1.An integrated prognostic model of nuclear-encoded mitochondrial gene signature and clinical information for hepatocellular carcinoma
Aishanjiang KEDEERYA ; Yi FU ; Donglin LAI ; Hailong WU ; Wei GONG
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(1):1-12
Objective·To establish a prognostic model for the overall survival(OS)of hepatocellular carcinoma(HCC)based on mitochondrial genes and clinical information.Methods·The gene expression and the clinical data of 369 HCC patients and 50 controls with normal liver were downloaded from The Cancer Genome Atlas(TCGA)database.The nuclear-encoded mitochondrial genes(NEMGs)were obtained from the MitoCarta3.0 database.The"DESeq2"R package and univariate Cox analysis were used to select NEMGs[ubiquinol cytochrome C reductase hinge protein(UQCRH),ATP citrate lyase(ACLY),phosphoenolpyruvate carboxykinase 2(PCK2),Bcl-2 homologous antagonist/killer1(BAK1),Bcl-2-associated X protein(BAX)and Bcl-2/adenovirus E1B interacting protein 3-like(BNIP3L)]in HCC that were associated with OS of HCC and participated in dysregulation of oxidative phosphorylation,tricarboxylic acid cycle and cell apoptosis.Multivariate Cox analysis was applied to select independent risk factors for OS of HCC.A comprehensive prognostic model and a prognostic nomogram with 6-NEMG risk characteristics and TNM staging were established.By using the median of prognostic scores as a cut-off,HCC patients were classified into low-risk and high-risk group.Kaplan-Meier survival curve analysis was conducted and log-rank test was performed to evaluate the survival rates between the low-risk and high-risk group.The area under the curve(AUC)values of receiver operating characteristic(ROC)curve were calculated via using the"timeROC"package.The prognostic model for HCC was validated by using the GEO HCC cohort(GSE14520)for 1,3 and 5 years.Finally,the relative expression level of 6-NEMG was validated in 34 clinical samples of HCC from Xinhua Hospital,Shanghai Jiao Tong University School of Medicine by using real-time quantitative polymerase chain reaction(qPCR)method.Results·Compared to 6-NEMG risk signature only(AUCs for 1,3 and 5 years were 0.77,0.66 and 0.65,respectively)or TNM stage only(AUCs for 1,3 and 5 years were 0.66,0.67 and 0.63,respectively),ROC curve analysis showed that this integrated prognostic model displayed better predictive performance for 1-year(AUC,0.78),3-year(AUC,0.73)and 5-year(AUC,0.69)OS of HCC.The Kaplan-Meier survival curve analysis showed that the OS of HCC patients in the high-risk group was significantly worse than that in the low-risk group(P=0.001).In addition,predictive performance of the prognostic model(AUC for 1,3 and 5 years is 0.67,0.66 and 0.74,respectively)and prognostic differences between the high-risk and low-risk group(P=0.001)were further validated in GEO(GSE14520)external cohort,and these results were consistent with the TCGA data.In addition to BNIP3L,dysregulation of five other NEMGs in the clinical HCC cohort was validated.The correlation analysis in GSE14520 and HCC clinical cohort showed a positive correlation between prognosis score and the size and number of tumors.Conclusion·A new prognostic model that combines 6-NEMG risk characteristics with TNM staging for predicting OS in HCC patients was constructed and validated.This model may help improve the prognosis prediction of HCC patients.
2.Research progress on SENP1/HIF-1α regulation of vascular differentiation of dental pulp stem cells
Juan TANG ; Donglin YU ; Honghai FU
Journal of Chinese Physician 2024;26(1):146-150
Dental pulp stem cells (DPSC) are pluripotent stem cells with high differentiation potential isolated from dental pulp. Using DPSC for vascular regeneration may be a good option. Hypoxia inducible factor-1α (HIF-1α) is an upstream gene of vascular endothelial growth factor (VEGF), and the small ubiquitin like protease 1 (SENP1) can reverse the small ubiquitin like (SUMO) modification of HIF-1α. Through the regulation of SENP1/HIF-1α, good vascular regeneration characteristics have been demonstrated in many in vitro and in vivo experiments. The SENP1/HIF-1α signaling axis has varying degrees of promoting and inhibiting effects on many solid tumors. Although there is relatively little literature on the role of the SENP1/HIF-1α signaling axis in dental pulp stem cells, it can be determined that SENP1/HIF-1α plays an important role in the angiogenesis of dental pulp stem cells. This article will elucidate the SENP1/HIF-1α signaling pathway and its mechanism of promoting vascular differentiation of DPSC.
3.Effect of sevoflurane inhalation anesthesia on postoperative extubation time and major adverse cardiovascular events incidence in patients undergoing mitral valve replacement
Shuangqin WANG ; Yuguang XU ; Wenlong GUO ; Xianhui TAN ; Donglin FU ; Guiping XING ; Gui LI ; Shuangyi LIU
Journal of Chinese Physician 2020;22(4):535-538,543
Objective:To explore the application value of sevoflurane inhalation anesthesia in mitral valve replacement.Methods:A total of 94 patients who underwent mitral valve replacement in our hospital (October 2016-October 2018) were randomly divided into the control group ( n=47) and the observation group ( n=47). The control group received target-controlled infusion of propofol, and the observation group inhaled sevoflurane.The postoperative conditions [intensive care unit (ICU) stay time, extubation time of tracheal tube, spontaneous cardiac rebound], hemodynamic indexes [mean arterial pressure (MAP), heart rate (HR)], serum creatine phosphokinase isoenzyme (CK-MB), cardiac troponin I (cTnI), malondialdehyde (MDA) and superoxide dismutase (SOD) in the two groups were analyzed. The patients were followed up for one month. The incidence of major adverse cardiovascular events (MACE) was calculated. Results:⑴ Postoperative situation: the time of stay in ICU and extubation of tracheal tube in the observation group was shorter than that in the control group, and the rate of spontaneous cardiac rebound (93.62%) was higher than that in the control group (72.34%) ( P<0.05); ⑵ Hemodynamic index level: there was no statistically significant difference in MAP and HR levels between two groups before operation, before cardiopulmonary bypass, after cardiopulmonary bypass, and after operation ( P>0.05); ⑶ CK-MB and cTnI: the levels of serum CK-MB and cTnI in the two groups were higher at 2, 6, 24, and 48 h after aortic cross-clamp release than before anesthesia induction, but the indicators of the observation group were lower than those in the control group; ⑷ MDA and SOD: the serum SOD level in the two groups at 2, 6, 24, and 48 h after aortic cross-clamp release were lower than before anesthesia induction, and the MDA level in the two groups at 2, 6, 24, and 48 h after aortic cross-clamp release were higher than before anesthesia induction. The level of SOD in the observation group was higher than that in the control group, and the level of MDA was lower than that in the control group ( P<0.05); ⑸ MACE: the incidence of MACE in the observation group (12.77%) was lower than that of the control group (29.79%) ( P<0.05). Conclusions:During mitral valve replacement, sevoflurane inhalation anesthesia can maintain hemodynamic stability. The duration of ICU stay and tracheal tube extubation time is shorter, and the fluctuation of serum CK-MB, cTnI, MDA and SOD is small, and it can reduce the risk of MACE.
5.Total synthesis of cyclodepsipeptide Hikiamides A-C
Donglin FU ; Xuemin RAO ; Jinyi XU ; Weijia XIE ; Xiaoming WU
Journal of China Pharmaceutical University 2018;49(2):181-186
Total synthesis of cyclodepsipeptide Hikiamides A-C was described. Fragment convergent condensation method was applied for the preparation of Hikiamides A-C, starting from Commercially available amino acid such as L-N-Boc-Phe-OH, L-N-Boc-Trp-OH, L-N-Cbz-Van-OH etc. Tripeptide fragments(compounds 5a/5b)and dipeptide fragments(compounds 8a/8b)were first prepared. The subsequent condensation of the resulted two fragments provided protected linear pentapetides(compounds 9a/9b/9c); Finally, the linear pentapetide was cyclized by a mixed condensing agents comprised of PyBOP and HBTU. Hikiamides A-C was obtained with total yields of 9%, 11% and 6. 5%, respectively. Compared with the natural source, this method has the advantages of low cost, convenient operation and high yield, which effectively solves the problem of low isolated yield of Hikiamides A-C from Fusarium sp.
6.Effect of Ultrasound Elastic Imaging and Contrast-enhanced ultrasound in the Evaluation of Hepatic Fibro-sis in Patients with Chronic Hepatitis B
Tangna WU ; Shaoqing FU ; Bingyan LIU ; Donglin WANG
The Journal of Practical Medicine 2017;33(23):3983-3986
Objective To evaluate the effect of ultrasound elastography and radiography in the assessment of hepatic fibrosis in chronic hepatitis B patients. Methods Seventy patients with chronic hepatitis B were en-rolled in our hospital from August 2014 to August 2016. Liver ultrasonography was performed in all patients. HAVTT1 and HAVTT2 were measured by visual method. SWV was measured by ultrasonic elasticity imaging. Re-sults With the increase of liver fibrosis,SWV test also increased,while HAVTT gradually shortened.The correct rates of HAVTT1 and HAVTT2 and SWV in the diagnosis of liver fibrosis were 72.36%,76.84% and 89.78%.The diagnostic accuracy of SWV was higher than that of HAVTT1 and HAVTT2,the difference was statistically sig-nificant(P<0.05).Conclusion Acoustic contrast measurement of HAVTT1 and HAVTT2 can reflect the chang-es of liver microcirculation,which is helpful to distinguish liver cirrhosis,fibrosis and no fibrosis. The measure-ment of SWV can reflect the difference of texture hardness of liver,which can be used as a kind of judgment on the degree and effect of hepatic fibrosis new method.
7.Application of high frequency ultrasound in triangular fibrous cartilage complex injury of wrist joint
Donglin WANG ; Bingyan LIU ; Shaoqing FU ; Tangna WU
Chinese Journal of Interventional Imaging and Therapy 2017;14(9):552-555
Objective To discuss the ultrasonic features and diagnostic value of high frequency ultrasound in the diagnosis of the injury of triangular fibrous cartilage complex (TFCC) of wrist joint.Methods The ultrasonic features of 32 patients with pathology confirmed unilateral TFCC injury were retrospectively analyzed.The preoperative MRI and ultrasound data were complete.The difference between the two methods in diagnosis of TFCC injury were contrasted.Results The major ultrasonic features of the injure of TFCC included form swelled,structures disorganized,inhomogeneous echoes,irregular echoless in damaged place.The flow signals could be displayed from the tear opening edge of the injured TFCC by CDFI.Among 32 cases of TFCC injury,there were 26 cases (26/32,81.25%) diagnosed by ultrasound and 27 cases (27/32,84.38%) diagnosed by MRI.There was no significant difference in the detection rate of the two methods for TFCC injury (x2 =0.143,P=0.706).Conclusion High frequency ultrasound can be used to diagnose the injury of TFCC accurately,and can provide imaging evidence simply and rapidly for clinical therapy.
8.EGFP gene transfection into the joint synovial tissues of rheumatoid arthritis rats by ultrasound-mediated microbubble destruction
Xiangxiang JING ; Jie LIU ; Bingang YANG ; Shaoqing FU ; Bingyan LIU ; Tangna WU ; Donglin WANG
Chinese Journal of Ultrasonography 2013;22(10):897-900
Objective To explore the feasibility of enhanced green fluorescent protein (EGFP) transfection into the joint synovial tissues of rheumatoid arthritis (RA) rats by ultrasound-mediated microbubble destruction.Methods Twenty-eight normal rats were established the RA rat model,four rats were control group,twenty-four rats were categorized into four experimental groups:EGFP,ultrasound +EGFP,microbubbles + EGFP,and ultrasound + microbubbles + EGFP.The last group was irradiated with ultrasound for 10 min after the mixture consisting of 300 μl Sono Vue and 10 μg EGFP was injected into the joint cavity.The rats were sacrificed after 3 days and the joint synovial tissues were collected for EGFP observation under fluorescence microscopy and quantitative analysis by real-time polymerase chain reaction (RT-PCR).Results Comparing with control group,EGFP expression was observed in the rat joint synovial tissues from all groups.However,a strong EGFP expression was observed in the ultrasound + microbubbles +EGFP group.EGFP expression had no statistically significant difference (the P values were 0.89,0.93,and 0.82,respectively,P > 0.05) in the EGFP,ultrasound + EGFP and microbubbles + EGFP groups.However,EGFP expression in the EGFP,ultrasound + EGFP,microbubbles + EGFP groups significantly differed (all P values were <0.01) from that in the ultrasound + microbubbles + EGFP group.Conclusions Ultrasound-mediated microbubble destruction can improve EGFP transfection efficiency into the joint synovial tissues of RA rats.
9.Monitoring on extravascular lung water in patients with septic shock and its prognostic value
Yusheng CHEN ; Yonghong FU ; Donglin XV ; Jiyun LIU ; Zhi YANG
Chinese Journal of Postgraduates of Medicine 2011;34(16):9-12
Objective To analyze the alterative characteristics of the extravascular lung water (EVLW ) in the patients with septic shock and clarify its value on the prognosis of these patients.Methods By the methods of retrospective analysis,according to the ultimate survival,21 patients with septic shock were divided into survivor group (10 cases) and non-survivor group (11 cases).The clinical features of the patients were observed and hemodynamic monitoring was made with PiCCO monitor.The EVLW was measured and the relationship between the EVLW and the prognosis of patients was analyzed.Results On the first,second and third day,EVLW was (12.7 ±1.8),(11.3 ±1.3),(10.1 ±1.3) ml/kg in survivor group,and (14.4 ± 1.0),(14.6 ± 1.4),(14.6 ±1.3) ml/kg in non-survivor group respectively,and there were statistical differences between two groups (P <0.05).However,on the second day after the intensive therapy,EVLW in survivor group dropped significantly(P<0.05),but the non-survivor group only declined slightly,and compared with the result of the first day,there was no obvious difference (P >0.05).Conclusions The EVLW in the patients with septic shock increases significantly.The dynamic changes of the EVLW may be one of the factors for predicting the prognosis of patients with septic shock.
10.Bioeffects of ultrasound combined with contrast media on joints synovial of normal rats
Xiangxiang JING ; Jie LIU ; Bingang YANG ; Shaoqing FU ; Tangna WU ; Donglin WANG
Chinese Journal of Medical Imaging Technology 2010;26(4):609-611
Objective To observe the bioeffects on the normal rats synovial with diagnostic ultrasound combined with different doses contrast medium. Methods Twenty normal cleaning level Wister rats were divided into 5 groups (each with 4 rats and 8 knees): ultrasound+100 μl contrast medium, ultrasound+200 μl contrast medium, ultrasound+300 μl contrast medium, ultrasound+500 μl contrast medium, a simple ultrasound irradiation (control group). Each group was irradiated with diagnostic ultrasound for 10 min. Rats were sacrificed after 1 week and joints synovial tissues were observed with pathological HE staining. Results In group ultrasound+100 μl contrast medium, ultrasound+200 μl contrast medium, ultrasound+300 μl contrast medium and control group, no significant damage in synovial tissues was found. In group ultrasound+500 μl contrast medium, synovial cells swelling, showing round, oval or polygonal, synovial tissues hyperplasia, arranged disorder, capillary proliferation, some muscle fiber structure dissolved fracture, inflammatory cell infiltration in the surrounding tissue were found. Conclusion Ultrasound combined with contrast medium can significantly enhance the bioeffects of synovial tissues, and the more the contrast medium doses, the more serious injury occurs in synovial tissues.

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