Chronic heart failure （CHF） is a complex clinical syndrome caused by ventricular dysfunction， with mitochondrial energy metabolism disorder being a critical factor in disease progression. Heart-Yang deficiency syndrome， as the core pathogenesis of CHF， persists throughout the disease course. Insufficiency of heart-Yang leads to weakened warming and propelling functions， resulting in the accumulation of phlegm-fluid， blood stasis， and dampness. This eventually causes Qi stagnation with phlegm obstruction and blood stasis with water retention， forming a vicious cycle that exacerbates disease progression. According to the theory of reinforcing Yang， the clinical experience of the traditional Chinese medicine （TCM） master Tang Zuxuan in treating CHF with heart-Yang deficiency syndrome， and achievements from molecular biological studies， this study innovatively proposes an integrated research framework of "TCM syndrome differentiation and staging-mitochondrial metabolism mechanisms-intervention with Yang-reinforcing prescriptions" which is characterized by the integration of traditional Chinese and Western medicine. Heart-Yang deficiency syndrome is classified into mild （Stage Ⅰ-Ⅱ）， severe （Stage Ⅲ）， and critical （Stage Ⅳ） stages. The study elucidates the precise correlations between the pathogenesis of each stage and mitochondrial metabolism disorders from theoretical， pathophysiological， and therapeutic perspectives. The mild stage is characterized by impaired biogenesis and substrate-utilization imbalance， corresponding to heart-Yang deficiency and phlegm-fluid aggregation. Linggui Zhugantang and similar prescriptions can significantly improve the expression of peroxisome proliferator-activated receptor gamma co-activator-1α（PGC-1α）/silent information regulator 2 homolog 1 （SIRT1） and ATPase activity. The severe stage centers on oxidative stress and structural damage， reflecting Yang deficiency with water overflow and phlegm-blood stasis intermingling. At this stage， Zhenwu Tang and Qiangxin Tang can effectively mitigate oxidative stress damage， increase adenosine triphosphate （ATP） content， and repair mitochondrial structure. The critical stage arises from calcium overload and mitochondrial disintegration， leading to the collapse of Yin-Yang equilibrium. At this stage， Yang-restoring and crisis-resolving prescriptions such as Fuling Sini Tang and Qili Qiangxin capsules can inhibit abnormal opening of the mitochondrial permeability transition pore （MPTP）， reduce cardiomyocyte apoptosis rate， and protect mitochondrial function. By summarizing the characteristics of mitochondrial energy metabolism disorders at different stages of CHF， this study explores the application of the theory of reinforcing Yang in treating heart-Yang deficiency syndrome and provides new insights for the clinical diagnosis and treatment of CHF.

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

BACKGROUND: Post-stroke disability diminishes the physical activity (PA) level of survivors, potentially affecting their long-term prognosis. This study endeavors to explore the correlation between daily PA level and the all-cause mortality in patients with a history of stoke in the United States. METHODS: Data of stroke survivors were sourced from the National Health and Nutritional Examination Survey (NHANES) 2007-2018. The population was stratified into three groups based on their PA level. Kaplan-Meier method with log-rank tests for significance was used for survival analysis. Weighted Cox proportional hazards regression models were employed to estimate the hazard ratios (HRs) for all-cause mortality. Subgroup analysis was conducted to strengthen the results. RESULTS: A total of 1395 participants were recruited, comprising 679 males and 716 females, with a median age of 68 years. Based on their PA levels, 779 individuals were classified as inactive, 156 as insufficiently active, and 460 as sufficiently active. Following a median observation period of 59 months, there were 476 recorded deaths, with 349, 47, and 80 cases in the three respective groups. Compared to the inactive group, the HRs and 95% confidence intervals (CIs) for all-cause mortality in participants who were insufficiently active and sufficiently active were 0.58 (0.40, 0.84) and 0.47 (0.33, 0.67), respectively. The Kaplan-Meier curve revealed a significant difference in overall survival between the three groups, as confirmed by the log-rank test (P < 0.0001). Subgroup analysis further validated our results and demonstrated that the protective impact of PA on stroke prognosis varies according to distinct characteristics. CONCLUSIONS The results indicate that increased levels of PA are associated with a protective effect on long-term mortality among stroke survivors. Further prospective longitudinal studies are necessary to elucidate the optional PA level and special exercise guideline targeting this population.
Humans ; Male ; Female ; Aged ; Exercise ; Middle Aged ; Nutrition Surveys ; Stroke/mortality* ; United States/epidemiology* ; Survivors/statistics & numerical data* ; Aged, 80 and over ; Mortality

Background and Aims:Sleeve gastrectomy(SG)has become the most widely performed bariatric procedure worldwide,but postoperative gastroesophageal reflux disease(GERD)remains a major concern.This multicenter study aimed to identify independent risk factors associated with GERD after SG to guide preoperative assessment and intraoperative management.Methods:Clinical data of 672 patients who underwent SG between January 2020 and December 2022 in six bariatric centers and completed a 12-month follow-up were retrospectively analyzed.Demographic characteristics,esophagogastric junction(EGJ)integrity graded by the AFS system,operative parameters,and postoperative outcomes were compared between patients with and without GERD.Multivariate logistic regression was used to identify predictors of postoperative GERD.Results:The overall incidence of GERD after SG was 24.7%(166/672).Multivariate analysis revealed that a preoperative BMI>35 kg/m2(OR=1.68,P=0.033),EGJ integrity AFS grade>2(OR=2.90,P=0.006),and preoperative reflux symptoms(OR=2.44,P=0.030)were independent risk factors for GERD.A staple line more than 1 cm from the angle of His(OR=0.45,P<0.001)and a bougie size>36 Fr(OR=0.08,P=0.001)were protective factors.Conclusion:High BMI,impaired EGJ integrity,and preoperative reflux symptoms significantly increase the risk of GERD after SG,whereas adequate preservation of the His angle and appropriate bougie calibration may reduce it.Comprehensive preoperative EGJ assessment and standardized surgical techniques are essential for minimizing postoperative reflux.

Objective:To analyze the anatomical characteristics and surgical management measures of acute Stanford type A aortic dissection (AAD) involving coronary arteries, and to preliminarily explore the clinical efficacy of different coronary artery treatment techniques.Methods:A retrospective analysis was conducted on the clinical data of 42 patients who underwent surgery for AAD involving coronary arteries in Hunan Provincial People′s Hospital from January 2022 to May 2025. They were divided into the MI group (14 cases) and the nMI group (28 cases) according to whether they had acute myocardial infarction before surgery. The clinical data such as the actual surgical methods and mortality in the two groups were summarized.Results:Among 294 surgeries, 42 cases (14.3%) had definite coronary artery involvement, including 14 cases in the MI group and 28 cases in the nMI group; 1 case had bilateral coronary artery involvement and 41 cases had right coronary artery involvement. Regarding injury types: 16 cases were of the coronary trunk compression type, 12 cases were of the sinus intimal tear neal to ostium type, and 14 cases were of the coronary trunk intimal type. There was no statistically significant difference in the types of coronary artery involvement between the two groups ( P>0.05). There were 18 cases of Sun′s procedure with preserved aortic sinus and aortic valve, 7 cases of Bentall procedure without bypass, and 17 cases of Bentall procedure plus bypass. There was no statistically significant difference in the surgical plans between the two groups ( P>0.05). There were 4 deaths within 30 days (2 cases in each group). Conclusions:AAD involving coronary arteries is a critical condition, and accurate diagnosis is somewhat difficult. Myocardial ischemia is not significantly associated with the type of coronary artery involvement. The surgical plan depends on the type of coronary artery involvement. The classification method in this study is conducive to selecting appropriate surgical methods and improving surgical prognosis.

BACKGROUND:Oxidative stress is one of the main causes of osteoporosis,and reducing the level of oxidative stress with increasing antioxidant defense is an important research direction for the treatment of osteoporosis.Studies have confirmed that astragaloside IV has anti-osteoporosis effects,but its mechanism of action is not clear.OBJECTIVE:To investigate the osteogenic effect of astragaloside IV in MC3T3-E1 cells under oxidative stress conditions.METHODS:MC3T3-E1 cells were randomly divided into four groups:the control group was cultured in a complete medium;the model group was cultured in the complete medium containing hydrogen peroxide which was replaced with another complete medium after 24 hours of intervention;the astragaloside IV group was cultured with the complete medium containing hydrogen peroxide and astragaloside IV which was replaced with another complete medium containing astragaloside IV after 24 hours of intervention;and the inhibitor group was cultured in the complete medium containing hydrogen peroxide,astragaloside IV,and extracellular signal-regulated kinases(ERK)inhibitor which was replaced with complete medium containing hydrogen peroxide,astragaloside IV,and ERK inhibitor after 24 hours of intervention.After 48 hours of intervention with hydrogen peroxide,malondialdehyde content was detected to evaluate the mitigating effect of astragaloside IV on the oxidative stress in MC3T3-E1 cells.Osteogenic induction was performed after 48 hours of intervention with hydrogen peroxide,and the osteogenic and mineralizing ability of MC3T3-E1 cells was verified by alkaline phosphatase staining and alizarin red staining;the expression of osteogenesis-related genes was detected by RT-qPCR;and the expression of osteogenesis-related proteins and ERK/AMP-activated protein kinase(AMPK)signaling pathway proteins was detected by western blot.RESULTS AND CONCLUSION:The intracellular alkaline phosphatase content and mineralized nodule formation were less in the model group than in the control group(P<0.05),and were more in the astragaloside IV group than in the model group(P<0.05).Compared with the control group,intracellular malondialdehyde content increased in the model group(P<0.05),mRNA and protein expression of osteocalcin,RUNX2,and type Ⅰ collagen decreased(P<0.05),and AMPK mRNA and p-AMPK protein expressions were elevated(P<0.05);compared with the model group,intracellular malondialdehyde content in the astragaloside IV group decreased(P<0.05),the mRNA and protein expressions of osteocalcin,RUNX2,and type Ⅰ collagen were elevated(P<0.05),the mRNA expressions of ERK1/2 and AMPK were elevated(P<0.05),and the protein expressions of p-AMPK and p-ERK1/2 were elevated(P<0.05).Additionally,ERK inhibitors partially inhibited the above effects of astragaloside IV.To conclude,astragaloside IV can promote osteogenic differentiation of MC3T3-E1 cells by activating the ERK/AMPK pathway.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To analyze the anatomical characteristics and surgical management measures of acute Stanford type A aortic dissection (AAD) involving coronary arteries, and to preliminarily explore the clinical efficacy of different coronary artery treatment techniques.Methods:A retrospective analysis was conducted on the clinical data of 42 patients who underwent surgery for AAD involving coronary arteries in Hunan Provincial People′s Hospital from January 2022 to May 2025. They were divided into the MI group (14 cases) and the nMI group (28 cases) according to whether they had acute myocardial infarction before surgery. The clinical data such as the actual surgical methods and mortality in the two groups were summarized.Results:Among 294 surgeries, 42 cases (14.3%) had definite coronary artery involvement, including 14 cases in the MI group and 28 cases in the nMI group; 1 case had bilateral coronary artery involvement and 41 cases had right coronary artery involvement. Regarding injury types: 16 cases were of the coronary trunk compression type, 12 cases were of the sinus intimal tear neal to ostium type, and 14 cases were of the coronary trunk intimal type. There was no statistically significant difference in the types of coronary artery involvement between the two groups ( P>0.05). There were 18 cases of Sun′s procedure with preserved aortic sinus and aortic valve, 7 cases of Bentall procedure without bypass, and 17 cases of Bentall procedure plus bypass. There was no statistically significant difference in the surgical plans between the two groups ( P>0.05). There were 4 deaths within 30 days (2 cases in each group). Conclusions:AAD involving coronary arteries is a critical condition, and accurate diagnosis is somewhat difficult. Myocardial ischemia is not significantly associated with the type of coronary artery involvement. The surgical plan depends on the type of coronary artery involvement. The classification method in this study is conducive to selecting appropriate surgical methods and improving surgical prognosis.

BACKGROUND:Oxidative stress is one of the main causes of osteoporosis,and reducing the level of oxidative stress with increasing antioxidant defense is an important research direction for the treatment of osteoporosis.Studies have confirmed that astragaloside IV has anti-osteoporosis effects,but its mechanism of action is not clear.OBJECTIVE:To investigate the osteogenic effect of astragaloside IV in MC3T3-E1 cells under oxidative stress conditions.METHODS:MC3T3-E1 cells were randomly divided into four groups:the control group was cultured in a complete medium;the model group was cultured in the complete medium containing hydrogen peroxide which was replaced with another complete medium after 24 hours of intervention;the astragaloside IV group was cultured with the complete medium containing hydrogen peroxide and astragaloside IV which was replaced with another complete medium containing astragaloside IV after 24 hours of intervention;and the inhibitor group was cultured in the complete medium containing hydrogen peroxide,astragaloside IV,and extracellular signal-regulated kinases(ERK)inhibitor which was replaced with complete medium containing hydrogen peroxide,astragaloside IV,and ERK inhibitor after 24 hours of intervention.After 48 hours of intervention with hydrogen peroxide,malondialdehyde content was detected to evaluate the mitigating effect of astragaloside IV on the oxidative stress in MC3T3-E1 cells.Osteogenic induction was performed after 48 hours of intervention with hydrogen peroxide,and the osteogenic and mineralizing ability of MC3T3-E1 cells was verified by alkaline phosphatase staining and alizarin red staining;the expression of osteogenesis-related genes was detected by RT-qPCR;and the expression of osteogenesis-related proteins and ERK/AMP-activated protein kinase(AMPK)signaling pathway proteins was detected by western blot.RESULTS AND CONCLUSION:The intracellular alkaline phosphatase content and mineralized nodule formation were less in the model group than in the control group(P<0.05),and were more in the astragaloside IV group than in the model group(P<0.05).Compared with the control group,intracellular malondialdehyde content increased in the model group(P<0.05),mRNA and protein expression of osteocalcin,RUNX2,and type Ⅰ collagen decreased(P<0.05),and AMPK mRNA and p-AMPK protein expressions were elevated(P<0.05);compared with the model group,intracellular malondialdehyde content in the astragaloside IV group decreased(P<0.05),the mRNA and protein expressions of osteocalcin,RUNX2,and type Ⅰ collagen were elevated(P<0.05),the mRNA expressions of ERK1/2 and AMPK were elevated(P<0.05),and the protein expressions of p-AMPK and p-ERK1/2 were elevated(P<0.05).Additionally,ERK inhibitors partially inhibited the above effects of astragaloside IV.To conclude,astragaloside IV can promote osteogenic differentiation of MC3T3-E1 cells by activating the ERK/AMPK pathway.