1.Effects of glycolipid transfer protein on proliferation,migration and invasion of pancreatic cancer PANC-1 cells and their mechanisms
Mengyun LU ; Yucheng HAN ; Yihong HU ; Minhui HE ; Yanqun ZHANG ; Xianqiong ZOU
Journal of Jilin University(Medicine Edition) 2025;51(2):284-295
Objective:To investigate the effects of human glycolipid transfer protein(GLTP)on proliferation,migration and invasion of pancreatic cancer(PC)cells,and to elucidate their mechanisms.Methods:The difference in the expression levels of GLTP proteins between PC tissue and normal pancreas tissue was analyzed by University of Alabama at Birmingham Cancer Data Analysis Platform(UALCAN)Database,as well as the difference in the expression levels of GLTP protein between PC tissue and normal pancreas tissue of the PC patients with different clinicopathological characteristics.The PANC-1 cells were cultured in vitro and divided into control group(transfected with pFLAG-CMV4 plasmid)and GLTP-overexpression(GLTP-OE)group(transfected with pFLAG-GLTP plasmid).The stably GLTP transfected cells were established using the antibiotic screening method.Knock-down experiments were performed using non-specific siRNA transfected PANC-1 cells as control group and si-GLTP transfected PANC-1 cells as si-GLTP group.Western blotting method was used to detect the expression of GLTP protein in the cells in various groups,cell counting kit-8(CCK-8)method was used to detect the proliferation activities of PANC-1 cells,clone formation assay was used to detect the number of clone formation,and Transwell chamber assay were used to detect the numbers of migration and invasion cells in various groups.Transcriptomics sequencing analyses were conducted to assess the possible mechanism of GLTP in the PANC-1 cells.Western blotting method was employed to detect the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt)proteins in the PANC-1 cells in various groups;Real-time fluorescence quantitative PCR(RT-qPCR)was used to assess the expression levels of amphiregulin(AREG)and kinase insertion domain receptor(KDR)mRNA in the cells in various groups.The mice were randomly divided into control group(injected with pFLAG-GMV4 transfected PANC-1 cells)and experimental group(injected with pFLAG-GLTP stably transfected PANC-1 cells),and the subcutaneously transplanted tumor models were prepared;the volumes and weights of the transplanted tumors of the mice in two groups were measured.Results:UALCAN database analysis showed that the expression level of GLTP protein in PC tissue was lower than that in normal pancreas tissue(P<0.01),and there were statistically significant differences in the GLTP protein expression between PC tissue and normal pancreas tissue of the PC patients with different cancer stages(P<0.05),tumor grades(P<0.05),ages(P<0.001),and genders(P<0.05).Compared with control group,the proliferation activity(P<0.01)and the number of clone formation(P<0.001)of the cells in GLTP-OE group were decreased,while the numbers of migration cells(P<0.001)and invasion cells(P<0.01)were decreased.In the knock-down experiment,compared with control group,the proliferation activity(P<0.01)and the number of clone formation(P<0.05)of the cells in GLTP-OE group were increased,while the numbers of migration cells(P<0.001)and invasion cells(P<0.001)were increased.Compared with control group,the tumor weight and volume of the mice in experimental group were decreased(P<0.01),following the injection of tumor cells for a period of four weeks.In the over-expression experiment,compared with control group,the expression levels of p-PI3K(P<0.01),p-Akt-S473(P<0.01),and p-Akt-T308(P<0.05)proteins in the cells in GLTP-OE group were decreased;the expression levels of AREG(P<0.01)and KDR(P<0.01)mRNA were decreased.In the knock-down experiment,compared with control group,the expression levels of p-PI3K(P<0.01),p-Akt-S473(P<0.01),and p-Akt-T308(P<0.01)in the cells in si-GLPT group were increased,and the expression levels of AREG(P<0.01)and KDR(P<0.05)mRNA were increased.Conclusion:Low expression levels of GLTP in PC tissue are present.The over-expression of GLTP can inhibit the proliferation,migration and invasion of PANC-1 cells,as well as the growth of subcutaneously transplanted tumors in the nude mice;its possible mechanism may be related to decreasing the activity of the PI3K/Akt signaling pathway.
2.Two types of coumarins-specific enzymes complete the last missing steps in pyran- and furanocoumarins biosynthesis.
Yucheng ZHAO ; Yuedong HE ; Liangliang HAN ; Libo ZHANG ; Yuanzheng XIA ; Fucheng YIN ; Xiaobing WANG ; Deqing ZHAO ; Sheng XU ; Fei QIAO ; Yibei XIAO ; Lingyi KONG
Acta Pharmaceutica Sinica B 2024;14(2):869-880
Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.
3.IgG4-related disease presenting as a ureteral tumor: a case report
Longzhi HE ; Yucheng GE ; Zhenqiang ZHAO ; Yukun LIU ; Siyu QI ; Chen NING ; Wenying WANG
Chinese Journal of Urology 2024;45(5):395-396
IgG4-related disease (IgG4-RD) involving the ureter manifested as a ureteral tumor is rare. This paper reports a case of a female patient who was found with a mass at the left ureteropelvic junction for one week during physical examination. Urinary ultrasound and MRI showed a 3 cm mass at the left ureteropelvic junction with hydronephrosis, and the serum level of IgG4 was elevated. B-ultrasonic guided biopsy of the mass was performed. Histopathological findings showed lymphoplasmic infiltration and the ratio of IgG4/IgG positive cells>0.5. We finally diagnosed IgG4-RD and started using glucocorticoid for her treatment. One month later, CT-scan revealed that the tumor became smaller and the serum IgG4 decreased to the normal range.
4.Ectopic prostate in the pelvis: a case report
Longzhi HE ; Yucheng GE ; Zhenqiang ZHAO ; Yukun LIU ; Siyu QI ; Chen NING ; Wenying WANG
Chinese Journal of Urology 2024;45(8):631-632
Ectopic prostate is rare.This paper reports a case of a male patient who was found a mass in the pelvis for 20 days during physical examination.Urinary ultrasound, CT scan and MRI showed a pelvic mass that was about 4 cm×5 cm in size.Serum total prostate specific antigen (tPSA) was 6.09 ng/ml, and free PSA (fPSA) was 1.97 ng/ml. B-ultrasonic guided biopsy of the prostate and the mass was performed. Pathological findings suggest benign prostatic hyperplasia, weakly positive P504S and positive 34βE12. Pelvic mass is the prostate tissue with negative P504S and positive 34βE12. Finally, the ectopic prostate was diagnosed. Although it is rare, ectopic prostate should also be considered as a differential diagnosis of the pelvic tumor.
5.Minimally invasive robot-assisted treatment of tibial plateau fractures of Schatzker types Ⅱ and Ⅲ that can be indirectly reduced
Fei XIAO ; Wenping HE ; Junwen WANG ; Jing JIAO ; Ming CHEN ; Yucheng HUANG ; Keke CHENG ; Tianrun LEI
Chinese Journal of Orthopaedic Trauma 2024;26(7):604-610
Objective:To explore the advantages of minimally invasive internal fixation assisted by an orthopedic robot in the treatment of tibial plateau fractures of Schatzker types Ⅱ and Ⅲ that can be indirectly reduced.Methods:A retrospective study was conducted of the 18 patients who had been treated for tibial plateau fractures of Schatzker types Ⅱ and Ⅲ at Department of Orthopaedics, The Fourth Hospital of Wuhan from December 2019 to December 2021. They were 12 males and 6 females with an age of (45.2±9.6) years. All fractures were closed. Of them, 6 were complicated with an avulsion fracture at the insertion point of the anterior cruciate ligament, 1 with tear of the medial collateral ligament, and 8 with tear of the lateral meniscus. All patients were treated with minimally invasive internal fixation using the "fence" screw technique after indirect reduction assisted by an orthopedic surgical robot. Those combined with avulsion fracture of the anterior cruciate ligament and meniscus tear underwent one-stage arthroscopic surgery, while those combined with tear of the medial collateral ligament underwent one-stage open repair. The fracture reduction was evaluated according to the Rasmussen radiological scoring system, and the knee joint function evaluated using the American Hospital for Special Surgery (HSS) scoring system.Results:All the 18 patients were fully followed up for (10.6±1.9) months. The X-ray films immediately after surgery showed good fracture reduction. The fractures healed after (11.3±1.2) weeks. At 6 months after surgery, the Rasmussen knee score was (16.8±1.0) points, giving 5 excellent and 13 good cases; the HSS score was (93.2±3.0) points, giving 17 excellent and 1 good cases. By the last follow-up, no serious complications occurred, such as common peroneal nerve injury, popliteal vascular injury, postoperative infection, or internal fixation failure.Conclusion:Since minimally invasive internal fixation assisted by an orthopedic robot can lead to fine clinical efficacy for tibial plateau fractures of Schatzker types Ⅱ and Ⅲ, this technique can be widely applied in clinical practice.
6.TITE(e)-U-Keyboard:a Two-stage Phase Ⅰ/Ⅱ Design
Juan HE ; Wenyun YANG ; Yucheng ZHANG
Chinese Journal of Health Statistics 2023;40(6):811-816
Objective Aiming at the problem of delayed therapeutic effect of tumor targeting agents and cellular immunotherapy,an innovative TITE(e)-U-Keyboard design is established based on the framework of phaseⅠ/Ⅱclinical trial design.Methods Approximated binomial likelihood method was used to incorporate the unobserved efficacy outcome information and construct approximated distribution to assist decision making.TITE(e)-U-Keyboard was compared with theⅠ/Ⅱ trial design method(U-BOIN、BOIN12)from multiple perspectives.Results Simulation results show that the accuracy of OBD selection and the number of patients allocated at optimal dose of the three methods were similar,but TITE(e)-U-Keyboard requires the shortest trial duration.Sensitivity analysis shows that the effectiveness evaluation window has an effect on the TITE(e)-U-Keyboard duration,which increases with the increase of effectiveness evaluation window.Conclusion TITE(e)-U-Keyboard significantly reduces the trial duration while maintaining good simulation performance and it can address the problem of delayed treatment effects in phase Ⅰ/Ⅱ clinical trials,thus accelerating the clinical trial process.
7.Research on a portable shielding-free ultra-low field magnetic resonance imaging system.
Yuxiang ZHANG ; Wei HE ; Lei YANG ; Yucheng HE ; Jiamin WU ; Zheng XU
Journal of Biomedical Engineering 2023;40(5):829-836
The portable light-weight magnetic resonance imaging system can be deployed in special occasions such as Intensive Care Unit (ICU) and ambulances, making it possible to implement bedside monitoring imaging systems, mobile stroke units and magnetic resonance platforms in remote areas. Compared with medium and high field imaging systems, ultra-low-field magnetic resonance imaging equipment utilizes light-weight permanent magnets, which are compact and easy to move. However, the image quality is highly susceptible to external electromagnetic interference without a shielded room and there are still many key technical problems in hardware design to be solved. In this paper, the system hardware design and environmental electromagnetic interference elimination algorithm were studied. Consequently, some research results were obtained and a prototype of portable shielding-free 50 mT magnetic resonance imaging system was built. The light-weight magnet and its uniformity, coil system and noise elimination algorithm and human brain imaging were verified. Finally, high-quality images of the healthy human brain were obtained. The results of this study would provide reference for the development and application of ultra-low-field magnetic resonance imaging technology.
Humans
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Magnetic Resonance Imaging/methods*
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Magnetic Resonance Spectroscopy/methods*
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Head
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Equipment Design
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Magnets
8.Short-term clinical and echocardiographic outcomes of the novel domestic transcatheter edge-to-edge repair Neonova? system in patients with mitral regurgitation
Yun YANG ; He LI ; Wenqian WU ; Xiaoke SHANG ; Shu CHEN ; Yucheng ZHONG ; Manwei LIU ; Lin HE ; Zhenxing SUN ; Ziming ZHANG ; Yi ZHOU ; Xin ZHANG ; Nianguo DONG ; Lingyun FANG ; Mingxing XIE
Chinese Journal of Ultrasonography 2023;32(1):51-59
Objective:To investigate short-term safety, efficacy and the learning curve of this self-developed novel transcatheter valve repair system (Neonova?) in patients with mitral regurgitation, and explore the role of perioperative echocardiography.Methods:Ten patients who visited the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from June 2021 to March 2022 and met the inclusive criteria were prospectively enrolled. All the patients were at high risk of surgery with moderate to severe or severe mitral regurgitation (MR). Clamps of Neonova? were implanted under guidance of transesophageal echocardiography and digital subtraction angiography. Clinical outcomes, echocardiography indexes and learning curves of this technique were evaluated immediately after intervention, 7 d, 1 month and 3 months post-intervention.Results:The technical success rate was 100% with MR relieved in all patients immediately after intervention. The device and procedural success rates were both 90.0% with 1 patient received surgical replacement at 37 days post-intervention while the others′ reduced to mild (8/9) and moderate (1/9) MR. New York Heart Association class and the Kansas City Cardiomyopathy Questionnaire improved significantly (all P<0.001). Mean mitral valve pressure gradient didn′t increase significantly after intervention when compared with that before intervention( P=0.324), and no mitral stenosis was observed. Left ventricular end-diastolic diameter decreased significantly ( P=0.008) during follow up.Procedure duration ranged from 60 to 300 (175.8±75.2)minutes. The simple linear regression model between procedure volume and duration showed that procedure duration decreased significantly with the increase of procedure volume ( F=15.857, P=0.004). Conclusions:Neonova? implantation can improve MR severity and clinical symptoms safely and effectively. Transthoracic echocardiography and transesophageal echocardiography are essential for perioperative management of transcatheter mitral valve repair.
9.Epidemiological characteristics of varicella in schools of Yunnan Province in 2018 - 2020
Rongbing ZHANG ; Jin HONG ; Lihua CHEN ; Xia PENG ; Jibo HE ; Zhenhui LI ; Yan LIN ; Yucheng JIA
Journal of Public Health and Preventive Medicine 2023;34(4):55-58
Objective To analyze the epidemiological characteristics of school varicella and varicella public health emergency event (PHEE) in Yunnan Province, and to provide a scientific basis for the prevention and control of varicella in schools. Methods The descriptive epidemiological method was used to analyze the reported PHEE of varicella in students and varicella in schools in Yunnan Province from 2018 to 2020. Results From 2018 to 2020, a total of 69,391 cases of varicella were reported in students in Yunnan Province, accounting for 71.48% (69 391 / 97 080) of the total cases in the province, and the annual average reported incidence rate was 255.56/100 000 (69 391/27.1522 million). The time distribution of the incidence showed double peaks, which were from May to July (26.48%) and October to January of the following year (53.88%). The incidence rates of different schools from high to low were 301.74/100 000 for primary schools (34 816/11.538 3 million), 250.43/100 000 for kindergarten (11 526/4.6024 million), 202.74/100 000 for middle school (16 779/8.276 1 million), and 119.07/100 000 for others (3 257/2.735 4 million). The age distribution was mainly concentrated in 5-9 years old, accounting for 39.81% (27 625/69 391). Varicella PHEE accounted for 25.64% (180/702)of the province's PHEE in the same period, school varicella PHEE accounted for 100% of varicella PHEE, and the attack rate was 3.38% (6 566/194 260). The sources of reported varicella PHEE were hospitals 45.40% (58/123), epidemic analysis 36.78% (44/123), schools 13.22% (15/123), and others 4.60% (6/123). Conclusion The incidence of varicella in schools in Yunnan Province is high, which is harmful to students. PHEE reported in rural schools are relatively lagging behind. On the basis of doing two doses of varicella vaccination, emergency prevention should be focused on epidemic seasons, lower grade schools and rural schools. The source of infection shall be controlled and managed in time to prevent the outbreak of the epidemic. It is recommended that varicella should be included in the management of Class C infectious diseases.
10.A comparative study on the success rate and safety between computed tomography-guided gastrostomy and endoscopic gastrostomy
Kepu DU ; Yucheng HE ; Xiaofei LOU ; Meng WANG ; Yadan LI ; Mengyu GAO ; Fei GAO ; Zhigang ZHOU
Chinese Journal of Digestion 2023;43(2):102-106
Objective:To compare and analyze the technical success rate and safety between computed tomography(CT)-percutaneous radiological gastrostomy (PRG) and percutaneous endoscopic gastrostomy (PEG).Methods:From January 2017 to January 2022, at the First Affiliated Hospital of Zhengzhou University, the data of 76 patients who underwent gastrostomy due to inability to eat orally were collected, including 38 patients in PEG group and 38 patients in CT-PRG group. Surgical outcomes and complications were compared between the PEG and CT-PRG groups. Surgical outcomes included technical success rate, operation time, postoperative body mass index and hospital stay; while complications included minor complications (such as perifistula infection, granulation tissue proliferation, leakage, pneumoperitoneum, fistula tube obstruction, fistula tube detachment and persistent pain) and serious complications (such as bleeding, peritonitis, colonic perforation and death within 30 d). Independent sample t test, chi-square test, and Fisher exact probability test were used for statistical analysis. Results:The technical success rate of CT-PRG group was higher than that of the PEG group (100.0%, 38/38 vs. 78.9%, 30/38), and the operation time was shorter than that of the PEG group ((17.16±8.52) min vs. (29.33±16.22) min), and the differences were statistically significant ( χ2=1.19, t=2.36; P=0.038 and 0.011). There were no significant differences in postoperative body mass index ((16.29±3.56) kg/m 2 vs. (16.12±3.17) kg/m 2) and hospital stay ((4.13±1.26) d vs. (3.52±1.13) d) between PEG group and CT-PRG group (both P>0.05). The incidence of minor complications in the PEG group was 42.1% (16/38), including 6 cases of perifistulal infection, 1 case of leakage, 5 cases of fistula tube obstruction, 1 case of fistula tube detachment, and 3 cases of persistent pain. The incidence of serious complications was 5.3% (2/38), including 1 case of bleeding and 1 case of colonic perforation. The incidence of minor complications in the CT-PRG group was 39.5% (15/38), including 5 cases of perifistula infection, 1 case of granulation tissue proliferation, 3 cases of pneumoperitoneum, 3 cases of fistula tube obstruction, 2 cases of fistula tube detachment, and 1 case of persistent pain. The incidence of serious complications was 0. There was no significant difference in the incidence of minor complications between the PEG group and the CT-PRG group ( P>0.05), while the incidence of serious complications in the CT-PRG group was lower than that of the PEG group, and the difference was statistically significant (Fisher exact probability test, P=0.043). Conclusion:PEG is a safe and effective method of gastrostomy, but for patients with esophageal obstruction, CT-PRG can be an effective supplement to PEG.


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