Mass-Spectrometry-Based Assay at Single-Base Resolution for Simultaneously Detecting m6A and m6Am in RNA.

The methylation modifications of adenosine, especially N6-methyladenosine (m6A) and N6, 2'-odimethyladenosine (m6Am), play vital roles in various biological, physiological, and pathological processes. However, current methods for detecting these modifications at single-base resolution have limitations. Mass spectrometry (MS), a highly accurate and sensitive technique, can be utilized to differentiate between m6A and m6Am by analyzing the molecular weight differences in their fragments during tandem MS analysis. In this study, we present an MS-based method that allows for the simultaneous determination of m6A and m6Am sites in targeted RNA fragments at single-nucleotide resolution. The approach involves the utilization of tandem MS in conjunction with targeted RNA enrichment and enzymatic digestion, eliminating the need for PCR amplification. By employing this strategy, we can accurately identify m6A and m6Am sites in targeted RNA fragments with high confidence. To evaluate the effectiveness of our method, we applied it to detect m6A and m6Am sites in cell and tissue samples. Furthermore, we verified the accuracy of our approach by performing CRISPR/Cas9-mediated knockout of the corresponding methyltransferases. Overall, our MS-based method offers a reliable and precise means for the simultaneous detection of m6A and m6Am modifications in targeted RNA fragments, providing valuable insights into the functional characterization of these modifications in various biological contexts.

An artificial intelligence model based on transrectal ultrasound images of biopsy needle tract tissues to differentiate prostate cancer.

PURPOSE: We aimed to develop an artificial intelligence (AI) model based on transrectal ultrasonography (TRUS) images of biopsy needle tract (BNT) tissues for predicting prostate cancer (PCa) and to compare the PCa diagnostic performance of the radiologist model and clinical model. METHODS: A total of 1696 2D prostate TRUS images were involved from 142 patients between July 2021 and May 2022. The ResNet50 network model was utilized to train classification models with different input methods: original image (Whole model), BNT (Needle model), and combined image [Feature Pyramid Networks (FPN) model]. The training set, validation set, and test set were randomly assigned, then randomized 5-fold cross-validation between the training set and validation set was performed. The diagnostic effectiveness of AI models and image combination was accessed by an independent testing set. Then, the optimal AI model and image combination were selected to compare the diagnostic efficacy with that of senior radiologists and the clinical model. RESULTS: In the test set, the area under the curve, specificity, and sensitivity of the FPN model were 0.934, 0.966, and 0.829, respectively; the diagnostic efficacy was improved compared with the Whole and Needle models, with statistically significant differences (P < 0.05), and was better than that of senior radiologists (area under the curve: 0.667). The FPN model detected more PCa compared with senior physicians (82.9% vs. 55.8%), with a 61.3% decrease in the false-positive rate and a 23.2% increase in overall accuracy (0.887 vs. 0.655). CONCLUSION: The proposed FPN model can offer a new method for prostate tissue classification, improve the diagnostic performance, and may be a helpful tool to guide prostate biopsy.

The Complement Component 4 Binding Protein α Gene: A Versatile Immune Gene That Influences Lipid Metabolism in Bovine Mammary Epithelial Cell Lines.

Complement component 4 binding protein α (C4BPA) is an immune gene which is responsible for the complement regulation function of C4BP by binding and inactivating the Complement component C4b (C4b) component of the classical Complement 3 (C3) invertase pathway. Our previous findings revealed that C4BPA was differentially expressed by comparing the transcriptome in high-fat and low-fat bovine mammary epithelial cell lines (BMECs) from Chinese Holstein dairy cows. In this study, a C4BPA gene knockout BMECs line model was constructed via using a CRISPR/Cas9 system to investigate the function of C4BPA in lipid metabolism. The results showed that levels of triglyceride (TG) were increased, while levels of cholesterol (CHOL) and free fatty acid (FFA) were decreased (p < 0.05) after knocking out C4BPA in BMECs. Additionally, most kinds of fatty acids were found to be mainly enriched in the pathway of the biosynthesis of unsaturated fatty acids, linoleic acid metabolism, fatty acid biosynthesis, and regulation of lipolysis in adipocyte. Meanwhile, the RNA-seq showed that most of the differentially expressed genes (DEGs) are related to PI3K-Akt signaling pathway. The expressions of 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 (HMGCS1), Carnitine Palmitoyltransferase 1A (CPT1A), Fatty Acid Desaturase 1 (FADS1), and Stearoyl-Coenzyme A desaturase 1 (SCD1) significantly changed when the C4BPA gene was knocked out. Collectively, C4BPA gene, which is an immune gene, played an important role in lipid metabolism in BMECs. These findings provide a new avenue for animal breeders: this gene, with multiple functions, should be reasonably utilized.

Rigid-Flexible Coupled Dendritic Molecule Doping: General Approach to Activate Commercial Polymers into Harsh Condition- Tolerant Multi-Reusable Strong Supramolecular Adhesives.

Developing functional adhesives combining strong adhesion, good recyclability and diverse harsh-condition adaptability is a grand challenge. Here, we introduce a general dendritic molecule doping strategy to activate commercial polymers into a new family of supramolecular adhesives integrating high adhesion strength, ultralow temperature, water resistant and multi-reusable properties. Our method involves rational design of a new rigid-flexible coupled dendritic molecule - M4C8OH as a versatile dopant, while simple M4C8OH doping into commercial polymers can modulate internal and external non-covalent interaction to enable H-bonding enhanced interchain cross-linking for tough cohesion along with enhanced interphase interaction. This endows 20 wt% M4C8OH-doped polycaprolactone (PCL) adhesives (PCL-M4C8OH) with improved adhesion strength on various substrates with the maximum increase up to 2.87 times that of PCL. In particular, the adhesion strengths of PCL-M4C8OH on polymethyl methacrylate at 25 °C and -196 °C reach 4.67 and 3.58 MPa - 1.9 and 2.3 times those of PCL and superior to diverse commercial adhesives and most reported adhesives. PCL-M4C8OH also displays markedly-improved multi-usability and tolerance against ultralow temperature and diverse wet environments. Mechanism studies reveal the crucial role of  M4C8OH molecular structures toward superior adhesion. Our method can be expanded to other polymer matrices, yielding diverse new supramolecular adhesives.

Robust, Ultrafast and Reversible Photoswitching in Bulk Polymers Enabled by Octupolar Molecule Design.

Improving the photoswitching rate and robustness of photochromic molecules in bulk solids is paramount for practical applications but remains an on-going challenge. Here, we introduce an octupolar design paradigm to develop a new family of visible light organic photoswitches, namely multi-branched octupolar Stenhouse Adducts (MOPSAs) featuring a C3-symmetrical A3-(D-core) architecture with a dipolar donor-acceptor (D-A) photochrome in each branch. Our design couples multi-dimensional geometric and electronic effects of MOPSAs to enable robust ultrafast reversible photoswitching in bulk polymers. Specifically, the optimal MOPSA (4 wt %) in commercial polyurethane films accomplishes nearly 100 % discoloration in 6 s under visible light with ∼ 100 % thermal-recovery in 17.4 s at 60 °C, while the acquired kinetics constants are 3∼7 times that of dipolar DASA counterpart and 1∼2 orders of magnitude higher than those of reported DASAs in polymers. Importantly, the MOPSA-doped polymer films sustain 500 discoloration/recovery cycles with slow degradation, superior to the existing DASAs in polymers (≤30 cycles). We discover that multi-dipolar coupling in MOPSA enables enhanced polarization and electron delocalization, promoting the rate-determining thermal cyclization, while the branched and non-planar geometry of MOPSA induces large free volume to facilitate the isomerization. This design can be extended to develop spiropyran or azobenzene-based ultrafast photochromic films. The superior photoswitching performance of MOPSAs together with their high-yield and scalable synthesis and facile film processing inspires us to explore their versatile uses as smart inks or labels for time-temperature indicators, optical logic encryption and multi-levelled data encryption.

Appendicitis in pregnant women: A systematic review and meta-analysis of the diagnostic performance of ultrasonography.

OBJECTIVES: The accuracy of ultrasound in the detection of appendicitis in pregnant women was examined in a meta-analysis. METHODS: Pregnant women with suspected acute appendicitis were evaluated using ultrasound in a systematic search of PubMed, EMBASE, and Cochrane Library databases from January 1, 2011 to August 10, 2023. The sensitivity and specificity values and diagnostic odds ratios were obtained using the pooled data. RESULTS: A total of 239 patients were studied in four relevant investigations. Ultrasonography has a sensitivity of 56% and a specificity of 88% for the diagnosis of acute appendicitis, with an area under the receiver operating characteristic curve of 0.66%. Ultrasonography had a positive likelihood ratio of 4.65 (95% confidence interval, 1.42-15.23) and a negative likelihood ratio of 0.50 (95% confidence interval, 0.41-0.62). There was no evidence of publication bias (p = 0.93). CONCLUSIONS: Ultrasound has moderate sensitivity for identifying appendicitis in pregnant women and may be utilized as an alternative diagnostic method.

Tuning the Metal Ions of Prussian Blue Analogues in Separators to Enable High-Power Lithium Metal Batteries.

The Li dendrite issue is the major barrier that limits the implement of Li metal anode practically, especially at high current density. From the perspective of the nucleation and growth mechanism of the Li dendrite, we rationally develop a novel Prussian blue analogues (PBA)-derived separator, where tuning the metal ions bestows the PBAs with open metal site to confine anion movement and thereby afford a high Li+ transference number (0.78), and PBA with ordered micropores could act as an ionic sieve to selectively extract Li+ and thereby homogenize Li+ flux. This demonstrates a highly reversible Li plating/stripping cycling for 3000 h at a practically high current density (5.0 mA cm-2). Consequently, a high loading Li||LiFeO4 battery (∼10.0 mg cm-2) demonstrates ultralong cycling life at high current densities (∼5.1 mA cm-2). This work highlights the prospect of optimizing PBAs in regulating ion transport behavior to enable high-power Li metal batteries.

[Therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea in rats and its metabolomic analysis].

This study aimed to investigate the therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea(PD) and explore the underlying mechanism in conjunction with untargeted metabolomics. Forty adult female rats were randomly divi-ded into a normal group, a model control group, ibuprofen(0.12 g·kg~(-1)) group, and high-and low-dose Leonuri Herba aqueous decoction(5 and 2.5 g·kg~(-1)) groups, with eight rats in each group. The PD rat model was prepared using intramuscular injection of estradiol benzoate combined with intraperitoneal injection of pitocin. Drugs were administered by gavage from the 4th day of modeling for 7 d. After the last administration, pitocin was injected intraperitoneally, and the writhing latency and writhing times within 30 min were recorded. The uterine and ovarian coefficients were determined. Estradiol(E_2), progesterone(Prog), oxytocin(OT), cyclooxyge-nase 2(COX-2), prostaglandin E_2(PGE_2), prostaglandin F_(2α)(PGF_(2α)), and Ca~(2+) levels in uterine tissues were measured by ELISA and biochemical kits. Morphological changes in uterine and ovarian tissues were observed by hematoxylin-eosin(HE) staining. The protein expression of oxytocin receptor(OTR), prostaglandin E_2 receptor 3(EP3), and estrogen receptor alpha(ERα) in uterine tissues was detected by immunohistochemistry. The mRNA expression of OTR, PGE_2 receptors 1-4(EP1, EP2, EP3, and EP4), and PGF_(2α) receptor(FP) in uterine tissues was detected by quantitative real-time PCR. Untargeted metabolomics analysis was performed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-QTOF-MS) technology to screen potential biomarkers and enrich metabolic pathways. The results showed that Leonuri Herba was able to significantly reduce the writhing times in PD rats(P<0.05 or P<0.01), significantly reduce the uterine and ovarian coefficients(P<0.01), and improve their histomorphology. After treatment with Leonuri Herba, PGE_2 content was significantly increased(P<0.05), COX-2, PGF_(2α) and Ca~(2+) content, and PGF_(2α)/PGE_2 was significantly decreased(P<0.05 or P<0.01), and OT content was decreased, while E_2 and Prog content tended to further increase in uterine tissues of PD rats. Correspondingly, OTR and EP3 protein expression was significantly downregulated(P<0.05 or P<0.01) and ERα protein expression was upregulated(P<0.05) in uterine tissues. The mRNA expression of FP and EP4 in uterine tissues was significantly downregulated(P<0.01), and the mRNA expression of EP1, EP3, and OTR showed a decreasing trend. The untargeted metabolomics results showed that 10 differential metabolites were restored in the plasma of PD rats after Leonuri Herba treatment. The results indicate that Leonuri Herba is effective in the prevention and treatment of PD, and the underlying mechanism may be attributed to the regulation of PGs synthesis and corresponding receptor binding.

1.7 µm figure-9 Tm-doped ultrafast fiber laser.

The evolution of multiphoton microscopy is critically dependent on the development of ultrafast laser technologies. The ultrashort pulse laser source at 1.7 µm waveband is attractive for in-depth three-photon imaging owing to the reduced scattering and absorption effects in biological tissues. Herein, we report on a 1.7 µm passively mode-locked figure-9 Tm-doped fiber laser. The nonreciprocal phase shifter that consists of two quarter-wave plates and a Faraday rotator introduces phase bias between the counter-propagating beams in the nonlinear amplifying loop mirror. The cavity dispersion is compensated to be slightly positive, enabling the proposed 1.7 µm ultrafast fiber laser to deliver the dissipative soliton with a 3-dB bandwidth of 20 nm. Moreover, the mode-locked spectral bandwidth could be flexibly tuned with different phase biases by rotating the wave plates. The demonstration of figure-9 Tm-doped ultrafast fiber laser would pave the way to develop the robust 1.7 µm ultrashort pulse laser sources, which could find important application for three-photon deep-tissue imaging.

The relationship between Lipocalin-2 level and hepatic steatosis in obese patients with NAFLD after bariatric surgery.

BACKGROUND: Lipocalin-2 (LCN2) has a critical effect on obesity as well as its associated comorbidities. The present study focused on analyzing serum LCN2 levels of obese patients with nonalcoholic fatty liver disease (NAFLD) and on determining relationship of hepatic steatosis improvement with LCN2 levels after laparoscopic sleeve gastrectomy (LSG). METHODS: This work enrolled ninety patients with obesity and NAFLD. Twenty-three of them underwent LSG. Anthropometric and biochemical parameters and serum LCN2 levels were determined at baseline and those at 6-month post-LSG. Controlled attenuation parameter (CAP) measured by FibroScan was adopted for evaluating hepatic steatosis. RESULTS: Among severe obesity patients, serum LCN2 levels were significantly increased (111.59 ± 51.16 ng/mL vs. 92.68 ± 32.68 ng/mL, P = 0.035). The CAP value was higher indicating higher liver fat content (360.51 ± 45.14 dB/m vs. 340.78 ± 45.02 dB/m, P = 0.044). With regard to surgical patients, liver function, glucose, and lipid levels were significantly improved after surgery. Serum LCN2 levels significantly decreased (119.74 ± 36.15 ng/mL vs. 87.38 ± 51.65 ng/mL, P = 0.001). Decreased CAP indicated a significant decrease in liver fat content (358.48 ± 46.13 dB/m vs. 260.83 ± 69.64 dB/m, P < 0.001). The decrease in LCN2 levels was significantly related to the reduced hepatic fat content and improvement in steatosis grade after adjusting for gender, age, and BMI decrease. CONCLUSIONS: Serum LCN2 levels are related to obesity and NAFLD. The decreased serum LCN2 levels could be an indicator of hepatic steatosis improvement.

Anti-Inflammatory Activity of Mulberry Leaf Flavonoids In Vitro and In Vivo.

Mulberry (Morus alba L.) is a flowering tree traditionally used in Chinese herbal medicine. Mulberry leaf flavonoids (MLFs) have been reported to exert important anti-inflammatory and antioxidant properties. The purpose of this study was to select the MLF with the best anti-inflammatory and antioxidative activities from MLFs eluted by different ethanol concentrations (30%, 50%, and 75%) and explore its pharmacological properties. Three types of MLFs inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines in lipopolysaccharide (LPS)-induced RAW 264.7 cells. All MLFs boosted the antioxidative capacity by decreasing the reactive oxygen species (ROS) production and the scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and improving the metal ion chelating activity and reducing power. The results revealed that the MLFs eluted by 30% ethanol exhibited the best anti-inflammatory and antioxidative activities. A nontargeted metabolomic analysis was used to analyze 24 types of differential flavonoids between the MLFs. Quercetin, kaempferol, and their derivatives in 30%MLF were more abundant than the other two MLFs. Furthermore, we evaluated the pharmacological activities of 30%MLF in dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) mice. The 30%MLF could alleviate the clinical symptoms, reduce the secretion of inflammatory cytokines, and inhibit the activation of the inflammatory pathway in DSS-induced colitis mice. This study will provide valuable information for the development of MLFs eluted by 30% ethanol as a functional food.

Advantage of Using of High-Sensitivity Troponin I Compared to Conventional Troponin I in Shortening Time to Rule out/in Acute Coronary Syndrome in Chest Pain Patients Presenting to the Emergency Department.

Background and Objectives: We aimed to compare the time to diagnosis for acute coronary syndromes using high-sensitivity troponin I (hsTnI) and conventional troponin I (TnI) in patients presenting to the emergency department (ED) with chest pain. Materials and Methods: This was an observational prospective study involving patients presenting to the ED of Sant'Andrea Hospital University la Sapienza in Rome (Italy) with chest pain from January to December 2014. Serum troponin was drawn at presentation, and at 3, 6, 9, and/or 12 h if clinically indicated. Depending on date of recruitment, patients had either hsTnI (Abbott Laboratories) or TnI (Abbott Laboratories) performed. The primary endpoint was the time to diagnosis at index visit. Results: A total of 1059 patients were recruited, (673 [63.6%] male, median age 60 years [interquartile range 49−73 years]), out of whom 898 (84.8%) patients were evaluated with hsTnI and 161 (15.2%) with TnI. A total of 393 (37.1%) patients had the diagnosis of acute coronary syndrome in ED. The median time to diagnosis for those evaluated with TnI was 400 min, IQR 120−720 min, while the use of hsTnI led to a significantly shorter time to diagnosis (median 200 min, IQR 100−200 min, p < 0.001). Conclusions: This study confirms that in patients presenting to the emergency department with chest pain, the use of hsTnI is associated with a reduced time to ruling in/out ACS, and, consequently, hsTnI should be routinely used over TnI for more rapid identification of ACS with benefits for patients and related costs.

Comparative Proteomic Analysis of Tolerant and Sensitive Varieties Reveals That Phenylpropanoid Biosynthesis Contributes to Salt Tolerance in Mulberry.

Mulberry, an important woody tree, has strong tolerance to environmental stresses, including salinity, drought, and heavy metal stress. However, the current research on mulberry resistance focuses mainly on the selection of resistant resources and the determination of physiological indicators. In order to clarify the molecular mechanism of salt tolerance in mulberry, the physiological changes and proteomic profiles were comprehensively analyzed in salt-tolerant (Jisang3) and salt-sensitive (Guisangyou12) mulberry varieties. After salt treatment, the malondialdehyde (MDA) content and proline content were significantly increased compared to control, and the MDA and proline content in G12 was significantly lower than in Jisang3 under salt stress. The calcium content was significantly reduced in the salt-sensitive mulberry varieties Guisangyou12 (G12), while sodium content was significantly increased in both mulberry varieties. Although the Jisang3 is salt-tolerant, salt stress caused more reductions of photosynthetic rate in Jisang3 than Guisangyou12. Using tandem mass tags (TMT)-based proteomics, the changes of mulberry proteome levels were analyzed in salt-tolerant and salt-sensitive mulberry varieties under salt stress. Combined with GO and KEGG databases, the differentially expressed proteins were significantly enriched in the GO terms of amino acid transport and metabolism and posttranslational modification, protein turnover up-classified in Guisangyou12 while down-classified in Jisang3. Through the comparison of proteomic level, we identified the phenylpropanoid biosynthesis may play an important role in salt tolerance of mulberry. We clarified the molecular mechanism of mulberry salt tolerance, which is of great significance for the selection of excellent candidate genes for saline-alkali soil management and mulberry stress resistance genetic engineering.

Flow-Controlled Ventilation Attenuates Lung Injury in a Porcine Model of Acute Respiratory Distress Syndrome: A Preclinical Randomized Controlled Study.

OBJECTIVES: Lung-protective ventilation for acute respiratory distress syndrome aims for providing sufficient oxygenation and carbon dioxide clearance, while limiting the harmful effects of mechanical ventilation. "Flow-controlled ventilation", providing a constant expiratory flow, has been suggested as a new lung-protective ventilation strategy. The aim of this study was to test whether flow-controlled ventilation attenuates lung injury in an animal model of acute respiratory distress syndrome. DESIGN: Preclinical, randomized controlled animal study. SETTING: Animal research facility. SUBJECTS: Nineteen German landrace hybrid pigs. INTERVENTION: Flow-controlled ventilation (intervention group) or volume-controlled ventilation (control group) with identical tidal volume (7 mL/kg) and positive end-expiratory pressure (9 cm H2O) after inducing acute respiratory distress syndrome with oleic acid. MEASUREMENTS AND MAIN RESULTS: PaO2 and PaCO2, minute volume, tracheal pressure, lung aeration measured via CT, alveolar wall thickness, cell infiltration, and surfactant protein A concentration in bronchoalveolar lavage fluid. Five pigs were excluded leaving n equals to 7 for each group. Compared with control, flow-controlled ventilation elevated PaO2 (154 ± 21 vs 105 ± 9 torr; 20.5 ± 2.8 vs 14.0 ± 1.2 kPa; p = 0.035) and achieved comparable PaCO2 (57 ± 3 vs 54 ± 1 torr; 7.6 ± 0.4 vs 7.1 ± 0.1 kPa; p = 0.37) with a lower minute volume (6.4 ± 0.5 vs 8.7 ± 0.4 L/min; p < 0.001). Inspiratory plateau pressure was comparable in both groups (31 ± 2 vs 34 ± 2 cm H2O; p = 0.16). Flow-controlled ventilation increased normally aerated (24% ± 4% vs 10% ± 2%; p = 0.004) and decreased nonaerated lung volume (23% ± 6% vs 38% ± 5%; p = 0.033) in the dependent lung region. Alveolar walls were thinner (5.5 ± 0.1 vs 7.8 ± 0.2 µm; p < 0.0001), cell infiltration was lower (20 ± 2 vs 32 ± 2 n/field; p < 0.0001), and normalized surfactant protein A concentration was higher with flow-controlled ventilation (1.1 ± 0.04 vs 1.0 ± 0.03; p = 0.039). CONCLUSIONS: Flow-controlled ventilation enhances lung aeration in the dependent lung region and consequently improves gas exchange and attenuates lung injury. Control of the expiratory flow may provide a novel option for lung-protective ventilation.

Primary nitrate responses mediated by calcium signalling and diverse protein phosphorylation.

Nitrate, the major source of inorganic nitrogen for plants, is a critical signal controlling nutrient transport and assimilation and adaptive growth responses throughout the plant. Understanding how plants perceive nitrate and how this perception is transduced into responses that optimize growth are important for the rational improvement of crop productivity and for mitigating pollution from the use of fertilizers. This review highlights recent findings that reveal key roles of cytosolic-nuclear calcium signalling and dynamic protein phosphorylation via diverse mechanisms in the primary nitrate response (PNR). Nitrate-triggered calcium signatures as well as the critical functions of subgroup III calcium-sensor protein kinases, a specific protein phosphatase 2C, and RNA polymerase II C-terminal domain phosphatase-like 3 are discussed. Moreover, genome-wide meta-analysis of nitrate-regulated genes encoding candidate protein kinases and phosphatases for modulating critical phosphorylation events in the PNR are elaborated. We also consider how phosphoproteomics approaches can contribute to the identification of putative regulatory protein kinases in the PNR. Exploring and integrating experimental strategies, new methodologies, and comprehensive datasets will further advance our understanding of the molecular and cellular mechanisms underlying the complex regulatory processes in the PNR.

Circulating osteocalcin: A potential predictor of ketosis in type 2 diabetes.

AIMS: Osteocalcin contributes to the regulation of endocrine system. However, the association between osteocalcin and ketosis has not been evaluated. We thus aimed to explore the relationship between total osteocalcin and risk of ketosis in type 2 diabetes (T2DM). MATERIALS AND METHODS: We identified 6157 diabetes patients from Shanghai Tenth People's Hospital between 1 January 2011 and 1 March 2017. Six hundred eight subjects were enrolled in the retrospective cross-sectional study: 304 T2DM patients with ketosis whose age, gender, and body mass index were matched with 304 T2DM patients without ketosis. A further retrospective nested case-control study was conducted in 252 T2DM patients without ketosis for a mean duration of 21.58 ± 12.43 months to investigate the occurrence of ketosis. RESULTS: Osteocalcin levels were negatively correlated with blood ketones (adjusted r = -0.263) and urine ketones (adjusted r = -0.183). The inverse dose-dependent relationship of osteocalcin and risk of ketosis was present across osteocalcin level quintiles (top quintile as the reference, adjusted odds ratio [95% CI] = 2.56 [0.80-8.17], 3.71 [0.90-15.29], 10.77 [2.63-44.15], 23.81 [4.32-131.17] per osteocalcin quintile, respectively). Ketosis occurred in 17 of the 252 T2DM patients during follow-up. The Cox regression analysis indicated that osteocalcin was an independent protective factor against development of ketosis (adjusted hazard ratio [95% CI]: 0.668 [0.460-0.971]). CONCLUSIONS: Total osteocalcin can be used as a predictor of ketosis in T2DM.

Liuweibuqi capsules improve pulmonary function in stable chronic obstructive pulmonary disease with lung-qi deficiency syndrome by regulating STAT4/STAT6 and MMP-9/TIMP-1.

Context: Liuweibuqi (LWBQ) capsule has been reported to influence symptoms of patients with chronic obstructive pulmonary disease (COPD); however, specific function of LWBQ capsules in COPD with lung-qi deficiency syndrome remains elusive.Objective: This study investigates effect of LWBQ capsules on STAT4/STAT6 and MMP-9/TIMP-1 expression and pulmonary function in stable COPD with lung-qi deficiency syndrome.Materials and methods: Totally, 429 patients diagnosed with stable COPD and lung-qi deficiency syndrome were treated with starch capsules (each time for 9 capsules), or different doses: low (each dose for 8 capsules and 1 LWBQ capsules), medium (each time for 6 capsules and 3 LWBQ capsules), or high (each time for 9 LWBQ capsules) of LWBQ capsules for 30 days, 3 times a day. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC% and DLco%pred were evaluated by pulmonary function meter. STAT4/STAT6 and MMP-9/TIMP-1 expression was assessed by RT-qPCR and western blot analysis, and serum concentrations of IL-4, IFN-γ and IL-6 by ELISA.Results: Spearman rank correlation analysis and ROC curve showed that STAT4/STAT6 and MMP-9/TIMP-1 affected pulmonary functions and curative effect of stable COPD with lung-qi deficiency syndrome. After LWBQ capsule treatment, FEV1, FVC, FEV1/FVC% and DLco%pred elevated; STAT4/STAT6, MMP-9/TIMP-1, IFN-γ and IL-6 expression declined whereas IL-4 expression increased (p < 0.05). Logistic regression analysis demonstrated that FEV1/FVC was negatively correlated with STAT4/STAT6 and MMP-9/TIMP-1 expression in COPD patients.Conclusions: LWBQ capsules play a beneficial role in pulmonary function of stable COPD with lung-qi deficiency syndrome via STAT4/STAT6 and MMP-9/TIMP-1.

Risk Factors for Emergency Department Unscheduled Return Visits.

BACKGROUND AND OBJECTIVES: This study aims to identify reasons for unscheduled return visits (URVs), and risk factors for diagnostic errors leading to URVs, with comparisons to data from a similar study conducted in the same institution 9 years ago. MATERIALS AND METHODS: This retrospective study included adult patients who attended the emergency department (ED) of a tertiary hospital in Singapore between January 2014 and June 2014, with re-attendance within 72 h for the same or similar complaint. The primary outcome was wrong or delayed diagnoses. Secondary outcomes include admission to the ED observation unit or ward on return visit. Findings were compared with the previous study performed in 2005 to identify trends. RESULTS: Of 67,422 attendances, there were 1298 (1.93%) URVs from 1207 patients (median age 34, interquartile range 24 to 52 years; 59.7% male). The most common presenting complaint was abdominal pain (22.2%). One hundred ninety-one (15.8%) patients received an initial wrong or delayed diagnosis. Factors (adjusted odds ratio; 95% CI) associated with this were: presenting complaints of abdominal pain (2.99; 2.12-4.23), fever (1.60; 1.1-2.33), neurological deficit (4.26; 1.94-9.35), and discharge without follow-up (1.61; 1.1-2.26). Among re-attendances, 459 (38.0%) required admission. Factors (adjusted odds ratio; 95% CI) associated with admission were: male gender (1.88; 1.42 to 2.48); comorbidities of diabetes mellitus (2.07; 1.29-3.31), asthma (5.23; 1.59-17.26), and renal disease (7.48; 2.00-28.05); presenting complaints of abdominal pain (1.83; 1.32-2.55), fever (3.05; 2.10-4.44), and giddiness or vertigo (2.17; 1.26-3.73). There was a reduction in URV rate compared to the previous study in 2005 (1.93% versus 2.19%). Abdominal pain at the index visit remains a significant cause of URVs (22.2% versus 25.1%). CONCLUSIONS: Presenting complaints of neurological deficits, abdominal pain, fever, and discharge without follow-up were associated with wrong or delayed diagnoses among URVs.

Importance of Isobar Density Distributions on the Chiral Magnetic Effect Search.

Under the approximate chiral symmetry restoration, quark interactions with topological gluon fields in quantum chromodynamics can induce a chirality imbalance and parity violation in local domains. An electric charge separation (CS) could be generated along the direction of a strong magnetic field (B), a phenomenon called the chiral magnetic effect (CME). CS measurements by azimuthal correlators are contaminated by major backgrounds from elliptic flow anisotropy (v_{2}). Isobaric _{44}^{96}Ru+_{44}^{96}Ru and _{40}^{96}Zr+_{40}^{96}Zr collisions have been proposed to identify the CME (expected to differ between the two systems) out of the backgrounds (to be almost the same). We show, by using the density functional theory calculations of the proton and neutron distributions, that these expectations may not hold as originally anticipated because the two systems may have sizable differences in eccentricity and v_{2}.