Abstract:Objective：The current study aims to investigate the effect of 4 - hydroxysalicylaniline（HDS）on the proliferation and apoptosis of T-lymphoblastic leukemia cells，Jurkat and Hut-78，in vitro and in vivo. Methods：In vitro，HDS was used to treat Jurkat and Hut-78 cells with different concentration gradients. The CCK-8 assay and colony formation assay were used to detect the effect of HDS on cell proliferation. Cell cycle changes were detected by flow cytometry，and the expression levels of cycle-related proteins were detected by Western blot. The apoptosis level was detected by flow cytometry，and the expression levels of apoptosis-related proteins were detected by Western blot. DNA damage was detected by γ- H2AX immunofluorescence staining，and the expression levels of DNA damage related proteins were detected by Western blot. In vivo，the mouse T - cell lymphoblastic leukemia tumor model was constructed by subcutaneous injection of Jurkat cells，and HDS was injected to observe the effect of drugs on tumor volume and body weight of mice. HE staining was used to observe the morphological changes of tumors after 13 days of HDS creatment. Immunohistochemical staining of Ki67 and γ -H2AX protein was used to analyze the effect of drugs on cell proliferation and DNA damage in tumors. Results：In Jurkat and Hut-78 cell lines，HDS could induce cell cycle arrest at S phase，induce cell apoptosis，and block DNA damage repair through phosphorylation of CHK1/CHK2 signaling pathway，both in vitro and in vivo. HDS inhibited T-cell lymphoblastic leukemia tumors，and it had no obvious toxicity to mice. Conclusion：HDS can be used as a potential anti - T - celllymphoblastic leukemia drug. The effect of HDS on T-cell lymphoblastic leukemia may be accomplished by interfering cell cycle and apoptosis，and DNA damage repair through CHK1/CHK2 signaling pathway.

Abstract:Objective：To investigate the effects of bisphenol F（BPF）on the tryptophan（TRP）and tyrosine（TYR）- derived neurotransmitter metabolism in the liver，elucidating the metabolic characteristics of the neurotransmitter disturbance elicited by BPF. Methods：The SPF C57BL/6J mice were administrated with different concentrations of BPF[40，400，4 000 μg/（kg·d）]by gavage for 30 consecutive days，and the ultra -high -performance liquid chromatography -tandem mass spectrometry（UHPLC -MS/MS）assay was used to examine the characteristics and levels of TRP and TYR - derived neurotransmitters in the mouse livers after BPF exposure. Results：The levels of TRP and TYR in mouse livers were significantly decreased after BPF exposure ，and 5-hydroxytryptamine （5 - HT）was significantly decreased，while kynurine（KYN），another key metabolite of the TRP metabolic pathway，significantly increased. For the TYR metabolism，TYR and its metabolite dopamine（DA）obviously decreased；meanwhile，other excitatory neurotransmitters，such as glutamate（GLU），γ - aminobutyric acid（GABA），aspartic acid（ASP）and glycine（GLY），dramatically decreased. Conclusion：BPF exposure can decrease the levels of TRP，TYR and several other excitatory neurotransmitters，and promote the metabolic transformation of 5-HT into KYN in the TRP pathway. Therefore，the current study on the metabolism of hepatic neurotransmitters provides novel evidence for the liver and neuropsychiatric diseases caused by continuous exposure to BPF.

Abstract:Objective：The current study aims to investigate the effect and molecular mechanism of dapagliflozin on epithelial-mesenchymal transformation and fibrosis of renal tubular epithelial cells in diabetic kidney disease. Methods：Human renal tubular epithelial cells HK-2 were cultured in vitro and divided into control group，high glucose group，low dose dapagliflozin + high glucose group and high dose dapagliflozin +high glucose group. The expression levels of Rffl were detected by Western blot and RT-PCR， respectively. The expression levels of epithelial cadherin（E -cadherin），α- smooth muscle actin（α-SMA），Fibronectin，transforming growth factor β1（TGF-β1）and signal transducer and activator of transcription 1（STAT1）were detected by Western blot. After Rffl was overexpressed in HK -2 cells，the expression levels of E -cadherin，α- SMA，Fibronectin，TGF -β1 and STAT1 were detected by Western blot. Results：The expression level of Rffl was significantly lower in the high glucose group than in the control group，and the expression of Rffl was increased after adding dapagliflozin. Compared with the control group，the expression level of E-Cadherin in the high glucose group was decreased，while the expression level of Fibronectin and α-SMA was increased. After Rffl was overexpressed in cells，the expression level of E-Cadherin was increased，while the expression levels of Fibronectin and α-SMA were decreased. Compared with high glucose group，the expression levels of E-Cadherin in low-dose dapagliflozin+high glucose group and high-dose dapagliflozin + high glucose group were increased，but the expression levels of Fibronectin and α- SMA were decreased in a dose-dependent manner. Compared with the control group，the expression levels of STAT1 and TGF-β1 were increased in the high glucose group，but significantly decreased after overexpression of Rffl or addition of dapagliflozin. Conclusion：Dapagliflozin inhibits STAT1/ TGF-β1 signaling pathway by up-regulating Rffl expression，and improves epithelial-mesenchymal transformation and fibrosis of renal tubular epithelial cells in diabetic kidney disease.

Abstract:Objective：The current study aims to analyse the correlation between early inflammatory factor changes and severity as well as prognosis in elderly patients with sepsis. Methods：Retrospective analysis of the clinical data of 135 sepsis patients admitted to the First Affiliated Hospital of Nanjing Medical University between September 2020 and March 2022. According to age，patients were divided into the elderly group（≥ 65 years old）and the young adult group（＜65 years old）. The elderly patients（≥ 65 years old）with sepsis were divided into septic shock group and septic group according to whether they had septic shock，and divided into survival group and death group according to the 28-day mortality rate. The inflammatory factor changes were compared between the above sub- groups. The correlations between white blood cell（WBC），procalcitonin（PCT），C-reactive protein（CRP），interleukin（IL）-2，IL-4，IL-6， IL-10，tumor necrosis factor（TNF）-α，interferon（IFN）-γ，platelet（PLT），lymphocyte（Lym）and APACHE Ⅱ score in elderly patients with sepsis were analyzed by Spearman correlation analysis. ROC curve was used to compare above - mentioned indexes in the judgement of 28-day mortality rate in elderly patients with sepsis. Results：In patients with sepsis，the PLT and Lym in the elderly group were significantly lower than those in the young adult group，and APACHE Ⅱ score in the elderly group was significantly higher than that in the young adult group. In elderly patients with sepsis，the PCT，CRP，APACHE Ⅱ score in septic shock group were significantly higher than those in the septic group，and PLT in septic shock group was significantly lower than that in the septic group；and APACHE Ⅱ score in the survival group was significantly lower than that in the death group. IL-10 was positively correlated with APACHE Ⅱ score，and PLT was negatively correlated with APACHE Ⅱ score. According to ROC curve and area under the curve，the APACHE Ⅱ score alone，combination of all indicators except APACHE Ⅱ score and the combination of all indicators could predict the 28-day mortality rate of elderly patients with sepsis. Conclusion：In elderly patients with sepsis，the lower the PLT and the higher IL - 10 in the early stage，the worse the condition and prognosis of the elderly patients with sepsis. The combination of multiple indicators to predict 28-day mortality in elderly patients with sepsis has a higher accuracy than single indicator.

Abstract:Objective：The current study aims to explore the correlation between Chinese visceral adiposity index（CVAI）and cognitive impairment（CI），and further to analyze the correlation between CVAI and CI under different age levels，providing evidence for accurately evaluating the relationship between CVAI and CI，and seeking for new factors available for intervention associated with CI. Methods：The CHARLS database was used in the current study. The baseline data of 2011 and 2015 were collected，including gender，age，education level，alcohol consumption，smoking history，body mass index，and biochemical indicators. Logistic regression analysis was used to analyze the correlation of CVAI and CI，according to difterent age stratification. Results：①A total of 12 102 subjects were included in the curreut study，1 295（10.7%）subjects had CI. ② There was a correlation between CVAI and CI in people aged 65 and above（P ＜ 0.05），but no significant correlation between CVAI and CI in people aged below 65（P ＞ 0.05）；③The best cut- off value of CVAI for CI was 161.94. According to the cut-off value，all subjects was divided into high CVAI group（CVAI≥161.94）and low CVAI group（CVAI＜161.94）. ④ Age was positively correlated with CI（OR=2.24，95% CI：1.66-3.03），education level was negatively correlated with CI（OR=0.71，95%CI：0.53-0.94），and high CVAI was correlated with CI in people aged 65 and above（OR= 1.91，95%CI：1.24-2.93）. Conclusion：CVAI，age and education were correlated with CI. High CVAI is a risk factor for CI in people 65 years and older.

Abstract:Objective：The current study aims to explore the role of serum soluble growth stimulation expressed gene 2（sST2）in evaluating the severity of connective tissue disease associated pulmonary arterial hypertension（CTD - PAH）based on simplified risk stratification. Methods：A total of 48 patients with CTD-PAH diagnosed by right heart catheterization（RHC）were included from the Departments of Rheumatology，the First Affiliated Hospital of Nanjing Medical University between Jan 2017 and Nov 2021. Baseline clinical evaluation，laboratory index，RHC parameters and treatment regimen were collected. Pearson and analysis linear regression were used for the correlation between clinical characteristics of CTD-PAH and sST2 level. A receiver operating characteristics（ROC） curve assessed the diagnostic value of sST2 in assessing low risk and intermediate-high risk CTD-PAH patients. Results：CTD-PAH patients in intermediate -high risk group was higher in sST2 level than low risk group[45.97（30.24，75.68）ng/mL vs. 29.36（20.89， 41.25）ng/mL，P=0.006]. ROC curve analysis showed that sST2≥45.56 ng/mL could identify intermediate-high risk CTD-PAH patients with a sensitivity and specificity of 56% and 91%，respectively. Conclusion：The sST2 is significantly associated with parameters that can reflect disease severity of CTD -PAH，and the sST2 level is signficantly higher in intermediate - high risk group than in low risk group. The measurement of sST2 may serve as a prognostic biomarker of CTD-PAH patients.

Abstract:Objective：The current study aims to compare the similarities and differences between untargeted and targeted metabolomics in the detection of biomarkers of gestational diabetes mellitus（GDM）. Methods：Serum samples were collected from 20 patients with GDM and 20 normal pregnant women. Untargeted metabolomics and targeted metabolomics analyses were performed at the same time to compare the quality control results，metabolite detection and diagnostic efficacy between the two technologies. Results：The quality control of both techniques was good，and the detection system of untargeted metabolomics was more stable. The orthogonal-partial least squares-discriminant analysis model showed that the sample distribution trend of targeted metabolomics could better differentiate patients with GDM. Comparing the types of metabolites detected by the two methods，the untargeted metabolomics method detected 639，mainly lipids，while the target metabolomics method only detected 268，mainly amino acids and polypeptide analogues. Citric acid detected by targeted metabolomics had the highest diagnostic efficacy with an area under the curve of 0.983. Conclusion：Both technologies can screen out biomarkers with certain diagnostic efficiency，untargeted metabolomics covers a wider range of potential biomarkers，while targeted metabolomics can screen out biomarkers with higher diagnostic efficiency. The two methods have complementary advantages in screening biomarkers.

Abstract:Objective：To investigate the clinical characteristics in pediatric patients with acute lymphoblastic leukemia（ALL） during induction period，analyze the risk factors of severe infections，in order to provide theoretical basis for clinical intervention. Methods：A retrospective analysis was conducted for the clinical data of 188 pediatric patients underwent CCCG-ALL-2020 protocol with newly - diagnosed ALL from June 2020 to June 2022 in the Affiliated Children’s Hospital of Nanjing Medical University. The distribution of infections，pathogenic bacteria and susceptible factors of severe infections were analyzed during induction period. Results：The incidence of infection among pediatric patients with ALL during induction period was 95.7%（180/188）with unknown infections being the most common（28.4%），followed by upper respiratory tract infections（23.6%）and lower respiratory tract infections （16.9%）. Forty - eight cases（26.7%）of the patients developed severe infections，while 23.8%（43/180）experienced micro - biographically documented infections，in which Gram-negative and Gram-positive bacteria were equally represented. The duration of hospitalization，hospitalization expenses and antibiotic cost per unit body surface area were significantly greater in severe infection group，compared with the non - severe infection group（P ＜ 0.05）. Medium - high risk（OR=2.804，95%CI：1.234-6.375，P=0.014）， serum albumin ＜35 g/L（OR=4.708，95%CI：2.067-10.726，P=0.001）and duration of agranulocytosis ＞7 days（OR=3.697，95%CI： 1.393-9.816，P=0.009）were ascertained as independent risk factors for severe infection during induction period. Conclusion：Infection was most frequently observed during induction period of ALL. Independent risk factors for severe infections included medium-high risk， serum albumin ＜ 35 g/L and duration of agranulocytosis ＞7 days. It is imperative to implement appropriate preventive measures.

Abstract:Objective：To construct hybrid immune-radiomic（ImRad）phenotypes of clear cell renal cell carcinoma（ccRCC）based on ensemble machine learning（ML）and contrast - enhanced CT，and to investigate its predictive value for survival. Methods：The clinical，CT imaging and gene-expression information of 113 ccRCC patients were collected from TCGA database. Radiomic features were extracted from whole tumor. ImRad predictors were constructed on tumor immune infiltration，tumor mutational burden，immune exhaustion gene expression after feature selection based on ensemble ML. Further，the predictive value of ImRad for overall survival （OS）was assessed using multivariate Cox regression analysis. Results：Among the 30 ImRad contructed by ensemble ML and validated by 5 folds cross validation，Naive Bayes algorithm achieved the generally best performance（area under the curve：0717- 0.956）. Clinicopathologic immune comprehensive model on predicting OS achieved the best performance，surpassing single modality indicators based on clinical，pathological and ImRad. Among ImRad features，Rad-Mast_cells_activated was one of eight independent predictive factors for patients’prognosis. Conclusion：CT radiomics based on ensemble ML can predict immune microenvironment and improve the prediction efficiency of postoperative survival of ccRCC.

Abstract:Objective：To explore the value of extracellular volume fraction（ECV）measured by dual-energy computed tomography （DECT）in differentiating benign and malignant intraductal papillary mucinous neoplasms（IPMN）. Methods：A total of 57 patients with IPMN confirmed by surgical pathology and underwent DECT examination within one month before the operation were retrospectively collected between June 2018 and December 2021. According to pathological results，the patients were divided into benign group（28 cases）and malignant group（29 cases），and the iodine concentration（IC）of pancreatic parenchyma within 1 cm around the lesions and abdominal aorta on the same picture in the delayed-phase were measured respectively，and the value of DECT- ECV was calculated according to the formula：（IC_pancreas/IC_{abdominal aorta}）×（1-Hematocrit）. The clinical and imaging data of the two groups were analyzed by univariate analysis and multivariate logistic regression analysis to determine the independent risk factors，and the imaging model，clinical model and imaging combined clinical model were constructed respectively. The performance of each model was evaluated according to the area under curve（AUC）under the receiver operating characteristic（ROC）curve，and the diagnostic efficency of each model was compared by Delong test. Results：Multivariate analysis showed that the DECT-ECV，the elevated level of carbohydrate antigen（CA）19-9，and the history of acute pancreatitis（AP）were independent risk factors for differentiating benign andmalignant IPMN. The AUC of imaging model（DECT-ECV），clinical model（the elevated level of CA19-9 and the history of AP），and imaging combined clinical model（DECT-ECV，the elevated level of CA19-9 and the history of AP）in diagnosing malignant IPMN were 0.808，0.759，and 0.884，respectively. The diagnostic efficacy of imaging combined clinical model was significantly higher than that of clinical model. Conclusion：DECT-ECV of the pancreas parenchyma around the lesions may differentiate benign and malignant IPMN， and provide a certain reference for clinical treatment.

Abstract:Parkinson’s disease（PD）is a neurodegenerative disease with complex pathogenesis and variable clinical manifestations. However，there are still many challenges in the pathogenesis and early diagnosis. Recently，positron emission tomography -magnetic resonance（PET/MR）has emerged as a truly multi - modal imaging tool，which can precisely extract and combine physiological and metabolic information in different time and space，thereby enrich imaging basis for the research of PD from molecular level to clinical diagnosis and treatment.

Abstract:Uterine malignant tumors mainly include cervical cancer and endometrial cancer，which are the second and third most common female malignant tumors in China，respectively. The mortality of uterine malignant tumors is increasing by years，and the patients tend to be younger. In order to achieve individualized and accurate treatment，accurate staging of uterine lesions and high - quality therapeutic evaluation are needed. Positron emission tomography（PET）imaging of uterine malignant tumors，including glucose metabolism，cell proliferation，estrogen receptor，somatostatin receptor，hypoxia imaging and fibroblast activation protein inhibitor imaging，has significant advantages in tumor staging，monitoring response to targeted therapy，and early identification of chemoradiotherapy resistance. It has become a hot research topic in diagnosis and treatment of cervical and endometrial cancer.

Abstract:Exercise is an important component of diabetes management and plays a positive role in the prevention and treatment of diabetic kidney disease. Exercise reduces the albuminuria and improves renal outcomes in patients with diabetes，which is independent of blood glucose control. Previous studies have shown that exercise can improve renal function by improving glucose homeostasis and endothelial cell function，reducing oxidative stress and inflammation，regulating renin -angiotensin -aldosterone system and biological action of actin. Recommended types of exercise include aerobic exercise，resistance exercise，combination exercise and flexibility exercise. Appropriate exercise methods should be selected according to individual condition in clinical practice.

Abstract:With the gradual acceleration of China’s aging society，the incidence rate of various cardiovascular diseases is increasing， including chronic heart failure，myocardial infarction，and hypertension，etc. There is still a lack of effective prevention measures. More and more studies have found that the central nervous system has an inseparable interaction with the regulation of cardiovascular physiological functions. Among them，neurons and various cytokines in the paraventricular nucleus（PVN）of the hypothalamus participate in the regulation of cardiovascular activities，which is a key regulatory center for regulating cardiovascular activities. This article aims to summarize and conclude the recent research progress on the role and mechanism of PVN in regulating cardiovascular activity.

Abstract:Sirolimus（SRL）has been widely used to treat vascular anomalies in recent years. The routine therapeutic drug monitoring for SRL is required to ensure efficacy and prevent adverse effects，due to its narrow therapeutic window and large intra- and inter - individual variability in pharmacokinetics. This article reviewed the analytical methods for SRL blood concentration and the comparison studies between different assays，and discussed the target blood concentration range of SRL in vascular anomalies. The analytical methods for determination of SRL include immunoassays and liquid chromatography-based methods. Immunoassays exhibit significant positive bias，compared to chromatography. Liquid chromatography tandem mass spectrometry is regarded as the“gold standard”in most clinical labs. Generally，goal SRL blood concentrations maintain at 5-15 ng/mL or 10-15 ng/mL. However，there are several classifications of vascular anomalies，and treatment of SRL in these diseases is complicated，and no guidelines for the implementation of therapeutic drug monitoring can be adhered. Future investigations are needed to obtain a more high-level evidence- based medical evidence to guide the therapeutic monitoring and individualized medication of SRL