Evaluation of left ventricular structural and functional abnormalities and vascular calcification in kidney transplant recipients and the effect of bone metabolism on them / 中华器官移植杂志

Objective:To evaluate left ventricular structural and functional abnormalities and vascular calcification in kidney transplant (KT) recipients, explore their influencing factors and examine the effects of mineral and bone disorders.Methods:From January 2017 to December 2019, retrospective analysis was performed for 292 KT recipients. Biochemical markers of bone metabolism, bone mineral density (BMD), left ventricular hypertrophy (LVH), left ventricular ejection fraction (LVEF), left ventricular diastolic function, coronary artery calcification (CAC) score and thoracic aortic calcification (TAC) score were assessed. Linear regression and binary Logistic regression analyses were employed for evaluating the influencing factors of cardiovascular parameters and the influence of abnormal mineral and bone metabolism.Results:Postoperative abnormalities in mineral and bone disorders were manifested mostly as hypercalcemia (8.9%, 26/292), hypophosphatemia (27.1%, 79/292), low 25-hydroxyvitamin D (25(OH)vitD) (67.0%, 196/292), hyperparathyroidismhigh parathyroid hormone (PTH) (50.6%, 148/292), elevated bone turnover markers and bone loss rate of 25%-30%. The prevalence of LVH, LVEF<50%, left ventricular diastolic dysfunction, high CAC score and high TAC score were 39.9%(116/292), 0%, 13.1%(38/292), 17.3%(50/292) and 39.9%(116/292) respectively. The results of multivariate analysis indicated that LVH was correlated positively with hypertension and serum calcium (Ca) (95% CI: 1.242-28.080, P=0.026; 95% CI: 1.714-277.584, P=0.018); LVEF was correlated positively with lumbar vertebrae BMD (95% CI: 0.000 1-0.005 5, P=0.041); Left ventricular diastolic dysfunction was correlated positively with age, diabetes and parathyroid hyperplasia/nodules (95% CI: 1.050-1.176, P<0.001; 95% CI: 2.118-43.813, P=0.003 and 95% CI: 1.419-9.103, P=0.007); High CAC score was correlated positively with recipient age and dialysis time (95% CI: 1.036-1.160, P=0.001; 95% CI: 1.009-1.041, P=0.002); High TAC score was correlated positively with age (95% CI: 1.095-1.215, P<0.001). Correlation analysis indicated that TAC was correlated positively with serum Ca ( r=0.233, P=0.003), bone-specific alkaline phosphatase (BALP)( r=0.325, P<0.001) and type Ⅰ collagen cross-linked N-terminal peptide (NTX)( r=0.204, P=0.011) and negatively with femoral neck BMD ( r=0.194, P=0.017). Conclusions:There is a high prevalence of left ventricular structural and functional abnormalities and vascular calcification. It is closely correlated with mineral and bone disorders.

Exploring the potential mechanism of Fritiliariae Irrhosae Bulbus on ischemic stroke based on network pharmacology and experimental validation.

Objective: To study the potential targets and molecular mechanisms of Fritiliariae Irrhosae Bulbus (FIB) in the treatment of ischemic strokes based on a network pharmacology strategy, with a combination of molecular docking and animal experiments. Methods: The active components and targets of FIB were screened by TCMSP database and TCMIP database, and the related targets of ischemic strokes were screened by GeneCards, OMIM, CTD, and DrugBank, then the intersection targets of the two were taken. The protein interaction network was constructed by STRING, the PPI network diagram was drawn by using Cytoscape software, and the key targets of FIB treatment of ischemic strokes were analyzed by MCODE. The DAVID database was used for GO and KEGG enrichment analysis, and the potential pathway of FIB against ischemic strokes was obtained. Molecular docking was performed by using AutoDock Tools 1.5.6 software. Finally, a mouse model of ischemic stroke was established, and the results of network pharmacology were verified by in vivo experiments. Realtime Polymerase Chain Reaction was used to detect the expression levels of relevant mRNAs in the mouse brain tissue. Western blot was used to detect the expression levels of related proteins in the mouse brain tissue. Results: 13 kinds of active components of FIB were screened, 31 targets were found in the intersection of FIB and ischemic strokes, 10 key targets were obtained by MCODE analysis, 236 biological processes were involved in GO enrichment analysis, and key targets of KEGG enrichment analysis were mainly concentrated in Neuroactive light receptor interaction, Calcium signaling pathway, Cholinergic synapse, Hepatitis B, Apoptosis-multiple specifications, Pathways in cancer and other significantly related pathways. There was good binding activity between the screened main active components and target proteins when molecular docking was performed. Animal experiments showed that the infarct volume of brain tissue in the FIB treatment group was considerably reduced. RT-qPCR and the results of Western Blot showed that FIB could inhibit the expression of active-Caspase3, HSP90AA1, phosphorylated C-JUN, and COX2. Conclusion: Based on network pharmacology, the effect of FIB in the treatment of ischemic strokes was discussed through the multi-component-multi-target-multi-pathway. The therapeutic effect and potential mechanisms of FIB on ischemic strokes were preliminarily explored, which provided a ground work for further researches on the pharmacodynamic material basis, mechanism of action and clinical application.

The study of effect of Human macrophage polarization on Mouse Pericyte-to-Myofibroblast Transition in vitro / 中华器官移植杂志

Objective:To explore the role of macrophage polarization on pericyte-to-myofibroblast transition and renal allograft fibrosis after kidney transplantation(KT).Methods:Allograft tissues were harvestedfrom recipients with chronic allograft dysfunction(CGD)and normal kidney tissues.The expression and distribution of M1/M2 macrophages in kidney tissues were detected by routine and immunofluorescent staining; mRNA of CD68, CD206 and iNOS detected by polymerase chain reaction(PCR); Murine vascular pericytes subjected to TGF-β1 in vitro and the expressions of α-SMA and PDGFR-β in perivascular cells detected by immunoblotting and cellular fluorescence; The co-culturing models of vascular pericytes and M1/M2 macrophages were constructed.The expressions of α-SMA and PDGFR-β in pericytes were detected by immunoblotting, cellular fluorescence and PCR.Results:A marked infiltration of CD68+ iNOS+ M1 macrophages was present in allograft tissues of recipients with CGD while no obvious infiltration of CD68 + CD206 + was observed.The mRNA levels of CD68, iNOS and CD206 were significantly higher in CGD group than those in control group( P<0.05); In CGD allograft tissues, protein expressions of α-SMA and PDGFR-β spiked markedly( P<0.05)while cells with double staining of α-SMA and PDGFR-β were markedly infiltrated in interstitial area of CGD allograft.TGF-β1 could induce a marked elevation of PMT-related markers in a time-dependent manner( P<0.05); Immunoblotting and cellukar fluorescence indicated that M1 macrophages could promote the elevations of α-SMA and PDGFR-β in pericytes in vitro while M2 macrophages showed no effect on pericyte-to-myofibroblast transition in pericytes. Conclusions:M1 macrophage polarization may promote the formation of renal allograft interstitial fibrosis through promoting PMT.

Influence of metabolic syndrome and its components on the prognosis of patients with pancreatic cancer / 临床肝胆病杂志

ObjectiveTo investigate the association of metabolic syndrome (MS) and its components with the overall survival of pancreatic cancer (PC) patients who do not receive antitumor therapy. MethodsA retrospective analysis was performed for the data of patients who were diagnosed with PC in The Affiliated Hospital of Southwest Medical University from August 2013 to November 2018. Related data were collected, including age, sex, body weight, body height, body mass index (BMI), smoking, drinking, medical history of chronic pancreatitis, medical history of biliary tract diseases and gastritis, medical history of chronic hepatitis B/C, medical history of other tumors, presence or absence of PC in first-grade relatives, blood glucose, blood pressure, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), MS, and TNM stage. The log-rank test was used for comparison of survival curves between groups, and the univariate and multivariate Cox regression analyses were used to investigate the influencing factors for survival. ResultsA total 269 PC patients were enrolled in this study, with an average survival time of 3 months. The survival analysis showed no significant difference in survival time between the patients with MS and those without MS (P=0.754). There was no significant difference in median survival time between the patients with hypertension, high TG, high HDL-C, or abnormal BMI and those without such abnormality (all P＞0.05). There was a significant difference in median survival time between the patients with hyperglycemia and those without hyperglycemia (hazard ratio ［HR］=1.322, 95% confidence interval ［CI］: 0.985-1.775, P=0.028), and the multivariate Cox regression analysis achieved consistent results (HR=1481, 95% CI: 1.043-2.104, P=0.028). The analysis of the influencing factors for survival time in patients with stage Ⅳ PC showed that the patients with hyperglycemia had a significant reduction in median survival time (HR=1.524, 95%CI: 1.046-2.218, P=0004). ConclusionMS is not an influencing factor for the survival of PC patients, but hyperglycemia is an independent risk factor for poor prognosis in PC patients, especially in those with advanced PC.

Quadruple low-dose immunosuppressant maintenance therapy protocol in renal transplanted recipients within three months after renal transplantation / 中华器官移植杂志

Objective:To observe the efficacy and safety of quadruple low-dose immunosuppressant maintenance therapy of sirolimus(SRL), calcineurin inhibitors(CNIs), mycophenolate mofetil(MMF)and glucocorticoid in recipients switched within three months after renal transplantation.Methods:This retrospective study recruited 61 recipients on quadruple immunosuppressive therapy within three months after renal transplantation from 2013 to 2018. The changes of serum creatinine(SCr), blood urea nitrogen(BUN), hemoglobin(HGB), white blood cell(WBC), platelet(PLT), liver function, fasting blood-glucose(FBG), serum lipid, electrolyte and urine protein before and after using this protocol were recorded.Results:No significant difference existed between before and after protocol switching in WBC or serum sodium. But after protocol switching, significant differences could be observed in SCr, BUN, serum calcium, serum potassium, aspartate transaminase(AST), PLT, alanine transaminase(ALT), HGB, FBG, triglycerides(TG)and cholesterol(TC, P<0.05). Urine protein negative rate was 44.26 % before switching. However, it was 81.97 % after protocol switching. After switching during a 1-year follow-up period, the incidence of pulmonary infection rate was 24.59 %, the incidence of BKV infection rate 4.92 %, the incidence of transplant renal artery stenosis 3.28 % and the incidence of acute rejection 6.56 %. Conclusions:Quadruple low-dose immunosuppression maintenance therapy of SRL, CNIs, MMF and glucocorticoid switched within 3 months after renal transplantation may be an effective and safe protocol of improving renal allograft function and enhancing recipient prognosis.

Prognosis of chronic active antibody-mediated rejection in kidney transplantation / 中华器官移植杂志

Objective:To evaluate the values of bone mineral density(BMD)of renal transplant recipients and analyze the influencing factors so as to provide rationales for preventing and treating osteoporosis after renal transplantation.Methods:A retrospective study was conducted for clinical data of 254 renal transplant recipients hospitalized from January 2017 to May 2019. The values of BMD of right femoral neck and lumbar vertebrae were detected by dual-energy X-ray absorptiometry(DEXA)and their relationships with other clinical parameters analyzed.Results:The average age was(40.5±9.8)years. Males accounted for 66.1 %, and menopausal women 5.9 %. The prevalence of osteopenia/osteoporosis of right femoral neck bone mass and lumbar vertebrae was 20.1 %, 2.8 % and 26.1 %, 3.6 % respectively. Chi-square test showed that recipients with lower BMD of femoral neck and lumbar spine were elders, menopausal women and those with longer postoperative time( P<0.05). Multivariate linear regression analysis indicated that BMD of right femoral neck was positively correlated with BMI and negatively correlated with acute rejection( P<0.05). The BMD of lumbar vertebrae was positively correlated with BMI and negatively correlated with PTH level ( P<0.05). Conclusions:There is a high prevalence of bone loss in kidney transplant recipients. Regular monitoring of BMD, active control of hyperparathyroidism, maintaining an excellent nutritional status, tapering of glucocorticoid dose and using immunosuppressants with less effect on bone metabolism may prevent osteoporosis.

Retrospective study of a novel anti-rheumatic drugs to reduce the panel reactive antibody of kidney transplant recipients / 中华器官移植杂志

Objective:To observe the efficacy and safety of Iguratimod in reducing the level of panel reactive antibodies in renal transplant recipients.Methods:The clinical data of 35 patients with PRA-positive renal transplant recipients were retrospectively analyzed. All recipients were treated with Iguratimod for PRA-positive. The changes in PRA levels before and after treatment and the adverse events were observed.Results:Of the 35 recipients, 4 of them were discontinued due to pulmonary infection, and 2 patients were discontinued during the observation period. 3 patients were lost to follow-up. A total of 26 recipients were included. When Iguratimod was taken to 9 months, the PRA was reviewed. 71.5 % of the 207 sites showed a downward trend, 69.9 % of the 107 class I sites and 75.9 % of the 41 class II site showed a downward trend, and there was no difference in renal function before and after treatment. There were no significant changes in blood routine, liver function, blood lipids, and blood glucose. There were no other adverse events.Conclusions:Iguratimod can effectively reduce the level of PRA in renal transplant recipients with less adverse events.

Prospective comparison between DCE-MRR and 99m Tc-DTPA-based SPECT for determination of allograft renal function.

BACKGROUND: Glomerular filtration rate (GFR) is a preferred indicator of allograft renal function, but direct measurement of GFR remains complicated. PURPOSE: To prospectively compare dynamic contrast-enhanced MR renography (DCE-MRR) with 99m Tc-DTPA-based single-photon emission computed tomography (SPECT) for determination of allograft renal function. STUDY TYPE: Prospective. POPULATION: Seventy kidney-transplant recipients FIELD STRENGTH: A low-dose DCE-MRR with a 3.0T scanner and a 99m Tc-DTPA-based SPECT after renal transplantation were performed. ASSESSMENT: A Baumann-Rudin (BR) and a modified two-compartment model (JZ2C) were used for DCE-MRR analysis. Standard Gate's method was used for SPECT analysis. An endogenous creatinine clearance rate (CCr) constituted the reference standard. STATISTICAL TESTS: Pearson correlation test and Bland-Altman agreement analysis. RESULTS: The reference CCr-GFR was 59.58 ± 23.72 mL/min/1.73 m2 . GFR determined by eGFR, BR, JZ2C, and SPECT was 90.22 ± 34.38, 36.78 ± 14.46, 48.99 ± 23.88, and 67.32 ± 18.44 mL/min/1.73 m2 , respectively. DCE-MRR using JZ2C had the best overall performance, with a Pearson correlation coefficient of 0.81, a bias of -10.58 mL/min/1.73 m2 , and a precision of 14.61 mL/min/1.73 m2 , as well as high accuracy (30-50% intervals: 74.3-90.0%). Although SPECT had a small bias (7.74 mL/min/1.73 m2 ), it had a poor correlation coefficient (0.38), poor precision (23.93 mL/min/1.73 m2 ), and low accuracy (64.3-72.3%) as compared with DCE-MRR using JZ2C. DATA CONCLUSION: DCE-MRR using JZ2C is superior to 99m Tc-DTPA-based SPECT to determine allograft renal function. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:262-269.

Expression of LDB2 in lung cancer tissues and its correlation with S1PR1 / 临床检验杂志

Objective@#To investigate the expression of LIM domain binding 2 (LDB2) in lung cancer tissues and its correlation with sphingosine-1 phosphate receptor 1 (S1PR1). @*Methods@#Lung cancer tissues and the corresponding adjacent tissues from 52 patients in Nantong Tumor Hospital during April 2010 and May 2011 were collected as the experimental group and the control group, respectively. The expression levels of LDB2 and S1PR1 were detected by the real-time PCR (qRT-PCR). The expression results of LDB2 gene were further verified by the Oncomine database, and its correlations with clinicopathological parameters were analyzed. The ROC curve was drawn to evaluate the diagnosis value of LDB2 expression in lung cancer. The correlation of LDB2 expression with the prognosis of lung cancer was analyzed by the “Kaplan-Meier Plotter” database. In addition, the relationship between LDB2 and S1PR1 was also analyzed. @*Results@#The expression levels of LDB2 in lung cancer tissues (0.158 [0.062,0.383]) were significantly lower than that in the adjacent tissues (0.403 [0.261,0.711], U=700.0, P＜ 0.01). A total of 9 eligible studies were retrieved from the Oncomine database, and their expressions of LDB2 were also low (P＜0.01). The expressions of LDB2 in lung cancer tissues were not related to gender, age, smoking history, pathological type, tumor size, TNM staging and lymphatic metastasis (P＞0.05). The results of ROC curve showed that when the area under the ROC curve (AUC ROC ) was 0.741 (95% CI:0.643-0.839) and the cut-off value was 0.247, the sensitivity and specificity of LDB2 in the diagnosis of lung cancer were 80.8% and 61.5%, respectively. The Kaplan-Meier survival analysis showed that the 5-year overall survival time of the patients with low expression of LDB2 was shorter than that of the patients with high expression of LDB2(P＜0.01). In addition, the expression levels of S1PR1 in lung cancer tissues (0.710[0.337,1.523]) were significantly lower than that in the adjacent tissues (1.582[0.913,3.533],U=780.0, P＜0.01), and the expression levels of S1PR1 in lung cancer tissues were positively correlated with that of LDB2(r=0.827,P＜0.01). @*Conclusion@#The expressions of LDB2 and S1PR1 in lung cancer tissues are down-regulated, and have a positive correlation, and they may play an important role in the occurrence and development of lung cancer.

Development of new-type locating rod for radiotherapy / 医疗卫生装备

Objective To develop a new type of locating rod with easy installation and high reliability for radiotherapy.Methods The locating rod was composed of a joining beam,two clamping buckles and buckle holders.The joining beam had the length being 530+03 mm.One of the buckles was put at one end of the beam,and the other slided along a stool.An eccentric wheel drove the sliding buckle to determine the space between two buckles,and a returning spring was involved in to enhance the compliance of the sliding buckle.Results The rod gained easy installation and operation,and was compatible with the bed board with the width of 5300 mm.There was no sideslip occurred after locking the rod,and the sideslip shift was not more than 1 mm in case of 20 kgf (1 kgf=9.8 N) lateral traction.Conclnsion The rod has high performances and meets clinical requirements.