Objective:To preliminarily evaluate the lumen gain of sonodynamic therapy (SDT) mediated by sinoporphyrin sodium at carotid and femoral atherosclerotic plaque sites, and to assess whether concomitant statin use, lesion location, plaque echogenicity/type, and baseline stenosis severity modify the therapeutic response.Methods:This single-center, prospective, exploratory pilot clinical study enrolled patients with peripheral artery disease who attended the outpatient cardiology clinic of the First Affiliated Hospital of Harbin Medical University between February and September 2016. All enrolled patients received optimized oral medical therapy in combination with a single session of SDT. Vascular evaluation was performed using color Doppler ultrasound before treatment and 1 and 4 weeks after treatment. The primary efficacy endpoint was the percent change from baseline in luminal diameter stenosis at the site of the atherosclerotic plaque (%Δ) at week 4, while the secondary efficacy endpoint was %Δ at week 1. Subgroup analyses were conducted according to prior statin use, plaque location, plaque characteristics, and baseline degree of luminal stenosis.Results:A total of 24 patients, aged (70.7±2.2) years were enrolled. There were 20 (83%) males. Compared to baseline, luminal diameter stenosis at the plaque site reduced by week 4 ((50.1±1.2)% vs. (57.2±1.1)%, P<0.001), %Δ was(12.32±1.05)%; and luminal diameter stenosis also reduced by week 1 ((51.7±1.2)% vs. (57.2±1.1)%, P<0.001)), %Δ was(9.61±0.85)%. In subgroup analyses, the treatment effect on diameter stenosis was independent of prior statin use; SDT reduced stenosis in both carotid and femoral plaques; with superior efficacy observed in hypoechoic and mixed-echo plaques; and efficacy was observed across mild, moderate, and severe baseline stenosis categories (all P<0.05). Conclusion:In this single-center pilot study, SDT demonstrates therapeutic efficacy across mild, moderate, and severe stenoses, as well as in hypoechoic and mixed-echo plaques, showing potential to rapidly promote luminal gain at carotid and femoral atherosclerotic plaque sites.

As antibiotic resistance becomes increasingly concerning,antimicrobial peptides,as a new type of antibiotic alternative,have attracted more attention.However,the low enzymatic stability of antimicrobial peptides severely limits their clinical applications.To address this issue,researchers have developed various structural modification strategies,including the introduction of unnatural amino acids,peptide chain cyclization and chemical group modification.This article reviews the basic principles and cases of the above modification strategies analyzes the advantages and disadvantages of different modification strategies and recommends ways these strategies can be optimized.In addition,this article predicts the developments of and potential challenges to strategies for enhancing enzymatic stability of antimicrobial peptides in the hope of providing references for subsequent research and development of antimicrobial peptides.

Objective:To investigate the impact of circumferential tumor location (anterior wall, nonanterior wall, or circumferential) on circumferential resection margin (CRM) status, local recurrence, and survival in patients with mid-low rectal cancer.Methods:A retrospective cohort study was conducted using data from 696 patients with mid-low rectal adenocarcinoma who underwent surgery in the Department of Colorectal Surgery at the First Affiliated Hospital of Naval Medical University between December, 2018 and December, 2019. Based on MRI or contrast-enhanced CT findings, the rectal wall was divided into four quadrants: anterior, posterior, left, and right. Tumors were classified into three groups: anterior wall group ( n = 245), nonanterior wall group ( n = 286, tumors predominantly located on the posterior or lateral walls), and circumferential group ( n = 165, tumors involving ≥ 3/4 of the circumference). Propensity score matching (PSM) was used to balance baseline characteristics. Outcomes included pathological CRM positivity, local recurrence rate (LRR), overall survival (OS), and disease-free survival (DFS). Cox regression analysis was performed to identify risk factors for recurrence, and subgroup analysis was conducted in patients who did not receive neoadjuvant therapy. Results:After PSM, both the anterior and circumferential groups had significantly higher pathological CRM positivity rates compared to the nonanterior wall group ( P=0.040 and P=0.039, respectively). The median follow-up time was 64 months (range: 1-71 months). Compared to the nonanterior wall group, the anterior wall group also had a significantly higher 5-year LRR (8.8% vs. 2.3%, P=0.003), and significantly lower 5-year OS (80.7% vs. 91.6%, P=0.001) and DFS (76.6% vs. 84.6%, P=0.029). The circumferential group had a significantly higher 5-year LRR than the nonanterior wall group (11.4% vs. 3.8%, P=0.020), but no significant differences were observed in 5-year OS (81.8% vs. 89.5%, P=0.100) or DFS (70.7% vs. 78.3%, P=0.101). No significant differences were found between the anterior and circumferential groups in 5-year LRR (11.1% vs. 9.7%), OS (76.3% vs. 83.7%), or DFS (69.8% vs. 74.1%) either (all P>0.05). Cox univariate analysis and multivariate analysis identified anterior wall tumors (HR=3.751, 95%CI: 1.373-10.215, P=0.010), circumferential tumors (HR=3.240, 95%CI: 1.109-9.466, P=0.032), pathological CRM positivity (HR=3.071, 95%CI: 1.144-8.245, P=0.026), and lymph node metastasis (HR=2.584, 95%CI: 1.192-5.601, P=0.016) as independent risk factors for LRR. Conversely, a greater distance from tumor to the anal verge (per 1 cm increase, HR=0.831, 95%CI: 0.712-0.970, P=0.019), and neoadjuvant therapy (HR=0.442, 95%CI: 0.204-0.957, P=0.038) were identified as independent protective factors against LRR. In patients who did not receive neoadjuvant therapy, locally advanced nonanterior wall tumors exhibited markedly low LRR (1.3% for pathological stage II-III, 1.6% for pT3-4 stage). Conclusion:Rectal tumors located in the anterior wall or involving the circumference are associated with higher CRM positivity rates, increased local recurrence, and poorer survival. These patients should be prioritized for neoadjuvant therapy. In contrast, nonanterior wall tumors have a low recurrence rate, and selective omission of neoadjuvant therapy may be considered for these cases.

As antibiotic resistance becomes increasingly concerning,antimicrobial peptides,as a new type of antibiotic alternative,have attracted more attention.However,the low enzymatic stability of antimicrobial peptides severely limits their clinical applications.To address this issue,researchers have developed various structural modification strategies,including the introduction of unnatural amino acids,peptide chain cyclization and chemical group modification.This article reviews the basic principles and cases of the above modification strategies analyzes the advantages and disadvantages of different modification strategies and recommends ways these strategies can be optimized.In addition,this article predicts the developments of and potential challenges to strategies for enhancing enzymatic stability of antimicrobial peptides in the hope of providing references for subsequent research and development of antimicrobial peptides.

Objective:To investigate the impact of circumferential tumor location (anterior wall, nonanterior wall, or circumferential) on circumferential resection margin (CRM) status, local recurrence, and survival in patients with mid-low rectal cancer.Methods:A retrospective cohort study was conducted using data from 696 patients with mid-low rectal adenocarcinoma who underwent surgery in the Department of Colorectal Surgery at the First Affiliated Hospital of Naval Medical University between December, 2018 and December, 2019. Based on MRI or contrast-enhanced CT findings, the rectal wall was divided into four quadrants: anterior, posterior, left, and right. Tumors were classified into three groups: anterior wall group ( n = 245), nonanterior wall group ( n = 286, tumors predominantly located on the posterior or lateral walls), and circumferential group ( n = 165, tumors involving ≥ 3/4 of the circumference). Propensity score matching (PSM) was used to balance baseline characteristics. Outcomes included pathological CRM positivity, local recurrence rate (LRR), overall survival (OS), and disease-free survival (DFS). Cox regression analysis was performed to identify risk factors for recurrence, and subgroup analysis was conducted in patients who did not receive neoadjuvant therapy. Results:After PSM, both the anterior and circumferential groups had significantly higher pathological CRM positivity rates compared to the nonanterior wall group ( P=0.040 and P=0.039, respectively). The median follow-up time was 64 months (range: 1-71 months). Compared to the nonanterior wall group, the anterior wall group also had a significantly higher 5-year LRR (8.8% vs. 2.3%, P=0.003), and significantly lower 5-year OS (80.7% vs. 91.6%, P=0.001) and DFS (76.6% vs. 84.6%, P=0.029). The circumferential group had a significantly higher 5-year LRR than the nonanterior wall group (11.4% vs. 3.8%, P=0.020), but no significant differences were observed in 5-year OS (81.8% vs. 89.5%, P=0.100) or DFS (70.7% vs. 78.3%, P=0.101). No significant differences were found between the anterior and circumferential groups in 5-year LRR (11.1% vs. 9.7%), OS (76.3% vs. 83.7%), or DFS (69.8% vs. 74.1%) either (all P>0.05). Cox univariate analysis and multivariate analysis identified anterior wall tumors (HR=3.751, 95%CI: 1.373-10.215, P=0.010), circumferential tumors (HR=3.240, 95%CI: 1.109-9.466, P=0.032), pathological CRM positivity (HR=3.071, 95%CI: 1.144-8.245, P=0.026), and lymph node metastasis (HR=2.584, 95%CI: 1.192-5.601, P=0.016) as independent risk factors for LRR. Conversely, a greater distance from tumor to the anal verge (per 1 cm increase, HR=0.831, 95%CI: 0.712-0.970, P=0.019), and neoadjuvant therapy (HR=0.442, 95%CI: 0.204-0.957, P=0.038) were identified as independent protective factors against LRR. In patients who did not receive neoadjuvant therapy, locally advanced nonanterior wall tumors exhibited markedly low LRR (1.3% for pathological stage II-III, 1.6% for pT3-4 stage). Conclusion:Rectal tumors located in the anterior wall or involving the circumference are associated with higher CRM positivity rates, increased local recurrence, and poorer survival. These patients should be prioritized for neoadjuvant therapy. In contrast, nonanterior wall tumors have a low recurrence rate, and selective omission of neoadjuvant therapy may be considered for these cases.

Objective:To preliminarily evaluate the lumen gain of sonodynamic therapy (SDT) mediated by sinoporphyrin sodium at carotid and femoral atherosclerotic plaque sites, and to assess whether concomitant statin use, lesion location, plaque echogenicity/type, and baseline stenosis severity modify the therapeutic response.Methods:This single-center, prospective, exploratory pilot clinical study enrolled patients with peripheral artery disease who attended the outpatient cardiology clinic of the First Affiliated Hospital of Harbin Medical University between February and September 2016. All enrolled patients received optimized oral medical therapy in combination with a single session of SDT. Vascular evaluation was performed using color Doppler ultrasound before treatment and 1 and 4 weeks after treatment. The primary efficacy endpoint was the percent change from baseline in luminal diameter stenosis at the site of the atherosclerotic plaque (%Δ) at week 4, while the secondary efficacy endpoint was %Δ at week 1. Subgroup analyses were conducted according to prior statin use, plaque location, plaque characteristics, and baseline degree of luminal stenosis.Results:A total of 24 patients, aged (70.7±2.2) years were enrolled. There were 20 (83%) males. Compared to baseline, luminal diameter stenosis at the plaque site reduced by week 4 ((50.1±1.2)% vs. (57.2±1.1)%, P<0.001), %Δ was(12.32±1.05)%; and luminal diameter stenosis also reduced by week 1 ((51.7±1.2)% vs. (57.2±1.1)%, P<0.001)), %Δ was(9.61±0.85)%. In subgroup analyses, the treatment effect on diameter stenosis was independent of prior statin use; SDT reduced stenosis in both carotid and femoral plaques; with superior efficacy observed in hypoechoic and mixed-echo plaques; and efficacy was observed across mild, moderate, and severe baseline stenosis categories (all P<0.05). Conclusion:In this single-center pilot study, SDT demonstrates therapeutic efficacy across mild, moderate, and severe stenoses, as well as in hypoechoic and mixed-echo plaques, showing potential to rapidly promote luminal gain at carotid and femoral atherosclerotic plaque sites.

The ezrin,radixin,moesin(ERM)protein family plays a pivotal role in cell morphology,migration,and signal transduction.Ezrin,as a prominent member of this family,is highly involved in these processes.Ezrin phosphorylation is particularly crucial,by regulating the interaction between ezrin and the actin cytoskeleton.This interaction is a key mediator of cytotoxicity in host cells infected with Helicobacter pylori,significantly impacting cell morphology.In this review,we comprehensively summarize the multifaceted role of ezrin protein in H.pylori-induced nodular gastritis.We consider the relationships between ezrin's structure,function,signaling pathways,and phosphorylation in the context of nodular gastritis.Moreover,this review highlights the role of ezrin protein as a potential therapeutic target,offering novel insights for the prevention and treatment of nodular gastritis.

BACKGROUND:Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis,and the curative effect is definite,but the medication rule and mechanism are not clear. OBJECTIVE:Using the methodology of data mining and network pharmacology,to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis. METHODS:The relevant documents included in CNKI,WanFang,VIP and PubMed were used as data sources,and the relevant data were statistically counted and extracted by Microsoft EXCEL2019,IBMSPSS25.0 and other software.The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis,and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results.The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking. RESULTS AND CONCLUSION:Finally,151 articles were included and 207 prescriptions were selected,involving 285 flavors of Chinese herbs.(1)Ten groups of important drug combinations were obtained through the above two analyses,among which the core drug combination with the highest confidence and improvement was"Drynaria-Eucommia-Angelica."The key components of the combination in the treatment of primary osteoporosis were quercetin,kaempferol,naringenin and so on.The core targets were SRC proto-oncogene,phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene.The main pathways were cancer signaling pathway,JAK-STAT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.(2)The key active components were docked with the core targets,and the two showed a good combination.To conclude,Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets,which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis.

Objective N-methyl-D-aspartate(NMDA)receptor subunit 2B(NR2B)and its phosphorylation are involved in cerebral ischemia/hypoxic neural injury.Hypoxic preconditioning(HPC)can serve as an endogenous protective intervention to protect the brain from ischemic/hypoxic injury.This study intended to explore the effect of HPC on NR2B and the phosphorylation of its two tyrosine sites(1252 and 1336)in hippocampal cells through in vivo and in vitro experiments and thus determine the role of NR2B in HPC neuroprotection.Methods 6～8 weeks-old male SPF-grade ICR mice and the mouse hippocampal neuron cell line HT22 were repeatedly exposed to hypoxia to replicate HPC animal and cell models.Western blot and immunofluorescence were applied to detect the levels of NR2B and the phosphorylation levels of its tyrosine 1336(pY1336NR2B)and 1252(pY1252NR2B)residues in the hippocampus of mice and HT22 cells.The distributions of NR2B,pY1336NR2B,and pY1252NR2B in the synaptic site(TxP)and extrasynaptic site(TxS)were analyzed by Western blot.The levels of cleaved caspase-3 and α-spectrin,which indicate cell apoptosis,were also detected.Results HPC downregulated the levels of NR2B and pY1336NR2B in the mouse hippocampus and HT22 cells.Changes in NR2B and pY1336NR2B levels in the TxS of the mouse hippocampus were similar to those in hippocampus and HT22 cells,whereas changes in the TxP showed the opposite trend.Conclusions Downregulation of NR2B and pY1336NR2B may be involved in HPC-induced neuroprotection,and their localization at synapses and extrasynapses may play different roles in neuroprotection.

Objective N-methyl-D-aspartate(NMDA)receptor subunit 2B(NR2B)and its phosphorylation are involved in cerebral ischemia/hypoxic neural injury.Hypoxic preconditioning(HPC)can serve as an endogenous protective intervention to protect the brain from ischemic/hypoxic injury.This study intended to explore the effect of HPC on NR2B and the phosphorylation of its two tyrosine sites(1252 and 1336)in hippocampal cells through in vivo and in vitro experiments and thus determine the role of NR2B in HPC neuroprotection.Methods 6～8 weeks-old male SPF-grade ICR mice and the mouse hippocampal neuron cell line HT22 were repeatedly exposed to hypoxia to replicate HPC animal and cell models.Western blot and immunofluorescence were applied to detect the levels of NR2B and the phosphorylation levels of its tyrosine 1336(pY1336NR2B)and 1252(pY1252NR2B)residues in the hippocampus of mice and HT22 cells.The distributions of NR2B,pY1336NR2B,and pY1252NR2B in the synaptic site(TxP)and extrasynaptic site(TxS)were analyzed by Western blot.The levels of cleaved caspase-3 and α-spectrin,which indicate cell apoptosis,were also detected.Results HPC downregulated the levels of NR2B and pY1336NR2B in the mouse hippocampus and HT22 cells.Changes in NR2B and pY1336NR2B levels in the TxS of the mouse hippocampus were similar to those in hippocampus and HT22 cells,whereas changes in the TxP showed the opposite trend.Conclusions Downregulation of NR2B and pY1336NR2B may be involved in HPC-induced neuroprotection,and their localization at synapses and extrasynapses may play different roles in neuroprotection.