Objective:To investigate the influence and mechanisms of metformin on the proliferation and apoptosis of human keloid fibroblasts (Fbs).Methods:This study was an experimental research. The keloid tissue was collected from 7 keloid patients (2 males and 5 females, aged 20-65 years, with a disease course of more than 1 year) who underwent keloid excision surgery at the Department of Plastic, Cosmetic and Maxillofacial Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from September 2020 to September 2023. The primary Fbs were isolated and cultured, and cells from passages 3 to 6 were used for experiments. The cells were divided into control group and metformin group, and were cultured in complete medium. The medium for metformin group was supplemented with metformin at a final molarity of 60 mmol/L. The cell counting kit-8 was used to assess the proliferation activity of cells in two groups after 12 and 24 hours of culture, and the proliferation inhibition rate of cells in metformin group after 12 and 24 hours of culture was calculated, with a sample size of 6. The apoptosis detection kit was used to detect the apoptotic distribution of cells in control group after 0 hour (immediately) of culture and in metformin group after 12 and 24 hours of culture, with a sample size of 3. The cell cycle detection kit was used to detect the cycle distribution of cells in two groups after 12 and 24 hours of culture, with a sample size of 3. The eukaryotic mRNA sequencing was performed on suitable number of cells of two groups after 24 hours of culture, and the Kyoto encyclopedia of genes and genomes functional annotation analysis and functional enrichment analysis were performed after screening for differentially expressed genes (DEGs) with significantly differential expression between two groups. Western blotting was conducted to detect the protein expressions of phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR) in the PI3K/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway of cells in two groups after 24 hours of culture, with a sample size of 3.Results:After 12 and 24 hours of culture, the proliferation activity of cells in metformin group was significantly lower than that in control group (with t values of 4.70 and 24.02, respectively, P<0.05); the proliferation activity of cells in metformin group after 24 hours of culture was significantly lower than that after 12 hours of culture within the group ( t=4.73, P<0.05). Compared with that after 12 hours of culture within the group, the proliferation inhibition rate of cells in metformin group was significantly increased after 24 hours of culture ( t=5.29, P<0.05). Compared with that in control group after 0 hour of culture, the proportion of early apoptotic cells in metformin group was significantly increased (with t values of 6.62 and 4.58, respectively, P<0.05), and the proportion of early and late apoptotic cells was significantly increased after 12 and 24 hours of culture (with t values of 4.84 and 3.75, respectively, P<0.05). After 24 hours of culture, the proportion of late apoptotic cells in metformin group was significantly higher than that after 12 hours of culture within the group ( t=4.55, P<0.05). After 12 hours of culture, the proportion of S-phase cells in metformin group was significantly lower than that in control group ( t=5.90, P<0.05). After 24 hours of culture, compared with that in control group, the proportion of G0/G1-phase cells in metformin group was significantly increased ( t=5.36, P<0.05), while the proportion of G2/M-phase cells was significantly decreased ( t=17.63, P<0.05). The proportion of S-phase cells in metformin group after 24 hours of culture was significantly higher than that after 12 hours of culture within the group ( t=7.60, P<0.05). After 24 hours of culture, 4 814 DEGs with significantly differential expression were detected in the cells of metformin group compared with control group. The significantly upregulated and downregulated DEGs were mainly involved in biological functions related to signal transduction, cell growth and death, transport and catabolism, the endocrine system, the immune system, and cancer. The pathways that were significantly enriched with DEGs with significantly differential expression included the cell cycle and DNA replication, with the highest number of genes in the PI3K/Akt signaling pathway. After 24 hours of culture, the protein expressions of PI3K, p-Akt, and p-mTOR of cells in metformin group were 0.190±0.017, 0.170±0.017, and 0.247±0.005, respectively, which were significantly lower than 0.440±0.026, 0.300±0.060, and 0.547±0.025 in control group (with t values of 13.69, 3.61, and 20.12, respectively, P values all <0.05). Conclusions:Metformin can significantly inhibit the proliferation of human keloid Fbs through the PI3K/Akt/mTOR signaling pathway and effectively induce its apoptotic process, thereby exerting antifibrotic effects.

Objective:To investigate the influence and mechanisms of metformin on the proliferation and apoptosis of human keloid fibroblasts (Fbs).Methods:This study was an experimental research. The keloid tissue was collected from 7 keloid patients (2 males and 5 females, aged 20-65 years, with a disease course of more than 1 year) who underwent keloid excision surgery at the Department of Plastic, Cosmetic and Maxillofacial Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from September 2020 to September 2023. The primary Fbs were isolated and cultured, and cells from passages 3 to 6 were used for experiments. The cells were divided into control group and metformin group, and were cultured in complete medium. The medium for metformin group was supplemented with metformin at a final molarity of 60 mmol/L. The cell counting kit-8 was used to assess the proliferation activity of cells in two groups after 12 and 24 hours of culture, and the proliferation inhibition rate of cells in metformin group after 12 and 24 hours of culture was calculated, with a sample size of 6. The apoptosis detection kit was used to detect the apoptotic distribution of cells in control group after 0 hour (immediately) of culture and in metformin group after 12 and 24 hours of culture, with a sample size of 3. The cell cycle detection kit was used to detect the cycle distribution of cells in two groups after 12 and 24 hours of culture, with a sample size of 3. The eukaryotic mRNA sequencing was performed on suitable number of cells of two groups after 24 hours of culture, and the Kyoto encyclopedia of genes and genomes functional annotation analysis and functional enrichment analysis were performed after screening for differentially expressed genes (DEGs) with significantly differential expression between two groups. Western blotting was conducted to detect the protein expressions of phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR) in the PI3K/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway of cells in two groups after 24 hours of culture, with a sample size of 3.Results:After 12 and 24 hours of culture, the proliferation activity of cells in metformin group was significantly lower than that in control group (with t values of 4.70 and 24.02, respectively, P<0.05); the proliferation activity of cells in metformin group after 24 hours of culture was significantly lower than that after 12 hours of culture within the group ( t=4.73, P<0.05). Compared with that after 12 hours of culture within the group, the proliferation inhibition rate of cells in metformin group was significantly increased after 24 hours of culture ( t=5.29, P<0.05). Compared with that in control group after 0 hour of culture, the proportion of early apoptotic cells in metformin group was significantly increased (with t values of 6.62 and 4.58, respectively, P<0.05), and the proportion of early and late apoptotic cells was significantly increased after 12 and 24 hours of culture (with t values of 4.84 and 3.75, respectively, P<0.05). After 24 hours of culture, the proportion of late apoptotic cells in metformin group was significantly higher than that after 12 hours of culture within the group ( t=4.55, P<0.05). After 12 hours of culture, the proportion of S-phase cells in metformin group was significantly lower than that in control group ( t=5.90, P<0.05). After 24 hours of culture, compared with that in control group, the proportion of G0/G1-phase cells in metformin group was significantly increased ( t=5.36, P<0.05), while the proportion of G2/M-phase cells was significantly decreased ( t=17.63, P<0.05). The proportion of S-phase cells in metformin group after 24 hours of culture was significantly higher than that after 12 hours of culture within the group ( t=7.60, P<0.05). After 24 hours of culture, 4 814 DEGs with significantly differential expression were detected in the cells of metformin group compared with control group. The significantly upregulated and downregulated DEGs were mainly involved in biological functions related to signal transduction, cell growth and death, transport and catabolism, the endocrine system, the immune system, and cancer. The pathways that were significantly enriched with DEGs with significantly differential expression included the cell cycle and DNA replication, with the highest number of genes in the PI3K/Akt signaling pathway. After 24 hours of culture, the protein expressions of PI3K, p-Akt, and p-mTOR of cells in metformin group were 0.190±0.017, 0.170±0.017, and 0.247±0.005, respectively, which were significantly lower than 0.440±0.026, 0.300±0.060, and 0.547±0.025 in control group (with t values of 13.69, 3.61, and 20.12, respectively, P values all <0.05). Conclusions:Metformin can significantly inhibit the proliferation of human keloid Fbs through the PI3K/Akt/mTOR signaling pathway and effectively induce its apoptotic process, thereby exerting antifibrotic effects.

Objective To analyze the risk factors for iatrogenic pseudoaneurysm(PSA)occurring after cardiovascular interventional procedures.Methods The clinical data of 48 patients,who developed PSA after receiving cardiovascular interventional procedure at the Yantai Yuhuangding Hospital of China between January 2018 and December 2022,were retrospectively analyzed.The control group included 192 patients who had no PSA.At a case-control ratio of 1∶4,the PSA patients and non-PSA patients were paired,and the paired indicators included age,and puncture site.Univariate and multivariate logistic regression analyses were used to analyze the patients'basic data,hematological examination,and situation of the interventional procedure,and the independent risk factors were screened out.Results Multivariate logistic regression analysis showed that the high body mass index(BMI,OR=1.324,95％CI=1.097-1.598,P=0.003),smoking history(OR=4.477,95％CI=1.599-12.536,P=0.004),use of antiplatelet agents(OR=4.861,95％CI=1.018-23.214,P=0.047),combination use of antiplatelet and anticoagulant(OR=26.994,95％CI=2.353-309.686,P=0.008),the operator of the interventional procedure being an attending physician(OR=5.817,95％CI=1.139-29.717,P=0.034),low haemoglobin level(OR=0.946,95％CI=0.922-0.971,P＜0.01),elevated D-dimer level(OR=2.407,95％CI=1.367-4.239,P=0.002),long-time interventional operation(OR=1.019,95％CI=1.005-1.033,P=0.009),and sheath size＞6 F(OR=4.368,95％CI=1.196-15.947,P=0.026)were the independent risk factors for PSA occurring after cardiovascular interventional surgery.Conclusion High BMI,smoking history,use of antiplatelet agents,combination use of antiplatelet and anticoagulant,the operator of the interventional procedure being an attending physician,low haemoglobin level,elevated D-dimer level,long-time interventional operation,and sheath size＞6 F are the independent risk factors for PSA occurring after cardiovascular interventional procedure,which can provide a basis for the early prevention of PSA.(J Intervent Radiol,2024,33:646-650)

To analyze the positivity rate and titer of antinuclear antibody (ANA), as well as nuclear pattern and target antigen of ANA in healthy pregnant women during early pregnancy in Qingdao area. A prospective cohort study design was used to include a total of 9 528 healthy pregnant women registered at the Women and Children′s Hospital Affiliated to Qingdao University from March 2023 to June 2024.Indirect immunofluorescence assay (IIF) was used to detect ANA, its titer and cell staining pattern. Fifteen specific antibodies were tested using the magnetic bar code immunofluorescent luminescence method. Logistic regression model was used to analyze the risk factors of pregnancy with autoimmune disease(AID). The results showed that among 9 528 pregnant women in early pregnancy, 1 346 cases (14.1%) were positive of ANA, including 1 011 cases with a titer of 1∶100 (10.6%), 236 cases (2.5%) with a titer of 1∶320, and 99 cases (1.0%) were detected at a titer >1∶320. Among the 1 346 ANA-positive pregnant women, nuclear granular type accounted for the highest proportion (483 cases, 35.9%), followed by speckled type (347 cases, 25.8%) and cytoplasmic type (176 cases, 13.1%).Then, pregnant women with ANA titers ≥1∶100 were detected 15 specific antibodies.Anti-SSA was tested in 121 cases accounted for the majority, followed by 110 cases with anti-Ro-52, 56 cases with anti-SSB, 51 cases with anti-mitochondrial M2 subtype antibodies and 37 cases with anti-centromere B. In conclusion,in healthy pregnant women in Qingdao area, ANA positivity rate was 14.1%, and the titer of ANA was mainly at 1∶100.The predominant nuclear patterns were nuclear granular and speckled types.The specific autoantibodies were mainly anti-SSA antibodies and anti-Ro-52 antibodies.The detection of ANA and specific autoantibodies is of great significance for early prediction, diagnosis, and intervention of autoimmune diseases during pregnancy.

To analyze the positivity rate and titer of antinuclear antibody (ANA), as well as nuclear pattern and target antigen of ANA in healthy pregnant women during early pregnancy in Qingdao area. A prospective cohort study design was used to include a total of 9 528 healthy pregnant women registered at the Women and Children′s Hospital Affiliated to Qingdao University from March 2023 to June 2024.Indirect immunofluorescence assay (IIF) was used to detect ANA, its titer and cell staining pattern. Fifteen specific antibodies were tested using the magnetic bar code immunofluorescent luminescence method. Logistic regression model was used to analyze the risk factors of pregnancy with autoimmune disease(AID). The results showed that among 9 528 pregnant women in early pregnancy, 1 346 cases (14.1%) were positive of ANA, including 1 011 cases with a titer of 1∶100 (10.6%), 236 cases (2.5%) with a titer of 1∶320, and 99 cases (1.0%) were detected at a titer >1∶320. Among the 1 346 ANA-positive pregnant women, nuclear granular type accounted for the highest proportion (483 cases, 35.9%), followed by speckled type (347 cases, 25.8%) and cytoplasmic type (176 cases, 13.1%).Then, pregnant women with ANA titers ≥1∶100 were detected 15 specific antibodies.Anti-SSA was tested in 121 cases accounted for the majority, followed by 110 cases with anti-Ro-52, 56 cases with anti-SSB, 51 cases with anti-mitochondrial M2 subtype antibodies and 37 cases with anti-centromere B. In conclusion,in healthy pregnant women in Qingdao area, ANA positivity rate was 14.1%, and the titer of ANA was mainly at 1∶100.The predominant nuclear patterns were nuclear granular and speckled types.The specific autoantibodies were mainly anti-SSA antibodies and anti-Ro-52 antibodies.The detection of ANA and specific autoantibodies is of great significance for early prediction, diagnosis, and intervention of autoimmune diseases during pregnancy.

Objective:To investigate the value of intratumoral and peritumoral radiomics features of multi-parameter MRI in evaluation of the status of human epithelial growth factor receptor 2 in breast cancer.Methods:The clinical, pathological and imaging data of 340 patients with pathologically confirmed breast cancer in Henan Provincial People′s Hospital from September 2019 to December 2020 were retrospectively collected. All patients were female, 48 (42, 55) years old. All patients underwent multi-parameter breast MRI before surgery, including dynamic contrast-enhanced T 1WI (DCE-T 1WI), fat-suppressed T 2WI (T 2WI) and diffusion-weighted imaging (DWI). The region of interest (ROI) for lesions were manually delineated and the segmented ROIs were zoomed in ring shape by 4 mm to acquire ROI intra and ROI prei, respectively. Then six sets of radiomics features were extracted from ROI intra and ROI prei of DCE-T 1WI, T 2WI and DWI. The cases were divided into a training set (272 cases) and a test set (68 cases) by stratified sampling at a ratio of 4∶1. The Mann-Whitney U test, Select K Best and minimum absolute contraction and selection operator were used for feature selection of the 6 sets of radiomics features. The feature subsets after reduction were used to construct independent and combined radiomics signatures with support vector machine algorithm to predict the HER2 status of breast cancer. Receiver operating characteristic curve was generated and area under curve (AUC) was calculated to compare the prediction performance of different models. Results:Of the 340 patients, 80 were HER2-positive and 260 were HER2-negative. Among the radiomics signatures based on single sequence, the DWI peri showed the best performance in predicting HER2 status of breast cancer, with an AUC of 0.678 for the test set. Among the combination of intratumoral and peritumoral radiomics signatures based on same sequence, the DWI intra+DWI peri had the highest prediction value, achieving an AUC of 0.774 for the testing set. Among the intratumoral or peritumoral radiomics signatures derived from two different sequences, the DCE-T 1WI intra+DWI intra and T 2WI peri+DWI peri showed the best predictive performance, yielding AUC of 0.766 and 0.769 in the testing set, respectively. Among the combination of intratumoral or peritumoral radiomics signatures derived from all 3 sequences or combinations of all features, the DCE-T 1WI intra+T 2WI intra+DWI intra+DCE-T 1WI peri+T 2WI peri+DWI peri obtained the highest prediction efficiency, with an AUC of 0.913 for the testing set. Conclusion:The radiomics features of intratumoral and peritumoral regions based on multi-parameter MRI have a certain value in non-invasive evaluation of HER2 status of breast cancer, which can help clinicians to provide scientific basis for decision-making of targeted therapy in patients with breast cancer.

Objective: To evaluate the clinical efficacy of moxibustion with monkshood cake on the acupoints along related meridian for functional dyspepsia (FD) patients. Methods: Sixty patients suffering from functional dyspepsia who met with the inclusion criteria were enrolled in our randomized and controlled trial and randomly divided into two different groups, 30 and 28 patients have finished the treatment respectively. Patients of each group were given with moxibustion with monkshood cake on different acupoints, Group A chose acupoints along related meridian (ST 34, ST 36, ST 40 and ST42), while Group B chose acupoints along non-related meridian (GB 34, GB 36, GB 37 and GB 40) . Patients of each group received moxibustion treatment on alternate days, 3 times a week for a total of 12 times. The efficacy was evaluated using the Nepean Dyspepsia Index (NDI) and the Somatic Self-rating Scale (SSS) before, 2 weeks after and 4 weeks after the treatment, respectively. Results: Considering the NDI scale, the result showed that improvement scores of Group A were higher than that of Group B with statistical significance (P ＜ 0.01) . Both groups had improved patients' quality of life after the treatment (P ＜ 0.05), but the improvements in Group A were significantly better than those in Group B (P ＜ 0.01) . Conclusion: The clinical efficacy of moxibusion with monkshood cake on the acupoints along related meridian was better than that of the non-related meridian.