Effects of Oxygen Therapy on Patients with a Chronic Wound: A Systematic Review and Meta-analysis.

OBJECTIVE: To synthesize the effects of oxygen-based therapy on patients with a chronic wound. DATA SOURCES: The authors searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for relevant randomized controlled trials from database inception. Investigators measured risk of bias using the Cochrane Collaboration's Risk of Bias tool. STUDY SELECTION: The included randomized controlled trials focused on the effects (short- or long-term wound healing, amputation rate, percentage of reduction in ulcer size, and poststudy transcutaneous oxygen measurement [TcPO2]) of oxygen-based therapy (including hyperbaric oxygen therapy, topical oxygen therapy, and continuous diffusion of oxygen) on patients with a chronic wound. DATA EXTRACTION: Researchers extracted information regarding participant characteristics and primary and secondary outcomes from the included studies. DATA SYNTHESIS: Pooled effects of 31 included studies showed that patients treated with oxygen had better short-term wound healing (risk ratio [RR], 1.544; 95% CI, 1.199 to 1.987), a higher percentage reduction in the ulcer area (standardized mean difference [SMD], 0.999; 95% CI, 0.439 to 1. 599), lower amputation rates (RR, 0.529; 95% CI, 0.325 to 0.862), shorter wound healing time (SMD, -0.705; 95% CI, -0.908 to -0.501), and higher poststudy TcPO2 (SMD, 2.128; 95% CI, 0.978 to 3.278) than those in the control group. For long-term wound healing, there was no statistically significant difference (RR, 1.227; 95% CI, 0.976 to 1.542). CONCLUSIONS: Oxygen-based therapy improves short-term parameters of wound healing in patients with chronic wounds.

Effect of primary and secondary Fasciola gigantica infection on specific IgG responses, hepatic enzyme levels and weight gain in buffaloes.

Buffaloes, as highly susceptible definitive hosts of Fasciola gigantica, suffer from a high infection rate of fasciolosis, which causes enormous economic losses. Repeat infection is responsible for this high rate; thus, elucidating the protective immunity mechanism in repeat infection is decisive in fasciolosis prevention. Herein, a secondary experimental infection model was established to preliminarily reveal the protective immunity that occurs in repeat infection. In brief, animals were assigned to three groups: group A (uninfected control), group B (primary infection) and group C (secondary infection). Buffaloes were autopsied 20 weeks post-infection for measurements of the recovered flukes and hepatic examination. In addition, the detection of specific antibody (IgG) responses to F. gigantica excretory-secretory product (FgESP) throughout the whole period and weight gain throughout the first 4 months as a percentage (%) of the starting weight were also determined. The serum hepatic enzyme gamma glutathione transferase (GGT) levels were monitored to assess hepatic damage throughout the study period. Infection establishment was compared between group B and group C. Similar specific IgG patterns were observed between group B and group C, and hepatic damage was more severe in group C than group B. Significant differences in weight gain as a percentage of the start weight were observed between group A and group B at the 3rd and 4th months postprimary infection, while significant differences were not observed between group A and group C or group B and group C. Our results suggest that challenge infection cannot induce resistance against F. gigantica in buffaloes, which is consistent with the protective immunity against Fasciola hepatica reinfection observed in sheep and goats.

Analysis of risk factors and establishment of a risk prediction model for post-transplant diabetes mellitus after kidney transplantation.

Introduction: Post-transplant diabetes mellitus (PTDM) is a known side effect in transplant recipients administered immunosuppressant drugs, such as tacrolimus. This study aimed to investigate the risk factors related to PTDM, and establish a risk prediction model for PTDM. In addition, we explored the effect of PTDM on the graft survival rate of kidney transplantation recipients. Methods: Patients with pre-diabetes mellitus before kidney transplant were excluded, and 495 kidney transplant recipients were included in our study, who were assigned to the non-PTDM and PTDM groups. The cumulative incidence was calculated at 3 months, 6 months, 1 year, 2 years, and 3 years post-transplantation. Laboratory tests were performed and the tacrolimus concentration, clinical prognosis, and adverse reactions were analyzed. Furthermore, binary logistic regression analysis was used to identify the independent risk factors of PTDM. Results: Age ≥ 45 years (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 1.14-3.92; P = 0.015), body mass index (BMI) > 25 kg/m2 (aOR 3.12, 95% CI 2.29-5.43, P < 0.001), tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation (aOR 2.46, 95%CI 1.41-7.38; P < 0.001), transient hyperglycemia (aOR 4.53, 95% CI 1.86-8.03; P < 0.001), delayed graft function (DGF) (aOR 1.31, 95% CI 1.05-2.39; P = 0.019) and acute rejection (aOR 2.16, 95% CI 1.79-4.69; P = 0.005) were identified as independent risk factors of PTDM. The PTDM risk prediction model was developed by including the above six risk factors, and the area under the receiver operating characteristic curve was 0.916 (95% CI 0.862-0.954, P < 0.001). Furthermore, the cumulative graft survival rate was significantly higher in the non- PTDM group than in the PTDM group. Conclusions: Risk factors related to PTDM were age ≥ 45 years, BMI > 25 kg/m2, tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation, transient hyperglycemia, DGF and acute rejection.

Rifampicin impairs adipogenesis by suppressing NRF2-ARE activity in mice fed a high-fat diet.

Prolonged treatment with rifampicin (RFP), a first-line antibacterial agent used in the treatment of drug-sensitive tuberculosis, may cause various side effects, including metabolic disorders. The nuclear factor (erythroid-derived 2)-like 2 (NFE2L2, also known as NRF2) plays an essential regulatory role in cellular adaptive responses to stresses via the antioxidant response element (ARE). Our previous studies discovered that NRF2 regulates the expression of CCAAT-enhancer-binding protein ß (Cebpb) and peroxisome proliferator-activated receptor gamma (Pparg) in the process of adipogenesis. Here, we found that prolonged RFP treatment in adult male mice fed a high-fat diet developed insulin resistance, but reduced fat accumulation and decreased expression of multiple adipogenic genes in white adipose tissues. In 3 T3-L1 preadipocytes, RFP reduced the induction of Cebpb, Pparg and Cebpa at mRNA and protein levels in the early and/or later stage of hormonal cocktail-induced adipogenesis. Mechanistic investigations demonstrated that RFP inhibits NRF2-ARE luciferase reporter activity and expression of NRF2 downstream genes under normal culture condition and in the early stage of adipogenesis in 3 T3-L1 preadipocytes, suggesting that RFP can disturb adipogenic differentiation via NRF2-ARE interference. Taken together, we demonstrate a potential mechanism that RFP impairs adipose function by which RFP likely inhibits NRF2-ARE pathway and thereby interrupts its downstream adipogenic transcription network.

A new PKD1 mutation discovered in a Chinese family with autosomal polycystic kidney disease.

BACKGROUND/AIMS: Autosomal-dominant polycystic kidney disease (ADPKD), a heterogeneous genetic disorder characterized by massive kidney enlargement and progressive chronic kidney disease, is due to abnormal proliferation of renal tubular epithelium. ADPKD is known to be caused by mutations in PKD1 and PKD2 genes. METHODS: In the present study, the mutation analysis of PKD genes was performed in a new Chinese family with ADPKD using Long-Range (LR) PCR sequencing and targeted next-generation sequencing (targeted DNA-HiSeq). RESULTS: A unique 28 bp deletion (c.12605_12632del28) in exon 46 of the PKD1 gene was identified in two affected family members by LR PCR method, but not in any unaffected relatives or unrelated controls. Higher accuracy and less missing detection presented in LR PCR method compared with targeted DNA-HiSeq. This mutation c.12605_12632del28 (p.Arg4202ProextX146) resulted in a delayed termination of amino acid code, and was highly speculated pathogenic in this ADPKD family. Moreover, this newly identified frame-shift change was compared to the PKD gene database, but no similar mutation was yet reported. CONCLUSION: A novel frame-shift mutation, c. 12605_12632del28, in the PKD1 gene was found in a Chinese ADPKD family. All evidence available suggested that it might be the mutation responsible for the disease in that family.

Exendin-4 ameliorates renal ischemia-reperfusion injury in the rat.

BACKGROUND: Glucagon-like peptide-1 receptor (GLP-1R) activation exerts protective effects against reactive oxygen species by inducing the oxidative defense gene heme oxygenase-1 (HO-1), and provides protection in mice against transient focal cerebral ischemia and ischemia-reperfusion injury in the rat heart. GLP-1R is also expressed in the kidney, but it is unknown whether GLP-1R activation is able to protect against ischemia-reperfusion injury in the rat kidney. MATERIALS AND METHODS: We used a rat model of renal ischemia-reperfusion injury. The rats were pretreated with the GLP-1R agonist, exendin-4 before reperfusion. We used real-time polymerase chain reaction to evaluate expression of the oxidative defense gene HO-1 and Western blot analysis for HO-1 and GLP-1R. Renal function was assessed at baseline and 24 and 72 h after reperfusion. The kidneys were processed for histologic and morphometric analysis, caspase-3, and ED1 immunohistochemistry at 72 h. The degree of apoptosis of the renal tubular cells was determined using terminal deoxynucleotidyl transferase deoxyuridine triphosphate-biotin nick end labeling assays. RESULTS: Exendin-4 pretreatment resulted in GLP-1R activation and upregulation of HO-1. Preconditional activation of GLP-1R significantly improved the serum creatinine levels compared with vehicle (P < 0.05). Furthermore, tissue injury, caspase-3 and ED1 expression, and apoptosis were less severe, as quantified by application of a standardized histologic scoring system in a blinded manner. CONCLUSIONS: These results have demonstrated that preconditional activation of the GLP-1R with exendin-4 in the kidney significantly protected against ischemia-reperfusion injury in rats by increasing HO-1 expression.

Forensic identification of spilled biodiesel and its blends with petroleum oil based on fingerprinting information.

A case study is presented for the forensic identification of several spilled biodiesels and its blends with petroleum oil using integrated forensic oil fingerprinting techniques. The integrated fingerprinting techniques combined SPE with GC/MS for obtaining individual petroleum hydrocarbons (aliphatic hydrocarbons, polyaromatic hydrocarbons and their alkylated derivatives and biomarkers), and biodiesel hydrocarbons (fatty acid methyl esters, free fatty acids, glycerol, monoacylglycerides, and free sterols). HPLC equipped with evaporative scattering laser detector was also used for identifying the compounds that conventional GC/MS could not finish. The three environmental samples (E1, E2, and E3) and one suspected source sample (S2) were dominant with vegetable oil with high acid values and low concentration of fatty acid methyl ester. The suspected source sample S2 was responsible for the three spilled samples although E1 was slightly contaminated by petroleum oil with light hydrocarbons. The suspected source sample S1 exhibited with the high content of glycerol, low content of glycerides, and high polarity, indicating its difference from the other samples. These samples may be the separated byproducts in producing biodiesel. Canola oil source is the most possible feedstock for the three environmental samples and the suspected source sample S2.

Bioequivalue of two mycophenolate sodium enteric-coated tablets and the drug monitoring based on limited sampling strategy: A single-center, randomized, open-label, three-period, reference-replicated, crossover study.

OBJECTIVE: A mycophenolate sodium enteric-coated tablet has shown a satisfying anti-rejection effect in patients receiving solid organ transplantation. The current study evaluated the bioequivalence between the test (Ruiyirong®) vs. reference (Myfortic®) formulations by exploring equations for predicting their area under the concentration-time curve (AUC) using a limited sampling strategy in healthy subjects. METHODS: Forty-eight healthy Chinese subjects were randomized into three administration sequences (test-reference-reference, reference-reference-test, and reference-test-reference) to receive the Ruiyirong or Myfortic treatment on days 1, 8, and 15. RESULTS: The 90% confidential interval (CI) of the geometric mean ratios (test/reference) of maximum plasma concentration (Cmax), the AUC from time 0 to the last timepoint (AUC0-t), and the AUC from 0 to infinity (AUC0-∞) was 92.90%-110.57%, 96.91%- 101.80%, and 96.71%-101.84%, respectively. All these values fell into the bioequivalence criteria of 80.00%-125.00% (based on the criteria of the Food and Drug Administration). The adverse events were 10.4% in Ruiyirong test group and 14.6% in Myfortic reference group. Eight equations for estimating the AUC of the Ruiyirong test and Myfortic reference formulations were evaluated; most of them worked well with the R-value >0.8. Among the four chosen equations, the intragroup verification exhibited a high agreement with the R-value ranging from 0.857 to 0.971 and with the low predictive error (PE > 5% with absolute PE > 15%). Meanwhile, the intergroup verification indicated a high inter-agreement with the R-value ranging from 0.896 to 0.974 (all P < 0.001). CONCLUSION: The Ruiyirong test vs. Myfortic reference formulations meet the bioequivalent criteria and are well tolerated. The further linear regression analysis explores eight equations predicting the AUC value and the chosen four equations for the Ruiyirong test and Mayfortic reference formulations are interchangeable.

The protective effect of prolyl-hydroxylase inhibition against renal ischaemia requires application prior to ischaemia but is superior to EPO treatment.

BACKGROUND: Inhibition of the HIF regulating prolyl hydroxylation domain (PHDs) proteins prior to renal injury (preconditioning) has been shown to protect the kidney via activation of hypoxia-inducible transcription factors (HIF). Application of erythropoietin (EPO), one of the HIF target genes, has also been shown to be nephroprotective, and it remains unclear to what extent the effect of HIF induction is mediated by EPO. It is also unknown whether HIF activation after the onset of ischaemia (postconditioning) is still able to protect the kidney. METHODS: Using a rat model of renal ischaemia-reperfusion injury, animals were treated with the PHD inhibitor (PHD-I) 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetate (ICA), vehicle (Veh) or recombinant human EPO (300 IU/kg) 6 h (ICA or Veh) or 30 min (EPO) prior to ischaemia (preconditioning) or with ICA prior to reperfusion (postconditioning). Renal function was assessed at baseline, 24 h and 72 h. After 72 h, kidneys were processed for histology and morphometric analysis. HIF immunohistochemistry and real-time polymerase chain reaction for HIF target genes, including EPO, were performed to evaluate ICA effects. RESULTS: ICA treatment resulted in stabilization of HIF-1α and -2α and up-regulation of HIF target genes in a dose-dependent manner. Preconditional activation of HIF by ICA significantly improved serum creatinine levels and renal morphology in comparison to Veh (P < 0.05), while postconditional ICA treatment was ineffective. EPO therapy improved tissue morphology but had no impact on the course of serum creatinine. CONCLUSION: These findings are in line with the concept that PHD-Is exert their protective effects through accumulation of HIF target gene products, with time requirements for increased transcription and translation of HIF-dependent genes, and suggest that their renoprotective effect is not predominately mediated by EPO.

Fingerprinting of petroleum hydrocarbons (PHC) and other biogenic organic compounds (BOC) in oil-contaminated and background soil samples.

Total petroleum hydrocarbons (TPH) or petroleum hydrocarbons (PHC) are one of the most widespread soil contaminants in Canada, the United States and many other countries worldwide. Clean-up of PHC-contaminated soils costs the Canadian economy hundreds of millions of dollars annually. In Canada, most PHC-contaminated site evaluations are based on the methods developed by the Canadian Council of the Ministers of the Environment (CCME). However, the CCME method does not differentiate PHC from BOC (the naturally occurring biogenic organic compounds), which are co-extracted with petroleum hydrocarbons in soil samples. Consequently, this could lead to overestimation of PHC levels in soil samples. In some cases, biogenic interferences can even exceed regulatory levels (300 µg g(-1) for coarse soils and 1300 µg g(-1) for fine soils for Fraction 3, C(16)-C(34) range, in the CCME Soil Quality Level). Resulting false exceedances can trigger unnecessary and costly cleanup or remediation measures. Therefore, it is critically important to develop new protocols to characterize and quantitatively differentiate PHC and BOC in contaminated soils. The ultimate objective of this PERD (Program of Energy Research and Development) project is to correct the misconception that all detectable hydrocarbons should be regulated as toxic petroleum hydrocarbons. During 2009-2010, soil and plant samples were collected from over forty oil-contaminated and paired background sites in various provinces. The silica gel column cleanup procedure was applied to effectively remove all target BOC from the oil-contaminated sample extracts. Furthermore, a reliable GC-MS method in combination with the derivatization technique, developed in this laboratory, was used for identification and characterization of various biogenic sterols and other major biogenic compounds in these oil-contaminated samples. Both PHC and BOC in these samples were quantitatively determined. This paper reports the characterization results of this set of 21 samples. In general, the presence of petroleum-characteristic alkylated PAH homologues and biomarkers can be used as unambiguous indicators of the contamination of oil and petroleum product hydrocarbons; while the absence of petroleum-characteristic alkylated PAH homologues and biomarkers and the presence of abundant BOC can be used as unambiguous indicators of the predominance of natural organic compounds in soil samples.

Retrospective Analysis of the Risk Factors of Perioperative Bacterial Infection and Correlation with Clinical Prognosis in Kidney Transplant Recipients.

Background: Infection remains a leading cause of morbidity and mortality in kidney transplant patients. This study aimed to investigate the risk factors of bacterial infection during the perioperative period of transplantation and the effects of infection on long-term clinical outcomes. Methods: In total, 295 kidney transplantation recipients were included in this retrospective study and assigned to two groups: non-infected and infected. The tacrolimus concentration, pharmacogenomics, laboratory parameters, and clinical outcomes of both groups were evaluated. Results: A relatively low incidence of urinary tract infection was observed in our cohort, and lung was identified as the most frequent site of infection. Gram-negative bacteria, such as Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, were the most common infecting strains in kidney transplant recipients. Patients with diabetes showed greater susceptibility to infection. Compared with the non-infected group, tacrolimus concentration was significantly lower on day 7 and 14 in the infected group. White blood cell count, neutrophil count, and C-reactive protein (CRP) in the infected group were markedly higher post-transplantation, while albumin levels were lower relative to the non-infected group. ABCB1 (rs2032582) genotype showed clear associations with infection. Furthermore, the incidence of delayed graft function (DGF) and early acute rejection (AR) before infection was significantly greater in the infected group. Finally, early post-transplant infection was associated with a marked increase in the incidence of AR, post-transplant diabetes mellitus (PTDM), and secondary infection. Conclusion: Pre-diabetes, longer duration of catheterization, lower albumin, higher CRP, tacrolimus concentration on the day 7 and 14, early AR before infection, and DGF were closely related to postoperative infection in kidney transplantation recipients. Moreover, bacterial infection during the perioperative period was closely associated with AR, PTDM and secondary infection.

Tacrolimus Concentration Is Effectively Predicted Using Combined Clinical and Genetic Factors in the Perioperative Period of Kidney Transplantation and Associated with Acute Rejection.

Background: Tacrolimus has unpredictable pharmacokinetic (PK) characteristics, which are partially attributed to CYP3A5 polymorphism. The potential effects of clinical factors in the postoperative period of transplantation on tacrolimus PK and those of early tacrolimus PK variability on clinical outcomes are yet to be clarified. Methods: We examined the genetic and clinical factors affecting early tacrolimus PK variability in 256 kidney transplant recipients. The relationships among tacrolimus exposure, graft function delay (DGF), and acute rejection (AR) were further explored. Findings. The CYP3A5 genotype were strongly associated with tacrolimus concentration/dose ratio (C 0/D). Additionally, ABCB1 (rs1045642 and rs2032582) and ABCC2 (rs3740066) were found to have potential independent effects on early tacrolimus C 0/D in multivariate analysis. Red blood counts and albumin level were the most significant clinical factors associated with tacrolimus C 0/D. Wuzhi capsule also exerted an effect on tacrolimus PK. A model combined with pharmacogenetic and clinical factors explained 43.4% tacrolimus PK variability compared with 16.3% on the basis of CYP3A5 genotype only. Notably, increasing tacrolimus concentrations in the early postoperative stage were associated with AR, but not DGF. Conclusions: Combined analysis of genotype and specific clinical factors is important for the formulation of precise tacrolimus dose regimens in the early stage after kidney transplantation.

Determination of polar impurities in biodiesels using solid-phase extraction and gas chromatography-mass spectrometry.

This paper reports on a method for development and validation for simultaneous characterization and determination of oxygenated polar impurities--free fatty carboxylic acids (FFAs), partial glycerides (monoacylglycerides, MGs), residual glycerol and free sterols--in various biodiesels based on the combination of solid-phase extraction (SPE), silylation and GC/MS technologies. The effects of various SPE and silylation conditions on the method recoveries were evaluated. Using this integrated SPE-GC/MS method, 38 target polar compounds (13 FFAs, 17 glycerides and 8 sterols) in 9 biodiesels derived from 4 different feedstocks were successfully separated and quantified. It was found that the carbon chain length of FFAs was ranged from C(6) to C(24), with C(16) and C(18) being the most abundant in all biodiesels. The total FFAs concentration was consistent with the acid values (AVs) measured by standard method ASTM D974-04. MG congeners with carbon number of 18 (mono-C18) were most abundant in the biodiesel samples, followed by mono-C(16) and free glycerol. ß-Sitosterol and campesterol were found to be the prevailing phytosterols in all pure vegetable oil-based biodiesels, while brassicasterol and stigmasterol was only significant in the biodiesel from canola oil and soybean oil, respectively, and abundant cholesterol was only detected in animal fat-based biodiesels.

Method development for fingerprinting of biodiesel blends by solid-phase extraction and gas chromatography-mass spectrometry.

A method based on the combination of solid-phase extraction (SPE) with gas chromatography-mass spectrometry (GC/MS) for detailed chemical fingerprinting of biodiesel/petrodiesel blends was developed in the present study. Forensic identification, commonly referred to as chemical fingerprinting, is based on the relative distributions of individual aliphatic hydrocarbons, aromatic hydrocarbons, fatty acid alkyl esters, and free sterols. Fractionation of fuel samples is optimized for the separation of fatty acid esters and free sterols from petroleum hydrocarbons into four fractions: aliphatic, aromatic, fatty acid ester, and polar components. The final recoveries of aliphatic and aromatic hydrocarbons were determined to be in the range of 65-103%, 73-105% for FAMEs, and 78-103% for free sterols in the polar fraction. Excellent separation with negligible crossover of components with different polarities between fractions was observed. Quantitative analysis of blend levels and individual chemical distribution were achieved. The method has great potential for the identification of biodiesel in diesel fuel blends and could form the basis of a method for characterization of biodiesel-contaminated environmental samples.

Forensic fingerprinting and source identification of the 2009 Sarnia (Ontario) oil spill.

This paper presents a case study in which integrated forensic oil fingerprinting and data interpretation techniques were used to characterize the chemical compositions and determine the source of the 2009 Sarnia (Ontario) oil spill incident. The diagnostic fingerprinting techniques include determination of hydrocarbon groups and semi-quantitative product-type screening via gas chromatography (GC), analysis of oil-characteristic biomarkers and the extended suite of parent and alkylated PAH (polycyclic aromatic hydrocarbon) homologous series via gas chromatography-mass spectrometry (GC-MS), determination and comparison of a variety of diagnostic ratios of "source-specific marker" compounds, and determination of the weathering degree of the spilled oil, and whether the spilled oil hydrocarbons have been mixed with any other "background" chemicals (biogenic and/or pyrogenic hydrocarbons). The detailed chemical fingerprinting data and results reveal the following: (1) all four samples are mixtures of diesel and lubricating oil with varying percentages of diesel to lube oil. Both samples 1460 and 1462 are majority diesel-range oil mixed with a smaller portion of lube oil. Sample 1461 contains slightly less diesel-range oil. Sample 1463 is majority lubricating-range oil. (2) The diesel in the four diesel/lube oil mixture samples was most likely the same diesel and from the same source. (3) The spill sample 1460 and the suspected-source sample 1462 have nearly identical concentrations and distribution patterns of target analytes including TPHs, n-alkane, PAHs and biomarker compounds; and have nearly identical diagnostic ratios of target compounds as well. Furthermore, a perfect "positive match" correlation line (with all normalized ratio data points falling into the straight correlation line) is clearly demonstrated. It is concluded that the spill oil water sample 1460 (#1, from the water around the vessel enclosed by a boom) matches with the suspected source sample 1462 (#3, from the vessel engine room bilge pump). (4) From the n-alkane and PAH analysis, it appears that the oil in the spill sample 1460 is slightly more weathered in comparison with sample 1462. The minor differences in fingerprints of two samples were most likely caused by weathering effects. (5) Sample 1461 (#2, from the vessel engine room bilge) and sample 1463 (#4, from the vessel bilge waste collection tank) demonstrated significantly different fingerprints and diagnostic ratios of target compounds from that of spill sample 1460. This was caused most likely by percentages of diesel to lube oil in these two samples different from that in spill sample 1460.

The Effects of Oral Sodium Bicarbonate on Renal Function and Cardiovascular Risk in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: Oral sodium bicarbonate is often used to correct acid-base disturbance in patients with chronic kidney disease (CKD). However, there is little evidence on patient-level benign outcomes to support the practice. METHODS: We conducted a systematic review and meta-analysis to examine the efficacy and safety of oral sodium bicarbonate in CKD patients. A total of 1853 patients with chronic metabolic acidosis or those with low-normal serum bicarbonate (22-24 mEq/L) were performed to compare the efficacy and safety of oral sodium bicarbonate in patients with CKD. RESULTS: There was a significant increase in serum bicarbonate level (MD 2.37 mEq/L; 95% CI, 1.03 to 3.72) and slowed the decline in estimated glomerular filtration rate (eGFR) (MD -4.44 mL/min per 1.73 m2, 95% CI, -4.92 to -3.96) compared with the control groups. The sodium bicarbonate lowered T50-time, an indicator of vascular calcification (MD -20.74 min; 95% CI, -49.55 to 8.08); however, there was no significant difference between the two groups. In addition, oral sodium bicarbonate dramatically reduced systolic blood pressure (MD -2.97 mmHg; 95% CI, -5.04 to -0.90) and diastolic blood pressure (MD -1.26 mmHg; 95% CI, -2.33 to -0.19). There were no statistically significant body weight, urine pH and mean mid-arm muscle circumference. CONCLUSION: Treatment of metabolic acidosis with sodium bicarbonate may slow the decline rate of kidney function and potentially significantly improve vascular endothelial function in patients with CKD. PROSPERO REGISTRATION NUMBER: CRD42020207185.

Genetic Polymorphisms Affecting Tacrolimus Metabolism and the Relationship to Post-Transplant Outcomes in Kidney Transplant Recipients.

BACKGROUND: Tacrolimus is a key drug in kidney transplantation with a narrow therapeutic index. However, whether tacrolimus exposure variability affects clinical outcomes and adverse reactions remains unknown. OBJECTIVE: Our study investigated the factors that influence tacrolimus exposure in kidney transplantation recipients and the relationship between tacrolimus concentration and clinical outcomes and adverse reactions. SETTINGS AND METHODS: We examined the effect of tacrolimus concentration on clinical outcomes and adverse reactions in 201 kidney transplantation recipients, and identified clinical and pharmacogenetic factors that explain tacrolimus exposure. RESULTS: The CYP3A5 genotype was clearly associated with dose-adjusted trough blood tacrolimus concentrations (C0/D), whereas no significant difference was observed in patients with the CYP3A4*1B, CYP3A4*22, ABCB1, ABCC2, POR*28 or PXR alleles. Clinical factors such as red blood cell count, hemoglobin, and albumin were the most useful influence factors affecting tacrolimus C0/D. Besides, Wuzhi capsule increased tacrolimus C0/D in kidney transplantation recipients. Furthermore, higher tacrolimus concentrations were associated with higher diarrhea and post-transplant diabetes mellitus (PTDM) risk but not with acute rejection and chronic allograft kidney dysfunction. CONCLUSION: Clinical factors, medication, and CYP-enzyme polymorphisms accounted for tacrolimus concentration variability in kidney transplantation recipients. Furthermore, higher tacrolimus concentrations were associated with higher diarrhea and PTDM risk.

Diagnostic Accuracy of Donor-derived Cell-free DNA in Renal-allograft Rejection: A Meta-analysis.

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) is a potential noninvasive molecular marker of graft rejection after kidney transplant, whose diagnostic accuracy remains controversial. METHODS: We performed a systematic review and metaanalysis to evaluate the diagnostic accuracy of dd-cfDNA. Relevant literature was searched from online databases, and the data on the diagnostic accuracy of discriminating main rejection episodes (MRE) and antibody-mediated rejection (AMR) were merged, respectively. RESULTS: Nine studies were included in the metaanalysis, of which 6 were focused on the diagnostic accuracy of dd-cfDNA for MRE, whose pooled sensitivity, specificity, area under the receiver operating characteristics curve, diagnostic odds ratio, overall positive likelihood ratio, and negative likelihood ratio with 95% confidence intervals were 0.70 (0.57-0.81), 0.78 (0.70-0.84), 0.81 (0.77-0.84), 8.18 (5.11-13.09), 3.15 (2.47-4.02), and 0.39 (0.27-0.55), respectively. Five tests were focused on discriminating AMR, whose pooled indicators were 0.84 (0.75-0.90), 0.80 (0.74-0.84), 0.89 (0.86-0.91), 20.48 (10.76-38.99), 4.13(3.21-5.33), and 0.20(0.12-0.33), respectively. CONCLUSIONS: Donor-derived cell-free DNA can be a helpful marker for the diagnosis of AMR among those recipients suspected of renal dysfunction. Its diagnostic accuracy on the MRE remains uncertain, which requires further prospective, large-scale, multicenter, and common population research.

Reconstruction of a Transplant Recipient's External Iliac Artery Using Donor's Inferior Vena Cava in Renal Transplantation: 2 Case Reports.

Iliac atherosclerosis is common in renal transplant recipients. In severe cases, it affects intraoperative renal arterial anastomosis and increases the risk of postanastomosis complications. At present, safe and efficient vascular replacement methods are relatively limited. In the 2 renal transplant cases at our center, described here, the donors' iliac arteries were unavailable. We therefore attempted to replace the recipients' diseased external iliac artery with the donors' inferior vena cava and then performed an end-to-side grafting with the attachment in arterial reconstruction. One patient received a single kidney transplantation, while the other received a dual kidney transplantation. Antiplatelet/anticoagulation drug application was avoided, and both patients were observed for more than 6 months. Stable renal graft function was achieved without any vascular complications. During this study, all procedures were in compliance with the Helsinki Congress and the Declaration of Istanbul. For end-stage renal disease patients with severe iliac atherosclerosis who are waiting for kidney transplantation, a donor's vena cava graft could potentially be a promising replacement option to restore external iliac artery patency and reconstruct renal blood flow, without the necessity of harvesting a recipient's autologous vessels or looking for costly artificial ones.

CL316243 treatment mitigates the inflammation in white adipose tissues of juvenile adipocyte-specific Nfe2l1 knockout mice.

Nuclear factor-erythroid 2-related factor 1 (NFE2L1) is a key transcription factor that regulates cellular adaptive responses to various stresses. Our previous studies revealed that adult adipocyte-specific Nfe2l1-knockout [Nfe2l1(f)-KO] mice show adipocyte hypertrophy and severe adipose inflammation, which can be worsened by rosiglitazone, a peroxisome proliferator-activated receptor γ agonist. To further assess the crucial roles of NFE2L1 in adipocytes, we investigated the effect of CL316243, a ß3 adrenergic agonist that promotes lipolysis via a post-translational mechanism, on adipose inflammation in juvenile Nfe2l1(f)-KO mice. In contrast to adult mice, 4-week-old juvenile Nfe2l1(f)-KO mice displayed a normal fat distribution but reduced fasting plasma glycerol levels and elevated adipocyte hypertrophy and macrophage infiltration in inguinal and gonadal WAT. In addition, Nfe2l1(f)-KO mice had decreased expression of multiple lipolytic genes and reduced lipolytic activity in WAT. While 7 days of CL316243 treatment showed no significant effect on adipose inflammation in Nfe2l1-Floxed control mice, the same treatment dramatically alleviated macrophage infiltration and mRNA expression of inflammation and pyroptosis-related genes in WAT of Nfe2l1(f)-KO mice. Together with previous findings in adult mice, the current study highlights that NFE2L1 plays a fundamental regulatory role in lipolytic gene expression and thus might be an important target to improve adipose plasticity and lipid homeostasis.