Inflammatory bowel disease is a chronic, idiopathic, and recurrent gastrointestinal disorder with an unclear etiology and uncertain pathogenesis. Traditional treatment strategies rely on frequent administration of high doses of medication to reduce inflammation, whereas these approaches have limitations and may induce potential complications. Therefore, finding more effective and safe therapeutic drugs and methods is particularly important. Plant-derived exosome-like nanovesicles(PDELNs) are nano-sized vesicles with a lipid bilayer structure that are secreted by plant cells. The bioactive molecules contained within, such as lipids, proteins, and nucleic acids, can serve as information carriers, playing a role in the transmission of information and substances between cells and across species. PDELNs can carry and transfer their own bioactive substances or act as carriers for delivering other active components or drugs. Due to the high biocompatibility, low toxicity, and significant bioactivity, PDELNs have garnered widespread attention. Compared with other exosomes, PDELNs are not destroyed in the gastrointestinal tract when taken orally and can reach the intestines. This unique property makes PDELNs a promising oral nanodrug for treating intestinal diseases, showing great potential in this area. This article reviews recent research literature on PDELNs regarding the physicochemical characteristics, extraction and purification methods, functions, application characteristics and mechanisms in the treatment of intestinal diseases, and use as a carrier for treating intestinal diseases, aiming to provide a reference for the use of PDELNs in the treatment of intestinal diseases.
Humans ; Exosomes/metabolism* ; Animals ; Intestinal Diseases/metabolism* ; Plants/metabolism* ; Drug Carriers/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Drug Delivery Systems ; Nanoparticles/chemistry*

The quality of traditional Chinese medicine(TCM) is a critical foundation for ensuring the stability of its efficacy, as well as the safety and effectiveness of its clinical use. The identification of critical quality attributes(CQAs) is one of the core components of TCM preparation quality control. This study focuses on Jianwei Xiaoshi Tablets and explores their CQAs related to property and flavor from the perspective of taste receptor proteins. Three taste receptor proteins, T1R2, T1R3, and TRPV1, were selected, and a biosensor based on high-electron-mobility transistor(HEMT) was constructed to detect the interactions between Jianwei Xiaoshi Tablets and taste receptor proteins. Simultaneously, liquid chromatography-mass spectrometry(LC-MS) technology was used to analyze the chemical composition of Jianwei Xiaoshi Tablets. In examining the interaction strength, the results indicated that the interaction between Jianwei Xiaoshi Tablets and TRPV1 protein was the strongest, followed by T1R3, with the interaction with T1R2 being relatively weaker. By combining biosensing technology with LC-MS, 16 chemical components were identified from Jianwei Xiaoshi Tablets, among which six were selected as CQAs for sweetness and seven for pungency. Further validation experiments demonstrated that CQAs such as hesperidin and hesperetin had strong interactions with their corresponding taste receptor proteins. Through the combined use of multiple technological approaches, this study successfully determined the property and flavor-related CQAs of Jianwei Xiaoshi Tablets. It provides novel ideas and approach for the identification of CQAs in TCM preparations and offers comprehensive theoretical support for TCM quality control, contributing to the improvement and development of TCM preparation quality control systems.
Drugs, Chinese Herbal/chemistry* ; Biosensing Techniques/methods* ; TRPV Cation Channels/chemistry* ; Tablets/chemistry* ; Receptors, G-Protein-Coupled/genetics* ; Quality Control ; Taste ; Humans ; Mass Spectrometry

OBJECTIVES: To assess the regulatory effect of cannabidiol (CBD) on circadian rhythm sleep disorders following general anesthesia and explore its potential mechanism in a rat model of propofol-induced rhythm sleep disorder. METHODS: An electrode was embedded in the skull for cortical EEG recording in 24 male SD rats, which were randomized into control, propofol, CBD treatment, and diazepam treatment groups (n=6). Eight days later, a single dose of propofol (10 mg/kg) was injected via the tail vein with anesthesia maintenance for 3 h in the latter 3 groups, and daily treatment with saline, CBD or diazepam was administered via gavage; the control rats received only saline injection. A wireless system was used for collecting EEG, EMG, and body temperature data within 72 h after propofol injection. After data collection, blood samples and hypothalamic tissue samples were collected for determining serum levels of oxidative stress markers and hypothalamic expressions of the key clock proteins. RESULTS: Compared with the control rats, the rats with CBD treatment showed significantly increased sleep time at night (20:00-6:00), especially during the time period of 4:00-6:00 am. Compared with the rats in propofol group, which had prolonged SWS time and increased sleep episodes during 18:00-24:00 and sleep-wake transitions, the CBD-treated rats exhibited a significant reduction of SWS time and fewer SWS-to-active-awake transitions with increased SWS aspects and sleep-wake transitions at night (24:00-08:00). Diazepam treatment produced similar effect to CBD but with a weaker effect on sleep-wake transitions. Propofol caused significant changes in protein expressions and redox state, which were effectively reversed by CBD treatment. CONCLUSIONS CBD can improve sleep structure and circadian rhythm in rats with propofol-induced sleep disorder possibly by regulating hypothalamic expressions of the key circadian clock proteins, suggesting a new treatment option for perioperative sleep disorders.
Animals ; Rats, Sprague-Dawley ; Male ; Cannabidiol/therapeutic use* ; Rats ; Circadian Rhythm/drug effects* ; Propofol/adverse effects* ; Anesthesia, General/adverse effects* ; Sleep Wake Disorders/chemically induced* ; Hypothalamus/metabolism* ; Electroencephalography

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective:To understand the clinical characteristics of novel coronavirus reinfection and explore the risk factors of novel coronavirus reinfection.Methods:The clinical data of 340 patients with novel coronavirus infection who were admitted to the Fever Clinic of Beijing Traditional Chinese Medicine, Capital Medical University from December 2022 to January 2023 were included. The general characteristics, basic diseases, clinical symptoms, and examination results of the first and second infections in the non repeated infection group, the repeated infection group, and the repeated infection group were compared. Binary logistic multivariate analysis was used to explore the risk factors of novel coronavirus reinfection.Results:In this study, 340 patients with novel coronavirus infection were included, 180 of whom were repeatedly infected. There was no statistically significant difference (all P>0.05) in terms of gender, age, body mass index (BMI), exercise, smoking, daily routine, and underlying disease between the recurrent infection group and the non recurrent infection group. However, the vaccination rate of the recurrent infection group was lower than that of the non recurrent infection group [80.0%(144/180) vs 88.0%(142/169), P<0.05]; In the repeated infection group, 157 cases (87.2%) were accompanied by overall discomfort (including headache, fatigue, muscle and joint pain), which was significantly higher than 122 cases (76.2%) in the non repeated infection group. The proportion of pneumonia occurring during the first infection was higher than that in the non repeated infection group [15.6%(28/180)], and the difference was statistically significant ( P<0.05). The interval between the first and second infections in the repeated infection group was (166.2±8.3)days. Cough and phlegm were the main clinical manifestations of two infections; The duration of re infection was shorter than that of the first infection [(7.03±2.30)days vs (8.94±3.02)days, t=6.739, P<0.001]; Secondary infections had less incidence of pneumonia [5.0%(9/180) vs 15.6%(28/180), χ 2=10.874, P=0.001]; 153 patients (85.0%) reported milder secondary infections. The results of binary logistic regression showed that cough, expectoration, body discomfort and pneumonia during the first infection were risk factors for repeated infection of novel coronavirus ( OR=2.710, 2.293, 2.808, P<0.05), and vaccination was a protective factor to avoid repeated infection ( OR=0.470, P=0.019). Conclusions:The symptoms of novel coronavirus reinfection are generally mild and the course of disease is relatively short. For vulnerable people, novel coronavirus vaccine should be actively inoculated to strengthen protection.

Objective:To explore the expression and clinical significance of heme oxygenase-1 (HO-1) and quinone oxidoreductase (NQO-1) in children with different severity levels of mycoplasma pneumoniae (MP) infection.Methods:A total of 140 children with MP infection who were treated at the Affiliated Hospital of Jining Medical University from January to June 2022 were selected as the observation group, while 100 healthy children who underwent physical examination were selected as the control group. The serum levels of interleukin-2 (IL-2), IL-6, IL-10, IL-1β, tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), HO-1, and relative expression of NQO-1 protein were compared between the control group and the observation group, as well as between children with different degrees of MP infection, Forced vital capacity (FVC), maximum expiratory volume in the first second (FEV 1), peak expiratory flow rate (PEF), 50% forced expiratory flow rate and maximum mid expiratory flow rate (MEF 25-70), 50% forced expiratory flow rate (MEF 50), and 25% forced expiratory flow rate (MEF 25). Pearson correlation method was used to analyze the correlation between the expression of HO-1 and NQO-1 with inflammatory factors and lung function indicators. The receiver operating characteristic (ROC) curve was used to analyze the value of HO-1 and NQO-1 expression in predicting severe MP. Results:The serum levels of IL-2, IL-6, IL-10, IL-1β, TNF-α, IFN-γ, and HO-1 in the observation group were significantly higher than those in the control group (all P<0.05), while the relative expression level of NQO-1 protein was significantly lower than that in the control group ( P<0.05). The FVC, FEV 1, PEF, MEF 25-70, MEF 50, and MEF 25 in the observation group were significantly lower than those in the control group (all P<0.05). The serum levels of IL-2, IL-6, IL-10, IL-1β, TNF-α, IFN-γ, and HO-1 in the observation group of severe children were significantly higher than those in mild children (all P<0.05), while the relative expression of NQO-1 protein, FVC, FEV 1, PEF, MEF 25-70, MEF 50, and MEF 25 were significantly lower than those in mild children (all P<0.05). HO-1 in children with MP infection is positively correlated with IL-6, IL-1β, and IFN-γ, while the relative expression level of NQO-1 protein is negatively correlated with IL-6, IL-1β, and IFN-γ (all P<0.05); HO-1 was negatively correlated with MEF 50 and MEF 25, while the relative expression level of NQO-1 protein was positively correlated with MEF 50 (all P<0.05). The area under the ROC curve for predicting the relative expression levels of HO-1 and NQO-1 proteins in severe MP was 0.871 and 0.934, respectively (all P<0.05). Conclusions:The expression of serum HO-1 and NQO-1 in children with MP infection is correlated with cytokines and lung function indicators, and has certain application value in predicting severe illness.