1.Sunitinib induces autophagy via suppressing Akt/mTOR pathway in renal cell carci-noma
Pei CAO ; Xuejun JIANG ; Zhijun XI
Journal of Peking University(Health Sciences) 2016;48(4):584-589
Objective:To determine the mechanism of sunitinib-induced autophagy in renal cell carci-noma cells.Methods:MTS assay was applied to detect the cell viability alteration under the treatment of sunitinib (2,8 μmol /L).The sunitinib-induced autophagy as well as cell apoptosis was measured and compared after knocking down autophagy-related protein Beclin1 and microtubule associated protein 1 light chain 3 fusion protein (LC3)by RNA interference.The transmission electron microscope was used to observe the formation of autophagosomes in ACHN cells.The fluorescence microscope was used to mo-nitor distribution and aggregation of endogenous LC3-Ⅱ.The expressions of protein such as LC3-Ⅱ,the autophagic regulation molecules protein kinase B /mammalian target of rapamycin (Akt/mTOR)and the symbol of apoptosis poly ADP-ribose polymerase (PARP)were capable to be detected by immunoblotting assay.Results:Sunitinib was able to significantly trigger cell viability loss in the renal carcinoma cell ACHN,which was both in a concentration-dependent and time-dependent manner (P <0.05 ).After reducing the autophagy by knocking down Beclin1 and LC3,the number of cleavage of PARP was in-creased remarkably,whereas there was nearly not any cleavage in the mock group.By the transmission electron microscope,there were more autophagic vacuoles in ACHN cells after being administrated with sunitininb compared with the control.And the nuclear-to-cytosol translocation as well as aggregation of LC3-Ⅱ was presented after sunitinib treatment by the fluorescence microscope,which was the proof of the enhanced autophagy.According to the immunoblotting,sunitinib was able to increase the accumula-tion of LC3-Ⅱ.At the same time,the result of sunitinib combined with chloroquine,a drug which blocked the fusion of autophagosomes and lysosomes,demonstrated that the increasing amount of LC3-Ⅱwas due to the enhanced autophagy flux by sunitinib treatment in ACHN cells.However,phosphorylation of Akt as well as mTOR was decreased at the same time.The rapamycin (mTOR inhibitor)or knocking down Akt subunits could change the sunitinib-induced LC3-Ⅱ accumulation,whereas overexpression of Akt subunits decreased the autophagic flux,indicating that Akt/mTOR was the target of sunitinib in auto-phagy.Conclusion:Sunitinib induced autophagy via suppressing Akt/mTOR pathway,and the auto-phagy was involved in apopotosis.
2.Studies of TLC and determination of three components in Wenweishu Tablets
Guiru HAN ; Zhijun ZHAO ; Zhiliang PEI
Chinese Traditional Patent Medicine 1992;0(01):-
AIM: To establish a simple and rapid method for the quality control of Chinese traditional medicine. METHODS: Pericarpium Citri Reticulatae,Fructus Psoraleae,Rhizoma Atractylodis macrocephalae and Radix Codonopsis in Wenweishu Tablets were identified by TLC at two thin-layer chromatographic plates.The contents for hesperidin,psoralen and isopsoralen in this preparation were determined simultaneously by HPLC. RESULTS: The methodological study showd that a good linear correlation existed in the range of 0.039 6-0.495 ?g(r=(0.999 99)) of hesperidin,0.018 5-0.231 ?g(r=0.999 98) of psoralen and 0.019 7-0.246 2 ?g(r=0.999 91) of isopsoralen applied respectively.The average recovery of hesperidin was 98.42%(n=9),RSD was 2.69%;The average recovery of psoralen was 98.29%(n=9),RSD was 1.08%.The average recovery of isopsoralen was(98.93%)(n=9),RSD was 2.41%. CONCLUSION: The method is simple、rapid and practicle.
3.Mesohepatectomy for large and centrally located hepatocellular carcinoma
Lianyue YANG ; Lei PEI ; Dipeng OU ; Wei WU ; Zhijun ZENG
Chinese Journal of Hepatobiliary Surgery 2012;18(4):245-248
Objective To evaluate the safety and efficacy of mesohepatectomy for large and centrally located hepatocellular carcinoma.Methods A retrospective study was carried out on 136 pa tients who underwent mesohepatectomy for large and centrally located hepatocellular carcinoma at Xiangya Hospital,Central South University,from 2001 to 2007.Intraoperative/post operative data and long-term survivals were analyzed.Results Vascular occlusion time,operative time,intraoperative blood loss,intraoperative blood transfusion and hospital stay were (13.3 ± 9.1) min,(173.1 ±41.1)min,(548.7±320.5)ml,(511.4±231.7)ml and (18.6±8.8)d,respectively.Four patients developed major complications.There was no in-hospital death.The 1-,3-,and 5-year overall survival rates and disease-free survival rates were 71%,46%,29% and 65%,40%,24%,respectively.Conclusions Mesohepatectomy for large and centrally located hepatocellular carcinoma preserved the maximum amount of functional liver parenchyma.It is safe and reliable and may be used as the treatment of choice.
4.Determination of 5 Hazardous Elements in Animal Traditional Chinese Medicines by ICP-MS
Chaohai LEI ; Zhijun ZHANG ; Pei LI ; Pingxiang JIANG
China Pharmacist 2017;20(8):1482-1485
Objective: To establish a method to determine 5 hazardous elements in animal traditional Chinese medicines (TCM) by microwave digestion-inductively coupled plasma mass spectrometry (ICP-MS).Methods: HNO 3-H 2 O 2 was used to decompose animal TCM, the working parameters of ICP-MS were optimized, and the matrix effect and the mass spectrum interferences were corrected by the in-line addition of Ge, In and Bi internal standard solution and the collided reaction cell technology (KED mode), respectively.Results: The detection limits of 5 hazardous elements were within the range of 0.04-0.52 μg·L-1 , the relative standard deviations (RSD) were within the range of 1.1%-4.8% , and the recoveries were within the range of 92.4%-110.0%.The method was applied to determine the 5 hazardous elements in 40 batches of animal TCM.The results indicated that some kinds of hazardous elements in animal TCM were high, and more attention should be paid to the problems in the production and use of animal TCM.Conclusion: The analysis method is simple, rapid and accurate, and suitable for the determination of hazardous elements in animal TCM.
5.Clinical engineering professional certification in Germany and implications for China
Zhijun PEI ; Bo HAO ; Zhimin GAO ; Bo TU
Chinese Medical Equipment Journal 2015;36(5):146-147,158
The general system of clinical engineering professional certification in Germany was introduced from the aspects of history, certification authority, requirement of certification, skills and knowledge points, methods of implementation and so on. Through comparative study, some suggestions were proposed to promote clinical engineering staff technology level assessment and certification, which might provide some references for the further improvement of clinical engineering certification system in China.
6.Establishment of a three-dimensional finite element model of cervical spine using computed tomography scan and compute aided design
Yu FU ; Dike RUAN ; Bin LIU ; Zhijun LI ; Pei ZHANG ; Chenguang LI
Chinese Journal of Tissue Engineering Research 2009;13(48):9563-9566
A finite element model of cervical spine was three-dimensionally reconstructed through computed tomography (CT) scan, recording the edges of image using Snigraphics V18.0 software, and calibrating in sequence of point, line, area, and solid. The stress distribution of cervical C_(3-4) was analyzed using compute aided design to validate the availability of reconstructed models. Results showed that the three-dimensional finite element cervical C_(3-4) was feasible in simulation analysis. These indicate that the established three-dimensional finite element models can simulate biomechanical experiments, providing foundations for analyzing biomechanical performance of local structure of this finite element model under various pressure conditions.
7.Gene mutations in 32 family with phenylketonuria
Yafen CHEN ; Xinye JIANG ; Zhonghai CHEN ; Haitao JIA ; Jingjing PEI ; Yali QIU ; Zhijun WU ; Jing WANG
Chinese Journal of Applied Clinical Pediatrics 2015;(20):1554-1556
Objective By detecting the mutations spectrum of phenylalanine hydroxylase(PAH)gene in phe-nylketonuria(PKU)patients and their parents. The researchers analyzed the gene mutation features and high - frequency mutations and determined the relationship between the genotype and the phenotype,which would provide a theoretical basis for the early diagnosis and genetic consultation of PKU children in the region. Methods In this study,13 exons and their flanking introns of the PAH gene in 32 PKU patients and their parents from Wuxi and Suqian in Jiangsu province were sequenced by using the next - generation sequencing(NGS)technology. Results Sixty - one mutant sites and 32 mutant genes were detected in 32 PKU patients,and the mutation detection rate was 95. 31%(61 / 64 cases). The variants at c. 721C ﹥ T,c. 1068C ﹥ A,c. 611A ﹥ G,c. 1197A ﹥ T,c. 728G ﹥ A,c. 331C ﹥ T and c. 442 -1G ﹥ A were common mutations in the region with mutation frequency over 5% . What's more,4 novel variants of c. 699C ﹥ G,c. 265C ﹥ T,c. 722G ﹥ A and c. 1194A ﹥ G were found. Of those,c. 699C ﹥ G was not recorded in the PAH variant database and HGMD database and. c. 265C ﹥ T,c. 722G ﹥ A,and c. 1194A ﹥ G were first reported in the Chi-nese population. Genotype - accurate biochemical phenotype correlation by using the Guldberg AV system revealed con-sistency rate of 38. 0%(8 / 21 cases),which the consistency rate between accurate biochemical phenotype and predic-tive phenotype of moderate to severe genotype was 92. 3%(12 / 13 cases),and mild genotype was 50. 0%(4 / 8 cases). Conclusions The PAH gene variants of PKU patients in Jiangsu province are distributed mainly in exons 7,of which the highest frequency gene mutation is c. 721 c ﹥ T. Moreover,one novel variant c. 699C ﹥ G was reported for the first time. The PKU children inherit the PAH mutation gene mainly from both parents. There are definite correlation between the genotypes and phenotypes.
8.A study on treatment of visceral artery aneurysm
Chao SONG ; Qingsheng LU ; Yi HONG ; Junmin BAO ; Zhiqing ZHAO ; Jian ZHOU ; Xiang FENG ; Rui FENG ; Zhijun MEI ; Yifei PEI ; Liangxi YUAN ; Zaiping JING
Chinese Journal of General Surgery 2012;27(7):543-546
Objective To evaluate open and endovascular procedures for the treatment of visceral arterial naeurysms.Methods Clinical data of 93 cases were reviewed from Jan 2001 to Jan 2011,including 47 males,and 46 females.Splenic artery aneurysm in 45 cases,superior mesenteric artery aneurysm in 15 cases,renal artery aneurysms in 10 cases,common hepatic artery aneurysm in 7,celiac artery aneurysms in 11 and gastroduodenal artery aneurysm in 5 cases.All cases had either open procedures or endovascular procedures after comprehensive evaluation.Results Surgical open procedures were performed on 34 cases,and endovascular procedures were performed on 59 cases.The perioperative complication rate were 52.9% and 13.6% for open and endovascular groups respectively.The mean follow-up time was 36.8 months ( 11 months to 10 years).1 -year survival rate and 5-year survival rate were 100%and 60.6% in open surgery group,compared with 100% and 84.5% in endovascular group.Conclusions Endovascular repair is effective for visceral artery aneurysm with lower perioperative complication rate and better long-term survival rate.
9.Prognostic value of coagulation function combined with acute physiology and chronic health evaluationⅡ and sequential organ failure assessment scores for patients with bloodstream infection
Mingyue YANG ; Xiaojuan YANG ; Pei JING ; Xiaojun YANG ; Zhijun ZHAO
Chinese Critical Care Medicine 2021;33(12):1434-1439
Objective:To evaluate the prognostic value of platelet count (PLT), coagulation indexes, acute physiology and chronic health evaluationⅡ(APACHEⅡ), and sequential organ failure assessment (SOFA) in patients with bloodstream infection.Methods:A retrospective single center cohort study was conducted, patients with at least one positive blood culture bloodstream infection hospitalized in the intensive care unit (ICU) of Ningxia Medical University General Hospital from January 2016 to October 2020 were selected as the research objects, basic data and pathogen distribution, coagulation function, and prognosis at 28 days were collected, the APACHEⅡscore, SOFA score based on the results of laboratory examination within 24 hours of blood culture were calculated. Patients were divided into the survival group and the death group according to the 28-day prognosis, and the differences of the above indicators were compared. Multivariate Logistic regression analysis was used to screen out the risk factors for 28-day death of patients with bloodstream infection. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive efficacy of various risk factors for 28-day prognosis of patients with bloodstream infection.Results:A total of 215 patients with bloodstream infection were enrolled, of which 117 survived and 98 died within 28 days. The 256 strains of pathogenic bacteria were detected, including 161 (62.89%) Gram-negative bacteria (G -), 76 (29.69%) Gram-positive bacteria (G +), 17 fungi (6.64%), and 2 other strains (0.78%). The main pathogenic bacteria were Escherichia coli (53 strains, 20.70%), Enterococcus (37 strains, 14.45%), and Klebsiella pneumoniae (34 strains, 13.28%). Compared with the survival group, patients in the death group were older (years old: 60.98±16.08 vs. 55.64±16.35), had higher levels of body temperature, SOFA score, APACHEⅡ score, proportion of malignant tumor and pulmonary infection, blood lactic acid (Lac), and creatinine [Cr; body temperature (℃): 39.12±1.10 vs. 38.67±1.09, SOFA score: 13.05±4.40 vs. 7.85±3.74, APACHEⅡscore: 24.01±8.18 vs. 15.38±6.59, proportion of malignant tumor: 15.31% (15/98) vs. 12.82% (15/117), proportion of patients with pulmonary infection: 84.69% (83/98) vs. 72.65% (85/117), Lac (mmol/L): 7.13±6.04 vs. 4.31±2.98, Cr (μmol/L): 189.73±141.81 vs. 124.55±106.17, all P < 0.05]. The prothrombin time (PT), activated partial thrombin time (APTT), and thrombin time (TT) were significantly longer [PT (s): 19.51±15.16 vs. 14.94±2.86, APTT (s): 52.74±26.82 vs. 40.77±15.30, TT (s) : 21.59±18.46 vs. 17.38±2.59, all P < 0.05], PLT was significantly decreased [×10 9/L: 43.50 (18.75, 92.75) vs. 86.00 (36.00, 154.50), P < 0.05]. Logistic regression analysis showed that body temperature, age, SOFA score and APACHEⅡ score were independent risk factors [odds ratio ( OR) were 1.388, 1.023, 0.817 and 0.916, respectively, 95% confidence intervals (95% CI) were 1.001-1.926, 1.001-1.046, 0.730-0.913, 0.867-0.968, with respective P values of 0.046, 0.043, 0.000, 0.002]. ROC curve analysis showed that SOFA score, APACHEⅡ score, temperature, age had certain predictive values for the prognosis of patients with bloodstream infection, and area under ROC curve (AUC) was 0.815, 0.795, 0.625 and 0.594, respectively (all P < 0.05). The AUC predicted by the combination of the 4 variables was as high as 0.851, the specificity was 79.3%, and the sensitivity was 74.2%, suggesting that the combination variables could predict the death of patients with bloodstream infection with higher accuracy. Conclusions:PLT and coagulation indexes are helpful to evaluate the prognosis of patients with bloodstream infection in ICU. APACHEⅡscore and SOFA score are directly related to the prognosis of patients with bloodstream infection.
10.Clinical characteristics and risk factors of early septic patients complicated with bloodstream infection
Pei JING ; Qinfu LIU ; Mingyue YANG ; Yuting KANG ; Zhijun ZHAO ; Xiaojun YANG
Chinese Critical Care Medicine 2022;34(6):608-613
Objective:To analyze the clinical characteristics, risk factors and prognosis of early septic patients with bloodstream infection (BSI) in department of critical care medicine of Ningxia Medical University General Hospital.Methods:Patients with sepsis admitted to department of critical care medicine of Ningxia Medical University General Hospital from November 1, 2019 to August 31, 2021 were included in a prospective observational study. Blood samples were collected for culture within 24 hours of sepsis diagnosis. General information, laboratory test indicators and blood culture results within 24 hours of sepsis diagnosis were recorded. Patients were followed up and prognostic indicators [mechanical ventilation time, length of intensive care unit (ICU) stay, and 28-day survival] were observed. According to blood culture results, patients were divided into BSI group and non-BSI group. Univariate and multivariate Logistic regression analysis were performed on the general clinical characteristics of patients in the two groups to screen the risk factors of early BSI in septic patients. Receiver operator characteristic curve (ROC) was drawn to evaluate the predictive value of risk factors for early BSI in septic patients.Results:A total of 202 septic patients were included in this study, with 62 patients in BSI group and 140 patients in non-BSI group. The majority of patients in the BSI group were associated with abdominal infection (61.3%), and the majority of patients in the non-BSI group were associated with pulmonary infection (49.3%). A total of 76 strains were isolated from septic patients in BSI group, and the most common pathogens were Escherichia coli (26 strains, 34.2%), Klebsiella pneumoniae (11 strains, 14.4%), Enterococcus (7 strains, 9.2%), Bacteroides fragilis (6 strains, 7.9%) and Staphylococcus aureus (6 strains, 7.9%). There were no significant differences in mechanical ventilation time, the length of ICU stay and 28-day mortality between the BSI group and the non-BSI group. The difference of variables was statistically significant between two group according to Univariate analysis, which included body temperature, acute physiology and chronic health score Ⅱ (APACHEⅡ), use of antibiotics before admission to ICU, abdominal infection, hypersensitivity C-reactive protein (hs-CRP), serum creatinine (SCr), total bilirubin (TBil), platelet count (PLT), blood lactic acid (Lac) and hypercalcitonin (PCT). Multivariate analysis showed that low PLT [odds ratio ( OR) = 1.004, P = 0.019], high Lac ( OR = 1.314, P = 0.002), high body temperature ( OR = 1.482, P = 0.027), concomitant abdominal infection ( OR = 2.354, P = 0.040), no use of antibiotics before admission to ICU ( OR = 2.260, P = 0.049) were independent risk factors for early BSI in septic patients. The area under ROC curve (AUC) of PLT, Lac, body temperature, abdominal infection and no use of antibiotics before admission to ICU for predicting early BSI in septic patients were 0.711, 0.686, 0.594, 0.592 and 0.590, respectively. Youden index was used to calculate the optimal cut-off values, which was PLT 122.50×10 9/L, Lac 2.95 mmol/L, body temperature 39.45 ℃, respectively. The highest level of AUC was 0.754, the sensitivity was 75.8%, and the specificity was 68.8%, which were observed when the 5 items were combined. Conclusions:Early septic patients with BSI are more serious than those without BSI. Low PLT, high Lac, high temperature, concomitant abdominal infection and no use of antibiotics before admission to ICU are independent risk factors for early BSI in septic patients, and the combination of these five factors has good predictive value.