The diagnostic value of sST2 for myocardial fibrosis in idiopathic inflammatory myopathies in subclinical stage of cardiac involvement.

OBJECTIVE: Myocardial fibrosis occurs in the early subclinical stage of cardiac involvement in idiopathic inflammatory myopathies (IIMs). Soluble suppression of tumorigenicity 2 (sST2) is known to have an immunomodulatory impact during autoimmune disease development. The current study investigated the diagnostic value of sST2 for myocardial fibrosis during early stage of cardiac involvement in IIM. METHODS: A total of 44 IIM patients with normal heart function and 32 age- and gender-matched healthy controls (HCs) were enrolled. Serum sST2 levels were measured by ELISA and cardiac magnetic resonance (CMR) parameters for myocardial fibrosis [native T1, extracellular volume (ECV), late-gadolinium enhancement (LGE)] and oedema (T2 values) were analysed. RESULTS: IIM patients had significantly higher sST2 levels than HCs [67.5 ng/ml (s.d. 30.4)] vs 14.4 (5.5), P < 0.001] and levels correlated positively with diffuse myocardial fibrosis parameters, native T1 (r = 0.531, P = 0.000), ECV (r = 0.371, P = 0.013) and focal myocardial fibrosis index and LGE (r = 0.339, P = 0.024) by Spearman's correlation analysis. sST2 was an independent predictive factor for diffuse and focal myocardial fibrosis after adjustment for age, gender, BMI and ESR. Risk increased ≈15.4% for diffuse [odds ratio (OR) 1.154 (95% CI 1.021, 1.305), P = 0.022] and 3.8% for focal [OR 1.038 (95% CI 1.006, 1.072), P = 0.020] myocardial fibrosis per unit increase of sST2. Cut-off values for diagnosing diffuse and focal myocardial fibrosis were sST2 ≥51.3 ng/ml [area under the curve (AUC) = 0.942, sensitivity = 85.7%, specificity = 98.9%, P < 0.001] and 53.3 ng/ml (AUC = 0.753, sensitivity = 87.5%, specificity = 58.3%, P < 0.01), respectively. CONCLUSION: sST2 showed a marked elevation during the subclinical stage of cardiac involvement in IIM and has potential as a biomarker for predicting diffuse and focal myocardial fibrosis in IIM.

MTHFD2 suppresses glioblastoma progression via the inhibition of ERK1/2 phosphorylation.

Glioblastoma (GBM) is a WHO grade 4 tumor and is the most malignant form of glioma. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial enzyme involved in folate metabolism, has been reported to be highly expressed in several human tumors. However, little is known about the role of MTHFD2 in GBM. In this study, we aimed to explore the biological functions of MTHFD2 in GBM and identify the associated mechanisms. We performed experiments such as immunohistochemistry, Western blot, and transwell assays and found that MTHFD2 expression was lower in high-grade glioma than in low-grade glioma. Furthermore, a high expression of MTHFD2 was associated with a favorable prognosis, and MTHFD2 levels showed good prognostic accuracy for glioma patients. The overexpression of MTHFD2 could inhibit the migration, invasion, and proliferation of GBM cells, whereas its knockdown induced the opposite effect. Mechanistically, our findings revealed that MTHFD2 suppressed GBM progression independent of its enzymatic activity, likely by inducing cytoskeletal remodeling through the regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, thereby influencing GBM malignance. Collectively, these findings uncover a potential tumor-suppressor role of MTHFD2 in GBM cells. MTHFD2 may act as a promising diagnostic and therapeutic target for GBM treatment.

The diagnostic value of urinary N-terminal fragment of titin for skeletal muscle damage in idiopathic inflammatory myopathy.

OBJECTIVES: N-terminal fragment of titin (N-titin) is a marker of sarcomere damage in striated muscles; however, its value in patients with IIM (idiopathic inflammatory myopathy) is unclear. This study aimed to investigate the diagnostic value of N-titin for skeletal muscle damage in patients with IIM. METHODS: Urine samples from 62 patients with IIM, 59 patients with other CTD diseases, and 29 healthy controls were collected to detect N-titin by ELISA assays. Clinical features and laboratory data were all included in logistic regression analysis to obtain the independent predictive factor for skeletal muscle damage. RESULTS: Urinary N-titin level of the IIM group [168.3 (19.0, 1279.0) pmol/mg cr] was significantly higher than that in CTD controls [2.80 (1.53, 3.60)] and healthy controls [1.83 (1.09, 2.95)] (P < 0.001). IIM patients with skeletal muscle injury had a significantly higher level of urinary N-titin [1001.0, (181.8, 1977.0)] than those without [9.3, (5.8, 23.9)] (P < 0.001). The N-titin level was strongly correlated with CK (r = 0.907, P < 0.001) and muscle disease activity assessment scores by Spearman correlation analysis. After adjusting for the anti-MDA5 antibody and cardiac troponin T, N-titin was shown to independently predict skeletal muscle damage in patients with IIM (odds ratio = 1.035, 95% CI: 1.002, 1.069, P = 0.039). The cut-off value of urinary N-titin to diagnose skeletal muscle damage was 89.9 pmol/mg Cr, with a sensitivity of 87.8% and a specificity of 100% (AUC = 0.971, 95% CI: 0.938, 1.000, P < 0.001). CONCLUSION: Urinary N-titin is a non-invasive and independent predictive factor for determining skeletal muscle damage in patients with IIM.

Are couple-based psychological interventions beneficial for the mental health of prostate cancer patients and their spouses? A systematic review and meta-analysis.

As the survival rates for prostate cancer (PCa) have improved, there has been an increasing focus on the mental health of couples affected by this condition. There have been several couple-based psychological interventions, and yet the impact of this treatment modality on the mental health of PCa patients and their spouses is unclear. Consequently, a systematic search was conducted in PubMed, Embase, Cochrane, LILACS, and Web of Science up to March 2023 for randomized controlled trials (RCTs) addressing the impacts of couple-based psychological interventions on both PCa patients and their spouses. Besides, the Cochrane Risk of Bias Assessment Tool was employed to evaluate the methodological quality and potential bias of the included studies. Moreover, statistical analysis and meta-analysis were performed utilizing Revman 5.4, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was employed to assess the certainty of evidence. A total of nine RCTs were included, utilizing anxiety, depression, distress, communication, and self-efficacy as outcome indicators to assess mental health. Results demonstrated that couple-based psychological interventions increased spouses' self-efficacy (WMD, 0.21; 95% CI: -0.00 ~ 0.42; P = 0.05) and communication (SMD, 0.34; 95% CI: 0.09 ~ 0.59; P = 0.009), while reducing their distress (SMD, -0.21; 95% CI: -0.40 ~ -0.02; P = 0.03). Nonetheless, there is a need for additional research on the effect of couple-based psychological interventions on the mental health of PCa-affected couples given the limited evidence supporting this conclusion.

Phenotyping of myocardial involvement by cardiac magnetic resonance in idiopathic inflammatory myopathies.

OBJECTIVES: Cardiac dysfunction is commonly noted in patients with idiopathic inflammatory myopathies (IIMs). This study aimed to investigate the characteristics of cardiac dysfunction using cardiac magnetic resonance (CMR) in polymyositis (PM), dermatomyositis (DM) and necrotising myositis (NM). METHODS: Fifty-one patients with IIMs and 20 matched healthy controls (HCs) were assessed using CMR examination. The clinical data, cardiac serum markers and autoimmune antibodies were determined for all patients. Cardiac involvement was identified by myocardial native T1, extracellular volume (ECV), late gadolinium enhancement (LGE) and left ventricular ejection fraction (LVEF). RESULTS: Different subtypes of IIMs showed different patterns of LGE and varying degrees of myocardial damage. The PM subgroup showed higher native T1 (p = 0.010) and ECV (p = 0.000) than the HCs. The prevalence of LGE was comparable between the PM and DM subgroups (40.0% vs. 31.6%, p = 0.741); however, it was higher in the PM subgroup than in the NM subgroup (40% vs. 0.0%, p = 0.014). Patients with positive LGE in the PM subgroup showed a higher proportion of positive LGE (p = 0.018) and lower LVEF (p = 0.024) than those with positive LGE in the DM subgroup. In multivariate analysis, the presence of LGE could be predicted by increased NT-proBNP (p = 0.036, OR = 1.001) and anti-MDA-5 antibody positivity (p = 0.011, OR = 12.4). The risk factors associated with native T1 were NT-proBNP (p = 0.016, ß = 0.353) and body mass index (BMI) (p = 0.024, ß = - 0.331). CONCLUSIONS: Distinct cardiac involvements in different subtypes of IIMs were identified using CMR. Elevated NT-proBNP and a low BMI were the risk factors associated with LGE and elevated native T1. KEY POINTS: • The characteristics of cardiac involvement in different subtypes of IIMs could be identified with cardiac magnetic resonance. • The NT-proBNP levels could reflect focal and diffuse myocardial damage in patients with IIMs.

Gait analysis in the elderly patients with lumbar spinal stenosis.

PURPOSE: This study aims to analyze the gait characteristics of the elderly patients with lumbar spinal stenosis by an intelligent device for energy expenditure and activity (IDEEA) to assist clinical work. METHODS: A total of 98 subjects were included in this study from January 2017 to December 2018. A total of 49 elderly outpatients with symptomatic lumbar spinal stenosis in unilateral lower extremity were included as the experimental group, and another 49 healthy subjects matched with gender, age, and body mass index (BMI) were analyzed as the control group. The gait data of the subjects (including single support, double support, SLS/DLS, swing duration, step duration, cycle duration, pulling accel, swing power, ground impact, foot fall, foot off, push off, speed, cadence, step length, and stride length) were collected to compare between the experience group and control group, the affected leg and the healthy leg in experimental group. RESULTS: The results of this study presented that small intermittent claudication occurred in all patients. The time of single support was significantly increased (p < 0.05). Double support, step duration, and pulling accel were increased (p < 0.05), and the Push off, speed, step length, and Stride length were decreased (p < 0.05) in the experimental group compared with the control group. CONCLUSION: Small intermittent claudication was the basic gait composition of the elderly patients with lumbar spinal stenosis that can reflect the abnormal gait characteristics by IDEEA.

SGK1 enhances Th9 cell differentiation and airway inflammation through NF-κB signaling pathway in asthma.

This study aimed to explore the effect of Sgk1 on Th9 differentiation and the underlying mechanism in asthma. The asthmatic mouse model induced by ovalbumin (OVA) and CD4+T cells which were cultured with TGF-ß, IL-2, IL-4, and anti-IFN-γ were applied in vivo and in vitro, respectively. Flow cytometry, quantitative real-time PCR (qRT-PCR), and ELISA were performed to detect T-helper 9 (Th9) cells, IL-9 expression, and IL-9 release. Western blot was performed to examine phosphorylated(p)-IKKα, p-IκBα, p-p65, and IRF4 levels. Hematoxylin/eosin (H&E) staining was adopted to assess pathological changes of lung tissues. Inhibition of Sgk1 dramatically reversed elevated Th9 cells and IL-9 expression in the lung tissues of asthmatic mice. In vitro, Sgk1 promoted Th9 differentiation and elevated p-IKKα, p-IκBα, p-p65, and IRF4 levels, but inhibition of IKKα/IκBα/p65 pathway and IRF4 both reversed enhanced Th9 differentiation by Sgk1. Sgk1→IKKα/IκBα/NF-κBp65→IRF4→Th9 axis may be implicated in asthma development.

Methylation-driven model for analysis of dinucleotide evolution in genomes.

BACKGROUND: CpGs, the major methylation sites in vertebrate genomes, exhibit a high mutation rate from the methylated form of CpG to TpG/CpA and, therefore, influence the evolution of genome composition. However, the quantitative effects of CpG to TpG/CpA mutations on the evolution of genome composition in terms of the dinucleotide frequencies/proportions remain poorly understood. RESULTS: Based on the neutral theory of molecular evolution, we propose a methylation-driven model (MDM) that allows predicting the changes in frequencies/proportions of the 16 dinucleotides and in the GC content of a genome given the known number of CpG to TpG/CpA mutations. The application of MDM to the 10 published vertebrate genomes shows that, for most of the 16 dinucleotides and the GC content, a good consistency is achieved between the predicted and observed trends of changes in the frequencies and content relative to the assumed initial values, and that the model performs better on the mammalian genomes than it does on the lower-vertebrate genomes. The model's performance depends on the genome composition characteristics, the assumed initial state of the genome, and the estimated parameters, one or more of which are responsible for the different application effects on the mammalian and lower-vertebrate genomes and for the large deviations of the predicted frequencies of a few dinucleotides from their observed frequencies. CONCLUSIONS: Despite certain limitations of the current model, the successful application to the higher-vertebrate (mammalian) genomes witnesses its potential for facilitating studies aimed at understanding the role of methylation in driving the evolution of genome dinucleotide composition.

Multiparametric cardiovascular magnetic resonance characteristics and dynamic changes in myocardial and skeletal muscles in idiopathic inflammatory cardiomyopathy.

BACKGROUND: Idiopathic inflammatory myopathy (IIM) manifest as systematic muscle involvement. Multiparametric cardiovascular magnetic resonance (CMR) could be a useful technique to detect systemic involvement and disease progression in IIM patients. This study aimed to describe the tissue characteristics and dynamic changes in myocardial and skeletal muscles after treatment in IIM patients. METHODS: Forty-four consecutively recruited IIM patients (49.0 ± 12.0 years; 22 males) underwent 3 T CMR at first diagnosis, and 28 patients underwent follow-up scan after receiving standard treatment for more than 1 year. Thirty age- and sex-matched healthy subjects served as controls. The CMR protocol included: cines, T2-weighted (T2w), late gadolinium enhancement (LGE), T1 and T2 mapping, and extracellular volume (ECV) evaluated for the myocardium, and T1 and T2 mapping and ECV evaluated for skeletal muscles. Correlations between laboratory biomarkers and myocardial and skeletal tissue characteristics were analyzed. Comparisons between baseline and follow-up scans were performed using paired t-tests. RESULTS: At baseline, IIM patients showed significantly decreased hematocrit, higher left ventricular (LV) mass index, right ventricular (RV) volume index, myocardial and skeletal native T1, T2 mapping, and ECV than healthy controls. Significant correlations were found among myocardial native T1, T2 mapping, and ECV values and N-terminal pro b-type natriuretic peptide (NT-proBNP) levels, and significant correlations between skeletal T2 mapping and inflammatory biomarkers in IIM patients. During the follow-up, 28 patients underwent repeated CMR scan (median interval, 14.5 months, interquartile range: 13.2-15.5 months). Significant relief from clinical symptoms and decreased inflammatory biomarkers levels were observed. Significant reduction in myocardial native T1, T2, ECV, and skeletal native T1, T2, and ECV were observed during the follow-up assessment. CONCLUSIONS: Both myocardial and skeletal muscles in newly diagnosed IIM patients show distinct characteristics on multiparametric CMR. In addition, significant changes were observed in patients showing clinical remission after effective treatment, which suggests that quantitative T1, T2, and ECV techniques may have potential clinical value in IIM patients.

Zika Virus Attenuation by Codon Pair Deoptimization Induces Sterilizing Immunity in Mouse Models.

Zika virus (ZIKV) infection during the large epidemics in the Americas is related to congenital abnormities or fetal demise. To date, there is no vaccine, antiviral drug, or other modality available to prevent or treat Zika virus infection. Here we designed novel live attenuated ZIKV vaccine candidates using a codon pair deoptimization strategy. Three codon pair-deoptimized ZIKVs (Min E, Min NS1, and Min E+NS1) were de novo synthesized and recovered by reverse genetics and contained large amounts of underrepresented codon pairs in the E gene and/or NS1 gene. The amino acid sequence was 100% unchanged. The codon pair-deoptimized variants had decreased replication fitness in Vero cells (Min NS1 ≫ Min E > Min E+NS1), replicated more efficiently in insect cells than in mammalian cells, and demonstrated diminished virulence in a mouse model. In particular, Min E+NS1, the most restrictive variant, induced sterilizing immunity with a robust neutralizing antibody titer, and a single immunization achieved complete protection against lethal challenge and vertical ZIKV transmission during pregnancy. More importantly, due to the numerous synonymous substitutions in the codon pair-deoptimized strains, reversion to wild-type virulence through gradual nucleotide sequence mutations is unlikely. Our results collectively demonstrate that ZIKV can be effectively attenuated by codon pair deoptimization, highlighting the potential of Min E+NS1 as a safe vaccine candidate to prevent ZIKV infections.IMPORTANCE Due to unprecedented epidemics of Zika virus (ZIKV) across the Americas and the unexpected clinical symptoms, including Guillain-Barré syndrome, microcephaly, and other birth defects in humans, there is an urgent need for ZIKV vaccine development. Here we provided the first attenuated versions of ZIKV with two important genes (E and/or NS1) that were subjected to codon pair deoptimization. Compared to parental ZIKV, the codon pair-deoptimized ZIKVs were mammal attenuated and preferred insect to mammalian cells. Min E+NS1, the most restrictive variant, induced sterilizing immunity with a robust neutralizing antibody titer and achieved complete protection against lethal challenge and vertical virus transmission during pregnancy. More importantly, the massive synonymous mutational approach made it impossible for the variant to revert to wild-type virulence. Our results have proven the feasibility of codon pair deoptimization as a strategy to develop live attenuated vaccine candidates against flaviviruses such as ZIKV, Japanese encephalitis virus, and West Nile virus.

Optimal dose of pretreated-dexmedetomidine in fentanyl-induced cough suppression: a prospective randomized controlled trial.

BACKGROUND: To investigate the optimal dose of pretreated-dexmedetomidine in fentanyl-induced cough (FIC) suppression. METHODS: Patients of 180 undergoing elective surgery with general anesthesia, aged 18-65 years, BMI 18.5-30 kg/m2, ASA I or II, were equally randomized into four groups (n = 45) to receive intravenous pretreatment of dexmedetomidine with 0 (group 1), 0.3 (group 2), 0.6 (group 3) and 0.9 (group 4) mcg/kg over 10 mins, respectively. After the pretreatment, all patients were given a 5-s intravenous injection of fentanyl 4 mcg/kg. The symptoms of irritating cough including the severity and onset time were recorded for 1 min after fentanyl injection. General anesthesia induction was completed with midazolam, propofol and cisatracurium, then endotracheal tube or laryngeal mask was inserted and connected to an anesthesia machine. MAP, HR and SpO2 at the beginning of pretreatment (T0), 3 min (T1), 6 min (T2), 9 min (T3) and 12 min (T4) after the beginning of pretreatment were recorded. Side effects of dexmedetomidine, such as bradycardia, hypertension, hypotension, and respiratory depression were also recorded during the course. RESULTS: Totally 168 patients completed the study. The incidences of cough were 52.4, 42.9, 11.9, and 14.3% in groups 1, 2, 3, and 4, respectively, with no significant differences between groups 1 and 2 (P > 0.05) and between groups 3 and 4 (P > 0.05). The incidence and severity of cough in groups 3 and 4 were significantly lower than those in groups 1 and 2 (P < 0.05). Compared to T0, HR at T2 (P < 0.05), T3 (P < 0.01), and T4 (P < 0.01) decreased significantly and MAP at T4 decreased significantly (P < 0.05) in group 4. Bradycardia occurred in 1 case and respiratory depression occurred in 1 case in group 4. Compared to group 1, the onset time of cough in the other 3 groups were delayed significantly (P < 0.05). CONCLUSION: Pretreated dexmedetomidine 0.6 mcg/kg blous intravenous infusion over 10 mins could reduce FIC effectively without side effects. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (NCT03126422), April 13, 2017.

In-Fiber Closed Cavity Interferometric High-Resolution Aqueous Solution and Alcohol Gas Refractometer.

An optical fiber interferometric refractometer for alcohol gas concentration and low refractive index (RI) solution (with 1.33-1.38 RI range) measurement is theoretically and experimentally demonstrated. The refractometer is based on a single-mode thin-core single-mode (STS) interferometric structure. By embedding a suitably sized air cavity at the splicing point, high-order cladding modes are successfully excited, which makes the sensor more suitable for low RI solution measurement. The effect of the air cavity's diameter on the sensitivity of alcohol gas concentration was analyzed experimentally, which proved that RI sensitivity will increase with an enlarged diameter of the air cavity. On this basis, the air cavity is filled with graphene in order to improve the sensitivity of the sensor; and the measured sensitivity of the alcohol gas concentration is -1206.1 pm/%. Finally, the characteristics of the single-cavity structure, graphene-filled structure and double-cavity structure sensors are demonstrated, and the linear RI sensitivities are -54.593 nm/RIU (refractive index unit), -85.561 nm/RIU and 359.77 nm/RIU, respectively. Moreover, these sensor structures have the advantages of being compact and easily prepared.

ZIKV infection activates the IRE1-XBP1 and ATF6 pathways of unfolded protein response in neural cells.

BACKGROUND: Many viruses depend on the extensive membranous network of the endoplasmic reticulum (ER) for their translation, replication, and packaging. Certain membrane modifications of the ER can be a trigger for ER stress, as well as the accumulation of viral protein in the ER by viral infection. Then, unfolded protein response (UPR) is activated to alleviate the stress. Zika virus (ZIKV) is a mosquito-borne flavivirus and its infection causes microcephaly in newborns and serious neurological complications in adults. Here, we investigated ER stress and the regulating model of UPR in ZIKV-infected neural cells in vitro and in vivo. METHODS: Mice deficient in type I and II IFN receptors were infected with ZIKV via intraperitoneal injection and the nervous tissues of the mice were assayed at 5 days post-infection. The expression of phospho-IRE1, XBP1, and ATF6 which were the key markers of ER stress were analyzed by immunohistochemistry assay in vivo. Additionally, the nuclear localization of XBP1s and ATF6n were analyzed by immunohistofluorescence. Furthermore, two representative neural cells, neuroblastoma cell line (SK-N-SH) and astrocytoma cell line (CCF-STTG1), were selected to verify the ER stress in vitro. The expression of BIP, phospho-elF2α, phospho-IRE1, and ATF6 were analyzed through western blot and the nuclear localization of XBP1s was performed by confocal immunofluorescence microscopy. RT-qPCR was also used to quantify the mRNA level of the UPR downstream genes in vitro and in vivo. RESULTS: ZIKV infection significantly upregulated the expression of ER stress markers in vitro and in vivo. Phospho-IRE1 and XBP1 expression significantly increased in the cerebellum and mesocephalon, while ATF6 expression significantly increased in the mesocephalon. ATF6n and XBP1s were translocated into the cell nucleus. The levels of BIP, ATF6, phospho-elf2α, and spliced xbp1 also significantly increased in vitro. Furthermore, the downstream genes of UPR were detected to investigate the regulating model of the UPR during ZIKV infection in vitro and in vivo. The transcriptional levels of atf4, gadd34, chop, and edem-1 in vivo and that of gadd34 and chop in vitro significantly increased. CONCLUSION: Findings in this study demonstrated that ZIKV infection activates ER stress in neural cells. The results offer clues to further study the mechanism of neuropathogenesis caused by ZIKV infection.

Early detection of myocardial involvement by T1 mapping of cardiac MRI in idiopathic inflammatory myopathy.

BACKGROUND: Polymyositis (PM) and dermatomyositis (DM) are common types of idiopathic inflammatory myopathy (IIM), wherein patients are prone to adverse cardiovascular events. PURPOSE: To explore the value of cardiac magnetic resonance imaging (MRI) for detecting cardiac involvement in PM/DM patients using a T1 mapping technique. STUDY TYPE: Prospective observational study. POPULATION: In all, 25 PM/DM patients free of cardiovascular symptoms and preserved ventricular systolic function and 25 healthy volunteers matched for age and sex served as controls. FIELD STRENGTH/SEQUENCE: Cardiac MRI at 3T, including steady-state free precession (SSFP) cine imaging, late gadolinium enhancement (LGE), and T1 mapping with modified Look-Locker inversion recovery (MOLLI). ASSESSMENT: Myocardial native T1 and extracellular volume (ECV) of the left ventricle as well as the correlations with disease activity were analyzed. STATISTICAL TESTS: Independent sample's t-test, Fisher's exact test, or chi-square test, Pearson's correlation (r) were applied. P ≤ 0.05 was considered significant. RESULTS: Left ventricular end-diastolic/end-systolic volume index (P = 0.643, P = 0.325, respectively), mass index (P = 0.719), and ejection fraction (P = 0.144) were not significantly different between PM/DM patients and controls. LGE was found in 19% of PM/DM patients and none of the control subjects. PM/DM patients showed significantly higher native T1 values (1263.7 ± 84.0 msec vs. 1200.6 ± 43.0 msec, P = 0.002) and expanded extracellular volume (ECV) (32.6 ± 3.7% vs. 26.7 ± 2.3%, P < 0.001) compared with control subjects. ECV values in PM/DM patients had a high proportion (60%) over the 95% percentile of normal controls. Meanwhile, there was a significant correlation between native T1 (r = 0.710, P = 0.0001) or ECV (r = 0.508, P = 0.01) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP). DATA CONCLUSION: T1 mapping of cardiac MRI is valuable to detect subclinical myocardial involvement in PM/DM patients, and both myocardial native T1 and ECV could serve as early imaging markers for myocardial impairment in PM/DM. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2018;48:415-422.

Treatment for lupus nephritis: an overview of systematic reviews and meta-analyses.

The aim is to systematically review the treatment for lupus nephritis (LN) by performing an overview of systematic reviews and meta-analyses. Electronic databases of OVID MEDLINE, OVID EMBASE, and Cochrane Library were searched to identify published systematic reviews and meta-analyses investigating treatments for LN up to 13 July 2016. A measurement tool to assess systematic reviews (AMSTAR) was used to assess the quality of included studies. Totally, 24 studies were included. Of the eligible studies, 3 studies were rated as poor quality, 11 as moderate, and 10 as good. In LN induction therapy, comparing to cyclophosphamide, tacrolimus had higher complete remission rate, response rate, and anti-dsDNA negative conversion rate and led to lower risks of gastrointestinal symptoms and amenorrhea, and mycophenolate mofetil (MMF) was associated with higher response rate and less adverse events of leucopenia, alopecia, and ovarian failure. However, there was no difference in the efficacy and adverse events between tacrolimus and MMF. In LN maintenance therapy, the relapse rate and leucopenia rate were lower in MMF group than in azathioprine group, but there were no differences of end-stage kidney disease rate and mortality rate between the two groups. For LN induction therapy, both Tacrolimus and MMF are more effective and safer than cyclophosphamide, while there are no differences of efficacy or safety between the two treatments. For LN maintenance therapy, MMF seems to have less adverse events and lower relapse rate than azathioprine.

Bioconversion of lutein by Enterobacter hormaechei to form a new compound, 8-methyl-α-ionone.

OBJECTIVES: To investigate the final product of the bioconversion of lutein by a novel lutein-degrading bacterium, Enterobacter hormaechei A20, and the kinetics of the process. RESULTS: A new product, 8-methyl-α-ionone, was resolved by GC-MS. The compound was further identified by NMR. A conversion yield of 90% was achieved by E. hormaechei in 36 h with 10 g lutein l-1. CONCLUSIONS: This is the first report of the bioconversion of lutein to form 8-methyl-α-ionone. A degradation pathway is proposed.

Human cancer cells with stem cell-like phenotype exhibit enhanced sensitivity to the cytotoxicity of IL-2 and IL-15 activated natural killer cells.

Tumors harbor a population of cancer stem cells (CSCs) which can drive tumor progression and therapeutical resistance. Nature killer (NK) cells are best known for their ability to directly recognize and kill malignant cells. However, the susceptibility of cancer stem cells to NK cells is not fully understood. Here we demonstrated that human CD44+CD24- breast CSCs were shown enhanced sensitivity to IL-2 and IL-15 activated NK cells. CD44+CD24- CSCs expressed higher levels of NKG2D ligands ULBP1, ULBP2 and MICA. Blockade assay showed that the sensitivity of CSCs to NK cells-mediated lysis was mainly dependent on NKG2D. Furthermore, redox oxygen species (ROS)-low tumor cells were more sensitive to NK cells. The presence of antioxidant enzymes inhibitor L-S,R-buthionine sulfoximine or H2O2 retarded the cytotoxicity of NK cells to CD44+CD24- CSCs. In addition, NK cells could readily target CD133+ colonal CSCs. Our findings provide novel targets for NK cells-based immunotherapy and are of great importance for translational medicine.

Effects of pretreatment with different doses of cisatracurium on succinylcholine-induced fasciculations.

OBJECTIVE: To compare the effects of different doses of cisatracurium pretreatment on succinylcholine-induced fasciculations. METHODS: 90 patients scheduled for laparoscopic cholecystectomies were equally randomized into three groups to receive pretreatment of 0.005, 0.01, and 0.02 mg/kg cisatracurium, respectively. After the pretreatments, general anesthesia was induced 3.5 minutes later, train-of-four stimulation was monitored 4.5 minutes later, succinylcholine 1.5 mg/kg was injected 5 minutes later, and endotracheal intubation was implemented 6.5 minutes later. Side effects of cisatracurium, intensity of fasciculations, intubating conditions, time and extent to maximal depression of twitch and time for its recovery to 20% of control value, and severity of myalgia at 24 hours postoperatively were recorded. RESULTS: Fasciculations were alleviated significantly after the cisatracurium pretreatment of 0.02 mg/kg, more than with the other two doses (p < 0.01). Intubating conditions, time and extent to maximal depression of twitch, time for its recovery to 20% of the controls, and incidence of myalgia had no significant changes among the three groups (p > 0.05). Transient and tolerable diplopia and difficulty opening eyes emerged after pretreatment of 0.02 mg/kg cisatracurium. CONCLUSION: The pretreatment of 0.02 mg/kg cisatracurium given 5 minutes before succinylcholine injection could alleviate succinylcholine-induced fasciculations without influence on muscle relaxation effects or endotracheal intubating conditions, but did not affect the occurrence of myalgia, and might produce transient diplopia and difficulty opening eyes.

Diagnostic accuracy of combined tests of anti cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis: a meta-analysis.

OBJECTIVES: To evaluate the diagnostic properties of combined tests of anti cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor (RF) in the diagnosis of rheumatoid arthritis (RA). METHODS: We performed an extensive research between January 2000 and January 2013 of the published literature. A random-effects model was used to summarise data from 24 studies that conformed to our inclusion criteria. Heterogeneity among studies was evaluated by threshold effect analysis and meta-regression. RESULTS: The summary estimates for anti-CCP antibody and RF positivity (both serum markers had to be positive) in the diagnosis of RA were: sensitivity 57% (95% confidence interval (CI), 55% to 59%), specificity 96% (CI, 96% to 97%), positive likelihood ratio (LR) 13.84 (CI, 10.56 to 18.12), negative LR 0.46 (CI, 0.40 to 0.52), diagnostic odds ratio (DOR) 33.02 (CI, 23.89 to 45.64). The pooled data for anti-CCP antibody or RF positivity (one serum marker had to be positive) were: sensitivity 78% (CI, 76% to 80%), specificity 82% (CI, 81% to 84%), positive LR 4.24 (CI, 3.61 to 4.97), negative LR 0.27 (CI, 0.22 to 0.34), DOR 16.95 (CI, 12.96 to 22.18). CONCLUSIONS: Both anti-CCP antibody and RF positivity are useful for ruling in the diagnosis of RA, and positivity combined improves the probability of true positivity in the diagnosis. Anti-CCP antibody or RF positivity shows low specificity and positive LR, and should be integrated with other examinations to make a final diagnosis.