ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

Background Deoxynivalenol (DON), a priority contaminant for food safety risk monitoring, is produced by Fusarium spp. infesting crops, and its common derivatives are 3-acetyl-DON (3A-DON) and 15-acetyl-DON (15A-DON), which have been shown to possess gastrointestinal toxicity, immunotoxicity, reproductive toxicity, and cytotoxicity. Due to the stable physicochemical properties of the DON family of toxins (DONs), they cannot be effectively removed during food processing, thus following the food chain, entering the human body, and posing health risks. Objective To understand the contamination status of DONs in commercial foods (cereals and bakery products) in Shanghai in 2022–2023, and to assess the exposure risk of DONs in pregnant women by combining their dietary consumption data. Methods Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to determine the contamination level of DONs in 1 100 food samples (cereals and baked goods) collected in 2022 and 944 samples collected in 2023 from Shanghai. The dietary monitoring data of pregnant women in Shanghai from 2016 to 2017 were adopted. The monitoring employed the food frequency questionnaire distributed among pregnant women through a combination of online telephone enquiry and offline on-site face-to-face survey to estimate their food consumption levels. An exposure assessment model was established to calculate the exposure level to DONs, and the probability distribution of the DONs exposure level in the pregnant women group in Shanghai was obtained by applying @Risk 7.5 software and simulating the calculation according to the Monte Carlo principle. With reference to the tolerable daily intake (TDI) of DONs [1.00 µg·(kg·d)⁻¹] proposed by the Joint FAO/WHO Expert Committee on Food Additives, the risk of exposure to DONs from commercial cereals and bakery products in pregnant women in Shanghai was assessed. Results DONs were detected in cereal and bakery samples collected in 2022 and 2023 with different levels of contamination. The level of DONs in cereal foods in 2023 (mean: 36.33 µg·kg⁻¹) decreased compared to 2022 (mean: 23.64 µg·kg⁻¹). However, the positive rate (71.67%) and level (mean: 51.22 µg·kg⁻¹) of DONs in bakery products increased significantly compared with 2022 (positive rate: 10.00%, mean: 24.39 µg·kg⁻¹). The mean consumption of cereals in 783 pregnant women was 222.48 g·d⁻¹ and the mean consumption of bakery products was 36.07 g·d⁻¹, and there was no statistically significant difference in the intake of all types of cereals and bakery products across the early, middle, and late stages of pregnancy. The modelled intakes of DONs via commercial cereals and bakery products for pregnant women in Shanghai were calculated to be 0.20 and 0.57 µg·(kg·d)⁻¹ in 2022 for the mean level and the 95th percentile level, respectively, and 0.16 µg·(kg·d)⁻¹ and 0.35 µg·(kg·d)⁻¹ in 2023, respectively. The results of the health risk assessment showed that pregnant women in Shanghai had 2.6% and 1.4% probability of exposure to DONs from cereal consumption in 2022 and 2023, respectively. Conclusion The risk of exposure of pregnant women in Shanghai to DONs via commercial cereals and bakery products is relatively low (1.4%-2.6%). However, considering the physical sensitivity of pregnant women, they should avoid consuming moldy grains and appropriately reduce intake of bakery products.

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

ObjectiveTo study the effect of Qizhu Kang'ai prescription （QZAP） on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 （PCK1） in the liver of mouse model of liver cancer induced by diethylnitrosamine （DEN） combined with carbon tetrachloride （CCl₄） and Huh7 cells of human liver cancer， so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells. MethodDEN combined with CCl₄ was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group， a model group， and a QZAP group were set up， in which QZAP （3.51 g·kg^-1） or an equal volume of normal saline was administered daily by gavage， respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyltransferase （γ-GT）， and alpha-fetoprotein （AFP） in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment， Huh7 cells were divided into blank group， QZAP low， medium， and high dose groups and/or PCK1 inhibitor （SKF-34288 hydrochloride） group， and Sorafenib group. The corresponding drug-containing serum and drug treatment were given， respectively. Cell counting kit-8 （CCK-8） method， colony formation experiment， Edu fluorescent labeling detection， intracellular adenosine triphosphate （ATP） content detection， and cell cycle flow cytometry detection were used to evaluate the proliferation ability， energy metabolism changes， and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1， serine/threonine kinase （Akt）， phosphorylated Akt （p-Akt）， and cell cycle-dependent protein kinase inhibitor 1A （p21）. ResultCompared with the model group， the pathological changes such as cell atypia， necrosis， and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated， and the number of liver tumors was reduced （P<0.01）. The serum ALT， AST， γ-GT， and AFP levels were reduced （P<0.01）. At the cell level， compared with the blank group， low， medium， and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells （P<0.01） and the number of positive cells with Edu labeling （P<0.01） and inhibit clonal proliferation ability （P<0.01）. The QZAP groups could also reduce the intracellular ATP content （P<0.05） and increase the distribution ratio of the G₀/G₁ phase of the cell cycle （P<0.05） in a dose-dependent manner. Compared with the model group and blank group， PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced （P<0.05，P<0.01）， and the p-Akt protein level was significantly increased （P<0.01）. Compared with the blank group， the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased （P<0.05）， but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G₀/G₁ phase distribution. Compared with the SKF-34288 hydrochloride group， the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content， cell survival rate， and Edu-positive cell ratio of Huh7 cells （P<0.05） and significantly increased the G₀/G₁ phase distribution proportion （P<0.05）. ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression， thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.

Objective To study the mechanism of polyene phosphatidylcholine in improving metabolic disorders and fatty liver induced by high fat diet.Methods Thirty-two C57BL/6 mice were randomly divided into blank group,control group,model group and experimental group.The blank group was fed with low-fat diet and intraperitoneal injection of 10％glucose 200 μL twice a week.Control group was fed with low-fat diet twice a week and intraperitoneally injected 10％glucose solution 200 μL containing polyene phosphatidylcholine(PPC)20 μg.Model group was fed with high-fat diet and intraperitoneal injection of 10％glucose 200 μL twice a week.Experimental group was fed with high-fat diet twice a week and intraperitoneally injected 10％glucose solution 200 μL containing PPC 20 μg.The body weight of the mice was measured,blood glucose test strips and insulin resistance was analyzed.The levels of triglyceride(TG),high density lipoprotein(HDL),low density lipoprotein(LDL),glutamic oxalic aminotransferase(GOT)and glutamic pyruvic aminotransferase(GPT)in serum and liver were analyzed by biochemical method.The levels of tumor necrosis factor-α(TNF-α),interleukin-6 and IL-8 were detected by enzyme-linked immunosorbent assay(ELISA).Results The serum TG levels of blank group,control group,model group and experimental group were(0.15±0.01),(0.11±0.01),(0.21±0.01)and(0.12±0.01)mmol·L-1;LDL levels were(0.41±0.01),(0.25±0.01),(0.71±0.02)and(0.49±0.01)mmol·L-1;GOT levels were(30.30±0.89),(31.39±1.18),(43.04±2.82)and(25.64±0.72)mmol·L-1;GPT levels were(9.15±0.45),(7.39±1.88),(12.87±1.81)and(7.96±1.64)mmol·L-1;fasting blood glucose levels were(4.97±0.08),(6.08±0.18),(8.12±0.20)and(7.29±0.02)mmol·L-1;fasting insulin levels were(6.52±1.11),(5.45±0.28),(54.83±4.32)and(30.55±2.73)mU·L-1;the levels of TNF-α in liver tissues were(3.98±0.63),(3.95±0.98),(20.55±4.71)and(15.28±1.73)pg·g-1;IL-6 levels were(18.93±8.56),(17.64±3.29),(59.40±4.63)and(37.54±7.33)pg·g-1;IL-8 levels were(67.16±12.37),(59.44±3.58),(198.40±9.27)and(132.10±7.04)pg·g-1.The difference of above indicatory between experimental group and model group was statistically significant(all P＜0.05).Conclusion Polyene phosphatidylcholine may inhibit the expression of TNF-α,IL-6 and IL-8 inflammatory factors by mediating the inhibition of inflammation on liver tissue and then improve metabolic disorders.

Objective To analyze the risk factors influencing the occurrence of atherosclerosis in patients with type 2 diabetes, and to construct and evaluate a nomogram prediction model. Methods Multivariate logistic regression was used to analyze the risk factors of atherosclerosis in type 2 diabetes mellitus, and R software was used to build a nomogram prediction model. The accuracy and clinical validity of the model were verified by using H-L fit curve, area under ROC curve and calibration curve. Results The prevalence rate of atherosclerosis was 56.37%. Independent risk factors for atherosclerosis in type 2 diabetes mellitus (P<0.05) were body weight (OR=1.42，P<0.05), glycated serum protein (OR=1.35, P<0.05), lactate dehydrogenase (OR=1.17, P<0.05), alkaline phosphatase (OR=0.79, P<0.05), hyperlipidemia (OR=2.30, P<0.05), stroke (OR=4.20, P<0.05), coronary heart disease (OR=64.54, P<0.05), lower extremity artery disease (OR=24.52, P<0.05), and other endocrine diseases (OR=1.65 , P<0.05). The area under ROC curve was 0.91, the slope of the calibration curve was close to 1, and the H-L fit curve χ²=3.11. The internal verification result of the constructed nomogram prediction model was P=0.93. External verification of patients in the test set showed that the area under ROC curve was 0.91, indicating good differentiation and accuracy of the model. Conclusion The prediction model established by using the risk factors screened in this study has a high accuracy and differentiation, and medical staff can take effective prevention measures according to the individual factors of patients.

Dementia in traditional Chinese medicine （TCM） mainly presents amnesia and dullness. Alzheimer's disease and vascular dementia belong to the category of dementia in TCM. These progressive neurological diseases have a complex etiology and a long course， and the drugs that can reverse the disease course remain to be developed. Therefore， early intervention plays a vital role in delaying the disease progression. Apathy refers to a lack of motivation that leads to the attenuation or disappearance of goal-directed behaviors， cognitive functions， and emotional responses. Clinical studies have suggested that apathy exists in the early stage of a variety of neurodegenerative diseases， being one of the key symptoms to the early diagnosis of dementia. The severity of apathy is related to the severity of dementia. Therefore， early diagnosis and treatment of apathy are of great significance to the prevention and treatment of dementia. The preclinical research on apathy in dementia is still in its infancy， and the systematic evaluation method has not been prescribed. The clinical diagnosis and treatment are also in the exploratory stage， and the complex pathophysiological mechanisms of apathy and dementia development have not been fully elucidated. This article reviews the research progress of apathy in dementia， the apathetic behaviors of dementia animal models， the behaviors of patients with apathy， and the treatment methods in recent years and summarizes the research status of apathy in dementia. This review aims to provide a theoretical basis for exploring the behavior of apathy in dementia and conducting preclinical research and evaluation of the pathogenesis and to lay a foundation for the treatment of apathy in dementia.

Traditional Chinese medicine （TCM） has a long history of application in China and has consistently played a vital role in treating diseases and saving lives. TCM prescriptions （compounds） constitute the primary form of clinical TCM treatment and significantly differ from western medicine （chemicals） due to the diverse composition and chemical constituents of TCM （compounds）. Nevertheless， the potential multi-component， multi-target， and multi-pathway action characteristics of TCM prescriptions also demonstrate their possible （complementary） therapeutic advantages when compared with single-component chemical drugs. Therefore， driven by the development of modern science and technology and the demands of the modernization and internationalization of TCM， modern theories regarding the complexity of TCM prescription effects have been continuously proposed： Different from the abstract language of traditional prescription theory， the modern TCM prescription theory is more inclined to illustrate the connotation of prescription compatibility concretely and vividly from an experimental and scientific perspective. In this paper， new theories on the complexity of TCM prescriptions proposed in recent years are summarized to provide research references and ideas for the greater role of TCM prescriptions and a better scientific understanding.

The voltage-gated sodium channel subtype Nav1.7 is highly expressed in nociceptive sensory neurons and is a key pathogenic target in several human hereditary pain syndromes. In recent years, a large number of studies have shown that Nav1.7 plays an important role in inflammatory, neuropathic, and nociceptive pain. Therefore, targeting Nav1.7 is a new strategy and hotspot for the development of novel analgesics. This review introduces the structure and function of Nav1.7, its regulatory role in pain, highlights the development progress of small-molecule Nav1.7 inhibitors in clinical trials, and analyzes the preclinical development of highly specific Nav1.7 inhibitors, with a view to providing reference for the development of Nav1.7 analgesic drugs.