Enhanced Anti-Inflammatory Activity of Tilianin Based on the Novel Amorphous Nanocrystals.

Tilianin (Til), a flavonoid glycoside, is well-known for its therapeutic promise in treating inflammatory disorders. Its poor water solubility and permeability limit its clinical applicability. In order to overcome these restrictions, an antisolvent precipitation and ultrasonication technique was used to prepare amorphous tilianin nanocrystals (Til NCs). We have adjusted the organic solvents, oil-to-water ratio, stabilizer composition, and ultrasonic power and time by combining single-factor and central composite design (CCD) methodologies. The features of Til NCs were characterized using powder X-ray diffraction (PXRD), scanning calorimetry (DSC), and transmission electron microscopy (TEM). Specifically, the optimized Til NCs were needle-like with a particle size ranging from 90 to 130 nm. PVA (0.3%, w/v) and TPGS (0.08%, w/v) stabilized them well. For at least two months, these Til NCs stayed amorphous and showed an impressive stability at 4 °C and 25 °C. Remarkably, Til NCs dissolved almost 20 times faster in simulated intestinal fluid (SIF) than they did in crude Til. In RAW264.7 cells, Til NCs also showed a better cellular absorption as well as safety and protective qualities. Til NCs were shown to drastically lower reactive oxygen species (ROS), TNF-α, IL-1ß, and IL-6 in anti-inflammatory experiments, while increasing IL-10 levels and encouraging M1 macrophages to adopt the anti-inflammatory M2 phenotype. Our results highlight the potential of amorphous Til NCs as a viable approach to improve Til's anti-inflammatory effectiveness, solubility, and dissolving rate.

B(C6F5)3/CPA-Catalyzed Aza-Diels-Alder Reaction of 3,3-Difluoro-2-Aryl-3H-indoles and Unactivated Dienes.

Here we report B(C6F5)3/CPA-catalyzed enantioselective aza-Diels-Alder reaction of 3,3-difluoro-2-Aryl-3H-indoles with unactivated dienes to access chiral 10,10-difluoro-tetrahydropyrido[1,2-a]indoles. This protocol allows the formation of pyrazole-based C2-quaternary indolin-3-ones with high enantioselectivities and regioselectivities. Moreover, gram-scale synthesis of the 10,10-difluoro-tetrahydropyrido[1,2-a]indole skeleton was successfully achieved without any reduction in both yield and enantioselectivity.

Highly Enantioselective Synthesis of 3a-Fluorofuro[3,2-b]indolines via Organocatalytic Aza-Friedel-Crafts Reaction/Selective C-F Bond Activation.

Fluoroalkylated compounds are of high interest in drug discovery and have inspired the evolution of diverse C-F bond activation methodologies. However, the selective activation of polyfluorinated compounds remains challenging. Herein, we describe an unprecedented strategy for synthesizing enantioenriched fluorofuro[3,2-b]indolines through the organocatalytic aza-Friedel-Crafts reaction coupled with selective C-F bond activation. These reactions feature excellent enantioselectivities (≤96% ee) and yields (≤96%) as well as good functional group compatibility. Mechanistic investigations by means of 19F nuclear magnetic resonance experiments provided sufficient support for silica gel as the key medium in this transformation.

Herbal Medicine Nanocrystals: A Potential Novel Therapeutic Strategy.

Herbal medicines have gained recognition among physicians and patients due to their lower adverse effects compared to modern medicines. They are extensively used to treat various diseases, including cancer, cardiovascular issues, chronic inflammation, microbial contamination, diabetes, obesity, and hepatic disorders, among others. Unfortunately, the clinical application of herbal medicines is limited by their low solubility and inadequate bioavailability. Utilizing herbal medicines in the form of nanocrystals (herbal medicine nanocrystals) has shown potential in enhancing solubility and bioavailability by reducing the particle size, increasing the specific surface area, and modifying the absorption mechanisms. Multiple studies have demonstrated that these nanocrystals significantly improve drug efficacy by reducing toxicity and increasing bioavailability. This review comprehensively examines therapeutic approaches based on herbal medicine nanocrystals. It covers the preparation principles, key factors influencing nucleation and polymorphism control, applications, and limitations. The review underscores the importance of optimizing delivery systems for successful herbal medicine nanocrystal therapeutics. Furthermore, it discusses the main challenges and opportunities in developing herbal medicine nanocrystals for the purpose of treating conditions such as cancer, inflammatory diseases, cardiovascular disorders, mental and nervous diseases, and antimicrobial infections. In conclusion, we have deliberated regarding the hurdles and forthcoming outlook in the realm of nanotoxicity, in vivo kinetics, herbal ingredients as stabilizers of nanocrystals, and the potential for surmounting drug resistance through the utilization of nanocrystalline formulations in herbal medicine. We anticipate that this review will offer innovative insights into the development of herbal medicine nanocrystals as a promising and novel therapeutic strategy.

Circ-ERBB2 knockdown sensitized colorectal cancer cells to 5-FU via miR-181a-5p/PTEN/Akt pathway.

Colorectal cancer (CRC) is the fourth most deadly cancer worldwide, drug resistance impedes treatment of CRC. It is still urgent to find new molecular targets to improve the sensitivity of chemotherapeutic drugs. In this study, circ-ERBB2 was upregulated in CRC cells. Upregulation of circ-ERBB2 promoted CRC cells proliferation and clone formation, but inhibited apoptosis. We identified miR-181a-5p as circ-ERBB2's target. The effect of miR-181a-5p on CRC cells was contrary to circ-ERBB2, miR-181a-5p downregulation abolished the function of circ-ERBB2 silencing in CRC cells. In addition, phosphatase and tensin homolog (PTEN) was verified as miR-181a-5p's downstream target, circ-ERBB2 activates the Akt pathway and inhibits cell apoptosis through modulating miR-181a-5p/PTEN. Circ-ERBB2 silencing significantly reduced CRC cell resistance to 5-FU. miR-181a-5p downregulation abolished the role of circ-ERBB2 knockdown in CRC cell resistance to 5-FU. In conclusion, upregulation of circ-ERBB2 promoted the malignancy of CRC and reduced CRC cell resistance to 5-FU. Besides, additional mechanism study provided a novel regulatory pathways that circ-ERBB2 knockdown promoted CRC cell sensitivity to 5-FU by regulating miR-181a-5p/PTEN/Akt pathway. This research indicated that circ-ERBB2 may be a valuable biomarker for the diagnosis and treatment of CRC.

Survival benefits of oral anticoagulation therapy in acute kidney injury patients with atrial fibrillation: a retrospective study from the MIMIC-IV database.

OBJECTIVE: To find out the effect of different oral anticoagulation therapies (OAC) on mortality rate in patients with acute kidney injury (AKI) and atrial fibrillation (AF).DesignA retrospective study. SETTING: This study was conducted in the Medical Information Mart for Intensive Care IV database. PARTICIPANTS: A total of 19 672 patients diagnosed with AKI. MAIN OUTCOME MEASURES: Patients were categorised into three groups: (1) AF; (2) AKI and AF, OAC-; (3) AKI and AF, OAC+. The primary endpoint was 30-day mortality. Secondary endpoints were the length of stay (LOS) in the intensive care unit (ICU) and hospital. Propensity score matching (PSM) and Cox proportional hazards model adjusted confounding factors. Linear regression was applied to assess the associations between OAC treatment and LOS. RESULTS: After PSM, 2042 pairs of AKI and AF patients were matched between the patients who received OAC and those without anticoagulant treatment. Cox regression analysis showed that, OAC significantly reduce 30-day mortality compared with non-OAC (HR 0.30; 95% CI 0.25 to 0.35; p<0.001). Linear regression analysis revealed that OAC prolong LOS in hospital (11.3 days vs 10.0 days; p=0.013) and ICU (4.9 days vs 4.4 days; p<0.001). OAC did not improve survival in patients with haemorrhage (HR 0.67; 95% CI 0.34 to 1.29; p=0.23). Novel OAC did not reduce mortality in acute-on-chronic renal injury (HR 2.03; 95% CI 1.09 to 3.78; p=0.025) patients compared with warfarin. CONCLUSION: OAC administration was associated with improved short-term survival in AKI patients concomitant with AF.

Anti-freezing dual-network hydrogels with high-strength, self-adhesive and strain-sensitive for flexible sensors.

Hydrogels as flexible sensor have attracted significant attention due to its conductivity, stretchability and flexibility. However, it is still a great challenge to prepare hydrogels that simultaneously possess high strength, anti-fatigue, self-adhesion, and anti-freezing. Herein, a multifunctional dual-network hydrogel was prepared by in situ polymerization of acrylic monomer in chitosan chains, and coordinated with aluminum chloride and glycerol. Based on chain entanglement, hydrogen bonding and coordination interactions, this dual-network hydrogel exhibited excellent mechanical properties, good fatigue resistance, and excellent adhesion performance. It can be used as a strain sensor for its stable conductivity and high sensitivity, which could monitor both large human motions and subtle motions. Due to the presence of glycerol, the hydrogel showed outstanding freezing resistance and still kept flexible and conductive even at low temperatures (-20 °C). This hydrogel can be applied as a flexible wearable sensor for monitoring human motion in extreme low-temperature condition.

CEO Overconfidence, Corporate Governance, and R&D Smoothing in Technology-Based Entrepreneurial Firms.

The intertemporal stability of research and development (R&D) investment is a key issue in successfully promoting the continuation of innovation activities under high uncertainty in entrepreneurship. R&D smoothing helps firms to navigate the uncertainties of the external environment and maintain the stability of their investments in innovation. Chief executive officers (CEOs) are the most important decision-makers in firms' strategic planning. However, overconfident CEOs may overlook the importance of their firms' strategic actions on innovative activities. Drawing on upper echelons theory, this paper examines how CEO overconfidence affects firms' R&D smoothing. Using a sample of firms listed in China's Growth Enterprises Market between 2013 and 2020, this study finds that CEO overconfidence has a significant negative impact on R&D smoothing. Furthermore, our findings reveal that firms' internal control quality and institutional investor monitoring can mitigate the negative association between CEO overconfidence and R&D smoothing. Our findings provide new insights into the micro-level theoretical explanations for R&D smoothing and offer practical implications for technology-based entrepreneurial firms.

Mortality Risk Factors and Prognostic Analysis of Patients with Multi-Drug Resistant Enterobacterales Infection.

Background: The data from the China Network Antibacterial Surveillance Center (http://www.chinets.com) showed that the prevalence of Escherichia coli (E. coli), Klebsiella pneumoniae (KP), and Enterobacter cloacae (ecl), was 18.96%, 14.12%, and 2.74% in 2022, respectively. The resistance rates of E. coli and KP to 3rd or 4th generation cephalosporins were 51.7% and 22.1%, to carbapenems was 1.7% and 3.9%, to quinolones was 55.9% in Shanxi. The generation of extended-spectrum beta-lactamases (ESBLs) is a major mechanism resulting in drug resistance in Enterobacterales. To determine the mortality risk factors of multi-drug resistant Enterobacterales (MDRE) and multi-drug resistant Klebsiella pneumoniae (MDR-KP) infection. Methods: 91 MDR strains from 91 patients were collected from 2015 to 2019 in the second hospital of Shanxi Medical University. The mortality risk factors for the MDRE infections and clinical outcomes were analyzed by univariable and multivariable analysis. The independent predictors of 30-day mortality were analyzed through the Cox regression analysis including the variables with a value <0.2. Results: The majority of patients were admitted to ICUs. Pulmonary infection was a major infection (43.96%, 40/91). Thirty-three (36.26%, 33/91) strains of MDR-KP were only detected in 2018. The proportion of multi-drug resistant Escherichia coli (MDR E. coli) and multi-drug resistant Enterobacter cloacae (MDR ecl) were 16.48% (15/91) and 17.58% (16/91), respectively. The presence of cerebrovascular diseases (OR, 4.046; 95%Cl, 1.434-11.418; P=0.008) and central venous catheterization (OR, 4.543; 95%Cl, 1.338-15.425; P=0.015) were associated with mortality in patients with MDRE infections. Endotracheal intubation (OR, 4.654; 95%Cl, 1.5-14.438; P=0.008) was an independent mortality risk factor for patients infected with MDR-KP strains. Patients who received aminoglycoside antibiotics (P=0.057) had a higher 30-day survival rate. The ß-lactam antibiotics were the major agent in the clinic. Conclusion: This study implies that patients with cerebrovascular diseases, central venous catheterization, and endotracheal intubation are at risk of carrying MDR isolates.

Room-Temperature Solid-State UV Cross-Linkable Vitrimer-like Polymers for Additive Manufacturing.

In this paper, a UV cross-linkable vitrimer-like polymer, ureidopyrimidinone functionalized telechelic polybutadiene, is reported. It is synthesized in two steps. First, 2(6-isocyanatohexylaminocarbonylamino)-6-methyl-4[1H]-pyrimidinone (UPy-NCO) reacts with hydroxy-functionalized polybutadiene (HTPB) to obtain UPy-HTPB-UPy, and then the resulted UPy-HTPB-UPy is cross-linked under 365 nm UV light (photo-initiator: bimethoxy-2-phenylacetophenone, DMPA). Further investigation reveals that the density of cross-linking and mechanical properties of the resulting polymers can be tailored via varying the amount of photo-initiator and UV exposure time. Before UV cross-linking, UPy-HTPB-UPy is found to be vitrimer-like due to the quadruple hydrogen-bonding interactions. The UPy groups at the end of the chain also enable for rapid solidification upon the evaporation of the solvent. The unsaturated double bonds in the HTPB chains enable UPy-HTPB-UPy to be UV cross-linkable in the solid state at room temperature. After cross-linking, the polymers have good shape memory effect (SME). Here, we demonstrate that this type of polymer can have many potential applications in additive manufacturing. In the cases of fused deposition modelling (FDM) and direct ink writing (DIW), not only the strength of the interlayer bonding but also the strength of the polymer itself can be enhanced via UV exposure (from thermoplastic to thermoset) either during printing or after printing. The SME after cross-linking further helps to achieve rapid volumetric additive manufacturing anytime and anywhere.

SOAT1 is a new prognostic factor of colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant gastrointestinal cancers. Metastasis is the major leading cause of death in patients with CRC, and many patients treated with radical surgery were diagnosed with metastasis during follow-up. However, the underlying molecular mechanisms regulating CRC metastasis are still elusive. Sterol o-acyltransferase 1 (SOAT1) is a critical participant in maintaining intracellular cholesterol balance. Here, by analyzing the clinical specimens and in vitro cell line experiments, we evaluated the clinical relevance and role of SOAT1 in regulating CRC metastasis. The results revealed that SOAT1 was overexpressed in colon cancer tissues compared to peritumor tissues at mRNA and protein levels. High intratumor SOAT1 expression correlates to lymph node metastasis and indicates poor patient disease-free survival and overall survival. The silencing of SOAT1 strongly inhibited the migration and invasion ability of CRC tumor cells. These results demonstrated that SOAT1 was upregulated in colon cancer. Upregulation of SOAT1 expression may promote CRC progression by enhancing the migration and invasion ability of CRC. Our results indicate that targeting SOAT1 activity may be applied as a promising therapeutic strategy for preventing the metastasis of CRC after radical surgical treatment.

[Study on Influencing Factors of the Tip Softness of Epidural Anesthesia Catheter].

This article aims to study the factors affecting the flexibility of the tip of an epidural anesthesia catheter. The flexibility of the tip of the epidural anesthesia catheter was tested with a softness tester from four aspects:raw materials, tip structure, tip processing technology, and the outer diameter of the catheter. Highly flexible and malleable polymer material with a smooth tip, the tip softening process and the proper outer diameter can effectively improve the tip flexibility of the epidural anesthesia catheter.

Prediction of Peking duck intramuscle fat content by near-infrared spectroscopy.

Peking duck is the most representative of the meat-type duck breed, and it is also one of the most popular meats in Asia. Few studies were reported on the fast assessment of duck meat quality. This study aimed to develop a fast measuring of duck fat content by using the near-infrared spectroscopy (NIRS) method. We measured 273 duck breast muscle intramuscle fat (IMF) content and spectra. Partial least-squares regression (PLSR) was used to model the fat content prediction by using the spectra in the wavelengths between 950 and 1650 nm. The best predictive abilities were obtained after the first derivative pretreatment, with coefficient of calibration (R2C) of 0.92, with coefficient of prediction (R2P) of 0.90, ratio performance to deviation (RPD) of 2.72, and ratio of error range (RER) of 15.45, for samples of 30 g duck. Results demonstrated that the near-infrared spectroscopy is a useful tool for fat content assessment of Peking duck meat.

Combinations of V2C and Ti3C2 MXenes for Boosting the Hydrogen Storage Performances of MgH2.

Two-dimensional vanadium carbide (V2C) and titanium carbide (Ti3C2) MXenes were first synthesized by exfoliating V2AlC or Ti3AlC2 and then introduced jointly into magnesium hydride (MgH2) to tailor the hydrogen desorption/absorption performances of MgH2. The as-prepared MgH2-V2C-Ti3C2 composites show much better hydrogen storage performances than pure MgH2. MgH2 with addition of 10 wt % of 2V2C/Ti3C2 initiates hydrogen desorption at around 180 °C; 5.1 wt % of hydrogen was desorbed within 60 min at 225 °C, while 5.8 wt % was desorbed within 2 min at 300 °C. Under 6 MPa H2, the dehydrided MgH2-2V2C/Ti3C2 can start to recover hydrogen at room temperature, and 5.1 wt % of H2 is obtained within 20 s at a constant temperature of 40 °C. The reversible capacity (6.3 wt %) does not decline for up to 10 cycles, which shows excellent cycling stability. The addition of 2V2C/Ti3C2 can remarkably lower the activation energy for the hydrogen desorption reaction of MgH2 by 37% and slightly reduce the hydrogen desorption reaction enthalpy by 2 kJ mol-1 H2. It was demonstrated that the combination of V2C and Ti3C2 promotes the hydrogen-releasing process of MgH2 compared with addition of only V2C or Ti3C2, while Ti3C2 impacts MgH2 more significantly than V2C in the hydrogen absorption process of MgH2 at ambient temperatures. A possible mechanism in the hydrogen release and uptake of the MgH2-V2C-Ti3C2 system was proposed as follows: hydrogen atoms or molecules may preferentially transfer through the MgH2/V2C/Ti3C2 triple-grain boundaries during the desorption process and through the Mg/Ti3C2 interfaces during the absorption process. Microstructure studies indicated that V2C and Ti3C2 mainly act as efficient catalysts for MgH2. This work provides an insight into the hydrogen storage behaviors and mechanisms of MgH2 boosted by a combination of two MXenes.

Co-Production of NDM-1, CTX-M-9 Family and mcr-1 in a Klebsiella pneumoniae ST4564 Strain in China.

PURPOSE: To identify novel sequence types 4564 (ST4564) carbapenem-resistant Klebsiella pneumoniae (CRKP). Characterizing the feature of the clinic, resistance, and virulence of a co-producing NDM-1 and CTX-M-9 family and mcr-1 ST4564 strain. METHODS: A novel ST4564 CRKP was collected from June 2018 to July 2018. We investigated its antimicrobial susceptibility by the microdilution method. Using the modified carbapenem inactivation method (mCIM) to screen phenotype of carbapenemases. Resistance mechanisms, virulence-associated genes, multilocus sequence typing (MLST), and capsular serotypes were characterized by polymerase chain reaction (PCR) and DNA sequencing. Next-generation sequencing (NGS) was carried out to determine the genetic features of carbapenem resistance and virulence. RESULTS: ST4564, co-carrying NDM-1, CTX-M-9 and mcr-1, was resistant to carbapenems, cephamycin, third- or fourth-generation cephalosporins, ß-lactam combination agents, quinolones and tigecycline but remained susceptible to amikacin (AMK) and colistin (COL). Through the NGS analysis with the G+C content of 56.65%, multiple resistance and virulence genomes were detected. The genes encoding the ß-lactams, aminoglycosides, quinolones, macrolides, sulfonamide, polysaccharide capsule, type-I fimbriae cluster, siderophore genes, transporter and pumps, T6SS and pullulanase secretion protein. goeBURST analysis showed that ST4564 belonged to the CC1571 and it was not related to the prevalent high-risk clones. CONCLUSION: We first identified the novel ST4564 CRKP. Our finding suggested that the urgent need for infection control of the new clone to prevent it from becoming a high-risk clone of CRKP.

Polymorphism of MTHFR C677T Gene and the Associations with the Severity of Essential Hypertension in Northern Chinese Population.

OBJECTIVE: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of homocysteine metabolism and is closely related to the occurrence of hypertension. The aim of this study was to investigate the polymorphism of the (MTHFR) C677T and the factors influencing the severity of hypertension. Material and Methods. A total of 985 subjects were enrolled to analyze the polymorphisms of the MTHFR C677T gene by polymerase chain reaction (PCR). 306 people with essential hypertension were selected from 985 subjects to estimate the severity of hypertension by the ordinal multivariate logistical regression model. RESULTS: The frequencies of CC, CT, and TT genotypes were 19.5%, 49.95%, and 30.46%, respectively. The allelic frequency of mutant T was 55.43%. The plasma homocysteine level of the homozygous TT in individuals was significantly higher than in those with CC or CT (P < 0.01). MTHFR677CT genotype, MTHFR677TT genotype, smoking, family history of hypertension, Hcy, and triglycerides (TG) were independent risk factors for the severity of hypertension (OR = 2.29, 2.24, 2.04, 1.81, 1.04, 1.26). CONCLUSION: MTHFR gene, smoking, family history of hypertension, Hcy, and triglycerides could be important genetic and high-risk factors of the development of severe hypertension in northern Chinese. These factors will contribute to the identification of high-risk populations of hypertension and facilitate the development of hypertension control strategies.

Intravenous Administration of Pyroglutamyl Apelin-13 Alleviates Murine Inflammatory Pain via the Kappa Opioid Receptor.

Apelin is an endogenous neuropeptide, which has wide distribution in central nervous system and peripheral tissues. Pyroglutamyl apelin-13 [(pyr)apelin-13] is the major apelin isoform in human plasma. However, the role of peripheral (pyr)apelin-13 in pain regulation is unknown. The aim of this study was to investigate the effect of the peripheral injection of (pyr)apelin-13 on inflammatory pain using the formalin test as well as to evaluate the mechanistic basis for the effect. Results showed intravenous (i.v.) injection of (pyr)apelin-13 (10, 20 mg/kg) to significantly decrease licking/biting time during the second phase of the mouse formalin test. In contrast, i.v. injection of apelin-13 had no influence on such effect. Intramuscular injection of (pyr)apelin-13 reduced licking/biting time during the second phase only at a dose of 20 mg/kg. The antinociception of i.v. (pyr)apelin-13 was antagonized by the apelin receptor (APJ, angiotensin II receptor-like 1) antagonist, apelin-13(F13A). (pyr)apelin-13 (i.v. 20 mg/kg) markedly upregulated Aplnr and Adcy2 gene expression in the prefrontal cortex, whereas Fos gene expression was downregulated. The antinociception of i.v. (pyr)apelin-13 was blocked by the opioid receptor antagonist naloxone and the specific kappa opioid receptor (KOR) antagonist nor-binaltorphimine (nor-BNI). (pyr)Apelin-13 upregulated the dynorphin and KOR gene expression and protein levels in the mouse prefrontal cortex, not in striatum. (pyr)Apelin-13 did not influence the motor behavior. Our results demonstrate that i.v. injection of (pyr)apelin-13 induces antinociception via the KOR in the inflammatory pain mouse model.

Intrathecally Administered Apelin-13 Alleviated Complete Freund's Adjuvant-Induced Inflammatory Pain in Mice.

Apelin is the endogenous ligand for APJ, a G-protein-coupled receptor. Apelin gene and protein are widely distributed in the central nervous system and peripheral tissues. The role of apelin in chronic inflammatory pain is still unclear. In the present study, a mouse model of complete Freund's adjuvant (CFA)-induced inflammatory pain was utilized, and the paw withdrawal latency/threshold in response to thermal stimulation and Von Frey filament stimulation were recorded after intrathecal (i.t.) injection of apelin-13 (0.1, 1, and 10 nmol/mouse). The mRNA and protein expression, concentration of glutamic acid (Glu), and number of c-Fos immunol staining in lumbar spinal cord (L4/5) were determined. The results demonstrated that Apln gene expression in the lumbar spinal cord was down-regulated in the CFA pain model. Apelin-13 (10 nmol/mouse, i.t.) alleviated CFA-induced inflammatory pain, and it exhibited a more potent antinociceptive effect than apelin-36 and (pyr)apelin-13. The antinociception of apelin-13 could be blocked by APJ antagonist apelin-13(F13A). I.T. apelin-13 attenuated the increased levels of Aplnr, Grin2b, Camk2d, and c-Fos genes expression, Glu concentration, and NMDA receptor 2B (GluN2B) protein expression caused by CFA. Apelin-13 significantly reduced the number of Fos-positive cells in laminae III and IV/V of the dorsal horn. This study indicated that i.t. apelin-13 exerted an analgesic effect against inflammatory pain, which was mediated by activation of APJ, and inhibition of Glu/GluN2B function and neural activity of the spinal dorsal horn.

Peripheral Spexin Inhibited Food Intake in Mice.

Spexin (SPX, NPQ), a novel endogenous neuropeptide, was firstly identified by bioinformatics. Spexin gene and protein widely distributed in the central nervous system and peripheral tissues, such as the hypothalamus and digestive tract. The role of spexin in appetite regulation in mammalian is still unclear. The present study was designed to investigate the mechanism and effect of peripheral spexin on food intake in mice. During the light period, an intraperitoneal (i.p.) injection of spexin (10 nmol/mouse) significantly inhibited cumulative food intake at 2, 4, and 6 h after treatment in fasted mice. During the dark period, spexin (1 and 10 nmol/mouse, i.p.) significantly suppressed cumulative food intake at 4 and 6 h after treatment in freely feeding mice. The GALR3 antagonist SNAP37889, not GALR2 antagonist, significantly antagonized the inhibitory effect on cumulative food intake (0-6 h) induced by spexin. Spexin significantly reduced the mRNA level of Npy mRNA, not Agrp, Pomc, Cart, Crh, Orexin, or Mch, in the hypothalamus. Spexin (10 nmol/mouse, i.p.) increased the number of c-Fos positive neurons in hypothalamic AHA and SCN, but not in ARC, DMN, LHA, PVN, SON, or VMH. The hypothalamic p-CaMK2 protein expression was upregulated by spexin. This study indicated that acute peripheral injection of spexin inhibited mouse food intake. The anorectic effect may be mediated by GALR3, and inhibiting neuropeptide Y (NPY) via p-CaMK2 and c-Fos in the hypothalamus.

Impact of a Multifaceted Pharmacist-Led Intervention on Antimicrobial Stewardship in a Gastroenterology Ward: A Segmented Regression Analysis.

BACKGROUND: Irrational use of antimicrobial agents for gastrointestinal diseases deserves attention, but corresponding antimicrobial stewardship programs (ASPs) are generally not a priority for managers. We conducted this study to evaluate the effectiveness of multifaceted pharmacist-led (MPL) interventions in the gastroenterology ward (GW) to provide evidence for the efficacy of ASPs in a non-priority department. METHODS: This was an interventional, retrospective study implemented in China. The MPL intervention lasting 1.5 years involved daily ward rounds with physicians, regular review of medical orders, monthly indicator feedback, frequent physician training, and necessary patient education. Data on all hospitalized adults receiving antibiotics was extracted from the hospital information system over a 36-month period from January 2016 to December 2018. Segmented regression analysis of interrupted time series was performed to evaluate the effect of the MPL interventions (started in July 2017) on antibiotic use and length of hospital stay, which was calculated monthly as analytical units. RESULTS: A total of 1763 patients receiving antibiotics were enrolled. Segmented regression models showed descending trends from the baseline in the intensity of antibiotic consumption (coefficient = -0.88, p = 0.01), including a significant decline in the level of change of the proportion of patients receiving combined antibiotics (coefficient = -9.91, p = 0.03) and average length of hospital stay (coefficient = -1.79, p = 0.00), after MPL interventions. The MPL interventions led to a temporary increase in the proportion of patients receiving antibiotics (coefficient = 4.95, p = 0.038), but this was part of a declining secular trend (coefficient = -0.45, p = 0.05). CONCLUSION: The MPL interventions led a statistically significant decline in the number of patients receiving antibiotics, the antibiotic consumption, and the average hospital stay post-intervention compared to the pre-intervention phase of the study. Health policymakers should actively practice MPL interventions by clinical pharmacists in ASPs in those departments that are not included in priority management.