Aim To investigate the effect and mechanism of angiotensin Ⅱ(Ang Ⅱ)on ferroptosis in white adi-pocytes.Methods The 3T3-L1 preadipocytes were differentiated into white adipocytes by inducer stimulation.The experiment was divided into control group,Ang Ⅱ group,Ang Ⅱ+Fer-1(ferroptosis inhibitor)group and Ang Ⅱ+PFT-α(p53 inhibitor)group.Ang Ⅱ was used to treat cells.RT-qPCR and Western blot were used to detect the expression levels of ferroptosis factors and adipokines.JC-1 kit was used to detect mitochondrial membrane potential(MMP)level.Iron ion kit was used to detect intracellular iron content.Glutathione(GSH)kit was used to detect GSH content.Fer-1 and Ang Ⅱ were added to treat cells to detect the the changes of ferroptosis level.The expression of p53 and spermidine/spermine N1-acetyltransferase 1(SAT1)protein was detected.Subsequently,PFT-α and Ang Ⅱ were added to co-treat cells to detect the changes of p53 and SAT1 protein expression,and to observe the effect of inhibiting p53 expression on the expression levels of ferroptosis factors and adipokines.Results 3T3-L1 cells were successfully differentiated into white adipocytes by stimulator-induced differentiation.Ang Ⅱ induced ferroptosis in white adipocytes.RT-qPCR results showed that compared with control group,the mRNA expression of anti-ferroptosis factor glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11)and iron regulatory protein 1(IRP-1)was down-regulated in Ang Ⅱ group,and the mRNA expression of pro-ferroptosis factor acyl-CoA synthetase of long-chain family member 4(ACSL4)was up-regulated.Western blot results showed that compared with control group,the protein expression of SLC7A11 and GPX4 was down-regulated in Ang Ⅱ group,and the protein expression of ACSL4 was up-regulated.Ang Ⅱ treatment increased the content of intracellular iron ions and decreased the levels of GSH and MMP.Compared with Ang Ⅱ group,the mRNA expression of IRP-1 and SLC7A11 was up-regulated in Ang Ⅱ+Fer-1 group.Ang Ⅱ induced changes in the expression profile of adipokines in white adipocytes.Western blot results showed that compared with control group,the protein ex-pression of pro-inflammatory adipokine leptin(LEP),resistin(RETN),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)was up-regulated in Ang Ⅱ group,and the protein expression of anti-inflammatory adipokine adiponectin(AD-PN)and omentin 1(ITLN1)was down-regulated.In addition,Ang Ⅱ increased the protein expression of p53 and SAT1.Inhibition of p53 expression can improve the level of ferroptosis and adipokine expression in white adipocytes trea-ted with Ang Ⅱ.Western blot results showed that compared with Ang Ⅱ group,the protein expression of p53 and SAT1 was down-regulated in Ang Ⅱ+PFT-α group,the protein expression of SLC7A11 and GPX4 was up-regulated,and the protein expression of ACSL4 was down-regulated.The protein expression of ADPN was up-regulated in Ang Ⅱ+PFT-αgroup,and the protein expression of TNF-α,LEP and RETN was down-regulated.Conclusion Ang Ⅱ induces fer-roptosis in white adipocytes through activating the p53/SAT1 signaling pathway.

Objective To investigate the diagnostic value of serum carcinoembryonic antigen-related cell adhesion molecule 6(CEACAM6)in pancreatic cancer.Methods A total of 188 patients admitted to the Pancreas Center of the First Affiliated Hospital of Nanjing Medical University from May to December 2024 were consecutively enrolled,including 112 patients in the pancreatic cancer group and 76 patients in the benign pancreatic disease group(43 with pancreatitis and 33 with benign pancreatic tumors).Additional-ly,76 healthy individuals were included in the health control group.Serum CEACAM6 and carbohydrate antigen 19-9(CA19-9)levels were detected by ELISA and chemiluminescence immunoassay(CLIA),respectively.The receiver operating characteristic(ROC)curve was drawn to evaluate the diagnostic efficacy of serum CEACAM6 for pancreatic cancer.The positive rate of serum CEACAM6 in CA19-9-negative pancreatic cancer patients was also investigated.Results The levels of serum CEACAM6 in the pancreatic cancer group(20.3[11.1,34.0]ng/mL)were significantly higher than those in the benign pancreatic disease group(6.2[2.6,10.5]ng/mL,Z=64.1,P＜0.001)and healthy control group(0.8[0.4,4.4]ng/mL,Z=131.6,P＜0.001).The areas under the ROC curve(AUCROC),sensitivity,and specificity of CEACAM6 and CA19-9 in the diagnosis of pancreatic cancer were 0.889(95%CI:0.854-0.924)and 0.819(95%CI:0.761-0.863),81.3%and 65.2%,and 84.9%and 86.2%,respectively.The AUCROC,sensitivity,and specificity of the combined detection of the two reached 0.916(95%CI:0.875-0.946),91.1%,and 82.2%,respectively,which were better than any single indicator(P＜0.05).In addition,the positive rate of serum CEACAM6 in CA19-9-negative pancreatic canc-er patients was 83.3%,significantly higher than CEA and CA125(P＜0.01).Conclusion The detection of serum CEACAM6 is help-ful to the diagnosis of pancreatic cancer,and its combination with serum CA19-9 can improve the diagnostic efficacy of pancreatic cancer.

Objective To investigate the diagnostic value of serum carcinoembryonic antigen-related cell adhesion molecule 6(CEACAM6)in pancreatic cancer.Methods A total of 188 patients admitted to the Pancreas Center of the First Affiliated Hospital of Nanjing Medical University from May to December 2024 were consecutively enrolled,including 112 patients in the pancreatic cancer group and 76 patients in the benign pancreatic disease group(43 with pancreatitis and 33 with benign pancreatic tumors).Additional-ly,76 healthy individuals were included in the health control group.Serum CEACAM6 and carbohydrate antigen 19-9(CA19-9)levels were detected by ELISA and chemiluminescence immunoassay(CLIA),respectively.The receiver operating characteristic(ROC)curve was drawn to evaluate the diagnostic efficacy of serum CEACAM6 for pancreatic cancer.The positive rate of serum CEACAM6 in CA19-9-negative pancreatic cancer patients was also investigated.Results The levels of serum CEACAM6 in the pancreatic cancer group(20.3[11.1,34.0]ng/mL)were significantly higher than those in the benign pancreatic disease group(6.2[2.6,10.5]ng/mL,Z=64.1,P＜0.001)and healthy control group(0.8[0.4,4.4]ng/mL,Z=131.6,P＜0.001).The areas under the ROC curve(AUCROC),sensitivity,and specificity of CEACAM6 and CA19-9 in the diagnosis of pancreatic cancer were 0.889(95%CI:0.854-0.924)and 0.819(95%CI:0.761-0.863),81.3%and 65.2%,and 84.9%and 86.2%,respectively.The AUCROC,sensitivity,and specificity of the combined detection of the two reached 0.916(95%CI:0.875-0.946),91.1%,and 82.2%,respectively,which were better than any single indicator(P＜0.05).In addition,the positive rate of serum CEACAM6 in CA19-9-negative pancreatic canc-er patients was 83.3%,significantly higher than CEA and CA125(P＜0.01).Conclusion The detection of serum CEACAM6 is help-ful to the diagnosis of pancreatic cancer,and its combination with serum CA19-9 can improve the diagnostic efficacy of pancreatic cancer.

OBJECTIVE To establish a interview outline design process and quality control evaluation method based on grounded theory,providing ideas for qualitative research interview outline design in medical fields.METHODS A literature review was conducted to understand the current research status;a preliminary interview outline was developed around the research content.The triangulation method,group evaluation,expert review and pre-interview were adopted to execute the interview outline and conduct quality control.The evaluation indicators and target values were formulated(an average score for the overall quality evaluation of all indicators ≥4.5,and an average score for individual indicators ≥ 4.00)to evaluate the effect of the interview outline.Taking the research on the mechanism of physicians'prescribing behavior under the background of Diagnosis Related Groups(DRGs)payment as an example,the methodological contents of above interview outline were applied in practical research.RESULTS The interview outline included basic information and interview questions.The interview questions were divided into three parts:influencing factors survey,promoting and hindering factors of standardizing physician prescription behavior,and communication,with a total of 12 questions.After being reviewed by members of the research group,experts review and pre-interview,a total of 9 people participated in the quality control evaluation of the interview outline.The overall evaluation score was 4.94(＞4.50),and the average score of each indicator was greater than 4.00,indicating that the quality of the outline met the requirements for the interview and could be used for the formal interview.CONCLUSIONS The established interview outline design and quality control method based on grounded theory provides ideas for the qualitative research interview outline design in the medical field,and lays the foundation for further using grounded theory to study the influencing factors and mechanisms of physician prescription behavior under the DRG background.

Aim To investigate the effect and mechanism of angiotensin Ⅱ(Ang Ⅱ)on ferroptosis in white adi-pocytes.Methods The 3T3-L1 preadipocytes were differentiated into white adipocytes by inducer stimulation.The experiment was divided into control group,Ang Ⅱ group,Ang Ⅱ+Fer-1(ferroptosis inhibitor)group and Ang Ⅱ+PFT-α(p53 inhibitor)group.Ang Ⅱ was used to treat cells.RT-qPCR and Western blot were used to detect the expression levels of ferroptosis factors and adipokines.JC-1 kit was used to detect mitochondrial membrane potential(MMP)level.Iron ion kit was used to detect intracellular iron content.Glutathione(GSH)kit was used to detect GSH content.Fer-1 and Ang Ⅱ were added to treat cells to detect the the changes of ferroptosis level.The expression of p53 and spermidine/spermine N1-acetyltransferase 1(SAT1)protein was detected.Subsequently,PFT-α and Ang Ⅱ were added to co-treat cells to detect the changes of p53 and SAT1 protein expression,and to observe the effect of inhibiting p53 expression on the expression levels of ferroptosis factors and adipokines.Results 3T3-L1 cells were successfully differentiated into white adipocytes by stimulator-induced differentiation.Ang Ⅱ induced ferroptosis in white adipocytes.RT-qPCR results showed that compared with control group,the mRNA expression of anti-ferroptosis factor glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11)and iron regulatory protein 1(IRP-1)was down-regulated in Ang Ⅱ group,and the mRNA expression of pro-ferroptosis factor acyl-CoA synthetase of long-chain family member 4(ACSL4)was up-regulated.Western blot results showed that compared with control group,the protein expression of SLC7A11 and GPX4 was down-regulated in Ang Ⅱ group,and the protein expression of ACSL4 was up-regulated.Ang Ⅱ treatment increased the content of intracellular iron ions and decreased the levels of GSH and MMP.Compared with Ang Ⅱ group,the mRNA expression of IRP-1 and SLC7A11 was up-regulated in Ang Ⅱ+Fer-1 group.Ang Ⅱ induced changes in the expression profile of adipokines in white adipocytes.Western blot results showed that compared with control group,the protein ex-pression of pro-inflammatory adipokine leptin(LEP),resistin(RETN),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)was up-regulated in Ang Ⅱ group,and the protein expression of anti-inflammatory adipokine adiponectin(AD-PN)and omentin 1(ITLN1)was down-regulated.In addition,Ang Ⅱ increased the protein expression of p53 and SAT1.Inhibition of p53 expression can improve the level of ferroptosis and adipokine expression in white adipocytes trea-ted with Ang Ⅱ.Western blot results showed that compared with Ang Ⅱ group,the protein expression of p53 and SAT1 was down-regulated in Ang Ⅱ+PFT-α group,the protein expression of SLC7A11 and GPX4 was up-regulated,and the protein expression of ACSL4 was down-regulated.The protein expression of ADPN was up-regulated in Ang Ⅱ+PFT-αgroup,and the protein expression of TNF-α,LEP and RETN was down-regulated.Conclusion Ang Ⅱ induces fer-roptosis in white adipocytes through activating the p53/SAT1 signaling pathway.

Depression is a common mental illness in adolescents, and some patients do not respond well after medication, which may be partly related to vitamin D deficiency and insufficient calcium intake. This paper reports a 15-year-old patient with depression, whose condition was still unstable and the effect was not good despite routine use of antidepressant drugs and psychological intervention. After adequate supplementation of vitamin D and calcium, the patient's depression improved significantly, and the follow-up for 4 months, the condition was stable and did not recur.

Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Rats ; Animals ; Urinary Bladder Neck Obstruction/pathology* ; Survivin/genetics* ; Urinary Bladder/pathology* ; Fibrosis

Objective:To analyze the correlation between sleep midpoint and sleep quality in insomnia patients with type 2 diabetes mellitus (T2DM).Methods:By adopting current situation investigation research, total of 150 T2DM patients hospitalized in the Department of Endocrinology, the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from November 2021 to July 2022 were selected as the research objects. The general information questionnaire, Pittsburgh Sleep Quality Index (PSQI), anxiety scale (SAS) and Depression Scale (SDS) were used to investigate, and then analysis the datum.Results:Among 150 T2DM insomnia patients, 41 cases (27.33%) were in the early midpoint sleep group, 37 cases (24.67%) were in the middle midpoint sleep group, and 72 cases (48.00%) were in the late midpoint sleep group. There were significant differences in the distribution of sex, age and BMI level among different sleep midpoint groups ( χ2=7.24, 13.36, 15.93, all P<0.05). The scores of time to fall asleep at the midpoint of sleep in the 3 groups were (2.12 ± 1.25), (2.65 ± 0.79), (2.33 ± 1.02), the difference was significant ( F=2.14, P<0.05); the daytime disability scores in the 3 groups were (1.39 ± 1.36), (2.16 ± 1.12), (1.85 ± 1.32), the difference was significant ( F=3.17, P<0.05). Logistic regression analysis of disorder showed that the time to fall asleep ( OR=4.922, P<0.05) and daytime disability ( OR=4.043, P<0.05) had significant influence to the middle midpoint of sleep group when the early midpoint of sleep group as the control, while the male ( OR=2.182, P<0.05), 50 - 70 years old ( OR=5.005, P<0.05) and BMI over fat side ( OR=3.488, P<0.05) had significant influence to the late midpoint of sleep group. Conclusions:Medical staff should pay attention to the sleep quality of T2DM patients, pay attention to the sleep midpoint of patients, and improve patients′cognition of healthy sleep patterns.

Purpose: No consensus exists about the causal relationship between vitamin D (VD) and male factor infertility due to heterogeneity and confounding factors even in randomized controlled trials (RCTs). This study aimed to investigate the causal association between 25 hydroxyvitamin D (25OHD) levels and male factor infertility through Mendelian randomization (MR) and provide complementary information for optimization of future RCTs. Materials and Methods: Two-sample MR analyses with four steps were performed. Single-nucleotide polymorphisms (SNPs) for VD were extracted from 417,580 Europeans in the UK Biobank, and the summary-level data of male factor infertility (825 cases and 85,722 controls) were extracted from the FinnGen. Results: Totally 99 SNPs robustly associated with the 25OHD were included, and a 1-unit increase in genetically predicted natural-log transformed 25OHD levels was associated with decreased risk of male factor infertility (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.44–0.89; p=0.010), which was consistent in all three sensitivity analyses (MR-Egger, weighted median, and weighted mode methods). The conclusion still stands after removing SNPs which explained more variation in the male factor infertility than the 25OHD (OR, 0.61; 95% CI, 0.42–0.88; p=0.009; n=62), and which were associated with confounders (body mass index, type 2 diabetes, smoking, and coronary artery diseases) of male factor infertility (OR, 0.58; 95% CI, 0.39–0.85; p=0.005; n=55). Conclusions VD supplement to increase serum 25OHD levels may be clinically beneficial for male factor infertility in the general population. The well-designed RCTs should be performed in priority to address this question.