ObjectiveTo evaluate the impact of yang-reinforcing and blood-activating therapy on the long-term prognosis for patients with dilated cardiomyopathy （DCM） of yang deficiency and blood stasis syndrome. MethodsA retrospective cohort study was conducted involving 371 DCM patients with yang deficiency and blood stasis syndrome. The yang-reinforcing and blood-activating therapy was defined as the exposure factor. Patients were categorized into exposure group （186 cases） and non-exposure group （185 cases） according to whether they received yang-reinforcing and blood-activating therapy combined with conventional western medicine for 6 months or longer. The follow-up period was set at 48 months， and the Kaplan-Meier survival analysis was used to assess the cumulative incidence of major adverse cardiovascular events （MACE） in both groups. Cox regression analysis was used to explore the impact of yang-reinforcing and blood-activating therapy on the risk of MACE， and subgroup analysis was performed. Changes in traditional Chinese medicine （TCM） syndrome score， left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end-diastolic diameter （LVEDD）， and Minnesota Living with Heart Failure Questionnaire （MLHFQ） score were compared between groups at the time of first combined use of yang-reinforcing and blood-activating therapy （before treatment） and 1 year after receiving the therapy （after treatment）. ResultsMACE occurred in 31 cases （16.67%） in the exposure group and 47 cases （25.41%） in the non-exposure group. The cumulative incidence of MACE in the exposure group was significantly lower than that in the non-exposure group ［HR=0.559， 95%CI（0.361，0.895）， P=0.014］. Cox regression analysis showed that yang-reinforcing and blood-activating therapy was an independent factor for reducing the risk of MACE in DCM patients ［HR=0.623， 95%CI（0.396，0.980）， P=0.041］， and consistent results were observed in different subgroups. Compared with pre-treatment， the exposure group showed decreased TCM syndrome score and MLHFQ score， reduced LVEDD， and increased LVEF and LVFS after treatment （P＜0.05）； in the non-exposure group， TCM syndrome score decreased， LVEF and LVFS increased， and LVEDD reduced after treatment （P＜0.05）. After treatment， the exposure group had higher LVEF and LVFS， smaller LVEDD， and lower TCM syndrome score and MLHFQ score compared with the non-exposure group （P＜0.05）. ConclusionCombining yang-reinforcing and blood-activating therapy with conventional western medicine can reduce the risk of MACE in DCM patients with yang deficiency and blood stasis syndrome， meanwhile improving their clinical symptoms， cardiac function， and quality of life.

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).
Humans ; Male ; Middle Aged ; Female ; Bronchoscopy/adverse effects* ; Single-Blind Method ; Aged ; Drugs, Chinese Herbal/adverse effects* ; Treatment Outcome ; Resuscitation ; Adult ; Medicine, Chinese Traditional

Hypertrophic cardiomyopathy (HCM) is a major contributor to cardiovascular diseases (CVD), the leading cause of death globally. HCM can precipitate heart failure (HF) by causing the cardiac tissue to weaken and stretch, thereby impairing its pumping efficiency. Moreover, HCM increases the risk of atrial fibrillation, which in turn elevates the likelihood of thrombus formation and stroke. Given these significant clinical ramifications, research into the etiology and pathogenesis of HCM is intensifying at multiple levels. In this review, we discuss and synthesize the latest findings on HCM pathogenesis, drawing on key experimental studies conducted both in vitro and in vivo. We also offer our insights and perspectives on these mechanisms, while highlighting the limitations of current research. Advancing fundamental research in this area is essential for developing effective therapeutic interventions and enhancing the clinical management of HCM.
Cardiomyopathy, Hypertrophic/physiopathology* ; Humans ; Animals

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

Deep vein thrombosis(DVT)is a common complication after surgery for lower limb fracture.It has the features of high morbidity,high disability rate and high mortality.At present,the measures for clinical prevention and treatment of post-operative DVT in lower limb fracture mainly include perioperative nursing,intervention with medical auxiliary instruments,western medicine prevention and treatment,traditional Chinese medicine(TCM)intervention,and patients'self-cooperation.The patients'self-cooperation is the basis for the smooth implementation of other measures for prevention and treatment,and the patients'active cooperation is the premise of achieving the efficacy of prevention and treatment.Perioperative nursing is helpful for the patients to understand the risk factors of postoperative DVT and the possible risks after the occurrence of DVT,guides the patients to choose the food,assists the patients to do postoperative exercises,improves the level of patients'hemorheological indexes,and reduce the incidence of postoperative DVT.Medical devices are helpful for assisting patients to do postoperative rehabilitation exercises,improving the levels of hemodynamic indicators,promoting patients'rehabilitation and reducing the incidence of postoperative DVT.Western medicines such as low molecular weight heparin,Rivaroxaban,Enoxaparin and other anticoagulant drugs can reduce the aggregation of coagulation factors and blood viscosity,and reduce the incidence of postoperative DVT.TCM interventions mainly include oral administration of Chinese medicine and external treatment such as acupuncture,moxibustion and massage.Oral administration of Chinese medicine is helpful for improving blood flow status.Acupuncture,moxibustion and massage are beneficial to the activation of the function of zang-fu organs,and can stimulate the healthy qi to improve the qi-blood state of the whole body.Each method of prevention and treatment has its advantages and disadvantages.In clinical application,reasonable prevention and treatment methods should be selected according to the specific conditions and individual conditions of the patients.TCM intervention of DVT can be performed in patients with lower limb fracture before and after surgery,and has the advantages of low cost and definite efficacy,which is worthy of continuous research and inheritance and innovation.

ObjectiveTo investigate the effects of berbamine hydrochloride on sorafenib resistance in hepatocellular carcinoma cells and the underlying mechanisms. MethodThe sorafenib-resistant cell line SMMC-7721/S was selected by the concentration increment method starting at 1.25 μmol·L^-1 sorafenib. Both SMMC-7721 and SMMC-7721/S cells were treated with 0， 2.5， 5， 10， 15， 20 μmol·L^-1 sorafenib， and the cell counting kit-8 （CCK-8） assay was employed to determine the half maximal inhibitory concentration （IC₅₀） and calculate the resistance index （RI）. Western blot was conducted to compare the expression of proteins involved in autophagy and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway between SMMC-7721 and SMMC-7721/S cells. Furthermore， SMMC-7721/S cells were treated with 5 μmol·L^-1 berbamine hydrochloride alone or in combination with 2.5， 5， 10 μmol·L^-1 sorafenib， and the cell growth was assessed by the CCK-8 assay. In addition， SMMC-7721 and SMMC-7721/S cells were treated with 5 μmol·L^-1 berbamine hydrochloride alone or in combination with 5 μmol·L^-1 sorafenib， and the cell proliferation was examined by the colony formation assay. The immunofluorescence assays with Microtubule-associated protein 1 light chain 3 （LC3） and LysoTracker as probes were employed to assess the lysosomal acidification in SMMC-7721 cells treated with 5 μmol·L^-1 berbamine hydrochloride or 0.1 μmol·L^-1 autophagy inhibitor bafilomycin A1 （Baf）. Further， the expression of proteins involved in autophagy and PI3K/Akt/mTOR signaling pathway was determined by Western blot and compared between groups. ResultSorafenib showed the IC₅₀ of 9.56 mol·L^-1 （P<0.01） and 7.99 mol·L^-1 for SMMC-7721/S and SMMC-7721 cells， respectively， at 24 h. The resistance index （RI） of SMMC-7721/S for sorafenib was 1.20 （P<0.01）， which indicated mild resistance. Compared with SMMC-7721 cells， SMMC-7721/S cells exhibited up-regulated expression of p-mTOR， p-Akt， and LC3Ⅱ， down-regulated expression of p62 protein （P<0.01）， and unchanged Akt protein level. CCK-8 and colony formation assays demonstrated that the combination of berbamine hydrochloride and sorafenib exhibited a synergistic effect （Q>1.15）， with berbamine hydrochloride partially reversing the resistance of liver cancer cells to sorafenib. The immunofluorescence detection of LC3 revealed that berbamine hydrochloride and Baf significantly increased LC3 in SMMC-7721 cells. The detection with LysoTracker as the probe showed that berbamine hydrochloride inhibited the acidity of lysosomes in SMMC-7721 cells （P<0.01）， indicating the suppression of autophagy. Berbamine hydrochloride further enhanced the downregulation of p-mTOR and p-Akt protein levels and did not change the Akt protein level in SMMC-7721 cells exposed to sorafenib. Berbamine hydrochloride inhibited the increase in p-mTOR expression， down-regulated the p-Akt protein level， and did not change the total Akt protein level in the SMMC-7721/S cells exposed to sorafenib. ConclusionBerbamine hydrochloride can ameliorate the resistance of liver cancer cells to sorafenib by inhibiting cellular autophagy and the PI3K/Akt/mTOR signaling pathway.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

Humans ; Infant ; Child ; Infant, Newborn ; Developmental Disabilities ; Bronchopulmonary Dysplasia

BACKGROUND:Exosomes play a role in all stages of wound repair,and there is currently a large body of research on exosomes in skin wound repair,which has been shown to have great potential for clinical applications. OBJECTIVE:To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds,in order to promote the clinical translation of exosomes. METHODS:PubMed,clinicaltrials.gov,China National Knowledge Infrastructure,Food and Drug Administration database,and Chinese Clinical Trial Register were searched from inception to March 2023.The English search terms were"exosomes,wound healing,stem cells,chronic wound,immunoregulation,inflammation,skin,therapeutic use,isolation,characterization,infections".The Chinese search terms were"exosomes,wound healing,stem cells,immunomodulation,clinical applications".A total of 79 articles were included for the summary. RESULTS AND CONCLUSION:(1)Exosomes can improve and accelerate wound healing through inflammation regulation,immune protection,angiogenesis,cell proliferation and migration,and collagen remodeling.(2)Exosomes derived from stem cells have mature preparation techniques and related mechanism research,which is currently the mainstream research direction.Non-stem cell-derived exosomes have the advantages of convenience,economy,and easy production,and can be used as a supplement for clinical applications.(3)The clinical application of exosomes is still in its infancy,but has great potential for application.Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research.(4)The clinical translation of exosomes faces many challenges,such as low yield,high heterogeneity,lack of unified standards for isolation,purification,and quality control,and difficulties in storage.

Sarcopenia, which is characterized by progressive and generalized loss of skeletal muscle mass and strength, has been well described to be associated with numerous poor postoperative outcomes, such as increased perioperative mortality, postoperative sepsis, prolonged length of stay, increased cost of care, decreased functional outcome, and poorer oncological outcomes in cancer surgery. Multimodal prehabilitation, as a concept that involves boosting and optimizing the preoperative condition of a patient prior to the upcoming stressors of a surgical procedure, has the purported benefits of reversing the effects of sarcopenia, shortening hospitalization, improving the rate of return to bowel activity, reducing the costs of hospitalization, and improving quality of life. This review aims to present the current literature surrounding the concept of sarcopenia, its implications pertaining to colorectal cancer and surgery, a summary of studied multimodal prehabilitation interventions, and potential future advances in the management of sarcopenia.