Optimal threshold of urinary albumin-to-creatinine ratio (UACR) for predicting long-term cardiovascular and noncardiovascular mortality.

PURPOSE: Traditional cutoff values of urinary albumin-to-creatinine ratio (UACR) for predicting mortality have recently been challenged. In this study, we investigated the optimal threshold of UACR for predicting long-term cardiovascular and non-cardiovascular mortality in the general population. METHODS: Data for 25,302 adults were extracted from the National Health and Nutrition Examination Survey (2005-2014). Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of UACR for cardiovascular and non-cardiovascular mortality. A Cox regression model was established to examine the association between UACR and cardiovascular and non-cardiovascular mortality. X-tile was used to estimate the optimal cutoff of UACR. RESULTS: The UACR had acceptable predictive value for both cardiovascular (AUC (95% CI) for 1-year, 3-year and 5-year mortality, respectively: 0.769 (0.711-0.828), 0.764 (0.722-0.805) and 0.763 (0.730-0.795)) and non-cardiovascular (AUC (95% CI) for 1-year, 3-year and 5-year mortality, respectively: 0.772 (0.681-0.764), 0.708 (0.686-0.731) and 0.708 (0.690-0.725)) mortality. The optimal cutoff values were 16 and 30 mg/g for predicting long-term cardiovascular and non-cardiovascular mortality, respectively. Both cutoffs of UACR had acceptable specificity (0.785-0.891) in predicting long-term mortality, while the new proposed cutoff (16 mg/g) had higher sensitivity. The adjusted hazard ratios of cardiovascular and non-cardiovascular mortality for the high-risk group were 2.50 (95% CI 1.96-3.18, P < 0.001) and 1.92 (95% CI 1.70-2.17, P < 0.001), respectively. CONCLUSIONS: Compared to the traditional cutoff value (30 mg/g), a UACR cutoff of 16 mg/g may be more sensitive for identifying patients at high risk for cardiovascular mortality in the general population.

Melatonin alleviates lipopolysaccharide-induced myocardial injury by inhibiting inflammation and pyroptosis in cardiomyocytes.

BACKGROUND: Melatonin (MT) has been shown to protect against various cardiovascular diseases. However, the effect of MT on lipopolysaccharide (LPS)-induced myocardial injury is poorly understood. This study aims to evaluate the effects of MT on LPS-induced myocardial injury in vitro. METHODS: H9C2 cells were divided into a control group, MT group, LPS group, and MT + LPS group. The control group was treated with sterile saline solution, the LPS group received 8 µg/mL LPS for 24 h, MT + LPS cells were pretreated with 200 µmol/L MT for 2 h then with 8 µg/mL LPS for 24 h, and the MT group received only 200 µmol/L MT for 2 h. The CCK-8 assay and lactate dehydrogenase (LDH) activity assay were used to analyze cell viability and LDH release, respectively. Intracellular reactive oxygen species (ROS) and the rate of pyroptosis were measured using the fluorescent probe dichloro-dihydro-fluorescein diacetate (DCFH-DA) and propidium iodide (PI) staining, respectively. The cell supernatants were used to measure the levels of inflammatory cytokines, including IL-6, TNF-α, and IL-1ß by enzyme-linked immunosorbent assay (ELISA). The protein levels of iNOS, COX-2, NF-κB, p-NF-κB, NLRP3, caspase-1, and GSDMD were detected by western blot. RESULTS: MT pretreatment significantly improved LPS-induced myocardial injury by inhibiting inflammation and pyroptosis in H9C2 cells. Moreover, MT inhibited the activation of the NF-κB pathway, and reduced the expression of inflammation-related proteins (iNOS and COX-2), and pyroptosis-related proteins (NLRP3, caspase-1, and GSDMD). CONCLUSIONS: Our data suggests that MT can alleviate LPS-induced myocardial injury, providing novel insights into the treatment of sepsis-induced myocardial dysfunction.

RepSox, a small molecule inhibitor of the TGFß receptor, induces brown adipogenesis and browning of white adipocytes.

Unlike white adipose tissue (WAT), brown adipose tissue (BAT) is mainly responsible for energy expenditure via thermogenesis by uncoupling the respiratory chain. Promoting the differentiation of brown fat precursor cells and the browning of white fat have become a research hotspot for the treatment of obesity and associated metabolic diseases. Several secreted factors and a number of small molecules have been found to promote brown adipogenesis. Here we report that a single small-molecule compound, RepSox, is sufficient to induce adipogenesis from mouse embryonic fibroblasts (MEFs) in fibroblast culture medium. RepSox is an inhibitor of the transforming growth factor-beta receptor I (TGF-ß-RI), other inhibitors of TGF-ß pathway such as SB431542, LY2157299, A83-01, and Tranilast are also effective in inducing adipogenesis from MEFs. These adipocytes express brown adipocyte-specific transcription factors and thermogenesis genes, and contain a large number of mitochondria and have a high level of mitochondrial respiratory activity. More interestingly, RepSox has also been found to promote the differentiation of the brown fat precursor cells and induce browning of the white fat precursor cells. These findings suggest that inhibitors of TGF-ß signaling pathway might be developed as new therapeutics for obesity and type 2 diabetes.

New chalcone and pterocarpoid derivatives from the roots of Flemingia philippinensis with antiproliferative activity and apoptosis-inducing property.

Investigation of the roots of Flemingia philippinensis resulted in the isolation of two new chalcones, flemiphilippinones B (1) and C (2), and one new pterocarpoid, demethylwedelolactone-11-methyl ether (3), together with 12 known compounds (4-15). The antiproliferative activity against PC-3 cells was evaluated and most compounds showed cytotoxicity, among which, compound 2 exhibited GI50 value of 14.12µM. The antiproliferative activity of 2 against Bel-7402 and CaEs-17 cells was also measured, with GI50 values of 1.91 and 2.58µM, respectively. Intensive mechanism study showed that 2 caused cell-cycle arrest at S/G2 phase and induced apoptosis in Bel-7402 cells through mitochondria-related pathway.

Treatment of huge hypertensive putaminal hemorrhage by surgery and cerebrospinal fluid drainage.

OBJECTIVE: There is limited information available regarding the treatment of huge hypertensive putaminal hemorrhage (HPH). This study aimed to evaluate our experience of 33 patients with huge HPH who were treated by open surgery (decompressive craniectomy and hematoma evacuation) and external cerebrospinal fluid (CSF) drainage. METHODS: We reviewed the records of 33 consecutive patients admitted to our hospital with huge HPH (≥ 60 cm(3)). All patients were treated by decompressive craniectomy, hematoma evacuation, and CSF drainage. Data collected included age, gender, blood pressure at admission, Glasgow Coma Scale (GCS) score, intracranial hemorrhage (ICH) location, ICH volume, degree of midline shift, presence/absence of basal cistern obliteration at admission and before surgery, and presence/absence of intraventricular hemorrhage (IVH). Outcome was assessed by the Glasgow Outcome Scale score at 30 days after surgery. RESULTS: The median GCS score was 5.0 at admission, and improved to 8.0 at 1 week after surgery. The median ICH volume was 95 cm(3) before surgery and 4 cm(3) after surgery. IVH was observed in 93.9% of patients. The overall survival rate to discharge was 75.6% (25/33), including 15.1% (4/33) with good function, 36.4% (12/33) with disability, and 24.3% (8/33) in a vegetative state. The mortality rate was 24.3% (8/33). Patients with right-sided ICH had better outcomes than those with left-sided ICH. No patients with GCS score ≤ 6 and ICH volume ≥ 90cm(3) at admission achieved good postoperative function. Operative time was significantly shorter with hematoma evacuation via the transcortical approach than via the transsylvian approach (3.41 ± 0.75 h vs. 4.14 ± 0.59 h, P<0.001). There were no significant differences in the rates of mortality or survival with good function between the two groups. CONCLUSIONS: Treatment of huge HPH by decompressive craniectomy, hematoma evacuation, and CSF drainage is life-saving. Patients with GCS score 7-8, ICH volume 60-90 cm(3), and right-sided ICH may achieve good recovery. The transcortical approach appears to be more effective than the transsylvian approach for rapid decompression of the edematous brain.

An efficient and selective solvent-free oxidation of alcohols by shaking with chromium trioxide supported on aluminium silicate.

A selective oxidation of primary alcohols to the corresponding aldehydes by shaking with chromium trioxide supported on aluminium silicate at room temperature under solvent free conditions is reported. This new procedure can also oxidise secondary alcohols.

[Study on beta-cyclodexdrin sensitizing catalytic kinetic spectrophotometric determination of Mn(II)].

A new catalytic spectrophotometric method for the determination of trace amount of Mn(II) has been developed. The method is based on the oxidation of alizarin green(AG) by potassium periodate in the presence of beta-cylodexdrin(beta-CD) as a sensitizer and nitrilotriacetic acid as an activator. The linear range of the method was 0-2.4 ng x mL(-1) for Mn(II), the determination limit was 0.097 ng x mL(-1), the relative standard deviation was 0.45% (n = 12) for 1.6 ng x mL(-1) of Mn(II), and the sensitivity was increased by a factor of 2.5 compared to that in the absence of the beta-CD. The method was used for the determination of Mn(II) in cereal samples and wine samples with satisfactory results. The mechanism of this reaction system was also presented.

[The study of amphoteric surfacant sensitizing catalytic spectrophotometric determination of Mn (II)].

A new catalytic spectrophotometric method for the determination of trace amount of Mn(II) has been developed. The method is based on the oxidation of thionine by potassium periodate in the presence of nitrilo triaceticacid as an activator and amphoteric surfactant dodecyl dimethylamino acetic acid(DDMAA) as enhancing agent. Dodecye dimethylamino acetic acid (DDMAA) micelles accelerate the reaction and hence increase the sensitivity and selectivity of the determination of Mn(II) compared to reactions taking place in an aqueous medium. The mechanism of related reaction has been discussed. The sensitivity is increased by 7.1 times in the presence of the DDMAA than that in the absence of the DDMAA. The linear ranges of determination are 0-60 ng.(25 mL)-1, the relative standard deviation is 2% (n = 11). The method can be used for the determination of Mn(II) in aluminium alloy and water samples.