ObjectiveTo observe the effect of Yangxin Tongmai Formula （养心通脉方） by midnight-noon ebb-flow administration method for rat models of premature coronary heart disease （PCHD） with blood stasis syndrome， and to explore the possible mechanism of action from the perspective of DNA methylation differential gene expression. MethodsThere were 3 SD rats in each of the blank group， model group and Yangxin Tongmai Formula group， and the rats in the model group and Yangxin Tongmai Formula group were fed with high-fat chow plus vitamin D3 by gavage plus isoproterenol hydrochloride by subcutaneous injection to construct rat models of PCHD with blood stasis syndrome. After successful modelling， rats in Yangxin Tongmai Formula group were gavaged with 18 g/（kg‧d） of Yangxin Tongmai Formula， and rats in blank group and the model group were gavaged with 4 ml/（kg‧d） of 0.9% NaCl solution， and serum samples of rats in each group were collected for DNA methylation sequencing after 3 weeks to screen for the relevant DNA methylation differentiation genes. In addition， rats with successful modelling of PCHD with blood stasis were randomly divided into model group， Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice in the heart channel period （12：00） and pericardium channel period （20：00）］， the Yangxin Tongmai Formula control group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice at 8：00 and 18：00］ and the Atorvastatin Calcium group ［atorvastatin calcium tablets solution 1.8 mg/（kg‧d） at the same intervention time as that in Yangxin Tongmai Formula control group］， and set up a blank group of 8 rats in each group. The model group and blank group were gavaged with 0.9% NaCl solution 4 ml/（kg‧d） for the same time as the Yangxin Tongmai Formula control group. After 3 weeks of gavage， the blood lipids ［including total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）］ levels of rats in each group were detected； the HE staining of myocardial tissues and thoracic aorta was used to observe the pathomorphological changes； the levels of serum inflammation indexes ［tumour necrosis factor alpha （TNF-alpha）， lipopolysaccharide （LPS）， and interleukin 10 （IL-10）］ were detected； immunoprecipitation-realtime fluorescence quantitative PCR was used to detect the relative expression of cardiac tissue screening differential genes. ResultsThe genes screened for differentially methylated regions were calmodulin 2 （Calm2）， calcium voltage-gated channel subunit α1s （Cacna1s）， and phospholipase Cβ1 （Plcb1）. Compared with the blank group， rats in the model group showed elevated levels of TC， LDL， TNF-α and LPS， and decreased levels of HDL and IL-10 （P＜0.05 or P＜0.01）； HE staining showed obvious swelling of myocardial fibres， accompanied by a large number of inflammatory cell infiltration， and thickening of the inner wall of the aortic vessels with internal wall damage， which was visible as a large number of lipid cholesterol crystals and obvious inflammatory cell infiltration. Compared with the model group， the TC， LDL， TNF-α and LPS contents of rats in the Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group， the Yangxin Tongmai Formula control group， and the atorvastatin calcium group all reduced， and the contents of HDL and IL-10 all elevated （P＜0.05）， with the improvement of myocardial tissue damage and the reduction of inflammatory infiltration， and the improvement of the damage of the inner lining of the thoracic aorta and the reduction of lipid infiltration. Compared with Yangxin Tongmai Formula control group， LDL， TNF-α and LPS contents reduced， and IL-10 contents increased in the midnight-noon ebb-flow administration method group （P＜0.05）. Compared with the model group， the relative expression of Calm2 and Plcb1 genes decreased and the relative expression of Cacna1s gene increased in Yangxin Tongmai Formula control group and the midnight-noon ebb-flow administration method group （P＜0.05）； compared with the Yangxin Tongmai Formula control group， the relative expression of Calm2 gene decreased and the relative expression of Cacna1s gene increased in the midnight-noon ebb-flow administration method group （P＜0.05）. ConclusionThe intervention of Yangxin Tongmai Formula in the heart channel period （12：00） and pericardium channel period （20：00） was more effective in improving the blood lipid level， inhibiting inflammation， and improving myocardial tissue damage in rats of PCHD with blood stasis syndrome， and Calm2 and Cacna1s genes may be the key targets of Yangxin Tongmai Formula in intervening the blood stasis syndrome of PCHD.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

Objective:To investigate the impact of metformin on the Beh?et's disease (BD) mice model via the Treg/Th17 axis.Methods:The BD mice model was established by subcutaneous injection of HSV-1. Four groups were established, including healthy control group, model group, high-dose metformin group, and low-dose metformin group. The HSV-1 DNA copy number in the peripheral blood was measured using qRT-PCR. Plasma levels of TGF-β 1, IL-10, IL-17, IL-23, IL-6, and TNF-α were assessed by ELISA. Flow cytometry was employed to determine the proportion of Treg and Th17 cells in the spleen. One-way analysis of variance was used for inter-group comparisons, pairwise comparisons were performed using SNK- q test. Results:Thirty-eight BD models were successfully established, with 28 survived. Compared to the BD model group, the metformin treatment groups showed faster healing of genital ulcers, joint redness/swelling, and skin ulcers, along with better mental status. HSV-1 copy numbers decreased in the metformin groups compared to the model group at 20 and 30 days post-treatment. Compared to the healthy control group, the model group exhibited elevated levels of TGF-β 1, IL-17, IL-6, IL-23, and TNF-α, but a decrease in IL-10. Following high-dose metformin treatment, TGF-β 1, IL-17, IL-6, IL-23, and TNF-α were significantly reduced ( q=16.17, P<0.001; q=8.76, P<0.001; q=6.78, P=0.004; q=4.45, P=0.020; q=12.08, P<0.001), accompanied by elevated IL-10 (specific value) ( q=6.28, P<0.001). Compared with the control group [Treg: (1.82±0.68)%; Th17: (2.12±0.86)%], the model group showed significantly elevated proportions of Treg cells[(6.03±2.42)%] ( q=5.01, P<0.001) and Th17 cell [(3.40±0.58)%] ( q=2.96, P=0.017). After high-dose metformin treatment, both Treg cell proportion [(3.20±1.66)%] and Th17 cell proportion [(2.16±0.78)%] decreased compared to the model group ( q=3.05, P=0.014). No significant differences were observed between the high-and low-dose metformin groups across all measured indicators, indicating similar efficacy. Conclusion:Metformin could reduce HSV-1 virus replication, reduce the levels of inflammatory cytokines and regulate Treg/Th17 axis to alleviate the BD symptoms. This study provides evidence for repurposing metformin in the treatment of Beh?et's disease.

Objective:To evaluate the safety and clinical efficacy of enteral nutrition (EN) initiated within 24 h after heart transplantation in pediatric patients.Methods:A retrospective cohort study was conducted. Clinical data from 16 pediatric heart transplant recipients at the Seventh Medical Center of the Chinese People′s Liberation Army General Hospital between October 2022 and October 2024 were collected, including demographics, anthropometric measurements, biochemical markers, cytokine levels, and clinical outcomes. Based on the timing of EN initiation, the patients were divided into EN-initiated within 24 h and EN-initiated after 24 h 2 groups. Demographic data, preoperative extracorporeal membrane oxygenation (ECMO) support, physical examination indicators, laboratory parameters, and cytokine levels were compared between groups using independent samples t-test, Mann-Whitney U test, Fisher′s exact probability test. Results:The cohort comprised 16 patients (10 males and 6 females) with an age of (12.5±1.9) years. The EN-initiated within 24 h group comprised 6 cases, and the EN-initiated after 24 h group comprised 10 cases. No significant difference was observed between the two groups in age, preoperative body mass index Z-score, preoperative ECMO support, physical examination indicators, laboratory parameters (total protein, albumin, hemoglobin), or cytokine levels (all P>0.05). Compared to the EN-initiated after 24 h group, the EN-initiated within 24 h group exhibited a shorter intensive care unit stay ( t=2.65, P<0.05) and shorter mechanical ventilation duration ( t=2.23, P<0.05) than EN-initiated after 24 h group. Total hospitalization length had no significant difference ( P>0.05). At 72 h post-transplant, the EN-initiated within 24 h group had a lower interleukin-12 P70 ( t=2.46, P<0.05) and interferon-γ levels ( t=2.55, P<0.05) than EN-initiated after 24 h group. Prior to discharge, the EN-initiated within 24 h group has a lower mean skinfold thickness ( t=2.49, P<0.05) and lower mid-upper arm circumference ( t=2.36, P<0.05) compared with the EN-initiated after 24 h group. Conclusions:Initiating EN within 24 h postoperatively is safe and feasible in pediatric heart transplant recipients. Early EN may shorten the length of intensive care unit stay and mechanical ventilation while attenuating postoperative release of inflammatory cytokine.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective To clarify the active ingredients and the potential molecular mechanism of Guben Qushi Huayu Prescription in treating psoriasis recurrence.Methods An ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was applied to analyze the whole formula and the constituents absorbed into blood of Guben Qushi Huayu Prescription,and molecular docking technology was used to study the binding affinity of the constituents absorbed into blood with psoriasis-related immunomodulatory proteins such as CD69 and CD103 proteins.Results Mass spectrometry analysis identified 21 active ingredients such as paeoniflorin in Guben Qushi Huayu Prescription,including several known anti-inflammatory and immunomodulatory compounds.Analysis of the constituents absorbed into blood identified 11 ingredients,including paeoniflorin,that may affect the course of psoriasis through blood circulation.Molecular docking studies revealed that the constituents absorbed into blood,including astilbin,isoastilbin,chlorogenic acid,neochlorogenic acid,cryptochlorogenic acid,helicine,paeoniflorin,ononin,all had high binding affinities with CD69 and CD103 proteins.Conclusion This research reveals the main active ingredients of Guben Qushi Huayu Prescription and their potential mechanism for regulating the recurrence of psoriasis by mass spectrometry and molecular docking technology,contributing to providing scientific basis for further pharmacological research and clinical application.

Objective To investigate whether aberrant DNA methylation of ubiquinol-cytochrome C reductase core protein 1(UQCRC1)is related to cognitive impairment caused by neonatal sevoflurane exposure.Methods A total of 94 SPF C57 mice of either sex,aged 6 d,and weighing 4～6 g,were randomly divided into 7 groups:control group(Con,n=6),sevoflurane-6 and-24 h exposure groups(Sev-6 and-24 h,n=6),control+DMSO group(Con+DMSO,n=19),control+5-aza-2'-deoxycytidine(5-AZA,methylation inhibitor)group(Con+5-AZA,n=19),sevoflurane+DMSO group(Sev+DMSO group,n=19),and sevoflurane+5-AZA group(Sev+5-AZA group,n=19).From 6 to 8 d after birth,the mice of the Sev-6 and-24 h exposure groups were exposed to 3％sevoflurane daily(with 97％oxygen,2 L/min,2 h per day),while those from the Con groups were given exposure of 100％oxygen(2 L/min,2 h per day).For the mice of the 5-AZA and DMSO groups,1 mg/kg of 5-AZA or an equal volume of DMSO was injected intraperitoneally 30 min before daily exposure.In 6 and 24 h after the last exposure to sevoflurane,6 mice from the Con,Sev-6 h,and Sev-24 h groups were euthanized for biochemical analysis,and in 24 h post-exposure,6 mice from the Con+DMSO,Con+5-AZA,Sev+DMSO,and Sev+5-AZA groups were randomly selected for biochemical analysis,while another 3 mice from above each group were also randomly selected for morphological analysis.The remaining 10 mice in these groups underwent behavioral testing(open field test,novel object test,and Y-maze test)at 30～33 d after birth to assess cognitive function,and were euthanized in 24 h after the final behavioral test.RT-qPCR and Western blotting were used to detect the hippocampal expression of UQCRC1,DNA methyltransferases(Dnmts),and methyl CpG binding protein 2(Mecp2)at mRNA and protein levels,respectively.Immunofluorescence assay was employed to observe the distribution and expression of UQCRC1 in the hippocampus.Bisulfite sequencing PCR(BSP)was applied to measure the methylation in the UQCRC1 promoter region.Results Compared with the Con group,the mRNA and protein levels of UQCRC1 were down-regulated(P<0.05),and the mRNA level of Dnmts was up-regulated(P<0.05)in both the Sev-6 h and Sev-24 h exposure groups,while the methylation level in the UQCRC1 promoter region was enhanced in the Sev-24 h exposure group(P<0.05).Additionally,the Sev+5-AZA group had obviously increased mRNA and protein levels of UQCRC1(P<0.05),and notable improvement in cognitive impairment(P<0.05)when compared with the Sev+DMSO group.Conclusion Hypermethylation of UQCRC1 promoter region and thus down-regulating its mRNA and protein expression might be the main mechanism by which repeated neonatal sevoflurane exposure induces cognitive impairment later in life.

With the introduction and implementation of relevant policies such as the outline of "Healthy China 2030" plan and Healthy China Action (2019-2030), the health service function of traditional Chinese medicine (TCM) has been valued and developed. TCM health literacy has become one of the important ways to promote the health of the whole population. TCM health preservation literacy refers to the ability of individuals to obtain TCM health preservation concepts, knowledge and technical services, and to make correct health care decisions to promote their own health by using knowledge and information as well as medical and technical services. According to survey data from the National Administration of Traditional Chinese Medicine, the compliance rate of TCM health literacy among Chinese citizens has increased from 8.55% in 2014 to 24.62% in 2023, and is still on the rise. However, there are differences in the level of TCM health literacy among different regions, genders, and occupational groups. This article retrieves relevant literature published on CNKI and Wanfang Data from the establishment of the databases until December 2024. The content is sorted out using thematic analysis, and a review is conducted on the concept, evaluation tools, current status, and influencing factors of TCM health literacy. This article provides a reference for enhancing public health awareness and improving the level of TCM health literacy.

Objective To explore the application effect of foot massage based on the brain-gut axis theory in patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,and to provide references for improving patients' sleep quality and gastrointestinal symptoms.Methods A total of 88 patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,who were treated at a Blood Purification Center of a tertiary-A general hospital in Hangzhou,Zhejiang Province from April to September 2024,were selected as a study subjects.They were randomly divided into an experimental group and a control group using the random number table method,with 44 cases in each group.The experimental group received foot massage based on the guidance of the brain-gut axis theory in addition to conventional treatment and nursing care,while the control group received conventional treatment and nursing care only.The intervention lasted for 3 months.The differences in the Pittsburgh Sleep Quality Index(PSQI)scores,Gastrointestinal Symptom Rating Scale(GSRS)scores,traditional Chinese medicine(TCM)syndrome scores,and serum 5-hydroxytryptamine and melatonin levels between the 2 groups before and after the intervention were compared.Results During the study period,no cases were lost in the experimental group,while 5 cases were lost in the control group.Ultimately,44 cases were included in the experimental group and 39 cases in the control group.After the intervention,the PSQI scores,GSRS scores,and TCM syndrome scores in both groups were lower than those before the intervention,and those in the experimental group were lower than those in the control group.The serum 5-hydroxytryptamine and melatonin levels were higher than those before the intervention,and the levels in the experimental group were higher than those in the control group,with statistically significant differences(all P＜0.001).Conclusion Foot massage based on the brain-gut axis theory can improve gastrointestinal symptoms and TCM syndromes in patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,and enhance their sleep quality.

Pain modulation encompasses a complex neurobiological process, in which the lateral habenula (LHb) plays a crucial role in integrating, regulating and modulating pain signals. It is also involved in pain-related memory functions associated with perception, transmission and regulation of pain. Furthermore, the LHb collaborates with structures such as the spinal dorsal horn, forebrain, and amygdala to form an essential neural circuit that contributes to sensitization, development of tolerance, and adaptation processes related to pain. However, there remains limited understanding regarding the specific roles and interactions among different neuron subtypes within the LHb concerning pain regulation. Additionally, further investigation is warranted to explore functional changes and plasticity within both the LHb and its associated neural circuits in chronic pain models. Future research endeavors should utilize advanced neuroimaging techniques alongside optogenetics and gene editing technologies to elucidate intricate neural circuits, cellular architecture, and molecular mechanisms governing LHb function in pain regulation. In conclusion, this paper aims to comprehensively review existing literature on the involvement of the LHb and its neural circuits in modulating pain, thereby enhancing our understanding of their neurobiological mechanisms while providing novel targets for precise therapeutic strategies aimed at alleviating pain.