Objective To investigate the protective effect and underlying mechanisms of HydroMg, a novel sustained-release hydrogen donor, in a model of doxorubicin (DOX)-induced chronic cardiotoxicity. Methods H9C2 cells were treated with 1 μmol/L DOX and/or 1 μg/mL HydroMg, and mitochondrial membrane potential, reactive oxygen species (ROS) levels, and apoptosis were measured. In the animal experiment, mice were divided into control, HydroMg, DOX, and DOX＋HydroMg groups. The HydroMg group received intraperitoneal injection of HydroMg (100 mg/kg). Chronic cardiotoxicity was established by intraperitoneal injection of DOX (5 mg/kg every week) for four consecutive weeks; In the DOX＋HydroMg group, HydroMg (100 mg/kg) was administered intraperitoneally 4–5 h prior to each DOX injection. Cardiac function and remodeling were evaluated by echocardiography and heart weight index (HWI). The long-term survival of mice were analyzed. Subsequently, transcriptome sequencing was performed on myocardial tissues from the DOX group to identify key molecular alterations compared with controls. Results At the cellular level, HydroMg treatment effectively reversed DOX-induced mitochondrial dysfunction and oxidative stress, as evidenced by restored membrane potential, reductions in total ROS and mitochondrial superoxide levels by approximately 30% and 9%, respectively, and a decrease in the apoptosis rate from 34.13% to 18.27%. In the animal model, compared with the DOX group, HydroMg intervention increased left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) by 9.62% and 5.82%, respectively, attenuated the reduction in HWI (4.41 mg/mm vs 3.53 mg/mm), and improved the 4-week survival rate (80% vs 60%). Transcriptomic analysis revealed that the core molecular features of DOX-induced cardiotoxicity, including widespread suppression of oxidative phosphorylation and antioxidant pathways. Conclusions HydroMg protects against DOX-induced chronic cardiotoxicity by alleviating oxidative stress and improving mitochondrial function, and provides a potential therapeutic strategy against DOX-related cardiotoxicity.

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

This study aimed to investigate the effect and mechanism of Buyang Huanwu Decoction in regulating endoplasmic reticulum stress via the inositol-requiring enzyme 1α(IRE1α)/apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase(JNK) pathway to improve neurological function in rats with cerebral ischemia/reperfusion injury(CIRI). SPF-grade male sprague-dawley(SD) rats were randomly divided into Sham group, model group, Buyang Huanwu Decoction group, and edaravone group. Except for the Sham group, the other groups were subjected to the modified suture method to establish a middle cerebral artery occlusion/reperfusion(MCAO/R) model. After treatment, neurological function was assessed using the Zea Longa scoring system. Gait analysis was used to detect the motor function. Detection of relative infarct area in brain tissue using 2,3,5-triphenyltetrazolium chloride(TTC) staining. Nissl staining was used to observe the structure of neuronal cells. Western blot and real-time fluorescence quantitative PCR(RT-qPCR) were used to detect IRE1α, ASK1, JNK, B cell lymphoma-2(Bcl-2), Bcl-2 related X protein(Bax), and Caspase-3 in the brain tissue. Immunohistochemistry was used to detect the positive expression of IRE1α, ASK1, and JNK. Immunofluorescence was used to detect the fluorescence expression levels of Bax, Bcl-2, and Caspase-3. The results showed that compared with the Sham group, the model group exhibited increased neurological scores(P<0.01), increased ratio of ground contact area and strength in both forelimbs(P<0.01), enlarged relative infarct area of brain tissue(P<0.05), and a reduced number of Nissl staining-positive cells(P<0.01). The protein and mRNA expression levels of IRE1α, ASK1, JNK, Bax, and Caspase-3 in brain tissue were significantly elevated, while those of Bcl-2 were decreased(P<0.05). Compared with the model group, both the Buyang Huanwu Decoction group and edaravone group showed reduced neurological scores(P<0.05), decreased ratio of ground contact area and strength in both forelimbs(P<0.05), smaller relative infarct area(P<0.05), alleviated neuronal damage, and increased number of Nissl staining-positive cells(P<0.05). The expression levels of IRE1α, ASK1, JNK, Bax, and Caspase-3 protein and mRNA in brain tissue were significantly reduced, while those of Bcl-2 were significantly increased(P<0.05). The results indicated that Buyang Huanwu Decoction can effectively improve brain injury in CIRI rats, and its mechanism of action may be related to regulating the endoplasmic reticulum stress IRE1α/ASK1/JNK signaling pathway.
Animals ; Male ; Rats, Sprague-Dawley ; Protein Serine-Threonine Kinases/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; MAP Kinase Kinase Kinase 5/genetics* ; Ischemic Stroke/physiopathology* ; Humans ; MAP Kinase Signaling System/drug effects* ; Apoptosis/drug effects* ; Endoribonucleases/genetics* ; JNK Mitogen-Activated Protein Kinases/genetics* ; Endoplasmic Reticulum Stress/drug effects* ; Multienzyme Complexes

[This corrects the article DOI: 10.11909/j.issn.1671-5411.2017.08.005.].

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

CD47 is an immune checkpoint widely regarded as a 'don't eat me' signal. CD47-based anti-cancer therapy has received considerable attention, with a significant number of clinical trials conducted. While anti-cancer therapies based on CD47 remain a focal point of interest among researchers, it is noteworthy that an increasing number of studies have found that CD47-based therapy ameliorated the pathological status of non-cancer diseases. This review aims to provide an overview of the recent progress in comprehending the role of CD47-based therapy in non-cancer diseases, including diseases of the circulatory system, nervous system, digestive system, and so on. Furthermore, we sought to delineate the promising mechanisms of CD47-based therapy in treating non-cancer diseases. Our findings suggest that CD47-based agents may exert their effect by regulating phagocytosis, regulating T cells, dendritic cells, and neutrophils, and regulating the secretion of cytokines and chemokines. Additionally, we put forward the orientation of further research to bring to light the potential of CD47 and its binding partners as a target in non-cancer diseases.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People