OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To explore the imaging findings of atypical teratoid/rhabdoid tumor(AT/RT)in the central nervous sys-tem of children and to improve the understanding of this disease.Methods A retrospective analysis was conducted on the imaging data of 55 children with AT/RT confirmed by pathology.Results Among the 55 AT/RT children,74.5％were under 3 years old,with a male-to-female ratio of 1.5∶1.Intracranial AT/RT appeared hyperdense or slightly hyperdense on CT scans and accompa-nied by calcification or hemorrhage occasionally.32 cases showed peripheral cystic changes in MRI images.38 cases showed heteroge-neous enhancement,9 cases showed ring-like or band-like enhancement.13 cases showed cerebrospinal fluid dissemination.The mean minimum apparent diffusion coefficient(ADC)value was(0.61±0.11)× 10-3mm2/s.Spinal AT/RT manifested as solitary or mul-tiple intramedullary and/or extradural lesions on MRI,which showed unclear boundary from the spinal cord.Hemorrhage within or at the edge of the lesion was seen in 2 cases,involvement of nerve roots and adjacent muscle tissues in 3 cases,and cerebrospinal fluid dissemination of the intracranial and spinal cord at varying degrees in 5 cases.Conclusion The imaging findings of pediatric AT/RT in the central nervous system are diverse,combining imaging characteristics with age of onset facilitates the accurate diagnosis.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

This study aims to explore whether Naoxintong Capsules improve multiple cerebral infarctions and myocardial injury via promoting angiogenesis, thereby exerting a simultaneous treatment effect on both the brain and heart. Male SD rats were randomly divided into six groups: sham-operated group, model group, high-dose, medium-dose, and low-dose groups of Naoxintong Capsules(440, 220, and 110 mg·kg~(-1)), and nimodipine group(10.8 mg·kg~(-1)). Rat models of multiple cerebral infarctions were established by injecting autologous thrombus, and samples were collected and tested seven days after modeling. Evaluations included multiple cerebral infarction model assessments, neurological function scores, grip strength tests, and rotarod tests, so as to evaluate neuromotor functions. Morphological structures of brain and heart tissue were observed using hematoxylin-eosin(HE) staining, Nissl staining, and Masson staining. Network pharmacology was employed to screen the mechanisms of Naoxintong Capsules in improving multiple cerebral infarctions and myocardial injury. Neuronal and myocardial cell ultrastructures were observed using transmission electron microscopy. Apoptosis rate in brain neuronal cells was detected by TdT-mediated dUTP nick end labeling(TUNEL) staining, and reactive oxygen species(ROS) levels in myocardial cells were measured. Immunofluorescence was used to detect the expression of platelet endothelial cell adhesion molecule-1(CD31), antigen identified by monoclonal antibody Ki67(Ki67), hematopoietic progenitor cell antigen CD34(CD34), and hypoxia inducible factor-1α(HIF-1α) in brain and myocardial tissue. Western blot, and real-time quantitative polymerase chain reaction(RT-qPCR) were used to detect the expression of HIF-1α, vascular endothelial growth factor(VEGF), vascular endothelial growth factor receptor 2(VEGFR2), sarcoma(Src), basic fibroblast growth factor(bFGF), angiopoietin-1(Ang-1), and TEK receptor tyrosine kinase(Tie-2). Compared with the model group, the medium-dose group of Naoxintong Capsules showed significantly lower neurological function scores, increased grip strength, and prolonged time on the rotarod. Pathological damage in brain and heart tissue was reduced, with increased and more orderly arranged mitochondria in neurons and cardiomyocytes. Apoptosis in brain neuronal cells was decreased, and ROS levels in cardiomyocytes were reduced. The microvascular density and endothelial cells of new blood vessels in brain and heart tissue increased, with increased overlapping regions of CD31 and Ki67 expression. The relative protein and mRNA expression levels of HIF-1α, VEGF, VEGFR2, Src, Ang-1, Tie-2, and bFGF were elevated in brain tissue and myocardial tissue. Naoxintong Capsules may improve multiple cerebral infarctions and myocardial injury by mediating HIF-1α/VEGF expression to promote angiogenesis.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Cerebral Infarction/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Capsules ; Signal Transduction/drug effects* ; Humans ; Brain/metabolism* ; Myocardium/metabolism* ; Apoptosis/drug effects*

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Objective:To develop an exercise rehabilitation program based on the Temporal Self-regulation Theory and evaluate its effectiveness in elderly patients with hip fractures.Methods:A total of 84 elderly patients with hip fractures admitted to the Department of Trauma Orthopedics at the First Affiliated Hospital of University of South China from May to August 2024 were enrolled using convenience sampling. Participants were randomly assigned to an experimental group ( n=42) and a control group ( n=42) using a random number table. The control group received routine exercise rehabilitation, while the experimental group received an exercise rehabilitation program constructed based on the Temporal Self-regulation Theory. The program included components such as establishing a unified concept of "exercise-rehabilitation", enhancing time-limited efficacy, achieving behavioral advantages, and improving self-regulation of active movement. Both groups received interventions for 12 weeks. Functional exercise adherence, activities of daily living, and hip joint function were assessed using the Orthopedic Exercise Adherence Scale, Modified Barthel Index, and Harris Hip Score at four time points: before intervention, on the day of discharge, and at 4 and 12 weeks postoperatively. Results:During the study, two patients from each group dropped out. Results of the generalized estimating equations showed group effects, time effects, and interaction effects in adherence scores with statistically significant differences ( P<0.01). On the day of discharge, and at 4 and 12 weeks postoperatively, the adherence scores in the experimental group were significantly higher than those in the control group, and the differences were statistically significant ( P<0.05). Repeated measures ANOVA indicated that group effects, time effects, and interaction effects were also statistically significant in scores for daily living ability and hip joint function ( P<0.05). The experimental group scored higher than the control group at each time point with statistically significant differences ( P<0.05) . Conclusions:The exercise rehabilitation program based on the Temporal Self-regulation Theory is scientifically sound and practical. It can effectively improve functional exercise adherence, enhance daily living ability, and promote postoperative recovery of hip joint function in elderly patients with hip fractures.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Objective To explore the imaging findings of atypical teratoid/rhabdoid tumor(AT/RT)in the central nervous sys-tem of children and to improve the understanding of this disease.Methods A retrospective analysis was conducted on the imaging data of 55 children with AT/RT confirmed by pathology.Results Among the 55 AT/RT children,74.5％were under 3 years old,with a male-to-female ratio of 1.5∶1.Intracranial AT/RT appeared hyperdense or slightly hyperdense on CT scans and accompa-nied by calcification or hemorrhage occasionally.32 cases showed peripheral cystic changes in MRI images.38 cases showed heteroge-neous enhancement,9 cases showed ring-like or band-like enhancement.13 cases showed cerebrospinal fluid dissemination.The mean minimum apparent diffusion coefficient(ADC)value was(0.61±0.11)× 10-3mm2/s.Spinal AT/RT manifested as solitary or mul-tiple intramedullary and/or extradural lesions on MRI,which showed unclear boundary from the spinal cord.Hemorrhage within or at the edge of the lesion was seen in 2 cases,involvement of nerve roots and adjacent muscle tissues in 3 cases,and cerebrospinal fluid dissemination of the intracranial and spinal cord at varying degrees in 5 cases.Conclusion The imaging findings of pediatric AT/RT in the central nervous system are diverse,combining imaging characteristics with age of onset facilitates the accurate diagnosis.

Objective:To analyze the MYH9 gene sequence of a patient with hereditary thrombocytopenia and diffuse large B-cell lymphoma and his family members,and to explore the relationship between MYH9 gene and tumors.Methods:Peripheral blood samples were collected from the patients and their family members for complete blood count analysis.The platelet morphology was observed under microscope.The MYH9 gene sequence was analyzed by Whole Exon Sequencing and Sanger Sequencing.Results:The mutation site c.279C＞A:p.(Asn93Lys)in exon 2 of the MYH9 gene were found in patient and his family members,both presenting as thrombocytopenia.The platelet count was significantly increased after the administration of Avatrombopag.Conclusion:A novel mutation of MYH9 was found in this study,and the case was sensitive to Avatrombopag,by exploring the relationship between the MYH9 gene and tumors,suggesting that the MYH9 gene may be associated with the development of diffuse large B-cell lymphoma.

Objective:To develop an exercise rehabilitation program based on the Temporal Self-regulation Theory and evaluate its effectiveness in elderly patients with hip fractures.Methods:A total of 84 elderly patients with hip fractures admitted to the Department of Trauma Orthopedics at the First Affiliated Hospital of University of South China from May to August 2024 were enrolled using convenience sampling. Participants were randomly assigned to an experimental group ( n=42) and a control group ( n=42) using a random number table. The control group received routine exercise rehabilitation, while the experimental group received an exercise rehabilitation program constructed based on the Temporal Self-regulation Theory. The program included components such as establishing a unified concept of "exercise-rehabilitation", enhancing time-limited efficacy, achieving behavioral advantages, and improving self-regulation of active movement. Both groups received interventions for 12 weeks. Functional exercise adherence, activities of daily living, and hip joint function were assessed using the Orthopedic Exercise Adherence Scale, Modified Barthel Index, and Harris Hip Score at four time points: before intervention, on the day of discharge, and at 4 and 12 weeks postoperatively. Results:During the study, two patients from each group dropped out. Results of the generalized estimating equations showed group effects, time effects, and interaction effects in adherence scores with statistically significant differences ( P<0.01). On the day of discharge, and at 4 and 12 weeks postoperatively, the adherence scores in the experimental group were significantly higher than those in the control group, and the differences were statistically significant ( P<0.05). Repeated measures ANOVA indicated that group effects, time effects, and interaction effects were also statistically significant in scores for daily living ability and hip joint function ( P<0.05). The experimental group scored higher than the control group at each time point with statistically significant differences ( P<0.05) . Conclusions:The exercise rehabilitation program based on the Temporal Self-regulation Theory is scientifically sound and practical. It can effectively improve functional exercise adherence, enhance daily living ability, and promote postoperative recovery of hip joint function in elderly patients with hip fractures.