We present a new method for high-resolution nanoscale magnetic resonance imaging (nano-MRI) that combines the high spin sensitivity of nanowire-based magnetic resonance detection with ...high-spectral-resolution nuclear magnetic resonance (NMR) spectroscopy. Using a new method that incorporates average Hamiltonian theory into optimal control pulse engineering, we demonstrate NMR pulses that achieve high-fidelity quantum control of nuclear spins in nanometer-scale ensembles. We apply this capability to perform dynamical decoupling experiments that achieve a factor of 500 reduction of the proton-spin resonance linewidth in a(50−nm)3volume of polystyrene. We make use of the enhanced spin coherence times to perform Fourier-transform imaging of proton spins with a one-dimensional slice thickness below 2 nm.
Systemic lupus erythematosus (SLE) is a type of autoimmune disease that damages multiple organs, including the heart, joints, liver and kidneys. The main characteristics of SLE are the deposition of ...circulating autoantibodies; autoantigen complexes in the renal system; and abnormal expression of complements, cytokines and chemokines. Lupus nephritis (LN) is the most serious manifestation of SLE and is characterized by inflammation of the kidney.
This review summarizes recent clinical applications of protein biomarkers including autoantibodies, complements, cytokines and chemokines and some new protein biomarkers in SLE and LN. The clinical differential diagnosis of protein biomarkers related to prognosis and diagnosis is discussed and highlighted.
Protein biomarkers play crucial roles in the study of SLE and LN. Useful biomarkers will provide insights into effective treatments for these diseases.
•The increased levels of HMGB1 are correlated with the severity of preeclampsia.•The increased serum levels of uric acid are correlated with the expression of HMGB1.•Pathologic levels of uric acid ...(see in preeclampsia) did not induce further increase in the expression of HMGB1.
Preeclampsia is a pregnancy-specific disorder characterised by an inappropriate maternal inflammatory response during pregnancy. High mobility group box 1 (HMGB1) was originally characterised as a nuclear protein but when released into the extracellular environment following necrotic cell death, it is proinflammatory. HMGB1 is expressed in the syncytiotrophoblast of human placenta. Higher levels of uric acid are reported in preeclampsia. The aim of this study was to investigate whether the expression of HMGB1differed between early onset and late onset preeclampsia or severe and mild preeclampsia and whether its expression correlated with the levels of uric acid.
74 preeclamptic placentae and 110 normotensive placentae were included in this study. The levels of uric acid in women with preeclampsia were measured. The expression of HMGB1 in preeclamptic placentae or in first trimester and term placentae that had been treated with uric acid was measured.
HMGB1 was expressed predominantly in the syncytiotrophoblast of the placenta and the expression of HMGB1 in the cytoplasm of the syncytiotrophoblast was significantly increased in both severe preeclampsia and early onset preeclampsia compared to normotensive pregnancies. The circulating levels of uric acid were significantly increased in preeclampsia and correlated with the expression of HMGB1. Increased levels of HMGB1 were significantly correlated with the severity and the time of onset of preeclampsia, but pathologic levels of uric acid did not increase the expression of HMGB1.
Our data provides a better understanding of the function of HMGB1, a danger molecule in the pathogenesis of preeclampsia.
Background
Aliskiren might be beneficial for heart failure. However, the results of various studies are controversial. We conducted a systematic review and meta-analysis to explore the efficacy of ...aliskiren supplementation for heart failure.
Methods
PubMed, Embase, Web of Science, EBSCO, and the Cochrane Library databases were systematically searched. Randomized controlled trials (RCTs) assessing the efficacy of aliskiren for heart failure were included. Two investigators independently searched for articles, extracted data, and assessed the quality of included studies. The meta-analysis was performed using the random-effect model.
Results
Five RCTs comprising 1973 patients were included in the meta-analysis. Compared with control interventions in heart failure, aliskiren supplementation was found to significantly reduce NT-proBNP levels (standardized mean difference SMD = −0.12; 95% CI = −0.21 to −0.03 pg/ml;
p
= 0.008) and plasma renin activity (SMD = −0.66; 95% CI = −0.89 to −0.44 ng/ml.h;
p
< 0.00001) while increasing plasma renin concentration (SMD = 0.52; 95% CI = 0.30–0.75 ng/l;
p
< 0.00001); however, it demonstrated no significant influence on BNP levels (SMD = −0.08; 95% CI = −0.31–0.15 pg/ml;
p
= 0.49), mortality (RR = 0.97; 95% CI = 0.79–1.20;
p
= 0.79), aldosterone levels (SMD = −0.09; 95% CI = −0.32–0.14 pmol/l;
p
= 0.44), adverse events (RR = 3.03; 95% CI = 0.18–49.51;
p
= 0.44), and serious adverse events (RR = 1.34; 95% CI = 0.54–3.33;
p
= 0.53).
Conclusion
Aliskiren supplementation was found to significantly decrease NT-proBNP levels and plasma renin activity and to improve plasma renin concentration in the setting of heart failure.
.
We previously reported that treatment with P-glycoprotein (P-gp) substrates promotes
in vitro
invasion in multidrug-resistant (MDR) breast cancer cells. This effect is initiated by the P-gp pump ...function and mediated by interaction of P-gp with some unknown component(s). However, the underlying mechanism(s) remains poorly understood. Here we confirm a novel physical interaction between P-gp and cellular prion protein (PrP
c
). Blocking P-gp activity or depletion of PrP
c
inhibited paclitaxel (P-gp substrate)- induced invasion. Paclitaxel further facilitated the formation of P-gp/PrP
c
clusters residing in caveolar domains and promoted the association of P-gp with caveolin-1. Both caveolin-1 and the integrity of caveolae were required for the drug-induced invasion. In addition, the P-gp/PrP
c
complex also played an important role in anti-apoptotic activity of MCF7/Adr cells.These data provide new insights into the mode by which MDR breast cancers evade cytotoxic attacks from P-gp substrates and also suggest a role for P-gp/ PrP
c
interaction in this process.
Angiopoietin-like protein (ANGPTL) complexes 3/8 and 4/8 are established inhibitors of LPL and novel therapeutic targets for dyslipidemia. However, the effects of regular exercise on ANGPTL3/8 and ...ANGPTL4/8 are unknown. We characterized ANGPTL3/8 and ANGPTL4/8 and their relationship with in vivo measurements of lipase activities and cardiometabolic traits before and after a 5-month endurance exercise training intervention in 642 adults from the HERITAGE (HEalth, RIsk factors, exercise Training And GEnetics) Family Study. At baseline, higher levels of both ANGPTL3/8 and ANGPTL4/8 were associated with a worse lipid, lipoprotein, and cardiometabolic profile, with only ANGPTL3/8 associated with postheparin LPL and HL activities. ANGPTL3/8 significantly decreased with exercise training, which corresponded with increases in LPL activity and decreases in HL activity, plasma triglycerides, apoB, visceral fat, and fasting insulin (all P < 5.1 × 10−4). Exercise-induced changes in ANGPTL4/8 were directly correlated to concomitant changes in total cholesterol, LDL-C, apoB, and HDL-triglycerides and inversely related to change in insulin sensitivity index (all P < 7.0 × 10−4). In conclusion, exercise-induced decreases in ANGPTL3/8 and ANGPTL4/8 were related to concomitant improvements in lipase activity, lipid profile, and cardiometabolic risk factors. These findings reveal the ANGPTL3-4-8 model as a potential molecular mechanism contributing to adaptations in lipid metabolism in response to exercise training.
Summary
Immunological methods, which have been widely used in autoimmune blistering diseases (AIBDs) of the oral mucosa, can also be adopted as auxiliary diagnostic tools in oral lichen planus (OLP) ...and discoid lupus erythematosus (DLE). AIBDs, characterized by autoantibodies against structural proteins of keratinocytes or the basement membrane zone, clinically present as blisters and erosions of the oral mucosa. When atypical lesions occur, OLP or DLE may be confused with AIBDs. The improvement of diagnostic accuracy is necessary due to the significant differences in treatment and prognosis among these diseases. A variety of immunological methods are used for qualitative and quantitative detection of target antigens and autoantibodies. These methods can evaluate efficacy of treatment, monitor diseases and guide treatment decisions. In this review, we discuss the application of immunofluorescence, biochemical tests, and protein microarrays for AIBDs, OLP and DLE, as well as the differential diagnostic methods using immunological tests.
What's already known about this topic?
Oral lichen planus (OLP) or discoid lupus erythematosus (DLE) may be confused with autoimmune blistering diseases (AIBDs) when atypical lesions occur in the oral mucosa.
Immunological methods for diagnosis of oral mucosal diseases mainly refer to routine immunofluorescence, salt‐split skin test, biochemical tests and protein microarrays.
Under limited conditions, the most sensitive immunological methods for diagnosing oral mucosal diseases need to be selected.
What does this study add?
This review summarizes the principles, diagnostic characteristics and results of various immunological diagnostic methods for AIBDs, OLP and DLE.
Sensitivity of different immunological methods for AIBDs can provide guidance for clinicians.
Indirect immunofluorescence showed high diagnostic sensitivity in pemphigus vulgaris or paraneoplastic pemphigus.
Biochemical tests showed high diagnostic sensitivity in AIBDs.
Protein microarrays may serve as a future conventional diagnostic method with high sensitivity and specificity in AIBDs.
Linked Comment: Hashimoto and Nakahara. Br J Dermatol 2019; 181:9–10.
Plain language summary available online
In this paper, the seismic base isolation problem for all low-complexity networks containing one inerter, one spring, and one damper is studied based on a multi-degree-of-freedom model. The ...analytical solutions for the H2 performance optimization are derived, and the traditional tuned mass damper (TMD) is employed for comparison. Extensive numerical simulations are performed to verify the effectiveness of the obtained results. The results show that for different seismic wave excitations, some isolators are better than TMD in controlling the displacement of the main structure. Moreover, with the increase of the TMD mass ratio, the isolation performances of the inerter-based isolators are increasingly better than that of TMD.
Summary
This study analyzed the effects of combination therapy with sodium-glucose transporter-2 inhibitors (SGLT2is) and metformin on fracture risk. Summarizing available randomized controlled ...trials, we found that SGLT2is combined with metformin therapy did not influence fracture risk compared with metformin monotherapy or other comparators in patients with T2DM.
Introduction
No study is available evaluating the association between sodium-glucose transporter-2 inhibitors (SGLT2is) in combination with metformin use and fracture risk. Our study aimed to investigate the fracture risk of combination therapy with SGLT2is and metformin in patients with type 2 diabetes mellitus (T2DM).
Methods
PubMed, Embase,
ClinicalTrials.gov
site, and the Cochrane Library databases were scrutinized for all eligible randomized controlled trials (RCTs). The summarized odds ratios (ORs) and their 95% confidence intervals (CI) were calculated using Review Manager 5.3 software.
Results
A total of 25 RCTs involving 19,500 participants with T2DM were included in our studies. There were 88 fracture cases in the SGLT2is in combination with metformin therapy group and 79 in the control group. SGLT2is combined with metformin use did not influence fracture risk compared with metformin monotherapy or other comparators in patients with T2DM (OR = 0.97, 95% CI 0.71–1.32). After stratification by drug type, follow-up time, control regimen, and type of fracture, the upshots were still stable.
Conclusion
SGLT2is and metformin combination therapy did not influence fracture risk compared with metformin monotherapy or other comparators in patients with T2DM.
Prospero registration number
CRD42020168435.
Background: Clinical pharmacists play a significant role in clinical practice, but their work in the clinical pathway (CP) of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) ...remains undefined. Methods: This prospective study included patients who met the discharge criteria during hospitalization at the department of respiratory medicine of the Second Affiliated Hospital of Fujian Medical University from March to December 2017 (no pharmacists involved) and from March 2018 to January 2019 (pharmacists involved). The adverse drug reaction (ADR) reporting rate, the average DDD number of antibacterial drugs, the per capita cost of pharmaceutical services, and the benefit-cost ratio (B/C) were analyzed. Results and Discussion: Eighty participants were enrolled during the traditional period and eighty-five participants during the clinical pharmacist period. The average hospital stays (9.2 + or - 0.4 vs 10.7 + or - 0.6 days, P=0.032), the total cost of hospitalization expenses (yen 14,058 + or - 826 vs yen 18,765 + or - 1434, P=0.004), the total cost of drugs (yen 5717 + or - 449 vs yen 8002 + or - 755, P=0.004), and cost of antimicrobial drugs (yen 3639 + or - 379 vs yen 5636 + or - 641, P=0.007) were all lower in the clinical pharmacist group than in the traditional group. The B/C was 10.38 and 5.05 in the total cost of hospitalization expenses and the total cost of drugs, respectively. The clinical pharmacists' participation was independently associated with the total cost of hospitalization expenses (P=-0.201, 95% confidence interval: -0.390, -0.055, P=0.010). What is New and Conclusion: The participation of the clinical pharmacist in implementing an AECOPD CP significantly reduces patients' hospitalization days, the total cost of hospitalization expenses, and antibiotic use and improves the B/C of AECOPD management. The clinical pharmacists' participation was independently associated with the total hospitalization expenses. Keywords: clinical pharmacist, acute exacerbation of chronic obstructive pulmonary disease, clinical pathway, pharmaceutical services, cost-benefit analysis
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