Abstract:Objective：The study aims to investigate the role of Zfp212 on female fertility by generating Zfp212 knockout mice model. Methods：CRISPR/Cas9 system was used to generate Zfp212 knockout mice. Zfp212 expression pattern，subcellular location and Zfp212 knockout efficiency were detected by quantitative real-time PCR（RT-qPCR），immunofluorescence staining（IF）and Western blot. Ovary histological analysis and HE staining，in vitro fertilization（IVF），in vitro embryo culture and fertility test were performed to explore the effects of Zfp212 knockout on female mice fertility. Results：Zfp212 was expressed dominantly in oocytes and early embryos，and it showed a maternal expression pattern. The results of Western blot and sanger sequencing showed Zfp212 knockout mice model was constructed successfully. Compared with control groups，Zfp212 knockout female mice had no significant differences in follicle development，oocyte maturation，fertilization，preimplantation embryo development and litter size. Conclusion：These results indicated that Zfp212 gene is not necessary for the establishment of female fertility in mice.

Abstract:Objective：This study aims to explore the role of peptides in lung adenocarcinoma and its potential molecular mechanisms through peptideomics analysis. Methods：Endogenous peptides from 3 pairs of age-matched male lung adenocarcinoma and paracancerous tissues were extracted and detected by liquid chromatography-tandem mass spectrometry（LC-MS/MS）. Bioinformatics was used to infer the potential functions of differential peptides. CCK-8 assays，wound-healing assays，and Transwell assays were carried out to verify the effect of key peptides on the malignant phenotype of lung adenocarcinoma cell lines（A549，H1975）. Results：A total of 4 538 peptides were identified，of which 242 were differentially expressed（fold change≥2.0，FDR<0.05），corresponding to 202 precursor proteins. GO analysis and KEGG pathway enrichment analysis showed that these proteins were closely related to a series of important biological activities of tumorigenesis and development. Additionally，the novel peptide LACRP2 was also focused on. It was confirmed that this peptide could inhibit some malignant phenotypes of lung adenocarcinoma cell lines in vitro. Conclusion：The endogenous peptide LACRP2 may be related to some malignant phenotypes of lung adenocarcinoma. Peptidomics can aid in understanding the pathogenesis of lung cancer more comprehensively.

Abstract:Objective：This study aims to investigate the role of miR-484 in adipogenesis and its clinical potentiality. Methods：To explore the function of miR-484 in human pre-adipocyte（HPA）differentiation and proliferation，RT-qPCR，CCK-8，red oil staining and triglyceride content assays were conducted. Additionally，a dual-luciferase reporter assay demonstrated MAPK8，which predicted by Targetscan7.2，was a direct target gene of miR-484 during preadipocyte differentiation，and the results were confirmed by RT-qPCR and Western blot. Results：The miR-484 was down-regulated during HPA differentiation. The miR-484 inhibited the proliferation and differentiation in HPA，and silencing miR-484 had the opposite effects. A dual-luciferase reporter assay demonstrated MAPK8 was a direct target gene of miR-484. Additionally，over expression of MAPK8 could reserve the negative effect of miR-484 on differentiation and proliferation of pre-adipocytes. Conclusion：MiR-484 could inhibit HPA differentiation and proliferation by targeting MAPK8.

Abstract:Objective：This study aims to determine whether fructose Sirtuin 5（SIRT5）expression is associated with fluorine 18（18F）fluorodeoxyglucose（FDG）accumulation，glucose transporter 1（GLUTI）expression and clinical parameters in patients with colorectal cancer（CRC）. Methods：Seventy-eight patients with CRC underwent 18F-FDG combined positron emission tomography and computed tomography（PET/CT）were analyzed. The relationship between maximum standardized uptake（SUVmax）and expression of SIRT5 and GLUT1 was analyzed，and the clinical prognosis were analyzed. The effects of SIRT5 on glycolysis and HIF1α transcriptional activity in colorectal cancer cells were investigated by using CRISPR/Cas9 technique to knock-out SIRT5. Results：The expression of SIRT5 was higher in CRC tissues when compared with in para-carcinoma tissues（P < 0.01）. The prognosis was poor in patients with high SIRT5 expression（P < 0.01）. SUVmax and SIRT5 expression were higher in patients with poorly differentiated CRC than in those with well to moderately differentiated CRC（18.18±4.06 vs. 12.72±2.60，P < 0.01；2.14±0.74 vs. 1.10±0.77，P < 0.01）. There was a positive relationship between SIRT5 expression and SUVmax（Spearman correlation coefficient=0.648，P < 0.05）. Konck-out SIRT5 gene in CRC cells led to a significant decrease in GLUT1 expression，18F-FDG uptake，and HIF1α transcriptional activity. Conclusion：SIRT5 might inhibit 18F-FDG uptake via the HIF1α/GLUT1 pathway in CRC. SIRT5 might be a potential target for the treatment of CRC.

Abstract:Objective：This study aims to analyze the correlation between plasma exosomal miR-409-3p and perioperative neurocognitive disorders （PND） after coronary artery bypass grafting. Methods：A total of 76 patients undergoing coronary artery bypass graft surgery were enrolled in this study. Neuropsychological test assessments were performed 1 day before and 7 days after surgery，and the patients were divided into PND group（n=24） and non-PND group（n=52） according to the evaluation results. The plasma exosomes of all patients were extracted，and were identified by transmission electron microscopy，particle size analysis，and Western blot. The qRT-PCR was used to detect the expression level of exosomal miR-409-3p. Logistic regression analysis was used to evaluate the risk factors for PND. Results：There were statistical differences between the two groups in age，operation time and education years. The expression of plasma exosomal miR-409-3p in PND patients was higher than that in non-PND patients. Age，operation time，and plasma exosomal miR-409-3p were independent risk factors for PND. Conclusion：The highly expressed plasma exosomal miR-409-3p can be used as a new molecular marker for PND in patients undergoing coronary artery bypass graft surgery.

Abstract:Objective：This study was designed to investigate whether Kruppel-like factor 2 （KLF2） can play an important role in acute coronary syndrome（ACS）by regulating inflammatory response，providing a potential treatment for myocardial infarction in the future. Methods：The expressions of KLF2 mRNA and protein in peripheral blood mononuclear cells of ACS group（n=123）and control group（n=45）were determined by quantitative real time PCR and Western blot. Flow cytometry was used to detect the expressions of molecules on peripheral T cells of ACS group. The Gensini score of ACS patients were calculated，and the correlation between KLF2 and Gensini score in ACS patients was analyzed. Results：The expression of KLF2 protein and mRNA levels of peripheral blood mononuclear cells in ACS group were significantly lower than those in the control group. The expressions of CD62L and CCR7 on peripheral T cells in ACS group were lower than those in control group，while the expression levels of CXCR3 and CD44 were significantly higher than those in control group，and KLF2 was negatively correlated with Gensini score. Conclusion：KLF2 gene is significantly underexpressed in ACS patients，and may participate in the inflammatory response of ACS by regulating the levels of CD62L，CCR7，CXCR3 and CD44 on the surface of T cells，which may provide a new idea for the treatment of ACS.

Abstract:Objective：This study aims to investigate the predictive value of first-time high-sensitivity troponin T（hs-TnT）in patients with acute myocarditis to receive extracorporeal membrane oxygenation（ECMO）support. Methods：A retrospective study was conducted for 98 patients with acute myocarditis. They were divided into ECMO group（n=32） and non-ECMO group（n=66）. Baseline data，level of serum hs-TnT and N-terminal pro-B type natriuretic peptide （NT-proBNP） were collected and compared. Results：Total 98 patients were finally enrolled. The levels of serum hs-TnT- and NT-proBNP- in ECMO group［3 580（1 656，8 935）ng/L，10 577（3 701，24 164）pg/mL］were significantly higher than those in non-ECMO group［630（180，1 496）ng/L，565（240，3 736）pg/mL］ ，respectively（P < 0.001）. Logistic regression analysis showed first-time hs-TnT（OR=1.290，95%CI：1.024~1.626，P=0.031）and NT-proBNP level（OR=1.081，95%CI：1.019~1.146，P=0.009） were independently risk factors of ECMO therapy. Conclusion：The first-time hs-TnT and NT-proBNP level in patients with acute myocarditis could be used to predict whether the patient needs ECMO support.

Abstract:Objective：This study aims to assess the cardiac structure and function in patients of heart failure with mid-range ejection fraction（HFmrEF）by speckling tracking echocardiography after 3 months sacubitril/valsartan treatment. Methods：A total of 35 patients with HFmrEF（EF range：40%~49%）and New York Heart Association（NYHA）class Ⅱ~Ⅲ were enrolled in this study from Jul 2020 to Jan 2021. In these patients，echocardiographic assessments were performed at the baseline and after 3 months sacubitril/valsartan therapy. The left ventricular（LV） global longitudinal strain（LVGLS） and the time to the peak strain were evaluated by using speckling tracking，the LV end-diastolic volume index（LVEDVI），LV end-systolic volume index（LVESVI），LV ejection fraction（LVEF）and left atrial volume index（LAVI）were acquired by Simpson’s method. Color and tissue Doppler ultrasound were utilized to get the ratio of early transmitral Doppler velocity/early diastolic annular velocity（E/e’）. The level of serum amino-terminal pro-brain natriuretic peptide （NT-proBNP） was determined by electrochemiluminescence immunoassay method. Results：After the treatment，the NYHA function capacity class improved significantly（P=0.008），and the median NT-proBNP concentration decreased significantly（P < 0.001）. The LVGLS increased markedly compared with the baseline，and the time to peak longitudinal strain reduced significantly than the baseline（P < 0.001）. There was a modest improvement in the LVEF（P=0.001）. The LVEDVI and LVESVI decreased significantly compared with the baseline（P < 0.001）. However，there was no significant change for LAVI and the E/e’（both P > 0.05）. Conclusion：In HFmrEF patients，3 months sacubitril/valsartan therapy could induce benefit on the left cardiac structure and function. Strain analysis based on speckling tracking echocardiography may act as a useful tool for assessment of the left ventricle remodeling in these patients.

Abstract:Objective：This retrospective study aims to compare the performance for managing acute left colonic malignant obstruction by emergency surgery（ES） or stenting as a bridge to surgery（BTS）. Methods：The medical records were collected from May 2013 to December 2017 in two tertiary hospitals in Eastern China. Clinical success was defined as resumption of intestinal function for 30 days without morbidity or mortality after surgical procedure. All demographics，intervention procedures and follow-up were analyzed for short-term and long-term outcomes. Risk factors for long-term survival were discussed as well. Results：BTS group showed better short-term performance，including less intraoperative decompressive intervention（85.1% vs. 69.6%，P=0.045），more complete decompression（64.2% vs. 27.5%，P＜0.001），more primary anastomosis（65.7% vs. 17.4%，P＜0.001），less temporary and permanent stoma（34.3% vs. 82.6%，13.4% vs. 58.7%，both P＜0.001），less intensive care unit requirement（10.4% vs. 27.5%，P=0.011），less intraoperative complications（3.0% vs. 13.0%，P=0.031）and reduced 30-day mortality（0 vs. 8.7%，P=0.028）. No significant difference was observed about clinical success（73.1% vs. 63.8%，P=0.240），overall mortality（53.7% vs. 64.4%，P=0.247）or long-term survival（52.0 months vs. 35.0 months，P=0.121）. TNM stage Ⅳ，permanent stoma and postoperative complication were the independent risk factors for long-term survival. Conclusion：BTS is a safe and effective therapeutic option for acute left colonic malignant obstruction，without adverse effect on long-term survival. It significantly improves short-term outcomes by reducing perioperative complications，30-day mortality and permanent stoma. More prospective studies are necessary to confirm the clinical findings.

Abstract:Objective：This study aims to investigate the feasibility of ultra-short echo time（UTE） imaging for assessing the cartilage endplate（CEP）damage. Methods：MR imaging of 85 CEPs from 36 patients with low back pain was performed at 3T MR using UTE imaging and routine lumbar MR sequences. UTE image of CEP was postprocessed into subtracted UTE image. Signal to noise ratio（SNR）and contrast to noise ratio（CNR）were calculated to evaluate the subtracted UTE image quality. Based on the subtracted UTE images and Rajasekaran grading，the endplates were classified into six grades according to the damage of CEP and bony endplate. Two musculoskeletal radiologists assessed the grade of endplate damage based on the subtracted UTE images. Agreement between two radiologists was determined using Cohen’s kappa analysis. The distribution of Modic change in 85 endplates were evaluated. Results：The resultant subtracted UTE image quality was confirmed by high SNR and CNR（mean SNR：33.06±2.92；mean CNR：9.4±2.08）. Six grades of endplates were evaluated by two radiologists in substantial agreement with Cohen’s kappa of 0.816. Modic changes were found in 34 of 85 endplates. Cochran-Armitage analysis showed linear trend between the degree of endplate damage and Modic change（P < 0.000 5）. Conclusion：UTE imaging might be considered as an effective tool to assess the CEP damage in clinic. The distribution of Modic changes shows that the more serious the damage of endplate，the more likely Modic changes appear.

Abstract:Objective：This study is proposed to clarify the biological conversion process of p，p’-dichloro-diphenyl-trichloroethane（DDT）metabolized by cytochrome P450（CYP）2B6. The result will provide basis for the risk assessment and prevention of persistent organic pollutant. Methods：The detection method based on gas chromatography-mass spectrometry（GC-MS/MS）was established to detect DDT in biological samples. The metabolic model in vitro was established，using recombinant enzyme CYP2B6 and p，p’-DDT. The enzyme activity was calculated by Michaelis-Menten equation. The 8-MOP as enzyme inhibitor was used to verify the metabolical ability of CYP2B6 on p，p’-DDT. Meanwhile，the metabolic model in vivo was established in SD rat（rat CYP2B1 is homologous enzymes of human CYP2B6） by tail intravenous injection of p，p’-DDT and CYP2B6 specific chemical inhibitor KR-Ⅱ. The changes of p，p’-DDT prototypes and metabolites（p，p’-DDE，p，p’-DDD）and the changes of enzyme activity were assessed in the serum（0 min，5 min，10 min，20 min，30 min）and liver microsomes. Results：A detection method for DDT was successfully established and tested. Metabolic experiments in vitro confirmed that p，p’-DDT could metabolized by CYP2B6，and the main metabolite was p，p’-DDE. Kinetic parameter Km was 15.12 μmol/L，and the Vmax of per nanomolar P450 is 12.8 nmol/min. Inhibitor 8-MOP significantly inhibited the CYP2B6 activity and metabolites p，p’-DDE content significantly decreased. After CYP2B1 was inhibited，the metabolic enzyme activity was significantly decreased and the serum p，p’-DDE and p，p’-DDD product content was lowered. Conclusion：CYP2B6 can metabolize p，p’-DDT to produce metabolites dominated by p，p’-DDE，and it should be the dominant enzyme of DDT in the human body. Considering that there are differences in the expression and activity of CYP2B6. This study can provide a basis for screening of susceptible populations exposed to DDT and the optimization of risk assessment.

Abstract:Objective：This study aims to observe the levels of atmospheric polycyclic aromatic hydrocarbon（PAH）in Nanjing，and explore the correlation between PAH and air microbial community. Methods：The concentration of PAH was determined by GC-MS，and microbial community diversity was analyzed by 16S rRNA gene sequencing. Pearson correlation analysis was conducted between the concentration of atmospheric PAH and the microbial community. Results：It was found that Phe，Fla and Pyr are the main components of atmospheric PAH. The total concentration of atmospheric PAH in 2019 was higher than that in 2020. The concentration of atmospheric PAH in autumn of 2019 was significantly higher than that in spring. At the level of phylum，the dominant phylum in both 2019 and 2020 are Firmicutes，Actinobacteria and Proteobacteria. In terms of genus，Bacillus is the common dominant bacteria of 2019 and 2020. In the correlation analysis between PAH and microbial populations，it was found that the abundance of Bacillus in Firmicutes and Micrococcus in Actinobacteria were correlated with atmospheric PAH. Conclusion：Atmospheric PAH pollution may be related to the changes of species and abundance of air microorganisms which may be potential health risks.

Abstract:As a novel gaseous signal molecule，hydrogen gas exhibits selective antioxidant effect and anti-inflammatory effect. In the medical field，hydrogen gas was originally discovered to show the antitumor effect，thereafter hydrogen has shown therapeutic potential in more than 100 diseases，including ischemic stroke. Today，the high incidence and mortality of tumor，as well as the lack of effective means of cure of tumor，have imposed a heavy burden on the medical expenditure. Therefore，how to realize tumor prevention and prolongation of survival appears to be of greater importance，and hydrogen gas is expected to play an important role in this field. In this paper，a review of the research progress of hydrogen antitumor is presented，which contains the antitumor mechanism，synergistic and attenuated effects，combined therapy，clinical research，and hydrogen administration methods.

Abstract:This review introduces new situations of drug addicts and drug treatment in China since the 21st century. It describes the mechanisms of drug addiction and the currently status of drug use，and speculates on potential targets for drug addiction treatment based on existing research advances. The advantages and limitations of traditional Chinese medicine（TCM）treatment are elaborated by introducing the herbal medicines related to addiction treatment. We cannot ignore the role of traditional Chinese medicine in drug addiction treatment.

Abstract:Advanced pancreatic cancer has a poor prognosis and a short survival，and usually can not be treated by surgery. The efficacy of radiotherapy and chemotherapy alone in advanced pancreatic cancer is limited，and the overall survival time of patients is poor. Therefore，the exploration of ablation therapy for advanced pancreatic cancer has been a research hot spot in recent years. These include radio-frequency ablation（RFA），cryoablation，irreversible electroporation（IRE），high intensity focused ultrasound（HIFU） and many other methods. Moreover，ablation combined with chemoradiotherapy and immunotherapy can form a comprehensive treatment strategy for patients with advanced pancreatic cancer，often achieve the purpose of effectively improving the survival of patients. This article reviews the current status of comprehensive treatment strategies for advanced pancreatic cancer after ablation therapy.

Abstract:Stroke is one of the major causes of disease-induced death and disability in adults，and ischemic stroke is the main type. With the maturity of thrombolysis and mechanical thrombectomy，the mortality rate of stroke has decreased year by year，but most of the survivors may develop into patients with chronic dysfunction. Unfortunately，there is a lack of clinical drugs to promote functional repair after stroke. The expression of miR-124 changes in peripheral blood and brain tissue after ischemic stroke. The miR-124 is widely involved in the processes of oxidative stress，neuroinflammation，apoptosis and neural differentiation via targeting regulatory genes and regulating pathological processes. In this paper，it was reviewed the research progress on the role and mechanism of miR-124 in cerebral ischemia injury and repair after stroke .