1.Plasma and hepatic free fatty acid, tricarboxylic acid cycle, and ketone bodies metabolic profiles in progressive Gao-Binge model
Anqin LI ; Luxin PANG ; Yuanyuan CHAI ; Qinwei YU ; Zhenzhou JIANG ; Luyong WANG
Journal of China Pharmaceutical University 2025;56(2):196-206
To investigate the correlation between hepatic lipid accumulation and the metabolic profiles of free fatty acids(FFAs), tricarboxylic acid (TCA) cycle, and ketone body in alcoholic fatty liver disease (AFLD), a chronic plus acute alcohol feeding model (Gao-Binge model) was employed using C57BL/6N mice to simulate different stages of AFLD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to measure the levels of FFAs, TCA cycle intermediates, and ketone bodies in mouse liver tissue and plasma, followed by Pearson correlation analysis. The study revealed that both acute and chronic models showed significant increases in total FFAs, saturated FFAs and short-chain FFAs, as well as β-hydroxybutyric acid(HDBT) in plasma and liver, indicating FFA metabolic profile disturbances in the Gao-Binge model. Moreover, in both models, acetic acid (AA), 2-Methylbutyric acid (2-meBA), and HDBT displayed strong positive correlations with hepatic injury markers in plasma and liver samples (for instance, in the acute model plasma data, r = 0.834, 0.699, 0.818, P<0.05), while pyruvic acid (PRA) showed a strong negative correlation (r = −0.66, P<0.05). These findings suggest that FFAs, TCA cycle, and ketone body metabolism are disrupted in the alcoholic liver disease in mice model, and metabolites such as AA, 2-meBA, HDBT and PRA may serve as potential biomarkers for AFLD, which would be helpful in the diagnosis and treatment of this disease.
2.Parkin inhibits iron overload-induced cardiomyocyte ferroptosis by ubiquitinating ACSL4 and modulating PUFA-phospholipids metabolism.
Dandan XIAO ; Wenguang CHANG ; Xiang AO ; Lin YE ; Weiwei WU ; Lin SONG ; Xiaosu YUAN ; Luxin FENG ; Peiyan WANG ; Yu WANG ; Yi JIA ; Xiaopeng TANG ; Jianxun WANG
Acta Pharmaceutica Sinica B 2025;15(3):1589-1607
Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER T2 /Parkin fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.
3.Clinical analysis of metagenome next-generation sequencing for diagnosing invasive fungal disease in patients with early stage of hematopoietic stem cell transplantation
Yuhan JI ; Mingyue PAN ; Xiaoyu LAI ; Lizhen LIU ; Jimin SHI ; Yanmin ZHAO ; Jian YU ; Luxin YANG ; Yi LUO
Journal of Army Medical University 2024;46(4):311-318
Objective To analyze the clinical outcomes of early invasive fungal disease(IFD)in patients after allogenetic hematopoietic stem cell transplantation(allo-HCST)with metagenomic next-generation sequencing(mNGS).Methods A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation:① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer;② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past;③ Symptoms in lower respiratory tract associated with lung lesions on CT scan,and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS,and overall survival(OS)and non-relapse mortality(NRM)were analyzed.Results There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases,mNGS found that 19 cases were negative to pathogens,30 cases were non-fungal positive,and 11 case were fungal positive,including 3 cases of aspergillus,5 cases of mucor,2 cases of Candida tropicalis,and 1 case of Trichosporon asahii.Of the 11 patients with fungal positive,8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0%(95%CI:64.1%~75.9%)and 20.0%(95%CI:11.9%~32.5%),respectively,while those of the fungal infection patients were 54.5%(95%CI:49.5%~69.5%)and 36.4%(95% CI:15.5%~70.3%),respectively.No significant differences were seen in 1-year OS(P=0.487)and 1-year NRM(P=0.358)among the negative,fungal infection and non-fungal infection patients,neither OS(P=0.238)and NRM(P=0.154)between the fungal infection and the non-fungal infection patients.Conclusion mNGS can rapidly diagnose the early IFD after allo-HSCT,which is helpful for timely and effective treatment and improves the prognosis of patients.
4.Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia
Xiaolin YUAN ; Yibo WU ; Xiaolu SONG ; Yi CHEN ; Ying LU ; Xiaoyu LAI ; Jimin SHI ; Lizhen LIU ; Yanmin ZHAO ; Jian YU ; Luxin YANG ; Jianping LAN ; Zhen CAI ; He HUANG ; Yi LUO
Chinese Journal of Hematology 2024;45(1):41-47
Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) .Methods:In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed.Results:A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively ( P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively ( P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively ( P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively ( P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively ( P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively ( P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively ( P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively ( P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively ( P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion:There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.
5.Comparative study of lateral position and half lithotomy position in Asian proximal femur intramedullary nail antirotation system internal fixation for treatment of elderly patients with femoral inter-trochanteric fractures
Xiaohua ZHANG ; Shuqing ZHOU ; Bowen YANG ; Luxin YU ; Ming ZHU ; Youxin LIAO ; Jian YE ; Qiuwen ZHU
Chinese Journal of Trauma 2020;36(6):503-508
Objective:To compare the therapeutic effect of lateral position and half lithotomy position in Asian proximal femur intramedullary nail antirotation system (PFNA-II) for treating the elderly patients with femoral intertrochanteric fractures.Methods:A retrospective case control study was made on 141 patients with femoral intertrochanteric fractures admitted to Jiangjin Central Hospital from January 2016 to September 2017, including 54 males and 87 females, aged 65-99 years (mean, 80.4 years). According to AO classification, there were 42 patients with type A1 fractures, 88 with type A2 and 11 with type A3. Of all, 74 patients were stabilized by PFNA-II internal fixation in lateral position (lateral position group) and 67 patients by PFNA-II internal fixation in half lithotomy position (half lithotomy position group). The postural placement time, total incision length, operative time, intraoperative blood loss, fluoroscopy frequency, tip-apex distance, reduction quality, fracture healing time, postoperative complications and Harris hip function at 12 months after surgery were compared between the two groups.Results:All patients were followed up for 12-18 months (mean, 12.5 months), except that 13 patients were lost after 9 months, an average of 12.5 months. There were no statistically significant differences in postural placement time, operative time, fracture healing time, and Harris hip score between the two groups ( P>0.05). While significant differences were seen between lateral position group and half lithotomy position group regarding the incision length [(6.5±1.3)cm vs. (7.5±1.5)cm], intraoperative blood loss [(84.3±3.1)ml vs. (90.4±3.9)ml], fluoroscopy frequency [(13.1±1.9)times vs. (11.2±1.2)times], tip-apex distance [(20. 6±2.2)mm vs. (24.4±1.8)mm], good rate of reduction quality (80% vs. 85%) and implant related complications (5% vs. 2%) ( P<0.05 or 0.01). Conclusion:For treatment of elderly patients with intertrochanteric fractures, compared to the lateral position, the half lithotomy position in PFNA-II internal fixation can reduce frequency of fluoroscopy, improve quality of fracture reduction and reduce implant-related complications.
6.Design and Validation of Remote Radiotherapy System.
Luxin YU ; Xiangxiang LIU ; Weisha ZHANG ; Jinyou HU ; Lian ZOU
Chinese Journal of Medical Instrumentation 2018;42(6):417-420
Telemedicine technology is a means of deploying medical resources with low cost and high efficiency. A set of remote radiotherapy system based on Citrix was designed in this paper, so that the senior radiation therapists from the developed areas can provide medical services effectively for the patients in the rural areas. This paper focused on the design ideas and the detail of the technical implementation of how to design a remote radiotherapy system based on the existing equipment in the primary hospital. And the technical reliability and security of the remote radiotherapy system were verified by the scientific test method with pairwise comparison. The early practical experience shows that through the remote radiotherapy system the primary radiotherapy personnel and the radiotherapy experts from thirdgrade class-A hospital can form effective alliance in radiotherapy techniques to allow patients in rural areas to receive more professional radiation therapy.
Humans
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Information Systems
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Radiotherapy
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Reproducibility of Results
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Telemedicine
7.Research progress on chemical composition, analytical methods, and pharmacological effects of Ophiopogon polysaccharides
Luxin ZHANG ; Xueqian ZHOU ; Dekun LI ; Dazheng ZHOU ; Yuewu YANG ; Boyang YU ; Aichun JU
Drug Evaluation Research 2017;40(2):279-284
The main ingredients of Ophiopogonjaponicas include steroidal saponins,flavonoids,polysaccharides,and so on,but the research on polysaccharides is relatively less.This particle will mainly review the chemical composition,analytical methods,and pharmacological effects of Ophiopogon polysaccharides.The Ophiopogon polysaccharides contain a variety of substances,such as MDG-1,Md-1,Md-2,OJP-1,etc;The main analysis methods were sulfuric acid method,phenol-sulfuric acid method,3,5-dinitrosalicylic acid (DNS) colorimetric method,and near-infrared spectroscopy combined with partial least squares regression method.Ophiopogon polysaccharides can effectively improve the cardiovascular system diseases,with antihypoxia,anti-inflammatory,antitumor,anti-oxidation,and other pharmacological effects.
8.Effects of urinary calculi component analysis in improving the effective rate of health education in patients with urolithiasis
Luxin YU ; Tiantian DONG ; Guimin ZHUANG ; Ning WANG ; Yuhua LIU
Chinese Journal of Modern Nursing 2017;23(21):2721-2724
Objective To carry out multi-path health education referred to the results on urinary calculi component analysis based on the component of urinary calculi in Jiaodong area and to improve the effective rate of health education of patients.Methods A total of 190 inpatients with urolithiasis were selected by convenience sampling from January 2015 to January 2016. They were divided into experimental group (n=95, multi-path health education, routine educational mode + explaining in detail based on the analysis report of the composition of urinary stones) and control group (n=95, routine educational mode) according to the composition of urinary stones. The effects of health education were compared.Results The total scores of the dietary knowledge about urolithiasis of patients in experimental group and control group were (17.82±0.90) and (13.99±1.53) with a significant difference (t=9.875,P<0.01). In terms of complications, there were 12 patients with gross hematuria, 10 patients with backache, 8 patients with bladder irritation, 5 patients with urinary tract infection during intubation of double J tube in experimental group lower than those in control group with significant differences (χ2=4.74, 4.66, 5.22, 5.59;P<0.05).Conclusions The multi-path and targeted health education combined with the analysis report of the composition of urinary stones can help to improve the effects of health education and reduce the postoperative complications.
9.The role of peroxisome proliferator-activated receptor-γ/nuclear factor-κB transduction pathway on ;coagulation disorders induced by sepsis
Yizhu SUN ; Jing WANG ; Luxin YU ; Lin DAI
Chinese Critical Care Medicine 2015;(6):520-524
Objective To determine the role of activated status of peroxisome proliferator-activated receptorγ/nuclear factor-κB ( PPAR-γ/NF-κB ) in coagulation disorders induced by sepsis. Methods Forty male Sprague-Dawley ( SD ) rats were randomly divided into four groups, n = 10 in each group: control group, lipopolysaccharide ( LPS ) challenged group, rosiglitazone ( ROSI, selective agonist of PPAR-γ) pretreatment group, and GW9662 ( PPAR-γ antagonist ) pretreatment group. The sepsis model was reproduced by injection of 6 mg/kg LPS via sublingual vein, and the rats in control group were injected with 2 mL/kg normal saline. The rats in ROSI pretreatment group were given 0.3 mg/kg ROSI by sublingual venous injection followed by injection of LPS 30 minutes later;and in GW9662 pretreatment group rats were given 0.3 mg/kg GW9662 by sublingual venous injection followed by 0.3 mg/kg ROSI 15 minutes later, followed by injection of LPS 30 minutes later. Blood was collected at 4 hours after LPS administration, and the expressions of PPAR-γ and NF-κBp65 in peripheral blood mononuclear cell ( PBMC ) were determined with immunocytocheminal technique and graph analysis. Plasma prothrombin time ( PT ), activated partial thromboplastin time ( APTT ), fibrinogen ( FIB ), and D-dimer were determined simultaneously. Results① PPAR-γ/NF-κB pathway: the expressions of PPAR-γ and NF-κBp65 were lowered in control group, and they were expressed in cytoplasm. In LPS challenged group the expression of PPAR-γ ( gray value ) was slightly increased but with no significant difference as compared with control group ( 111.01±4.06 vs. 98.46±5.99, P >0.05 ). In ROSI pretreatment group the expression of PPAR-γ( gray value ) was significantly higher than that in LPS challenged group ( 214.38±5.79 vs. 111.01±4.06, P<0.01 ), with dislocation into nuclei. In GW9662 pretreatment group the expression of PPAR-γ ( gray value ) was lowered but without significant difference compared with that of control group ( 44.21±2.64 vs. 98.46±5.99, P>0.05 ). In LPS challenged group the expression of NF-κBp65 ( gray value ) was significantly higher than that in control group ( 249.48±6.86 vs. 105.81±10.19, P < 0.01 ), and it was translocated into the nuclei. In ROSI pretreatment group the expression of NF-κBp65 ( gray value ) was significantly lower than that in LPS challenged group ( 102.47±8.05 vs. 249.48±6.86, P < 0.01 ), and it lied in cytoplasm. In GW9662 pretreatment group the expression of NF-κBp65 ( gray value ) showed no significant difference as compared with that of LPS challenged group ( 214.84±7.91 vs. 249.48±6.86, P>0.05 ).②Coagulation:compared with control group, PT and APTT were significantly prolonged, FIB was significantly decreased, and D-dimer was significantly increased in LPS challenged group [ PT ( s ):18.32±2.03 vs. 12.22±1.38, APTT ( s ):40.05±2.72 vs. 26.64±2.73, FIB ( g/L ): 1.65±0.51 vs. 3.60±0.37, D-dimer ( mg/L ): 2.58±0.73 vs. 0.37±0.06, all P < 0.01 ]. Compared with LPS challenged group, APTT and PT were significantly shortened, FIB was significantly increased, and D-dimer was significantly lowered in ROSI pretreatment group [ PT ( s ):13.93±1.67 vs. 18.32±2.03, APTT ( s ):30.29±0.86 vs. 40.05±2.72, FIB ( g/L ):3.18±0.69 vs 1.65±0.51, D-dimer ( mg/L ):0.40±0.12 vs. 2.58±0.73, all P<0.01 ]. All parameters in GW9662 pretreatment group showed no significant difference as compared with those of LPS challenged group. Conclusions PPAR-γagonist ROSI may ameliorate coagulation disorders in septic rats. PPAR-γ/NF-κB transduction pathway plays an important role in septic coagulopathy.
10.Development of a Software for Automatically Generated Contours in Eclipse TPS.
Zhao XIE ; Jinyou HU ; Lian ZOU ; Weisha ZHANG ; Yuxin ZOU ; Kelin LUO ; Xiangxiang LIU ; Luxin YU
Chinese Journal of Medical Instrumentation 2015;39(3):225-227
OBJECTIVEThe automatic generation of planning targets and auxiliary contours have achieved in Eclipse TPS 11.0.
METHODSThe scripting language autohotkey was used to develop a software for automatically generated contours in Eclipse TPS. This software is named Contour Auto Margin (CAM), which is composed of operational functions of contours, script generated visualization and script file operations. RESULTS Ten cases in different cancers have separately selected, in Eclipse TPS 11.0 scripts generated by the software could not only automatically generate contours but also do contour post-processing. For different cancers, there was no difference between automatically generated contours and manually created contours.
CONCLUSIONThe CAM is a user-friendly and powerful software, and can automatically generated contours fast in Eclipse TPS 11.0. With the help of CAM, it greatly save plan preparation time and improve working efficiency of radiation therapy physicists.
Humans ; Radiotherapy Planning, Computer-Assisted ; Software

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