Objective To investigate the effect of berberine and its mechanism in delaying silica-induced lung injury via network pharmacology and molecular docking, followed by verification with animal experiments. Methods i) Targets of berberine and silicosis were obtained from multiple databases, and the common targets were identified. A protein-protein interaction network was constructed using the STRING database, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the common targets via the DAVID database. Molecular docking was conducted using AutoDock software for validation. ii) Specific pathogen-free Wistar rats were randomly divided into five groups, with six rats in each group. Rats in the model group, pirfenidone group, and low- and high-dose berberine groups received a single non-exposure intratracheal instillation of 1.00 mL silica suspension at a mass concentration of 100 g/L, whereas rats in the control group received an equal volume of 0.9% sodium chloride solution. Rats in the pirfenidone group were administered with pirfenidone solution at a dose of 100 mg/kg body weight, and rats in the low- and high-dose berberine groups were administered with berberine solutions at doses of 100 and 200 mg/kg body weight, respectively. The remaining two groups received equal volumes of 0.9% sodium chloride solution. All treatments were administered by gavage once daily for 28 consecutive days from 24 hours after silica exposure. After intervention, rats in each group were sacrificed. Histopathological changes in lung tissues were observed, and the lung organ coefficient was detected. Serum malondialdehyde (MDA) was detected by colorimetry. Serum inflammatory cytokine were detected by enzyme-linked immunosorbent assay. The expression of fibrosis markers in lung tissues was detected by immunohistochemistry. The protein expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and phosphorylated AKT (p-AKT) in lung tissues was determined by Western blot. Results i) Network pharmacology analysis identified 46 potential targets. The core targets included AKT1, tumor protein p53, caspase-3, matrix metalloproteinase-9, and albumin. GO enrichment analysis revealed that the targets related to the anti-fibrotic effect of berberine against silicosis were mainly enriched in biological processes including signal transduction, negative regulation of apoptosis, extracellular matrix degradation, and response to reactive oxygen species. KEGG enrichment analysis showed that berberine exerted anti-silicosis effects through multiple signaling pathways, such as the PI3K/AKT pathway, hypoxia-inducible factor-1 pathway, and advanced glycation end product (AGE)-receptor for AGE pathway. ii) Histopathological examination revealed that rats in the model group presented typical pulmonary fibrotic lesions. Pathological lung injury of rats was alleviated in all three intervention groups (pirfenidone group, low- and high-dose berberine group) compared with the model group. The improvement in the high-dose berberine group was superior to that in the low-dose berberine group and was comparable with that in the pirfenidone group. rats in the model group showed increased lung organ coefficient, serum MDA, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) (all P<0.05), as well as increased expression of typeⅠcollagen (COLⅠ), α-smooth muscle actin (α-SMA) and PI3K, and p-AKT/AKT ratio in lung tissues (all P<0.05) when compared with the control group. The above indicators were lower in rats in both the low- and high-dose berberine groups than those in the model group (all P<0.05). Serum MDA, IL-1β, and TNF-α, as well as relative expression of COLⅠ and α-SMA in lung tissues, were lower in the high-dose berberine group than in the low-dose berberine group (all P<0.05). Conclusion Berberine may alleviate pulmonary inflammation and fibrosis in rats through regulation of the PI3K/AKT signaling pathway, thereby delaying the progression of silicosis.

Objective:To explore the prognostic predictive value of deep neural network (DNN) assisted myocardial contrast echocardiography (MCE) quantitative analysis of ST-elevated myocardial infarction (STEMI) patients after successful percutaneous coronary intervention(PCI).Methods:A retrospective analysis was performed in 97 STEMI patients with thrombolysis in myocardial infarction-3 flow in infarct vessel after primary PCI in Renmin Hospital of Wuhan University from June to November 2021. MCE was performed within 48 h after PCI. Patients were followed up to 120 days. The adverse events were defined as cardiac death, hospitalization for congestive heart failure, reinfarction, stroke and recurrent angina. The framework consisted of the U-net and hierarchical convolutional LSTMs. The plateau myocardial contrast intensity (A), micro-bubble rate constant (β), and microvascular blood flow (MBF) for all myocardial segments were obtained by the framework, and then underwent variability analysis. Patients were divided into low MBF group and high MBF group based on MBF values, the baseline characteristics and adverse events were compared between the two groups. Other variables included biomarkers, ventricular wall motion analysis, MCE qualitative analysis, and left ventricular ejection fraction. The relationship between various variables and prognosis was investigated using Cox regression analysis. The ROC curve was plotted to evaluate the diagnostic efficacy of the models, and the diagnostic efficacy of the models was compared using the integrated discrimination improvement index (IDI).Results:The time-cost for processing all 3 810 frames from 97 patients was 377 s. 92.89% and 7.11% of the frames were evaluated by an experienced echocardiographer as "good segmentation" and "correction needed". The correlation coefficients of A, β, and MBF ranged from 0.97 to 0.99 for intra-observer and inter-observer variability. During follow-up, 20 patients met the adverse events. Multivariate Cox regression analysis showed that for each increase of 1 IU/s in MBF of the infarct-related artery territory, the risk of adverse events decreased by 6% ( HR 0.94, 95% CI =0.91-0.98). There was a 4.5-fold increased risk of adverse events in the low MBF group ( HR 5.50, 95% CI=1.55-19.49). After incorporating DNN-assisted MCE quantitative analysis into qualitative analysis, the IDI for prognostic prediction was 15% (AUC 0.86, sensitivity 0.78, specificity 0.73). Conclusions:MBF of the area supplied by infarct-related artery after STEMI-PCI is an independent protective factor for short-term prognosis. The DNN-assisted MCE quantitative analysis is an objective, efficient, and reproducible method to evaluate microvascular perfusion. Assessment of culprit-MBF after PCI in STEMI patients adds independent short-term prognostic information over qualitative analysis.It has the potential to be a valuable tool for risk stratification and clinical follow-up.

Objective:To investigate the diagnostic value of postsystolic shortening (PSS) and early systolic lengthening (ESL) on myocardial microvascular dysfunction in patients with ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI).Methods:A total of 83 patients with STEMI who received emergency PCI in Renmin Hospital of Wuhan University from June to October 2021 were retrospectively collected. All patiets underwent two-dimensional echocardiography and myocardial contrast echocardiography (MCE) within 7 days after PCI. The patients were divided into global normal perfusion group and poor perfusion group according to global myocardial perfusion score index (MPSI). Left ventricular myocardium was divided into left anterior descending branch (LAD), left circumflex branch (LCx) and right coronary artery (RCA) regions, which were divided into regional normal perfusion group and poor perfusion group based on whether there were segments with microvascular dysfunction. Left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were measured by modified biplane Simpson method. Tomtec software was used to obtain conventional echocardiographic parameters, global longitudinal strain (GLS), as well as PSS and ESL parameters including postsystolic index (PSI), duration of postsystolic shortening (PSSduration), early systolic index (ESI) and duration of early systolic lengthening (ESLduration). Differences of parameters of global normal and poor perfusion groups, as well as regional normal and poor perfusion groups were compared. ROC curve was used to analyze the diagnostic value of PSS and ESL parameters and GLS in myocardial regions with microvascular dysfunction.Results:Significant differences were observed in LVEF, LVESV, GLS, PSI, ESI and PSSduration between global poor perfusion group and global normal perfusion group (all P<0.05). Compared with regional normal perfusion group, PSI, ESI and ESLduration of LAD and LCx regions, as well as PSI of RCA region in regional poor perfusion group were increased (all P<0.05). For GLS in different myocardial regions, LAD-GLS was the only parameter that decreased in regional poor perfusion group compared to regional normal perfusion group ( P<0.05). ROC curve analysis showed LAD-PSI, LAD-GLS, LCx-PSI, LCx-ESLduration and RCA-PSI were valuable parameters for diagnosis of myocardial microvascular dysfunction in different regions, among which LAD-PSI had the highest area under curve (AUC=0.809). Conclusions:PSS and ESL parameters are helpful for early diagnosis of myocardial microvascular dysfunction in STEMI patients after PCI, and can provide regional myocardial perfusion information according to the blood supply of different coronary arteries.

OBJECTIVE: To investigate the inhibitory effect of elemene on the tumor growth of human laryngeal squamous carcinoma (LSCC) and to explore the possible mechanism of its inhibitory effect on LSCC. METHOD: Nude mice model engrafted with laryngocarcinoma was established by using human laryngeal squamous carcinoma cell line (Hep-2). When the transplantable tumor size is more than 10 mm, the mice were given elemene (120 mg/kg) in the treatment group or PBS in the control group, at the day of 1, 4, 7, 10, 13, 16, 19 and 22 respectively. The animals were killed three days after the last treatment. The tumor volume, tumor weight,mice net weight and tumor inhibition rate were measured. The expression of vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor receptor-3 (VEGFR-3) mRNA were quantitated by using reverse transcription and polymerase chain reaction technique. RESULT: Elemene could inhibit the tumor growth in vivo. The differences were statistically significant for the mice net weight, tumor weight, and tumor volume between the treatment group and the control group. The tumor inhibition percentage was 52.24%. The gene expression of VEGF-C and VEGFR-3 of the treatment group is lower than that of the control group and the differences were statistically significant (P < 0.01). CONCLUSION Elemene could inhibit the subcutaneous plantation of human laryngeal carcinoma in nude mice and its mechanism may be associated with inhibited expression of VEGF-C and VEGFR-3.
Animals ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; Cell Line, Tumor ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Laryngeal Neoplasms ; drug therapy ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Phytotherapy ; Sesquiterpenes ; therapeutic use ; Vascular Endothelial Growth Factor C ; metabolism ; Vascular Endothelial Growth Factor Receptor-3 ; metabolism ; Xenograft Model Antitumor Assays