Neutrophil-to-lymphocyte ratio in colorectal tissue affects prognosis in patients with colorectal cancer.

The objective of this investigation was to analyse the correlation between the neutrophil-to-lymphocyte ratio (NLR) status in the immune microenvironment (IME) and the prognostic outcomes of patients who have undergone radical surgery for colorectal cancer (CRC). In light of the continued prevalence of CRC in China, this study utilised Kaplan-Meier and Cox regression analyses to assess the prognostic relevance of NLR status in IME among patients with CRC. Furthermore, cellular experiments, such as cell scratching, were conducted to elucidate the underlying mechanisms of NLR's impact on CRC. The NLR status in IME has been found to have a significant impact on the prognosis of patients with CRC. Patients who exhibit elevated intratumoural and extratumoural NLR are associated with a poor prognosis. Experimental evidence indicates that tumour-associated neutrophil (TAN) augments the migratory, invasive, and proliferative potential of HT-29, HCT-116 and LOVO colorectal cancer cells, while concurrently reducing their sensitivity to oxaliplatin. Conversely, lymphocytes have demonstrated cytotoxic effects on HT-29 cells. The NLR status in IME may serve as a prognostic biomarker for resectable CRC.

3-O-Methyl-D-Glucose Blunts Cold Ischemia Damage in Kidney via Inhibiting Ferroptosis.

BACKGROUND: The glucose derivative 3-O-methyl-D-glucose (OMG) is used as a cryoprotectant in freezing cells. However, its protective role and the related mechanism in static cold storage (CS) of organs are unknown. The present study aimed to investigate the effect of OMG on cod ischemia damage in cold preservation of donor kidney. METHODS: Pretreatment of OMG on kidney was performed in an isolated renal cold storage model in rats. LDH activity in renal efflux was used to evaluate the cellular damage. Indicators including iron levels, mitochondrial damage, MDA level, and cellular apoptosis were measured. Kidney quality was assessed via a kidney transplantation (KTx) model in rats. The grafted animals were followed up for 7 days. Ischemia reperfusion (I/R) injury and inflammatory response were assessed by biochemical and histological analyses. RESULTS: OMG pretreatment alleviated prolonged CS-induced renal damage as evidenced by reduced LDH activities and tubular apoptosis. Kidney with pCS has significantly increased iron, MDA, and TUNEL+ cells, implying the increased ferroptosis, which has been partly inhibited by OMG. OMG pretreatment has improved the renal function (p <0.05) and prolonged the 7-day survival of the grafting recipients after KTx, as compared to the control group. OMG has significantly decreased inflammation and tubular damage after KTx, as evidenced by CD3-positive cells and TUNEL-positive cells. CONCLUSION: Our study demonstrated that OMG protected kidney against the prolonged cold ischemia-caused injuries through inhibiting ferroptosis. Our results suggested that OMG might have potential clinical application in cold preservation of donor kidney.

Evaluation and Application of Frailty Index in Colorectal Cancer: A Comprehensive Review.

Colorectal cancer (CRC) is a common malignant tumor that primarily affects the elderly population. Surgery is one of the main treatment modalities for CRC. Frailty is a prevalent characteristic among the elderly and a leading cause of mortality. The frailty index (FI) is a comprehensive tool for assessing patients' frailty status, quantifying indicators such as weight loss, fatigue, and nutritional status, to reflect the degree of frailty. In recent years, the FI has undergone modifications to more accurately evaluate the risk of surgical complications and prognosis in CRC patients. This review summarizes the methods for frailty assessment, the development and modifications of the FI, and compiles the research findings and applications of the FI in predicting surgical complications, postoperative recovery, and survival rates in CRC patients. Furthermore, limitations in the current modified frailty index (mFI) and future research directions are discussed. This review provides essential references for further understanding the role of frailty in CRC patients and the clinical application of the mFI.

The Influence of the Preoperative Albumin to Alkaline Phosphatase Ratio on Overall Survival in Post-Radical Surgery for Colorectal Cancer and the Construction of a Nomogram Prediction Model.

PURPOSE: The albumin to alkaline phosphatase ratio (AAPR) is a newly developed blood biomarker that has been reported to have prognostic value in several types of cancers. The aim of this study was to investigate the predictive value of AAPR in overall survival after radical colon cancer surgery in patients with stage I-III colorectal cancer (CRC). METHODS: The clinical data of 221 eligible patients with stage I ∼ III CRC were retrospectively analyzed. A series of survival analyses were performed to assess the prognostic value of AAPR. Univariate and multifactorial Cox analyses were performed to identify independent risk factors. Columnar graph prediction models were further constructed based on independent risk factors such as AAPR, and their predictive properties were validated. RESULTS: The optimal cutoff value of preoperative AAPR for postoperative overall survival (OS) in patients undergoing laparoscopic radical CRC was .495 as shown by univariate and multifactorial Cox regression analysis. The factors of age ≤65 years, Tumor-Node-Metastasis (TNM) stage I-II, tumor grading (high/medium differentiation), CEA ≤5, and AAPR ≥.495 were associated with better OS (P < .05). CONCLUSIONS: Preoperative AAPR level was a good predictor of postoperative survival in patients undergoing laparoscopic radical CRC surgery, and AAPR <.495 was an independent risk factor for decreased postoperative OS.

Effects of prolonged cold ischemia on the DCD kidney function and Inflammasome expression in rat kidney transplants.

BACKGROUND: Acute kidney injury (AKI) is the main reason for the bad outcome of the donation of circulatory death (DCD) kidney after transplantation. Prolonged cold storage (CS) is a risk factor for the occurrence of the delayed graft function in DCD kidney. The protein NLR-domain containing receptor 3 (NLRP3) plays a crucial role in renal ischemia reperfusion injury by triggering inflammasome formation. Herein, we investigated whether the NLRP3 signal participate in the CS-induced damage of DCD kidney in rat kidney transplantation models. MATERIALS AND METHODS: DCD kidney and living donor (LD) kidney of SD rats were preserved in UW solution at 4 °C for 2 h or 18 h, and then transplanted into syngeneic recipient. Thus, the animals were randomly divided into 4 groups: 2-h LD group, 2-h DCD group, 18-h LD group and 18-h DCD group. The renal function and pathological changes were determined. The expressions of NLRP3 and inflammatory factor IL-1ß were assessed. The concentration of ferrous iron (Fe2+) was analyzed both in kidneys and in the preservation solution. The renal morphological changes were examined by hematoxylin eosin staining. RESULTS: Our results showed that the levels of Cr and BUN were higher in 18-h LD group as compared to the 2-h LD group, which were remarkably increased in 18-h DCD group. The expression levels of NLRP3 and IL-1ß were increased by 18-h CS compared to 2-h CS in both LD kidney and DCD kidney. In addition, the Fe2+ concentration has significantly increased in 18-h LD group than that in 2-h LD group, and the elevation of Fe2+ was more remarkable in DCD kidneys. CONCLUSION: In conclusion, our study demonstrated that prolonged hypothermic storage of DCD kidney deteriorated the graft function via the increased Fe2+ concentration, which was associated with the upregulation of NLRP3 expression.

New taxa of tribe Gastrodieae (Epidendroideae, Orchidaceae) from Yunnan, China and its conservation implication.

Gastrodia longistyla, a new species of Orchidaceae from Yunnan Province, China, is described and illustrated. It is morphologically similar to Gastrodia peichatieniana, but can be easily distinguished from the latter by having a rhombic epichile, long column (6.0-7.5 mm long), and a needle-shaped appendage (1.8-3.2 mm in length) at the base of the stigma. Identification key and colour photographs are provided. A preliminary risk-of-extinction assessment, according to the IUCN Red List Categories and Criteria, is given for the new species. The plastome of G. longistyla is 30464 bp in length with GC content approximately 24.8%, and the plastome does not contain some housekeeping genes, such as matK, rpl16, or all photosynthesis genes. In addition, the G. longistyla plastome lacks an IR region. This indicates that the plastome is in the last stage of degradation.

[Preparation of pg-C3N4/BiOBr/Ag Composite and Photocatalytic Degradation of Sulfamethoxazole].

A pg-C3N4/BiOBr/Ag composite was successfully prepared by simple high-temperature calcination and co-precipitation methods. The composite was characterized by means of XRD, SEM, TEM, XPS, UV-Vis, BET, and photocurrent analyses alongside other detection methods, and the degradation of 10 mg·L-1 sulfamethoxazole was investigated under simulated visible light irradiation. The results showed that the pg-C3N4/BiOBr/Ag composite had the best degradation effect on sulfamethoxazole when the loading ratio of silver was 5%. Compared with pg-C3N4, BiOBr monomer, and pg-C3N4/BiOBr composite, the photocatalytic degradation effect of the pg-C3N4/BiOBr/Ag (5%) was significantly improved, and the degradation rate was almost 100% within 30 min. The reaction rate constant (0.21016 min-1) was 13.15 times that of pg-C3N4/BiOBr. Through radical quenching experiments, it was shown that the main active substances in the photocatalytic degradation were holes (h+), superoxide radicals (·O2-), and singlet oxygen (1O2), among which superoxide radicals (·O2-) contributed the most. Cyclic tests of pg-C3N4/BiOBr/Ag showed that the synthesized material has good recyclability and application prospects.

Validation of Gastrochilus prionophyllus (Vandeae, Orchidaceae), a new species from Yunnan Province, China.

Gastrochilus prionophyllus, which was previously not validly published, is here validated. The species is described along with illustration and photos. Morphologically, the long and pendulous stem and distichous leaves of this new species indicate that it belongs to the sect. Microphyllae. It is unique in having thick fleshy leaves and margin significantly serrate, small flowers, reniform epichile and margin with dentations, thickened cushion on the central epichile and subconic hypochile. Meanwhile, a preliminary conservation status assessment according to IUCN Red List categories and criteria is given to the new species.

[Passivation of Simulated Pb-and Cd-Contaminated Soil by Applying Combined Treatment of Phosphate, Humic Acid, and Fly Ash].

In this study, three kinds of amendments including superphosphate, humic acid, and fly ash and their complex combination were adopted to passivate the artificially simulated Pb-and Cd-containing soils. The passivation efficiency evaluation was performed via the CaCl2 and triethylenetriaminepentaacetic acid (DTPA) extraction method as well as a BCR morphological classification experiment. The microstructures and structures of the soil were explored further via X-ray diffraction (XRD) and scanning electron microscopy with X-ray energy dispersive spectroscopy (SEM-EDS) to elaborate the passivation mechanism. The results demonstrated that all passivation processes, excluding single humic acid addition, could reduce the CaCl2 and DTPA extraction contents of Pb and Cd in soils, where the optimal efficiency could be achieved by the sequential addition of superphosphate and humic acid, followed by fly ash. There was a weakly positive correlation between soil pH and CaCl2/DTPA extraction content of Pb, a negative correlation between soil pH and CaCl2/DTPA extraction content of Cd, and a significantly negative correlation between available phosphorous content and CaCl2/DTPA extraction contents of Pb and Cd, suggesting the crucial role of available phosphorous contents to control the activities of Pb and Cd. In the presence of phosphate, humic acid, and fly ash, the Pb and Cd could convert from active weak acid extraction to low-activity residual speciation, resulting in effectively reducing Pb and Cd transferability. Throughout the XRD and SEM-EDS analyses, it was found that ion exchange was the predominant mechanism in heavy metal passivation by single superphosphate, wherein the heavy metals were transformed into an insoluble Ca-containing phosphate mixture. The dissolving/precipitation or surface adsorption could be concluded as the main mechanism in the combination of the three passivation agents that converted heavy metals to lead phosphate precipitate[(Pb3(PO4)2] or mixed heavy metal mineral[PbFe3(SO4)(PO4)(OH)6], so as to obtain superior heavy metal passivation achievement.

Analysis for Risk Factors of Death in Atrial Fibrillation Patients With or Without Heart Failure / 中国循环杂志

Objective: To explore the risk factors of death in atrial fibrillation (AF) patients with or without heart failure (HF). Methods: A total of 2015 emergency AF patients from 20 hospitals in China from 2008-11 to 2011-10 were consecutively enrolled. Based on existing HF, the patients were divided into 2 groups: HF group, n=753 and Non-HF group, n=1263. The baseline condition and in-hospital treatment were recorded, patients were followed-up for 1 year to document all-cause death and the relevant risk factors were studied by multivariate Cox regression analysis. Results: Compared with Non-HF group, HF group had less male, lower heart rate (HR) and body mass index (BMI), less patients with previous histories of hypertension and hyperthyreosis, lower application rates of calcium antagonists and amiodarone, all P<0.05; HF group had the higher CHADS2score, more patients with previous histories of myocardial infarction, coronary artery disease, congenital heart disease (HD), valvular HD, rheumatic HD, left ventricular (LV) hypertrophy, smoking, LV dysfunction, cognitive disorder,pneumonectasis/chronic obstructive pulmonary disease (COPD), valvular surgery and major bleeding; higher application rates of diuretics, ACEI, digoxin, aspirin and warfarin, all P<0.05. 1991 patients finished follow-up study and during that period, compared with Non-HF group, HF group showed the lower usage rates of rhythm-control drugs and clopidogrel, while higher usage rates of ventricular-control drugs and warfarin, all P<0.05; higher incidences of death and major bleeding, all P<0.05. Cox regression analysis indicated that HF was the risk factor for 1 year mortality in AF patients (HR=1.50, 95% CI 1.17-1.92, P=0.001). In Non-HF group, age (HR=1.09, 95% CI 1.07-1.11, P<0.001), heart rate (HR=1.011, 95% CI 1.005-1.017, P<0.001), primary diagnosis (HR=1.63, 95% CI 1.13-2.35, P=0.01) and COPD (HR=2.18, 95% CI 1.47-3.22, P<0.001) were related to 1 year death. In HF group, age (HR=1.05, 95% CI 1.03-1.07, P<0.001), BMI (HR=0.92, 95% CI 0.88-0.96, P<0.001), systolic blood pressure (HR=0.991, 95% CI 0.984-0.998, P=0.012) and primary diagnosis (HR=2.50, 95% CI 1.48-4.21, P=0.001) were related to 1 year death. Conclusion: Baseline condition and in-hospital treatment were different in AF patients with or without HF. HF was the risk factor for 1 year mortality and the other risk factors were different in AF patients with or without HF.

CXC Chemokine Receptor Type 4 Antagonism Ameliorated Allograft Fibrosis in Rat Kidney Transplant Model.

OBJECTIVES: In this study, we evaluated the effects of CXC chemokine receptor type 4 and stromal cell-derived factor 1 signaling in the progression of chronic allograft nephropathy in a rat model. MATERIALS AND METHODS: Experimental rats were divided into 3 groups: Lewis-to-Lewis isograft transplant (group A), Fisher 344 rat-to-Lewis allograft transplant with immunosuppressant cyclosporine (group B), and Fisher 344 rat-to-Lewis allograft transplant treated with cyclosporine and the CXC chemokine receptor type 4 antagonist AMD3100 (1 mg/kg/d) (group C). On day 90 after the operation, renal graft function, proteinuria, and histologic Banff score were measured. The expression levels of transforming growth factor ß1 and collagen IV were determined by quantitative real-time polymerase chain reaction. RESULTS: Renal function and urinary protein were increased in allografts of groups B and C compared with isografts of group A. The Banff score was significantly decreased in the AMD3100-treated animals (group C), with renal fibrosis being reduced. In addition, overexpressed levels of transforming growth factor ß1 and collagen IV in group B allografts were significantly reduced versus that shown with treatment with the CXC chemokine receptor type 4 antagonist in group C. CONCLUSIONS: Together, these data strongly implicate that CXC chemokine receptor type 4 antagonism alleviated renal interstitial fibrosis in long-term surviving allografts by down-regulating expression of transforming growth factor ß1.

[Mixture Leaching Remediation Technology of Arsenic Contaminated Soil].

Soil contamination of arsenic pollution has become a severely environmental issue, while soil leaching is an efficient method for remediation of arsenic-contaminated soil. In this study, batch tests were primarily conducted to select optimal mixture leaching combination. Firstly, five conventional reagents were selected and combined with each other. Secondly, the fractions were analyzed before and after the tests. Finally, to explore the feasibility of mixed leaching, three soils with different arsenic pollution levels were used to compare the leaching effect. Comparing with one-step washing, the two-step sequential washing with different reagents increased the arsenic removal efficiency. These results showed that the mixture of 4 h 0.5 mol · L⁻¹ NaOH + 4 h 0.1 mol · L⁻¹ EDTA was found to be practicable, which could enhance the removal rate of arsenic from 66.67% to 91.83%, and the concentration of arsenic in soil was decreased from 186 mg · kg⁻¹ to 15.2 mg · kg⁻¹. Furthermore, the results indicated that the distribution of fractions of arsenic in soil changed apparently after mixture leaching. Leaching process could significantly reduce the available contents of arsenic in soil. Moreover, the mixture of 0.5 mol · L⁻¹ NaOH + 0.1 mol L⁻¹ EDTA could well decrease the arsenic concentration in aluminum-type soils, while the mixture of 0.5 mol · L⁻¹ OX + 0.5 mol · L⁻¹ NaOH could well decrease the arsenic concentration in iron-type soils.

[Preparation of Visible-light-induced g-C3N4/Bi2S3 Photocatalysts for the Efficient Degradation of Methyl Orange].

Visible light responsive heterojunctions of graphitic carbon nitride (g-C3N4) and Bi2S3 were successfully designed and constructed by a simple solvothermal process. The as-prepared samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM) and UV-vis diffuse reflectance spectroscopy (DRS). Under visible light irradiation, the as-prepared g-C3N4/Bi2S3 photocatalysts exhibited highly enhanced photochemical efficiency in the degradation of methyl orange (MO) compared with pure g-C3N4 and Bi2S3. On the basis of the calculated energy bands, the excellent enhancement was attributed to the efficient separation of photoinduced electron-hole pairs. In addition, a detailed degradation pathway of MO degradation by g-C3N4/Bi2S3 composites was proposed to further elucidate the inner photodegradation mechanism. This research may provide a cost-effective and easy-scaling up approach to develop visible-light-driven photocatalysts, which could be applied in wastewater treatment.

Prolonged ischemia elicits acute allograft rejection involved in CXCR3 activation in rat kidney transplants.

BACKGROUND: Acute rejection is a major obstacle in patients with prolonged ischemia in deceased-donor renal transplantation. Chemokines and their receptors play a critical role in leukocyte trafficking, resulting in allograft rejection; therefore, the role of chemokine receptor CXCR3 in acute rejection induced by prolonged ischemia in rat kidney transplantation models was evaluated. METHODS: Syngeneic and allogeneic renal transplantations were performed. For cold ischemia, grafts were stored in 4.0°C University of Wisconsin solution for 12 or 16 h. Serum and renal tissues were harvested 7.0 d after surgery and serum TNF-α, IL-6, and renal function were measured. Graft histology was stained with periodic acid-Schiff and immunohistochemical staining and further evaluated for signs of acute rejection. CXCR3 proteins were quantified by Western blot. The transplanted rats were divided into 4 groups as follows: iso-12-h = isogeneic transplant with 12-h CIT graft; iso-16-h = isogeneic kidney transplant with 16-h CIT graft; allo-12-h = allogeneic renal transplant with 12-h CIT graft; allo-16 h = allogeneic renal transplant with 16-h CIT graft; and 16 h+T = allogeneic 16-h CIT graft received tacrolimus. RESULTS: Prolonged cold ischemia time (CIT; 16 h) enhanced acute glomerular damage, interstitial inflammation, and tubulointerstitial cellular infiltration in allografts with and without immunosuppressant tacrolimus; but it was not apparent in the isografts. The expression of CXCR3 protein and the proportion of CXCR3-positive cells were significantly higher in the allo-16 h and 16 h +T groups than that in the allo-12 h group 7d post-surgery. CONCLUSIONS: CIT triggered acute rejection in allogeneic, but not in isogeneic, kidney transplants, accompanied by an elevation of leukocyte recruitment and damaged graft function. The upregulated expression of chemokine receptor CXCR3 promoted inflammatory infiltration and acute allograft rejection.

[Stabilization Treatment of Pb and Zn in Contaminated Soils and Mechanism Studies].

In the present work, the combined application of potassium dihydrogen phosphate, quick lime and potassium chloride was used to immobilize the Pb and Zn in contaminated soils. The efficiency of the process was evaluated through leaching tests and Tessier sequential extraction procedure. The mechanism of stabilization was analyzed by X-ray diffraction (XRD) and scanning electron microscope (SEM) to reveal the mechanism of stabilization. The results showed that the stabilizing efficiency of Pb contaminated soils was above 80% and the leaching concentrations of Pb, Zn were far below the threshold when the ratio of exogenous P and soil (mol · mol⁻¹) was 2:1-4: 1, the dosing ratio of CaO was 0.1%-0.5% ( mass fraction) and the dosage of potassium chloride was 0.02-0. 04 mol. Meanwhile, Pb and Zn in soil were transformed from the exchangeable fraction into residual fraction, which implied that the migration of Pb, Zn in soil could be confined by the stabilization treatment. XRD and SEM analysis revealed that Ca-P-Pb precipitation, lead orthophosphate [PbHP04, Pb3 (PO4)2], pyromorphite (Pb-PO4-Cl/OH) and mixed heavy metal deposits (Fe-PO4- Ca-Pb-Zn-OH) could be formed after solidification/stabilization in which Pb and Zn could be wrapped up to form a solidified composition and to prevent leaching.

Lack of association between COX-2 8473T>C polymorphism and breast cancer risk: a meta-analysis.

AIM OF THE STUDY: Results of recent published studies on the association between the COX-2 8473T>C polymorphism and the risk of breast cancer have often been conflicting. To make a more precise estimation of the potential relationship, a meta-analysis was performed. MATERIAL AND METHODS: A total of seven case-control studies with 7,033 cases and 9,350 controls were included in the current meta-analysis through searching the databases of PubMed, Embase, and Cochrane Library (up to March 1(st), 2013). The odds ratio (OR) and 95% confidence interval (95% CI) were calculated to assess the strength of the association. The meta-analysis was conducted in a fixed/random effect model. RESULTS: We found no significant associations for all genetic models after all studies were pooled into the meta-analysis (for C vs. T: OR = 0.974, 95% CI: 0.906-1.047, p = 0.471; for CC vs. TT: OR = 0.957, 95% CI: 0.803-1.140, p = 0.62; for TC vs. TT: OR = 0.964, 95% CI: 0.881-1.055, p = 0.421; for CC + TC vs. TT: OR = 0.963, 95% CI: 0.880-1.053, p = 0.406; for CC vs. TT + TC: OR = 0.978, 95% CI: 0.831-1.15, p = 0.788). We also observed no obvious associations in the subgroup analyses by ethnicity (Caucasian) and source of controls (population based, PB) for all genetic models. CONCLUSIONS: Current evidence suggests that the COX-2 8473T>C polymorphism is not associated with breast cancer risk.

[Characterizing composition and transformation of dissolved organic matter in subsurface wastewater infiltration system].

In the present study, the soil column with radius of 30 cm and height of 200 cm was used to simulate a subsurface wastewater infiltration system. Under the hydraulic loading of 4 cm x d(-1), composition and transformation of dissolved organic matter (DOM) from different depths were analyzed in a subsurface wastewater infiltration system for treatment of septic tank effluent using three-dimensional excitation emission matrix fluorescence spectroscopy (3D-EEM) with regional integration analysis (FRI). The results indicate that: (1) from different depth, the composition of DOM was also different; influent with the depth of 0.5 m was mainly composed of protein-like substances, and that at other depths was mainly composed of humic- and fulvic-like substances. (2) DOM stability gradually increased and part of the nonbiodegradable organic matter can be removed during organic pollutants degradation process. (3) Not only the organic pollutants concentration was reduced effectively, but also the stability of the DOM improved in subsurface wastewater infiltration system.

The XRCC3 Thr241Met polymorphism influences glioma risk - a meta-analysis.

BACKGROUND: Findings from previous published studies regarding the association of the XRCC3 Thr241Met polymorphism with glioma susceptibility have often been conflicting. Therefore, a meta-analysis including all available publications was carried out to make a more precise estimation of the potential relationship. METHODS: By searching the electronic databases of Pubmed and Embase (up to April 1st, 2013), a total of nine case-control studies with 3,752 cases and 4,849 controls could be identified for inclusion in the current meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association. RESULTS: This meta-analysis showed the XRCC3 Thr241Met polymorphism to be significantly associated with decreased glioma risk in the allelic model (Met allele vs. Thr allele: OR= 0.708, 95%CI= 0.631-0.795). Moreover, we also observed a statistically significant association between the XRCC3 Thr241Met polymorphism and reduced glioma risk in analyses stratified by ethnicity (Asian) and source of controls (hospital based) in the allelic model. CONCLUSIONS: Current evidence suggests that the XRCC3 Thr241Met polymorphism may be a risk factor for glioma development, especially in Asians.

Sirolimus use in heart transplantation recipients with chronic renal dysfunction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effect of sirolimus-based immunosuppression administered on heart transplant recipients with chronic renal dysfunction.</p><p><b>METHODS</b>From June 2004 to December 2008, standard calcineurin inhibitors (CNI)-based immunosuppressive regimen was changed to reduced-dose CNI plus sirolimus due to CNI-related chronic renal dysfunction in 20 out of 138 cardiac transplant recipients at Fuwai Hospital. The standard immunosuppressive regimen included steroid, CNI (cyclosporine or tacrolimus), and mycophenolate mofetil or azathioprine. Sirolimus was started at 0.75 - 1.50 mg/d with titration to achieve levels of 5 - 15 µg/L, and CNI dose was reduced gradually to 1/2-2/3 of the baseline level. Patients were followed for changes in renal function, lipid level and clinical side effects related to immunosuppressive therapy. Endomyocardial biopsy (EMB) was performed routinely at 3 weeks, 3, 6 and 12 months after transplantation. EMB was also performed at 3 months after regimen change within 1 year post-transplantation or when rejections were suspected in patients beyond 1 year post-transplantation. Echocardiography was performed for monitoring purpose.</p><p><b>RESULTS</b>The mean follow-up after regimen change was (7.9 ± 6.3) months. Final sirolimus dose was (0.89 ± 0.22) mg/d and blood drug level was (7.6 ± 3.8)µg/L. Cyclosporine dose was reduced from (191.7 ± 60.0) mg/d to (123.6 ± 34.8) mg/d, with blood drug concentration reduced from (175.5 ± 58.0) µg/L to (111.9 ± 56.0) µg/L in 18 patients (P < 0.01). Tacrolimus average dose was reduced from 4.25 mg/d to 3.00 mg/d, with blood drug concentration reduced from 13.5 µg/L to 10.5 µg/L in 2 patients. Serum creatinine level fell from (160.4 ± 25.5) µmol/L to (134.4 ± 26.8) µmol/L (P < 0.01) and urea nitrogen fell from (13.8 ± 4.7) µmol/L to (10.4 ± 3.0) µmol/L (P < 0.01) at one month after regimen change. Twenty two EMBs were performed in 11 patients within 1 year post-transplant, there were 4 episodes of acute rejected (ISHLT grade 2). Twenty patients are all alive and cardiac function was normal. The most common side effect was hyperlipidemia, and triglycerides, total cholesterol and low density lipoprotein levels were significantly increased at 1 month post regimen change (P < 0.05 or P < 0.01). Leukocyte, hemoglobin and platelet as well as liver function remained unchanged at 1 month post regimen change (all P > 0.05).</p><p><b>CONCLUSION</b>Our results show that change from CNI-based immunosuppressive regimen to reduced-dose CNI plus sirolimus is an effective and safe approach for the management of patients with CNI-related chronic renal dysfunction, leading to an improvement in renal function without compromise in anti-rejection efficacy and with tolerable side effects.</p>