Sick sinus syndrome (SSS) is a disease with bradycardia or arrhythmia. The pathological mechanism of SSS is mainly due to the abnormal conduction function of the sinoatrial node (SAN) caused by interstitial lesions or fibrosis of the SAN or surrounding tissues, SAN pacing dysfunction, and SAN impulse conduction accompanied by SAN fibrosis. Tongyang Huoxue Decoction (TYHX) is widely used in SSS treatment and amelioration of SAN fibrosis. It has a variety of active ingredients to regulate the redox balance and mitochondrial quality control. This study mainly discusses the mechanism of TYHX in ameliorating calcium homeostasis disorder and redox imbalance of sinoatrial node cells (SANCs) and clarifies the protective mechanism of TYHX on the activity of SANCs. The activity of SANCs was determined by CCK-8 and the TUNEL method. The levels of apoptosis, ROS, and calcium release were analyzed by flow cytometry and immunofluorescence. The mRNA and protein levels of calcium channel regulatory molecules and mitochondrial quality control-related molecules were detected by real-time quantitative PCR and Western Blot. The level of calcium release was detected by laser confocal. It was found that after H/R treatment, the viability of SANCs decreased significantly, the levels of apoptosis and ROS increased, and the cells showed calcium overload, redox imbalance, and mitochondrial dysfunction. After treatment with TYHX, the cell survival level was improved, calcium overload and oxidative stress were inhibited, and mitochondrial energy metabolism and mitochondrial function were restored. However, after the SANCs were treated with siRNA (si-β-tubulin), the regulation of TYHX on calcium homeostasis and redox balance was counteracted. These results suggest that β-tubulin interacts with the regulation of mitochondrial function and calcium release. TYHX may regulate mitochondrial quality control, maintain calcium homeostasis and redox balance, and protect SANCs through β-tubulin. The regulation mechanism of TYHX on mitochondrial quality control may also become a new target for SSS treatment.
To evaluate the clinical significance of fusion indocyanine green (ICG) fluorescence imaging in precise right hemihepatectomy for the treatment of hepatocellular carcinoma (HCC). 47 patients with HCC who underwent right hemihepatectomy were retrospectively analyzed. 18 of them guided by fusion ICG fluorescence imaging (FIGFI) while 29 patients underwent conventional right hepatectomy without guidance. Compared to the patients with conventional treatment, the intraoperative blood loss of the patients with guided surgery was significantly less, and no transfusion and hepatic occlusion were performed during the operation. Liver function recovery faster in guided group. The incidence of postoperative complications is also lower, and the recurrence rate in one year is significantly reduced. ICG fluorescence range of 18 patients in liver surface was consistent with the ischemic line, and their postoperative liver cross-sections were clearly demarcation. There were no significant differences in the mean operation time, blood loss, postoperative hospital stays, cases of blood transfusion, complication rate, or postoperative peak volume of ALT and TB between positive or negative staining groups. Pathology results of all patients demonstrated HCC and negative margins, and microvascular invasion occurred in 8 cases. The average follow-up time of 18 patients was 16.7 months, and recurrence was found in 5 cases after surgery. FIGFI could guide the anatomical right hepatectomy with real-time increased radical rate, accuracy and safety for the treatment of HCC, and therefore showed a promising prospect.
Objective To investigate in the CT manifestations of severe and critical Coronavirus Disease 2019 (COVID-19) patients. Methods Medical data was collected for 2 severe patients and 4 critical COVID-19 patients from onset to their recovery. Three or four CT scans for each patient were taken. The semi-quantitative analysis method was introduced for lesion and its distribution area. Results The ground-glass opacities (GGO) and mixed GGO with consolidation were found as the most frequent features. Consolidation followed, and the appearance of stripes which showed an increasing trend before the patient was discharged. Consolidation was associated with clinical severity and disease progression, and the rapid change of the lesion in a short period of time was also a notable feature within 2–3 weeks. After being discharged, the efficacy of treatment could be demonstrated by a follow up CT scan. The distribution of lesion also showed dynamic progress in the follow up CT scan. Conclusion CT scans in the whole course provided the entire inflammation information to assess clinical severity, disease progression and the treatment efficacy for COVID-19.
Objective. This study focuses on the role of Zishen Huoxue Decoction (ZSHX) in reducing mitochondrial membrane potential and reducing the proportion of apoptosis through the mTORC1 signaling pathway. Methods. In our experiment, we first constructed an in vitro hypoxia/reoxygenation (H/R) model of H9C2 cells. Then, the cells were divided into control group, model group (hypoxia/reoxygenation, H/R), ZSHX, ZSHX + Rapa, low-dose ZSHX (100 μg/ml), and middle-dose ZSHX. High-dose ZSHX (400 μg/ml) group was treated with Zishen Huoxue Decoction (ZSHX). Western Blot was used to detect the expression of cell-related protein and RT-PCR was used to detect the expression of the cell-related gene in each group. Flow cytometry was used to assay for ROS content and the apoptotic ratio of H9C2 cells, Seahorse Live Cell Energy Meter was used to detect the Mitochondrial Respiratory Function in H9C2 Cells, and confocal laser scanning was used to detect the mitochondrial membrane potential of H9C2 cells. Results. Western Blot assay showed that the relative expression of mTOR and Raptor in the H/R group was significantly lower than that in the control group (n = 3, P<0.05). The expression of mTOR and Raptor was upregulated and the relative expression of 4E-BP1 was downregulated in the middle- and high-dose ZSHX groups (n = 3, P<0.05). In addition, the ROS content of H9C2 cells was detected by flow cytometry, showing the ROS synthesis in H/R group (78.31 + 6.14) higher than that in the control group (34.53 + 6.10) (n = 3, P<0.01). The ROS value was increased significantly after rapamycin inhibited mTOR (66.18 (+4.03 vs. 52.31 (+6.01), n = 3, P<0.05). The basal mitochondrial respiration and ATP production in H/R group were significantly lower than those in the control group (38.17 + 17.76); the mitochondrial leakage in H/R model group was significantly higher than that in the control group (H/R: 40.93 + 5.18 vs. Ctrl: 27.17 + 8.92, n = 4, P<0.05). The apoptotic rate of cardiomyocytes in the H/R model group (70.91 + 4.57) was significantly higher than that in the control group (14.52 + 2.37, n = 3, P<0.01), and Zishen Huoxue Decoction could decrease the apoptotic rate of hypoxic-reoxygenated cardiomyocytes (ZSHX: 18.24 + 4.17 vs. H/R: 78.91 + 3.48, n = 3, P<0.01). Conclusion. ZSHX Decoction has the effects of activating mTORC1, inhibiting the overexpression of 4E-BP1, inhibiting fatty acid oxidation, protecting the respiratory function of mitochondria, reducing ROS and apoptosis, and thus protecting myocardial cells from injury.
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