This study investigates the effect and underlying mechanism of Guizhi Tongluo Tablets(GZTL) in treating atherosclerosis(AS) in a mouse model. Apolipoprotein E-knockout(ApoE~(-/-)) mice were randomly assigned to the following groups: model, high-, medium-, and low-dose GZTL, and atorvastatin(ATV), and age-matched C57BL/6J mice were selected as the control group. ApoE~(-/-) mice in other groups except the control group were fed with a high-fat diet for the modeling of AS and administrated with corresponding drugs via gavage for 8 weeks. General conditions, signs of blood stasis, and body mass of mice were monitored. Aortic plaques and their stability were assessed by hematoxylin-eosin, Masson, and oil red O staining. Serum levels of total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) were measured by biochemical assays, and those of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) were determined via enzyme-linked immunosorbent assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL). Single-cell RNA sequencing(scRNA-seq) was employed to analyze the differential expression of CD72hi macrophages(CD72hi-Mφ) in the aortas of AS patients and mice. The immunofluorescence assay was employed to visualize CD72hi-Mφ expression in mouse aortic plaques, and real-time fluorescence quantitative PCR was utilized to determine the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. The results demonstrated that compared with the control group, the model group exhibited significant increases in body mass, aortic plaque area proportion, necrotic core area proportion, and lipid deposition, a notable decrease in collagen fiber content, and an increase in apoptosis. Additionally, the model group showcased elevated serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6, alongside marked upregulations in the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. In comparison with the model group, the GZTL groups and the ATV group showed a reduction in body mass, and the medium-and high-dose GZTL groups and the ATV group demonstrated reductions in aortic plaque area proportion, necrotic core area proportion, and lipid deposition, an increase in collagen fiber content, and a decrease in apoptosis. Furthermore, the treatment goups showcased lowered serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6. The data of scRNA-seq revealed significantly elevated CD72hi-Mφ signaling in carotid plaques of AS patients compared with that in the normal arterial tissue. Animal experiments confirmed that CD72hi-Mφ expression, along with several pro-inflammatory cytokines, was significantly upregulated in the aortas of AS mice, which were downregulated by GZTL treatment. In conclusion, GZTL may alleviate AS by inhibiting CD72hi-Mφ activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atherosclerosis/immunology* ; Mice ; Mice, Inbred C57BL ; Macrophages/immunology* ; Male ; Humans ; Apolipoproteins E/genetics* ; Tablets ; Tumor Necrosis Factor-alpha/genetics* ; Apoptosis/drug effects* ; Interleukin-1beta/genetics* ; Interleukin-6/genetics* ; Disease Models, Animal ; Mice, Knockout

Objective To explore the mechanism of lncRNA-BC200 (BC200) targeting the ubiquitination of Beta-site APP cleaving enzyme 1 (BACE1) and regulating the repair of nerve cell injury. Methods Mouse hippocampal neuron cell line HT22 was divided into four groups: control group, oxygen-glucose deprivation/reoxygenation(OGD/R) group, OGD/R+si-NC group and OGD/R+si-BC200 group. In order to further explore the relationship between BC200 and BACE1, HT22 cells were divided into four groups: OGD/R group, OGD/R+si-BC200 group, OGD/R+si-BC200+NC group and OGD/R+si-BC200+ BACE1 group. Twenty male C57BL/6J mice were randomly assigned to the following four groups: control group, middle cerebral artery occlusion (MCAO) group, MCAO+si-BC200 group and MCAO+si-BC200+BACE1 group. The mRNA expression levels of BC200 and BACE1 in cells were measured by real-time quantitative reverse transcription polymerase chain reaction. The expressions of c-caspase-3, B-cell lymphoma 2 (Bcl2), Bcl2 associated X protein(BAX) and BACE1 were detected by western blot, and the apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. Results Compared with the control group, the activity of HT22 cells in OGD/R group decreased significantly, and the percentage of apoptotic cells increased significantly. Compared with OGD/R+si-NC group, the activity of HT22 cells in OGD/R+si-BC200 group increased significantly, and the percentage of apoptotic cells decreased significantly. Compared with the control group, the expression of BACE1 protein in HT22 cells in OGD/R group was significantly enhanced. Compared with OGD/R+si-NC group, the expression of BACE1 protein in HT22 cells in OGD/R+si-BC200 group decreased significantly. It was observed that after OGD/R treatment, the ubiquitination level of BACE1 decreased significantly and the expression of BACE1 protein increased significantly. After transfection with si-BC200, the ubiquitination level of BACE1 protein increased significantly, while the expression of BACE1 protein decreased significantly. Compared with OGD/R+si-BC200+NC group, the percentage of apoptotic cells, the expression of c-caspase-3 and Bax protein in HT22 cells in OGD/R+si-BC200+BACE1 group increased significantly, and the expression of Bcl2 protein decreased significantly. Compared with the control group, the number of cerebral infarction areas and TUNEL positive cells in MCAO group increased significantly, and the survival number of neurons decreased significantly. Compared with the MCAO group, the number of cerebral infarction areas and TUNEL positive cells in MCAO+si-BC200 group decreased significantly, and the survival number of neurons increased significantly, while the addition of BACE1 reversed the improvement of si-BC200 transfection. Conclusion The combination of BC200 and BACE1 inhibit the ubiquitination of BACE1, and participate in mediating the expression enhancement of BACE1 induced by OGD/R. Specific blocking of BC200/BACE1 axis may be a potential therapeutic target to protect neurons from apoptosis induced by cerebral ischemia/reperfusion.
Animals ; Amyloid Precursor Protein Secretases/genetics* ; RNA, Long Noncoding/physiology* ; Aspartic Acid Endopeptidases/genetics* ; Male ; Neurons/pathology* ; Mice ; Mice, Inbred C57BL ; Apoptosis/genetics* ; Ubiquitination ; Cell Line ; Hippocampus/metabolism* ; bcl-2-Associated X Protein/genetics* ; Caspase 3/genetics* ; Infarction, Middle Cerebral Artery/metabolism*

OBJECTIVES: To investigate the role and mechanism of Brahma-related gene 1 (Brg1) in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia (BPD) model. METHODS: Wild-type C57BL/6 and Brg1^f1/f1 mice were randomly divided into four groups: wild-type control, wild-type BPD, Brg1^f1/f1 control, and Brg1^f1/f1 BPD (n=5 each). Immortalized mouse pulmonary alveolar type 2 cells (imPAC2) were cultured, and Brg1 gene was knocked down using lentivirus transfection technology. Cells were divided into three groups: control, empty vector, and Brg1 knockdown. Hematoxylin and eosin staining and immunofluorescence were used to detect pathological changes in mouse lung tissue. Western blot and real-time fluorescent quantitative PCR were used to measure Brg1 protein and mRNA expression levels in mouse lung tissue. Western blot and immunofluorescence were used to detect the expression of homeodomain-containing protein homeobox (HOPX), surfactant protein C (SPC), and Wnt/β-catenin signaling pathway proteins in mouse lung tissue and imPAC2 cells. The CCK8 assay was used to assess the proliferation of imPAC2 cells, and co-immunoprecipitation was performed to verify the interaction between Brg1 and β-catenin proteins in imPAC2 cells. RESULTS: Compared to the Brg1^f1/f1 control group and wild-type BPD group, the Brg1^f1/f1 BPD group showed increased alveolar diameter and SPC protein expression, and decreased relative density of pulmonary vasculature and HOPX protein expression (P<0.05). Compared to the control group, the Brg1 knockdown group showed increased cell proliferation ability, protein expression levels of SPC, Wnt5a and β-catenin, and β-catenin protein fluorescence intensity, along with decreased HOPX protein expression (P<0.05). An interaction between Brg1 and β-catenin proteins was confirmed. CONCLUSIONS The Brg1 gene may promote the proliferation of alveolar type 2 epithelial cells by regulating the Wnt/β-catenin signaling pathway, thus influencing the occurrence and development of BPD.
Animals ; DNA Helicases/genetics* ; Transcription Factors/genetics* ; Wnt Signaling Pathway/physiology* ; Nuclear Proteins/genetics* ; Mice ; Bronchopulmonary Dysplasia/etiology* ; Mice, Inbred C57BL ; beta Catenin/physiology* ; Disease Models, Animal ; Cell Proliferation ; Lung/pathology* ; Male

Direct electrical stimulation of the human cortex can produce subjective visual sensations, yet these sensations are unstable. The underlying mechanisms may stem from differences in electrophysiological activity within the distributed network outside the stimulated site. To address this problem, we recruited 69 patients who experienced visual sensations during invasive electrical stimulation while intracranial electroencephalography (iEEG) data were recorded. We found significantly flattened power spectral slopes in distributed regions involving different brain networks and decreased integrated information during elicited visual sensations compared with the non-sensation condition. Further analysis based on minimum information partitions revealed that the reconfigured network interactions primarily involved the inferior frontal cortex, posterior superior temporal sulcus, and temporoparietal junction. The flattened power spectral slope in the inferior frontal gyrus was also correlated with integrated information. Taken together, this study indicates that the altered electrophysiological signatures provide insights into the neural mechanisms underlying subjective visual sensations.
Humans ; Male ; Female ; Adult ; Visual Perception/physiology* ; Electric Stimulation ; Middle Aged ; Young Adult ; Electrocorticography ; Electroencephalography ; Brain Mapping

Objective To determine the acute effects of blood flow restriction(BFR)running warm-up on Achilles tendon morphology and function in basketball players in order to provide a theoretical basis for optimizing warm-up protocols for military personnel and athletes susceptible to Achilles tendon injuries.Methods Twenty-seven male basketball players were subjected and asked to participate in 3 different running warm-up protocols:low-speed running(LSR),high-speed running(HSR),and BFR combined with LSR(BFR-LSR).The acute changes in Achilles tendon morphology,mechanical properties,and functional performance across the 3 testing sessions were analyzed and compared.Results Immediately after training,both HSR warm-up and BFR-LSR warm-up significantly improved Achilles tendon thickness,blood flow,stiffness,and gastrocnemius maximal voluntary isometric contraction(MVIC)when compared with LSR warm-up(P<0.05).No statistical differences were observed in above indicators between the BFR-LSR and HSR warm-ups(P>0.05).24 hours after training,compared with LSR warm-up,HSR warm-up still significantly improved Achilles tendon thickness,blood flow,stiffness,and gastrocnemius MVIC(P<0.05).Although BFR-LSR warm-up did not show statistically significant differences in these parameters compared to LSR warm-up,it still demonstrated positive trends.Immediately and 24 h after training,no obvious difference were found in jump performance among the 3 warm-up protocols(P>0.05),but,both BFR-LSR and HSR warm-ups exhibited superior performance than LSR warm-up.Conclusion Immediately after training,BFR-LSR warm-up demonstrates comparable effects to the HSR warm-up on improving Achilles tendon morphology and performance,as well as enhancing jump performance.However,its sustained and long-term effects require further investigation.

Objective:To analyze the current status of clinical trials of Chinese materia medica for the purpose of registration in China; To provide reference for the research and development of new TCM drugs.Methods:Clinical trials of Chinese materia medica/natural medicine registered in Drug Clinical Trial Registration and Information Disclosure Platform were retrieved from inception to December 31, 2024. Excel 2019 software was used to input and analyze the data such as the number of registered clinical trials, date of first publication, study status, field of indication, trial phases, sponsors, group leader, and design types.Results:A total of 1 137 Chinese materia medica clinical trials had been registered, accounting for 4.12% of the total number registered on the platform. Phase Ⅱ clinical trials accounted for the highest proportion (58.8%), and 99.7% of clinical trials conducted domestically. The sponsors were predominantly domestically pharmaceutical enterprises. These 1 137 clinical trials of Chinese materia medica clinical trials involved 752 drug categories, 28 dosage forms, and 796 varieties (the same class of drugs had different drug dosage forms), with capsules being the most common. The indications primarily focused on respiratory, digestive, cardio-cerebrovascular, neuropsychiatric, gynecological diseases. The group leader of clinical trials was distributed in 28 provinces, among which the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine as the group leader, undertook the most clinical trials of TCM. 89.9% of the clinical trials adopted the randomized controlled trial design, and only 31.9% of the clinical trials purchased insurance for the subjects.Conclusion:The research and development of new TCM drugs has entered a phase of vigorous development. Further efforts are still needed in establishing systematic guidelines for Chinese materia medica clinical trials, accelerating the internationalization of TCM, exploring innovative dosage forms and indications, and strengthening the protection of participants' rights.

Objective To investigate the impact of different antibiotic courses on intestinal floras and immune function in 28-day-old premature infants.Methods A retrospective analysis was conducted on 120 premature infants admitted to the First People's Hospital of Nanyang City between March 2021 and March 2024.According to different courses of antibiotics,they were divided into short-course group(n=82,antibiotics use≤3 d)and long-course group(n=38,antibiotics use≥7 d).General data were collected,and intestinal floras and immune function were assessed at 28 days of age.Shannon and Simpson indexes of intestinal flora α-diversity,bacterial phylum and genus distribution of intestinal floras,and peripheral blood CD8+,CD4+T cell percentages,and CD4+/CD8+ratio were compared between the two groups.Pearson correlation analysis was used to explore the relationship between intestinal floras and immune function,and adverse outcomes were recorded.Results The Shannon and Simpson indexes of intestinal flora α-diversity in long-course group were lower than those in short-course group(P<0.05).No significant differences were found between the two groups in the distribution of Actinobacteria,Bacteroidetes,Firmicutes or Proteobacteria at the bacterial phylum level and Bacteroides,Enterococcus,or Veillonella at genus distribution level(P>0.05).However,the long-course group had lower proportions of Clostridioides,Clostridium sensu stricto 1,Escherichia and Klebsiella,and higher proportions of Enterococcus,Robinsoniella and Streptococcus than those in short-course group(P<0.05).After antibiotics use,levels of CD4+and CD4+/CD8+were decreased(P<0.05),while CD8+was increased in both groups(P<0.05).Compared with short-course group,levels of CD4+and CD4+/CD8+were lower,while CD8+was higher in short-course group(P<0.05).Pearson correlation analysis revealed that Clostridioides,Clostridium sensu stricto 1,Escherichia,Klebsiella were positively correlated with CD4+and CD4+/CD8+,while negatively correlated with CD8+(P<0.05).Conversely,Enterococcus,Robinsoniella and Streptococcus were negatively correlated with CD4+and CD4+/CD8+,while positively correlated with CD8+(P<0.05).No adverse outcomes occurred in two groups.Conclusion Compared with short-term antibiotic use,long-term use affects the colonization and diversity of intestinal floras in premature infants,and cause intestinal flora disturbance,potentially impairing immune function.

Objective To explore the application effect of nursing intervention based on empow-erment theory in treatment of facial photoaging with fractional ablative fractional laser.Methods A total of 90 patients with facial photoaging who underwent fractional ablative fractional laser treatment were selected and divided into control group and observation group according to random number table method,with 45 cases in each group.The control group received routine nursing intervention,while the observation group received nursing intervention based on empowerment theory.The skin condi-tion,the incidence of adverse reactions,psychological state[Self-Rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS)]scores,and quality of life[Dermatology Life Quality Index(DLQI)]scores were compared between the two groups.Results After intervention,the percentages of skin characteristics such as enlarged facial pores,wrinkles,and spots in the observation group were higher than those in the control group;the incidence of adverse reactions in the observation group was lower than that in the control group(8.89％ versus 24.44％);the SAS scores,SDS scores,and total DLQI scores in the observation group were lower than those in the control group,with statistically sig-nificant differences(P＜0.05).Conclusion Nursing intervention based on empowerment theory can effectively improve the facial skin condition of patients with facial photoaging treated with fraction-al ablative fractional laser,reduce the incidence of adverse reactions,alleviate negative emotions,and enhance quality of life.

ObjectiveTo investigate the effects of maltol aluminum exposure on miR-193a-3p, demethylase AlkB homolog 5 (ALKBH5), phosphatase and tensin homolog deleted on chromosome ten (PTEN) and protein kinase B (AKT), and whether miR-193a-3p is involved in aluminum-induced cognitive impairment by regulating ALKBH5/PTEN/AKT signaling pathway. Methods Specific pathogen-free male SD rats were randomly divided into control group and low-, medium- and high- dose groups according to their body weight, with eight rats in each group. Rats in the low-, medium-, and high- dose groups were intraperitoneally injected with maltol aluminum solution at concentrations of 10.00, 20.00, and 40.00 μmol/kg body weight, respectively, while the rats in control group were given an equal volume of 0.9% sodium chloride solution. Rats were injected for five days every week for three months. After injection, the novel object recognized test was used to assess the learning and memory ability of the rats. The relative expression of miR-193a-3p and B-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartate protease-3 (Caspase-3) mRNA in rat hippocampus was detected using the real-time quantitative polymerase chain reaction. The relative protein expression of ALKBH5, PTEN, and AKT2 in the rat hippocampus was detected using Western blot. Results The discrimination index and the preference index of the new object recognition test of the rats in high-dose group were lower than those in control group and low-dose group (all P<0.05). The relative expression of miR-193a-3p and Bcl-2 mRNA in the hippocampus of the rats in high-dose group was lower than those in control group and low-dose group (all P<0.05). The relative mRNA expression of Bax in the high-dose group was higher than those in the control group and low-dose group (both P<0.05). The relative mRNA expression of Caspase-3 of the rats in the high-dose group was higher than that in the other three groups (both P<0.05). The relative protein expression of ALKBH5 in the hippocampus of the rats in the high-dose group was lower than that in the control group (P<0.05). The relative expression of PTEN protein was higher than those in the control group and low-dose group (both P<0.05). The relative protein expression of AKT2 was lower than those in the control group and low-dose group (both P<0.05). Conclusion Sub-chronic aluminum exposure can inhibit the expression of miR-193a-3p in the hippocampus of rats, which may disrupt the ALKBH5/PTEN/AKT pathway and affect normal neuronal homeostasis and cellular function. This pathway may play an important role in aluminum-induced cognitive impairment.