Superconductivity of cubic MB6 (M = Na, K, Rb, Cs).

Previous studies have shown that NaB6, KB6, and RbB6 adopting Pm3̄m are superconductors with a relatively high Tc under ambient conditions. In this paper, we conducted systematic structural and related properties research on CsB6 through a genetic evolution algorithm and total energy calculations based on density functional theory between 0 and 20 GPa. Our results reveal a cubic Pm3̄m CsB6, which is dynamically stable under the pressures we studied. We systematically calculated the formation enthalpies, electronic properties, and superconducting properties of Pm3̄m MB6 (M = Na, K, Rb, Cs). They all exhibit metallic features, and boron has high contributions to band structures, density of states, and electron-phonon coupling (EPC). The calculated results about the Helmholtz free energy difference of Pm3̄m CsB6 at 0, 10, and 20 GPa indicate that it is stable upon chemical decomposition (decomposition to simple substances Cs and B) from 0 to 400 K. The phonon density of states indicates that boron atoms occupy the high frequency area. The EPC results show that Pm3̄m CsB6 is a superconductor with Tc = 11.7 K at 0 GPa, close to NaB6 (13.1 K), KB6 (11.7 K), and RbB6 (11.3 K) at 0 GPa in our work, which indicates that boron atoms play an essential role in superconductivity: vibrations of B6 regular octagons lead to the high Tc of Pm3̄m MB6. Our work about Pm3̄m hexaborides provides a supplementary study on the borides of the group IA elements (without Fr and Li) and has an important guiding significance for the experimental synthesis of CsB6.

The Association Between Habitual Tea Consumption and Frailty Transition in Community-Dwelling Older Adults: A Prospective Cohort Study.

OBJECTIVES: To investigate the association between habitual tea consumption and transitions between frailty states among older adults in China. DESIGN: A prospective cohort study based on the Chinese Longitudinal Healthy Longevity Study. SETTING AND PARTICIPANTS: A total of 23,720 older adults aged ≥65 years with complete data regarding frailty status and tea consumption were recruited. METHODS: The frequency and consistency of tea consumption were introduced to evaluate levels of tea consumption. The frailty index was used to define frailty status (frail and nonfrail). Frailty transition was classified into remaining nonfrail, improvement, worsening, and remaining frail groups. Logistic regression models were applied. RESULTS: The overall frailty prevalence at baseline was 19.1%, being lower among consistent daily tea drinkers (12.5%) and higher among non-tea drinkers (21.9%). Logistic regression analyses showed that the risk of frailty was significantly reduced among consistent daily tea drinkers after adjusting for all confounders [odds ratio (OR), 0.81; 95% CI, 0.67-0.98]. During the 3-year follow-up, improvement in frailty status was more common among consistent daily tea drinkers (50.9%) than non-tea drinkers (40.9%), and this trend was opposite in participants with worsened frailty status (consistent daily tea drinkers: 12.2%) vs non-tea drinkers: 19.2%). Further analysis showed that consistent daily tea drinkers were significantly associated with improvement in frailty status (OR, 3.24; 95% CI, 1.02-10.31) and remaining in a nonfrail state (OR, 1.35; 95% CI, 1.00-1.83). In addition, daily tea consumption was observed to be positively associated with remaining in a nonfrail state and inversely associated with worsened frailty status in men, but not in women. CONCLUSIONS AND IMPLICATIONS: Older people consuming tea daily tend to have an improved frailty status in the future. Men with daily tea consumption were less likely to have a worsened frailty status. Advocating for the traditional lifestyle of drinking tea could be a promising way to advance healthy aging for older adults.

The role of MOTS-c-mediated antioxidant defense in aerobic exercise alleviating diabetic myocardial injury.

Myocardial remodeling and dysfunction are commonly observed in type 2 diabetes mellitus (T2DM). Aerobic exercise can partly alleviate diabetes-induced myocardial dysfunction through its antioxidant actions. MOTS-c is a potential exercise mimic. This study aimed to investigate the effects of MOTS-c on improving diabetic heart function and its mechanism and to identify whether MOTS-c improved antioxidant defenses due to aerobic exercise. Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection. Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks. Myocardial ultrastructure was assessed using transmission electron microscopy (TEM), myocardial lipid peroxidation levels (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) levels were assessed using colorimetric methods, and molecular analyses including MOTS-c, Kelch-like ECH-associated protein 1 (Keap1), Nuclear factor E2-related factor 2 (Nrf2), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)and phospho-AMPK (p-AMPK) were examined using Western blot. The results showed that MOTS-c, with or without exercise, reduced myocardial ultrastructural damage and improved glucolipid metabolism and cardiac function in T2DM. Furthermore, MOTS-c increased antioxidant markers such as SOD, CAT, and the protein expression of myocardial MOTS-c, Keap1, Nrf2, and p-AMPK. MOTS-c with exercise treatment reduced myocardial MDA and increased p-AMPK significantly comparing to only exercise or MOTS-c alone. Our findings suggest that MOTS-c may be a helpful supplement for overcoming exercise insufficiency and improving myocardial structure and function in diabetes.

[Effect of guarana on lipid metabolism in obese rats: a study based on lipidomics].

This study investigated the effect of guarana on plasma lipid metabolites in obese rats and analyzed its mechanism in the treatment of dyslipidemia in obesity. High-fat diet was used to establish obese rat models, and the therapeutic effect of guarana on obese rats was evaluated by measuring body weight, white fat, liver weight, and lipid content, as well as observing liver histomorphology. Lipid metabolites in plasma of rats in each group were detected by UHPLC-Q-TOF-MS lipidomics. The protein expressions of fatty acid synthase, acetyl-CoA carboxylase 1, triglyceride synthesis enzyme, carnitine palmitoyltransferase Ⅰ, and acetyl-coenzyme A acyltransferase 2 in rat liver were detected using Western blot. The results revealed that guarana significantly reduced body weight, white fat, and liver weight of obese rats due to high-fat diet, and alleviated dyslipidemia and liver steatosis. Lipidomics showed that some triglycerides and phospholipids were significantly elevated in the high-fat model group, and part of them was reduced after guarana treatment. Western blot found that guarana inhibited the expression of hepatic fatty acid and triglyceride synthesis-related proteins and increased the expression of fatty acid ß-oxidation-related proteins. Abnormalities in triglyceride and phospholipid metabolism are the main characteristics of plasma lipid metabolism in obese rats induced by high-fat diet. Guarana may regulate partial triglyceride and phospholipid metabolism by inhibiting hepatic fatty acid and triglyceride synthesis and increasing fatty acid ß-oxidation, thereby improving rat obesity and dyslipidemia.

Correlation between Polyphenol Contents and Antioxidant Activities in Different Echinacea Purpurea Varieties.

OBJECTIVE: Polyphenols are complex compounds containing multiple phenolic hydroxyl groups. They are widely distributed in plants and have antioxidant activities. Whether the antioxidant activities of the cultivated varieties of Echinacea are similar to or better than those of the wild ones and the relationship between the accumulation of polyphenols and their antioxidant activities are still not clear. METHODS: Folin-Ciocalteu method, high performance liquid chromatography (HPLC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, ferric ion reducing antioxidant power (FRAP) assay, 2,2'-azino-bis(3-ethylbenzothiazoline-6)-sulfonic acid (ABTS) radical scavenging assay, and Fe2+ chelating ability assay were used, respectively, to detect the total polyphenols and 5 kinds of caffeic acid derivatives (chicoric acid, caffeic acid, caftaric acid, chlorogenic acid, and 1,5-dicaffeoylquinic acid) in the roots, stems, leaves, and flowers, and the antioxidant activities of 3 varieties of Echinacea: E. purpurea L., cultivar E. purpurea 'Aloha', and E. purpurea 'White Swan'. RESULTS: E. purpurea L. had the highest contents of total polyphenols, 5 caffeic acid derivatives and antioxidant activities, followed by E. purpurea 'White Swan' and E. purpurea 'Aloha', respectively. E. purpurea 'White Swan' had the strongest ability to remove the DPPH, ABTS•+ and free radicals, and to chelate Fe2+; E. purpurea L. had the strongest ability to reduce FRAP. The correlation analyses revealed that the contents of total polyphenols and caffeic acid derivatives of E. purpurea L. and E. purpurea 'White Swan' were correlated with their antioxidant activities. CONCLUSION: E. purpurea L. was the most appropriate material for the development of medicinal plants. E. purpurea 'White Swan' could be used as a substitute for E. purpurea L. in terms of its antioxidant activity.

Effects of Juhongtanke oral solution on alleviating the symptoms of community-acquired pneumonia: A multicenter, prospective, randomized controlled trial.

Introduction: The timely alleviation of symptoms is essential for managing community-acquired pneumonia (CAP). Juhongtanke oral solution is a traditional marketed Chinese patent medicine believed to ease CAP symptoms. The currently available evidence is based on a few retrospective studies of patients with various types of pneumonia, whereas robust randomized controlled trials (RCTs) that support this notion are lacking. Material and methods: In this multi-center, prospective RCT, patients were randomly allocated to receive routine treatment alone or a combination of Juhongtanke oral solution (20 mL q8h) for 5 days and maintained for an additional 3-day safety observation period. The primary outcome was Breathlessness, Cough, and Sputum Scale (BCSS) score evaluated on day 5. Secondary outcomes included the evaluation of cough and dyspnea items in the Visual Analogue Scale (VAS) from days 1-5, remission rate in BCSS and VAS during the treatment course, and the length of hospitalization and in-hospital mortality. Results: Of 272 patients assessed for eligibility, 240 were enrolled in the study (n =120 per group). The mean difference in BCSS evaluated on day 5 was a median 1 point [95%CI (1.00, 2.00)], significantly lower in the treatment group compared with the control group (p < 0.001). Similar results were observed in VAS on day 5, with statistics of a median 2 points [95%CI (1.40, 2.50)] in the cough item and a median 1 point [95%CI (0.50, 2.00)] in the dyspnea item, significantly lower in the treatment group compared with the control group (both p < 0.001). The treatment group had a favorable outcome in BCSS and VAS remission rate assessments compared with the control group, with 99.50% vs. 89.17% in BCSS (p = 0.01), 98.33% vs. 75% in the cough item of VAS (p < 0.001), and 88.33% vs. 62.50% in the dyspnea item of VAS (p < 0.001), respectively. No notable adverse effects were observed during the study. No differences were observed in the length of hospitalization between groups (with a median of 7 days for both groups, p = 0.871). Conclusion: Juhongtanke oral solution may be considered to alleviate the clinical symptoms of CAP.

Rehabilitation programme including EMG-biofeedback- assisted pelvic floor muscle training for rectus diastasis after childbirth: a randomised controlled trial.

OBJECTIVE: To evaluate the effect of a comprehensive rehabilitation programme on closure of the rectus diastasis (RD) and quality of life in women after delivery. DESIGN: A randomised controlled trial with blinded assessment. SETTING: A tertiary hospital and participants' homes in Foshan, China. SUBJECTS: Sixty-six women with RD 2-6 months after delivery were recruited into this study (study group n = 33, control group n = 33). The mean age of participants was 29.9 [standard deviation (SD) 4.3] years. INTERVENTIONS: Each participant performed abdominal exercises. Patients in the study group received electromyographic-biofeedback-assisted pelvic floor muscle training (BAPFMT) in combination with neuromuscular electrical stimulation (NMES) of the rectus abdominis, and patients in the control group underwent NMES of the rectus abdominis alone. MAIN OUTCOMES: The main study outcomes were inter-recti distance (IRD) and change in Short-Form Health Survey-36 (SF-36) scores 6 weeks after the intervention. RESULTS: A significant decrease in IRD was observed in the study group at 6 weeks [study group 1.6 (SD 0.3) cm vs control group 2.0 (SD 0.3); mean difference - 0.4, 95% confidence interval (CI) - 0.59 to - 0.26]. Similarly, the physical component summary, an integral component of SF-36, showed a significant improvement in the study group compared with the control group at 6 weeks [study group 45.5 (SD 1.2) vs control group 41.2 (SD 2.6); mean difference 4.3, 95% CI 3.72-4.50]. CONCLUSION: A postpartum programme including BAPFMT for women with RD is feasible and improves the physical domain of quality of life. CLINICAL TRIAL REGISTRATION: ClinicalTrials.fimmu, No: RCT 02561078. CONTRIBUTION OF THE PAPER.

Progress in advanced nanotherapeutics for enhanced photodynamic immunotherapy of tumor.

Clinically, the conventional treatments of cancer are still often accompanied by tumor recurrence, metastasis and other poor prognosis. Nowadays, more attention has been paid to photodynamic therapy (PDT), which is regarded as an adjuvant antineoplastic strategy with superiorities in great spatiotemporal selectivity and minimal invasiveness. In addition to eliminating tumor cells via reactive oxygen species (ROS), more meaningfully, this phototherapy can trigger immunogenic cell death (ICD) that plays a vital role in photodynamic immunotherapy (PDIT). ICD-based PDIT holds some immunotherapeutic potential due to further enhanced antitumor efficacy by utilizing various combined therapies to increase ICD levels. To help the PDIT-related drugs improve pharmacokinetic properties, bioavailability and system toxicity, multifunctional nanocarriers can be reasonably designed for enhanced PDIT. In further consideration of severe hypoxia, low immunity and immune checkpoints in tumor microenvironment (TME), advanced nanotherapeutics-mediated PDIT has been extensively studied for boosting antitumor immunity by oxygen-augment, ICD-boosting, adjuvant stimulation and combined checkpoints blockade. Herein, this review will summarize different categories of nanocarriers consisting of their material type, targeting and stimuli-responsiveness. Moreover, we will focus on the latest progress of various strategies to enhance the antitumor immune effect for PDIT and elucidate their corresponding immune-activation mechanisms. Nevertheless, there are several thorny challenges in PDIT, including limited light penetration, tumor hypoxia, immune escape and the development of novel small-molecule compounds that replace immune checkpoint inhibitors (ICIs) for easy integration into nanosystems. It is hoped that these issues raised will be helpful to the preclinical study of nanotherapeutics-based PDIT, thus accelerating the transformation of PDIT to clinical practice.

The Effects of Oral Energy-Dense Supplements on Nutritional Status in Nondiabetic Maintenance Hemodialysis Patients: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Fat-based energy-dense nutritional supplements may offer benefits over protein- or carbohydrate-dense supplements for patients receiving dialysis because of the adverse metabolic consequences of the latter. We conducted a randomized controlled trial to assess the effects of the short-term use of a fat-based nutritional supplement on various measures of nutritional status in patients receiving maintenance hemodialysis who have low dietary energy intake. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We enrolled nondiabetic patients receiving hemodialysis for >3 months who had inadequate dietary energy intake (<30 kcal/kg per day). The participants were randomly assigned in a 1:1 ratio to receive an oral fat-based energy-dense supplement (300 kcal daily) or routine care for 12 weeks (n=120 per group). The primary outcome was the change in phase angle measured by bioelectrical impedance analysis, a marker of cell integrity and body cell mass, from the baseline to week 12. The secondary outcomes were changes in quality of life. Other outcomes included laboratory nutritional indicators and physical examinations. RESULTS: The average age of the total population was 47 (SD: 12) years, and 55% were men. The median of dialysis vintage was 43.4 (22.5-76.3) months; 240 participants were randomly assigned to the intervention (n=120) or control group (n=120). In total, 228 (95%) participants completed the trial. The change in phase angle did not differ significantly between the intervention and control groups (estimate, 0.0; 95% confidence interval, -0.1 to 0.1 versus estimate, 0.0; 95% confidence interval, -0.1 to 0.1; estimated difference, 0.0; 95% confidence interval -0.2 to 0.2; P=0.99). None of the 19 domains of quality of life differed between the groups. Adverse events were reported in 23 (19%) participants in the control group and 40 (33%) participants in the intervention group. CONCLUSIONS: In nondiabetic patients on maintenance hemodialysis, short-term administration of fat-based energy-dense nutritional supplement has no clinically significant effect on nutritional status as measured by phase angle. PODCAST: This article contains a podcast at https://https://www.asn-online.org/media/podcast/CJASN/2021_08_03_CJN16821020.mp3.

Superiority of motor imagery acupuncture in improving muscle tension for patients with upper limb hemiplegia of stroke in early stage / 中国针灸

OBJECTIVE@#To verify the superiority of motor imagery acupuncture in improving muscle tension for patients with upper limb hemiplegia in early stroke.@*METHODS@#A total of 64 patients of stroke hemiplegia with upper limb flaccid paralysis were randomly divided into an observation group (32 cases, 1 case dropped off ) and a control group (32 cases, 4 cases dropped off ). The observation group was treated with motor imagery acupuncture (both acupuncture and motor imagery therapy at affected upper limb were performed).The control group was treated with acupuncture plus motor imagery therapy at affected lower limb, 2 h later after acupuncture, motor imagery therapy was applied to upper limb. Baihui (GV 20) to Taiyang (EX-HN 5) of healthy side, Fengchi (GB 20) and Jianyu (LI 15), Jianjing (GB 21), Quchi (LI 11), Waiguan (TE 5) on the affected side, ect. were selected in both groups, once a day, 5 times a week for 4 weeks. Before and after treatment, 4, 8 weeks after treatment, the modified Ashworth scale (MAS) grade and Brunnstrom stage were compared in the two groups.@*RESULTS@#Compared before treatment, the muscle tension of shoulder, elbow and wrist each time point after treatment was increased in the two groups (@*CONCLUSION@#Motor imagery acupuncture could promote hemiplegia upper limb muscle tension recovery in patients of stroke hemiplegia with upper limb flaccid paralysis, make the patients gradually shift to the separate fine movement mode, inhibit and relieve the appearance and development of spasm.

Efficacy and safety of different doses of ropivacaine for laparoscopy-assisted infiltration analgesia in patients undergoing laparoscopic cholecystectomy: A prospective randomized control trial.

BACKGROUND: Wound infiltration analgesia provides effective postoperative pain control in patients undergoing laparoscopic cholecystectomy (LC). However, the efficacy and safety of wound infiltration with different doses of ropivacaine is not well defined. This study investigated the analgesic effects and pharmacokinetic profile of varying concentrations of ropivacaine at port sites under laparoscopy assistance. METHODS: In this randomized, double-blinded study, 132 patients were assigned to 4 groups: Group H: in which patients were infiltrated with 0.75% ropivacaine; Group M: 0.5% ropivacaine; Group L: 0.2% ropivacaine; and Group C: 0.9% normal saline only. The primary outcome was pain intensity estimated using numeric rating scale (NRS) at discharging from PACU and at 4 hours, 6 hours, 8 hours, and 24 hours after infiltration. Secondary outcomes included plasma concentrations of ropivacaine at 30 minutes after wound infiltration, rescue analgesia requirements after surgery, perioperative vital signs changes, and side effects. RESULTS: The NRS in Group C was significantly higher at rest, and when coughing upon leaving PACU and at 4 hours, 6 hours, 8 hours, and 24 hours after infiltration (P < .05) and rescue analgesic consumption was significantly higher. Notably, these parameters were not significantly different between Groups H, Group M and Group L (P > .05). Intra-operative consumption of sevoflurane and remifentanil, HR at skin incision and MAP at skin incision, as well as 5 minutes after skin incision were significantly higher in Group C than in the other 3 groups (P < .01). In contrast, these parameters were not significantly different between Groups H, Group M and Group L (P > .05). The concentration of ropivacaine at 30 minutes after infiltration in Group H was significantly higher than that of Group L and Group M (P < .05). No significant differences were observed in the occurrence of side effects among the 4 groups (P > .05). CONCLUSIONS: Laparoscopy-assisted wound infiltration with ropivacaine successfully decreases pain intensity in patients undergoing LC regardless of the doses used. Infiltration with higher doses results in higher plasma concentrations, but below the systematic toxicity threshold.

Plasma selenium levels and risk of new-onset diabetes in hypertensive adults.

OBJECTIVE: The association between plasma selenium and new-onset diabetes in hypertensive adults is still unclear. We aimed to evaluate the relationship of baseline plasma selenium with new-onset diabetes and examine possible effect modifiers in a post-hoc analysis of the China Stroke Primary Prevention Trial (CSPPT). METHODS: A total of 2367 hypertensive, non-diabetic patients with plasma selenium measurements at baseline were included. The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during the follow-up period, or fasting glucose (FG) ≥126.0 mg/dL at the exit visit. RESULTS: At baseline, higher FG levels were found among participants with plasma selenium in quartile 4 (≥94.8 µg/L) (ß, 1.64 mg/dL; 95%CI: 0.54, 2.73) compared to those in quartiles 1-3. During a median follow-up duration of 4.5 years, new-onset diabetes occurred in 270 (11.4%) participants. Graphic plot showed a positive association between baseline selenium levels and risk of new-onset diabetes. This was further confirmed by adjusted regression analyses; the odds ratios (OR) for new-onset diabetes comparing quartile 4 (≥94.8 µg/L) to quartiles 1-3 was 1.36 (95%CI: 1.01, 1.83). No clear trend was evident across quartiles 1-3. CONCLUSIONS: Our data suggest that high plasma selenium (≥94.8 µg/L) was associated with increased risk of new-onset diabetes in hypertensive patients.

Quantitative reduction in short-chain fatty acids, especially butyrate, contributes to the progression of chronic kidney disease.

Chronic kidney disease (CKD) affects 10-15% of the population worldwide, results in high morbidity and mortality, and requires costly treatment and renal replacement therapy. Glomerulosclerosis, tubulointerstitial fibrosis, and persistent intestinal flora disturbance are common in CKD. Short-chain fatty acids (SCFAs), produced by the intestinal microbiota, have been previously reported to ameliorate kidney injury; however, the specific concentrations and types that are required to improve renal function remain unknown. The present study aims to evaluate the levels of SCFAs in healthy and CKD patients, and to test the hypothesis that SCFAs play a critical role in delaying CKD progression. One hundred and twenty-seven patients with CKD and 63 healthy controls from China were enrolled in the present study. Butyrate, which is considered beneficial to humans, was almost three-times higher in healthy volunteers than that in CKD5 subjects (P=0.001). Moreover, the serum SCFA levels in controls were significantly higher than that in CKD patients (P<0.05), and the butyrate level among CKD5 patients (1.48 ± 0.60 µmol/l) was less than half of that in controls (3.44 ± 2.12 µmol/l, P<0.001). In addition, we observed an inverse correlation between butyrate level and renal function (P<0.05). A CKD rat model transplanted with microbiota obtained from CKD patients exhibited accelerated CKD progression via increased production of trimethylamine N-oxide (TMAO), which was reversed by supplementation with extra butyrate. Our results showed that SCFA levels were reduced in CKD patients and that butyrate supplementation might delay CKD progression.

3'-Desmethylarctigenin induces G2/M cell cycle arrest and apoptosis through reactive oxygen species generation in hepatocarcinoma cells.

Previous studies have shown that arctigenin is a promising chemopreventive or therapeutic agent against various cancers. However, less is known about anticancer activity of 3'-desmethylarctigenin (3'-DMAG), which is a biotransformed product from arctigenin or arctin. In this study, we compared the anticancer activity of 3'-DMAG with its parent compound arctigenin and demonstrated that 3'-DMAG exerted a more potent inhibitory effect on HepG2 cells than arctigenin. Mechanistically, reactive oxygen species generation played an apical role in 3'-DMAG-induced G2/M cell cycle arrest and apoptosis in HepG2 cells. Furthermore, the Chk2-Cdc25c-Cdc2-cyclin B1 cascade was found to contribute to the cell cycle arrest, whereas the activation of mitochondrial pathway was involved in the cell apoptosis by 3'-DMAG. Additionally, a mouse xenograft hepatocellular carcinoma model was used to evaluate the antitumor effect of 3'-DMAG in vivo, and the results indicated that 3'-DMAG treatment significantly inhibited tumor growth without apparent toxicity. Taken together, 3'-DMAG is highly effective against liver cancer both in vitro and in vivo. The findings of the present study suggest that this compound deserves to be further investigated for its potential anticancer activity.

Aldosterone Antagonists Reduce the Risk of Cardiovascular Mortality in Dialysis Patients: A Meta-Analysis.

Background and Purpose. Cardiovascular disease is the major cause of death in dialysis patients. Although aldosterone antagonists were considered a treatment for severe heart failure patients to reduce cardiac mortality, whether treating patients undergoing maintenance dialysis with aldosterone antagonists could reduce the risk of cardiocerebrovascular (CCV) remains unclear. We aim to systematically assess the efficacy and tolerability of the addition of aldosterone antagonists to conventional therapy in patients undergoing maintenance dialysis. Materials and Methods. We searched PubMed, EMBASE, the Cochrane Library, the Chinese Biomedical Literature Database (CBM), and the China National Knowledge Infrastructure (CNKI) for relevant articles. The primary endpoint of interest was CCV mortality. The secondary endpoints were all-cause mortality, left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF). Publication bias was evaluated using funnel plots and Egger's test. The meta-analysis was performed using Review Manager software version 5.3. Results. This analysis included 10 randomized controlled trials (RCTs) with 1172 total chronic dialysis patients. The use of aldosterone antagonists in the dialysis population resulted in a marked reduction in CCV mortality (RR 0.42, 95% CI 0.26-0.65, P=0.0002) and all-cause mortality (RR0.46, 95%CI 0.32-0.66, P<0.0001). The LVEF was improved by treatment with aldosterone antagonists (WMD 6.35%, P<0.00001). Moreover, aldosterone antagonists decreased the LVMI (WMD -8.69 g/m2, P=0.0006), whereas aldosterone antagonists increased the occurrence of hyperkalemia (RR1.70, 95%CI 1-2.88, P=0.05) and gynecomastia (RR 8.01, 95% CI 2.44- 26.27, P=0.0006). Conclusions. Addition of aldosterone antagonists to conventional treatment in chronic dialysis patients may reduce CCV mortality, improve cardiac function, and simultaneously decrease LVMI.

SuHeXiang Essential Oil Inhalation Produces Antidepressant- and Anxiolytic-Like Effects in Adult Mice.

SuHeXiang (SHX) has been used to treat a wide range of diseases, including those related to the central nervous system. However, the effects of SHX on mood disorders are still elusive. This study aimed to investigate the effects of SHX essential oil on stress-induced depression of mice. In an acute stress-induced depression model, mice inhaled vehicle (1% Tween 80) for 10 min or 10% SHX for 10 or 30 min once daily for 12 continuous days. In the chronic mild stress (CMS)-induced depression model, mice were exposed to a 28-d CMS treatment. Tail suspension test (TST), forced swimming test (FST), sucrose preference test (SPT), open field test (OFT), and novelty suppressed feeding (NSF) test were conducted. In addition, serum levels of angiogenin (ANG), thrombopoietin (TPO), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated by enzyme-linked immunosorbent assay (ELISA) assays. The results showed that in mice exposed to acute stress, repeated SHX inhalation exerted significant antidepressant and anxiolytic activities, and also reduced the serum levels of ANG, TPO, IL-6, and TNF-α. It also significantly reversed the depressive and anxiety-like behaviors, and reduced the serum levels of ANG and TPO in mice exposed to CMS. This is the first report to show that SHX inhalation could produce significant antidepressant and anxiolytic-like effects. These effects might be mediated by SHX ability to modulate the inflammatory response, and reduce dysfunction of vascular genesis and thrombosis. These results support further exploration for developing SHX inhalation as a novel therapeutic strategy for depression and stress-related disorders.

High Loading Dose of Atorvastatin for the Prevention of Serum Creatinine and Cystatin C-Based Contrast-Induced Nephropathy Following Percutaneous Coronary Intervention.

The aim of this study is to assess the efficacy of high-dose atorvastatin on the prevention of contrast-induced nephropathy (CIN) in patients with acute coronary syndrome (ACS) undergoing percutaneous intervention and observe the incidence of cystatin C (CyC)-based CIN. A total of 496 patients with ACS were randomly assigned to either the control group (247 patients receiving conventional dose atorvastatin 10 mg daily from 1 day before to 3 days after contrast administration) or the high-dose atorvastatin group (249 patients receiving atorvastatin 40 mg daily for the same perioperative period). The baseline characteristics of the 2 groups were similar. The primary end point of serum creatinine (SCr)-based CIN occurred in 31 patients in the control group and 16 patients in the high-dose atorvastatin group (12.6% vs 6.4%; P = .02). Cystatin C-based CIN developed in 90 patients in the control group and 46 patients in the high-dose atorvastatin group (36.4% vs 18.5%; P < .001). A multivariable analysis revealed that high-dose atorvastatin was independently associated with a decreased risk of CIN. Our study demonstrated that prophylactic treatment with high-dose atorvastatin reduced the risk of both SCr and CyC-based CIN and suggested that CyC was a more reliable marker for early diagnosis of CIN compared with SCr.

Efficacy of short-term moderate or high-dose rosuvastatin in preventing contrast-induced nephropathy: A meta-analysis of 15 randomized controlled trials.

BACKGROUND: The prophylactic efficacy of statin pretreatment for the prevention of contrast-induced nephropathy (CIN) in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) remains controversial. The aim of the study was to perform a meta-analysis of randomized controlled trials (RCTs) to assess the effectiveness of short-term moderate or high-dose rosuvastatin pretreatment in preventing CIN. METHODS: We included RCTs comparing short-term moderate or high-dose rosuvastatin treatment versus low-dose rosuvastatin treatment or placebo for preventing CIN. The primary endpoint was the incidence of CIN within 2 to 5 days after contrast administration, and related-parameters including serum creatinine (SCr), cystatin C (CysC), hypersensitive C-reactive protein (hs-CRP), urine microalbumin (mALB) were also extracted. RESULTS: Fifteen RCTs with a total of 2673 patients were identified and analyzed. Patients who received moderate or high-dose rosuvastatin pretreatment had a 55% lower risk of CIN compared with low-dose rosuvastatin pretreatment or placebo group based on a fixed effect model (RR = 0.45, 95% CI 0.35-0.58, P < .0001). The benefit of moderate or high-dose rosuvastatin was consistent in both comparisons with low-dose rosuvastatin (RR = 0.40, 95% CI 0.27-0.59, P < .0001) or placebo (RR = 0.45, 95% CI 0.35-0.58, P < .0001). And moderate (20 mg) or high dose (≥40 mg) rosuvastatin significantly reduced the incidence of CIN compared with the control (RR = 0.39, 95% CI 0.29-0.54, P < .0001, RR = 0.56, 95% CI 0.37-0.85, P = .006, respectively). Subgroup analysis showed that moderate or high-dose rosuvastatin pretreatment could decrease the incidence of CIN in patients with chronic kidney disease (CKD) (RR = 0.53, 95% CI 0.30-0.93, P = .03) or diabetes mellitus (DM) (RR = 0.51, 95% CI 0.31-0.86, P = .01) or acute coronary syndrome (ACS) patients undergoing PCI (RR = 0.52, 95% CI 0.35-0.76, P = .0009) or in studies which received mean contrast volume ≥110 mL (RR = 0.43, 95% CI 0.32-0.58, P < .0001). The SCr, CysC, hs-CRP, and mALB after the operation in the moderate or high-dose rosuvastatin group were lower than those of low-dose rosuvastatin group. CONCLUSION: This meta-analysis demonstrated that moderate or high-dose rosuvastatin treatment could reduce the incidence of CIN in patients undergoing CAG or PCI. Moreover, moderate or high-dose rosuvastatin would be beneficial in high-risk patients with CKD or DM or undergoing PCI.

Targeting ERK enhances the cytotoxic effect of the novel PI3K and mTOR dual inhibitor VS-5584 in preclinical models of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease in urgent need of newer therapeutic modalities. Majority of patients with PDAC have mutations in KRAS, which unfortunately remains an ineffectual target. Our strategy here is to target KRAS downstream effectors PI3K and mTOR. In this study, we investigated the antitumor efficacy of the novel PI3K and mTOR dual inhibitor VS-5584 in PDAC. Our data shows that PI3K/mTOR dual inhibition causes ERK activation in all tested PDAC cell lines. Although the MEK inhibitor GSK1120212 could abrogate VS-5584-induced ERK activation, it did not substantially enhance cell death in all the cell lines tested. However, combination with ERK inhibitor SCH772984 not only mitigated VS-5584-induced ERK activation but also enhanced VS-5584-induced cell death. In a xenograft model of PDAC, we observed 28% and 44% tumor inhibition for individual treatment with VS-5584 and SCH772984, respectively, while the combined treatment showed superior tumor inhibition (80%) compared to vehicle control treatment. Our findings support the clinical development of VS-5584 and ERK inhibitor combination for PDAC treatment.

Folic acid therapy reduces serum uric acid in hypertensive patients: a substudy of the China Stroke Primary Prevention Trial (CSPPT).

Background: The effect of folic acid supplementation on uric acid (UA) concentrations is still inconclusive.Objective: We aimed to test the efficacy of folic acid therapy in reducing serum UA in hypertensive patients.Design: A total of 15,364 hypertensive patients were randomly assigned to a double-blind daily treatment with a single tablet that contained 10 mg enalapril and 0.8 mg folic acid (n = 7685) or 10 mg enalapril alone (n = 7679). The main outcome was the change in serum UA, which was defined as UA at the exit visit minus that at baseline. Secondary outcomes were as follows: 1) controlled hyperuricemia (UA concentration <357 µmol/L after treatment) and 2) new-onset hyperuricemia in participants with normal UA concentrations (<357 µmol/L).Results: After a median of 4.4 y of treatment, the mean ± SD UA concentration increased by 34.7 ± 72.5 µmol/L in the enalapril-alone group and by 30.7 ± 71.8 µmol/L in the enalapril-folic acid group, which resulted in a mean group difference of -4.0 µmol/L (95% CI: -6.5, -1.6 µmol/L; P = 0.001). Furthermore, compared with enalapril alone, enalapril-folic acid treatment showed an increase in controlled hyperuricemia (30.3% compared with 25.6%; OR: 1.31; 95% CI: 1.01, 1.70) and a decrease in new-onset hyperuricemia (15.0% compared with 16.3%; OR: 0.89; 95% CI: 0.79, 0.99). A greater beneficial effect was observed in subjects with hyperuricemia (P-interaction = 0.07) or higher concentrations of total homocysteine (tHcy) (P-interaction = 0.02) at baseline. Furthermore, there was a significant inverse relation (P < 0.001) between the reduction of tHcy and the change in UA concentrations.Conclusions: Enalapril-folic acid therapy, compared with enalapril alone, can significantly reduce the magnitude of the increase of UA concentrations in hypertensive adults. This trial was registered at clinicaltrials.gov as NCT00794885.