Myocardial infarction is a cardiovascular disease (CVD) with high morbidity and mortality, which can trigger a cascade of cardiac pathophysiological changes, including fibrosis, inflammation, ischemia-reperfusion injury (IRI), and ventricular remodeling, ultimately leading to heart failure (HF). While conventional pharmacological treatments and clinical reperfusion therapy may enhance short-term prognoses and emergency survival rates, both approaches have limitations and adverse effects. Natural products (NPs) are extensively utilized as therapeutics globally, with some demonstrating potentially favorable therapeutic effects in preclinical and clinical pharmacological studies, positioning them as potential alternatives to modern drugs. This review comprehensively elucidates the pathophysiological mechanisms during myocardial infarction and summarizes the mechanisms by which NPs exert cardiac beneficial effects. These include classical mechanisms such as inhibition of inflammation and oxidative stress, alleviation of cardiomyocyte death, attenuation of cardiac fibrosis, improvement of angiogenesis, and emerging mechanisms such as cardiac metabolic regulation and histone modification. Furthermore, the review emphasizes the modulation by NPs of novel targets or signaling pathways in classical mechanisms, including other forms of regulated cell death (RCD), endothelial-mesenchymal transition, non-coding ribonucleic acids (ncRNAs) cascade, and endothelial progenitor cell (EPC) function. Additionally, NPs influencing a particular mechanism are categorized based on their chemical structure, and their relevance is discussed. Finally, the current limitations and prospects of NPs therapy are considered, highlighting their potential for use in myocardial infarction management and identifying issues that require urgent attention.
Humans ; Myocardial Infarction/genetics* ; Biological Products/therapeutic use* ; Animals ; Oxidative Stress/drug effects* ; Signal Transduction/drug effects*

Stroke is a cerebrovascular disease characterized by high rates of disability,recurrence and mortal-ity.It results primarily from cerebrovascular rupture or transient/permanent occlusion.Due to the complex pathological mechanism of stroke and the lack of early-stage biomarkers,effective treatment options remain limited.Circular RNAs(circRNAs)are stable and conserved endogenous long noncoding RNA that regulate the pathological process of stroke,in-cluding oxidative stress,inflammation,apoptosis and autophagy.In addition,the regulatory roles of circRNAs in stroke include ceRNA,DNA methylation and histone modification.This review provides a comprehensive overview of circRNA biogenesis,major functions and characteristics.Furthermore,it presents the latest research findings on circRNAs in the context of stroke pathology,with the aim of providing new insights and potential approaches for unraveling the underlying mechanism,diagnosis and treatment of such diseases.

OBJECTIVE To investigate the potential of low-frequency, low-power ultrasound to enhance the transdermal absorption and efficacy of ketoprofen gel. METHODS Ketoprofen gel was used as a model drug to compare the in vitro transdermal permeation of ultrasound treated group and untreated group. Additionally, a rat model of collagen-induced inflammation provided a basis for evaluating pharmacodynamic differences. Pharmacokinetic studies further elucidated the effects of ultrasound on ketoprofen gel's penetration process. RESULTS Ultrasound treatment enhanced the cumulative transdermal permeation of ketoprofen gel by 3.5-fold over 24 hours compared to untreated. Significant pharmacokinetic improvements in AUC0-t from (4289.02±763.58)ng·h·mL−1 to (11301.10±3386.30)ng·h·mL−1 and a reduction in Tmax from (6.0±1.4)h to (3.0±2.0)h. Ultrasound notably improved the gel's anti-inflammatory effects in the rat model, effectively and rapidly reducing inflammation-induced swelling. CONCLUSION Low-frequency, low-power ultrasound can significantly improve the amount and rate of transdermal absorption of ketoprofen gel and enhance its pharmacological potency, from the aspects of skin permeation tests, pharmacodynamic evaluation, and pharmacokinetic studies, which is an effective penetration enhancer for transdermal administration of ketoprofen gel.

Objective:To explore whether anlotinib or bevacizumab has better efficacy in patients with recurrent glioblastoma.Methods:The clinical characteristics and treatment data of patients with recurrent glioblastoma admitted to Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine,were collected retrospectively.All patients received maximal resection of the tumor combined with postoperative adjuvant radiotherapy and chemotherapy,and the recurrence was detected by head contrast-enhanced MRI.According to the choice of anti-vascular therapy,the patients were divided into anlotinib group and bevacizumab group.Survival curves were drawn to compare the overall survival time of the two groups of patients,and subgroup analysis was performed according to the basic information of the patients and whether they received temozolomide chemotherapy or radiotherapy after recurrence.Results:A total of 37 patients were enrolled in the study,19 in the anlotinib group and 18 in the bevacizumab group.The median overall survival time was 16.3 months,with 19.6 months in the anlotinib group and 12.8 months in the bevacizumab group.However,survival analysis showed that there was no significant difference in survival time between the anlotinib group and the bevacizumab group(P=0.88).Further subgroup analysis showed that there was no significant difference in survival time between the two groups in all subgroups.Conclusion:This study provided an initial indication of the efficacy of anlotinib in patients with recurrent glioblastoma and suggested that oral anlotinib may be a viable option for patients who were unable to tolerate bevacizumab or who had.

Objective:To explore whether anlotinib or bevacizumab has better efficacy in patients with recurrent glioblastoma.Methods:The clinical characteristics and treatment data of patients with recurrent glioblastoma admitted to Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine,were collected retrospectively.All patients received maximal resection of the tumor combined with postoperative adjuvant radiotherapy and chemotherapy,and the recurrence was detected by head contrast-enhanced MRI.According to the choice of anti-vascular therapy,the patients were divided into anlotinib group and bevacizumab group.Survival curves were drawn to compare the overall survival time of the two groups of patients,and subgroup analysis was performed according to the basic information of the patients and whether they received temozolomide chemotherapy or radiotherapy after recurrence.Results:A total of 37 patients were enrolled in the study,19 in the anlotinib group and 18 in the bevacizumab group.The median overall survival time was 16.3 months,with 19.6 months in the anlotinib group and 12.8 months in the bevacizumab group.However,survival analysis showed that there was no significant difference in survival time between the anlotinib group and the bevacizumab group(P=0.88).Further subgroup analysis showed that there was no significant difference in survival time between the two groups in all subgroups.Conclusion:This study provided an initial indication of the efficacy of anlotinib in patients with recurrent glioblastoma and suggested that oral anlotinib may be a viable option for patients who were unable to tolerate bevacizumab or who had.

Objective:To analyze the influencing factors of clozapine plasma concentration in patients with mental disorders after oral administration, so as to provide reference for individualized treatment.Methods:Retrospective analysis was made on 221 inpatient reports of Clozapine blood concentration monitoring in the Therapeutic Drug Monitoring Laboratory (TDM) of the Pharmacy Department of the Chaohu Hospital Affiliated to Anhui Medical University from January to October 2021, and information such as patient gender, age, body mass index (BMI), smoking history, clozapine dose, combined drug use and blood concentration monitoring results were collected; Single factor analysis of variance and binary logistic regression were used to analyze the monitoring results of clozapine blood concentration in patients with mental disorders and its influencing factors.Results:Among 221 monitoring reports, 74 cases (normal concentration group) had clozapine plasma concentration within the effective plasma concentration range (350-600 ng/ml), 103 cases (low concentration group) were lower than the effective plasma concentration range (<350 ng/ml), and 44 cases (high concentration group) were higher than the effective plasma concentration range (>600 ng/ml). The results of single factor analysis of variance showed that there were statistically significant differences in daily dose of clozapine, standard dose, smoking history, course of disease, and abnormal liver function of patients in different blood concentration groups of clozapine (all P<0.05). The most frequently used antipsychotic drugs in 221 patients with clozapine were sodium valproate, amisulpride, aripiprazole and lithium carbonate in turn. The proportion of clozapine combined with ≥2 antipsychotics in the normal concentration group was higher than that in the low concentration group and the high concentration group, and the difference was statistically significant ( P<0.05). The results of binary logistic regression analysis showed that the combination of one antipsychotic drug and ≥ two antipsychotic drugs might help the blood concentration of clozapine in patients with mental disorders reach the target concentration (350-600 ng/ml), and the combination of two drugs was more beneficial [ OR(95% CI): 1.795(0.753-4.282)], with a statistically significant difference ( P<0.05). Conclusions:Clozapine plasma concentration varies greatly among individuals, and the therapeutic window is narrow. It is necessary to adjust the dosage in combination with the basic information and clinical information of patients, and regularly monitor the plasma concentration, so as to achieve the safety and effectiveness of individualized drug use.

Objective:To investigate the role of cholinergic anti-inflammatory pathway in the regulation of peptide transporter 1 (PepT1) expression in small intestinal epithelium of septic rats by Ghrelin.Methods:One hundred adult male Sprague-Dawley (SD) rats were randomly divided into sham operation group, sepsis group, sepsis+vagotomy group, sepsis+Ghrelin group, and sepsis+vagotomy+Ghrelin group, with 20 rats in each group. In the sham operation group, the cecum was separated after laparotomy, without ligation and perforation. In the sepsis group, the rats received cecal ligation puncture (CLP). In the sepsis+vagotomy group, the rats received CLP and vagotomy after laparotomy. In the sepsis+Ghrelin group, 100 μmol/L Ghrelin was intravenously injected after CLP immediately. The rats in the sepsis+vagotomy+Ghrelin group received CLP and vagotomy at the same time, then the Ghrelin was intravenously injected immediately with the same dose as the sepsis+Ghrelin group. Ten rats in each group were taken to observe their survival within 7 days. The remaining 10 rats were sacrificed 20 hours after the operation to obtain venous blood and small intestinal tissue. The condition of the abdominal intestine was observed. The injury of intestinal epithelial cells was observed with transmission electron microscopy. The contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum and small intestinal tissue were detected by enzyme-linked immunosorbent assay (ELISA). The brush border membrane vesicle (BBMV) was prepared, the levels of mRNA and protein expression of PepT1 in the small intestinal epithelium were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:All rats in the sham operation group survived at 7 days after operation. The 7-day cumulative survival rate of rats in the sepsis group was significantly lower than that in the sham operation group (20% vs. 100%, P < 0.05). The cumulative survival rate of rats after Ghrelin intervention was improved (compared with sepsis group: 40% vs. 20%, P < 0.05), but the protective effect of Ghrelin was weakened after vagotomy (compared with sepsis+Ghrelin group: 10% vs. 40%, P < 0.05). Compared with the sham operation group, in the sepsis group, the small intestine and cecum were dull red, the intestinal tubules were swollen and filled with gas, the intestinal epithelial cells were seriously injured under transmission electron microscopy, the levels of TNF-α and IL-1β in serum and small intestinal were significantly increased, and the expression levels of PepT1 mRNA and protein in the small intestinal epithelium were significantly decreased. It indicated that the sepsis rat model was successfully prepared. After vagotomy, the intestinal swelling and gas accumulation became worse in septic rats, leading to the death of all rats. Compared with the sepsis group, the abdominal situation in the sepsis+Ghrelin group was improved, the injury of intestinal epithelial cells was alleviated, the serum and small intestinal TNF-α and IL-1β were significantly decreased [serum TNF-α (ng/L): 253.27±23.32 vs. 287.90±19.48, small intestinal TNF-α (ng/L): 95.27±11.47 vs. 153.89±18.15, serum IL-1β (ng/L): 39.16±4.47 vs. 54.26±7.27, small intestinal IL-1β (ng/L): 28.47±4.13 vs. 42.26±2.59, all P < 0.05], and the expressions of PepT1 mRNA and protein in the small intestinal epithelium were significantly increased [PepT1 mRNA (2 -ΔΔCt): 0.66±0.05 vs. 0.53±0.06, PepT1 protein (PepT1/GAPDH): 0.80±0.04 vs. 0.60±0.05, both P < 0.05]. Compared with the sepsis+Ghrelin group, after vagotomy in the sepsis+vagotomy+Ghrelin group, the effect of Ghrelin on reducing the release of inflammatory factors in sepsis rats was significantly reduced [serum TNF-α (ng/L): 276.58±19.88 vs. 253.27±23.32, small intestinal TNF-α (ng/L): 144.28±12.99 vs. 95.27±11.47, serum IL-1β (ng/L): 48.15±3.21 vs. 39.16±4.47, small intestinal IL-1β (ng/L): 38.75±4.49 vs. 28.47±4.13, all P < 0.05], the up-regulated effect on the expression of PepT1 in small intestinal epithelium was lost [PepT1 mRNA (2 -ΔΔCt): 0.58±0.03 vs. 0.66±0.05, PepT1 protein (PepT1/GAPDH): 0.70±0.02 vs. 0.80±0.04, both P < 0.05], and the injury of small intestinal epithelial cells was worse. Conclusion:Ghrelin plays a protective role in sepsis by promoting cholinergic neurons to inhibit the release of inflammatory factors, thereby promoting the transcription and translation of PepT1.

Objective:To investigate the role of LncRNA-TUG1 in the injury of intestinal epithelial cells induced by lipopolysaccharide (LPS).Methods:LPS was used to treat HIEC-6 human intestinal epithelial cells for 24 h to construct a sepsis injury model. Whole transcriptome RNA sequencing was used to analyze the expression changes of mRNA, microRNA and lncRNA in HIEC-6 cells after LPS treatment. Real-time fluorescence quantitative (qRT-PCR) and Western blot was performed to detect the expression changes of lncRNA-TUG1, microRNA-132-3p (miR-132-3p), SIRT1 mRNA and SIRT1 protein in HIEC-6 cells after LPS treatment. The expression levels of LncRNA-TUG1, miR-132-3p and SIRT1 were artificially changed by in vitro transfection. qRT-PCR and Western blot were used to confirm the regulatory effect of lncRNA-TUG1 on microRNA-132-3p and SIRT1. CCK-8 and flow cytometry were used to analyze the effects of LncRNA-TUG1, miR-132-3p and SIRT1 on the proliferation and apoptosis of HIEC-6 cells. The dual luciferase report analysis was used to verify the targeting relationship between LncRNA-TUG1, miR-132-3p and SIRT1. Statistical analysis was performed using SPSS 17.0, and differences between the two groups were compared using independent sample t test. Results:RNA sequencing results showed that the expressions of lncRNA-TUG1 and SIRT1 were decreased in HIEC-6 cells after LPS treatment ( t=3.26, P<0.05 and t=2.55, P<0.05), but the expression of miR-132-3p was increased ( t=4.12, P<0.05). In vitro cell experiments, the expression of lncRNA-TUG1 and SIRT1 were decreased in HIEC-6 cells treated with LPS ( t=5.69, P<0.05 and t=5.712, P<0.05), while the expression of miR-132-3p was increased ( t=3.88, P<0.05). Overexpression of lncRNA-TUG1 increased the proliferation rate ( t=6.55, P<0.05) and decreased the apoptosis rate ( t=3.94, P<0.05) of LPS-treated cells. Upregulation of lncRNA-TUG1 decreased the expression of miR-132-3p ( t=4.66, P<0.05), and increased the mRNA and protein levels of SIRT1 ( t=3.91, P<0.05). Transfection of miR-132-3P mimic could inhibit the mRNA ( t=4.08, P<0.05) and protein levels of SIRT1. In LPS-treated cells, the cells co-transfected with miR-132-3pmimic and siRNA-SIRT1 had a lower proliferation rate ( t=4.55, P<0.05 and t=5.67, P<0.05) and a higher apoptosis rate ( t=3.90, P<0.05 and t=4.22, P<0.05) than those transfected with only pcDNA3.1-lncRNA-TUG. Conclusions:lncRNA-TUG1 may act as a ceRNA to regulate miR-132-3p/SIRT1, therefore alleviating HIEC-6 cell injury caused by LPS. Intervention of lncRNA-TUG1/miR-132-3p/SIRT1 regulatory pathway may become a potential strategy to prevent sepsis-induced intestinal mucosal damage.

objective:To investigate the tolerability of early enteral nutrition (EN), and to further explore the association of early EN with clinical outcome in critically ill patients with hemodynamic instability.Methods:The adult patients from Zhejiang Provincial People’s Hospital with an expected admission to ICU for at least 24 h were consecutively recruited from May 2014 to May 2016, and all clinical, laboratory, and survival data were prospectively collected. The AGI grade was daily assessed on the first week of ICU admission. Enteral nutrition (EN) started after 6 h of hemodynamic stability (MAP ≥ 65 mmHg) when the patients took vasoactive medication. The patients were divided into three groups based on the timing of EN initiation: early EN group (EN initiation within 48 h of ICU admission), late EN group (EN initiation at more than 48 h of ICU admission), and no initiation of enteral feeding within 7 days of ICU admission.Results:Of 201 patients enrolled, the mean age was 65.3 ± 16.4 years, APACHE II score was 22.4 ± 6.85, and 191 patients (95.0%) took mechanical ventilation. There were no differences in high gastric residual volume, diarrhea, and gastrointestinal (GI) bleeding between the early EN group and late EN group ( P>0.05). Whereas, patients in the no initiation of EN within 7 days of ICU admission had a lower prevalence of gastric residual volume (16.7% vs. 33.3%, P=0.05), but higher prevalence of GI bleeding (47.2% vs. 26.1%, P=0.02). Compared with those in the late EN group and in no initiation of EN within 7 days of ICU admission, patients in the early EN group had lower 28- (30.4% vs. 47.9% vs. 55.6%, P=0.01) and 60-day mortality rates (38.0% vs. 53.4% vs. 63.9%, P=0.017). Multivariate Cox regression analysis showed that the timing of EN initiation on the admission to ICU (early EN vs. late EN, χ 2≥5.83, P<0.05; early EN vs. no initiation of EN, χ 2≥7.90, P<0.01), serum creatinine ( χ 2=5.06, P<0.05), plasma albumin ( χ 2≥6.41, P<0.01), AGI grade ( χ 2≥8.15, P<0.01), and APACHE II score ( χ 2≥9.62, P<0.01) were independent predictors for 28- and 60-day mortality. Conclusions:Early EN on admission to ICU could be tolerated, and is significantly associated with lower risk of 28- and 60-day mortality in critically ill patients with vasoactive medication to maintain hemodynamic stability.

Objective:To investigate the related risk factors for the prognosis of hospital-acquired carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections in elderly patients with critical illness.Methods:Clinical data of elderly patients with nosocomial CRKP bloodstream infection in intensive care unit (ICU) from Jan. 2010 to Dec. 2016 were retrospectively analyzed. Patients were divided into the death and survival groups according to the prognosis. Clinical characteristics were compared between the two groups. Influencing factors for the prognosis of nosocomial CRKP bloodstream infections in elderly ICU patients were screened by multivariate Logistic regression analysis.Results:A total of 119 elderly ICU patients with nosocomial CRKP bloodstream infection were enrolled. The overall ICU mortality rate was 62.2% (74/119 patients), among which the ICU mortality was lower in patients treated with tigecycline than without tigecycline treatment (50.0% or 25/50 vs. 71.0% or 49/69, χ2=4.770, P=0.029). And the ICU mortality was lower in patients with combination therapy than with mono-therapy (54.9% or 39/71 vs. 72.9% or 35/48, χ2=3.940, P=0.047). Multivariate Logistic regression analysis revealed that the administration of vasoactive drugs ( OR=25.545, 95% CI: 9.743-52.242, P=0.001), and the resistance to tigecycline ( OR=8.990, 95% CI: 0.957-24.488, P=0.049) were independent risk factors for ICU mortality. While the early initiated appropriate antibiotics treatment, which was defined as using at least one susceptible antibiotic within 48 hours ( OR=0.081, 95% CI: 0.014-0.463, P=0.005), and appropriate antibiotics and adequate duration ( OR=0.785, 95% CI: 0.631-0.977, P=0.030), were protective factors for the good outcome. Conclusions:Nosocomial CRKP bloodstream infection in elderly ICU patients leads a high ICU mortality rate. The early initiated appropriate antibiotics treatment and optimum antibiotics duration could reduce the risk for death.