1.Preliminary study of the value of ultrasound parameters combined with cystatin C in monitoring early acute kidney injury after liver transplantation
Di ZHANG ; Jing SUN ; Kai ZHAO ; Chuanshen XU ; Shiwen DING ; Jinzhen CAI ; Jianhong WANG
Organ Transplantation 2025;16(4):574-581
Objective To explore the value of combined ultrasound parameters, including the hepatorenal index (HRI) and renal resistance index (RRI), with cystatin C (CysC) in monitoring early acute kidney injury (AKI) after liver transplantation. Methods Perioperative data from 121 liver transplant recipients who received organs from donation after brain death were collected. The HRI and RRI of the recipients were measured on postoperative days 1-7 and at 1 month, and the CysC levels were measured on postoperative day 1. The recipients were divided into the AKI group (n=53) and the non-AKI group (n=68) based on whether AKI occurred within 7 days after operation. The data of the two groups were compared, and the ultrasound parameters before and after recovery in the AKI group were analyzed. The value of combined HRI, RRI and CysC in monitoring AKI was also analyzed. Results AKI occurred in 53 recipients, with an incidence rate of 43.8%, including 30 cases of stage 1, 18 cases of stage 2, and 5 cases of stage 3. Among them, 49 cases occurred on postoperative day 1, and 4 cases occurred on postoperative day 2. Of these, 43 cases recovered within 7 days after surgery, 8 cases recovered within 2 months after surgery, 1 case was lost to follow-up, and 1 case received renal replacement therapy. The body mass index and preoperative CysC levels were higher in the AKI group than in the non-AKI group, and the operative time was longer in the AKI group than in the non-AKI group (all P < 0.05). The HRI on postoperative day 1 was lower in the AKI group than in the non-AKI group, while the RRI and CysC levels were higher (all P < 0.05). When AKI occurred, the HRI was lower than the baseline level, and the RRI was higher than the baseline level. As AKI recovered, the HRI gradually increased, and the RRI gradually decreased. The receiver operating characteristic curve analysis showed that the sensitivity and specificity of HRI ≤ 1.12 for predicting AKI were 0.623 and 0.878, respectively, with an area under the curve (AUC) of 0.801. The sensitivity and specificity of RRI ≥ 0.65 for predicting AKI were 0.878 and 0.676, respectively, with an AUC of 0.825. The sensitivity and specificity of CysC ≥ 1.38 mg/L for predicting AKI were 0.736 and 0.882, respectively, with an AUC of 0.851 (all P<0.01). The combination of HRI and CysC (AUC=0.897, P<0.01), RRI and CysC (AUC=0.910, P<0.01), and all three parameters combined (AUC=0.934, P<0.01) were more effective than using each parameter alone. Conclusions HRI and RRI may be used to monitor the occurrence and recovery of early AKI after liver transplantation. The combination of these two parameters with CysC has a high application value in monitoring early AKI after liver transplantation.
2.Mechanism of Wenfei Huaxian Decoction-containing Serum in Delaying Inflammatory Senescence of Lung Mesenchymal Stem Cells Based on NAMPT/SIRT1
Junxia HU ; Yueqi XU ; Jun WANG ; Guoshaung ZHU ; Shiwen KE ; Mingliang QIU ; Liangji LIU ; Lisha MO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):45-53
ObjectiveThe lung mesenchymal stem cells (LMSCs) induced by D-galactose (D-gal) were intervened by Wenfei Huaxian decoction-containing serum to explore the mechanism of Wenfei Huaxian decoction in delaying the senescence of LMSCs through the nicotinamide phosphoribosyltransferase/silent information regulator 1 (NAMPT/SIRT1) signaling pathway. MethodWenfei Huaxian decoction-containing serum was prepared. LMSCs were isolated by gradient density centrifugation, and they were cultured and identified in vitro. The senescence model in vitro was established by stimulating cells via D-gal for 24 h. LMSCs cells were modeled after being treated with different volume fractions (5%, 10%, 20%, 40%, and 80%) of Wenfei Huaxian decoction-containing serum for 24 h, and the cell proliferation level was detected by methyl thiazolyl tetrazolium (MTT) method. The cells were randomly divided into blank serum group, model group, and high, medium, and low dose groups of Wenfei Huaxian decoction-containing serum. Senescence-associated β-galactosidase (SA-β-gal) staining was used to detect the senescence of LMSCs in each group. The content of NAD + was detected by colorimetry. The levels of senescence-associated factors (p16 and p53), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in cell culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the relative expression of senescence-associated proteins and NAMPT/SIRT1 signaling pathway-related proteins. ResultCompared with the blank serum group, the proliferation of LMSCs was significantly inhibited after D-gal stimulation for 24 h (P<0.01). Compared with the model group, the proliferation of LMSCs could be promoted after intervention with the corresponding Wenfei Huaxian decoction-containing serum (P<0.05, P<0.01). Compared with the blank serum group, the SA-β-gal staining of LMSCs in the model group after D-gal stimulation was enhanced, and the content of NAD+ was increased (P<0.01). The expression levels of senescence factors p16 and p53, as well as SASP pro-inflammatory factors IL-6 and TNF-α in the cell culture supernatant, were significantly increased (P<0.01). The expression of senescence-associated proteins p16, p21, and p53 increased (P<0.01), and the protein expression of NAMPT, SIRT1, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), and forkhead box family transcription factor O1 (FoxO1) decreased (P<0.01). Compared with the model group, the SA-β-gal staining of LMSCs in each group of Wenfei Huaxian decoction-containing serum was significantly reduced, and the content of NAD+ was decreased (P<0.01). The senescence factors (p16 and p53) and inflammatory factors (IL-6 and TNF-α) in the cell culture supernatant were significantly decreased (P<0.01). The expression of senescence-associated proteins (P16, P21, and P53) decreased (P<0.05, P<0.01). The protein expressions of NAMPT, SIRT1, PGC-1α, and FoxO1 were significantly up-regulated (P<0.05, P<0.01). ConclusionWenfei Huaxian decoction can alleviate senescence and inflammatory response damage of D-gal-induced LMSCs, and its mechanism may be related to the regulation of the NAMPT/SIRT1 signaling pathway.
3.Exploration of Basement Membrane-related Markersand Prediction of Therapeutic Drugs in Idiopathic Pulmonary Fibrosis
Yifeng XU ; Shiwen KE ; Hang XIAO ; Wenqiang ZHANG ; Shaobin XIONG ; Xiaogang XU ; Yu WANG ; Liangji LIU
Herald of Medicine 2024;43(8):1338-1346
Objective To explore basement membrane markers and potential drugs for treatment in idiopathic pulmona-ry fibrosis(IPF).Methods IPF-related datasets were downloaded from the Gene Expression Omnibus(GEO)database,processed to construct basement membrane gene expression matrices associated with IPF,and screened for differential basement membrane genes(DEBMs);DEBMs were enriched for function and pathways,and machine learning algorithms were used to ob-tain candidate signature genes,receiver operating characteristic(ROC)curves were used to identify signature genes and con-struct a nomogram.We performed ssGSEA analysis to explore the correlation between signature genes and immune cells and their functions and predicted the corresponding miRNAs and therapeutic drugs by signature genes.Results A total of 56 DEBMs were extracted;enrichment analysis showed that DEBMs were mainly enriched in"extracellular matrix tissue","extracellular structural tissue",etc.,and were closely related to"ECM-receptor interaction"and"local adhesion spot"pathways.The ma-chine learning has identified six candidate signature genes(TIMP3,P3H2,ITGA7,ITGA4,ADAMTS2,COL8A2),all of which meet the requirements of the signature genes by the ROC curve test,and the nomogram diagnostic value was outstanding(AUC=0.991 523);B cells and Macrophages in IPF were significantly different from the normal group.Finally,miRNAs were predicted to be dominated by miR-4305,miR-3684,progesterone,and tert-butyl hydroperoxide as therapeutic agents with strong relevance to IPF.Conclusion Signature genes and predictive miRNAs may serve as novel markers for IPF diagnosis,and pre-dictive drugs may be a potential source of drugs for treating IPF.
4.Role of oxidative stress and immune infiltration in idiopathic pulmonary fibrosis and study of Chinese medicine for prevention and treatment
Yifeng XU ; Shiwen KE ; Keke LI ; Zhaoqi YAN ; Yueqi XU ; Xiaogang XU ; Yu WANG ; Liangji LIU
Chinese Journal of Immunology 2024;40(10):2108-2115,中插5
Objective:To explore the role and relationship between oxidative stress and immune infiltration in idiopathic pul-monary fibrosis(IPF),and to predict the relevant therapeutic herbal medicines and active ingredients.Methods:GSE10667 gene expression profiles were downloaded from GEO database to obtain differential expression genes,differential expression of oxidative stress genes(DEOSGs)were identified in combination with oxidative stress genes.GSEA was used to evaluate the pathways and biologi-cal processes in IPF,and GO,KEGG and PPI network analysis were performed on DEOSGs.Candidate central genes were derived from PPI results and CytoHubba,and GSE110147 was validated as an independent group to identify central genes;in addition,the immune microenvironment of samples was evaluated using CIBERSORTF,and correlation between central gene levels and relative proportion of immune cells was explored;finally,therapeutic herbal medicines and components were predicted by central genes,and mole-cular docking verification was carried out.Results:A total of 51 DEOSGs,four central genes(ICAM-1,APOE,MMP-1,TGF-β2)were obtained;DEOSGs were mainly related to oxidative stress,immune response,etc;four central gene levels were closely correlated with 8 relative proportions of immune cells;therapeutic herbal medicines included 4 flavors such as Huangqi and Chuanxiong,and the active ingredients included 8 kinds of β-carotene,etc,the molecular docking results were stable.Conclusion:Oxidative stress and immune firing are exist in IPF,and oxidative stress may be recognized by immune cells or directly activate immune cells.
5.A digital classification system of pelvic fractures based on close reduction techniques
Xu SUN ; Yuneng LI ; Qiyong CAO ; Chunpeng ZHAO ; Yimin CHEN ; Minghui YANG ; Shiwen ZHU ; Honghua WU ; Xinbao WU
Chinese Journal of Orthopaedic Trauma 2024;26(5):428-434
Objective:To explore the feasibility and consistency of a new digital classification system of pelvic fractures named as JST classification based on close reduction techniques.Methods:A retrospective collection was conducted of the data from the 63 patients with pelvic fracture who had undergone surgical treatment after JST classification at Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital from March 2021 to March 2023. Digital classification of the pelvic fractures was performed based on their locations and displacements. The classification first divides the pelvis into 4 parts: left half pelvis and right half pelvis; sacral Denis Ⅲ area and pubic symphysis. The symmetrical left and right sacral Denis Ⅰ and Denis Ⅱ areas are also included in the left/right half pelvis. Subsequently, the left half pelvis and right half pelvis are divided into 4 regions and marked by capitalized English letters: Sacrum Area (including Denis Ⅰ and Denis Ⅱ, denoted as S), Sacroiliac Joint Area (denoted as J), Iliac Area (denoted as I), and Pubic Area (denoted as P); to distinguish right/left, R and L are used as prefixes. The 2 asymmetric parts are also marked with English letters: Denis Ⅲ area of the sacrum (denoted as Sac), and pubic symphysis (denoted as C). Afterwards, the fracture line morphology and displacement in each region are marked digitally to form a complete JST classification system. The inter- and intra-observer reliabilities (Fleiss' and Cohen's Kappa) of the JST classification system were tested by 3 observers with more than 10 years of experience in pelvic fracture treatment.Results:Consistency analysis of the JST classification results showed that the mean κ value of the intra-observer reliability was 0.818 (from 0.658 to 0.946, P<0.001) and the inter-observer reliability 0.873 (from 0.674 to 1.000, P<0.001), both indicating excellent agreement. Of the 63 patients, 59 obtained successful closed reduction with the assistance of the Rossum Robot R-Universal intelligent orthopedic surgical robot system after fracture classification by the JST system, yielding a success rate of 93.7% (59/63). Conclusions:The new JST classification system for pelvic fractures demonstrates strong intra and inter-observer reliabilities compared with traditional classification systems. As JST classification system labels each fracture site and key bones, it is of great significance for the deep learning and intraoperative operations of intelligent fracture robots.
6.Predictive value of contrast-enhanced ultrasound plus transient elastography for early allograft dysfunction after liver transplantation from C-I donors
Jiao SUN ; Di ZHANG ; Shiwen DING ; Chuanshen XU ; Jinzhen CAI ; Jianhong WANG
Chinese Journal of Organ Transplantation 2024;45(1):26-33
Objective:Exploring the value of contrast enhanced ultrasound (CEUS) plus transient elastography in evaluating donor livers for C-I donors and predicting the occurrence of early allograft dysfunction (EAD).Methods:Between September 1, 2022 and August 31, 2023, the relevant clinical data were retrospectively reviewed for 75 pairs of donors and recipients. Based upon whether or not there was a postoperative onset of EAD, the recipients were assigned into two groups of EAD (16 cases) and non-EAD (59 cases) . All donors were examined by contrast-enhanced ultrasonography and FibroScan. QLAB analysis software was utilized for analyzing the results of contrast-enhanced ultrasound. Liver parenchyma at 3 cm below liver capsule was selected as a region of interest for plotting the time-intensity curve (TIC) . And the contrast-enhanced ultrasonic parameters of two groups were recorded. FibroScan transient elastography instrument was employed for quantifying liver stiffness 12 times in right lobe of donor liver and recording quantitative parameters of liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) .Results:Inter-group comparison of gender, age, body mass index (BMI) and ICU length of stay showed no statistically significant differences ( P>0. 05) . However, significant differences existed in the levels of platelet [ (122. 44±85. 82) vs (197. 22± 140. 93) ×10 9/L]and cholinesterase [ (3 473. 44±1 368. 54) vs (4 252. 93±1 365. 37) U/L]within the first 24h pre-operation ( P=0. 047, P=0. 047) . Peak intensity (PKI) and area under the curve (AUC) were lower in EAD group than those in non-EAD group [ (16. 44±4. 70) dB vs 19. 85±4. 39 dB, P=0. 009; (1 366. 76±508. 10) dB·s vs (1 675. 23±498. 77) dB·s, P=0. 014]. There were statistically significant differences ( P=0. 009, P=0. 032) . Arterial-portal arrival interval (APAI) and LSM were higher in EAD group than those in non-EAD group[6. 50 (5. 00, 10.75) s vs 5. 00 (4. 00, 7. 00) s, P =0. 24; 8. 60 (6. 32, 11. 65) kPa vs 6. 10 (5. 40, 7. 90) kPa, P=0. 014]. Receiver operating characteristic (ROC) curve analysis revealed that PKI, AUC, APAI and LSM had AUC values of 0. 703, 0. 664, 0. 683 and 0. 702, respectively in predicting postoperative EAD. And combined prediction of EAD occurrence based upon these parameters had an AUC of 0. 776, a Youden index of 0. 508 with cutoff values, sensitivity and specificity of 0. 800, 0. 813 and 0. 695 respectively. Spearman' s correlation analysis revealed a negative correlation between APAI and AUC values ( r= -0. 404, P<0. 001) . Conclusions:The combination of CEUS and transient elastography can comprehensively evaluate the status of microcirculatory perfusion, fibrosis and steatosis of liver grafts from brain death donors. It offers a great predictive value for postoperative occurrence of EAD.
7.Development of a magnetic particle chemiluminescence immunoassay for creatine kinase MM
Shu ZHANG ; Chunyan ZHANG ; Yujun ZHOU ; Xiuli XU ; Yuxuan CHENG ; Yang SHU ; Shiwen WU ; Yaping TIAN
Chinese Journal of Laboratory Medicine 2024;47(6):667-671
Objectives:Aimed to establish a rapid, high-throughput, automated method for determining the creatine kinase (CK-MM) isoform levels.Methods:Magnetic beads labeled with anti-CK-MM antibodies were combined with alkaline phosphatase-based chemiluminescence detection. Clinical and diagnostic performance validation of the assay was determined by analysis of 998 and 75 dried blood spot samples from healthy newborns and Duchenne muscular dystrophy (DMD) patients, respectively, and the CK activity was also determined. The blank and detection limits, cross-reactivity, recovery rate of the method, intra-and inter-assay coefficient, and the hook effect were evaluated.Results:Blank and detection limits were 17.4 and 39.3 ng/ml, respectively. Cross-reactivity toward CK-MB and CK-BB isoforms was 0.2% and 0.02%, respectively. Intra-and inter-assay coefficients of variation were<1%. Mean recovery was 100.32%, with no hook effect in CK-MM levels<50 000 ng/ml. Overall, the mean CK-MM concentrations in newborns and DMD patients were (27.05±0.97) and (3 720±300.5) ng/ml, respectively. A significant positive correlation between the dried blood spot detected CK-MM levels and total CK enzyme activity, evaluated in corresponding serum samples from the 75 DMD patients, was observed ( r=0.91, P<0.001), ?which is in good agreement with the clinical. Conclusions:An assay for rapid quantitative determination of CK-MM that meets clinical newborn screening requirements was established. It had a good value for application.
8.Full-profile pharmacokinetics, anticancer activity and toxicity of an extended release trivalent PEGylated irinotecan prodrug.
Shiwen SONG ; Dong SUN ; Hong WANG ; Jinliang WANG ; Huijing YAN ; Xuan ZHAO ; John Paul FAWCETT ; Xin XU ; Deqi CAI ; Jingkai GU
Acta Pharmaceutica Sinica B 2023;13(8):3444-3453
Irinotecan is an anticancer topoisomerase I inhibitor that acts as a prodrug of the active metabolite, SN-38. Unfortunately, the limited utility of irinotecan is attributed to its pH-dependent stability, short half-life and dose-limiting toxicity. To address this problem, a novel trivalent PEGylated prodrug (PEG-[Irinotecan]3) has been synthesized and its full-profile pharmacokinetics, antitumor activity and toxicity compared with those of irinotecan. The results show that after intravenous administration to rats, PEG-[Irinotecan]3 undergoes stepwise loss of irinotecan to form PEG-[Irinotecan]3‒x (x = 1,2) and PEG-[linker] during which time the released irinotecan undergoes conversion to SN-38. As compared with conventional irinotecan, PEG-[Irinotecan]3 displays extended release of irinotecan and efficient formation of SN-38 with significantly improved AUC and half-life. In a colorectal cancer-bearing model in nude mice, the tumor concentrations of irinotecan and SN-38 produced by PEG-[Irinotecan]3 were respectively 86.2 and 2293 times higher at 48 h than produced by irinotecan. In summary, PEG-[Irinotecan]3 displays superior pharmacokinetic characteristics and antitumor activity with lower toxicity than irinotecan. This supports the view that PEG-[Irinotecan]3 is a superior anticancer drug to irinotecan and it has entered the phase II trial stage.
9.Diagnostic value of imaging examinations for hepatic portal posttransplant lymphoproliferative disorder after liver transplantation
Shiwen DING ; Xiaodong WU ; Zizhen YANG ; Chuansen XU ; Jinzhen CAI ; Jianhong WANG
Chinese Journal of Organ Transplantation 2023;44(12):754-758
Posttransplant lymphoproliferative disorder(PTLD)is one of the more serious complications of organ transplantation.From October 2021 to December 2022, 3 patients with hepatic portal PTLD were hospitalized.Conventional ultrasonography hinted at hypoechoic area in porta hepatis.Enhanced CT revealed heterogeneous enhancement of soft tissue density in porta hepatis.PET/CT indicated higher metabolism of hilar mass.Two patients underwent contrast-enhanced ultrasound. "Fast-in-and-fast-out" sign(n=1)and no enhancement in all stages(n=1)were noted.Pathological examination revealed T/NK cell lymphoma(n=2)and B cell lymphoma(n=1). In conjunctions with previous literature reports, conventional ultrasound is frequently employed for detecting early cases of PTLD during clinical follow-ups.Contrast-enhanced ultrasound and enhanced CT may aid in making a differential diagnosis of PTLD.And PET/CT has high diagnostic accuracy for PTLD.
10.Correlation between chronic periodontitis and pulmonary ventilation function
Lin QIU ; Chengjun SHU ; Xiaodong WU ; Shiwen XU ; Rui FANG
Chinese Journal of Primary Medicine and Pharmacy 2022;29(7):961-966
Objective:To investigate the correlation between chronic periodontitis and pulmonary ventilation function.Methods:A total of 135 patients with chronic periodontitis who received treatment in Yuyao People's Hospital of Zhejiang Province between June 2014 and December 2019 were included in this study. They were divided into group A (stage I, initial lesion, n = 45), group B (stage II, early lesion, n = 45), group C (stage III, confirmed lesion, n = 45) according to the severity of periodontal lesion. Lung ventilation function indexes and serum levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha (TNF-α) were compared among the three groups. The correlation between periodontal condition and lung ventilation function indexes was analyzed. Results:Probing depth (PD), clinical attachment loss (CAL), number of missing teeth, alveolar bone resorption level were (1.67 ± 0.65) mm, (2.48 ± 0.44) mm, 0 pieces, and (1.38 ± 0.23) mm in group A, (2.05 ± 0.30) mm, (4.04 ± 0.97) mm, 1 piece, (3.37± 0.73) mm in group B, and (2.23 ± 0.47) mm, (5.17 ± 0.75) mm, 3 pieces, (6.48 ± 0.62) mm in group C. With the worsening of the disease, PD, CAL, number of missing teeth, and alveolar bone resorption level were gradually increased. PD, CAL and alveolar bone resorption level in group C were significantly higher than those in group A ( t = 4.68, 20.75, 51.74, all P < 0.001) and group B ( t = 2.17, 6.18, 21.78, P = 0.033, < 0.001, < 0.001). PD, CAL and alveolar bone resorption level in group B were significantly higher than those in group A ( t = 3.56, 9.82, 17.44, all P < 0.001). There was no significant difference in the number of missing teeth ( P > 0.05). Serum IL-6, IL-8 and TNF-α levels were (11.28 ± 4.26) ng/L, (7.48 ± 1.97) ng/L, (14.59 ± 2.11) ng/L in group A, (17.09 ± 4.91) ng/L, (10.82 ± 2.10) ng/L, (19.95 ± 4.48) ng/L in group B, and (26.47 ± 5.86) ng/L, (15.06 ± 2.75) ng/L, (33.76 ± 6.30) ng/L] in group C. With the worsening of the disease, serum IL-6, IL-8 and TNF-α levels were gradually increased. Serum IL-6, IL-8 and TNF-α levels in group C were significantly higher than those in group A ( t = 14.06, 15.03, 19.36, P < 0.001) and group B ( t = 8.23, 8.22, 11.98, all P < 0.001). Serum IL-6, IL-8 and TNF-α levels in group B were significantly higher than those in group A ( t = 6.00, 7.78, 7.26, P < 0.001). The percentage of the maximum expiratory volume in the first second to the predicted value (FEV 1%pre) and the ratio of the maximum expiratory volume in the first second to the forced vital capacity (FEV 1/FVC) were (81.53 ± 6.30)% and (68.73 ± 4.65)% in group A, (70.47 ± 5.25)% and (60.86 ± 3.42)% in group B, and (59.02 ± 3.41)% and (56.93 ± 4.21)% in group C. With the worsening of the disease, FEV 1%pre and FEV 1/FVC were gradually decreased. FEV 1%pre and FEV 1/FVC in group C were significantly lower than those in group A ( t = 21.08, 12.62, both P < 0.001) and group B ( t = 12.27, 4.86, both P < 0.001). FEV 1%pre and FEV 1/FVC in group B were significantly lower than those in group A ( t = 9.05, 9.25, both P < 0.001). Spearman correlation analysis showed that serum IL-6, IL-8 and TNF-α levels were negatively correlated with FEV1%pre and FEV 1/FVC ( r = -0.50, -0.28, -0.42, -0.61, -0.34, -0.51, all P < 0.05). Conclusion:There is a correlation between chronic periodontitis and pulmonary ventilation function. Inflammatory mediators may be involved in chronic periodontitis as internal systemic factors.

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