Background: Advances in intensive care have markedly improved survival after severe brain injury, leading to a growing population of patients with prolonged disorders of consciousness (pDOC). Current management of pDOC remains largely supportive, and evidence-based neuromodulatory interventions are limited; moreover, existing guidelines provide insufficiently explicit recommendations regarding mechanisms of action and objective biomarkers of treatment response. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a potential noninvasive intervention; however, its modulatory effects on brain function in pDOC are not yet well characterized, and the paucity of integrative mechanistic evidence has constrained its translation into routine clinical practice. Objectives: Within a multimodal assessment framework, this study aims to systematically elucidate the neurobiological mechanisms by which taVNS modulates brain function and autonomic activity in patients with pDOC, and to evaluate its clinical potential to enhance levels of consciousness. Methods: In this randomized controlled trial, 60 patients with vegetative state/minimally conscious state will be enrolled and randomly allocated to a taVNS group, a transcutaneous nonauricular vagus nerve stimulation group (sham), or a control group (n = 20 per group) for a 4-week intervention. The primary outcome will be changes in the Coma Recovery Scale-Revised scores from baseline to weeks 1, 2, and 4 of treatment. Secondary outcomes will include functional brain activity assessed by electroencephalography and functional near-infrared spectroscopy, as well as autonomic modulation indexed by heart rate variability. Functional prognosis will be evaluated using the Glasgow Outcome Scale-Extended at the end of treatment and at a 6-month follow-up. Safety will be assessed by continuous monitoring and documentation of adverse events throughout the study period. Results and discussion: By integrating electroencephalography–functional near-infrared spectroscopy with heart rate variability, this study will characterize the effects of taVNS on functional brain networks and consciousness recovery in pDOC across complementary behavioral, electrophysiological, hemodynamic, and autonomic domains, while interrogating potential sources of clinical and neurobiological heterogeneity. The findings are expected to provide a mechanistic and evidence-based foundation for the mechanism-driven clinical implementation of taVNS and the optimization of stimulation protocols in pDOC. Clinical trial registration: International Traditional Medicine Clinical Trial Registry, ITMCTR20250021041, https://itmctr.ccebtcm.org.cn.

Objective To investigate the effects of SAC/VAL on myocardial fibrosis and miR-21 expression in rats induced by AAC.Methods A total of 72 SPF SD male rats were randomly di-vided into sham operation group,AAC group,low-and high-dose SAC/VAL groups,high-dose SAC/VAL+agomiR-NC group,and high-dose SAC/VAL+miR-21 agomiR group,with 12 rats in each group.Echocardiography was used to test cardiac function.HE staining and Masson staining were applied to observe the pathological changes in myocardial tissues and myocardial tissue fi-brosis,respectively.Immunohistochemical assay was employed to detect the expression of α-SMA and COL-l in myocardial tissue.Real-time fluorescence quantitative polymerase chain reaction was conducted to detect miR-21 level.Results Compared with the sham operation group,the AAC group had thicker and broken myocardial fibers in disordered arrangement,hypertrophic myocar-dial cells with condensed and deeply stained nuclei,and extensive infiltration of inflammatory cells,and obvious myocardial fibrosis,increased LVEDD and LVESD values,and up-regulated miR-21,α-SMA and COL-1 expression,but decreased LVEF and LVFS levels(P＜0.05).Low-and high-dose SAC/VAL treatment resulted in well-arranged less broken myocardial fibers in uniform distribution,relatively normal myocardial cells,less inflammatory cell infiltration,and reduced severity of myocardial fibers,lower LVEDD and LVESD values,decreased miR-21,α-SMA and COL-1 levels,but increased LVEF and LVFS levels when compared to the AAC group(P＜0.05).When compared to the high dose SAC/VAL+agomiR NC group,the high-dose SAC/VAL+miR-21 agomiR group had disorderly-arranged myocardial fiber with thickening and breakage,aberrant myocardial cells,obvious infiltration of inflammatory cells,and intensified my-ocardial fibrosis,higher LVEDD and LVESD values and miR-21,α-SMA and COL-1 expression levels,and lower LVEF and LVFS levels[7.11±0.45 mm vs 6.05±0.38 mm,P＜0.05;5.58±0.35 mm vs 4.01±0.28 mm,P＜0.05;2.57±0.14 vs 0.98±0.10,P＜0.05;0.62±0.06 A vs 0.41±0.04 A,P＜0.05;0.79±0.08 A vs 0.53±0.05 A,P＜0.05;(58.26±2.61)％vs(80.24±2.87)％,P＜0.05;(24.52±1.03)％vs(33.72±1.25)％,P＜0.05].Conclusion SAC/VAL inhibits AAC-induced myocardial fibrosis in rats,which is related to its regulation of miR-21 expression.

Objective To conduct a scoping review of studies related to latent class trajectory analysis of glucose metabolism indicators in diabetes mellitus patients,so as to clarify the method of latent category trajectory analysis,evaluation indicators and the changing trajectories of different glucose metabolism indicators in diabetes mellitus patients,and to establish foundation for diabetes management and research.Methods Based on Arksey's framework for scoping study,a literature search was performed in CNKI,Wanfang,CBM,Web of Science,PubMed,Embase,Cochrane Library,CINAHL database inception to January 28,2024.Totally 2 researchers independently screened the literature and extracted data.Results A total of 22 pieces of the literature were included.Latent class growth model was the most commonly used model in latent class trajectory analysis,and 4 softwares are available for implementation.The current evaluation indicators for trajectory results are various,with the Bayesian information criterion and average posterior probability as the most frequently utilized.Hemoglobin is the most commonly used glucose metabolism indicators for trajectory analysis,and the number of identified trajectories ranged from 2 to 5.Most studies showed that diabetic patients exhibited a"low-stable"pattern in glucose metabolism indicators.Conclusion Latent class trajectory analysis represents a novel longitudinal data analysis approach that can identify potential subgroups of diabetic patients with similar development trajectory.The models and evaluation indicators employed are diverse,and the stability test of the models can be enhanced in the future.Through trajectory identification,it is recommended that clinical staff pay greater attention to the longitudinal trend of the glucose metabolism indicators and incorporate it into the long-term blood glucose management goal of diabetic patients.

Objective To investigate the influence of remifentanil infusion at different speed on propofol injection pain.Methods Totally 200 patients who accepted elective surgery under general anesthesia with tracheal intubation were selected.The patients were divided into C group,R2 group,R3 group,R4 group and R5 group by random number table method,with 40 patients in each group,and they were injected with remifentanil at a constant rate of 0 μg·kg-1·min-1,0.2 μg·kg-1·min-1,0.3 μg·kg-1·min-1,0.4 μg·kg-1·min-1,and 0.5 μg·kg-1·min-1,respectively.After 2 minutes of remifentanil infusion,a target controlled infusion of propofol at an effect-site concentration of 2.5 μg/mL was initiated.The incidence of propofol injection pain,the severity of injection pain,heart rate and mean arterial pressure before remifentanil infusion and before tracheal intubation were compared among the 5 groups.The incidence of complications such as hypotension,bradycardia and chest wall stiffness of patients was recorded.Results The incidence and the severity of propofol injection pain of patients in R2 group,R3 group,R4 group and R5 group were significantly lower than those in C group(P<0.05).The incidence of propofol injection pain of patients in R4 group was significantly lower than those in R2 group and R3 group,and the severity of propofol injection pain of patients in R4 group was significantly lower than that in R2 group(P<0.05).The incidence and the severity of propofol injection pain of patients in R5 group was significantly lower than those in R2 group and R3 group(P<0.05).However,there were no statistically significant differences in the incidence or severity of injection pain between R2 group and R3 group,and between R4 group and R5 group(P>0.05).None of the patients in each group had complications such as hypotension,bradycardia,decreased pulse oxygen saturation,and chest wall stiffness that required drug treatment.And there was no adverse reactions such as pain,edema,redness at the injection site occurred within 24 hours after operation.Conclusion Remifentanil infused at a constant rate of 0.4 μg·kg-1·min-1 and 0.5 μg·kg-1·min-1 starting at 2 minutes before propofol administration is effective in reducing propofol injection pain without causing serious complications.

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.

Objective:To investigate whether herb cake-insulated moxibustion affects the expression of cholesterol metabolism-related protein 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGR)and inhibits the development of atherosclerosis by regulating the exosomal miR-223 expression.Methods:Thirty-six male New Zealand rabbits were randomly assigned to a normal group,a model group,and an herb cake-insulated moxibustion group,with 12 rabbits in each group.The model and the herb cake-insulated moxibustion groups were fed a high-fat diet for 8 weeks to induce an atherosclerosis model.Following successful modeling,the herb cake-insulated moxibustion group was subjected to bundling and herb cake-insulated moxibustion intervention,while the other two groups were subjected only to bundling without moxibustion.After 8 weeks of intervention,hematoxylin-eosin(HE)staining was used to observe aortic morphology;the serum levels of total cholesterol(TC),triglyceride(TG),and low-density lipoprotein cholesterol(LDL-C)were detected using an automatic biochemical analyzer in each group.Exosome morphology was observed using the transmission electron microscope;Western blotting(WB)was used to detect the protein levels of serum exosomal CD63 and CD9 markers,as well as liver HMGR;additionally,real-time fluorescence quantitative polymerase chain reaction was used to quantify serum exosomal miR-223.Results:HE staining showed thickened aortic intima,lipid infiltration,foam cell aggregation,and structural damage to the arterial wall in the model group.Meanwhile,after modeling,the serum levels of LDL-C,TC,and TG increased significantly in the model and herb cake-insulated moxibustion groups compared to the normal group(P<0.05),suggesting successful atherosclerosis rabbit model preparation.The serum exosomes of rabbits in the model group exhibited a saucer-like or semi-concave spherical shape with diameters of 120-150 nm.WB detection results showed positive expression of the exosomal markers CD63 and CD9.After 8 weeks of intervention,the miR-223 level in the model group was significantly lower than that in the normal group(P<0.01).In contrast,the herb cake-insulated moxibustion group demonstrated significantly reduced serum levels of TC,TG,and LDL-C(P<0.05),increased miR-223 expression(P<0.01),and decreased relative liver HMGR protein expression(P<0.05)compared to the model group.Conclusion:Herb cake-insulated moxibustion may alleviate the progression of atherosclerosis by up-regulating exosomal miR-223 expression and down-regulating HMGR protein expression,thereby inhibiting cholesterol anabolic metabolism.

Objective To investigate the effects of SAC/VAL on myocardial fibrosis and miR-21 expression in rats induced by AAC.Methods A total of 72 SPF SD male rats were randomly di-vided into sham operation group,AAC group,low-and high-dose SAC/VAL groups,high-dose SAC/VAL+agomiR-NC group,and high-dose SAC/VAL+miR-21 agomiR group,with 12 rats in each group.Echocardiography was used to test cardiac function.HE staining and Masson staining were applied to observe the pathological changes in myocardial tissues and myocardial tissue fi-brosis,respectively.Immunohistochemical assay was employed to detect the expression of α-SMA and COL-l in myocardial tissue.Real-time fluorescence quantitative polymerase chain reaction was conducted to detect miR-21 level.Results Compared with the sham operation group,the AAC group had thicker and broken myocardial fibers in disordered arrangement,hypertrophic myocar-dial cells with condensed and deeply stained nuclei,and extensive infiltration of inflammatory cells,and obvious myocardial fibrosis,increased LVEDD and LVESD values,and up-regulated miR-21,α-SMA and COL-1 expression,but decreased LVEF and LVFS levels(P＜0.05).Low-and high-dose SAC/VAL treatment resulted in well-arranged less broken myocardial fibers in uniform distribution,relatively normal myocardial cells,less inflammatory cell infiltration,and reduced severity of myocardial fibers,lower LVEDD and LVESD values,decreased miR-21,α-SMA and COL-1 levels,but increased LVEF and LVFS levels when compared to the AAC group(P＜0.05).When compared to the high dose SAC/VAL+agomiR NC group,the high-dose SAC/VAL+miR-21 agomiR group had disorderly-arranged myocardial fiber with thickening and breakage,aberrant myocardial cells,obvious infiltration of inflammatory cells,and intensified my-ocardial fibrosis,higher LVEDD and LVESD values and miR-21,α-SMA and COL-1 expression levels,and lower LVEF and LVFS levels[7.11±0.45 mm vs 6.05±0.38 mm,P＜0.05;5.58±0.35 mm vs 4.01±0.28 mm,P＜0.05;2.57±0.14 vs 0.98±0.10,P＜0.05;0.62±0.06 A vs 0.41±0.04 A,P＜0.05;0.79±0.08 A vs 0.53±0.05 A,P＜0.05;(58.26±2.61)％vs(80.24±2.87)％,P＜0.05;(24.52±1.03)％vs(33.72±1.25)％,P＜0.05].Conclusion SAC/VAL inhibits AAC-induced myocardial fibrosis in rats,which is related to its regulation of miR-21 expression.

Objective To investigate the adverse pregnancy outcomes of fetuses with increased nuchal translucency(NT).Methods A total of 376 pregnant women at the Third Affiliated Hospital of Zhengzhou University from May 2023 to January 2024 were selected as research subjects,who had a diagnosis of fetal NT ≥ the 95th percentile and complete pregnancy outcomes for singleton pregnancies.The fetuses were divided into simple thickening group(n=320)and thickening with structural abnormalities group(n=56)based on NT ultrasound results.The interventional prenatal diagnosis outcomes and pregnancy outcomes of two groups were compared.Results The rate of chromosomal abnormalities and the incidence of adverse pregnancy outcomes were higher in thickening with structural abnormalities group compared to simple thickening group with statistically significant differences(P＜0.05).The overall incidence of adverse pregnancy outcomes in NT thickened fetuses was 31.65％,but after excluding chromosomal abnormalities and structural malformations,the good pregnancy outcome rate in NT thickened fetuses was 98.09％.Conclusion NT thickening is associated with adverse pregnancy outcomes in fetuses,and the risk of poor fetal outcome is further increased when NT thickening combined with structural abnormalities in early pregnancy,but the pregnancy outcome is better in fetuses with NT thickening after excluding chromosomal abnormalities and structural malformations.

Objective:To investigate whether herb cake-insulated moxibustion affects the expression of cholesterol metabolism-related protein 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGR)and inhibits the development of atherosclerosis by regulating the exosomal miR-223 expression.Methods:Thirty-six male New Zealand rabbits were randomly assigned to a normal group,a model group,and an herb cake-insulated moxibustion group,with 12 rabbits in each group.The model and the herb cake-insulated moxibustion groups were fed a high-fat diet for 8 weeks to induce an atherosclerosis model.Following successful modeling,the herb cake-insulated moxibustion group was subjected to bundling and herb cake-insulated moxibustion intervention,while the other two groups were subjected only to bundling without moxibustion.After 8 weeks of intervention,hematoxylin-eosin(HE)staining was used to observe aortic morphology;the serum levels of total cholesterol(TC),triglyceride(TG),and low-density lipoprotein cholesterol(LDL-C)were detected using an automatic biochemical analyzer in each group.Exosome morphology was observed using the transmission electron microscope;Western blotting(WB)was used to detect the protein levels of serum exosomal CD63 and CD9 markers,as well as liver HMGR;additionally,real-time fluorescence quantitative polymerase chain reaction was used to quantify serum exosomal miR-223.Results:HE staining showed thickened aortic intima,lipid infiltration,foam cell aggregation,and structural damage to the arterial wall in the model group.Meanwhile,after modeling,the serum levels of LDL-C,TC,and TG increased significantly in the model and herb cake-insulated moxibustion groups compared to the normal group(P<0.05),suggesting successful atherosclerosis rabbit model preparation.The serum exosomes of rabbits in the model group exhibited a saucer-like or semi-concave spherical shape with diameters of 120-150 nm.WB detection results showed positive expression of the exosomal markers CD63 and CD9.After 8 weeks of intervention,the miR-223 level in the model group was significantly lower than that in the normal group(P<0.01).In contrast,the herb cake-insulated moxibustion group demonstrated significantly reduced serum levels of TC,TG,and LDL-C(P<0.05),increased miR-223 expression(P<0.01),and decreased relative liver HMGR protein expression(P<0.05)compared to the model group.Conclusion:Herb cake-insulated moxibustion may alleviate the progression of atherosclerosis by up-regulating exosomal miR-223 expression and down-regulating HMGR protein expression,thereby inhibiting cholesterol anabolic metabolism.

Long-term spaceflight,characterized by drastic changes in spatial position,disrupts the Earth's inherent environmental periodic signals,such as the day-night light-dark cycle.This leads to a misalignment between the external environmental cycles and the body's endogenous biological rhythms.The cumulative effect of this persistent"time difference"severely disrupts the core biological pathways that regulate the circadian rhythm.It triggers a series of neuroendocrine and behavioral stress responses,exemplified by sleep-wake disorders,which have become a core medical problem constraining the success of long-term space missions and astronaut health.Traditional Chinese Medicine(TCM)posits that aligning with the rhythmic changes of heaven,earth,day,night,and the four seasons,and maintaining the dynamic balance and harmonious functioning of the body's Yin and Yang vital energies,are fundamental principles for safeguarding vitality and resisting external pathogens and internal injuries.However,in the prolonged weightlessness,confinement,and abnormal lighting environment of deep space flight,the bond between the human body and natural rhythms is forcibly severed.Yin and Yang Qi become difficult to sustain,the mechanisms of ascent,descent,exit,and entry are obstructed,the visceral Qi transformation functions are impaired,and the circulation of Qi and Blood becomes disordered,ultimately leading to the onset of various disorders.This paper,grounded in the TCM temporal medicine perspective of"correspondence between heaven and human"(tian ren xiang ying)and the theories of Yin-Yang and Qi-Blood,meticulously reviews the historical classics and modern research on acupoint intervention strategies for addressing rhythm disorders and harmonizing Yin and Yang.Building upon this foundation,it innovatively proposes and argues for an integrated acupoint prescription strategy:the"Bei Xin Wu Xue"combined with the classic paired points Zhaohai(KI6)-Shenmai(BL62)on the lower limbs to regulate the dynamic balance of the Yin and Yang Heel Vessels(Yin/Yang Qiao Mai),and the classic paired points Taichong(LR3)-Yongquan(KI1)to guide Qi downward.This combination aims to work at multiple levels-"Heart-Brain,Yin-Yang,Liver-Kidney"-to calm the Heart Spirit,clear the Brain Mansion,and tonify the Liver and Kidney.The goal is to restore Yin and Yang Qi to an orderly and coordinated state,thereby assisting the disordered biological rhythm system in regaining homeostasis.This provides a novel TCM-inspired approach of"rhythm regulation and equilibrium restoration"(tiao shi fu heng)to safeguard the long-term in-orbit health of astronauts.