Objective:To investigate the differences in cross-frequency coupling (CFC) characteristics of electroencephalography (EEG) between narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2).Methods:A total of 23 NT1 and 31 NT2 patients were included from the Chinese Clinical Sleep Database (CCSD) between October 2022 and September 2023. All participants underwent overnight polysomnography and a multiple sleep latency test. CFC features were extracted from EEG signals during polysomnography, encompassing various combinations of sleep stages, electrode pairs, frequency bands, and coupling types. Feature selection was performed using elastic net regularization. The Spearman correlation between key CFC features and the Epworth Sleepiness Scale (ESS) scores was analyzed. Finally, a support vector classification (SVC) model was constructed to distinguish NT1 from NT2, and leave-one-out cross-validation was used to assess the generalization performance.Results:Among all coupling features during non-rapid eye movement sleep stage 1 (N1), the fronto-occipital θ-α1 and central δ-α1 couplings showed the highest absolute coefficients, reaching 1.13 and 1.10, respectively. In the NT1 group, the α1-β2 imaginary part of phase-locking value (iPLV) of the F3-C3 pair during N1 was significantly positively correlated with ESS scores ( r=0.52, P=0.012). In the machine learning classification task, the SVC model achieved an accuracy of 85% using leave-one-out cross-validation. Conclusion:The CFC features during the sleep-wake transition stage play an important role in distinguishing NT1 from NT2 and show a significant correlation with excessive daytime sleepiness (EDS) in NT1. CFC may serve as a potential biomarker for differentiating narcolepsy subtypes and provide new insights into the mechanisms and clinical evaluation of EDS.

Objective:To investigate the differences in cross-frequency coupling (CFC) characteristics of electroencephalography (EEG) between narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2).Methods:A total of 23 NT1 and 31 NT2 patients were included from the Chinese Clinical Sleep Database (CCSD) between October 2022 and September 2023. All participants underwent overnight polysomnography and a multiple sleep latency test. CFC features were extracted from EEG signals during polysomnography, encompassing various combinations of sleep stages, electrode pairs, frequency bands, and coupling types. Feature selection was performed using elastic net regularization. The Spearman correlation between key CFC features and the Epworth Sleepiness Scale (ESS) scores was analyzed. Finally, a support vector classification (SVC) model was constructed to distinguish NT1 from NT2, and leave-one-out cross-validation was used to assess the generalization performance.Results:Among all coupling features during non-rapid eye movement sleep stage 1 (N1), the fronto-occipital θ-α1 and central δ-α1 couplings showed the highest absolute coefficients, reaching 1.13 and 1.10, respectively. In the NT1 group, the α1-β2 imaginary part of phase-locking value (iPLV) of the F3-C3 pair during N1 was significantly positively correlated with ESS scores ( r=0.52, P=0.012). In the machine learning classification task, the SVC model achieved an accuracy of 85% using leave-one-out cross-validation. Conclusion:The CFC features during the sleep-wake transition stage play an important role in distinguishing NT1 from NT2 and show a significant correlation with excessive daytime sleepiness (EDS) in NT1. CFC may serve as a potential biomarker for differentiating narcolepsy subtypes and provide new insights into the mechanisms and clinical evaluation of EDS.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.

Liquid chromatography-multiple-reaction monitoring (LC-MRM) has been widely recognized as the golden standard for multiple components-targeted quantitative analysis of complicated matrices,with extensive applications for analysis in such fields as chemical drugs, traditional Chinese medicines and foods.Unfortunately, when facing the task of quantitatively analyzing trace chemical components in complex matrices, MRM suffers dramatically from the background noise or matrix interference, leading to undesirable sensitivity and selectivity in terms of the lower limits of quantification (LOQ) and detection (LOD).In recent years, MRM cubed (MRM3), also known as MS3 scan, has received much attention because of its unique ability to significantly improve detection selectivity and sensitivity attributing to the successive ion filtering function, enabling LC-MRM3 as an emerging analytical tool.In this review,our attention is devoted to: 1) the illustration of the principle for MRM3; 2) parameter settings; and 3) the application progress of LC-MRM3 in such fields as the pursuit of biomarkers, pharmaceutical analysis, forensic analysis, toxicological analysis, food chemistry, and environmental analysis, aiming to provide a promising analytical tool of LC-MRM3 advantageous in the quantification analysis of trace chemical components in complex matrices.

Objective:To study the roles of resveratrol in reducing neuroinflammation and improving neurobehavioral functions after germinal matrix hemorrhage (GMH) in neonatal rat model.Methods:GMH model was established intraparenchymally injecting bacterial collagenase in 7-day-old SD rats. 108 rats were randomly assigned into 18 groups (6 in each group), including 4 sham groups, GMH (12 h, 24 h, 72 h, 7 d) groups, 3 GMH+vehicle (dimethylsulfoxide, DMSO) groups, 5 GMH+resveratrol (10 mg/kg, 100 mg/kg, 1 000 mg/kg) groups and 2 GMH+resveratrol+EX527 (SIRT1 inhibitor) groups. Negative geotaxis and righting reflex tests were used to evaluate the short-term neurobehavior. Water maze, foot fault and Rotor-Rod tests were used to assess the long-term neurobehavior. Immunofluorescence was used to quantify the IL-1β and MPO positive cells (inflammatory markers) in peri-hematoma area. Western blot was used to evaluate the expression of relevant proteins in the brain.Results:Endogenous sirtuin-1(SIRT1) decreased to the lowest level at 24 h and then increased gradually. Phosphorylated NF-κB increased at 12 h, peaked at 72 h and returned to normal level at 7 d after GMH. Compared with the control group and other doses groups, GMH treated with resveratrol (100 mg/kg) had higher short-term behavioral scores at 48 h and 72 h. Compared with the control group, the resveratrol (100 mg/kg) group also had higher scores in water maze, foot fault and Rotor-Rod tests 22 days later. Immunofluorescence showed less positive IL-1β and MPO cells around hematoma in GMH+resveratrol group than both GMH+vehicle group and GMH+resveratrol+EX527 group. Western blot indicated that IL-1, TNF-α and IL-6 expressions were decreased in GMH+resveratrol group and Ex527 could offset the effects of resveratrol.Conclusions:Resveratrol (optimal dose: 100 mg/kg) can improve the short-term and long-term neurobehavioral functions of neonatal GMH rats. It can reduce GMH cells with positive inflammatory markers around the hematoma, possibly via inhibition of the SIRT1/NF-κB pathway. Resveratrol may be promising for the treatment of GMH patients.

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.

AIM: To study protective effects of the extract from Toona sinensis seeds on gastric mucosal injury in experimental mice. METHODS: The mice were given 200 mg/kg, 400 mg/kg of Toona sinensis seeds every day for 2 weeks and ethanol or aspirin was used to induce gastric mucosa injury model. The gastric mucosal injury index and injury inhibition rate were calculated, the levels of SOD, MDA in serum and the contents of ET-1, PGE

A 45-year-old male patient underwent craniotomy and biopsy for intracranial lesions. In order to prevent epilepsy, sodium valproate 800 mg dissolved in 0.9% sodium chloride injection 8 ml was injected intravenously after operation, and then the sodium valproate solution of this concentration was continuously pumped at a speed of 0.6 ml/h. One hour after administration, the serum lactate level of the patient increased gradually, reaching the highest level of 14.7 mmol/L, accompanied by metabolic acidosis and compensatory respiratory alkalosis, and with the lowest pH of 7.09 and the lowest base excess of -26.3. The patient fell into a coma. The hyperlactatemia and metabolic acidosis were considered to be related to sodium valproate. Sodium valproate was stopped, intravenous infusion of 5% sodium bicarbonate injection and blood purification were given at the same time. After 3 days, the lactate level of the patient returned to normal, metabolic acidosis was basically corrected, and his mind was clear.

A 45-year-old male patient underwent craniotomy and biopsy for intracranial lesions. In order to prevent epilepsy, sodium valproate 800 mg dissolved in 0.9% sodium chloride injection 8 ml was injected intravenously after operation, and then the sodium valproate solution of this concentration was continuously pumped at a speed of 0.6 ml/h. One hour after administration, the serum lactate level of the patient increased gradually, reaching the highest level of 14.7 mmol/L, accompanied by metabolic acidosis and compensatory respiratory alkalosis, and with the lowest pH of 7.09 and the lowest base excess of -26.3. The patient fell into a coma. The hyperlactatemia and metabolic acidosis were considered to be related to sodium valproate. Sodium valproate was stopped, intravenous infusion of 5% sodium bicarbonate injection and blood purification were given at the same time. After 3 days, the lactate level of the patient returned to normal, metabolic acidosis was basically corrected, and his mind was clear.