6 vs. 38.6 ± 11.4 vs. 35.6 ± 9.6，P < 0.05）. Other outcomes such as peak heart rate，respiratory exchange rate（RER），oxygen uptake efficiency platform（OUEP），and peak end-tidal CO2 partial pressure（PetCO2） showed no significant differences among the three groups（P > 0.05）. Conclusion：Compared with COPD-nonPH patients，gas exchange and exercise tolerance significantly decreased in COPD-PH patients，and further deteriorated with the severity of PH. CPET could be used as an effective tool for noninvasive evaluation of COPD related PH.

Abstract:Objective：To investigate the combined physiologic effects of different positive end-expiratory pressure（PEEP）and decreased inspired oxygen fraction（FiO2）during one lung ventilation（OLV）. Methods：This study is a prospective，single-blind，randomized controlled study. One-hundred and twenty patients were equally randomized into four groups of A（OLV with 0 cmH2O），B（OLV with 5 cmH2O），C（OLV with 8 cmH2O），and D（OLV with 10 cmH2O）. All patients breathed an inspiratory oxygen fraction of 0.6. Arterial blood and venous blood were taken for gas analysism，and intrapulmonary shunt rate（Qs/Qt）were calculated before OLV（T1），OLV 10 min（T2），OLV 15 min（T3），OLV 30 min（T4），OLV 60 min（T5），and OLV 120 min（T6）. Haemodynamics and respiratory mechanics parameters were monitored continuously. The clinical pulmonary infection score（CPIS）was recorded on the second day after the surgery and the incidence of postoperative pulmonary complication was recorded. Results：Among the 120 patients assessed for eligibility，118 completed the study. At T2~T6，PaO2 in group D was significantly higher than that in group A，Qs/Qt in group D was significantly lower than that in group A（P < 0.05）. At T3~T4，PaO2 in group C was significantly higher than that in group A，Qs/Qt in group C was significantly lower than that in group A（P < 0.05）. At T4，PaO2 in group B were significantly higher than that in group A，Qs/Qt in group B were significantly lower than that in group A（P < 0.05）. At T2~T5，PaO2 in group D were significantly higher than that in group B，At T2 ~ T4，Qs/Qt in group D were significantly lower than that in group B（P < 0.05）. At T5，PaO2 in group D were significantly higher than that in group C（P < 0.05）. At T2~T6，driving pressure（DP）in group B，C，and D were significantly lower than that in group A（P < 0.05）. At T2~T5，DP in group C and D were significantly lower than that in group B（P < 0.05）. At T4~T6，dynamic compliances in group C and D were significantly higher than those in group A and B（P < 0.05）. The CPIS score was significantly lower in group B，C and D than that in group A on the second day after the surgery（P < 0.05）. Conclusion：During one lung ventilation with 0.6 FiO2，10 cmH2O PEEP improves pulmonary function without changing the hemodynamic parameters and reduces driving pressure，and plays an important role in lung protection.

Abstract:Objective：To investigate the alterations of functional connectivity among Parkisnon’s disease（PD）patients with anxiety，and to explore its pathological mechanism. Methods：Totally 112 PD patients and 54 healthy controls underwent rs-fMRI scanning. According to the Hamilton anxiety scale（HAMA），112 PD patients were divided into 50 PD with anxiety group（PD-A）and 62 PD without anxiety（PD-NA）. ANCOVA and post-hoc t test were performed to assess intergroup difference of voxel-mirrored homotopic connectivity（VMHC）value to obtain the abnormal brain regions. Bilateral amygdala were chosen as seeds to calculate functional connectivity with abnormal brain regions. Estimated a Pearson’s correlation coefficient between functional connectivity calculated above and HAMA scores. Results：VMHC value had significant differences among three groups，post hoc t test showed a decrease of VMHC value in bilateral inferior frontal gyri（IFG）triangular part and opercular part in PD-A group compared to the PD-NA group. Functional connectivity increased between the left amygdala and the left IFG. Furthermore，functional connectivity was positively correlated with HAMA scores. Conclusion：Abnormal brain functional activity exists in PD-A group，suggesting that anxiety in PD is associated with abormalities in IFG-amygdala loop network.

Abstract:Objective：To investigate the diagnostic value of quantitative flow ratio（QFR）combined with coronary stenosis assessed by related optical coherence tomography（OCT）parameters in intermediate coronary lesions. Methods：From October 2016 to February 2020，a total of 89 patients with 109 lesions were enrolled in the First Affiliated Hospital of Nanjing Medical University. All patients underwent coronary angiography suggesting intermediate lesions（stenosis between 50% and 90% by visual estimation）and lesions were evaluated by OCT. Baseline data，quantitative coronary angiography data（QCA）and coronary lesions characteristics were collected and lesions were retrospectively analyzed by QFR. The diagnostic value of QFR in intermediate coronary lesions was evaluated when coronary significant stenosis defined as minimal lumen area（MLA）<2.5 mm2 or area stenosis（AS）≥75% by OCT. Results：Compared with the non-significant stenosis group，QFR in the significant stenosis group was significantly lower（P < 0.001）. AS assessed by 2D-QCA was significantly higher than that assessed by OCT（P=0.007）and 3D-QCA（P < 0.001）derived from QFR. AS evaluated by 3D-QCA and OCT had no significant difference（P=0.356）. According to linear regression，OCT-MLA was correlated positively with QFR significantly（r=0.56，P < 0.001）. OCT-AS was correlated negatively with QFR significantly（r=-0.60，P < 0.001）. ROC-analysis revealed that 0.81 is the ideal QFR cut-off to identify coronary lesions with significant stenosis（AUC：0.837，95% CI：0.754~0.901，P＜0.001，sensitivity 83.3% and accuracy 80.0%）. Conclusion：The application of QFR combined with OCT can accurately predict the coronary stenosis and evaluate the coronary functional parameters，which can guide the diagnosis and treatment in intermediate coronary lesions.

Abstract:Objective：To investigate the value of urinary activating transcription factor 3（ATF3） and kidney injury molecule 1（Kim-1）in the early diagnosis of acute kidney injury（AKI） after cardiopulmonary bypass（CPB）heart surgery. Methods：A total of 83 patients who underwent elective CPB surgery in the Department of Cardiac Surgery of Shanghai 10th People’s Hospital from January 2018 to December 2019 were selected and divided into AKI group and non-AKI group according to KIDGO diagnostic criteria. Urine samples were collected preoperatively and 2 h，6 h，12 h，24 h，and 48 h after surgery，the levels of ATF3 and Kim-1 in urine were determined by enzyme-linked immunosorbent assay（ELISA），and［ATF3］·［Kim-1］was calculated. The area under the curve（AUC）was obtained by drawing the receiver operating curve（ROC）to evaluate the clinical value of urinary ATF3，Kim-1，and［ATF3］·［Kim-1］for early diagnosis of AKI. Results：A total of 42 patients developed AKI. Compared with the non-AKI group，urinary ATF3 was significantly increased at 6 h and 12 h postoperatively，and the AUC for the diagnosis of AKI at 12 h postoperatively was 0.691（95%CI：0.576~0.807，the sensitivity and specificity were 0.43 and 0.85 when the cutoff value was 1 216 pg/mL）. The AUC of［ATF3］·［Kim-1］combined detection was 0.712 at 6 h after surgery，reaching the highest value，and the sensitivity and specificity were 0.57 and 0.78，respectively. Conclusion：Urinary ATF3 is expressed early in the urine of patients after CPB，and can be used as a diagnostic marker for AKI after CPB in adults. The predictive value of combined use is higher than that of single test，and it is a feasible way to increase the diagnostic accuracy.

Abstract:Objective：This study investigated the clinical significance of red blood cell distribution width（RDW）in Waldenstrom macroglobulinemia（WM）. Methods：Data of patients diagnosed with WM in the First Affiliated Hospital of Nanjing Medical University from June 2009 to September 2018 were retrospectively analyzed. The best cut-off value of RDW was determined by receiver operating characteristic（ROC）curve. Univariate and multivariate analysis were performed to find out the factors of progression-free survival（PFS）and overall survival（OS）. Results：Seventy-eight patients were finially enrolled in this study. The ROC curve indicated that 16.4% was the best cut-off value to predict survival outcomes. The median follow-up time was 39.5 months，patients with a high level of RDW（＞16.4%）had worse survival outcome. Multivariate analysis revealed that a high level of RDW was an independent risk factor for PFS and OS. Furthermore，a high level of RDW together with the revised international prognostic score system for WM improved the prognostic capacity of WM. Conclusion：RDW is a feasible clinical parameter which could be used to predict the prognosis of WM.

Abstract:Objective：To observe the effect of radiotherapy dose on cervical esophageall carcinoma，and to analyze the prognostic factors of cervical esophageal carcinoma. Methods：A retrospective analysis was performed on 96 patients with cervical esophageal carcinoma who received three dimensional conformal radiation therapy or intensity-modulated radiation therapy from 2013 to 2018 according to inclusion criteria. All the patients are divided into three groups according to the radiation dose of gross tumor：the low-dose group（≤60 Gy），the medium-dose group（>60~<66 Gy）and the high-dose group（≥66 Gy）respectively. The clinical effect，acute adverse effects，and treatment failure mode were compared among three groups，and the prognostic factors of cervical esophageal carcinoma were analyzed. Results：The short-term efficacy was observed one month after radiotherapy，and the objective response rate was 66.7%，85.4%，and 85.7%，respectively. There was no statistical difference among three groups（P=0.114）. The univariate analysis showed that radiotherapy dose was the influencing factor of overall survival（P=0.031），progression-free survival（P=0.045）and local-regional failure-free survival（P=0.020），and there was no difference in the efficacy between the middle-dose group and the high-dose group，and all of them better than the low-dose group（P<0.05）. The independent prognostic factors of OS for cervical esophageal carcinoma are radiotherapy dose，synchronous chemotherapy，and invasion of adjacent organs. Conclusion：Radical chemoradiotherapy is effective for cervical esophageal cancer，and the medium dose，i.e. >60~<66 Gy，may be a more reasonable radiotherapy dose for cervical esophageal cancer. Radiotherapy dose，concurrent chemotherapy and invasion of adjacent organs are independent prognostic factors of OS.

Abstract:Objective：To explore the risk factors of the central nervous system recurrence in children with acute lymphoblastic leukemia. Methods：Retrospectively analyzed clinical data of 426 children with ALL treated in our hospital from January 2013 to July 2018. The subjects were divided into two groups according to different treatment plan and clinical characteristics to compare the recurrence rate of the central nervous system，and to analyze the risk factors of central recurrence and the poor prognostic factors of children with recurrence. Results：①The central recurrence rate of Children treated with CCCG-ALL-2015 scheme（scheme 2015）was lower than that of children treated with diagnosis and treatment of childhood acute lymphoblastic leukemia（scheme 2006）（P < 0.01）；②The central recurrence rate of children with male，leukocyte count≥50×109/L and T-ALL was significantly higher（P < 0.05）；③Logistic regression analysis suggested that leukocyte count≥50×109/L and T-ALL were independent risk factors of central recurrence（P < 0.05）；④K-M survival analysis showed that the overall survival rate of children with hormone induced peripheral blood immature cell count≥1×109/L and platelet count≤20×109/L was lower（P < 0.05）. Conclusion：Scheme 2015 effectively reduced central recurrence compared with scheme 2006. The risk factors of the 2015 regimen were the same as those of the 2006 regimen，and the prevention of central recurrence should be strengthened in the cases with central recurrence risk factors.

Abstract:Objective：To evaluate the effect of a new collagen-type artificial bone graft on the repair of alveolar bone defect after single tooth extraction. Methods：A total of 89 patients with a single molar planned to be extracted at our institution were included and randomly divided into two groups. The experimental group was implanted with the new collagen-type bone graft while the control group was implanted with Bio-Oss collagen immediately after tooth extraction. After then，all wounds were coated by the absorbable biological membrane. The height，width and density of alveolar bone were tested by CBCT immediately and 6 months after surgery，and clinical examinations were conducted three times during the period. Results：There was no significant difference in the change of alveolar bone height and width between the experimental group and the control group（P > 0.05）. In the experimental group，the lingual bone height decreased by（0.75 ± 0.95）mm，while no significant change was found in the buccal bone height and the width. In the control group，the height decreased by（0.54 ± 1.47）mm in the buccal and decreased by（1.20 ± 1.18）mm in the lingual，whereas bone width did not change significantly. Bone density of the experimental group was higher than that of the control group immediately after surgery（P < 0.01），but no significant differences were found between the two groups 6 months after surgery（P > 0.05）. Clinical examination showed that there was no significant difference in wound healing score between the two groups. Conclusion：The new collagen-type artificial bone graft has similar effects to Bio-Oss collagen on the repair of alveolar bone defect after extraction，and is slightly better in preservation of the buccal bone.

Abstract:Objective：To study correlation of cancer-associated fibroblasts（CAFs），CD4+，CD8+ T lymphocyte with developments and lymph node metastasis of breast carcinoma. Methods：Immunohistochemistry method（S-P）was used to examine the expression of α-smooth muscle actin（α-SMA），CD4 and CD8 in breast invasive ductal carcinoma，and the relationships with the clinicopathological features of breast carcinoma were analyzed to explore the correlation between CAFs induced immunosuppression and the development and lymph node metastasis of breast carcinoma. Results：The positive rate of α-SMA was significantly higher in breast carcinoma than that in control. The expression rate of α-SMA was positively correlated to the tumor size，TNM stage and lymph nodal involvement（P＜0.05）. The expression of CD4 was negatively correlated to the grade and lymph nodal involvement（P＜0.05）. The expression of CD8 was positively correlated to the grade and lymph nodal involvement（P＜0.05）. The expression of α-SMA was positively correlated to the expression of CD8（P＜0.01），and it was negatively correlated to the expression of CD4（P＜0.01）. Conclusion：Abnormal CAFs and CD4+，CD8+ T lymphocytes promote the occurrence，development and lymphatic metastasis of breast cancer，and they provide reliable laboratory basis to evaluate the survival and prognosis of breast cancer patients.

Abstract:Objective：To observe the expression of Nup107 in colon cancer tissues，and explore the relationship of Nup107 with the clinicopathological characteristics and prognosis of colon cancer patients. Methods：Ualcan database and real-time quantitative PCR were used to observe the expression level of Nup107 mRNA in colon cancer tissues. A total of 226 colon cancer patients from the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University were selected. Immunohistochemical staining was used to detect the expression level of Nup107 protein in colon cancer tissues and normal colon tissues. The relationship of Nup107 expression level with the clinical characteristics and prognosis was analyzed based on clinical data. Preliminary study on the mechanism of Nup107 in colon cancer was performed by gene set enrichment analysis. Results：The mRNA and protein expression levels of Nup107 in colon cancer tissues were significantly higher than those in normal colonic mucosal tissues（P < 0.05）. The expression of Nup107 was significantly associated with tumor size（P=0.004），lymph node metastasis（P=0.002），distant metastasis（P=0.007），AJCC stage（P=0.003），and Ki67 expression（P=0.001）. Colon cancer patients with high level of Nup107 had poorer overall survival than those with low level of Nup107（P < 0.001）. Nup107 might be involved in basic transcription factors，mismatch repair，homologous recombination，ribosome，spliceosome，RNA degradation and other pathways in colon cancer. Conclusion：Nup107 is an independent risk factor for prognosis，and it is expected to provide new strategies for diagnosis and treatment of colon cancer.

Abstract:Objective：To investigate the clinical distribution and resistance characteristics of pathogens isolated from bloodstream infection patients in a intensive care unit of geriatric medicine（geriatric ICU）in a tertiary teaching hospital. Methods：Blood culture results and clinical data of hospitalized patients in geriatric ICU from 2016 to 2019 were collected and then analyzed using WHONET 5.6 software. Patients with positive blood culture were divided into old group（≥60 years）and non-old group（<60 years）according to age. And the constitute as well as drug resistance of blood culture pathogens were compared between the two groups. Results：A total of 100 strains of pathogen were isolated from 96 patients with positive blood culture. Of the 100 isolates，gram negative bacilli，gram positive cocci，fungi and anaerobes accounted for 63%，22%，10%，and 5%，respectively. The top three gram negative pathogens were K. pneumoniae（25%），E. coli（13%）and A. baumannii（11%）. The top three gram positive pathogens were Enterococcus（25%），S. aureus（13%）and viridians Streptococcus（11%）. The proportion of carbapenem-resistant Enterobacteriaceae（CRE）in K. pneumoniae，carbapenem-resistant A. baumannii（CRAB）in A. baumannii and methicillin-resistant Staphylococcus aureus（MRSA）in S. aureus were 72.0%，81.3% and 57.2%，respectively. E. coli resistant to carbapenem and S.aureus resistant to vancomycin or linezolid were not found. One strain of E. faecium was identified as resistant to vancomycin. Almost all CRE strains were not resistant to tigecyclin，polymyxin B or ceftazidime-avibactam except one strain of K. pneumoniae that was determined to be resistant to ceftazidime-avibactam. Among CRAB，only one strain showed resistance to tigecyclin，and no resistance to tigecyclin or polymyxin B was detected in others. There was no significant differences in pathogen distribution between old and non-old group. Compared with non-old group，pathogens in old group showed higher drug resistance. Conclution：Gram-negative bacteria with high drug resistance to carbapenem were the dominant pathogens associated with bloodstream infection in old severe patients in geriatric ICU. And bacterial resistance surveillance might be helpful for guiding rational use of antimicrobial agents in clinic.

Abstract:Objective：To investigate the change of HIV subtypes and drug resistance in the follow-up HIV/AIDS population in Wuxi，Jiangsu in 2014 and 2016. Methods：HIV molecular epidemiological survey and follow-up study were carried out among HIV/AIDS patients who did not receive antiviral treatment in Wuxi in 2014. The basic information of the infected person was collected and DNA was extracted from blood samples. The pol，env，and gag gene fragments of HIV were amplified by nest-PCR and sequenced to determine the HIV genotype of the infected person. The pol sequence was submitted to the HIV drug resistance database for drug resistance mutation site analysis. In 2016，the same population was followed up and selected for antiviral treatment. HIV subtypes and drug resistance mutations were detected again，and the changes of subtypes and drug resistance in two years were analyzed. Results：A total of 117 HIV/AIDS cases were collected，and 234 samples were detected. Seven subtypes of HIV-1，CRF01_ AE，CRF07_ BC，B，CRF67_ 01B，CRF08_ BC，CRF55_ 01B，and CRF68_ 01B，and six unique recombinant types（URFs）were detected. The transmitted drug resistance rate was 4.95% in 2014，acquired drug resistance rate was 5.75% in 2016. The drug resistance of 5 cases changed，and one of the subtypes changed. Conclusion：The HIV-1 subtypes of HIV/AIDS patients in Wuxi are diverse and complex. The subtypes and drug resistance have changed greatly. Therefore，it is necessary to strengthen the surveillance of subtypes and drug resistance mutations.

Abstract:Objective：To investigate the correlation between CT radiomics features and pathological classification of pulmonary nodules，and to evaluate the predictive performance of three radiomics models on pathological classification of pulmonary nodules. Methods：A total of 189 patients with pathologically-proven pulmonary nodule and complete clinical data and CT images were obtained from July 2017 to August 2019 in our hospital，including 71 benign nodules，51 non-invasive nodules and 67 invasive nodules. Three radiomics models were established. Model 1 was established to distinguish benign and malignant nodules（including non-invasive and invasive nodules）；model 2 was established to differentiate non-invasive and invasive nodules；model 3 was established to distinguish benign，non-invasive and invasive nodules. The high throughput features from the region of interests（ROIs）within the radiologist-drawn contour were extracted for classification analysis by use of a radiomics software. The classification model was established by selecting features and classifiers intelligently. The prediction performances were evaluated with ROC analysis and AUC. The sensitivity，specificity，accuracy，positive predictive value（PPV），and negative predictive value（NPV）in classification of three models were calculated. Results：Twenty radiomics features were screened out in model 1. Classification test results of the model 1 showed the AUC of 0.85，accuracy of 79.66%，sensitivity of 70.42%，specificity of 84.59%，PPV of 81.74%，NPV of 67.57%，respectively. Two radiomics features were selected in model 2. Classification test results of the model 2 showed the AUC of 0.89，accuracy of 88.06%，sensitivity of 74.51%，specificity of 82.2%，PPV of 81.94%，NPV of 82.61%，respectively. In model 3，20 radiomics features were selected，and classification test results of the model 3 showed the AUC of 0.84，accuracy of 71.34%，sensitivity of 85.05%，specificity of 70.37%，PPV of 83.2%，NPV of 76.3%，respectively. Conclusion：CT radiomics has high value in the identification of benign，non-invasive and invasive nodules.

Abstract:The interaction between oral microorganisms is critical for the maintenance of oral microecological balance and the occurrence of oral diseases. Studies have shown that there is a complex interkingdom interaction between the main cariogenic bacteria，Streptococcus mutans，and the main opportunistic pathogenic fungus in the mouth，Candida albicans，which may affect the clinical pathogenicity of each other. In this review，we summarized the influence of the interaction between Streptococcus mutans and Candida albicans on pathogenicity and known mechanisms. The application of natural products to control biofilms of Streptococcus mutans and Candida albicans and the virulence were also summarized.