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Yoona Oh,1,2,* Chang-Hyun Han,3,4,* Yeonhak Kim,1 Jihun Kim,1 Changsop Yang,3 Young Eun Choi,5 Byoung-Kab Kang,3 Kun Hyung Kim,1,2 Gi Young Yang,1,2 Byung Ryul Lee,1,2 Eunseok Kim1,2 1Department of Acupuncture and Moxibustion Medicine, Pusan National University Korean Medicine Hospital, Yangsan, Republic of Korea; 2Division of Clinical Medicine, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 3KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 4Korean Convergence Medicine, University of Science & Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 5Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea*These authors contributed equally to this workCorrespondence: Eunseok Kim, Division of Clinical Medicine, School of Korean Medicine, Pusan National University, 49, Busandaehak-ro, Mulgeum-eup, Yangsan-si, Gyeongnam, 50612, Republic of Korea, Tel +82 55 360 5950, Fax +82 55 360 5890, Email eskim@pusan.ac.krPurpose: Pharmacopuncture therapy (PPT) combines medicinal extracts with acupuncture and is widely used as an adjunct in clinical practice. This study assessed the safety and feasibility of PPT in addition to conventional Korean Medicine treatment (CKMT), including electroacupuncture, cupping and infra-red, for lumbar spinal stenosis (LSS).Patients and Methods: Forty patients diagnosed with LSS were randomly assigned to undergo PPT with CKMT (experimental group) or CKMT alone (control group) at a 1:1 ratio, receiving 10 sessions of each intervention over five weeks. The primary clinical outcome was measured using the 100-mm Visual Analog Scale (VAS) for buttock and leg pain five weeks post-treatment. Secondary outcomes included clinically important difference (CID), Zurich Claudication Questionnaire, self-reported walking capacity, Modified–Modified Schober test, EuroQol 5-dimension 5-level questionnaire, and the patient’s global impression of change. The adverse events were assessed at each visit. The analysis of covariance was conducted to compare between two groups.Results: Intervention completion rates were 95% and 100% in the experimental and control groups, respectively. No statistically significant differences were found between groups regarding the primary outcome (adjusted mean difference: 8.0; 95% confidence interval: − 1.4– 17.4). The mean difference in the 100-mm VAS for low back pain at week 5 (adjusted mean difference: 12.9; 95% confidence interval: 2.4– 23.4) and the proportion of patients who reached the minimum CID was higher in the experimental group than in the control group. However, no significant differences were observed with other secondary outcomes. One patient in the experimental group experienced a systemic skin rash that resolved the same day, whereas the adverse events in the other group were mild and transient.Conclusion: This trial demonstrated the feasibility of add-on effects and the safety of pharmacopuncture in patients with LSS. Further studies are warranted to evaluate the add-on effects of PPT in treating LSS.Trial Registration: Clinical Research Information Service (CRIS), KCT0007229; registered on April 26, 2022.Keywords: lumbar spinal stenosis, pharmacopuncture therapy, add-on effect, conventional Korean medicine treatment, pragmatic randomized pilot trial

Bin Huang,1 Wei-Jiang Dong,2 Gao-Yi Yang,3 Wei Wang,1 Cong-Hua Ji,1 Fei-Ni Zhou4 1Department of Ultrasound, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 2Department of Ultrasonography, Tongxiang Chinese Medicine Hospital, Jiaxing, 3Department of Ultrasound, Hangzhou Red Cross Hospital, 4Department of Medical Records and Statistics, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China Abstract: The purpose of the present study was to develop a novel transdermal drug-delivery system comprising a polyamidoamine dendrimer coupled with sonophoresis to enhance the permeation of diclofenac (DF) through the skin. The novel transdermal drug-delivery system was developed by using a statistical Plackett–Burman design. Hairless male Wistar rat skin was used for the DF-permeation study. Coupling media concentration, ultrasound-application time, duty cycle, distance from probe to skin, and a third-generation polyamidoamine-dendrimer concentration were selected as independent variables, while in vitro drug release was selected as a dependent variable. Independent variables were found to be statistically significant (P

Gang Wang1,2, Jun Jie Wang1, Guang Yi Yang1, Shi Ming Du1, Nan Zeng2, Dong Sheng Li3, Rui Ming Li3, Ji Yan Chen1, Jin Bo Feng3, Shen Hao Yuan1, Fang Ye11Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, 2Department of Pharmacy, Chendu Traditional Chinese Medical University, Chendu City, Sichuan Province, 3Hubei Provincial Key Laboratory of Embryo Stem Cells, Shiyan City, Hubei Province, People's Republic of ChinaBackground: Quercetin has been shown to induce apoptosis in a number of cancer cell lines, but a quercetin-loaded nanoliposomal formulation with enhanced antitumor activity in C6 glioma cells and its effect on cancer cell death has not been well studied. The aim of this study was to examine if quercetin-loaded liposomes (QUE-NL) has enhanced cytotoxic effects and if such effects involve type III programmed cell death in C6 glioma cells.Methods: C6 glioma cells were treated with QUE-NL and assayed for cell survival, apoptosis, and necrosis. Levels of reactive oxygen species production and loss of mitochondrial membrane potential (ΔΨm) were also determined by flow cytometry assay to assess the effects of QUE-NL. ATP levels and lactate dehydrogenase activity were measured, and Western blotting was used to assay cytochrome C release and caspase expression.Results: QUE-NL induced type III (necrotic) programmed cell death in C6 glioma cells in a dose-dependent and time-dependent manner. High concentrations of QUE-NL induced cell necrosis, which is distinct from apoptosis and autophagy, whereas liposomes administered alone induced neither significant apoptosis nor necrosis in C6 glioma cells. QUE-NL-induced ΔΨm loss and cytochrome C release had no effect on caspase activation, but decreased ATP levels and increased lactate dehydrogenase activity indicated that QUE-NL stimulated necrotic cell death.Conclusion: C6 glioma cells treated with QUE-NL showed a cellular pattern associated with necrosis without apoptosis and was independent of caspase activity. Nonapoptotic cell death induced by high concentrations of QUE-NL for controlling caspase-independent type III programmed cell death may provide the basis for novel therapeutic approaches to overcome avoidance of apoptosis by malignant cells.Keywords: quercetin, liposome, type III programmed cell death, reactive oxygen species, ATP, mitochondria, C6 glioma cells

Abstract Background The quantification of mRNA expression in urinary sediments is a reliable biomarker for various diseases. However, few studies have investigated the clinical relevance of urinary mRNA levels in IgA nephropathy (IgAN). Thus, we investigated the expression of urinary mRNAs and their clinical significance in IgAN. Methods Overall, 200 patients with biopsy-proven IgAN, 48 disease controls, and 76 healthy controls were enrolled. We identified the differential expression of mRNAs in renal tissue between patients with IgAN and normal subjects using the Gene Expression Omnibus dataset and selected candidate mRNAs. mRNA expression in the urinary sediment was measured using quantitative real-time polymerase chain reaction. Associations between urinary mRNA levels and clinicopathological parameters were analyzed and the predictive value of mRNAs for disease progression was evaluated. Results The urinary expression of CCL2, CD14, DNMT1, FKBP5, Nephrin, and IL-6 was significantly upregulated in patients with IgAN compared with healthy controls. C3, FLOT1, and Podocin levels were significantly correlated with renal function, where C3, FLOT1, and TfR levels were significantly correlated with urinary protein excretion. During follow-up, 26 (13.0%) patients with IgAN experienced disease progression, defined as a greater than 50% reduction in the estimated glomerular filtration rate or progression to end-stage renal disease. Urinary mRNA levels of FLOT1 (HR 3.706, 95% CI 1.373–10.005, P = 0.010) were independently associated with an increased risk of disease progression. Conclusions Our results suggest that urinary sediment mRNAs are a useful biomarker in IgAN patients. Further studies with larger sample sizes and longer follow-up durations are required.

Abstract The sebum on human skin is generated for various causes. The composition of the formed sebum increases the proliferation of Cutibacterium acnes (C. acnes) residing on the skin. As C. acnes proliferates, it produces skin irritants that stimulate the sebaceous glands, increasing sebum production. Skin troubles such as acne may occur. The lysate concentrates of Bacillus stratosphericus (B. stratosphericus), first discovered in the stratosphere, confirmed a 66.35% inhibition of Nitric Oxide (NO) production at 0.50 mg/ml concentration in vitro. Additionally, the growth inhibition efficacy of B. stratosphericus lysate concentrate (BSLC) against C. acnes was confirmed, showing a 95.1% inhibition of growth proliferation at a consistency of 0.50 mg/ml. Based on the in vitro results, the efficacy of BSLC in degrading and reducing sebum was confirmed by reacting it with artificial sebum to various concentrations. The results showed a concentration-dependent decrease in artificial sebum ccording to the efficacy results confirmed in vitro, a clinical trial was conducted to evaluate the daily sebum reduction efficacy of a serum formulation containing 50 mg/ml of BSLC. After a 4-week application, the test group containing BSLC determined a significant 28.68% reduction in sebum levels, demonstrating the practical implications of the research. In conclusion, BSLC is considered to have sufficient industrial value as a valuable ingredient for the cosmetics industry aimed at sebum improvement.

Abstract Background IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis, although the definitive markers are unknown. We aimed to investigate the clinical significance of urinary cytokines in patients with IgAN. Methods From 2009 to 2018, the patients were divided into three groups: IgAN (n = 191), disease control (n = 53), and normal control (n = 76). We used a multiplex enzyme-linked immunosorbent assay to measure 16 selected urinary inflammatory cytokines, evaluated the correlation between clinical and pathological features following regression analysis on progression. Results The IgAN group exhibited significantly different levels of urinary cytokines compared to the normal control and disease control groups. Urinary levels of B-cell-activating factor, vascular endothelial growth factor receptor-2, monocyte chemoattractant protein-1, C–X–C motif chemokine 10, C–X–C motif ligand 16, epidermal growth factor (EGF), endocan, endostatin, growth/differentiation factor-15 (GDF-15), interleukin-6 (IL-6), mannose-binding lectin, transferrin receptor, and kidney injury molecule-1 were significantly correlated with both the estimated glomerular filtration rate and urine protein–creatinine ratio. In a multivariate Cox regression analysis, urinary EGF (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.17–0.95, P = 0.04), GDF-15 (HR 2.45, 95% CI 1.01–5.94, P = 0.048), and IL-6 (HR 3.02, 95% CI 1.05–8.64, P = 0.04) were associated with progression in IgAN. Conclusions Urinary inflammatory biomarkers may serve as alternative predictive biomarkers in patients with IgAN. Further studies are needed to elucidate the physiological mechanisms and confirm the results.

Background Endostatin is released during extracellular matrix remodeling and is involved in the development of vascular pathology and cardiovascular (CV) disease. However, the role of circulating endostatin as a biomarker of vascular calcification and CV events in patients undergoing hemodialysis (HD) remains unclear. Methods A total of 372 patients undergoing HD were prospectively recruited. Plasma endostatin levels were measured at baseline, and their associations with circulating mineral bone disease (MBD) biomarkers and abdominal aortic vascular calcification scores were analyzed. The primary endpoint was defined as a composite of CV and cardiac events. Results Plasma levels of patients in endostatin tertile 3 were significantly associated with low-density lipoprotein cholesterol levels and predialysis systolic blood pressure in multivariate analysis. However, endostatin levels did not correlate with circulating MBD biomarkers or vascular calcification scores. Patients in endostatin tertile 3 had a significantly higher cumulative event rate for the composite of CV events (p = 0.006). Endostatin tertile 3 was also associated with an increased cumulative rate of cardiac events (p = 0.04). In multivariate Cox regression analyses, endostatin tertile 3 was associated with a 4.37-fold risk for composite CV events and a 3.88-fold risk for cardiac events after adjusting for multiple variables. Conclusion Higher circulating endostatin levels were independently associated with atherosclerotic risk factors but did not correlate with MBD markers or vascular calcification. Higher circulating endostatin levels were associated with a greater risk of composite CV events in patients undergoing HD, and endostatin is a biomarker that helps to determine the high risk of CV events.

Xerosis, characterized by dry, rough skin, causes discomfort and aesthetic concerns, necessitating effective treatment. Traditional treatments often show limited efficacy, prompting the need for innovative therapies. This study highlights the efficacy of microbiome therapeutic LP51, derived from a healthy vaginal microbiome, in improving xerosis. A double-blind clinical trial involving 43 subjects with dry inner arm skin compared the effects of a 2.9% LP51 extract formulation to a placebo over 4 weeks. The LP51 group exhibited a significant increase in stratum corneum hydration (10.0 A.U.) compared to the placebo group (4.8 A.U.) and a 21.4% decrease in transepidermal water loss (TEWL), whereas the placebo group showed no significant change. LP51 also demonstrated benefits in enhancing skin hydration, improving the skin barrier, and exhibited anti-atopic, anti-inflammatory, and antioxidant properties. Safety was confirmed through in vitro cytotoxicity tests. These effects are attributed to the microbiome-safe component in LP51 and its role in improving xerosis, reflected by an increase in the xerosis-microbiome index, defined by the Firmicutes/Actinobacteria ratio. These findings position microbiome therapeutic LP51 as a promising novel treatment for xerosis.

Abstract Hemodialysis patients are susceptible to cardiovascular remodeling, which increases the risk of cardiovascular morbidity and mortality. Circulating extracellular matrix (ECM)-associated molecules increase during cardiovascular remodeling and can be potential biomarkers of adverse cardiovascular outcomes. However, their clinical significance in patients undergoing hemodialysis remain unclear. This study aimed to elucidate the association between circulating ECM-associated molecules and cardiovascular outcomes in patients undergoing hemodialysis. To this end, we measured levels of plasma matrix metalloproteinase (MMP)-2, MMP-9, tenascin-C, and thrombospondin-2 in 372 patients with hemodialysis. Plasma MMP-2 levels were significantly higher in patients with future cardiovascular events than in those without future cardiovascular events (P = 0.004). All measured molecules had significant correlations with amino-terminal pro-brain natriuretic peptide levels, but the correlation coefficient was the strongest for plasma MMP-2 (rho = 0.317, P

Background/Objectives: This study aimed to investigate trends in antidiabetic drug use and assess the risk of metformin-associated lactic acidosis (MALA) in patients with chronic kidney disease (CKD). Methods: A retrospective observational analysis based on the common data model was conducted using electronic medical records from 2010 to 2021. The patients included were aged ≥18, diagnosed with CKD and type 2 diabetes, and had received antidiabetic medications for ≥30 days. MALA was defined as pH ≤ 7.35 and arterial lactate ≥4 mmol/L. Results: A total of 8318 patients were included, with 6185 in CKD stages 1–2 and 2133 in stages 3a–5. Metformin monotherapy was the most prescribed regimen, except in stage 5 CKD. As CKD progressed, metformin use significantly declined; insulin and meglitinides were most frequently prescribed in end-stage renal disease. Over the study period, the use of SGLT2 inhibitors (13.3%) and DPP-4 inhibitors (24.5%) increased significantly, while sulfonylurea use decreased (p < 0.05). Metformin use remained stable in earlier CKD stages but significantly decreased in stage 3b or worse. The incidence rate (IR) of MALA was 1.22 per 1000 patient-years, with a significantly increased IR in stage 4 or worse CKD (p < 0.001). Conclusions: Metformin was the most prescribed antidiabetic drug in CKD patients in Korea with a low risk of MALA. Antidiabetic drug use patterns varied across CKD stages, with a notable decline in metformin use in advanced CKD and a rise in SGLT2 inhibitor prescriptions, underscoring the need for further optimized therapy.

Abstract Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. The clinical relevance of 11 urinary exosomal microRNAs (miRNAs) was evaluated in patients with IgAN. From January 2009 to November 2018, IgAN (n = 93), disease control (n = 11), and normal control (n = 19) groups were enrolled. We evaluated the expression levels of urinary exosomal miRNAs at the baseline and their relationship with clinical and pathologic features. This study aimed to discriminate statistically powerful urinary exosomal miRNAs for the prognosis of IgAN. Urinary miRNA levels of miR-16-5p, miR-29a-3p, miR-124-3p, miR-126-3p, miR-199a-3p, miR-199b-5p, and miR-335-3p showed significant correlation with both estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio (uPCR). In univariate regression analysis, age, body mass index, hypertension, eGFR, uPCR, Oxford classification E, and three miRNAs (miR-16-5p, miR-199a-3p, and miR-335-3p) were associated with disease progression in patients with IgAN. The area under the curve (AUC) of miR-199a-3p was high enough (0.749) without any other clinical or pathologic factors, considering that the AUC of the International IgAN Risk Prediction Tool was 0.853. Urinary exosomal miRNAs may serve as alternative prognostic biomarkers of IgAN with further research.

BackgroundPatients undergoing hemodialysis (HD) have a high risk of novel coronavirus disease 2019 (COVID-19) and poor clinical outcomes. This study aimed to investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine effectiveness against infection and deaths in the South Korean population undergoing HD.MethodsWe conducted a retrospective cohort study to compare the incidence of COVID-19 and post-diagnosis mortality between patients who were either never vaccinated or fully or partially vaccinated. The Korean nationwide COVID-19 registry and the Korean National Health Insurance Service databases were used. Adult patients without a history of COVID-19 were included between October 8, 2020, and December 31, 2021. The study outcomes were COVID-19 diagnosis, severe clinical COVID-19-related events, and post-diagnosis death.ResultsEighty-five thousand eighteen patients undergoing HD were included, of whom 69,601 were fully vaccinated, 2,213 were partially vaccinated and 13,204 were unvaccinated. Compared with the unvaccinated group, the risk of being diagnosed with COVID-19 in patients who were fully vaccinated decreased during the study period (adjusted odds ratio [aOR] = 0.147; 95% confidence interval [CI] = 0.135–0.159). There were 1,140 (1.3%) patients diagnosed with COVID-19. After diagnosis, fully vaccinated patients were significantly less likely to die than unvaccinated patients (aOR = 0.940; 95% CI = 0.901–0.980) and to experience severe clinical events (aOR = 0.952; 95% CI = 0.916–0.988).ConclusionFull vaccination against COVID-19 was associated with a reduced risk of both infection and severe clinical outcomes in the South Korean population undergoing HD. These findings support the use of vaccination against SARS-CoV-2 among patients undergoing HD.

Abstract Follistatin-like protein-1 (FSTL-1) is secreted glycoprotein, which regulates cardiovascular, immune and skeletal system. However, the clinical significance of circulating FSTL-1 levels remains unclear in hemodialysis patients. A total 376 hemodialysis patients were enrolled from June 2016 to March 2020. Plasma FSTL-1 level, inflammatory biomarkers, physical performance, and echocardiographic findings at baseline were examined. Plasma FSTL-1 levels were positively correlated with TNF-α and MCP-1. Handgrip strength showed weak positive correlation in male patients only, and gait speed showed no correlation with FSTL-1 levels. In multivariate linear regression analysis, FSTL-1 level was negatively associated with left ventricular ejection fraction (β = − 0.36; p = 0.011). The cumulative event rate of the composite of CV event and death, and cumulative event rate of CV events was significantly greater in FSTL-1 tertile 3. In multivariate Cox-regression analysis, FSTL-1 tertile 3 was associated with a 1.80-fold risk for the composite of CV events and death(95% confidence interval (CI) 1.06–3.08), and a 2.28-fold risk for CV events (95% CI 1.15–4.51) after adjustment for multiple variables. In conclusion, high circulating FSTL-1 levels independently predict the composite of CV events and death, and FSTL-1 level was independently associated with left ventricular systolic dysfunction.

Aims: To examine the antinociceptive effects of N-Methyl-D-aspartate (NMDA) receptor NR2 subunit antagonists in a rat model of the facial formalin test. Methods: Experiments were carried out on adult male Sprague-Dawley rats weighing 220 to 280 g. Anesthetized rats were individually mounted on a stereotaxic frame and a polyethylene tube was implanted for intracisternal injection and, 72 hours later, formalin tests were performed. NMDA receptor antagonists were administered intracisternally 10 minutes prior to subcutaneous injection of 5% formalin (50 MuL) into the vibrissal pad. Results: The intracisternal administration of 25, 50, or 100 Mug of memantine, an antagonist that acts at the NMDA ion channel site, significantly suppressed the number of scratches in the second phase of the behavioral responses to formalin. Intracisternal administration of a range of doses of 5,7-dichlorokynurenic acid, a glycine site antagonist, or DL-2-amino-5-phosphonopentanoate (AP-5), a nonselective NMDA site antagonist, produced significant antinociceptive effects in the second phase. Intracisternal administration of 1, 2.5, or 5 Mug of (2R,4S)-4-(3 Phosphonopropyl)-2-piperidine_carboxylic acid (PPPA), a competitive NR2A antagonist, significantly suppressed the number of scratches in the second phase, while only the highest dose of PPPA (5 Mug) significantly suppressed the number of scratches in the first phase. The antinociceptive effects of intracisternal injection of (_R,_S)-_-(4Hydroxyphenyl)-_ methyl-4-(phenylmethyl)-1-Piperidinepropanol maleate(Ro 25-6981), a selective NR2B antagonist, were similar to those of PPPA. Injection of memantine, AP-5, Ro 25-6981, or vehicle did not result in any motor dysfunction. A low dose of PPPA (1 _g) or 5,7-dichlorokynurenic acid (2.5 _g) did not affect motor function. However, higher doses of PPPA and 5,7-dichlorokynurenic acid produced motor dysfunction. Conclusion: The present results suggest that central NR2 subunits play an important role in orofacial nociceptive transmission. Moreover, this data also indicate that targeted inhibition of the NMDA receptor NR2 subunit is a potentially important new treatment approach for inflammatory pain originating in the orofacial area. J Orofac Pain 2010;24:203-211. [ABSTRACT FROM AUTHOR]

AIMS: To investigate the effects of morphine on mechanical allodynia following compression of the trigeminal ganglion in the rat. METHODS: Experiments were carried out on male Sprague-Dawley rats weighing between 250 and 260 g. For compression, a 4% agar solution (8 microL) was injected into the trigeminal ganglion. In the control group, rats were sham operated without agar injections. The authors evaluated the effects of intraperitoneal or intracisternal administration of morphine on mechanical allodynia evoked by air-puff stimulation of the vibrissa pad area 14 days following compression of the trigeminal ganglion. RESULTS: Mechanical allodynia was established within 3 days and lasted beyond postoperative day 24. Intraperitoneal administration of morphine (2 or 5 mg/kg) significantly blocked mechanical allodynia ipsilateral to the compression of the trigeminal ganglion. Intraperitoneal administration of morphine also inhibited mechanical allodynia on the contralateral side. Moreover, intracisternal administration of morphine (5 microg) strongly suppressed both ipsilateral and contralateral mechanical allodynia. The antiallodynic effects of morphine were blocked by pretreatment with naloxone, an opioid receptor antagonist. CONCLUSION: These results suggest that the application of a high dose of morphine may be of great benefit in treating trigeminal neuralgia-like nociception. [ABSTRACT FROM AUTHOR]

Abstract Background Low physical activity (PA) increases the prevalence of chronic kidney disease (CKD). This study aimed to investigate the effects of PA and sedentary time (ST) on the changes in renal function and the development of CKD in the middle‐aged Korean population. Methods From the Korean Genome and Epidemiology Study Database, 7988 participants in their 40s and 60s were identified and stratified by (1) PA: high‐PA (>24 MET‐h/day), moderate‐PA (9–24 MET‐h/day) and low‐PA (6 h/day), moderate‐ST (3–6 h/day) and low‐ST (

Introduction: End-stage renal disease (ESRD) is a growing disease in Korea and worldwide and is an important condition that affects patient outcomes. In order to provide optimal management for mineral disturbance, vascular calcification, and bone disease of ESRD patients, the ORCHESTRA study (Korean dialysis cohort for mineral, vascular calcification, and fracture) was conducted and enrolled Korean dialysis patients. Methods: Sixteen university-affiliated hospitals and one Veterans Health Service Medical Center participated in this study. This prospective cohort study enrolled approximately 900 consecutive dialysis patients between May 2019 and January 2021. Enrolled subjects were evaluated at baseline for demographic information, laboratory tests, radiologic imaging, and bone mineral densitometry (BMD) scans. After enrollment, regular assessments of patients were performed and their biospecimens were collected according to the study protocol. Primary outcomes were occurrence of major adverse cardiovascular events (MACE), invasive treatment for peripheral artery disease (PAD), and osteoporotic fractures. Secondary outcomes were hospitalization for cerebro-cardiovascular disease or progression of abdominal aortic calcification (AAC). Participants will be assessed for up to three years to determine whether primary or secondary outcomes occur. Results: From May 2019 to January 2021, all participating centers recruited 900 consecutive dialysis patients, including 786 undergoing hemodialysis (HD) and 114 undergoing peritoneal dialysis (PD). The mean age of subjects was 60.4 ± 12.3 years. Males accounted for 57.7%. The mean dialysis vintage was 6.1 ± 6.0 years. The HD group was significantly older, had a longer dialysis vintage, and more comorbidities. Overall, the severity of vascular calcification was higher and the level of BMD was lower in the HD group than in the PD group. Conclusion: This is a nationwide, multicenter, prospective cohort study that focuses on CKD-mineral and bone disorder (CKD-MBD) and aims to provide clinical evidence to establish optimal treatment guidelines for Asian dialysis patients.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disease caused by mutations in the GLA gene that encodes α-galactosidase A (α-GAL). Clinical phenotypes tend to vary in monozygotic female twins because mutations are located on the X-chromosome, whereas similar phenotypes are found in male monozygotic twins. Here we report the case of male monozygotic twins with FD presenting with distinguishable renal phenotypes.Case: A 49-year-old male patient who visited the hospital with proteinuria 14 years prior was readmitted for the same issue. His monozygotic twin brother had started hemodialysis 6 months prior due to renal failure of unknown origin. The patient’s renal function was within the normal range, while his spot urine protein-to-creatinine ratio was 557 mg/g. Echocardiography revealed left ventricular hypertrophy (LVH). The findings of a renal biopsy were consistent with FD. Genetic testing identified a c.656T>C mutation in the GLA gene, and α-GAL activity was significantly decreased. Genetic screening of his family clarified that his mother, older sister, twin brother, and his daughter had the same genetic mutations. The patient received enzyme replacement therapy 34 times. Subsequently, migalastat was initiated that continues today. Renal function and proteinuria remain stable, and the LVH has mildly improved.Conclusion: This is the first case of male monozygotic twins expressing different progressions of FD. Our findings demonstrate the possibility that environmental or epigenetic factors may critically influence genotype–phenotype discordance.

IntroductionAcute rejection (AR) continues to be a significant obstacle for short- and long-term graft survival in kidney transplant recipients. Herein, we aimed to examine urinary exosomal microRNAs with the objective of identifying novel biomarkers of AR.Materials and methodsCandidate microRNAs were selected using NanoString-based urinary exosomal microRNA profiling, meta-analysis of web-based, public microRNA database, and literature review. The expression levels of these selected microRNAs were measured in the urinary exosomes of 108 recipients of the discovery cohort using quantitative real-time polymerase chain reaction (qPCR). Based on the differential microRNA expressions, AR signatures were generated, and their diagnostic powers were determined by assessing the urinary exosomes of 260 recipients in an independent validation cohort.ResultsWe identified 29 urinary exosomal microRNAs as candidate biomarkers of AR, of which 7 microRNAs were differentially expressed in recipients with AR, as confirmed by qPCR analysis. A three-microRNA AR signature, composed of hsa-miR-21-5p, hsa-miR-31-5p, and hsa-miR-4532, could discriminate recipients with AR from those maintaining stable graft function (area under the curve [AUC] = 0.85). This signature exhibited a fair discriminative power in the identification of AR in the validation cohort (AUC = 0.77).ConclusionWe have successfully demonstrated that urinary exosomal microRNA signatures may form potential biomarkers for the diagnosis of AR in kidney transplantation recipients.

Dialysis patients are more likely to die or become hospitalized from coronavirus disease 2019 (COVID-19). Currently, only a few studies have evaluated the efficacy of a fourth booster vaccination in hemodialysis (HD) patients and there is not enough evidence to recommend for or against a fourth booster vaccination. This study compared the humoral response and disease severity of patients on HD who received either three or four doses of COVID-19 vaccine. A total of 88 patients were enrolled. Humoral response to vaccination was measured by quantifying immunoglobulin G levels against the receptor binding domain of SARS-CoV-2 (anti-RBD IgG) at five different times and plaque reduction neutralization tests (PRNT) at two different times after vaccination over a period of 18 months. Antibody levels were measured at approximately two-month intervals after the first and second dose, then four months after the third dose, and then one to six months after the fourth dose of vaccine. PRNT was performed two months after the second and four months after the third dose of vaccine. We classified patients into four groups according to the number of vaccine doses and presence of COVID-19 infection. Severe infection was defined as hospital admission for greater than or equal to two weeks or death. There was no difference in antibody levels between naïve and infected patients except after a fourth vaccination, which was effective for increasing antibodies in infection-naïve patients. Age, sex, body mass index (BMI), dialysis vintage, and presence of diabetes mellitus (DM) did not show a significant correlation with antibody levels. Four patients who experienced severe COVID-19 disease tended to have lower antibody levels prior to infection. A fourth dose of SARS-CoV-2 vaccine significantly elevated antibodies in infection-naïve HD patients and may be beneficial for HD patients who have not been previously infected with SARS-CoV-2 for protection against severe infection.

The Korean government decided to schedule heterologous vaccinations on dialysis patients for early achievement of immunization against Coronavirus disease 2019(COVID-19). However, the effects of heterologous immunizations in hemodialysis (HD) patients are unclear. One hundred (HD) patients from Gangdong Kyung Hee University Hospital and Kyung Hee Medical Center and 100 hospital workers from Gangdong Kyung Hee University Hospital were enrolled in this study. The HD patients received the mixing schedule of ChAdOx1/BNT162b2 vaccinations at 10-week intervals, while hospital workers received two doses of ChAdOx1 vaccines at 12-week intervals. Serum IgG to a receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2 was measured 1 month after the first dose, 2 months and 4 months after the second dose. The median [interquartile range] anti-RBD IgG was 82.1[34.5, 176.6] AU/ml in HD patients and 197.1[124.0, 346.0] AU/ml in hospital workers (P < 0.001) after the first dose. The percentage of positive responses (IgG > 50 AU/ml) was 65.0% and 96.0% among the both group, respectively (P < 0.001). The anti-RBD IgG levels increased significantly by 2528.8 [1327.6, 5795.1] AU/ml with a 100.0% positive response rate in HD patients 2 months after the second dose, which was higher than those in hospital workers 981.4[581.5, 1891.4] AU/ml (P < 0.001). Moreover, anti-RBD IgG remains constantly high, and positive response remains 100% in HD patients 4 months after the second dose. This study suggests that heterologous vaccinations with ChAdOx1/BNT162b2 can be an alternative solution on HD patients for early and strong induction of humoral response.

Abstract Background Low physical performance in patients undergoing maintenance hemodialysis is associated with a high mortality rate. We investigated the clinical relevance of gait speed and handgrip strength, the two most commonly used methods of assessing physical performance. Methods We obtained data regarding gait speed and handgrip strength from 277 hemodialysis patients and evaluated their relationships with baseline parameters, mental health, plasma inflammatory markers, and major adverse clinical outcomes. Low physical performance was defined by the recommendations suggested by the Asian Working Group on Sarcopenia. Results The prevalence of low gait speed and handgrip strength was 28.2 and 44.8%, respectively. Old age, low serum albumin levels, high comorbidity index score, and impaired cognitive functions were associated with low physical performance. Patients with isolated low gait speed exhibited a general trend for worse quality of life than those with isolated low handgrip strength. Gait speed and handgrip strength showed very weak correlations with different determining factors (older age, the presence of diabetes, and lower serum albumin level for low gait speed, and lower body mass index and the presence of previous cardiovascular events for low handgrip strength). Patients with low gait speed and handgrip strength had elevated levels of plasma endocan and matrix metalloproteinase-7 and the highest risks for all-cause mortality and cardiovascular events among the groups (adjusted hazard ratio of 2.72, p = 0.024). Elderly patients with low gait speed and handgrip strength were at the highest risk for poor clinical outcomes. Conclusion Gait speed and handgrip strength reflected distinctive aspects of patient characteristics and the use of both factors improved the prediction of adverse clinical outcomes in hemodialysis patients. Gait speed seems to be a better indicator of poor patient outcomes than is handgrip strength.

Background : : Online hemodiafiltration (OL-HDF) offers considerable advantages in clearance of molecules of various sizes. However, evidence of clinical effects of OL-HDF is scarce in Korea. In this study, we investigated changes in laboratory values over more than 12 months after switching to OL-HDF. Methods : : Adult patients with end-stage renal disease undergoing hemodialysis (HD) were prospectively enrolled in a K-cohort (CRIS no. KCT0003281) from 6 tertiary hospitals in South Korea. We recruited 435 patients, 339 of whom were on HD at enrollment. One hundred eighty-two patients were followed for more than 24 months. Among them, 44 were switched to OL-HDF for more than 12 months without conversion to HD. We used a paired t test to compare baseline and 24-month follow-up results. Results : : The mean age of the subjects was 61.2 ± 12.2 years, and 62.6% were male. The baseline hemoglobin level was not significantly different between HD and OL-HDF group (10.61 ± 1.15 vs. 10.46 ± 1.03 g/dL, P = 0.437). However, the baseline serum protein and albumin levels were significantly lower in the OL-HDF group (6.82 ± 0.49 vs. 6.59 ± 0.48 g/dL, P = 0.006; 3.93 ± 0.28 vs. 3.73 ± 0.29 g/dL, P < 0.001). In patients switched to OL-HDF, levels of hemoglobin and serum albumin significantly increased (10.46 ± 1.03 vs. 11.08 ± 0.82 g/dL, P = 0.001; 3.73 ± 0.29 vs. 3.87 ± 0.30 g/dL, P = 0.001). The normalized protein catabolic rate decreased after 24 months, but the change was not significant (1.07 ± 0.25 vs. 1.03 ± 0.21 g/kg/day, P = 0.433). Although the dose of erythropoiesis-stimulating agent was lower in patients who converted to HDF, it was not significantly different (-115.7 ± 189.7 vs. -170.5 ± 257.1 P = 0.206). Conclusion : : OL-HDF treatment over more than 12 months was associated with no harmful effects on anemia and nutritional status.

Traditional histologic methods are limited in detecting dynamic changes in immune cells during acute kidney injury (AKI). Recently, optical tissue clearing combined with multiphoton microscopy (MPM) or light sheet fluorescence microscopy (LSFM) has become an emerging method for deep tissue evaluation and three-dimensional visualization. These new approaches have helped expand our understanding of tissue injury and repair processes, including tracing the changes in immune cells. We designed this study to investigate the morphological and functional alterations of renal mononuclear phagocytes (MNPs) in lipopolysaccharide (LPS)-induced AKI using renal clearing in CD11c-YFP mice. We also evaluated the effect of the NLRP3 inhibitor MCC950 to determine whether NLRP3 inhibition attenuates the activation of CD11c+ cells in an LPS-induced AKI model. Transverse sectioned whole mouse kidney imaging by LSFM showed that CD11c+ cells were mainly distributed in the cortex, especially the tubulointerstitial area. The number of CD11c+ cells was significantly more densely interspersed, particularly in periglomerular and perivascular lesions, in the saline-treated LPS-exposed kidney than in the control kidney. Deep imaging of the kidney cortex by MPM demonstrated an increased number of CD11c+ cells in the saline-treated LPS group compared with the control group. This quantitative alteration of CD11c+ cells in AKI was accompanied by morphological changes at high resolution, showing an increased number and level of dendrites. These morphological and behavioral changes in the saline-treated LPS group were accompanied by increased MHC class II and CD86 on CD11c-YFP+ cells. MCC950 attenuated the activation of CD11c+ cells after AKI and improved renal function. In conclusion, wide and deep three-dimensional visualization using MPM or LSFM combined with kidney clearing uncovers dynamic changes of renal MNPs, which are directly linked to renal function in AKI.

BackgroundAge-related alterations in renal sodium handling affect blood pressure (BP). We aimed to clarify whether the pressure-natriuresis response changes with age, leading to BP elevation.MethodsA total of 4,859 participants with normal renal function from the Korean Genome and Epidemiology Study (KoGES) and 235 patients with non-diabetic chronic kidney disease (CKD) from the ESPECIAL trial were included and divided into the younger and older groups. In ESPECIAL, participants took olmesartan from weeks 0 to 16 and were educated about a low-salt diet (LSD) from weeks 8 to 16.ResultsIn both studies, older participants showed lower estimated glomerular filtration rate (eGFR) and urine concentration index and higher albuminuria. In KoGES, BP was higher and urine sodium was lower in older participants. In ESPECIAL, diastolic BP at 0 week was lower in older participants. Olmesartan reduced BP in both groups, whereas LSD decreased systolic BP only in older participants. Urine sodium increased in younger participants but decreased in older participants after olmesartan use. In KoGES, urine sodium was correlated with BP in both groups after adjusting for age, sex, and eGFR; however, the correlation coefficient was lower in older participants. In ESPECIAL, only younger participants showed a significant positive association between systolic BP and urine sodium in multiple regression analysis.ConclusionsThe pressure-natriuresis response was diminished in older participants with or without CKD.

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The clinical manifestations of diabetic kidney disease (DKD) are more heterogeneous than those previously reported, and these observations mandate the need for the recruitment of patients with biopsy-proven DKD in biomarker research. In this study, using the public gene expression omnibus (GEO) repository, we aimed to identify urinary mRNA biomarkers that can predict histological severity and disease progression in patients with DKD in whom the diagnosis and histologic grade has been confirmed by kidney biopsy. We identified 30 DKD-specific mRNA candidates based on the analysis of the GEO datasets. Among these, there were significant alterations in the urinary levels of 17 mRNAs in patients with DKD, compared with healthy controls. Four urinary mRNAs—LYZ, C3, FKBP5, and G6PC—reflected tubulointerstitial inflammation and fibrosis in kidney biopsy and could predict rapid progression to end-stage kidney disease independently of the baseline eGFR (tertile 1 vs. tertile 3; adjusted hazard ratio of 9.68 and 95% confidence interval of 2.85–32.87, p < 0.001). In conclusion, we demonstrated that urinary mRNA signatures have a potential to indicate the pathologic status and predict adverse renal outcomes in patients with DKD.

Background: Vascular adhesion protein-1 (VAP-1) is an oxidative enzyme of primary amines that facilitates the transmigration of inflammatory cells. Its oxidative and inflammatory effects are prominently increased in pathological conditions, such as metabolic, atherosclerotic, and cardiac diseases. However, the clinical significance of circulating VAP-1 levels in hemodialysis (HD) patients is unclear.Methods: A total of 434 HD patients were enrolled in a prospective multicenter cohort study between June 2016 and April 2019. Plasma VAP-1 levels were measured at the time of data entry, and the primary endpoint was defined as a composite of cardiovascular (CV) and cardiac events.Results: Circulating VAP-1 levels were positively correlated with plasma levels of cardiac remodeling markers, including brain natriuretic peptide, galectin-3, and matrix metalloproteinase-2. Multivariable logistic regression analysis revealed that patients with higher circulating VAP-1 levels were more likely to have left ventricular diastolic dysfunction [odds ratio, 1.40; 95% confidence interval [CI], 1.04–1.88]. The cumulative event rate of the composite of CV events was significantly greater in VAP-1 tertile 3 than in VAP-1 tertiles 1 and 2 (P = 0.009). Patients in tertile 3 were also associated with an increased cumulative event rate of cardiac events (P = 0.015), with a 2.06-fold higher risk each for CV (95% CI, 1.10–3.85) and cardiac (95% CI, 1.03–4.12) events after adjusting for multiple variables.Conclusions: Plasma VAP-1 levels were positively associated with left ventricular diastolic dysfunction and the risk of incident CV and cardiac events in HD patients. Our results indicate that VAP-1 may aid clinicians in identifying HD patients at a high risk of CV events.

Abstract Background Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Recent evidence suggests that genetic factors are related to the pathogenesis of IgAN. We conducted a genome-wide association study (GWAS) to identify novel genetic susceptibility loci for IgAN in a Korean population. Methods We enrolled 188 biopsy-confirmed IgAN cases and 455 healthy controls for the discovery stage and explored associations between IgAN and single nucleotide polymorphisms (SNPs) using a customized DNA chip. The significant SNPs from the discovery samples were then selected for replication in an independent cohort with 310 biopsy-confirmed IgAN cases and 438 healthy controls. Results In the first stage, two SNPs (rs10172700 in LOC105373592 and rs2296136 in ANKRD16) were selected for further association analysis in the next stage. In the replication cohort, rs2296136 in ANKRD16 was significantly associated with IgAN (odds ratio [OR] = 1.40, 95% confidence interval [CI] 0.99–1.98, p = 0.05 in log-additive model, OR = 1.55, 95% CI = 1.06–−2.27, p = 0.02 in dominant model, and OR = 0.70, 95% CI = 0.17–−2.84, p = 0.62 in recessive model). rs2296136 in ANKRD16 also showed a significant association with IgAN in the entire study population combining GWAS and replication study (p = 0.0045 in log-additive model, p = 0.0027 in dominant model, and p = 0.76 in recessive model). Conclusions The SNPs identified in the present study could be good candidate markers for predicting IgAN in Koreans, although further experimental validation is needed.

Inflammation: A decoy peptide treats arthritis and sepsis in mice A newly discovered peptide drug that disrupts signaling through a critical immune pathway could offer a new treatment for inflammatory diseases. Sangdun Choi from Ajou University in Suwon, South Korea, and colleagues designed the drug to look similar to—and thus act as kind of decoy for—a protein that regulates signaling through Toll-like receptors (TLRs), proteins found on immune cells that initiate responses to pathogens and also play a role in autoimmunity. In mouse and human cells, the drug inhibited multiple TLR signaling pathways, including a pathway that normally activates a multiprotein complex implicated in a variety of inflammatory diseases. In mouse models of rheumatoid arthritis and sepsis, the drug limited the release of proinflammatory molecules in the blood and reduced disease symptoms.

The accumulation of protein-bound uremic toxins (PBUT) is associated with increased cardiovascular outcomes in patients on dialysis. However, the efficacy of PBUT removal for a medium-cutoff (MCO) membrane has not been clarified. This study was designed to assess the efficacy of PBUT clearance according to dialysis modalities. In this prospective and cross-over study, we enrolled 22 patients who received maintenance hemodiafiltration (HDF) thrice weekly from three dialysis centers. The dialysis removal of uremic toxins, including urea, beta 2-microglobulin (B2MG), lambda free light chain (λ-FLC), indoxyl sulfate (IS), and p-cresyl sulfate (pCS), was measured in the 22 patients on high-flux HD (HF-HD), post-dilution online HDF (post-OL-HDF), and MCO-HD over 3 weeks. The average convection volume in post-OL-HDF was 21.4 ± 1.8 L per session. The reduction rate (RR) of B2MG was higher in post-OL-HDF than in MCO-HD and HF-HD. The RR of λ-FLC was the highest in MCO-HD, followed by post-OL-HDF and HF-HD. The dialysate albumin was highest in MCO-HD, followed by post-OL-HDF and HF-HD. Post-dialysis plasma levels of IS and pCS were not statistically different across dialysis modalities. The total solute removal and dialytic clearance of IS and pCS were not significantly different. The clearance of IS and pCS did not differ between the HF-HD, post-OL-HDF, and MCO-HD groups.

Background: Neprilysin inhibition has demonstrated impressive benefits in heart failure treatment, and is the current focus of interest in cardiovascular (CV) and kidney diseases. However, the role of circulating neprilysin as a biomarker for CV events is unclear in hemodialysis (HD) patients.Methods: A total of 439 HD patients from the K-cohort were enrolled from June 2016 to April 2019. The plasma neprilysin level and echocardiographic findings at baseline were examined. The patients were prospectively followed up to assess the primary endpoint (composite of CV events and cardiac events).Results: Plasma neprilysin level was positively correlated with left ventricular (LV) mass index, LV end-systolic volume, and LV end-diastolic volume. Multivariate linear regression analysis revealed that neprilysin level was negatively correlated with LV ejection fraction (β = −2.14; p = 0.013). The cumulative event rate of the composite of CV events was significantly greater in neprilysin tertile 3 (p = 0.049). Neprilysin tertile 3 was also associated with an increased cumulative event rate of cardiac events (p = 0.016). In Cox regression analysis, neprilysin tertile 3 was associated with a 2.61-fold risk for the composite of CV events [95% confidence interval (CI), 1.37–4.97] and a 2.72-fold risk for cardiac events (95% CI, 1.33–5.56) after adjustment for multiple variables.Conclusions: Higher circulating neprilysin levels independently predicted the composite of CV events and cardiac events in HD patients. The results of this study suggest the importance of future studies on the effect of neprilysin inhibition in reducing CV events.

Portulaca oleracea L. is a traditional oriental medicine known for its pharmacological effects. The present study aimed to investigate the immunostimulatory effects of PPCE on cyclophosphamide-stimulated rat model and in isolated spleen cells. The result showed that PPCE exerted an immunostimulatory effect in vivo and in vitro. Specifically, PPCE significantly enhanced splenocyte proliferation and upregulated inflammatory cytokines (IL-2, IL-12, TNF-α, and IFN-γ) and NK cell activity in vitro. The immunostimulatory effect was further investigated through various immunological assays. Oral administration of PPCE increased the swimming time and number of immune cells in rats. Histological analysis revealed that PPCE administration exerted splenic recovery. Thus, P. oleracea L. based complex extracts may be used as an immunostimulatory agent in medicine or functional foods.

Substance P (SP), an injury-inducible messenger that mobilizes bone marrow stem cells and modulates the immune response, has been suggested as a novel target for therapeutic agents. We evaluated the role of SP as an immune cell modulator during the progression of renal ischemic/reperfusion injury (IRI). Unilateral IRI induced the transient expression of endogenous SP and the infiltration of CCR7+ M1 macrophages in injured kidneys. However, SP altered the intrarenal macrophage polarization from CCR7+ M1 macrophages to CD206+ M2 macrophages in injured kidneys. SP also modulated bone marrow-derived neutrophils and mesenchymal stromal cells after IRI. SP treatment for 4 weeks starting one week after unilateral IRI significantly preserved kidney size and length and normal tubular structures and alleviated necrotic tubules, inflammation, apoptosis, and tubulointerstitial fibrosis. The beneficial effects of SP were accompanied by attenuation of intrarenal recruitment of CD4, CD8, and CD20 cells and abnormal angiogenesis. The immunomodulatory effect of SP suggested that SP could be a promising therapeutic target for preventing the progression of acute kidney injury to chronic kidney disease.

Background: Soluble epoxide hydrolase (sEH) metabolizes anti-inflammatory epoxyeicosatrienoic acids (EETs) into their much less active dihydroxy derivatives dihydroxyeicosatrienoic acids. Thus, targeting sEH would be important for inflammation.Aims: To determine whether knockout or inhibition of sEH would attenuate the development of inflammatory bowel disease (IBD) in a mouse model of IBD in IL-10(-/-) mice.Methods: Either the small molecule sEH inhibitor trans/-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB) or sEH knockout mice were used in combination with IL-10(-/-) mice. t-AUCB was administered to mice in drinking fluid. Extensive histopathologic, immunochemical, and biochemical analyses were performed to evaluate effect of sEH inhibition or deficiency on chronic active inflammation and related mechanism in the bowel.Results: Compared to IL-10 (-/-) mice, sEH inhibition or sEH deficiency in IL-10(-/-) mice resulted in significantly lower incidence of active ulcer formation and transmural inflammation, along with a significant decrease in myeloperoxidase-labeled neutrophil infiltration in the inflamed bowel. The levels of IFN-γ, TNF-α, and MCP-1, as well VCAM-1 and NF-kB/IKK-α signals were significantly decreased as compared to control animals. Moreover, an eicosanoid profile analysis revealed a significant increase in the ratio of EETs/DHET and EpOME/DiOME, and a slightly down-regulation of inflammatory mediators LTB(4) and 5-HETE.Conclusion: These results indicate that sEH gene deficiency or inhibition reduces inflammatory activities in the IL-10 (-/-) mouse model of IBD, and that sEH inhibitor could be a highly potential in the treatment of IBD. [ABSTRACT FROM AUTHOR]

Objective: To establish the device and model of motorcyclist ejection injury.Methods: Based on our laboratory devices, a motorcyclist ejection injury simulation system was developed. A total of 18 pigs were approved by the local animal experimentation and ethics committee to serve as the motorcyclist substitutes. In this ejection motion, the animal rode freely at the motor driver seat and was straightly accelerated by means of our custom motorcyclist ejection injury simulation system. When it was speeded up to the preset velocity (v equal to 30, 40 or 50 km/h) at the preset position, the animal was ejected forward. Pathological and dynamic analyses were conducted, accompanied with the high-speed photograph, acceleration/velocity signal test, gross observation and light microscope examination as well as the abbreviated injury score-injury severity score (AIS-ISS) scale.Results: The high-speed photograph indicated that during the ejection procedure the motorcycle was first arrested and decelerated suddenly, and then the motorcycle driver was ejected forward, accompanied with the rotation motion in the air. Finally, the head, shoulder and thorax of the ejected animal impacted directly on the hard ground. Varying degrees of injury focusing on the liver, heart, lung and spleen were found. There existed a significant positive correlation between ISS and the ejection velocity of the motorcycle drivers (ISS equal to 16.7+/-2.9 for 30 km/h, 25.0+/-0.0 for 40 km/h and 37.3+/-1.0 for 50 km/h). The detailed injury characteristics were as follows: for the mildly injured animals, there were interlobar gaps or leaf gaps and lobar surface blood coagulation blocks in the liver, and mild lung hemorrhage; for the severely injured animals, there were liver comminuted laceration, moderate lung hemorrhage and heart injury. Animals suffering from the most severe injuries died half an hour later.Conclusion: The new injury model stated in this paper has a high stability and good repeatability, and is likely to be helpful to deeply investigate the injury mechanisms and protection countermeasures of motorcyclist ejection injury. [ABSTRACT FROM AUTHOR]