Arachidonic acid metabolism as a therapeutic target in AKI-to-CKD transition.

Arachidonic acid (AA) is a main component of cell membrane lipids. AA is mainly metabolized by three enzymes: cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP450). Esterified AA is hydrolysed by phospholipase A2 into a free form that is further metabolized by COX, LOX and CYP450 to a wide range of bioactive mediators, including prostaglandins, lipoxins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acids and epoxyeicosatrienoic acids. Increased mitochondrial oxidative stress is considered to be a central mechanism in the pathophysiology of the kidney. Along with increased oxidative stress, apoptosis, inflammation and tissue fibrosis drive the progressive loss of kidney function, affecting the glomerular filtration barrier and the tubulointerstitium. Recent studies have shown that AA and its active derivative eicosanoids play important roles in the regulation of physiological kidney function and the pathogenesis of kidney disease. These factors are potentially novel biomarkers, especially in the context of their involvement in inflammatory processes and oxidative stress. In this review, we introduce the three main metabolic pathways of AA and discuss the molecular mechanisms by which these pathways affect the progression of acute kidney injury (AKI), diabetic nephropathy (DN) and renal cell carcinoma (RCC). This review may provide new therapeutic targets for the identification of AKI to CKD continuum.

Host/microbiota interactions-derived tryptophan metabolites modulate oxidative stress and inflammation via aryl hydrocarbon receptor signaling.

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that induces the expression of a broad range of downstream genes such as cytochromes P450 enzymes and cyclooxygenase-2. Recent research focuses are shifting from AhR activation induced by xenobiotics to its response patterns to physiological ligands that expand our understanding of how endogenous metabolites as ligands to modulate AhR signaling pathway under homeostasis and pathological conditions. With increasing interest in AhR and its endogenous ligands, it would seem advisable to summarize a variety of endogenous ligands especially host/gut microbiota-derived tryptophan metabolites. Mounting evidence has indicated that AhR play a critical role in the regulation of redox homeostasis and immune responses. In this review, we outline the canonical and non-canonical AhR signalling pathway that is mediated by host/gut microbiota-derived tryptophan metabolites. Through several typical endogenous AhR ligands, we investigated the molecular mechanisms of AhR-induced oxidative stress and inflammation in the pathological milieu, including diabetes, diabetic kidney disease and end-stage renal disease. Finally, we summarize and emphasize the limitations and breakthrough of endogenous AhR ligands from host/microbial tryptophan catabolites. This review might provide novel diagnostic and prognostic approach for refractory human diseases and establish new therapeutic strategies for AhR activation.

The development and evaluation of a sub-health self-rating scale for university students in China.

BACKGROUND: Sub-health status is defined as declines in vitality, physiological function and capacity for adaptation, but without the presence of clinical or sub-clinical disease. We have developed and evaluated a comprehensive questionnaire, the Sub-Health Self-Rating Scale (SSS), to assess sub-health status in university students. METHOD: The items for the draft questionnaire were discussed in focus groups. The WHOQOL-BREF was selected as the validity reference. From a professional perspective and large sample evaluation, the scale ultimately consisted of 58 items. The reliability and validity of the SSS was examined in undergraduate students and 1000 questionnaires were randomly selected from the samples for expert evaluation. RESULTS: Cronbach's α of the total scale was 0.942. The dimensions of physiological, psychological and social had high reliability: 0.915, 0.856 and 0.850, respectively. Based on scree plot and related theories, there were 10 factors to be extracted. The correlation coefficient between the total scale and sub-scale was high. The dimensions of physiological, psychological and social had high correlations with the total scale: 0.929, 0.803 and 0.774, respectively. The sub-health cut-off point of the total scale was 72; for the physiological field, it was 72; for the psychological field, it was 60; and the social field, it was 56. The fit between the expert evaluation method and the scale method was 0.758. The lower the score, the worse the health condition. CONCLUSION: We established and evaluated a valid instrument (SSS) that encompasses physiological, psychological and social factors to investigate sub-health status. It is short and easy to complete, and therefore suitable for use with undergraduate students.

Prevalence, awareness, treatment, and control of hypertension among very elderly Chinese: results of a community-based study.

The epidemiologic distribution of hypertension among very elderly Chinese is still not clear. This study aimed to investigate the prevalence, awareness, treatment, and control rate of hypertension among very elderly in Chengdu. From May 2013 to May 2015, a total of 1056 participants from 20 residential communities were sampled. Standard face-to-face interviews, physical examinations, and biochemical analysis were undertaken. Participants had a mean age of 83.6 ± 3.4 years (range: 80-100), and 49.8% were men. Mean systolic blood pressure (BP) and diastolic BP were 146.4 ± 20.6 and 74.1 ± 11.9 mm Hg, respectively, and both of the highest BP levels were among participants aged 80-84 years. Mean pulse pressure was 72.5 ± 17.1 mm Hg, and the highest pulse pressure level was among participants aged 90 years and older. The overall estimated hypertension prevalence was 75.3% (95% confidence interval: 72.6%-77.9%), and among overall participants, 51.9% were aware of their hypertensive condition and 45.5% were treated. However, only 18.1% of hypertensive participants were controlled (BP < 140/90 mm Hg). Among very elderly Chinese in Chengdu, the prevalence of hypertension is predominantly high, whereas awareness, treatment, and control rates are considerably low. Effective primary and secondary prevention strategies are needed.

Hyperuricemia is associated with cardiovascular diseases clustering among very elderly women - a community based study in Chengdu, China.

Cardiovascular epidemiological features among very elderly Chinese are still uncertain. This study aimed to describe the distribution of cardiovascular diseases and sex difference, and investigate potential risk factors for diseases clustering among very elderly Chinese. From May 2013 to May 2015, a total of 1056 very elderly were sampled in this cross-sectional study. Demographic characteristics collection, physical examination and biochemical analysis were performed. Totally, 1038 participants (men: 49.8%) with a median age of 83.0 years (age range: 80.0-100.0 years) were included. In this very elderly group, the prevalences of hypertension, diabetes mellitus, renal dysfunction, hyperuricemia, obesity, visceral obesity, and hypercholesterolaemia were 76.9%, 20.0%, 23.3%, 33.0%, 9.4%, 54.5% and 35.8%, respectively. About 17.5% of very elderly (men vs. women: 15.1% vs 19.8%, p = 0.007) have ≥3 cardiovascular diseases clustering. Logistic analysis found that hyperuricemia (odds ratio 3.850, 95%CI 2.189-6.770) was associated with of cardiovascular diseases clustering among very elderly women. Prevalences of prehypertension, hyperuricemia, visceral obesity and dyslipidaemia are apparent in very elderly women, while diabetes mellitus, renal dysfunction are common in very elderly men. Women are more likely to have ≥3 cardiovascular diseases. Hyperuricemia is associated with cardiovascular diseases clustering among very elderly women.

[Predictability of the corneal flap creation with the femtosecond laser in LASIK].

OBJECTIVE: To observe the predictability of corneal flap creation with the FEMTO LDV femtosecond laser and analyze preliminarily the factors correlating to the thickness and diameter of the flap . METHODS: It was a study of serial cases. 260 eyes of 130 consecutive patients were treated with the FEMTO LDV. The eyes were assigned to two groups according to intended flap thickness, 110 µm (208 eyes) and 90 µm (52 eyes). Intended flap diameter varied from 8.5 to 9.5 mm. Difference analysis of flap diameter and intended diameter as well as flap thickness and intended thickness were made. The data was analyzed with SPSS to sum up a multiple stepwise regression formula that could express their quantitative relationship. RESULTS: The 90 µm flap group had a average flap thickness of (95.12 ± 7.65) µm, while for the 110 µm group the average flap thickness was (104.81 ± 3.09) µm. The difference between right and left eyes was not statistically significant (t(110 µm) = -1.223, t(90 µm) = -1.343, P > 0.05). Corneal flap thickness was inversely correlated with flap diameter (r(110 µm) = -0.143, r(90 µm) = -0.315, P < 0.05), but was not related to preoperative patient age, corneal thickness, keratometric value K or intraocular pressure (r(110 µm) = -0.160, 0.054, -0.011, -0.363; r(90 µm) = 0.024, 0.074, -0.212, -0.434, all P > 0.05). Corneal flap diameter was positively correlated with preoperative corneal keratometric value K and thickness (P < 0.001, P < 0.05). Multiple stepwise regression analysis showed flap diameter was an influencing factor for flap thickness. Preoperative corneal keratometric value K and thickness were influencing factors for flap diameter. CONCLUSIONS: The LASIK flap creation with the FEMTO LDV laser has relatively good predictability. Flap diameter is an influencing factor for flap thickness.

(E)-2-[2-(3-Fluoro-phen-yl)ethen-yl]quinolin-8-yl acetate.

In the crystal of the title compound, C(19)H(14)FNO(2), the mol-ecules are linked by C-H⋯O hydrogen bonds in translational chains along the b axis. The dihedral angles formed by the quinoline system with the fluoro-benzene ring and the acet-oxy group are 8.15 (3) and 77.42 (4)°, respectively.

[Therapeutic effect of total glucosides of paeony on lupus nephritis in MRL/lpr mice].

OBJECTIVE: To observe the therapeutic effect of total glucosides of paeony (TGP) on lupus nephritis (LN) in MRL/lpr mice. METHODS: MRL/lpr mice with lupus nephritis were randomized into model group and TGP group. The urinary protein content was detected using Coomassie brilliant blue, and the serum levels of IgG anti-double-stranded DNA (dsDNA) antibodies and antinuclear antibodies (ANA) were measured by enzyme-linked immunosorbent assay (ELISA). The changes in the renal pathology were examined microscopically, and the spleen and thymus were weighed to calculate the spleen and thymus indexes. RESULTS: At 15 and 30 days after TGP administration, the urinary protein content in the TGP group was significantly lower than that in the model group (P<0.05). TGP treatment significantly lowered the serum levels of anti-dsDNA antibodies and ANA and the weight and index of spleen (P<0.05), resulting also in lessened renal pathology at 30 days after the administration. Compared to those before TGP treatment, the urinary protein content and the levels of anti-dsDNA antibodies and ANA decreased significantly at 15 and 30 days after TGP administration (P<0.05), while in the model group, the level of anti-dsDNA increased significantly without obvious changes in urinary protein content or ANA. At 30 days after TGP administration, the urinary protein content was significantly lowered in the TGP group as compared to that at 15 days (P<0.05), but the antibodies showed no significant changes. CONCLUSION: TGP can reduce urinary protein content and serum levels of anti-dsDNA antibodies and ANA, and lessen renal pathology in MRL/lpr mice with lupus nephritis, suggesting its therapeutic effect on lupus nephritis.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decrease the incidence of atrial fibrillation: a meta-analysis.

BACKGROUND: There is not a general agreement regarding antiarrhythmic effects on atrial fibrillation (AF) of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). This study was to assess whether ACEIs and ARBs could decrease the incidence of AF. MATERIALS AND METHODS: Medline, Embase and Cochrane Library databases were searched for trials reported from 1950 to May 2009. Search terms included 'randomized controlled trial (RCT), controlled clinical trials, random allocation' and medical subject headings that included all spellings of ACEIs and ARBs agents, 'atrial fibrillation' and 'atrial flutter'. Randomized, controlled human trials of ACEIs or ARBs reporting AF were included. Data were extracted independently by two reviewers using a predefined data extraction sheet, including study quality indicators. Meta-analysis and subgroup analyses were carried out with a random effects model. RESULTS: Twenty-one trials including 91,381 patients and 5730 AF events were identified. Overall, ACEIs/ARBs reduced the relative risk (c) of AF by 25%. In primary and secondary prevention, ACEIs/ARBs decreased the incidence of AF by 24% and 27%, respectively. Patients with hypertension (RR: 0·71, 95%CI: 0·54-0·92), patients with chronic heart failure (RR: 0·58, 95%CI: 0·39-0·87) and those with AF (RR: 0·71, 95%CI: 0·52-0·96) benefited from ACEIs/ARBs treatment. CONCLUSIONS: ACEIs/ARBs are effective for primary prevention and secondary prevention of AF. They decrease the incidence of AF especially in patients with hypertension, patients with chronic heart failure and those with AF.

Contrast sensitivity and higher-order aberrations in patients with astigmatism.

BACKGROUND: Astigmatism is one of the most significant obstacles for achieving satisfactory visual function. This study was to evaluate the influence of astigmatism on contrast sensitivity (CS) and higher-order aberrations. METHODS: CS, accommodation response and wavefront aberration were measured in 113 patients with astigmatism, aged 18 - 36 years. Both single and binocular visual performance were examined under four lighting conditions: photopia, photopia with glare, scotopia and scotopia with glare respectively. Accommodation response was classified as normal, abnormal and low. The contribution of the power and axis of astigmatism to CS, accommodation response and wavefront aberration was analyzed. RESULTS: As the dioptric power of astigmatism increased, the loss of CS spatial frequency changed from high to intermediate, and then to low frequency. CS scores varied at different illuminance levels, descending in the following sequence: photopia, photopia with glare, scotopia, and scotopia with glare. However, the normal accommodation group showed better CS values under photopia with glare than without glare. The range of influenced direction of sine-wave gratings remained mostly at the meridian line of high dioptric power, which would be expanded when optical accommadation attenuated. The patients with symmetrical astigmatism got higher CS scores with binoculus vision than with dominant eye vision, while the patients with asymmetrical astigmatism did this only at scotopia with glare. Among higher-order aberrations, coma aberration, secondary coma aberration and the total higher order aberration were influenced by astigmatism, all of which rising with the power of astigmatism increased. CONCLUSIONS: Reducing astigmatism might improve the performance of visual function. Not only the power of astigmatism should be cut down, but also the binocular axes should be made symmetrically.

[Correlation between B-natriuretic peptide and hemodynamics in patients with decompensated heart failure and clinical significance].

OBJECTIVE: To determine the correlation between the serum level of B-natriuretic peptide (BNP) and hemodynamic variables and to evaluate the diagnostic value of BNP in patients with decompensated heart failure (HF). METHODS: BNP levels (TRIAGE BIOSITE Diagnostics, San Diego, USA) were obtained by a rapid immunofluorescence assay in 117 patients with dyspnea including cardiogenic group (75 patients) and lung disease (42 patients). Hemodynamic parameters of 53 patients [male 28, female 25, mean age (71.6 +/- 9.8) years] with HF were determined and left ventricular end-diastolic diameter (LVEDD) of all patients were measured by echocardiogram. RESULTS: Pulmonary capillary wedge pressure (PCWP, mm Hg), mean pulmonary arterial pressure (MPAP, mm Hg), right atrial pressure (RAP, mm Hg) and BNP (ng/L) levels according to New York Heart Association (NYHA) class were: 16.10 +/- 3.50, 22.50 +/- 4.68, 3.11 +/- 1.90, 271.25 +/- 159.29 in NYHA class II, respectively; 21.50 +/- 4.42, 28.60 +/- 9.35, 8.95 +/- 3.86, 619.58 +/- 237.48 in NYHA class III; 29.28 +/- 8.61, 36.50 +/- 12.32, 15.27 +/- 4.96, 1519.28 +/- 618.62 in NYHA class IV (P < 0.01-0.05), respectively. PCWP, MPAP, RAP and plasma BNP levels were directly proportional to cardiac function. The plasma BNP levels had also significant positive correlations with PCWP, MPAP, RAP, (r = 0.59, 0.50, 0.32, P < 0.05-0.01). BNP level [(918.48 +/- 453.25) ng/L] of the group with LVEDD (n = 24) > or = 60 mm was much higher than that of the group with LVEDD (n = 29) < 60 mm [(298.58 +/- 167.51) ng/L]. However, the latter was significantly higher than that in pulmonary dyspnea group with a normal left and right ventricular end-diastolic diameter [(35.4 +/- 26.4) ng/L, P < 0.01]. There was a great difference of BNP between cardiogenic dyspnea group [(761.30 +/- 480.47) ng/L]and lung dyspnea group [(35.4 +/- 26.4) ng/L], P < 0.01. CONCLUSIONS: The plasma BNP levels had significant positive correlations with PCWP, MPAP, RAP. BNP is a cardiac neurohormone secreted from cardiac ventricles as a response to ventricular volume expansion and pressure overload. Rapid testing BNP should be of help to differentiate pulmonary dyspnea from cardiac etiologies.