Cost-effectiveness analysis of pharmaceutical care in adult critically ill patients: based on a prospective cohort study.

Background: The medication regimen for critically ill patients is complex and dynamic, leading to a high incidence of drug-related problems. This study aimed to assess the effectiveness and economic efficiency of pharmaceutical care for these patients. Methods: In this prospective cohort study conducted in a tertiary hospital, adult patients were assigned either to a clinical pharmaceutical care group or a control group based on existing clinical grouping rules. Health outcomes and economic indicators were collected, followed by a cost-effectiveness analysis. Results: The acceptance rate for clinical pharmacist interventions was 89.31%. The pharmaceutical care group exhibited significant reductions in the rate of medication errors (40.65% vs. 61.69%, P < 0.001) and adverse drug events (44.52% vs. 56.45%, P = 0.020). The usage rates for special-grade antibiotics (85.16% vs. 91.13%, P = 0.009) and proton pump inhibitors (77.42% vs. 88.71%, P = 0.002) were also lower in the pharmaceutical care group. Secondary outcomes did not show significant differences in total hospital stay (21 days vs. 22 days, P = 0.092). However, ICU stay was significantly shorter (9 days vs. 11 days, P = 0.003) in the pharmaceutical care group. Cost-effectiveness analysis demonstrated that each 1% reduction in adverse drug events associated with ICU pharmaceutical care saved $226.75 in ICU hospitalization costs and $203.42 in total ICU drug costs. A 1% reduction in the medication error rate saved $128.57 in ICU hospitalization costs and $115.34 in total ICU drug costs. Conclusions: Pharmaceutical care significantly reduces adverse drug events and medication errors, promotes rational use of medications, decreases the length of ICU stay, and lowers treatment costs in critically ill patients, establishing a definitive advantage in terms of cost-effectiveness.

Geniposide exerts the antidepressant effect by affecting inflammation and glucose metabolism in a mouse model of depression.

Depression is a severe mental illness affecting patient's physical and mental health. However, long-term effects of existing therapeutic modalities for depression are not satisfactory. Geniposide is an iridoid compound highly expressed in gardenia jasminoides for removing annoyance. The activity of geniposide against depression has been widely studied while most studies concentrated on the expression levels of gene and protein. Herein, the aim of the present study was to employ non-target metabolomic platform of serum to investigate metabolic changes of depression mice and further verify in hippocampus for analyzing the antidepressant mechanism of geniposide. Then we discovered that 9 metabolites of serum were significantly increased in depressive group (prostaglandin E2, leukotriene C4, arachidonic acid, phosphatidylcholine (PC, 16:0/16:0), LysoPC (18:1 (9Z)/0:0), phosphatidylethanolamine (14:0/16:0), creatine, oleamide and aminomalonic acid) and 6 metabolites were decreased (indoxylsulfuric acid, testosterone, lactic acid, glucose 6-phosphate, leucine and valine). The levels of arachidonic acid, LysoPC, lactic acid and glucose 6-phosphate in hippocampus were consistent change with serum in depression mice. Most of them showed significant tendencies to be normal by geniposide treatment. Metabolic pathway analysis indicated that arachidonic acid metabolism and glucose metabolism were the main pathogenesis for the antidepressant effect of geniposide. In addition, the levels of serum tumor necrosis factor-α and interleukin-1 were increased in depressive mice and reversed after geniposide treatment. This study revealed that abnormal metabolism of inflammatory response and glucose metabolism of the serum and hippocampus involved in the occurrence of depressive disorder and antidepressant effect of geniposide.

Posterior Thoracic Antidisplacement and Fusion Surgery for a Special Type of Ossification of the Posterior Longitudinal Ligament in the Thoracic Spine: Indications and Preliminary Clinical Results of 2-Year Follow-Up.

OBJECTIVE: To describe a novel technique, posterior thoracic antidisplacement and fusion (PTAF), for a special type of ossification of the posterior longitudinal ligament in the thoracic spine (T-OPLL), and to evaluate its safety and efficacy. METHODS: From July to December 2020, 5 consecutive patients with beak-type T-OPLL located at the thoracic vertebral body level underwent PTAF surgery. Their demographic data, radiological parameters, perioperative complications, and surgery-related findings were recorded and analyzed. The surgical outcomes were assessed using a modified Japanese Orthopedic Association scale, and the recovery rate was calculated using the Hirabayashi's method. RESULTS: All patients were followed up for at least two years. The mean thickness of OPLL was 9.4 ± 1.0 mm, and the OPLL spinal canal occupying ratio was 67.7% ± 8.5%. Postoperatively, the mean antidisplacement distance of OPLL was 8.1 ± 1.8 mm, and the average shortened distance of the spinal column was 6.0 ± 1.13 mm. The mean operation time and blood loss were 158.2 ± 26.3 minutes and 460 ± 89.4 mL, respectively. Perioperative complications were cerebrospinal fluid leakage and instrument failure, 2 cases each. The mean modified Japanese Orthopedic Association score was increased from 3.6 ± 2.9 before surgery to 9.4 ± 3.0 at the last follow-up, and the average recovery rate was 84.2 ± 30.5%. CONCLUSIONS: The preliminary clinical outcomes indicate that PTAF is a safe and effective method for the treatment of beak-type T-OPLL, which has its apex located at the vertebral body level and has a high spinal canal occupation ratio.

Combining bioinformatics and multiomics strategies to investigate the key microbiota and active components of Liupao tea ameliorating hyperlipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia as a major health issue has attracted much public attention. As a geographical indication product of China, Liupao tea (LPT) is a typical representative of traditional Chinese dark tea that has shown good potential in regulating glucose and lipid metabolism. LPT has important medicinal value in hyperlipidemia prevention. However, the active ingredients and metabolic mechanisms by which LPT alleviates hyperlipidemia remain unclear. AIM OF THE STUDY: This study aimed to systematically investigate the metabolic mechanisms and active ingredients of LPT extract in alleviating hyperlipidemia. MATERIALS AND METHODS: Firstly, we developed a mouse model of hyperlipidemia to study the pharmacodynamics of LPT. Subsequently, network pharmacology and molecular docking were performed to predict the potential key active ingredients and core targets of LPT against hyperlipidemia. LC-MS/MS was used to validate the identity of key active ingredients in LPT with chemical standards. Finally, the effect and metabolic mechanisms of LPT extract in alleviating hyperlipidemia were investigated by integrating metabolomic, lipidomic, and gut microbiome analyses. RESULTS: Results showed that LPT extract effectively improved hyperlipidemia by suppressing weight gain, remedying dysregulation of glucose and lipid metabolism, and reducing hepatic damage. Network pharmacology analysis and molecular docking suggested that four potential active ingredients and seven potential core targets were closely associated with roles for hyperlipidemia treatment. Ellagic acid, catechin, and naringenin were considered to be the key active ingredients of LPT alleviating hyperlipidemia. Additionally, LPT extract modulated the mRNA expression levels of Fxr, Cyp7a1, Cyp8b1, and Cyp27a1 associated with bile acid (BA) metabolism, mitigated the disturbances of BA and glycerophospholipid (GP) metabolism in hyperlipidemia mice. Combining fecal microbiota transplantation and correlation analysis, LPT extract effectively improved species diversity and abundance of gut microbiota, particularly the BA and GP metabolism-related gut microbiota, in the hyperlipidemia mice. CONCLUSIONS: LPT extract ameliorated hyperlipidemia by modulating GP and BA metabolism by regulating Lactobacillus and Dubosiella, thereby alleviating hyperlipidemia. Three active ingredients of LPT served as the key factors in exerting an improvement on hyperlipidemia. These findings provide new insights into the active ingredients and metabolic mechanisms of LPT in improving hyperlipidemia, suggesting that LPT can be used to prevent and therapeutic hyperlipidemia.

Integrated bioinformatics and multiomics reveal Liupao tea extract alleviating NAFLD via regulating hepatic lipid metabolism and gut microbiota.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) poses a significant global public health concern. Liupao tea (LPT) is a Chinese national geographical indication product renowned for its lipid-lowering properties. However, the precise mechanisms and active constituents contributing to the efficacy of LPT against NAFLD remain unclear. PURPOSE: This study aims to comprehensively explore the therapeutic potential of Liupao tea extract (LPTE) in alleviating NAFLD through an integrated strategy. METHODS: Initially, network pharmacology analysis was conducted based on LPTE chemical ingredient analysis, identifying core targets and key components. Potential active ingredients were validated through chemical standards based on LC-MS/MS. To confirm the pharmacological efficacy of LPTE in NAFLD, NAFLD mice models were employed. Alterations in hepatic lipid metabolism were comprehensively elucidated through integration of metabolomics, lipidomics, network pharmacology analysis, and real-time PCR analysis. To further explore the binding interactions between key components and core targets, molecular docking and microscale thermophoresis (MST) analysis were employed. Furthermore, to investigate LPTE administration effectiveness on gut microbiota in NAFLD mice, a comprehensive approach was employed. This included Metorigin analysis, 16S rRNA sequencing, molecular docking, and fecal microbiome transplantation (FMT). RESULTS: Study identified naringenin, quercetin, luteolin, and kaempferol as the potential active ingredients of LPTE. These compounds exhibited therapeutic potential for NAFLD by targeting key proteins such as PTGS2, CYP3A4, and ACHE, which are involved in the metabolic pathways of hepatic linoleic acid (LA) and glycerophospholipid (GP) metabolism. The therapeutic effectiveness of LPTE was observed to be comparable to that of simvastatin. Furthermore, LPTE exhibited notable efficacy in alleviating NAFLD by influencing alterations in gut microbiota composition (Proteobacteria phylum, Lactobacillus and Dubosiella genus) that perhaps impact LA and GP metabolic pathways. CONCLUSION: LPTE could be effective in preventing high-fat diet (HFD)-induced NAFLD by modulating hepatic lipid metabolism and gut microbiota. This study firstly integrated bioinformatics and multi-omics technologies to identify the potential active components and key microbiota associated with LPTE's effects, while also primally elucidating the action mechanisms of LPTE in alleviating NAFLD. The findings offer a conceptual basis for LPTE's potential transformation into an innovative pharmaceutical agent for NAFLD prevention.

Appropriate Stubble Height Can Effectively Improve the Rice Quality of Ratoon Rice.

Ratoon rice, the cultivation of a second crop from the stubble after the main harvest, is recognized as an eco-friendly and resource-saving method for rice production. Here, a field experiment was carried out in the Yangtze River region to investigate the impact of varying stubble heights on the grain quality of ratoon rice, as well as to compare the grain quality between the main and ratoon season. This study, which focused on 12 commonly cultivated rice varieties, conducted a comprehensive analysis assessing milling characteristics, appearance, and cooking quality. The results show that ratoon rice crops exhibited a higher milled rice rate and head rice rate compared to the main rice crops. Conversely, chalky rice percentage, chalkiness degree, and amylose content were lower in ratoon rice crops. Principal component analysis grouped eight relevant quality indicators of rice quality which were concentrated into three categories, with amylose content identified as the key indicator of rice quality for distinguishing between different stubble heights. Random forest results reveal a robust and significant correlation between appearance quality index and amylose content. Subordinate function analysis indicated that a stubble height of 30 cm resulted in optimal rice quality, with Lingliangyou 211 exhibiting the highest quality and Xiangzao Xian 32 the lowest. Overall, our study suggests that ratoon rice crops generally outperform main rice crops in terms of quality, with the optimal measurement at a stubble height of 30 cm. This study holds substantial importance for selecting appropriate stubble heights for ratoon rice crops and enhancing overall rice quality.

Revealing the intrinsic relationship between microbial communities and physicochemical properties during ripening of Xuanwei ham.

To clarify the relationship between microorganisms and physicochemical indicators of Xuanwei ham. Six ham samples for the first, second and third year were selected, respectively. The changes of physicochemical properties, the free fatty acids and microbial communities of Xuanwei ham were investigated by GC-MS and high-throughput sequencing technology. Results showed that scores of colour, overall acceptability, texture, taste and aroma were the highest in the third year sample. With increasing ripening time, moisture content, water activity (Aw), lightness (L*), springiness, and resilience decreased continuously, and yellowness (b*) was the highest in the second year sample. 31 free fatty acids were detected, and unsaturated fatty acids such as palmitoleic acid, oleic acid, and linoleic acid were the major fatty acids. The content of palmitoleic acid, oleic acid and eicosenoic acid increased significantly during processing. At the phylum level, the dominant bacteria were Proteobacteria and Firmicutes, and fungi were Ascomycota. At the genus level, the dominant bacteria were Staphylococcus and Psychrobacter, and fungi were Aspergillus. Correlation analysis showed that water content and Aw were closely related to microorganisms, and most unsaturated fatty acids were significantly correlated with microorganisms. These findings showed that microorganisms played an important role in the quality of Xuanwei ham, and provided a scientific basis for the quality control of Xuanwei ham.

Deciphering the Performance Enhancement, Cell Failure Mechanism, and Amelioration Strategy of Sodium Storage in Metal Chalcogenides-Based Andes.

Transition metal chalcogenides (TMCs) emerge as promising anode materials for sodium-ion batteries (SIBs), heralding a new era of energy storage solutions. Despite their potential, the mechanisms underlying their performance enhancement and susceptibility to failure in ether-based electrolytes remain elusive. This study delves into these aspects, employing CoS2 electrodes as a case in point to elucidate the phenomena. The investigation reveals that CoS2 undergoes a unique irreversible and progressive solid-liquid-solid phase transition from its native state to sodium polysulfides (NaPSs), and ultimately to a Cu1.8S/Co composite, accompanied by a gradual morphological transformation from microspheres to a stable 3D porous architecture. This reconstructed 3D porous structure is pivotal for its exceptional Na+ diffusion kinetics and resilience to cycling-induced stress, being the main reason for ultrastable cycling and ultrahigh rate capability. Nonetheless, the CoS2 electrode suffers from an inevitable cycle life termination due to the microshort-circuit induced by Na metal corrosion and separator degradation. Through a comparative analysis of various TMCs, a predictive framework linking electrode longevity is established to electrode potential and Gibbs free energy. Finally, the cell failure issue is significantly mitigated at a material level (graphene encapsulation) and cell level (polypropylene membrane incorporation) by alleviating the NaPSs shuttling and microshort-circuit.

Effects of Virtual Reality Therapy Combined With Conventional Rehabilitation on Pain, Kinematic Function, and Disability in Patients With Chronic Neck Pain: Randomized Controlled Trial.

BACKGROUND: Neck pain is a common condition that leads to neck motor dysfunction and subsequent disability, with a significant global health care burden. As a newly emerging tool, virtual reality (VR) technology has been employed to address pain and reduce disability among patients with neck pain. However, there is still a lack of high-quality studies evaluating the efficacy of VR therapy combined with conventional rehabilitation for patients with chronic neck pain, particularly in terms of kinematic function. OBJECTIVE: This study aims to investigate the effect of VR therapy combined with conventional rehabilitation on pain, kinematic function, and disability in patients with chronic neck pain. METHODS: We conducted an assessor-blinded, allocation-concealed randomized controlled trial. Sixty-four participants experiencing chronic neck pain were randomly allocated into the experimental group that underwent VR rehabilitation plus conventional rehabilitation or the control group receiving the same amount of conventional rehabilitation alone for 10 sessions over 4 weeks. Pain intensity, disability, kinematic function (cervical range of motion, proprioception, and mean and peak velocity), degree of satisfaction, and relief of symptoms were evaluated at 3 timepoints (baseline, postintervention, and at 3 months follow-up). A 2*3 mixed repeated measures analysis of variance was utilized for analyzing the difference across indicators, with a significant difference level of .05. RESULTS: Both groups demonstrated significant improvements in pain, disability, and kinematic functions (P<.05) at postintervention and at 3-month follow-up. The experimental group showed superior therapeutic outcomes compared to the control group in pain reduction (mean difference from the baseline: 5.50 vs 1.81 at posttreatment; 5.21 vs 1.91 at the 3-month follow-up, respectively; P<.001), disability improvement (mean difference from baseline: 3.04 vs 0.50 at posttreatment; 3.20 vs 0.85 at the 3-month follow-up, respectively; P<.001), and enhanced kinematic functions (P<.05). Moreover, participants in the experimental group reported better satisfaction and relief of symptoms than the control group (P<.05), with better initiative for exercising during the follow-up period. However, there was no between-group difference of improvement in proprioception. No adverse events were reported or observed in our research. CONCLUSIONS: The findings of our study support the efficacy of combining VR therapy with conventional rehabilitation in alleviating pain, enhancing kinematic function, and reducing disability of patients with chronic neck pain. Future research should focus on refining the therapeutic protocols and dosages for VR therapy as well as on optimizing its application in clinical settings for improved convenience and effectiveness. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000040132; http://www.chictr.org.cn/showproj.aspx?proj=64346.

Indirect co-culture of osteoblasts and endothelial cells in vitro based on a biomimetic 3D composite hydrogel scaffold to promote the proliferation and differentiation of osteoblasts.

The field of orthopedics has long struggled with the challenge of repairing and regenerating bone defects, which involves a complex process of osteogenesis requiring coordinated interactions among different types of cells. The crucial role of endothelial cells and osteoblasts in bone vascularization and osteogenesis underscores the importance of their intimate interaction. However, efforts to bioengineer bone tissue have been impeded by the difficulty in establishing proper angiogenesis and osteogenesis in tissue structures. This study presents a novel approach to bone tissue engineering, involving a three-dimensional composite hydrogel scaffold composed of sodium alginate microspheres encapsulated in type I collagen. Using this scaffold, a three-dimensional indirect co-culture system was established for osteoblasts and endothelial cells to evaluate the osteogenic differentiation potential of osteoblasts. Results demonstrate that the non-contact co-culture system of endothelial cells and osteoblasts constructed by the composite hydrogel scaffold loaded with microspheres holds promise for bone tissue engineering. The innovative concept of an indirect co-culture system presents exciting prospects for conducting intercellular communication studies and offers a valuable in vitro tissue platform to investigate tissue regeneration.

Circular RNA CircFOXO3 Functions as a Competitive Endogenous RNA for Acid-Sensing Ion Channel Subunit 1 Mediating Oxeiptosis in Nucleus Pulposus.

Oxeiptosis is a reactive oxygen species (ROS)-induced pathway of cell death. The involvement of circular RNAs (circRNAs) has been confirmed in the incidence and progression of intervertebral disc degeneration (IVDD). However, whether oxeiptosis occurs in IVDD and how circRNAs regulate oxeiptosis is still unclear. In this study, we discovered that oxeiptosis could be induced in nucleus pulposus cells (NPCs), and circFOXO3 was significantly upregulated after oxeiptosis induction. Transfection using circFOXO3 small interfering RNA (siRNA) significantly inhibited oxeiptosis in NPCs. Mechanistically, circFOXO3 upregulated acid-sensing ion channel subunit 1 (ASIC1) expression by functioning as a molecular sponge for miR-185-3p and miR-939-5p. Subsequent rescue experiments validated that circFOXO3 could regulate oxeiptosis in NPCs via the miR-185-3p/miR-939-5p-ASIC1 axis. Further research on ASIC1 functions indicated that this regulation was achieved by affecting the Calcium ion (Ca2+) influx mediated by ASIC1. A mouse IVDD model was established, and silencing circFOXO3 in vivo was found to inhibit IVDD development and the activation of the oxeiptosis-related pathway. Overall, circFOXO3 is one of the factors contributing to the progression of IVDD by mediating oxeiptosis.

Dietary Galacto-oligosaccharides Ameliorate Atopic Dermatitis-like Skin Inflammation and Behavioral Deficits by Modulating Gut Microbiota-Brain-Skin Axis.

Atopic dermatitis (AD), a chronic, highly pruritic, and inflammatory skin disorder, often coexists with psychiatric comorbidities including anxiety and depression, posing considerable challenges for treatment. The current research aims at evaluating the efficacy and potential therapeutic mechanism of galacto-oligosaccharides (GOS) on AD-like skin lesions and comorbid anxiety/depressive disorders. Macroscopical and histopathological examination showed that GOS could markedly relieve skin inflammation by decreasing the production of IgE, IL-4, IL-13, IFN-γ, and TNF-α and regulating the PPAR-γ/NF-κB signaling in DNFB-induced AD mice. Moreover, GOS significantly improved the anxiety- and depressive-like symptoms as mirrored by the behavior tests including FST, TST, OFT, and EZM through normalizing the neurotransmitter levels of 5-HT, DA, NE, and CORT in the brain. Mechanistically, by virtue of the high-throughput 16S rRNA gene sequencing and GC-MS techniques, GOS restructured the gut microbiota and specifically induced the proliferation of Lactobacillus and Alloprevotella, leading to an increase in the total content of fecal SCFAs, in particular acetate and butyrate. Pearson correlation analysis found a marked correlation among the altered gut microbiota/SCFAs, AD-associated skin manifestations, and comorbid behavioral phenotypes. Collectively, this work highlights that GOS is a promising strategy against both AD and associated depressive symptoms by modulating the gut microbiota-brain-skin axis.

Granulation characteristics of anammox sludge in response to different signal-molecule-stimulants; mediated through programmed cell death.

During the anammox process, mitigation of biomass washout to increase sludge retention is an important parameter of process efficiency. Signal molecular stimulants (SMS) initiate the sludge granulations controlled by programmed cell death (PCD) of microorganisms. In this study, the aerobic granular sludge (AGS), cell fragments, extracellular polymeric substances (EPS), and AGS process effluent were tested as SMS to identify their effect on anammox granulation. The results showed that the addition of SMS increased the nitrogen removal efficiency to varying degrees, whereas the addition of AGS process supernatant, as SMS, increased the ammonia removal efficiency up to 96%. The addition of SMS was also found to increase EPS production and contributed to sludge granulation. In this process, the proportion of PCD increased and both Gaiella and Denitratisoma abundance increased from 3.54% to 5.59%, and from 1.8% to 3.42%, respectively. In conclusion, PCD was found important to increase anaerobic ammonia oxidation performance through the granulation mechanism.

Application of Patient-Based Real-Time Quality Control Based on Artificial Intelligence Monitoring Platform in Continuously Quality Risk Monitoring of Down Syndrome Serum Screening.

BACKGROUND: Patient-based real-time quality control (PBRTQC) has gained attention because of its potential to continuously monitor the analytical quality in situations wherein internal quality control (IQC) is less effective. Therefore, we tried to investigate the application of PBRTQC method based on an artificial intelligence monitoring (AI-MA) platform in quality risk monitoring of Down syndrome (DS) serum screening. METHODS: The DS serum screening item determination data and relative IQC data from January 4 to September 7 in 2021 were collected. Then, PBRTQC exponentially weighted moving average (EWMA) and moving average (MA) procedures were built and optimized in the AI-MA platform. The efficiency of the EWMA and MA procedures with intelligent and traditional control rules were compared. Next, the optimal EWMA procedures that contributed to the quality assurance of serum screening were run and generated early warning cases were investigated. RESULTS: Optimal EWMA and MA procedures on the AI-MA platform were built. Comparison results showed the EWMA procedure with intelligent QC rules but not traditional quality rules contained the best efficiency. Based on the AI-MA platform, two early warning cases were generated by using the optimal EWMA procedure, which finally found were caused by instrument failure. Moreover, the EWMA procedure could truly reflect the detection accuracy and quality in situations wherein traditional IQC products were unstable or concentrations were inappropriate. CONCLUSIONS: The EWMA procedure built by the AI-MA platform could be a good complementary control tool for the DS serum screening by truly and timely reflecting the detection quality risks.

Androgen signaling inhibits de novo lipogenesis to alleviate lipid deposition in zebrafish.

Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males. However, the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood, especially in teleosts. In this study, cyp17a1-/- zebrafish ( Danio rerio) exhibited excessive visceral adipose tissue (VAT), lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis (DNL) enzymes. The assay for transposase accessible chromatin with sequencing (ATAC-seq) results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/- fish compared to cyp17a1+/+ male fish, including stearoyl-CoA desaturase ( scd) and fatty acid synthase ( fasn). Androgen response element (ARE) motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+ male fish but not in cyp17a1-/- fish. Both androgen receptor ( ar)-/- and wild-type (WT) zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue, lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis enzymes. The Ar agonist BMS-564929 reduced the content of VAT and lipid content, and down-regulated acetyl-CoA carboxylase a ( acaca), fasn, and scd expression. Mechanistically, the rescue effect of testosterone on cyp17a1-/- fish in terms of phenotypes was abolished when ar was additionally depleted. Collectively, these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish, thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.

Imaging signs for preoperative diagnosis of dural ossification in patients with thoracic ossification of the ligamentum flavum: a blind, randomized diagnostic accuracy study.

Background: Dural ossification (DO) is the leading cause of surgery-related dural tear in patients with ossification of the ligamentum flavum (OLF). An accurate preoperative diagnosis of DO is conducive to the selection of appropriate surgical methods. Although several imaging signs, such as Banner cloud sign (BCs), tram-track sign (TTs), and comma sign (Cs) have been proposed for the preoperative diagnosis of DO, their diagnostic value has not been well studied. The aim of this study was to explore the diagnostic value of BCs, TTs, and Cs, and provide evidence-based data for their clinical application. Methods: This is a blind, randomized diagnostic study using retrospectively collected data from 102 consecutive patients who were diagnosed with OLF and underwent decompression surgery between January 2018 and June 2019. A total of 8 surgeons with different qualifications were recruited to read these imaging signs to identify the presence of DO. Surgical records were used as the reference standard. Sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC) were used to evaluate the diagnostic accuracy of each imaging sign and their different combinations. Results: Of the 102 patients, 21 were diagnosed with DO. BCs had a significantly higher diagnostic accuracy than TTs and Cs, with the AUC of 0.704, 0.607, and 0.593, respectively. The specificity of BCs, Cs, TTs, and their combination in diagnosing DO was 91.5%, 92.1%, 68.3%, and 62.2%, respectively. In the combined diagnostic test, the results showed that the combined diagnosis accuracy of BCs and Cs was the highest, and the AUC was 0.738. The combination of BCs, Cs, and TTs increased the sensitivity of diagnosing DO (77.5%), but did not improve the diagnostic accuracy, and the AUC was 0.699. Conclusions: BCs had higher diagnostic accuracy than TTs and Cs. BCs and Cs were highly specific for DO, whereas TTs could be confusing due to their non-specific presentations. The combination of BCs, TTs, and Cs improved the sensitivity of DO diagnosis, but not the specificity and accuracy.

Parenting behaviors, inhibitory control, and aggression: Moderation by serotonin receptor 2A haplotypes.

Despite the well-established relationship between parenting and child aggression, the mechanisms by which children incur this risk and whether genetic sources contribute to the heterogeneity in their vulnerability are not entirely clear. This study utilized a longitudinal sample of adolescents (n = 1,047, 50.2% females, Mage = 13.32 ± 0.48 years at Time 1) to examine the effects of positive and negative parenting on aggression, as mediated by inhibitory control and moderated by the serotonin receptor 2A (5-HTR2A) haplotype. Mediation analysis revealed that inhibitory control indirectly mediated the link between both positive and negative parenting and overt aggression but not relational aggression. Further, the indirect effect of negative parenting on overt aggression via inhibitory control was moderated by the 5-HTR2A haplotype. Compared to adolescents carrying zero copies of Thymine-Thymine haplotype, those with one copy of Thymine-Thymine haplotype had better inhibitory control when experiencing less negative parenting, which buffers the risk for overt aggression. However, the mediating role of inhibitory control did not hold in the positive parenting model. These findings elucidate the manner by which adolescents with different genetic predispositions develop aggressive behaviors in the context of family and suggest different etiology of overt and relational aggression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Testosterone synthesis was inhibited in the testis metabolomics of a depression mouse model.

INTRODUCTION: Depression is a common emotional disorder. Previous studies have suggested that depression is associated with the central nervous system. Recent studies have suggested that reduced testosterone level is the core inducement of depression. Testis is the vital organ for the synthesis of testosterone. How does testis mediate depression is still unknown. OBJECTIVES: We adopted a classical depression model of mouse caused through chronic mild stress (CMS). The metabolomics liquid chromatography-mass spectrometry was adopted to analyse the influence of CMS on testis metabolism. Then we confirmed the possible abnormal metabolism of the testis in depression mice by pathway analysis and molecular biological technique. RESULTS: Compared with control mice, 16 differential metabolites were found in CMS mice by multivariate statistical analysis. In comparison with control mice, CMS mice showed higher levels for campesterol, ribitol, citric acid, platelet activating factor, guanosine, cytosine and xanthine and lower levels for docosahexaenoic acid, hippuric acid, creatine, testosterone, dehydroepiandrosterone, progesterone, l-carnitine, acetyl carnitine and propionyl carnitine. The pathway analysis indicated that these differential metabolites are associated with steroid hormone synthesis, purine metabolism and phenylalanine metabolism. In addition, we also first discovered that testicular morphology in depression mice was damaged and steroid hormone synthetases (including steroidogenic acute regulatory protein and P450 cholesterol side chain cleavage) were inhibited. CONCLUSION: These findings may be helpful to parse molecular mechanisms of pathophysiology of depression. It also pointed out the direction to search for potential therapy schedules for male depression and provide novel insights into exploring the pathogenesis of male depression.

M1 macrophage-derived oncostatin M induces osteogenic differentiation of ligamentum flavum cells through the JAK2/STAT3 pathway.

Background: M1 macrophages (Mφs) are involved in osteogenic differentiation of ligamentum flavum (LF) cells and play an important role in heterotopic ossification. However, the mechanism by which M1 Mφs influence osteogenic differentiation of LF cells has not been studied. Methods: The effect of conditioned medium including secretions of M1 Mφs (CM-M1) on LF cells was analyzed by GeneChip profiling and ingenuity pathway analysis (IPA). THP-1 cells were polarized into M1 Mφs and CM-M1 was used to induce LF cells. In addition, LF cells were induced by CM-M1 in the presence of cyclooxygenase 2 (COX-2) inhibitors or oncostatin M (OSM)-neutralizing antibodies. Based on the presence of OSM, knockout of OSMR or GP130 receptors, or addition of the Janus kinase 2 (JAK2) inhibitor AZD1480 or signal transducer and activator of transcription 3 (STAT3) inhibitor Stattic were examined for effects on osteogenic differentiation of LF cells. OSM secretion was quantified by ELISA, while qPCR and western blot were used to evaluate expression of osteogenic genes and receptor and signaling pathway-related proteins, respectively. Results: GeneChip and IPA results indicate that the OSM signaling pathway and its downstream signaling molecules JAK2 and STAT3 are significantly activated. ELISA results indicate that OSM is highly expressed in cells treated with CM-M1 and lowly expressed in cells treated with CM-M1 and a COX-2 inhibitor. Besides, CM-M1 induces osteogenic differentiation of LF cells, which is weakened when COX-2 inhibitors or OSM-neutralizing antibody are added to it. Recombinant OSM could induce osteogenic differentiation of LF cells and upregulate expression of OSMR, GP130, phosphorylated (P)-JAK2, and P-STAT3. Upon knockdown of OSMR or GP130, or the addition of AZD1480 or Stattic, P-JAK2 and P-STAT3 expression were decreased and osteogenic differentiation was reduced. Conclusion: M1 Mφ-derived OSM induces osteogenic differentiation of LF cells and the JAK2/STAT3 signaling pathway plays an important role.

Evaluation of the effects of compound curing agents on the lipid profiles and volatile flavors in Nuodeng ham based on lipidomics and GC-IMS analysis.

Eighteen raw legs were evenly divided into two groups and salted with 100% NaCl and compound curing agent (60% NaCl + 40% KCl + 90 mg/kg NaNO2) to investigate the effect of compound curing agent on lipid metabolites and volatile flavor compounds in Nuodeng ham. The results of UHPLC-QE-MS and GC-IMS combined with multivariate statistical analysis showed that 27 lipid metabolites and 30 characteristic volatile flavor compounds were identified as characteristic markers in different treatment groups. The compound curing agent promoted the release of TG, SQDG, Hex1Cer, and LPC in Nuodeng ham, and accelerated the formation of volatile compounds such as 2-propanone, nonanal-d, gamma-butyrolactone, ethhyl acetate and benzeneacetaldehyde et al. Through correlation analysis, ketones were positively correlated with some PUFAs and negatively correlated with most MUFAs. Processing Nuodeng ham with compound curing agents has a positive effect on improving its quality. These findings provide a scientific theoretical basis for the development and utilization of compound curing agent.