ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 （ACSL4） signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group， sham-operation group， model group， trimetazidine group （5.4 mg·kg^-1）， low-， medium-， and high-dose group （3.51， 7.02，14.04 g·kg^-1） of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome， and continuous treatment for 7 d was conducted， while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed， and indicators such as electrocardiogram， echocardiography， and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin （HE） staining， and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid （12-HETE） and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe²⁺， lipid peroxidation （LPO）， glutathione （GSH）， and T-GSH/glutathione disulfide （GSSG） in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species （ROS）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， ACSL4， and ly-sophosphatidylcholine acyltransferase3 （LPCAT3） in myocardial tissue. ResultsCompared with those in the normal group， the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage， bow-back elevation of the ST segments， elevated T waves， J-point elevation， and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction （LVEF） and left ventricular fraction shortening （LVFS） （P<0.01）. Blood rheology showed that the viscosity of the whole blood （low， medium， and high rate of shear） was significantly increased （P<0.01）. HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken， and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles， and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased （P<0.01）. The content of Fe²⁺， LPO， and ROS in myocardial tissue was significantly increased （P<0.01）. The content of GSH was significantly decreased （P<0.01）， and T-GSH/GSSG was decreased （P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased （P<0.05， P<0.01）， while those of ACSL4 and LPCAT3 increased significantly （P<0.01）. Compared with the model group， the general macroscopic symptoms and electrocardiogram results of rats in low-， medium- and high-dose groups of Xuefu Zhuyutang were alleviated， and the differences in LVEF/LVFS ratios were all significantly increased （P<0.05， P<0.01）. The differences in whole-blood viscosity （low， medium， and high rate of shear） were all significantly decreased （P<0.01）. The results of HE staining and transmission electron microscopy showed that the morphology， structure， and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. The content of Fe²⁺， LPO， and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and the content of GSH and T-GSH/GSSG was significantly increased （P<0.05， P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and ACSL4 and LPCAT3 were decreased to different degrees in the low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway， thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.

This paper systematically summarizes the practical experience of the 2025 Dingri earthquake emergency medical rescue in Tibet. It analyzes the requirements for earthquake medical rescue under conditions of high-altitude hypoxia, low temperature, and low air pressure. The paper provides a detailed discussion on the strategic layout of earthquake medical rescue at the national level, local government level, and through social participation. It covers the construction of rescue organizational systems, technical systems, material support systems, and information systems. The importance of building rescue teams is emphasized. In high-altitude and cold conditions, rapid response, scientific decision-making, and multi-party collaboration are identified as key elements to enhance rescue efficiency. By optimizing rescue organizational structures, strengthening the development of new equipment, and promoting telemedicine technologies, the precision and effectiveness of medical rescue can be significantly improved, providing important references for future similar disaster rescues.

OBJECTIVE: To investigate the correlation between platelet alloantibodies and CD8⁺ T cell with platelet desialylation and apoptosis in platelet transfusion refractoriness(PTR). METHODS: The expression of RCA-1, CD62P and Neu1 on platelets were detected in 135 PTR patients and 260 healthy controls. The ability of PTR patients' sera with anti-HLA antibody, anti-CD36 antibody and antibody-negative groups to induce platelet desialylation and apoptosis, and the potential effect of FcγR inhibitors on desialylation and apoptosis were evaluated. Additionally, the association between CD8⁺ T cells and platelet desialylation in patients was analyzed. RESULTS: The expression of RCA-1 and Neu1 on platelets in PTR patients were significantly higher than those in healthy donors（P < 0.05）, but were not related to platelet alloantibody (P >0.05). The sera of PTR patients generally induced platelet desialylation in vitro （P < 0.05）, with no significant differences among the groups（P >0.05）. However, the sera with anti-CD36 antibodies could induce platelet apoptosis significantly higher than that in the anti-HLA antibody group and antibody-negative group in vitro (P < 0.05). In PTR patients with anti-CD36 antibodies, platelet apoptosis was dependent on FcγR signaling, while desialylation is not. Moreover, CD8⁺ T cells in PTR patients were significantly associated with platelet desialylation (P < 0.05). CONCLUSION Platelet desialylation is a common pathological phenomenon in PTR patients， which involves the participation of CD8⁺ T cell, but isn't associated with platelet alloantibody; while anti-CD36 antibodies have potential clinical significance in predicting platelet apoptosis in PTR patients.
Humans ; Apoptosis ; CD8-Positive T-Lymphocytes/immunology* ; Blood Platelets/metabolism* ; Platelet Transfusion ; Isoantibodies ; Male ; Female ; Middle Aged

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Disrupted bone morphogenetic protein type 2 receptor (BMPR2) signaling in endothelial cells drives pulmonary arterial hypertension (PAH). However, targeted recovery of this signaling pathway by lipid nanoparticles (LNPs) has not been explored as a therapy. Here, we employed Design of Experiments to optimize the delivery efficiency of LNPs targeting pulmonary endothelial cells developed by our laboratory, resulting in a remarkable 35-fold increase in a simplified three-component formulation without helper lipids. Administration of BMPR2 mRNA LNPs effectively reversed established PAH in two experimental rat models (monocrotaline or SU5416-hypoxia) by reversing pulmonary vascular remodeling. Specifically, BMPR2 mRNA LNPs replenished the expression of BMPR2 protein and subsequently activated downstream pathways, as confirmed by elevated levels of p-SMAD1/5/9 and ID1 proteins. The relief of pulmonary arterial occlusion was demonstrated by thinned pulmonary arterial media and decreased proportion of full muscularized vessels. Alleviation of right ventricular hypertrophy was indicated by declined Fulton index, the cross-sectional area of right ventricular cardiomyocytes as well as collagen deposition. Effective recovery of right ventricular function was evidenced by increased pulmonary artery flow acceleration time/pulmonary artery flow ejection time ratio. These findings underscore the potential of restoring BMPR2 signaling through pulmonary endothelial cell-specific LNPs for treating PAH.

OBJECTIVES: To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining. RESULTS: After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups. CONCLUSIONS Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals ; Periodontitis/microbiology* ; Mice ; Mice, Inbred C57BL ; Cognition ; Alveolar Bone Loss ; Hippocampus/pathology* ; Male ; Inflammation ; Maze Learning

BACKGROUND: A growing body of research is exploring the role of antioxidant and anti-inflammatory dietary supplements in the treatment of osteoarthritis, highlighting an increasing emphasis on non-pharmacological interventions. Although more patients are turning to supplements to manage osteoarthritis, their actual effectiveness remains uncertain. OBJECTIVE: This study aims to provide a comprehensive evaluation of the available evidence concerning the efficacy of various dietary supplements in osteoarthritis treatment. SEARCH STRATEGY: We searched PubMed, Embase, Cochrane Library and Web of Science for studies on the use of various dietary supplements in the treatment of osteoarthritis from the creation of each database until Jan 20, 2025. INCLUSION CRITERIA: (1) Research object: osteoarthritis. (2) Intervention measures: patients in the treatment group received dietary supplements, while the control group received placebos. (3) Research type: randomized controlled trials (RCTs). DATA EXTRACTION AND ANALYSIS: Two researchers independently examined the literature and retrieved data based on predefined criteria. The information gathered included the first author, year of publication, sample size, participant demographics, length of the follow-up period, intervention and control measures, and inclusion indications. RCTs comparing dietary supplements to placebo with the pain and function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) among patients with osteoarthritis were included. The optimal dietary supplement was identified based on the total ranking by summing the surface under the cumulative ranking curve (SUCRA) of these two scores. Furthermore, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to confirm the quality of the evidence. RESULTS: Overall, 23 studies covering 21 dietary supplements and involving 2455 participants met the inclusion criteria. In the WOMAC pain score, the SUCRA of passion fruit peel extract was 91% (mean difference [MD]: -9.2; 95% confidence interval [CI]: [-16.0, -2.3]), followed by methylsulfonylmethane (89%), undenatured type II collagen (87%), collagen (84%), and Lanconone (82%). The SUCRA (99%) of passion fruit peel extract (MD: -41.0; 95% CI: [-66.0, -16.0]) ranked first in terms of the WOMAC function score, followed by Lanconone (95%), collagen (86%), ParActin (84%), and Lactobacillus casei strain Shirota (83%). The top three total rankings are passion fruit peel extract (95.0%), Lanconone (88.5%), and collagen (85.0%). However, the GRADE revealed low evidence quality. CONCLUSION Passion fruit peel extract was the best supplement for improving WOMAC pain and function scores in patients with osteoarthritis, followed by Lanconone and collagen. However, further large-scale, well designed RCTs are required to substantiate these promising findings. Please cite this article as: Chen CS, Wen L, Yang F, Deng YC, Ji JH, Chen RJ, Chen Z, Chen G, Gu JY. Effects of dietary supplements on patients with osteoarthritis: A systematic review and network meta-analysis. J Integr Med. 2025; 23(4): 357-369.
Humans ; Dietary Supplements ; Osteoarthritis/drug therapy* ; Randomized Controlled Trials as Topic

As a new strategy for the application of sacubitril/valsartan (LCZ696) in patients with CKD, much evidence showed that it improved the prognosis of patients with CKD. This review summarizes the efficacy and safety of sacubitril/valsartan in physiology, pathology, pharmacology and clinical application by searching Wanfang, CNKI, PubMed and other databases for related articles on the application of sacubitril/valsartan in CKD patients. Although LBQ657, the active product of sacubitril, has a high drug accumulation in patients with moderate, severe renal injury, and ESRD, it is not cleared in hemodialysis, and has very little eliminated in peritoneal dialysis, which does not affect its safety. Compared with angiotensin converting enzyme inhibitor and angiotensin receptor blocker drugs, LCZ696 could increase the blood pressure control rate, improve cardiac function, slow down the decline of glomerular filtration rate, and significantly improve cardiovascular outcomes without more adverse events. Sacubitril/valsartan can be used in all levels of CKD patients complicated with hypertension and/or heart failure, with reliable safety and tolerance.

Aim To observe the role of salvianolic acid B(Sal B)in enhancing the survival of random skin flaps and to preliminarily explore its potential mecha-nisms.Methods The appearance,degree of edema,color and hair condition of the skin flap were evaluated seven days after operation.The vascular network and blood flow of random flaps were measured by laser Doppler flow measurement.HE staining was used to detect the growth of microvessels in random flaps.The expressions of VEGF and CD34 were detected by im-munohistochemistry,the expressions of RIPK1,2 and LC3 Ⅱ were detected by immunofluorescence,and the effects of autophagy related proteins and signaling path-ways were detected by Western blot.Results The ex-perimental results showed that Sal B induced autophagy in the random skin flaps,promoted angiogenesis,and reduced oxidative stress and necrotic apoptosis,signifi-cantly increasing the survival rate of the flaps.Immu-nohistochemistry,immunofluorescence staining,and Western blot confirmed that Sal B induced autophagy in the random skin flaps by activating TFE3 protein.Conclusion Sal B can promote autophagy in cells of random skin flaps and reduce their necrotic apoptosis by activating TFE3 protein.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.