1.Efficacy and mechanism of astragaloside Ⅳ derivatives on chronic heart failure in mice
Kai JING ; Cirong YANG ; Zhen ZHANG ; Yibei ZANG ; Xia LIU
Journal of Pharmaceutical Practice and Service 2024;42(5):190-197
Objective To evaluate the pharmacodynamics of astragaloside Ⅳ derivatives for chronic heart failure,screen the candidate compounds and preliminarily explore the mechanism of the candidate compound HHQ16 against heart failure.Methods Chronic heart failure was induced by left anterior descending artery ligation in C57BL/6 mice for 4 weeks,and the mice were divided into 4 groups,including sham group,model group,positive control captopril group,and astragaloside Ⅳ derivatives group.After continuous intragastric administration for four weeks,the cardiac function was detected by echocardiography,and the optimal astragaloside Ⅳ derivative HHQ16 was selected for the treatment of heart failure.The preliminary mechanism for HHQ16 was further explored.The size of heart was observed by gross morphology;pathological changes were observed by HE staining;collagen deposition in the myocardium was observed by Masson staining;protein levels of myocardial fibrosis indexes COL1,COL3,and αSMA were detected by immunohistochemical staining,and mRNA levels of myocardial fibrosis indexes COL1,COL3,αSMA,and TGF-β1 were determined by qPCR technique.Results All astragaloside Ⅳ derivatives significantly improved cardiac function with increasing LVEF and LVFS,of which HHQ16 was the optimal compound.Compared with the model group,the heart volume of HHQ16 group was significantly reduced;myocardial hypertrophy was reduced;collagen deposition in myocardial tissues was reduced;and myocardial fibrosis indexes,COL1,COL3,αSMA and TGF-β1 mRNA levels,as well as the protein levels of COL1,COL3 and αSMA were significantly reduced.Conclusion HHQ16 is an optimal astragaloside Ⅳ derivatives for the treatment of chronic heart failure in mice,which could improve cardiac function by improving myocardial remodeling,and inhibit myocardial hypertrophy and myocardial fibrosis.
2.Application of Hisense computer-assisted surgery system in perioperative period of laparoscopic hepatectomy for liver cancer
Xin-Yu LI ; Zi-Qi ZANG ; Qi-Sheng HAO ; Li-Chao CHA ; Ming-Kai GONG ; Guo-Fei DONG ; Qing-Ze LI ; Lan-Tian TIAN
Chinese Journal of Current Advances in General Surgery 2024;27(6):435-441
Objective:To explore the clinical application of Hisense Computer-Assisted Sur-gery System(CAS)in the perioperative period of hepatectomy for liver cancer.Methods:Clinical data of patients undergoing laparoscopic hepatectomy(LH)for liver cancer from January 2021 to December 2022 were collected.Patients were divided into three groups based on surgical difficulty(low,medium,high)and further stratified into CAS-assisted subgroup and control subgroup ac-cording to whether the CAS system was used.Demographic and perioperative data were com-pared among different groups.Results:A total of 317 patients'clinical data were collected,in-cluding 31 cases in the low difficulty group,132 cases in th medium difficulty group,and 154 cases in the high difficulty group,with 108 cases(34.1%)in the CAS-assisted subgroup and 209 cases(65.9%)in the control group.In the medium difficulty group,the CAS-assisted subgroup had shorter operation time,drainage tube duration,and postoperative hospital stay compared to the control group(P<0.001),and the AFP levels at 1 month postoperatively in the CAS-assisted sub-group were lower than those in the control group(P<0.001).In the high difficulty group,the CAS-assisted subgroup showed shorter operation time,drainage tube duration,and postoperative hospi-tal stay,less intraoperative blood loss,and lower AFP levels 1 month post-operation compared to the control group(P<0.001 for all).Conclusion:Preoperative CAS in medium and high difficulty laparoscopic liver resections improves perioperative outcomes.Hisense CAS effectively assists general surgeons in accurately identifying the anatomical site of liver tumors,providing precise pre-operative simulation and intraoperative navigation,thereby optimizing surgical strategies for pa-tients.
3. Effects of AR on proliferation and lipid synthesis of myocardial fibroblasts in high glucose environment
Xin WEN ; Hong-Mei ZANG ; Xin WEN ; Yang ZHOU ; Kai SONG ; Li-Chan LIN ; Zhi-Yan LIU ; Hui TAO
Chinese Pharmacological Bulletin 2023;39(12):2274-2280
Aim To explore the effect of androgen receptor AR on the proliferation and lipid synthesis of cardiac fibroblasts under high-glucose conditions and the possible molecular mechanism.Methods The hearts of neonatal rats were dissected for primary culture of cardiac fibroblasts. Then the growth status of CFs was observed under the inverted microscope, and the identification of CFs was performed by immunofluorescence staining using anti-vimentin. After cell adherence, the cells were divided into blank control group, high glucose model group, negative control group, and overexpressed AR group. The glucose concentration was 33.0 mmol·L-1 except that the blank control group was 5.5 mmol·L-1. After 24 hours of CFs culture, Western blot and RT-qPCR were used to detect the expression of AR, FASN, PCNA, cyclin D1, α-SMA, and collagen . Oil red O and CCK-8 were used to detect the changes in lipid synthesis and cell proliferation ability, respectively.Results Compared with the blank control group, the lipid synthesis and proliferation of CFs in the high glucose model group were enhanced. Western blot and RT-qPCR results showed that the expression of AR decreased, while the expression of fat lipid synthase(FASN), proliferation marker PCNA, cyclin D1 and fibrosis marker α-SMA and collagen increased. After AR overexpressed plasmid was transfected into the CFs treated by high glucose, AR overexpression markedly decreased the expression of FASN, PCNA, cyclin D1, α-SMA and collagen compared with the empty plasmid‐transfected group. Meanwhile, oil red O staining and CCK-8 results showed that the lipid synthesis and proliferation ability of the overexpressed AR group decreased compared with the empty vector group, respectively. Conclusions High glucose promotes the proliferation and lipid synthesis of cardiac fibroblasts. Besides, the mechanism may be related to the regulation of lipid synthesis regulated by AR.
4. Expression change and role of myeloma cancer gene mRNA and the non-coding RNA in the hepatocyte cycle initiation and termination during the rat liver regeneration
Qi-Jie XUE ; Cui-Fang CHANG ; Zi-Hui WANG ; Xia-Yan ZANG ; Kai-Lin LIN ; Chun-Bo ZHANG ; Lu HAN ; Bing-Yu YE ; Cun-Shuan XU ; Qi-Jie XUE ; Cui-Fang CHANG ; Zi-Hui WANG ; Xia-Yan ZANG ; Kai-Lin LIN ; Chun-Bo ZHANG ; Lu HAN ; Bing-Yu YE ; Cun-Shuan XU
Acta Anatomica Sinica 2023;54(4):41-419
Objective To explore the role pathway and pattern of the myeloma cancer gene (MYC) and its mRNA interaction with the microRNAs(miRNAs) and circular RNA(circRNAs) at hour 0, hour 6 and hour 72 in the rat liver regeneration. Methods The rat 2/3 hepatectomy (PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al. The expression changes of mRNA, miRNA and circRNA [together named as competing endogenous RNA (ceRNA)] were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at hour 0 and hour 6 after PH, the ratio value of MYC mRNA showed 0.15±0.03 and 2.36±0.20, miR-134-5p indicated 3.22±0.61 and 0.08±0.02, circRNA_12112 displayed 0.68±0.21 and 13.35±3.53. At the same time, the cell cycle initiation-related genes ras association domain family member 1 (RASSF1), cyclin dependent kinase 2 (CDK2), superoxide dismutase 2 (SOD2), which were promoted in expression by MYC, were down-regulated at hour 0 after PH, but the cell cycle initiation-related genes nestin (NES), RAD21 cohesin complex component (RAD21), CUE domain containing 2 (CUEDC2), which are inhibieted in expression by MYC, had no meaningful express changes at hour 0 after PH. On the other hand, the cell cycle initiation-related gene SOD2, which was promoted in expression by MYC, was up-regulated at hour 6 after PH, but the cell cycle initiation-related genes NES, RAD21, CUEDC2, which are inhibieted in expression by MYC, were down-regulated at hour 6 after PH. In contrary, at hour 72 after PH, the ratio value of MYC mRNA showed 2.36±0.20, miR-880-3p indicated 0.54±0.01, circRNA_09599 displayd 0.54±0.16. At the same time, the cell cycle termination-related gene hepatocyte growth factor (HGF), which is promoted in expression by MYC, was up-regulated 72 hours after PH, the cell cycle termination-related genes MET proto-oncogene receptor tyrosine kinase (MET) and cyclin dependent kinase inhibitor 1A (CDKN1A), which are inhibieted in expression by MYC, were down-regulated 72 hours after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, MYC, its mRNA is inhibited by miRNAs, and the cell cycle initiation-related and cell cycle termination-related genes, which are regulated by MYC, are helpful for the hepatocyte to be in cell cycle initiation state at hour 6 after PH and to be in cell cycle termination state at hour 72 after PH.
5. Expression change and role of Kruppel-like factor 4 mRNA, microRNA-881-3p, circular RNA_20298 and circular RNA_14826 in the hepatocyte apoptosis during the rat liver regeneration
Kai-Lin LIN ; Xian-Guang YANG ; Zi-Hui WANG ; Xia-Yan ZANG ; Qi-Jie XUE ; Lu HAN ; Chun-Bo ZHANG ; Cun-Shuan XU ; Kai-Lin LIN ; Xian-Guang YANG ; Zi-Hui WANG ; Xia-Yan ZANG ; Qi-Jie XUE ; Lu HAN ; Chun-Bo ZHANG ; Cun-Shuan XU ; Zhi-Hu ZHAO
Acta Anatomica Sinica 2023;54(4):420-424
[ Abstract] Objective To explore the role pathway and pattern of the Kruppel-like factor 4 (KLF4) and its mRNA interaction with microRNA (miRNAs) and circular RNA (circRNAs) at 0 hour and the 120 th hour in the rat liver regeneration. Methods The rat 2 / 3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNA (ceRNA) were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3. 2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and the 120th hour PH, the ratio value of KLF4 mRNA showed 1. 00±0. 16 and 3. 14±0. 27, miR-881-3p displays 18. 30±1. 44 and 0. 47±0. 02, circRNA_20298 indicated 0. 32±0. 10 and 4. 24±0. 22, circRNA_14826 showed 0. 42±0. 13 and 0. 61±0. 08. At the same time, the four kinds of cell apoptosis-related genes adrenoceptor beta 2 (ADRB2), dimethylarginine dimethylaminohydrolase 2 (DDAH2), annexin A5 (ANXA5), ect, which were promoted in expression by KLF4, were down-regulated at 0 hour after PH, but the cell apoptosis-related genes synuclein gamma (SNCG), glutathione-disulfide reductase (GSR), FYVE, RhoGEF and PH domain containing 4 (FGD4), ect, which were inhibited in expression by KLF4, were up-regulated at 0 hour after PH. On the other hand, the cell apoptosis-related genes ANXA5 and thymosin beta 10 (TMSB10), which are promoted in expression by KLF4, were up-regulated at the 120th hour after PH, but the cell apoptosis-related genes chloride intracellular channel 4 (CLIC4) and ataxin 3 (ATXN3), ect, which were inhibited in expression by KLF4, were down-regulated at the 120th hour after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, KLF4, its mRNA is inhibited by miRNAs, and the cell apoptosis-related genes, which are regulated by KLF4, are helpful for the hepatocyte to be in active state 0 hour after PH and to be in apoptotic state 120-hour after PH.
6. Expression change and role of sex determining region box transcription factor 2 mRNA and the non-coding RNA in the hepatocyte stem changes during the rat liver regeneration
Zi-Hui WANG ; Jian-Lin GUO ; Xia-Yan ZANG ; Qi-Jie XUE ; Kai-Lin LIN ; Chun-Bo ZHANG ; Lu HAN ; Cun-Shuan XU ; Zi-Hui WANG ; Jian-Lin GUO ; Xia-Yan ZANG ; Qi-Jie XUE ; Kai-Lin LIN ; Chun-Bo ZHANG ; Lu HAN ; Cun-Shuan XU ; Jun-Tang LIN
Acta Anatomica Sinica 2023;54(2):202-207
Objective To explore the role pathway and pattern of the sex determining region box transcription factor 2 (SOX2) and its mRNA interaction with microRNA(miRNAs, miR) and circular RNA(circRNA) at 0 hour and 2 hours in the rat liver regeneration. Methods The rat 2/3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA [together named as competing endogenous RNAs(ceRNA)] were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and 2 hours after PH, the ratio value of SOX2 mRNA shows 1.00±0.09 and 2.15±0.48, miR-3558-3p displays 4.53± 0.10 and 0.81±0.16, circRNA_18404 shows 1.24±0.04 and 11.10±0.57, circRNA_18045 displays 1.97±0.47 and 4.44± 0.23. At the same time, the eight kinds of cell dedifferentiation-related genes AT-rich interaction domain 5A (ARID5A), activating transcription factor 3 (ATF3), BTG anti-proliferation factor 2 (BTG2), etc, which are prometed in expression by SOX2, were down-regulated at 0 h after PH, but the cell differentiation-related genes interferon regulatory factor 6 (IRF6) and somatostatin (SST), which are inhibited in expression by SOX2, were up-regulated at 0 hour after PH. On the other hand, the eight kinds of cell dedifferentiation-related genes ARID5A, ATF3, BTG2, etc, which are promoted in expression by SOX2, were up-regulated at 2 hours after PH, but the cell differentiation-related gene SST, which is inhibited in expression by SOX2, was down-regulated, and IRF6 had no meaningful changes in expression at 2 hours after PH. Conclusion The correlation in expression and role of the miRNA, which are inhibited by circRNA, SOX2, its mRNA is inhibited by miRNA, and the cell stem-related genes, which are regulated by SOX2, are helpful for the hepatocyte to be in differentiation state at 0 hour after PH and to be in stem state at 2 hours after PH.
7. Expression change and role of myeloma cancer gene mRNA, microRNA-540-3p, circular RNA-04996 in the liver inflammatory reaction during the rat liver regeneration
Chun-Bo ZHANG ; Gai-Ping WANG ; Zi-Hui WANG ; Xia-Yan ZANG ; Qi-Jie XUE ; Kai-Lin LIN ; Lu HAN ; Qi-Wen WANG ; Cun-Shua XU ; Chun-Bo ZHANG ; Gai-Ping WANG ; Zi-Hui WANG ; Xia-Yan ZANG ; Qi-Jie XUE ; Kai-Lin LIN ; Lu HAN ; Qi-Wen WANG ; Cun-Shua XU
Acta Anatomica Sinica 2023;54(1):70-74
Objective To explore the role pathway and pattern of the transcription factor myeloma cancer gene (MYC) and its mRNA interaction with microRNA(miRNA, miR) and ciccular RNA(circRNAs) at 0 hour and 6 hour in the rat liver regeneration. Methods The rat 2/3 hepatectomy (partial hepatectomy,PH) model was prepared as described by Higgins, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNAs(ceRNA) of remnant liver were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at 0 hour and 6 hours after PH, the ratio value of MYC mRNA showed 0.15±0.03 and 2.36±0.20, miR-540-3p displays 3.00±0.43 and 0.79±0.01, circRNA_04996 showed 1.43±0.43 and 3.14±0.94. At the same time, the four kinds of inflammatory reaction-related genes plasminogen activator urokinase receptor (PLAUR), tumor necrosis factor (TNF), interleukin 1 receptor type 2 (IL1R2), ect, which were prometed in expression by MYC, were down-regulated at 0 hour after PH, but the inflammatory reaction-related genes natriuretic peptide A (NPPA), nuclear receptor subfamily O group B member 2 (NROB2) and peroxisome proliferator activated receptor alpha (PPARA), which were inhibited in expression by MYC, were up-regulated at 0 hour after PH. On the other hand, the three kinds of inflammatory reaction-related genes PLAUR, TNF, IL1R2, ect, which are prometed in expression by MYC, were up-regulated at 6 hours after PH, but the inflammatory reaction-related genes NPPA, NROB2 and PPARA, which were inhibited in expression by MYC, were down-regulated at 6 hours after PH. Conclusion The correlation in expression and role of the miRNA, which are inhibited by circRNAs, MYC, its mRNA is inhibited by miRNAs, and the inflammatory reaction-related genes, which are regulated by MYC, and are helpful for the hepatocyte to be in non-inflammatory reaction state at 0 hour after PH and to be in inflammatory reaction state at 6 hours after PH.
8.Reconstuctive strategy of the defect of anterior rectus fascia and rectus abdominus muscle
Guangxue LI ; Yan LIU ; Cai WANG ; Huiran ZANG ; Kai YANG
Chinese Journal of Medical Aesthetics and Cosmetology 2021;27(1):42-45
Objective:To discuss the reconstuctive strategy of the defect of anterior rectus fascia and rectus abdominus muscle in the clinical practice.Methods:Between November 2009 and Janurary 2020, clinical data of 24 female patients that underwent 29 anterior rectus fascia and rectus abdominus muscle reconstructions of defect were reviewed retrospectively. The median age was 42.5 years (range, 35-60 years), including 20 breast reconstructions, 2 pelvic reconstructions, 1 thoracic defect after tumor resection and 1 abdominal defect after tumor resection. According to the location and size of the anterior rectus fascia and rectus abdominus muscle defect, three reconstructive methods were applied: 6 direct clousres were applied if the width of defect was less than half of the anterior rectus fascia, 21 polypropylene mesh onlay reconstructions were applied for which the width of defect was or more than half of the anterior rectus fascia, and 2 direct suture closure were applied for the simple rectus abdominus muscle defect.Results:All the patients healed eventfully without abdominal wound complications, such as infection, hematoma, dehiscence. The patients were followed up for a median period of 30 months (range, 5-126 months). 1 patient died of breast cancer recurrence and matastasis at 36 months postoperatively. No patient developed a mesh infection or required mesh removal secondary to infection or foreign body reaction. There was no abdominal wall hernia, 1 patient developed abdominal bulge without further treatment because of no abdominal wall discomfort.Conclusions:The key of successful operation is different reconstructive methods applied to reconstruct the integrity and stability of abdominal wall, based on the location and size of the anterior rectus fascia and rectus abdominus muscle defect.
9.68Ga-PSMA PET/CT-targeted biopsy for the diagnosis of clinically significant prostate cancer in patients with serum PSA levels <20.0 ng/ml
Zheng XU ; Lele ZHANG ; Fei YU ; Wencheng LI ; Shiming ZANG ; Luwei XU ; Feng WANG ; Wenbin HUANG ; Kai LIANG ; Jianghao SU ; Jiageng ZHU ; Hongbin SUN
Chinese Journal of Urology 2020;41(10):752-756
Objective:To evaluate the feasibility and efficacy of 68Ga-PSMA PET/CT-guided targeted prostate biopsy for the diagnosis of clinically significant prostate cancer(csPCa). Methods:This retrospective analysis allocated 89 patients with elevated PSA levels between 4.0-20.0 ng/ml to PET group(n=48) or TRUS group(n=41) between September 2017 and June 2019. Patients with PSMA-avid lesions (SUV max≥8.0) underwent PET-TB via a single-puncture percutaneous transgluteal approach (n=19), while patients with negative PSMA-PET underwent systematic TRUS-GB (n=29). Patients in the TRUS group who did not get 68Ga-PSMA PET/CT examination underwent TRUS-GB directly (n=41). The mean age, prostate volume, PSA value of PET group and TURS group were (71.2±9.1) years vs. (68.0±12.0) years, (62.9±29.1)ml vs. (65.4±38.9)ml , 8.8(6.6, 13.6) ng/ml vs. 9.8(7.1, 13.1)ng/ml, respectively (all P>0.05). The diagnostic efficacy and difference of PCa and csPCa between the two groups were compared. PET-TB adopts a new mode of percutaneous gluteus approach and carries out precise image fusion of PSMA-PET/CT and pelvic CT in the same machine and in the same position (prone position). Under the direct guidance of CT, the biopsy is performed with only one precise puncture. Results:PCa and csPCa were detected in 27/89(30.3%)and 20/89(22.5%)in all patients. PET group detected significantly more cases of PCa and csPCa than those of TRUS group [PCa: 41.7%(20/48) vs. 17.1%(7/41), χ2=6.328; csPCa: 33.3%(16/48) vs. 9.8%(4/41), χ2=7.055, P<0.01]. Of 19 patients with PSMA-PET positive, PET-TB detected 16 cases of PCa(84.2%) by a single needle puncture, and the proportions of cancer tissues were ≥80% in 2, 50%-79% in 8, and <50% in 6 cases. Among these, Gleason score was underestimated by biopsy histopathology in 2 patients. Of 3 patients with PET-TB negative, 1 case of low-risk PCa(Gleason 3+ 3) was detected by complementary TRUS-GB. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy of 68Ga-PSMA PET/CT(SUV max≥8.0) for the diagnosis of csPCa were 73.9%(14/19), 93.1%(27/29), 87.5%(14/16), 81.3%(26/32)and 85.4%(41/48), respectively. For PET-TB, only one patient had slight symptoms of haematuria after the puncture, no cases of hematochezia, hemospermia, urinary retention or pelvic infection were observed. Conclusions:68Ga-PSMA PET/CT is a feasible novel puncture technique that may serve as a triage tool for prostate biopsy, and PET-TB may improve the detection rate of csPCa compared with TURS-GB, especially in patients with serum PSA 4.0-20.0 ng/ml.
10.Common errors analysis on measuring the APPLS related future liver remnant with CT′s image post-processing software
Kai TAN ; Xilin DU ; Zhou LIU ; Ke WU ; An CHEN ; Tao YANG ; Li ZANG ; Xiaojun HE ; Zhenyu YANG
Chinese Journal of General Surgery 2020;35(4):288-291
Objective:To explore whether CT image post-processing software can accurately measure (associating liver partition and portal vein ligation for staged hepatectomy, ALPPS) related (future liver remnant, FLR).Methods:Clinical data of 9 liver cancer patients undergoing ALPPS were retrospectively analyzed in the Second Affiliated Hospital of Air Force Military Medical University from Mar 2015 to May 2019. All cases were divided into 2 groups by measurement: CT′s image post-processing software, or Myrian software. Two groups were compared with each other by paired t-test. Results:FLR from group CT′s image post-processing software was larger than that by Myrian software, there was statistical difference ( t=2.512, P=0.019). The mistakes of FLR measurements by the radiologist using CT′s image post-processing software couldbe caused by: (1)Lacking theoretical knowledge of liver surgery; (2) Adding devitalized tissue of hepatic section into future liver remnant; (3) Concept confusion about liver anatomy; (4) Lack of precision measurement. Conclusions:The inaccuracies generated during the ALPPS related future liver remnant measurements in CT′s image post-processing technique are all caused by human factors. These problems could be solved if the radiologist who operates 3D reconstruction receives liver surgery training or works with liver surgeons.

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