Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

The clinical characteristics of a neonatal patient with movement disorder and arthrogryposis (NDEEMA) caused by gain-of-function mutation of the SCN1A gene were reported in this article. The 1-year-and-9-month-old boy started seizures since 2 hours after birth. He had funnel-breast, dislocation of the hip, and bipedal varus. Genetic testing showed SCN1A gene de novo missense mutation c.706A>G(p.Ile236Val), causing overall gain-of-function effect. The frequency of seizures decreased significantly after treatment of oxcarbazepine.

Signal detection is a critical task in drug safety regulation. However, it inevitably generates irrelevant or false signals, posing challenges for resource allocation by marketing authorization holders. To reasonably assess these signals, different countries have established various principles for prioritizing the evaluation of risk signals. This study systematically compares these principles and finds that the U.S. Food and Drug Administration(FDA) focuses on practical issues, such as identifying drug confusion or drug interactions. However, China's Good Pharmacovigilance Practices and the European Medicines Agency(EMA) emphasize a comprehensive evaluation framework. The Council for International Organizations of Medical Sciences(CIOMS) emphasizes the consistency of multiple data sources, highlighting the reliability of signal evaluation. China practices a multidisciplinary approach combining traditional Chinese and western medicine, and the risk signals related to traditional Chinese medicine(TCM) have unique characteristics, including complex components, cumulative toxicity, specific theoretical foundations, and drug interactions. The different priorities in risk signal evaluation principles across countries suggest that China should strengthen clinical trial research, emphasize corroboration with evidence of multiple sources, and pay particular attention to the risks of drug interactions in the TCM regulatory science. Establishing the risk signal prioritization principles that align with the characteristics of TCM enables more precise and efficient scientific regulation of TCM.
Humans ; Medicine, Chinese Traditional/standards* ; China ; Drugs, Chinese Herbal/adverse effects* ; United States ; United States Food and Drug Administration

This study aims to explore the scientific connotation of sinking Rehmanniae Radix has the best quality and compare the quality between floating and sinking fresh Rehmanniae Radix samples. Ultra-performance liquid chromatography tandem quadrupole electrostatic field Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was employed to detect the chemical components in floating and sinking fresh Rehmanniae Radix samples. The fingerprint of fresh Rehmanniae Radix was established by high performance liquid chromatography(HPLC), and four index components were determined simultaneously. The cluster analysis, principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were conducted to compare the quality of floating and sinking fresh Rehmanniae Radix samples. An evaporative light-scattering detector was used to compare the content of five sugars. The extract yield and drying rate were determined, and the quality connotation of sinking Rehmanniae Radix has the best quality was explained by multiple indicators. A total of 41 components were preliminarily identified from fresh Rehmanniae Radix by UHPLC-Q-Orbitrap HRMS, including 7 iridoid glycosides, 9 phenylethanol glycosides, 6 amino acids, 4 sugars, 3 phenolic acids, 5 nucleosides, 3 organic acids, 1 ionone, 1 furan, 1 coumarin, and 1 phenylpropanoid. The results showed that the main chemical components were consistent between floating and sinking fresh Rehmanniae Radix. Nine common peaks were identified in the fingerprints of 15 batches of floating and sinking fresh Rehmanniae Radix samples, and the similarity of fingerprints was greater than 0.9. The cluster analysis, PCA, and OPLS-DA classified floating and sinking fresh Rehmanniae Radix sasmples into two categories, indicating differences in the quality between them. The total content of catalpol, rehmannioside D, ajugol, and verbascoside in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was catalpol. The total content of fructose, glucose, sucrose, raffinose, and stachyose in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was stachyose. The extract yield and drying rate of the sinking samples were higher than those of floating samples. This study preliminarily showed that floating and sinking fresh Rehmanniae Radix samples had the same components but great differences in the content of medicinal substance basis. The total content of four glycosides and five sugars, extract yield, and drying rate of sinking fresh Rehmanniae Radix samples is higher than that of floating samples of the same batch and specification. These findings, to a certain extent, explains the scientificity of sinking Rehmanniae Radix has the best quality recorded in ancient books and provide a reference for the quality control and clinical application of fresh Rehmanniae Radix.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Rehmannia/chemistry* ; Chemometrics ; Mass Spectrometry/methods* ; Quality Control ; Principal Component Analysis ; Plant Extracts

A method for determination and targeted screening of diflorasone components in health products using ultra performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF/MS)was established.Four representative diflorasone and esters(diflorasone,diflorasone diacetate,diflorasone-17-propionate,and diflorasone-21-propionate)were selected to optimize the pretreatment conditions,and 10 mL of extraction solvent dosage,15 min of extraction time and 5 g of salting-out agent as the optimal conditions were selected by response surface methodology.The results showed that the four analytes exhibited good linearity within the concentration range of 2.0?100 μg/L with the chromatographic peak area,and the correlation coefficients(R2)were all greater than 0.9990,while the results of recovery and relative standard deviation could satisfy the requirements of determination.The common characteristic ions of diflorasone and esters werem/z121 andm/z335,and their specific structures were obtained by analyzing the cleavage pathway based on the optimized determination conditions.A targeted screening method for other esters of diflorasone based on characteristic ions guidance strategy was established.This method had many advantages such as high efficiency,high sensitivity and good reproducibility,and could be used for targeted screening of diflorasone and esters in health products.The developed characteristic ion guided strategy could be employed to construct mass spectral databases for various glucocorticoids,enabling comprehensive targeted screening across a broad range of compounds.

Objective To explore the characteristics and diagnostic value of coronary computed tomography angiography(CCTA)and dynamic load computed tomography myocardial perfusion imaging(CT-MPI)in patients with obstructive coronary artery disease(CAD)complicated by type 2 diabetes mellitus(T2DM).Methods A total of 187 patients with obstructive CAD were selected and divided into T2DM group(n=70)and non-T2DM group(n=117).All patients underwent CCTA and dynamic load CT-MPI exami-nations.The characteristics of CCTA and dynamic load CT-MPI were observed,and their diagnostic values were analyzed.Results The degree of stenosis,total plaque volume,lipid plaque volume,calcified plaque volume,myocardial perfusion abnormality,and myocardial blood flow(MBF)were independent influencing factors for obstructive CAD complicated by T2DM(P＜0.05).These parameters demonstrated significant diagnostic efficiency on patients with obstructive CAD complicated by T2DM(P＜0.05).Conclusion Obstruc-tive CAD patients complicated by T2DM exhibit characteristics such as high vascular stenosis,severely reduced blood perfusion,and a high prevalence of high-risk plaques.Both CCTA and dynamic load CT-MPI have substantial diagnostic value on this population.

Objective To investigate the influence of oxygen supply flow rate in high-flow nasal cannula(HFNC)oxygen therapy on pressure distributions in the upper airway.Methods A three-dimensional(3D)model of the upper airway was reconstructed using CT images from an adult male,and then coupled with a high-flow nasal cannula model to establish a coupled model of the nasal cannula and the upper airway.Subsequently,a physical model of this upper airway,which was combined with a head model,artificial lungs,and a monitoring system was created by 3D printing technology to form a physical simulation platform in vitro.Computational and physical simulations were carried out respectively to determine the air pressure at typical locations in the upper airway under different oxygen supply flow rates.Results Pressures at typical upper airway locations obtained by computational and physical simulations turned out to be in good agreement;both peak inspirational pressure(PIP)and positive end-expiratory pressure(PEEP)increased quadratically with the increase of oxygen supply flow rate;and the air pressure distribution was more uniform in the laryngeal cross-section as compared to the nasal part of the upper airway.Conclusions This study may provide a theoretical support for optimization of the setting of oxygen suppy flow rate and the selection of PEEP effect assessment position in the clinical application of HFNC oxygen therapy.

Epilepsy is a chronic neurological disorder caused by an imbalance between excitation and inhibition in the central nervous system.Recently,the role of the orexin system in the pathogenesis of epilepsy has garnered significant attention.Orex-in primarily regulates arousal states and enhances neuronal excit-ability through activation of OX1-R/OX2-R receptors.Studies have shown that elevated orexin levels lower the seizure thresh-old,while orexin receptor antagonists(ORAs)exhibit potential antiepileptic effects.ORAs suppress epileptiform discharges by reducing glutamate release,enhancing GABAergic inhibitory effects,and modulating the thalamocortical circuit.Animal ex-periments and preliminary clinical studies demonstrate that OX1R antagonists decrease excitatory synaptic transmission,whereas OX2 R antagonists primarily strengthen GABA-mediated inhibition.With the widespread application of ORAs in sleep disorders,exploring their clinical value as antiepileptic drugs will become a key focus for future research.This review summa-rizes the role of the orexin system in epileptogenesis and discus-ses the research progress and future directions of ORAs as poten-tial antiepileptic agents.

Objective To investigate the association between nutritional status and serum hepcidin and pentraxin 3(PTX3)levels in patients undergoing maintenance hemodialysis(MHD).Methods A total of 76 patients with MHD who met the inclusion criteria were recruited from the hemodialysis center at the Affiliated Hospital of Chengde Medical University.Nutritional status was assessed using the Subjective Global Assessment(SGA),which categorizes patients into three grades:SGA-A,SGA-B,and SGA-C.Serum levels of PTX3 and hepcidin were mea-sured by enzyme-linked immunosorbent assay(ELISA).Statistical analyses were conducted using SPSS software.One-way analysis of variance(ANOVA)was applied to compare differences across the three SGA groups.Logistic regression analysis was performed to identify influencing factors,and receiver operating characteristic(ROC)curve analysis was used to evaluate diagnostic value.Among the participants,45 patients were classified as malnourished based on SGA-B and SGA-C scores,while those with SGA-A constituted the well-nourished control group.Results Among the 76 MHD patients,59.2%were malnourished.We then compared clinical characteristics across the three groups.The results showed that the malnourished group was older and exhibited significantly higher levels of hs-CRP,PTX3,and hepcidin(P<0.05),while serum albumin,creatinine,and phosphorus levels were significantly lower(P<0.05).Pearson correlation analysis revealed positive correlations between SGA grades and hs-CRP,PTX3,and hepcidin levels(all P<0.05).Logistic regression analysis with"malnutrition"as the dependent variable indicated that elevated hs-CRP,PTX3,and hepcidin levels,along with age and male gender,were associated with increased risk of malnutrition in MHD patients,whereas higher serum phosphorus and creatinine levels were protec-tive factors.Further multivariate logistic regression analysis demonstrated that serum PTX3 level was an independent risk factor for malnutrition(P=0.032),while higher creatinine level was an independent protective factor(P=0.047).ROC curve analysis showed that the combination of serum PTX3 and creatinine levels had a high diagnostic value for identifying malnutrition in MHD patients,yielding an AUC of 0.789(P<0.001),a Youden index of 0.448,sensitivity of 77.8%,and specificity of 71.0%.Conclusions Elevated levels of PTX3 and hepcidin,along with reduced serum creatinine levels,are associated with an increased risk of malnutrition in patients undergoing MHD.Notably,elevated serum PTX3 and decreased serum creatinine independently predict malnutrition in this population and demonstrate high predictive value.