Current status and influencing factors of prophylactic use of proton pump inhibitors in internal medicine inpatients receiving glucocorticoid therapy.

Background: The actual situation and influencing factors of prophylactic use of proton pump inhibitors (PPIs) in internal medicine inpatients receiving glucocorticoid therapy are rarely reported. This study aimed to investigate the current status and influencing factors of prophylactic use of PPIs in internal medicine inpatients receiving glucocorticoid therapy to provide a basis for rational prophylactic use of PPIs. Methods: Internal medicine inpatients receiving glucocorticoid therapy from February 2023 to September 2023 were included. Information on the prophylactic use of PPIs was collected and analyzed by clinical pharmacists. Associated factors with prophylactic use of PPIs were analyzed by univariable and multivariable logistic regression. Results: 980 inpatients were finally included in our study, of which 271 (27.7%) inpatients received prophylactic use of PPIs. Among the inpatients prescribed PPIs, 90 inpatients received a standard dose of PPIs twice a day. Multiple logistic regression analysis showed that age ≥80 years [OR = 7.009, 95% CI (1.424, 34.495), p = 0.017], history of gastroesophageal reflux disease (GERD) [OR = 2.047, 95% CI (1.338, 3.133), p = 0.001], low platelet count [OR = 0.997, 95% CI (0.994, 0.999), p = 0.004], number of concomitant diseases [OR = 1.104, 95% CI (1.056, 1.153), p < 0.001], junior doctors [OR = 1.755, 95% CI (1.248, 2.468), p = 0.001], glucocorticoid dose (higher than 50 mg, measured by methylprednisolone) [OR = 2.455, 95% CI (1.371, 4.395), p = 0.003], antiplatelet agents [OR = 2.567, 95% CI (1.456, 4.524), p = 0.001], immunosuppressants [OR = 1.477, 95% CI (1.014, 2.153), p = 0.042], and betahistine [OR = 5.503, 95% CI (1.124, 26.950), p = 0.035] were associated with more prophylactic use of PPIs. Conclusion: The prophylactic use of PPIs in internal medicine inpatients receiving glucocorticoid therapy is common in China. Clinical pharmacists will take targeted measures to promote the rational use of PPIs according to the results of this study.

Exploration of potential antidiabetic and antioxidant components from the branches of Mitragyna diversifolia and possible mechanism.

In this study, sixteen compounds were isolated from the branches of Mitragyna diversifolia, including twelve triterpenes (1-12), a phenolic compound (13), and three flavonoids (14-16). Among them, compounds 1-7, and 10-16 were reported for the first time from this plant. Compounds 7, 14, and 15 exhibited significant inhibitory activities against α-glucosidase, with IC50 values of 18.48 ± 2.74, 12.14 ± 1.58 and 35.77 ± 4.52 µM, respectively. Furthermore, the inhibitory kinetics of α-glucosidase revealed that all fractions, active compounds 7, 14, and 15 belong to the mix inhibition type. In molecular docking, the analysis showed that compounds 13, 14, 15, and 16 possessed superior binding capacities with α-glucosidase (-8.3, -9.6, -9.9, and -9.2 kcal/mol, respectively). The results of the glucose uptake experiment indicated that only compound 14 showed a significant promotion effect on the glucose uptake rate of 3T3-L1 adipocytes (P < 0.05). Meanwhile, compounds 13, 14, 15, and 16 possessed potent antioxidant abilities with DPPH, ABTS, and FRAP. In DNA and protein oxidative damage assays, compound 15 had a stronger effect than the positive control Vc. The network-based pharmacological analysis platform was used to predict the diabetes-related target proteins of active compounds 7, 13, 14, 15, and 16, and two candidate targets (ALB and PPARG) related to their therapeutic effects on diabetes were identified.

Optical coherence tomography angiography for microaneurysms in anti-vascular endothelial growth factor treated diabetic macular edema.

BACKGROUND: We aimed to evaluate microaneurysms (MAs) after treatment with anti-vascular endothelial growth factor (anti-VEGF) therapy to understand causes of chronic edema and anti-VEGF resistance. METHODS: Patients with non-proliferative diabetic retinopathy, with or without macular edema were recruited. Optical coherence tomography angiography (OCTA) MAs-related parameters were observed, including the maximum diameter of overall dimensions, material presence, and flow signal within the lumen. OCTA parameters also included central macular thickness (CMT), foveal avascular zone, superficial and deep capillary plexuses, and non-flow area measurements on the superficial retinal slab. RESULTS: Overall, 48 eyes from 43 patients were evaluated. CMT differed significantly between the diabetic macular edema (DME ) and non-DME (NDME) groups at 1st, 2nd, 3rd, and 6th months of follow-up (P < 0.001; <0.001; 0.003; <0.001, respectively). A total of 55 and 59 MAs were observed in the DME (mean = 99.40 ± 3.18 µm) and NDME (mean maximum diameter = 74.70 ± 2.86 µm) groups at baseline, respectively (significant between-group difference: P < 0.001). Blood flow signal was measurable for 46 (83.6%) and 34 (59.3%) eyes in the DME and NDME groups, respectively (significant between-group difference: P < 0.001). CONCLUSIONS: Compared to the NDME group, the DME group had larger MAs and a higher blood-flow signal ratio. Following anti-VEGF therapy, changes in the diameter of MAs were observed before changes in CMT thickness.

Therapeutic effect of three-dimensional hanging drop cultured human umbilical cord mesenchymal stem cells on osteoarthritis in rabbits.

BACKGROUND: Mesenchymal stem cells (MSCs) have shown a positive effect on Osteoarthritis (OA), but the efficacy is still not significant in clinical. Conventional two-dimensional (2D) monolayer culture method is prone to cause MSCs undergoing replication senescence, which may affect the functions of MSCs. Three-dimensional (3D) culture strategy can sustain cell proliferative capacity and multi-differentiation potential. This study aimed to investigate the therapeutic potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) cultured by 3D hanging drop method on OA. METHODS: hUC-MSCs were isolated from umbilical cord and cultured by 3D hanging drop method for 48 h. Scanning electron microscopy (SEM) was used to observe gross morphology 2D and 3D hUC-MSCs. Transcriptome comparison of gene expression differences between 2D and 3D hUC-MSCs. GO enrichment analysis, KEGG pathway enrichment analysis and GSEA enrichment analysis were used to analyze the impact of 3D hanging drop culture on the biological functions of hUC-MSCs. Female New Zealand rabbits (n = 12) were divided into 4 groups: Normal group, Model group, 2D hUC-MSCs treatment group and 3D hUC-MSCs treatment group. After 8 weeks, the gross and histological appearance of the cartilage was evaluated by safranin O-fast green staining and Mankin scoring system. The expression of type I collagen and type II collagen was detected by immunohistochemistry. The levels of IL-6, IL-7, TNFα, TGFß1 and IL-10 in the knee joint fluid were tested by ELISA. RESULTS: 3D hanging drop culture changed cell morphology but did not affect phenotype. The MSCs transcriptome profiles showed that 3D hanging drop culture method enhanced cell-cell contact, improved cell responsiveness to external stimuli and immunomodulatory function. The animal experiment results showed that hUC-MSCs could promote cartilage regeneration compared with Model group. 3D hUC-MSCs treatment group had a higher histological score and significantly increased type II collagen secretion. In addition, 3D hUC-MSCs treatment group increased the expression of anti-inflammatory factors TGFß1 and IL-10. CONCLUSION: The above experimental results illustrated that 3D hanging drop culture method could enhance the therapeutic effect of hUC-MSCs, and showed a good clinical application prospect in the treatment of OA.

Multi-pesticide residue screening, identification, and quantification analysis in various fruits and vegetables by UHPLC-Q Exactive HRMS.

A general strategy for qualitative screening and quantitative analysis of 403 pesticides in various fruits and vegetables was developed using ultrahigh-performance liquid chromatography (UHPLC) in conjunction with a Thermo Q Exactive Focus high-resolution mass spectrometer, relying on an executable compound database comprised of the exacted mass of precursor ions, retention times, and fragment ions. Taking advantage of the powerful separation capacity of UHPLC, an Orbitrap analyzer with high sensitivity in full scan mode and elevated mass resolution of product ions in the MS/MS mode, eight pairs of isomers and fifty-seven groups of isobaric compounds were selectively identified. The method was then systematically assessed and validated for eight fruits and vegetables, in terms of screening detection limit (SDL), matrix effects, recovery, and precision over 400 pesticides. The results showed that the SDLs of 68.0-84.4% for the pesticides were less than or equal to 10 µg kg-1 in the representative matrices, recoveries in the range of 60-120% accounting for 48.6-84.4% of all the targets at three lower fortified levels of 5, 20, and 50 µg kg-1 with a precision of less than 20% while the range of overall average recoveries for the majority of the pesticides were from 82.4% to 105.1% in the as-selected matrices with RSDs between 3.9% and 7.7%. Using this method, screening data from a survey of pesticide residues in 68 practical samples across 32 different matrix types provides scientific data for the inspection and supervision of pesticide residue safety of fruits and vegetables.

Novel Identification of Ankyrin-R in Cardiac Fibroblasts and a Potential Role in Heart Failure.

Altered ankyrin-R (AnkR; encoded by ANK1) expression is associated with diastolic function, left ventricular remodeling, and heart failure with preserved ejection fraction (HFpEF). First identified in erythrocytes, the role of AnkR in other tissues, particularly the heart, is less studied. Here, we identified the expression of both canonical and small isoforms of AnkR in the mouse myocardium. We demonstrate that cardiac myocytes primarily express small AnkR (sAnkR), whereas cardiac fibroblasts predominantly express canonical AnkR. As canonical AnkR expression in cardiac fibroblasts is unstudied, we focused on expression and localization in these cells. AnkR is expressed in both the perinuclear and cytoplasmic regions of fibroblasts with considerable overlap with the trans-Golgi network protein 38, TGN38, suggesting a potential role in trafficking. To study the role of AnkR in fibroblasts, we generated mice lacking AnkR in activated fibroblasts (Ank1-ifKO mice). Notably, Ank1-ifKO mice fibroblasts displayed reduced collagen compaction, supportive of a novel role of AnkR in normal fibroblast function. At the whole animal level, in response to a heart failure model, Ank1-ifKO mice displayed an increase in fibrosis and T-wave inversion compared with littermate controls, while preserving cardiac ejection fraction. Collagen type I fibers were decreased in the Ank1-ifKO mice, suggesting a novel function of AnkR in the maturation of collagen fibers. In summary, our findings illustrate the novel expression of AnkR in cardiac fibroblasts and a potential role in cardiac function in response to stress.

Effects of different doses of alfentanil on cardiovascular response to rapid sequence intubation in elderly patients: a parallel-controlled randomized trial.

BACKGROUND: Rapid sequence intubation (RSI) have been shown to be effective in preventing reflux aspiration in patients with a full stomach during anaesthesia induction and endotracheal intubation. However, there is currently no standardized operation protocol or anaesthesia induction drug standard for RSI. Furthermore, there is a lack of evidence regarding the use of RSI in patients older than 65. In this study, we aimed to investigate the cardiovascular effects of different doses of alfentanil combined with propofol and etomidate during RSI in elderly patients aged 65-80 years. METHODS: A total of 96 patients aged 65-80 years who underwent general anaesthesia with tracheal intubation were selected for this study. The patients were randomly assigned to one of four groups using a random number table. Group A patients received an induction dose of 10 µg/kg alfentanil, group B patients received 15 µg/kg alfentanil, group C patients received 20 µg/kg alfentanil, and group D patients received 25 µg/kg alfentanil. Heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), and ejection fraction (EF) were measured at three time points: 5 min before anaesthesia induction (T0), 1 min after endotracheal intubation (T1), and 5 min after endotracheal intubation (T2). Concurrently, 4 ml of arterial blood was collected from patients at three time points, and the concentrations of norepinephrine (NE) and cortisol (Cor) in plasma were detected. Occurrences of hypertension, hypotension, bradycardia and tachycardia during anesthesia induction to 5 min after tracheal intubation were noted. RESULTS: Compared with T0, the HR, MAP, NE and Cor concentrations in group A and group B were increased at the T1 and T2 time points, CI and EF values were decreased (P < 0.05). HR and MAP in groups C and D were increased at the T1 time point, while they were decreased at the T2 time point in group D (P < 0.05). The changes in CI and EF values, concentrations of NE and Cor, were not significant at T1 and T2 time points in group C (P > 0.05). Additionally, they were not significant in group D at the T1 time point (P > 0.05), but decreased at the T2 time point (P < 0.05). Compared with group A, the HR, MAP, NE and Cor concentrations in groups C and D were decreased at T1 and T2 time points (P < 0.05). The CI and EF values of groups C and D were increased at T1 time point but decreased at T2 time point in group D (P < 0.05). The incidence of hypertension and tachycardia in group A was significantly higher than that in group C and group D (P < 0.05), and the incidence of hypotension and bradycardia in group D was significantly higher than that in group A and group B (P < 0.05). CONCLUSION: Alfentanil 20 µg/kg for RSI in elderly patients, can effectively inhibit the violent cardiovascular reaction caused by intubation, and avoid the inhibition of cardiovascular system caused by large dose, hemodynamics more stable. TRIAL REGISTRATION: ChiCTR2200062034 ( www.chictr.org.cn ).

Soil metagenomics reveals the effect of nitrogen on soil microbial communities and nitrogen-cycle functional genes in the rhizosphere of Panax ginseng.

Nitrogen (N) is the primary essential nutrient for ginseng growth, and a reasonable nitrogen application strategy is vital for maintaining the stability of soil microbial functional communities. However, how microbial-mediated functional genes involved in nitrogen cycling in the ginseng rhizosphere respond to nitrogen addition is largely unknown. In this study, metagenomic technology was used to study the effects of different nitrogen additions (N0: 0, N1: 20, N2: 40 N g/m2) on the microbial community and functional nitrogen cycling genes in the rhizosphere soil of ginseng, and soil properties related to the observed changes were evaluated. The results showed that N1 significantly increased the soil nutrient content compared to N0, and the N1 ginseng yield was the highest (29.90% and 38.05% higher than of N0 and N2, respectively). N2 significantly decreased the soil NO3 -N content (17.18 mg/kg lower than N0) and pH. This resulted in a decrease in the diversity of soil microorganisms, a decrease in beneficial bacteria, an increase in the number of pathogenic microorganisms, and an significant increase in the total abundance of denitrification, assimilatory nitrogen reduction, and dissimilatory nitrogen reduction genes, as well as the abundance of nxrA and napA genes (17.70% and 65.25% higher than N0, respectively), which are functional genes involved in nitrification that promote the soil nitrogen cycling process, and reduce the yield of ginseng. The results of the correlation analysis showed that pH was correlated with changes in the soil microbial community, and the contents of soil total nitrogen (TN), ammonium nitrogen (NH4 +-N), and alkaline-hydrolyzed nitrogen (AHN) were the main driving factors affecting the changes in nitrogen cycling functional genes in the rhizosphere soil of ginseng. In summary, nitrogen addition affects ginseng yield through changes in soil chemistry, nitrogen cycling processes, and functional microorganisms.

Magnetic Activation: A Novel Approach to Enhance Hydrogen Evolution Activity of Co0.85Se@CNTs Heterostructured Catalyst.

The heterostructure strategy is currently an effective method for enhancing the catalytic activity of materials. However, the challenge that is how to further improve their catalytic performance, based on the principles of material modification is must addressed. Herein, a strategy is introduced for magnetically regulating the catalytic activity to further enhance the hydrogen evolution reaction (HER) activity for Co0.85Se@CNTs heterostructured catalyst. Building on heterostructure modulation, an external alternating magnetic field (AMF) is introduced to enhance the electronic localization at the active sites, which significantly boosts catalytic performance (71 to 43 mV at 10 mA cm-2). To elucidate the catalytic mechanism, especially under the influence of the AMF, in situ Raman spectroscopy is innovatively applied to monitor the HER process of Co0.85Se@CNTs, comparing conditions with and without the AMF. This study demonstrates that introducing the AMF does not induce a change in the true active site. Importantly, it shows that the Lorentz force generated by the AMF enhances HER activity by promoting water molecule adsorption and O─H bond cleavage, with the Stark tuning rate indicating increased water interaction and bond cleavage efficiency. Theoretical calculations further support that the AMF optimizes energy barriers for key reaction intermediates (steps of *H2O-TS and *H+*1/2H2).

Pivotal Role of Modifiable A-Site Doping in Enhancing Valence Stability and Excited State Dynamics of MnO6.

The controlled regulation of A-site in rare earth manganate perovskites can orderly arrange the electronic states, leading to the emergence of unique transport properties. However, it is challenging to balance crystal structure stability and property variations during the multi-ion doping. In this study, a series of multivalent manganate perovskites are synthesized by hydrothermal method through the A-site multielement doping, which enables the manganese atoms with varying valence states to orderly arrange at the B site. Powder X-ray diffraction (PXRD) and X-ray absorption spectra (XAS) confirm that the splitting of the K─O hybrid orbitals in the crystal effectively prevents any distortion of the MnO6 octahedron, thereby facilitating the ordered arrangement of Mn (III) -Mn (IV) -Mn (V) at the B-site and promoting superstructure formation. The transient absorption spectra (TAS) reveals that the sequential arrangement of Mn (III) - Mn (IV) - Mn(V) better forms the charge transfer channels, and thereby makes the photodynamic properties of the sample composition-dependent. These photodynamic properties will facilitate the study of exciton-electron coupling behavior in LCKMO crystals during electrical transport.

Amugulang virus, a novel hantavirus harboured by small rodents in Hulunbuir, China.

The Hulunbuir region, known for its diverse terrain and rich wildlife, is a hotspot for various natural epidemic diseases. Between 2021 and 2023, we collected 885 wild rodent samples from this area, representing three families, seven genera, and eleven species. Metagenomic analysis identified three complete nucleic acid sequences from the S, M, and L segments of the Hantaviridae family, which were closely related to the Khabarovsk virus. The nucleotide coding sequences for S, M, and L (1392 nt, 3465 nt, and 6491 nt, respectively) exhibited similarities of 82.34%, 81.68%, and 81.94% to known sequences, respectively, while protein-level analysis indicated higher similarities of 94.92%, 94.41%, and 95.87%, respectively. Phylogenetic analysis placed these sequences within the same clade as the Khabarovsk, Puumala, Muju, Hokkaido, Topografov, and Tatenalense viruses, all of which are known to cause febrile diseases in humans. Immunofluorescence detection of nucleic acid-positive rodent kidney samples using sera from patients with hemorrhagic fever and renal syndrome confirmed the presence of viral particles. Based on these findings, we propose that this virus represents a new member of the Hantaviridae family, tentatively named the Amugulang virus, after its primary distribution area.

Emerging therapeutic strategies targeting extracellular histones for critical and inflammatory diseases: an updated narrative review.

Extracellular histones are crucial damage-associated molecular patterns involved in the development and progression of multiple critical and inflammatory diseases, such as sepsis, pancreatitis, trauma, acute liver failure, acute respiratory distress syndrome, vasculitis and arthritis. During the past decade, the physiopathologic mechanisms of histone-mediated hyperinflammation, endothelial dysfunction, coagulation activation, neuroimmune injury and organ dysfunction in diseases have been systematically elucidated. Emerging preclinical evidence further shows that anti-histone strategies with either their neutralizers (heparin, heparinoids, nature plasma proteins, small anion molecules and nanomedicines, etc.) or extracorporeal blood purification techniques can significantly alleviate histone-induced deleterious effects, and thus improve the outcomes of histone-related critical and inflammatory animal models. However, a systemic evaluation of the efficacy and safety of these histone-targeting therapeutic strategies is currently lacking. In this review, we first update our latest understanding of the underlying molecular mechanisms of histone-induced hyperinflammation, endothelial dysfunction, coagulopathy, and organ dysfunction. Then, we summarize the latest advances in histone-targeting therapy strategies with heparin, anti-histone antibodies, histone-binding proteins or molecules, and histone-affinity hemoadsorption in pre-clinical studies. Finally, challenges and future perspectives for improving the clinical translation of histone-targeting therapeutic strategies are also discussed to promote better management of patients with histone-related diseases.

Association of geriatric nutritional risk index with bone mineral density and osteoporosis in postmenopausal elderly women with T2DM.

BACKGROUND AND OBJECTIVES: To investigate the relationship between geriatric nutritional risk index (GNRI) and osteoporosis (OP) in postmenopausal elderly women with type 2 diabetes mellitus (T2DM). METHODS AND STUDY DESIGN: A total of 141 postmenopausal elderly women with T2DM was divided into OP and normal bone mineral density (BMD) groups, the differences in GRNI levels between the two groups were compared. According to the tertile levels of GRNI, T2DM were divided into three groups (T1, T2, T3 groups), and the differences in OP prevalence and levels of BMD among the three groups were compared. RESULTS: Among postmenopausal elderly women with T2DM, GNRI levels were lower in the OP group compared to the nor-mal BMD group [(103±5.46) vs. (105±5.46), p<0.05)]. With elevated GNRI levels, the BMD levels of femoral, total hip, total body, and lumbar vertebrae (L) were gradually increased, which were higher in the T3 group than in the T1 group (all p< 0.05). GNRI levels were positively correlated with the BMD levels of femoral, spine, total hip, total body, L1, L2, L3, L4, and L1-L4. GNRI was an independent influencing factor for the occurrence of OP (OR=0.887, 95%CI [0.795,0.988]). The ROC curve showed that the GNRI combined with serum ALP and P levels had a high predictive value for OP, with an area under the curve of 0.725 (p<0.01). CONCLUSIONS: In postmenopausal elderly women with T2DM, GNRI was independently and positively correlated with BMD levels. GNRI may be a predictor development of OP.

[Change Characteristics of Carbonaceous Aerosol in Chengdu from 2018 to 2021].

Carbonaceous aerosol is an important component of atmospheric fine particulates （PM2.5） that has an important effect on global climate change, atmospheric visibility, regional air quality, and human health. In order to investigate the long-term change characteristics of carbonaceous aerosols under the background of emission reduction, the concentrations of organic carbon （OC）, elemental carbon （EC） in PM2.5 samples, and volatile organic compounds （VOCs） in Chengdu from 2018 to 2021 and the corresponding meteorological factors were obtained through real-time online monitoring. The results showed that the average ρ（OC） and ρ（EC） during the monitoring period were （10.9 ±5.7） µg·m-3 and （2.6 ±1.9） µg·m-3, accounting for 25.2% and 6.0% of PM2.5, respectively, and the average ρ（SOC） was （5.7 ±3.3） µg·m-3, accounting for 52.9% of OC. The concentrations of OC, EC, and PM2.5 showed a downward trend from 2018 to 2020 [PM2.5： The concentration of average annual decrease was -7.1 µg·ï¼ˆm3·a） -1, with an average annual decrease of -14.6 %·a-1； OC： -1.7 µg·ï¼ˆm3·a）-1, -14.2 %·a-1； EC： -0.1 µg·ï¼ˆm3·a）-1, -4.4 %·a-1], and the concentrations of each pollutant in 2021 rebounded in different ranges compared with those in 2020. The concentrations of PM2.5 and OC were as follows： winter > spring > autumn > summer, and the concentrations of EC were as follows： winter > autumn > spring > summer. The proportions of OC and EC were higher in summer and autumn than in other seasons, with the average proportions of 26.8% and 6.9%, respectively. With the aggravation of the pollution level, OC, EC, and SOC concentrations gradually increased, but the proportions in PM2.5 showed a gradual downtrend, indicating that the control factor of PM2.5 pollution in Chengdu was not the carbon component. Source apportionment results showed that carbonaceous aerosols in Chengdu were mainly affected by motor vehicles, industrial sources, biomass combustion sources, and VOCs secondary reaction. From 2019 to 2021, EC was affected by the characteristic components of motor vehicles and decreased yearly. OC and EC were affected by VOCs more in spring and autumn than in other seasons. VOCs emission management should be increased in spring and autumn to reduce the impact of secondary reaction.

Measuring the Scientific Impact of Growth Hormone Treatment in Burns: A Bibliometric Analysis Based on CiteSpace.

This study utilized CiteSpace software to conduct a bibliometric analysis of the literature related to the use of growth hormone in treating burns. The results showed that the research on this topic has attracted increasing attention from scholars worldwide, with the number of publications increasing annually. The research teams and institutions involved in this field are mainly concentrated in China, followed by the United States, Russia, and other countries. The analysis also revealed the prominent co-cited literature and the most influential authors in the field, such as Herndon，DN.and Li Y. The main research themes identified in the literature included the effects of growth hormone on wound healing, tissue repair and regeneration, inflammatory responses, and cell proliferation. Additionally, the research on the clinical applications of growth hormone in burn treatment has been expanded to include areas such as metabolic regulation, immune function, and the prevention of infections. The findings of this study provide useful insights into the current status and future directions of research in the field of growth hormone treatment of burns.

Olanzapine Modulate Lipid Metabolism and Adipose Tissue Accumulation via Hepatic Muscarinic M3 Receptor-Mediated Alk-Related Signaling.

Olanzapine is an atypical antipsychotic drug and a potent muscarinic M3 receptor (M3R) antagonist. Olanzapine has been reported to cause metabolic disorders, including dyslipidemia. Anaplastic lymphoma kinase (Alk), a tyrosine kinase receptor well known in the pathogenesis of cancer, has been recently identified as a key gene in the regulation of thinness via the regulation of adipose tissue lipolysis. This project aimed to investigate whether Olanzapine could modulate the hepatic Alk pathway and lipid metabolism via M3R. Female rats were treated with Olanzapine and/or Cevimeline (an M3R agonist) for 9 weeks. Lipid metabolism and hepatic Alk signaling were analyzed. Nine weeks' treatment of Olanzapine caused metabolic disturbance including increased body mass index (BMI), fat mass accumulation, and abnormal lipid metabolism. Olanzapine treatment also led to an upregulation of Chrm3, Alk, and its regulator Ptprz1, and a downregulation of Lmo4, a transcriptional repressor of Alk in the liver. Moreover, there were positive correlations between Alk and Chrm3, Alk and Ptprz1, and a negative correlation between Alk and Lmo4. However, cotreatment with Cevimeline significantly reversed the lipid metabolic disturbance and adipose tissue accumulation, as well as the upregulation of the hepatic Alk signaling caused by Olanzapine. This study demonstrates evidence that Olanzapine may cause metabolic disturbance by modulating hepatic Alk signaling via M3R, which provides novel insight for modulating the hepatic Alk signaling and potential interventions for targeting metabolic disorders.

Analysis of sleep quality, disease uncertainty, and psychological tolerance in patients undergoing chemotherapy for digestive tract malignancies.

BACKGROUND: Colorectal cancer is the second leading cause of cancer-related deaths among digestive tract malignancies, following gastric cancer. Sleep is of great significance for maintaining human health. The incidence of sleep disorders in patients with cancer is approximately twice that observed in the general population. Lack of sleep can prolong hospital stays, increase the likelihood of infection, and increase mortality rates. Therefore, studying the factors related to sleep quality is significant for improving the quality of life of patients with malignant tumors of the digestive tract. AIM: To investigate the relationships among sleep quality, disease uncertainty, and psychological resilience in patients undergoing chemotherapy for digestive tract malignancies. METHODS: A total of 131 patients with malignant digestive tract tumors who were treated at Hefei BOE Hospital between April 2021 and September 2022 were selected as research participants. Based on their Pittsburgh Sleep Quality Index (PSQI) scores, participants were divided into either the sleep disorder group (PSQI score > 7) or the normal sleep group (PSQI score ≤ 7). The clinical data-together with the Mishel Uncertainty in Illness Scale for Adults (MUIS-A) and Connor-Davidson Resilience Scale (CD-RISC) scores-were compared. RESULTS: In this study, 78 (59.54%) patients with digestive tract malignancies developed sleep disorders after chemotherapy. Sleep disorder incidence was higher in patients with colorectal cancer than in those with gastric and esophageal cancers (P < 0.05). The total MUIS-A score and those for each item in the sleep disorder group were higher than those in the normal sleep group. The total CD-RISC score and those for each item in the sleep disorder group were lower than those in the normal sleep group (P < 0.05). The PSQI scores of patients with malignant digestive tract tumors were positively correlated with the scores for lack of disease information, disease uncertainty, and unpredictability in the MUIS-A and negatively correlated with the scores for tenacity, self-improvement, and optimism in the CD-RISC (P < 0.05). CONCLUSION: Patients undergoing chemotherapy for digestive tract malignancies are prone to sleep problems related to disease uncertainty and psychological resilience. Therefore, interventions can be implemented to improve their sleep quality.

Is Dosage Adjustment Based on Age Necessary for Intravenous Lidocaine in Patients Undergoing General Anesthesia: A Prospective Multi-Arm Comparative Study.

It remains unclear whether dosage adjustment of intravenous lidocaine is necessary during general anesthesia for elderly patients over 75 years old. This study aimed to investigate the effects of age on the pharmacokinetics (PK) and safety of intravenous lidocaine in patients undergoing general anesthesia. A total of 599 plasma samples were collected from 76 general anesthesia patients across three age groups: 18-64, 65-74, and ≥ 75 years. Lidocaine was administered intravenously at a dose of 1.5 mg/kg for the 18-64 and 65-74 years groups, while the dose was adjusted to 1.0 mg/kg for the ≥ 75 years group. The plasma concentrations of lidocaine and its active metabolites were measured using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay, and the data were analyzed using a noncompartmental analysis. The results revealed no significant age-related differences in the PK of lidocaine and its metabolites. Among the three age groups, over 90 % of patient achieved a lidocaine concentration within a safe and effective range when the dosage was normalized to 1.5 mg/kg. In conclusion, age-based dosage adjustment was unnecessary for intravenous lidocaine in patients below 86 years undergoing general anesthesia.

Regulation of gut microbiota and serum neurotransmitters in mice by Streptococcus thermophilus GA8- and Lacticaseibacillus rhamnosus HAO9-fermented milk containing high levels of gamma-aminobutyric acid.

BACKGROUND: Gamma-aminobutyric acid (GABA) is an important neurotransmitter in the human body, with several negative emotions reported as being associated with GABA dysregulation. This study investigates the safety and modulatory effects of GABA-enriched milk, fermented by Streptococcus thermophilus GA8 and Lacticasebacillus rhamnosus HAO9, on the gut microbiota and neurotransmitter profiles in mice. RESULTS: Through rigorous culturing and fermentation processes, we achieved consistent GABA production in milk, with concentrations reaching 4.6 and 8.5 g L-1 for GA8-fermented and co-fermented milk, respectively, after 48 h. Using SPF male C57BL/6J mice, we administered either mono-culture or combined-culture milk treatments and monitored physiological impacts. The treatments did not affect mouse body weight but induced significant changes in gut microbiota composition. Beta diversity analysis revealed distinct microbial profiles between treatment groups, highlighting fermentation-specific microbial shifts, such as an increase in Verrucomicrobia for the GA8 group and a modulation in Saccharibacteria_genera_incertae_sedis for the GA8 + HAO9 group. Serum neurotransmitter levels were elevated in both treatment groups, with significant increases in l-glutamine, l-tryptophan and, notably, serotonin hydrochloride in the GA8 + HAO9 group. Correlation analysis identified a positive association between specific bacterial genera and neurotransmitter levels, suggesting a probiotic effect on neuroactive substances. CONCLUSION: These findings suggest that fermented milk has potential as a probiotic supplement for mood improvement and stress relief, highlighting its role in modulating the gut-brain axis. © 2024 Society of Chemical Industry.