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 role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice. Methods: Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue. Results: Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group. Conclusion Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.

OBJECTIVE: To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments. METHODS: The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape Database. Molecular docking analysis was used to confirm the binding affinity of the core compounds with key therapeutic targets. Finally, the effects of LGS on key signaling pathways and biological processes were determined by in vitro and in vivo experiments. RESULTS: A total of LGS-related targets and 496 ARDS-related targets were obtained from the databases. Network pharmacological analysis suggested that LGS could treat ARDS based on the following information: LGS ingredients luteolin, wogonin, and baicalein may be potential candidate agents. Mitogen-activated protein kinase 14 (MAPK14), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), and tumor necrosis factor alpha (TNF-α) may be potential therapeutic targets. Reactive oxygen species metabolic process and the apoptotic signaling pathway were the main biological processes. The p38MAPK/NF-κ B signaling pathway might be the key signaling pathway activated by LGS against ARDS. Moreover, molecular docking demonstrated that luteolin, wogonin, and baicalein had a good binding affinity with MAPK14, RELA, and TNF α. In vitro experiments, LGS inhibited the expression and entry of p38 and p65 into the nucleation in human bronchial epithelial cells (HBE) cells induced by LPS, inhibited the inflammatory response and oxidative stress response, and inhibited HBE cell apoptosis (P<0.05 or P<0.01). In vivo experiments, LGS improved lung injury caused by ligation and puncture, reduced inflammatory responses, and inhibited the activation of p38MAPK and p65 (P<0.05 or P<0.01). CONCLUSION LGS could reduce reactive oxygen species and inflammatory cytokine production by inhibiting p38MAPK/NF-κ B signaling pathway, thus reducing apoptosis and attenuating ARDS.
Drugs, Chinese Herbal/pharmacology* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Humans ; Male ; Network Pharmacology ; Apoptosis/drug effects* ; Mice

Platelets are indispensable for physiological hemostasis and pathological thrombus formation, and platelet adhesion to endothelial collagen is a critical initial step in thrombus formation, often overlooked in current antiplatelet therapies. This study aims to elucidate how ginsenoside CK enhances hemodynamic circulation, alleviates stasis, and proposes therapeutic mechanisms. Inspired by the effects on improving microcirculatory disturbances in an acute soft tissue injury model, CK was identified as a PHD2 inhibitor, effectively suppressing platelet adhesion to collagen. It was proposed that targeting PHD2 regulates collagen hydroxylation modification, thereby influencing the formation of its three-dimensional structure, reducing the binding affinity between VWF and collagen, and ultimately suppressing thrombotic events. The efficacy of this mechanism was subsequently confirmed through a mouse DIC model, demonstrating the feasibility of CK in alleviating circulatory disorders. It is worth noting that when Phd2 was knocked down in mice's lungs, pulmonary embolism was significantly reduced. Additionally, PHD2 inhibitors approved for other diseases have exhibited similar anti-thrombotic effects. Moreover, when PHD2 inhibitors were combined with aspirin, they more effectively inhibited arterial thrombosis in rats. The findings offer valuable insights into potential targets for developing antiplatelet drugs or expanding therapeutic applications for existing PHD2 inhibitors in treating thrombotic diseases.

ObjectiveThis study aims to investigate the effects of Linggui Zhugantang （LGZGT） on ventricular remodeling （VR） in mice with myocardial infarction （MI） and its impact on the Ras homologgene A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway. MethodsThe MI model of mice was established by ligating the left anterior descending coronary artery （LAD）. They were divided into the sham-operated group， the model group， the low-dose， medium-dose， and high-dose groups of LGZGT （2.34， 4.68， 9.36 g·kg^-1）， and the captopril group （3.25 mg·kg^-1）， with 10 mice in each group. After four weeks of continuous drug administration by gavage， the level of cardiac function in each group of mice was examined using small animal Doppler ultrasound. Hematoxylin-eosin （HE） staining and Masson staining was used to assess the morphological changes of myocardial tissue and calculate the rate of collagen fiber deposition in mouse myocardial tissue. Wheat germ agglutinin （WGA） staining was employed to compare the cross-sectional area of cardiomyocytes in each group of mice. The expression levels of α-smooth muscle actin （α-SMA）， matrix metalloproteinase-2 （MMP-2）， type Ⅰcollagen （Col Ⅰ）， Col Ⅲ， tissue inhibitor of metalloproteinase 1（TIMP1）， B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， Bcl-2， Caspase-3， and cleaved Caspase-3 were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to evaluate the mRNA levels of the pathway-related genes RhoA， ROCK1， and ROCK2. The protein expression levels of RhoA， ROCK1， and ROCK2 were tested by Western blot. ResultsThe level of cardiac function was markedly declined in the model group compared to the sham-operated group（P<0.01）. Myocardial tissue morphology changed significantly. The cross-sectional area of cardiomyocytes was significantly enlarged. The expression of α-SMA， MMP-2， Col Ⅰ， and Col Ⅲ was significantly upregulated（P<0.01）， and TIMP1 protein expression was significantly reduced（P<0.01）. The expressions of apoptosis-related proteins Bax were significantly up-regulated（P<0.01）， while the expression of Bcl-2 protein was significantly decreased（P<0.01）. The mRNA expression of RhoA， ROCK1， and ROCK2 were significantly upregulated （P<0.01）. Compared to the model group， the low-dose， medium-dose， and high-dose groups of LGZGT and the captopril group significantly reversed the experimental results of the model group in a dose-dependent manner （P<0.05， P<0.01）. ConclusionLGZGT significantly attenuated myocardial fibrosis， myocardial hypertrophy， and cardiomyocyte apoptosis after MI in mice and effectively reversed VR， the mechanism of which may be related to the modulation of the RhoA/ROCK signaling pathway.

ObjectiveThis study aims to investigate the effects of Linggui Zhugantang （LGZGT） on ventricular remodeling （VR） in mice with myocardial infarction （MI） and its impact on the Ras homologgene A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway. MethodsThe MI model of mice was established by ligating the left anterior descending coronary artery （LAD）. They were divided into the sham-operated group， the model group， the low-dose， medium-dose， and high-dose groups of LGZGT （2.34， 4.68， 9.36 g·kg^-1）， and the captopril group （3.25 mg·kg^-1）， with 10 mice in each group. After four weeks of continuous drug administration by gavage， the level of cardiac function in each group of mice was examined using small animal Doppler ultrasound. Hematoxylin-eosin （HE） staining and Masson staining was used to assess the morphological changes of myocardial tissue and calculate the rate of collagen fiber deposition in mouse myocardial tissue. Wheat germ agglutinin （WGA） staining was employed to compare the cross-sectional area of cardiomyocytes in each group of mice. The expression levels of α-smooth muscle actin （α-SMA）， matrix metalloproteinase-2 （MMP-2）， type Ⅰcollagen （Col Ⅰ）， Col Ⅲ， tissue inhibitor of metalloproteinase 1（TIMP1）， B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， Bcl-2， Caspase-3， and cleaved Caspase-3 were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to evaluate the mRNA levels of the pathway-related genes RhoA， ROCK1， and ROCK2. The protein expression levels of RhoA， ROCK1， and ROCK2 were tested by Western blot. ResultsThe level of cardiac function was markedly declined in the model group compared to the sham-operated group（P<0.01）. Myocardial tissue morphology changed significantly. The cross-sectional area of cardiomyocytes was significantly enlarged. The expression of α-SMA， MMP-2， Col Ⅰ， and Col Ⅲ was significantly upregulated（P<0.01）， and TIMP1 protein expression was significantly reduced（P<0.01）. The expressions of apoptosis-related proteins Bax were significantly up-regulated（P<0.01）， while the expression of Bcl-2 protein was significantly decreased（P<0.01）. The mRNA expression of RhoA， ROCK1， and ROCK2 were significantly upregulated （P<0.01）. Compared to the model group， the low-dose， medium-dose， and high-dose groups of LGZGT and the captopril group significantly reversed the experimental results of the model group in a dose-dependent manner （P<0.05， P<0.01）. ConclusionLGZGT significantly attenuated myocardial fibrosis， myocardial hypertrophy， and cardiomyocyte apoptosis after MI in mice and effectively reversed VR， the mechanism of which may be related to the modulation of the RhoA/ROCK signaling pathway.

Objective To assess the clinical value of multimodal ultrasound score for assessment of endometrial receptivity among patients with polycystic ovary syndrome (PCOS), and to provide guidance for improving pregnancy outcomes among PCOS patients. Methods A total of 48 PCOS patients admitted to Jiangning Hospital Affiliated to Nanjing Medical University between January and December 2023 were enrolled as the case group, while 50 healthy women of childbearing age received ovulation monitoring at the same hospital during the same period served as the control group. Subjects received two-dimensional grayscale ultrasound during the implantation window (19 to 23 days of the menstrual cycle) for measurement of endometrial thickness, Gonen classification, and endometrial peristalsis. Two-dimensional color Doppler ultrasound was used for assessment of endometrial blood flow and three-dimensional ultrasound was used for assessment of endometrial volume and vascularization flow index (VFI). The endometrium multimodal ultrasound scores were estimated, and various parameters were compared between the two groups. The diagnostic performance of these parameters for PCOS was evaluated with receiver operating characteristic (ROC) curves. Results The age of subjects in the case group ranged from 20 to 38 years, with a mean age of (28.20 ± 2.82) years, and their body mass index (BMI) ranged from 21.23 to 29.11 kg/m², with a mean BMI of (26.25 ± 1.60) kg/m². The age of subjects in the control group ranged from 22 to 38 years, with a mean age of (28.10 ± 1.99) years, and their BMI ranged from 21.33 to 29.03 kg/m², with a mean BMI of (26.10 ± 1.78) kg/m². There were no significant differences between the case and control groups in terms of mean age, BMI, estradiol, and testosterone (t = 0.218, 0.422, 0.010, and 0.221; all P > 0.05). The endometrial thickness, endometrial volume, and VFI were significantly higher in the control group than in the case group (t = 4.838, 4.978, and 7.115; all P < 0.05). There were significant differences between the two groups in terms of endometrial classification, endometrial peristalsis pattern, and endometrial and sub-endometrial blood flow (Z = −4.136, −4.048, and −3.884; all P < 0.05). The scores of endometrial classification, endometrial peristalsis, endometrial and sub-endometrial blood flow, endometrial volume, VFI, and multimodal ultrasound were significantly lower in the case group than in the control group (t = 4.539, 4.449, 4.205, 3.209, 5.206, and 4.495; all P < 0.05). No significant difference was detected in the endometrial thickness score between the two groups (t = -0.149, P = 0.882). The areas under the ROC curves for endometrial thickness, endometrial volume, VFI, and multimodal ultrasound scores in diagnosis of PCOS were 0.753, 0.747, 0.809, and 0.858, respectively. Conclusion Multimodal ultrasound score provides a comprehensive assessment of the endometrium, and is effective in the assessment of endometrial receptivity, which may provide a reference for guiding pregnancy planning in PCOS patients.

Objective:To analyze the clinical characteristics and related factors of cognition disorders in elderly hypertensive patients.Methods:It was a cross-sectional study. A total of 612 hypertensive patients with the age of (69.06±6.58) years (median 68.00 years) admitted in the Department of Cardiology, General Hospital of Chinese People′s Liberation Army from October 2022 to April 2024 were enrolled. The demographic and clinical data were collected, the cognition status was assessed with Mini-Mental State Examination (MMSE) at admission. The related factors of cognition disorders were analyzed with univariate and multivariate logistic regression.Results:The results showed that female hypertensive patients and those with older age, lower education, higher fasting blood glucose (FBG) and diabetes mellitus, higher low-density lipoprotein cholesterol (LDL-C) level, higher systolic blood pressure (SBP) and more cardiovascular comorbidities were likely to have cognition disorders (all P<0.05). Multivariate logistic regression analysis showed that smoking history, elevated SBP, elevated heart rate, elevated FBG, and elevated LDL-C were independent risk factors for cognition disorders in elderly hypertensive patients,while higher education level was an independent protective factor (all P<0.05). Conclusion:Smoking, increased SBP, increased heart rate, increased FBG, increased LDL-C and lower education level are independently associated with cognition disorders in elderly hypertensive patients.

Objective: To investigate the prevalence of abnormal foot arch morphology and its associated factors among primary and secondary school students in Ganzhou City, so as to provide evidence for the prevention of such abnormalities. Methods: From November 2023 to May 2024, a questionnaire was conducted among 1 013 primary and secondary school students, who were selected from one primary school and one nine year continuous school with stratified cluster random sampling method. Professional equipment, including 2D foot scanning and plantar pressure plates, was utilized to screen pupils for abnormal foot arch morphology (including flatfoot and high arched foot). The Chi square was employed for intergroup comparisons, whilst multifactorial Logistic regression analysis was utilized to investigate the associated factors for the occurrence of foot morphological abnormality of arch among students. Results: The prevalence rate of flatfoot among primary and secondary school students at 61.1%, with bilateral cases accounting for 37.5% and unilateral cases for 23.6%; the prevalence of high arched foot was 8.0%, comprising 3.9% in both feet and 4.0% in one foot. The prevalence rates of flatfoot among boys and girls were 68.7% and 53.6% respectively. Multivariate Logistic regression analysis revealed that boys had a 1.45 times higher risk of developing flatfoot compared to girls ( OR =1.45, 95% CI = 1.05- 2.02), primary and secondary students aged 6-8 and 9-10 had 4.00, 3.81 times higher risk of flatfoot respectively compared to those aged 15-16 ( OR =4.00, 3.81, 95% CI =2.18-7.36, 2.08-6.99) (all P <0.05). Compared to girls, boys had a lower risk of developing high arched foot ( OR=0.52, 95%CI =0.28-0.95), primary and secondary students who frequently corrected their sitting and standing posture also had a lower risk of high arched foot ( OR = 0.30, 95% CI =0.10-0.88) (both P <0.05). Conclusions The prevalence of abnormal foot arch morphology among primary and secondary school students is relatively high, with exercise habits, and postural behaviour identified as associated factors. It is recommended to enhance early screening and behavioural interventions for key populations, thereby advancing the prevention and correction of foot morphological abnormality of arch.

Objective:To analyze the clinical characteristics and related factors of cognition disorders in elderly hypertensive patients.Methods:It was a cross-sectional study. A total of 612 hypertensive patients with the age of (69.06±6.58) years (median 68.00 years) admitted in the Department of Cardiology, General Hospital of Chinese People′s Liberation Army from October 2022 to April 2024 were enrolled. The demographic and clinical data were collected, the cognition status was assessed with Mini-Mental State Examination (MMSE) at admission. The related factors of cognition disorders were analyzed with univariate and multivariate logistic regression.Results:The results showed that female hypertensive patients and those with older age, lower education, higher fasting blood glucose (FBG) and diabetes mellitus, higher low-density lipoprotein cholesterol (LDL-C) level, higher systolic blood pressure (SBP) and more cardiovascular comorbidities were likely to have cognition disorders (all P<0.05). Multivariate logistic regression analysis showed that smoking history, elevated SBP, elevated heart rate, elevated FBG, and elevated LDL-C were independent risk factors for cognition disorders in elderly hypertensive patients,while higher education level was an independent protective factor (all P<0.05). Conclusion:Smoking, increased SBP, increased heart rate, increased FBG, increased LDL-C and lower education level are independently associated with cognition disorders in elderly hypertensive patients.