1.Value of diffusion-weighted magnetic resonance imaging in differential diagnosis of primary gallbladder cancer and hepatocellular carcinoma
Haiyi WANG ; Jia WANG ; Huiyi YE ; Xinkun WANG ; Jing YUAN ; Dianjun WANG ; Jiahong DONG
Chinese Journal of Digestive Surgery 2011;10(2):103-106
Objective To investigate the value of diffusion-weighted magnetic resonance imaging in the differential diagnosis of primary gallbladder cancer with liver invasion and primary hepatocellular carcinoma (HCC) with gallbladder invasion. Methods From January 2009 to October 2010, 11 patients with primary gallbladder cancer and 19 patients with primary HCC were admitted to the PLA General Hospital. The clinical data of the 30 patients were retrospectively analyzed. All patients underwent diffusion-weighted magnetic resonance imaging with b value of 800 s/mm2, and the receiver operating curve (ROC) was drawn. The apparent diffusion coefficient (ADC) values of the patients with gallbladder cancer and HCC were compared by independent sample t test. Results Thirty tumors were detected in the 30 patients. All tumors showed high signal on DWI, slightly low signal on T1 WI and slightly high signal on T2 WI. The foci of 11 patients with primary gallbladder cancer were at the gallbladder fossa, and 10 of them had liver involvement. The mean ADC value of the 11 patients was (0.89 ±0. 14)mm2/s. Of the 19 patients with primary HCC, the foci of 15 patients were at the right lobe of liver, and 4were at the left lobe. The mean ADC value of the 19 patients was (1.04 ±0.18)mm2/s. There was a significant difference in the ADC value between patients with primary gallbladder cancer and those with primary HCC ( t =2.425, P<0. 05). The area under the ROC was 0. 756 (95% confidence interval: 0.577-0. 935), and the sensitivity and specificity were 68.4% and 81.8%, respectively, when the threshold value was 0.96 mm2/s.Conclusion The ADC value of patients with primary gallbladder cancer is lower than those with primary HCC when the b value is 800 s/mm2, which is helpful in the differential diagnosis of primary gallbladder cancer and primary HCC.
2.Detection of Focal Liver Lesions with Diffusion Weighted Imaging:Results of A Multi-center Clinical Trial
Xiaoqiang LI ; Xun YAO ; Dawei YANG ; Xinkun WANG ; Huiyi YE ; Tao JIANG ; Zhenghan YANG
Chinese Journal of Medical Imaging 2015;(5):356-360
PurposeTo investigate the role of diffusion weighted imaging (DWI) in the detection of focal liver lesions (FLL).Materials and Methods T2WI, dynamic contrast enhancement (DCE) and DWI (b=100 s/mm2 and 600 s/mm2 respectively) were performed in 205 patients with 310 FLLs. All images were read by two reviewers to determine the detection of FLLs and score the confidence. The consistency of the results given by the two reviewers was evaluated. The confidence scores between different sequences and the detection rate of different sequences were also compared.Results The consistency of the two reviewers was excellent or good in T2WI, high b value DWI, low b value DWI, and DCE (Kappa=0.71, 0.85, 0.82 and 0.64,P<0.05). As to the confidence score of lesion detection, high b value DWI and low b value DWI were both significantly higher than T2WI (P<0.01), but both were lower than DCE (P<0.01). DWI yielded higher score and detection rate for detecting FLLs than T2WI (86.5%vs. 70.3%,P<0.01), but lower than DCE (91.6%,P<0.05). For small malignant lesions (≤2 cm in diameter), DWI showed similar detection rate with DCE (P>0.05), but higher than T2WI (P<0.01). The combination of DWI and DCE detected more small malignant lesions than DWI or DCE alone (P<0.01).Conclusion DWI can detect more FLLs than T2WI, and can help DCE detect small malignant FLLs. Therefore DWI is suggested to be included in the routine protocol of liver MRI examination.
3.Preventive effect of Guizhi decoction on myocardial injury after chemical sympathectomy
Yuehua JIANG ; Dufang MA ; Jinlong YANG ; Xue WANG ; Haiqing LIN ; Xinkun CAO ; Xiao LI
Chinese Journal of Pathophysiology 2015;33(4):750-754
[ ABSTRACT] AIM:To investigate the preventive effect of Guizhi decoction on myocardial injury after chemical sympathectomy induced by 6-hydroxydopamine (6-OHDA).METHODS:Wistar rats (n=54) were randomly divided in-to 6 groups.Methycobal and Guizhi decoction ( with different proportions between Ramulus Cinnamomi and Radix paeoniae Alba at 2∶1, 1∶2 or 1∶1) were pre-administered to the rats.Immunohistochemical method was used to observe the cardiac sympathetic nerve distribution.The contents of tyrosine hydroxylase (TH), choline acetylaminotransferase (ChAT) and growth-associated protein 43 (GAP-43) in the left ventricle were measured by ELISA.The serum levels of myocardial en-zymes and morphology of myocardial tissues were also observed.RESULTS:6-OHDA successfully induced cardiac sympa-thetic denervation as the contents of TH and GAP-43 in the left ventricle declined significantly.Compared with model group, the content of TH was elevated in both methycobal group and Guizhi decoction groups, while the content of GAP-43 was elevated only in Guizhi decoction groups.The serum levels of myocardial enzymes and the histopathological changes of the cardiac tissues were deteriorated after injection of 6-OHDA, indicating that the myocardial injury was established. Methycobal and Guizhi decoction normalized the abnormal change.Guizhi decoctions at 2∶1 and 1∶1 showed the best effi-cacy.CONCLUSION:6-OHDA-induced sympathetic denervation causes myocardial injury.Guizhi decoction with the proportions between Ranulus Cinnamomi and Radix paeoniae Alba at 2∶1 and 1∶1 effectively alleviate the myocardial injury after cardiac sympathetic denervation induced by 6-OHDA.
4.Clinical efficacy of artificial dermis and flap transfer in treatment of soft tissue defect around interphalangeal joint: a comparative study
Keyue YANG ; Tao SUN ; Jie YIN ; Kejie WANG ; Xinkun HE ; Xin WANG ; Jianwu QI ; Xiaofeng TENG
Chinese Journal of Microsurgery 2023;46(5):505-510
Objective:To compare the clinical effecacy of artificial dermal regeneration matrix (as "artificial dermis" hereafter) and flap transfer in the treatment of soft tissue defects around interphalangeal joint.Methods:Through postoperative follow-up at outpatient clinic, a retrospective study was conducted on the clinical data of 60 patients who had soft tissue defects around the interphalangeal joints and received treatment in the Department of Hand Surgery, the Sixth Hospital of Ningbo from January 2018 to January 2022. According to applied surgical procedures, patients were divided into a flap transfer group (group A, n=30) and an artificial dermis group (group B, n=30). Group A included 19 males and 11 females aged 44.83 years ± 11.56 years including 5 patients with simple soft tissue defects, and 6 with soft tissue defects and fractures, 10 with soft tissue defects with tendon and (or) ligament injuries, 3 with soft tissue defects and vessel and (or) nerve injuries, and 6 with soft tissue defects and over 2 other types of compound injuries. The defect areas ranged from 2.5 cm×1.2 cm to 5.0 cm×1.6 cm. After emergency debridement and treatment for bone and tendon injuries, the patients in group A received transfers of free flap or transfers with adjacent digit flaps or island flaps. Postoperative functional exercise started from 1-6 weeks after surgery. Patients in group B included 17 males and 13 females, aged 44.70 years ± 11.20 years and there were 6 patients with simple soft tissue defects, 6 with soft tissue defects and fractures, 9 with soft tissue defects and tendon and (or) ligament injuries, 5 with soft tissue defects and vessel and (or) nerve injuries, and 4 with soft tissue defects and over 2 other types of compound injuries. The defect area ranged from 3.1 cm ×1.3 cm to 4.5 cm × 1.8 cm. Debridement and treatment of the bone and tendon injury in group B were the same as what in group A, but the patients in group B received artificial dermis coverage other than transfer of flap. After an artificial dermis had completely vascularised, a split-thickness skin graft was performed over the neo-dermis in the second phase surgery. Postoperative functional exercise started from 1-2 weeks after artificial dermis grafting surgery. The interval time of flap transfer or split-thickness skin grafting, survival rate of flap transfer or split-thickness skin grafting, Vancouver Scar Scale(VSS), TPD and total active movement(TAM) were compared between the 2 groups. The count data were analysed by Chi-square test. All measured data were analysed by independent sample t test or Mann-Whitney U test. P<0.05 indicates a statistically significant difference. Results:The interval time of flap transfer in group A and artificial dermis grafting in group B were 2.93 days ± 2.48 days and 19.87 days ± 3.35 days, respectively. There was a statistically significant difference between the 2 groups( P<0.05). All patients were entered in postoperative outpatient follow-up for 11-14 months(12.00 months ± 0.93 months). The appearance of flaps of some patients in group A was bloated with slightly limited digit movement. In group B, the digit movement was normal, without obvious scar hyperplasia in both of the recipient and donor sites. The survival rate of flap transfer or artificial dermis graft, TPD, VSS score and TAM score for group A and group B were 96.00% ± 9.32% and 98.17% ± 3.07%, respectively, 8.67 mm ± 2.01 mm and 9.50 mm ± 1.81 mm, 3.40 ± 1.07 and 3.17 ± 0.91 and 18.30 ± 1.97 and 18.93 ± 1.64, respectively. There were no significant differences between the 2 groups( P>0.05). Conclusion:In comparison with the transfer of flap, an artificial dermis is also effective and satisfactory in the treatment of soft tissue defects around the interphalangeal joint. Further large scale and multi-centre investigations are required.
5.Mechanism of nuclear translocation of hypoxia-inducible factor-1α in influenza A (H1N1) virus infected-alveolar epithelial cells
Xiaoxiao MENG ; Xinkun GUO ; Yong ZHU ; Hui XIE ; Ruilan WANG
Chinese Critical Care Medicine 2020;32(1):8-13
Objective:To investigate the molecule mechanism of nuclear translocation of hypoxia-inducible factor-1α (HIF-1α) in influenza A (H1N1) virus infected-alveolar epithelial cells.Methods:Human lung adenocarcinoma epithelial cells (A549 cells) were cultured in vitro, and cells in logarithmic growth phase were selected for experiments. ① Experiment 1: the A549 cell model with H1N1 virus infection was established by using H1N1 virus infected cells with multiplicity of infection (MOI) 1.0 for 24 hours (H1N1 virus infection group), and the blank control group was set up. Importin 4 and Importin 7 protein expressions were detected by Western Blot to investigate whether HIF-1α nuclear translocation depended on Importin 4 or Importin 7. ② Experiment 2: the A549 cells were infected with H1N1 virus under different MOI (0, 0.1, 0.5, 1.0, 2.0, 4.0) for 24 hours. Then the A549 cells were infected with H1N1 virus (MOI 1.0) for different time (0, 3, 6, 12, 18, 24, 36 hours). The septin 9 isoform 1 (SEPT9_i1) mRNA expression was detected by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) to investigate the effect of different MOI and infection time on the expression of SEPT9_i1. ③ Experiment 3: a cell model with SEPT9_i1 silencing was established by transfection of small interfering RNA (siRNA) for 24 hours (siRNA-SEPT9_i1 group), and the blank control group and blank vector control group (siControl group) were set up. Then the cells in the three groups were infected with H1N1 virus (MOI 1.0) for 24 hours after 24-hour transfection, and the SEPT9_i1 mRNA expression was detected by real-time fluorescence quantitative RT-PCR to investigate the interference efficiency of siRNA-SEPT9_i1. ④ Experiment 4: the cells were divided into siControl group and siRNA-SEPT9_i1 group. The transfection methods of two groups was as the same as experiment 3, and then the cells were infected with H1N1 virus (MOI 1.0) after 24-hour transfection. The distribution of HIF-1α was detected by immunofluorescence at 24 hours after infection. The M gene expression of virus was detected by real-time fluorescence quantitative RT-PCR at 6, 12, 24, 36, 48 hours after infection. The effects of SEPT9_i1 on HIF-1α translocation and virus replication were explored. ⑤ Experiment 5: the cells were divided into blank control group (complete medium), SP600125 group [100 μmol/L c-Jun N-terminal kinase (JNK) signaling pathway inhibitor SP600125 for 2 hours], H1N1 virus infection group (H1N1 virus of MOI 1.0 for 24 hours), H1N1 virus+SP600125 group (pretreated with 100 μmol/L SP600125 for 2 hours before 24-hour H1N1 virus infection). Real-time fluorescence quantitative RT-PCR was used to detect the expressions of SEPT_i1 mRNA and viral M gene to investigate the effect of JNK signaling pathway on SEPT9_i1 expression and virus replication. Results:① Experiment 1: compared with the blank control group, the protein expressions of Importin 4 and Importin 7 in the H1N1 virus infection group had no significant changes [Importin 4 protein (Importin 4/GAPDH): 1.08±0.03 vs. 1.05±0.03, Importin 7 protein (Importin 7/GAPDH): 0.87±0.11 vs. 0.78±0.03, both P > 0.05]. These indicated that the HIF-1α nuclear translocation in A549 cells might not be independent of Importin 4 and Importin 7 during H1N1 virus infection. ② Experiment 2: the SEPT9_i1 mRNA expression in A549 cells was increased with the increase in MOI and infection time of H1N1 virus, and peaked at MOI 2.0 or 18 hours after infection, and the differences were statistically significant as compared with MOI 0 or 0 hour after infection (2 -ΔΔCT: 1.39±0.05 vs. 1.00±0.00 at MOI 2.0, 1.47±0.04 vs. 1.00±0.00 at 18 hours, both P < 0.01). This indicated that the SEPT9_i1 expression in A549 cells was related to the MOI and the infection time during H1N1 virus infection. ③ Experiment 3: compared with the blank control group, the SEPT9_i1 mRNA expression in A549 cells was significantly decreased in the siRNA-SEPT9_i1 group (2 -ΔΔCT: 0.38±0.11 vs. 1.00±0.00, P < 0.01), and there was no significant difference between the siControl group and blank control group (2 -ΔΔCT: 1.03±0.16 vs. 1.00±0.00, P > 0.05). This indicated that SEPT9_i1 silence could inhibit the expression of SEPT9_i1 mRNA in H1N1 virus-infected A549 cells. ④ Experiment 4: HIF-1α nuclear translocation in the H1N1 virus-infected A549 cells in the siRNA-SEPT9_i1 group was significantly reduced as compared with the siControl group. The virus M gene expression after H1N1 virus infection in the siControl group was gradually increased, and peaked at 48 hours. The expression of virus M gene in A549 cells in the siRNA-SEPT9_i1 group was significantly down-regulated, and showed a statistically significant difference at 48 hours as compared with the siControl group (2 -ΔΔCT: 3.47±0.66 vs. 8.17±0.38, P < 0.05). This indicated that HIF-1α nuclear translocation and virus replication in H1N1 virus-infected A549 cells were inhibited after silencing SEPT9_i1. ⑤ Experiment 5: the expressions of SEPT9_i1 mRNA and virus M gene in A549 cells in the H1N1 virus infection group were significantly higher than those in the blank control group. However, the expressions of SEPT9_i1 mRNA and viral M gene in A549 cells in the H1N1 virus+SP600125 group were significantly lower than those in the H1N1 virus infection group (2 -ΔΔCT: SEPT9_i1 mRNA was 0.12±0.10 vs. 1.53±0.14, viral M gene was 2.13±0.10 vs. 4.66±0.14, both P < 0.05). There was no significant difference in above indicators between the SP600125 group and the blank control group. This indicated that the JNK signaling pathway could regulate the expression of SEPT9_i1 in A549 cells during H1N1 virus infection, and the JNK signaling pathway inhibition could down-regulate the expression of SEPT9_i1 and inhibit virus replication. Conclusion:The H1N1 virus regulates the expression of SEPT9_i1 by activating the JNK signaling pathway, thus increase HIF-1α transport efficiency and H1N1 replication.
6. Influences of hypoxia inducible factor-1α on the expression of inflammatory cytokines in mice with influenza A (H1N1) virus infection
Peng HAN ; Zhaoqin ZHU ; Wanju ZHANG ; Xiaoxiao MENG ; Yong ZHU ; Xiaohui ZHOU ; Xinkun GUO ; Yunwen HU ; Ruilan WANG
Chinese Journal of Microbiology and Immunology 2018;38(7):494-499
Objective:
To analyze the changes in the expression of hypoxia inducible factor-1α (HIF-1α) and inflammatory cytokines and to investigate the role of HIF-1α in regulating the production of inflammatory cytokines during influenza A (H1N1) virus infection.
Methods:
BALB/c mice were injected with H1N1 virus to establish the mouse model of H1N1 virus infection. Fifteen BALB/c mice were randomly divided into three groups: control group, H1N1 virus group and H1N1 virus+ HIF-1α inhibitor group. Inflammatory cytokines (IL-6, TNF-α, IL-1β and IL-10) in samples of serum and lung tissues were detected by Luminex and ELISA. Levels of HIF-1α in serum and lung tissue samples were detected by Western blot and ELISA, respectively.
Results:
Compared with the control group, the levels of inflammatory cytokines in serum (IL-6, TNF-α, IL-1β and IL-10) and lung tissues (IL-6 and TNF-α) and the expression of HIF-1α in serum and lung tissues in the H1N1 virus group were significantly increased. The levels of HIF-1α, IL-6, TNF-α IL-1β and IL-10 in lung tissues in H1N1 virus+ HIF-1α inhibitor group were significantly lower than those of the H1N1 virus group.
Conclusion
During H1N1 virus infection, the levels of inflammatory cytokines and HIF-1α were significantly increased. The production of inflammatory cytokines was significantly reduced after inhibiting HIF-1α expression, suggesting that HIF-1α might promote the production of inflammatory cytokines.