Exosomal transfer of activated neutrophil-derived lncRNA CRNDE promotes proliferation and migration of airway smooth muscle cells in asthma.

Activated neutrophil-derived exosomes reportedly contribute to the proliferation of airway smooth muscle cells (ASMCs), thereby aggravating the airway wall remodeling during asthma; however, the specific mechanism remains unclear. Lipopolysaccharide (LPS)-EXO and si-CRNDE-EXO were extracted from the media of human neutrophils treated with LPS and LPS + si-CRNDE (a siRNA targets long non-coding RNA CRNDE), respectively. Human ASMCs were co-cultured with LPS-EXO or si-CRNDE-EXO, and cell viability, proliferation and migration were measured. The interplay of colorectal neoplasia differentially expressed (CRNDE), inhibitor of nuclear factor kappa B kinase subunit beta (IKKß) and nuclear receptor subfamily 2 group C member 2 (TAK1) was explored using RNA immunoprecipitation (RIP) and Co-IP assays. A mouse model of asthma was induced using ovalbumin. CRNDE was upregulated in LPS-EXO and successfully transferred from LPS-treated neutrophils to ASMCs through exosome. Mechanically, CRNDE loaded in LPS-EXO reinforced TAK1-mediated IKKß phosphorylation, thereby activating the nuclear factor kappa B (NF-κB) pathway. Functionally, silencing CRNDE in LPS-EXO, an IKKß inhibitor, and an NF-κB inhibitor all removed the upregulation of cell viability, proliferation and migration induced by LPS-EXO in ASMCs. In the end, the in vivo experiment demonstrated that CRNDE knockdown in neutrophils effectively reduced the thickness of bronchial smooth muscle in a mouse model for asthma. Activated neutrophils-derived CRNDE was transferred to ASMCs through exosomes and activated the NF-κB pathway by enhancing IKKß phosphorylation. The latter promoted the proliferation and migration of ASMCs and then contributed to airway remodeling in asthma.

A phase IV study to evaluate the safety of fruquintinib in Chinese patients in real-world clinical practice.

INTRODUCTION: Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. METHODS: Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). RESULTS: Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. CONCLUSIONS: The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting.

Exogenous indole-3-acetic acid promotes the plant growth and accumulation of selenium in grapevine under selenium stress.

To alleviate the selenium (Se) stress in fruit trees and improve its accumulation, the effects of exogenous indole-3-acetic acid (IAA) on the growth and Se accumulation of grapevine under Se stress were studied. The application of exogenous IAA increased the biomass of grapevine, and the concentration of exogenous IAA had a regression relationship with the biomass. The root and shoot biomass were the maximum at 60 mg L- 1 IAA, increasing by 15.61% and 23.95%, respectively, compared with the control. Exogenous IAA also increased the photosynthetic pigments and the activities of superoxide dismutase and peroxidase in grapevine. Moreover, exogenous IAA increased the contents of total Se, organic Se, and inorganic Se, and the concentration of exogenous IAA had a regression relationship with the total Se content. The highest contents of root total Se and shoot total Se were accumulated at 90 mg L- 1 IAA, increasing by 29.94% and 55.77% respectively,. In addition, the correlation and path analyses revealed that the carotenoid content and root total Se content were closely associated with the shoot total Se content. Therefore, the application of exogenous IAA can alleviate the stress of Se to grape and promote its uptake and the most effective amount for the uptake of Se is 90 mg L- 1 IAA.

A Comparative Study of the Effects of Electronic Cigarette and Traditional Cigarette on the Pulmonary Functions of C57BL/6 Male Mice.

INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.

The W-Plasty Serial Excision Method for Treating Medium Congenital Melanocytic Nevi: A Retrospective Analytical Study.

BACKGROUND: Serial excision remains the most commonly used surgical procedure for treating congenital melanocytic nevus (CMN). It is critical to remove as much of the lesion as possible with each procedure to reduce the number of procedures and to shorten the treatment duration. OBJECTIVE: To investigate the clinical efficacy of W-plasty serial excision for the repair of postoperative CMN defects. METHODS: A retrospective analysis of patients with medium CMN was conducted from April 2018 to March 2022. Treatment options were divided into elliptical serial excision (10 cases) and W-plasty serial excision (10 cases). RESULTS: Follow-up occurred over 6 months. The number of elliptical excision procedures was 2 to 4 (mean 2.9). The scar-to-lesion length ratio was 1.5 to 2.0 (mean 1.7). The mean Vancouver Scar Scale (VSS) score was 5.40 ± 0.42. The number of W-plasty excision procedures was 2 to 3 (mean 2.2). The scar-to-lesion length ratio was 1.2 to 1.5 (mean 1.4). The mean VSS score was 2.70 ± 0.26. W-plasty excision was superior to elliptical excision regarding the number of procedures and the effect on postoperative scars. CONCLUSION: W-plasty serial excision can be considered a suitable option for the excision of medium CMN, leading to excellent results.

Fabrication of Flower-like Rhodium-Doped ß-Ni(OH)2 as an Efficient Electrocatalyst for Methanol Oxidation Reaction in Alkaline Media.

In this study, ß-Ni(OH)2 with a unique flower-like morphology was synthesized through a hydrothermal method. The doping of Rh in ß-Ni(OH)2 was achieved by a reduction method. The as-synthesized catalysts were characterized by X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy for the crystal structure, morphology, composition, and chemical state analysis. The electrochemical tests revealed that the doping of Rh can significantly increase the electrocatalytic performance of ß-Ni(OH)2 in 1.0 M KOH solution. The methanol oxidation peak current density of Rh-doped ß-Ni(OH)2 reached 95 mA cm-2 with a Tafel slope of 40 mV dec-1. The reason for these improvements is that Rh can suppress the phase transformation of NiOOH from ß to α. Meanwhile, the electronic structure change of nickel in ß-Ni(OH)2 and the defect ratio increase caused by Rh doping are beneficial to methanol oxidation reaction (MOR) catalytic activity. Furthermore, the synergistic effect between Rh and Ni(OH)2 improved the surface activity of ß-NiOOH. The doping of Rh in ß-Ni(OH)2 is initiative in this work, which provides a new strategy to design highly efficient and cost-effective MOR electrocatalysts for alkaline DMFCs.

The platform development, adherence and efficacy to a digital Brief therapy for insomnia (dBTI) during the COVID-19 pandemic.

Brief therapy for insomnia (BTI) is a short-term cognitive behavioral therapy for insomnia. At present, there is no study combining BTI with digital technology. However, in the context of the outbreak of coronavirus disease 2019 (COVID-19), patients with acute insomnia may need an online treatment which can quickly improve insomnia symptoms. Our team built a digital BTI (dBTI) platform based on the WeChat mini program. This research provides a framework design and a course design of dBTI, and evaluates the system via recruiting participants suffering from acute insomnia in pandemic. What's more, it explores patients' adherence, the efficiency of the system and their relationship. As the result demonstrates, 68% of participants have completed more than half of the course with medium to high adherence. Gender, pre-sleep arousal scale (PSAS) somatic score and insomnia severity index (ISI) score have affected participants' adherence, and higher adherence has led to better improvement in the severity of insomnia and somatic pre-sleep arousal. It is proved that the platform we built is effective, which not only offers an entry point for the study of how to set up a dBTI platform, but also provides theoretical basis for its clinical application.

Impact of Hemodialysis on Left Ventricular-Arterial Coupling in End-Stage Renal Disease Patients.

INTRODUCTION: As a key determinant of cardiovascular performance, vascular-arterial coupling (VAC) has been reported to be a predictor of clinical outcomes in various clinical scenarios. However, few studies have explored how acute fluid removal during hemodialysis (HD) impacts the interaction between cardiac function and the arterial system. METHODS: We recruited 317 HD patients from an established renal dialysis unit for this cross-sectional study and a total of 285 were included in the final analyses. We measured left ventricle end-systolic elastance (Ees), the effective arterial elastance (Ea), and VAC before and after HD using noninvasive echocardiographic measurements. We also compared echocardiographic and hemodynamic parameters in ventriculo-arterial coupling and ventriculo-arterial uncoupling patients. RESULTS: HD significantly altered partial ventricular and vascular function parameters such as blood pressure, left ventricular end-diastolic volume, stroke volume, left ventricular ejection fraction, and systemic vascular resistance index. Ea increased following HD from 3.5 ± 1.4 to 4.2 ± 1.8 mm Hg/mL (p < 0.0001), Ees increased following HD from 7.9 ± 5.5 to 9.2 ± 6.9 mm Hg/mL (p = 0.04), whereas VAC did not markedly alter as a result of HD. Ventriculo-arterial uncoupling was found to be related to abnormal cardiac structure and worse systolic function. CONCLUSIONS: VAC obtained from echocardiography is likely to be load-independent and useful as a reliable index for stratifying the risk of cardiovascular diseases in HD patients. Further investigations on larger patient cohorts are needed to further validate our findings.

Effects of L-Cysteine and γ-Aminobutyric Acid Treatment on Postharvest Quality and Antioxidant Activity of Loquat Fruit during Storage.

Sichuan is the China's leading producer of loquat, with the largest cultivation area and yield ranked first in China. Loquat is a seasonal fruit highly appreciated by consumers; however, the fruit is prone to browning and lignification after harvest, affecting its storage quality. The effects of L-Cysteine (L-Cys, 0.01, 0.05, 0.1, 0.2%) and γ-aminobutyric acid (GABA, 0.025, 0.05, 0.075, 0.1%) on the sensory quality and antioxidant activity of loquat fruit during cold storage at 4 °C for 35 days and simulated shelf life for 5 days were investigated. The results showed that after 40 days of storage, compared with the control, 0.05% L-Cys and 0.05% GABA treatment of 'Zaozhong No. 6' loquat fruit effectively reduced the weight loss rate, browning index, decay index, respiratory rate, firmness, and lignin content and slowed the decreases in total soluble solids, soluble sugar, titratable acidityand vitamin C contents. The application of 0.05% L-Cys and 0.05% GABA significantly increased the contents of total phenols, total flavonoids, flavanols, and carotenoids; delayed the increase of relative electric conductivity, MDA, POD, and PPO activities; and significantly enhanced the activities of SOD and CAT, DPPH free radical scavenging ability, and FRAP, thereby improving antioxidant capacity. In summary, 0.05% L-Cys and 0.05% GABA treatment promotes the quality of loquat fruit after 40 days of storage, and significantly enhances antioxidant capacity, thus delaying senescence after harvest.

Baseline radiologic features as predictors of efficacy in patients with pancreatic neuroendocrine tumors with liver metastases receiving surufatinib.

Objective: Currently, pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases (PNELM) receiving surufatinib treatment was unsatisfying. Our objective was to examine the association between radiological characteristics and efficacy/prognosis. Methods: We enrolled patients with liver metastases in the phase III, SANET-p trial (NCT02589821) and obtained contrast-enhanced computed tomography (CECT) images. Qualitative and quantitative parameters including hepatic tumor margins, lesion volumes, enhancement pattern, localization types, and enhancement ratios were evaluated. The progression-free survival (PFS) and hazard ratio (HR) were calculated using Cox's proportional hazard model. Efficacy was analyzed by logistic-regression models. Results: Among 152 patients who had baseline CECT assessments and were included in this analysis, the surufatinib group showed statistically superior efficacy in terms of median PFS compared to placebo across various qualitative and quantitative parameters. In the multivariable analysis of patients receiving surufatinib (N=100), those with higher arterial phase standardized enhancement ratio-peri-lesion (ASER-peri) exhibited longer PFS [HR=0.039; 95% confidence interval (95% CI): 0.003-0.483; P=0.012]. Furthermore, patients with a high enhancement pattern experienced an improvement in the objective response ratio [31.3% vs. 14.7%, odds ratio (OR)=3.488; 95% CI: 1.024-11.875; P=0.046], and well-defined tumor margins were associated with a higher disease control rate (DCR) (89.3% vs. 68.2%, OR=4.535; 95% CI: 1.285-16.011; P=0.019) compared to poorly-defined margins. Conclusions: These pre-treatment radiological features, namely high ASER-peri, high enhancement pattern, and well-defined tumor margins, have the potential to serve as predictive markers of efficacy in patients with PNELM receiving surufatinib.

pH-Responsive Liposomes Loaded with Targeting Procoagulant Proteins as Potential Embolic Agents for Solid Tumor-Targeted Therapy.

Selectively inducing tumor thrombosis and subsequent necrosis is a novel and promising antitumor strategy. We have previously designed a targeting procoagulant protein, called tTF-EG3287, which is a fusion of a truncated tissue factor (tTF) with EG3287, a short peptide against the neuropilin-1 (NRP1) binding site of vascular endothelial growth factor-A 165 (VEGF-A 165). However, off-target effects and high-dose requirements limit the further use of tTF-EG3287 in antitumor therapy. Therefore, we encapsulated tTF-EG3287 into poly(2-ethyl-2-oxazoline)-distearoyl phosphatidyl ethanolamine (PEOz-DSPE)-modified liposomes to construct pH-responsive liposomes as a novel vascular embolization agent, called tTF-EG3287@Liposomes. The liposomes had an average particle size of about 100 nm and showed considerable drug-loading capacity, encapsulation efficiency, and biocompatibility. Under the stimulation of acidic microenvironments (pH 6.5), the lipid membrane of tTF-EG3287@Liposomes collapsed, and the cumulative drug release rate within 72 h was 83 ± 1.26%. When administered to a mouse model of hepatocellular carcinoma (HCC), tTF-EG3287@Liposomes showed prolonged retention and enhanced accumulation in the tumor as well as a superior antitumor effec, compared with tTF-EG3287. This study demonstrates the potential of tTF-EG3287@Liposomes as a novel embolic agent for solid tumors and provides a new strategy for tumor-targeted infarction therapy.

SRSF1 promotes ASMC proliferation in asthma by competitively binding CCND2 with miRNA-135a.

BACKGROUND: Asthma is an inflammatory syndrome characterized by airway hyperresponsiveness, bronchial inflammation, and airway remodeling. Abnormal proliferation of airway smooth muscle cells (ASMCs) is the main pathological feature of asthma. This study investigated the function and mechanism of serine arginine-rich splicing factor 1 (SRSF1) in ASMC proliferation in asthma. METHODS: SRSF1 expressions in the bronchi of ovalbumin-induced asthmatic mice and IgE-treated mouse ASMCs (mASMCs) were evaluated using quantitative real-time PCR and Western blot. The localization and expression of SRSF1 in the bronchi of asthmatic mice were assessed by immunohistochemistry. Functionally, gain- and loss-of-function assays, flow cytometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were conducted. Mechanistically, RNA degradation assay, RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter gene assays were carried out. RESULTS: SRSF1 was highly expressed in the bronchi of ovalbumin-induced asthma mice and IgE-treated mASMCs and was mainly located in the nucleus. Experiments on the function of SRSF1 showed that the silencing of SRSF1 induced the cell cycle of mASMC arrest and restrained mASMC proliferation. Investigations into the mechanism of SRSF1 revealed that SRSF1 and miR-135a are competitively bound to the 3'UTR region of Cyclin D2 (CCND2). SRSF1 overexpression repressed the degradation of CCND2 mRNA, and miR-135a negatively regulated CCND2 expression. Furthermore, SRSF1 knockdown inhibited ASMC proliferation in asthma mouse models by regulating the levels of miR-135a and CCND2. CONCLUSION: SRSF1 knockdown repressed ASMC proliferation in asthma by regulating miR-135a/CCND2 levels.

Methylated Septin9 has moderate diagnostic value in colorectal cancer detection in Chinese population: a multicenter study.

BACKGROUND: The detection rate of methylated Septin9 (mSEPT9) in colorectal cancer (CRC) is varied greatly across the studies. This study aimed to evaluate the diagnostic ability of mSEPT9 in CRC, and compare the diagnostic efficacy with fecal immunochemical test (FIT). METHODS: 326 subjects from four centers were prospectively recruited, including 179 CRC and 147 non-CRC subjects. The plasma was collected for mSEPT9 and CEA, AFP, CA125, CA153 and CA199 test, and fecal samples for FIT tests. Sensitivity, specificity and area under the curve (AUC) of receiver operating characteristic curve were calculated to evaluate the diagnostic value of each biomarker. RESULTS: The positive rate in mSEPT9 and FIT, and the level of CEA, CA125 and CA199 were significantly higher in CRC compared with non-CRC subjects. The mSEPT9 positive rate was not associated with TNM stage and tumor stage. The sensitivity, specificity and AUC of mSEPT9 in diagnostic CRC were 0.77, 0.88 and 0.82, respectively, while the value in FIT was 0.88, 0.80 and 0.83, respectively. mSEPT9 and FIT have higher AUC value than that of CEA, CA125 and CA199. Combination of both mSEPT9 and FIT positive increased sensitivity and AUC to 0.98 and 0.83, respectively, but the specificity was declined. mSEPT9 has a slightly low sensitivity in diagnosis of colon cancer (0.87) compared with rectal cancer (0.93). CONCLUSION: mSEPT9 demonstrated moderate diagnostic value in CRC detection, which was similar to the FIT but superior to the CEA, CA125 and CA199. Combination of mSEPT9 and FIT further improved diagnostic sensitivity in CRC. TRIAL REGISTRATION: ChiCTR2000038319.

Infralow-frequency transcranial magnetic stimulation as a therapy for generalized anxiety disorder: A randomized clinical trial.

BACKGROUND: Generalized anxiety disorder (GAD) is a common chronic mental disorder, and it also can cause depressive symptoms and cognitive impairment. The primary aim of this study was to determine whether inflow-frequency transcranial magnetic stimulation (ILF-TMS) improves anxiety symptoms in patients with GAD. METHODS: Sixty-two patients with GAD were randomly divided into 2 groups. Thirty-one patients in the active ILF-TMS group and 31 patients in the sham ILF-TMS group. All participants were assessed at baseline, week 2, week 4 and week 12. The intention-to-treat methodology was used for the analysis. RESULTS: The response rate was higher in the active group than in the sham group, with a significant difference at week 12 (response rate: 80.6% vs. 54.8%, respectively; P = 0.03). Although the remission rate was higher in the active group at week 12, there was no statistically significant difference between the groups (remission rate: 71.0% vs. 48.4%; P > 0.05). No statistically significant differences on the Hamilton Depression Rating Scale, Clinical Global Impression scale, and neurocognitive test between groups were observed (overall P > 0.05). Adverse events that occurred in the active group were similar to those in the sham group, with no significant differences (P > 0.05). CONCLUSION: The response rate was higher in the active group at the end of the trial, which indicated that ILF-TMS may be an effective and safe adjunctive tool to improve anxiety symptoms in patients with GAD.

The Combination of the Mini-Punch Technique and Photodynamic Therapy for the Treatment of Mandibular Keloids and Hypertrophic Scars.

BACKGROUND: Mandibular keloids and hypertrophic scars can exert significant effects on the appearance of a patient. However, current treatments are not effective in all cases. Consequently, it is vital to identify a safe and effective treatment method. OBJECTIVE: To investigate the therapeutic effect of the mini-punch technique combined with photodynamic therapy (PDT) on mandibular keloids and hypertrophic scars. PATIENTS AND METHODS: Twenty patients with mandibular keloids and hypertrophic scars were enrolled, including 5 cases of keloids and 15 cases of hypertrophic scars, with a total of 40 lesions. The mini-punch technique was performed first, and then, PDT was conducted, once a week on 3 occasions in total. RESULTS: After 12 months of follow-up, 30 lesions had improved by more than 50%, thus achieving a good therapeutic effect. The Vancouver Scar Scale score of patients ranged between 8 and 12 points with a mean of 9.60 ± 1.09 points before surgery and between 2 and 9 points with a mean of 4.15 ± 2.05 points at 12 months after surgery. The mean Vancouver Scar Scale score after treatment was significantly lower than that before treatment (t = 11.80, p < .001). CONCLUSION: A combination of the mini-punch technique and PDT is an effective treatment for mandibular keloids and hypertrophic scars.

Quercetin attenuates lipopolysaccharide-mediated inflammatory injury in human nasal epithelial cells via regulating miR-21/DMBT1/NF-κB axis.

BACKGROUND: Quercetin (Qu) belongs to a flavonoid polyphenolic compound present in fruits and vegetables which has been confirmed to exert anti-inflammatory properties. Our study aimed to explore the impacts of quercetin on lipopolysaccharide (LPS)-induced inflammatory injury and signal transduction of miR-21/DMBT1/NF-κB axis in human nasal epithelial cells (HNEpC). METHODS: HNEpCs were cultured and treated with 1 µg/mL of LPS and a gradient concentration (10, 100, and 200 µM) of quercetin for 24 h. Cell viability, apoptosis, and cytokines were detected to assess the inflammatory injury in LPS-exposed HNEpCs. The expressions of miR-21, DMBT1, and NF-κB mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The levels of DMBT1 and NF-κB protein were measured by western blotting. RESULTS: LPS treatment reduced cell viability, promoted cell apoptosis and inflammatory response, down-regulated miR-21 expression and up-regulated DMBT1, and NF-κB in HNEpC cells. Quercetin exerted the opposite effects to attenuate LPS-induced inflammatory injury in HNEpC cells at a concentration-dependent way. Additionally, miR-21 directly targeted DMBT1 to reduce its expression and further inducing cell viability via inhibiting cell apoptosis and inflammatory response. MiR-21 inhibition or DMBT1 over-expression weakened the protective effects of quercetin against LPS-induced inflammatory injury in HNEpC cells. CONCLUSIONS: Quercetin could protect HNEpC cells against LPS-induced inflammatory injury via inducing miR-21/DMBT1/NF-κB axis. Therefore, quercetin could be utilized as a potential compound to treat for allergic rhinitis.

Normalization of Samples of Limited Amounts in Quantitative Metabolomics Using Liquid Chromatography Fluorescence Detection with Dansyl Labeling of Metabolites.

Quantitative metabolomics requires the analysis of the same or a very similar amount of samples in order to accurately determine the concentration differences of individual metabolites in comparative samples. Ideally, the total amount or concentration of metabolites in each sample is measured to normalize all the analyzed samples. In this work, we describe a very sensitive method to measure a subclass of metabolites as a surrogate quantifier for normalization of samples with limited amounts. This method starts with low-volume dansyl labeling of all metabolites containing a primary/secondary amine or phenol group in a sample to produce a final solution of 21 µL. The dansyl-labeled metabolites generate fluorescence signals at 520 nm with photoexcitation at 250 nm. To remove the interference of dansyl hydroxyl products (Dns-OH) formed from the labeling reagents used, a fast-gradient liquid chromatography separation is used to elute Dns-OH using aqueous solution, followed by organic solvent elution to produce a chromatographic peak of labeled metabolites, giving a measurement throughput of 6 min per sample. The integrated fluorescence signals of the peak are found to be related to the injection amount of the dansyl-labeled metabolites. A calibration curve using mixtures of dansyl-labeled amino acids is used to determine the total concentration of labeled metabolites in a sample. This concentration is used for normalization of samples in the range from 2 to 120 µM in 21 µL with only 1 µL consumed for fluorescence quantification (i.e., 2-120 pmol). We demonstrate the application of this sensitive sample normalization method in comparative metabolome analysis of human cancer cells, MCF-7 cells, treated with and without resveratrol, using a starting material of as low as 500 cells.

Annular and supra-annular structure assessments for transcatheter aortic valve replacement in patients with bicuspid aortic stenosis.

The clinical use indications for transcatheter aortic valve replacement (TAVR) for the treatment of severe symptomatic aortic stenosis (AS) have expanded from patients at high surgical risk to those at low risk based on the results of multiple large-scale randomized trials. However, patients with bicuspid AS have traditionally been excluded from clinical trials due to their unfavorable morphological characteristics. Bicuspid aortic valve (BAV) is the most frequent congenital heart disease, occurring in 1% to 2% of the total population and affects more than 20% of octogenarians undergoing isolated aortic valve replacement for AS. In recent years, TAVR in patients with bicuspid AS has been the focus of research, especially with respect to the standard of prosthesis size selection. Annulus-based prosthesis size selection using computed tomography (CT) is the standard sizing strategy for tricuspid AS, but no standard sizing for bicuspid AS has been developed thus far. According to Western TAVR experiences, transcatheter heart valve (THV) size selection for BAV patients should be based on the annular structure assessment by CT measurement, whereas Chinese experiences favor adopting the supra-annulus structure assessment for THV size selection. This article will review annular and supra-annular sizing for prosthesis size selection in patients with bicuspid AS before TAVR and discuss which has more favorable clinical outcomes.

14N NMR as a General Tool to Characterize the Nitrogen-Containing Species and Monitor the Nitration Process.

The usefulness of 14N NMR spectroscopy was highly underestimated compared with 15N NMR, which usually required tedious and expensive 15N-labeling manipulations. It is of great significance to make the 14N NMR spectroscopy convenient and useful considering 14N nuclei's high natural abundance of 99.6%. Herein, lots of efforts have been made to generalize routine 14N NMR to characterize nitrogen-containing species by tuning the balance between the solubility and viscosity of the samples. Satisfactory 14N NMR spectra of more than 60 nitrogen-containing compounds have been recorded, and the chemical shifts and the peaks' full width at half-maxima of more than 10 nitrogen-based functionalities have been summarized. Successful monitoring of the ortho-selective nitration of aniline has been demonstrated using the 14N NMR protocol developed in this paper, which will help realize the visualization of nitration processes in the industry.

[Preventive and therapeutic effects and mechanism of Xiaoer Feike Granules on chronic bronchitis induced by lipopolysaccharide in rats].

The aim of this paper was to investigate the preventive and therapeutic effects of Xiaoer Feike Granules(XEFK) on chronic bronchitis in rats and its mechanism. Except for 10 rats in the blank group, the remaining 50 of the 60 SD rats were used to establish a model of chronic bronchitis induced by LPS. On the 22 nd day, the model rats were randomly divided into 5 groups according to their body weight, and administrated with purified water, Keteling Capsules 0.11 g·kg~(-1), XEFK 3.2, 1.6 and 0.8 g·kg~(-1)(the dosing concentrations were 0.32, 0.16, 0.08 g·mL~(-1), respectively). These rats took the corresponding drug orally once a day, for consecutive 21 days. The rats were anesthetized 1 hour after the last administration, and the lavage bronchus and alveoli were collected. Then, after the fixation of the smear, neutrophils were counted microscopically, and the contents of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and malondialdehyde(MDA) in the bronchoalveolar lavage fluid(BALF) were detected by colorimetric method. Flow cytometry was used to detect the content changes of T cell subsets CD4~+, CD8~+, CD4~+/CD8~(+ )in serum. Hemorheology related indexes were detected by automatic hemorheology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the contents of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), IL-2, IL-6 and IL-10 in serum. The expression of TNF-α and IL-10 mRNA in lung was detected by Real-time quantitative PCR(RT-qPCR). HE staining was used to observe the pathological changes in the bronchitis tissues. Compared with the model group, XEFK high and medium dose groups could significantly reduce the contents of neutrophils and MDA in bronchial lavage fluid, and increase the activities of GSH-Px and SOD in BALF, and repair the chronic inflammatory cell infiltration and lymphoid tissue hyperplasia in the bronchial mucosal layer and submucosal layer. The high-dose group could reduce the plasma viscosity of rats, but there was no statistical difference in other hemorheological indexes. CD4~+, CD8~+, CD4~+/CD8~+, IL-2 and IL-10 contents in each dose group were significantly increased, and TNF-α, IL-1ß and IL-6 contents were significantly decreased in serum. Each dose group could significantly down-regulate the expression level of TNF-α mRNA in the lung and increase the expression of IL-10 mRNA. XEFK could reduce lipid peroxidation, increase the content of peripheral blood T cell subsets, regulate the release and secretion of inflammatory factors, and repair the morphological and pathological changes of bronchial tissue. Its mechanism might be related to the improvement of inflammatory response and the enhancement of immune function.