Tongguan capsule for treating myocardial ischemia-reperfusion injury: integrating network pharmacology and mechanism study.

CONTEXT: Although Tongguan capsule (TGC) is used in the treatment of coronary atherosclerotic disease, the exact mechanism remains unclear. OBJECTIVE: Network pharmacology and experimental validation were applied to examine the mechanism of TGC for treating myocardial ischemia-reperfusion injury (MIRI). MATERIALS AND METHODS: The components and candidate targets were searched based on various databases such as TCMSP, TCMID, BATMAN-TCM. The binding ability was determined by molecular docking. The ischemia-reperfusion (I/R) model was constructed by ligating the left anterior descending (LAD) coronary artery. APOE-/- mice were divided into three groups (n = 6): Sham group, I/R group, and TGC group (1 g/kg/d). To further verification, HCAEC cells were subjected to hypoxia-reoxygenation (H/R) to establish in vitro model. RESULTS: The compounds, such as quercetin, luteolin, tanshinone IIA, kaempferol and bifendate, were obtained after screening. The affinity values of the components with GSK-3ß, mTOR, Beclin-1, and LC3 were all <-5 kcal/mol. In vivo, TGC improved LVEF and FS, reducing infarct size. In vitro, Hoechst 33258 staining result showed TGC inhibited apoptosis. Compare with the H/R model, TGC treatment increased the levels of GSK-3ß, LC3, and Beclin1, while decreasing the expression of mTOR and p62 (p < 0.05). DISCUSSION AND CONCLUSION: The findings revealed that TGC exerted a cardioprotective effect by up regulating autophagy-related proteins through the mTOR pathway, which may be a therapeutic option for MIRI. However, there are still some limitations in this research. It is necessary to search more databases to obtain information and further demonstrated through randomized controlled trials for generalization.

[Recognition of Similarities and Differences--a New Thinking Paradigm of Critically Care Integrative Medicine].

"Wise men could recognize similarities, but the fool only recognizes differences" in Su-wen, which expounded clinical thinking methods of Chinese medicine (CM). "To recognize similarities and differences simultaneously" is of important clinical significance in understanding the laws of diseases. CM pays much attention to recognize similarities, while modern medicine emphasizes the differences observed. In order to develop integrative medicine (IM), similarities recognition and differences identification must be combined together to innovate new thinking methods of IM.

[Experimental study of the myocardial protection on septic rats by tongguan capsule].

OBJECTIVE: To study the myocardial protection on septic rats by Tongguan Capsule (TC). METHODS: Totally 120 SD rats were used to prepare the septic rat model using cecal, ligation and puncture (CLP). After modeling they were divided into three groups, i.e., the sham-operation group, the model group, the treatment group (treated by TC), 40 in each group. Each group was further divided into 5 subgroups according to different time points, i.e., 12 h, 24 h, 48 h, 72 h, and 7 days after CLP, 8 in each subgroup. CLP was performed in rats of the model group and the treatment group. The abdominal cavity of rats in the sham-operation group was opened. The incision of the abdominal wall was then sutured after their cecum was slightly flipped without puncture. Normal saline (at the daily dose of 10 mL/kg) was given by gastrogavage to rats in the model group and the sham-operation group. TC (at the daily dose of 600 mg/kg) was given to rats in the treatment group by gastrogavage, once daily, for 7 successive days. The hemodynamic changes such as left ventricular systolic pressure (LVSP), left ventricular pressure maximal rate of fall (- dp/dtmax), left ventricular pressure maximal rate of rise ( +dp/dtmax), inflammatory factors [such as tumor necrosis factor-alpha (TNF-alpha) and, IL-6, troponin I (CTn I )] were observed in all groups at each time point. The morphological changes of myocardial cells were observed under light and electron microscope 3 days later. RESULTS: Compared with the sham-operation group, the LVSP and +dp/dtmax decreased, and -dp/dtmax, CTn I , TNF-alpha, and IL-6 increased 24 -72 h after surgery in the model group, showing statistical difference (P<0.01). Compared with the model group, the LVSP and +dp/dtmax increased, and -dp/dtmax, CTn I , TNF-alpha, and IL-6 decreased 24 -72 h after surgery in the treatment group, showing statistical difference (P<0.05, P<0.01). Images under light microscope showed granular degeneration of myocardial cells could be occasionally seen in the treatment group. The transverse striation of myocardial cells was quite clear. The coronary artery was dilated and congested, with mild inflammation of interstitium. Images under electron microscope showed that the nucleus of myocardial cells was complete with quite clear Z-line in the treatment group. The number of the mitochondria increased. The mitochondria was swollen, but with more clear structure of cristae and mild fibrosis of interstitium. CONCLUSION: TC could improve the depression state of myocardial cells of septic rats, thus improving the prognosis of sepsis.

Heart Rate Variability in Patients with Acute Ischemic Stroke at Different Stages of Renal Dysfunction: A Cross-sectional Observational Study.

BACKGROUND: Renal function is associated with mortality and functional disabilities in stroke patients, and impaired autonomic function is common in stroke, but little is known regarding its effects on stroke patients with renal dysfunction. This study sought to evaluate the association between autonomic function and stroke in patients with renal dysfunction. METHODS: This study comprised 232 patients with acute ischemic stroke consecutively enrolled from February 2013 to November 2014 at Guangdong Provincial Hospital of Chinese Medicine in China. All patients recruited underwent laboratory evaluation and 24 h Holter electrocardiography (ECG). Autonomic function was measured based on the heart rate variability (HRV) using 24 h Holter ECG. Renal damage was assessed through the estimated glomerular filtration rate (eGFR), and stroke severity was rated according to the National Institutes of Health Stroke Scale (NIHSS). The Barthel index and modified Rankin score were also determined following admission. All the clinical covariates that could potentially affect autonomic outcome variables were adjusted with linear regression. RESULTS: In the patients with a mild or moderate decreased eGFR, the values for the standard deviation of the averaged normal-to-normal RR interval (SDANN) index (P = 0.022), very low frequency (VLF) (P = 0.043), low frequency (LF) (P = 0.023), and ratio of low-to-high frequency power (LF/HF) (P = 0.001) were significantly lower than those in the patients with a normal eGFR. A multinomial linear regression indicated that eGFR (t = 2.47, P = 0.014), gender (t = -3.60, P < 0.001), and a history of hypertension (t = -2.65, P = 0.008) were the risk factors of LF/HF; the NIHSS score (SDANN index: t = -3.83, P < 0.001; VLF: t = -3.07, P = 0.002; LF: t = -2.79, P = 0.006) and a history of diabetes (SDANN index: t = -3.58, P < 0.001; VLF: t = -2.54, P = 0.012; LF: t = -2.87, P = 0.004) were independent factors for the SDANN index, VLF, and LF; the Oxfordshire Community Stroke Project (t = -2.38, P = 0.018) was related to the SDANN index. CONCLUSIONS: Autonomic dysfunction is aggravated with the progression of eGFR stage in patients with acute ischemic stroke; the eGFR is an independent factor of LF/HF in the adjusted models. Stroke severity and a history of diabetes are more significantly associated with HRV in patients with acute ischemic stroke at different stages of renal dysfunction.

Strong correlation between lung ultrasound and chest computerized tomography imaging for the detection of acute lung injury/acute respiratory distress syndrome in rats.

BACKGROUND: Lung ultrasound (LUS) is a clinical imaging technique for diagnosing acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In humans and several large animals, LUS demonstrates similar specificity and sensitivity to computerized tomography (CT) scanning. Current study evaluated the degree of agreement between LUS and CT imaging in characterizing ALI/ARDS in rats. METHODS: Thirty male Sprague-Dawley rats were imaged by LUS before randomization into three groups to receive intratracheal saline, 3 or 6 mg/kg LPS respectively (n=10). LUS and CT imaging was conducted 2 hours after instillation. Cross table analyses and kappa statistics were used to determine agreement levels between LUS and CT assessments of lung condition. RESULTS: Before instillation, rats presented with a largely A-pattern in LUS images, however, a significantly increase B-lines were observed in all groups after instillation and showed dose response to LPS or to saline. One rat treated with 6 mg/kg lipopolysaccharide (LPS) presented with lung consolidation. The agreement between the LUS and the CT in detecting the main characteristics of ALI/ARDS in rat was strong (r=0.758, P<0.01, k=0.737). CONCLUSIONS: In conclusion, LUS detects ALI/ARDS with high agreement with micro PET/CT scanning in a rat model, suggesting that LUS represents a positive refinement in rat ALI/ARDS disease models.

Effects of tetramethylpyrazine on cardiac function and mortality rate in septic rats.

OBJECTIVE: To study the effects of tetramethylpyrazine (TMP) on cardiac function and mortality rate in septic rats. METHODS: Fifty male Sprague-Dawley rats were randomized into a sham-operation group (sham group, n=10), normal saline group (NS group, n=20), and TMP group (n=20). The rats in the NS and TMP groups underwent cecal ligation and puncture (CLP) to induce sepsis. Rats in the NS group were injected with NS (10 mL/kg) immediately after CLP and 6 h after CLP. Rats in the TMP group were injected with TMP (10 mg/kg) at the same time points. Twenty-four hours after modeling, the mortality rates were observed in each group. Cardiac function and serum concentration of tumor necrosis factor α (TNF-α) were also tested. The correlation between TNF-α and the ejection fraction (EF) was observed. Left ventricle specimens were reserved for histomorphologic study. RESULTS: Compared with the sham group, the NS and TMP groups had decreased EF values and increased mortality rates and serum TNF-α levels (P <0.05). The TMP group had a comparatively lower mortality rate and TNF-α level and a higher EF value compared with the NS group (P <0.05). Histomorphology indicated that myocardial inflammation in the TMP group was mild compared with that in the NS group. There was a negative correlation between TNF-α level and EF value (r=-0.583,P=0.000). CONCLUSION: TMP could reduce the mortality rate of septic rats and had certain protective effects on cardiac function.

[Retrospective investigation and analysis of endemic situation of schistosomiasis in hilly regions of Sichuan Province].

OBJECTIVE: To explore the rules of the changes of schistosomiasis infection and Oncomelania snails in areas where schistosomiasis transmission was controlled or interrupted or rebounded after interruption. METHODS: Qingbaijiang District, Longquanyi District and Xide County were selected and investigated retrospectively to collect schistosomiasis epidemiological information 10 years before they reached the criterion of transmission control and the subsequent years until 2008. The database of retrospective investigation was established for analyzing the trends and rules of changes of snail status and human infection status. RESULTS: In Qingbaijiang District, there was a positive correlation between density of living snails and snail area (r = 0.74, P < 0.01), and the infection rate of population was declining. In Longquanyi District, the snail area presented a declining trend. In Xide County, the human infection rate was positively correlated with snail area (R = 0.53, P < 0.01) and the density of living snails (r = 0.42, P < 0.05) respectively. CONCLUSIONS: The rebound of snail situation is always prior to the emerging of human infection, and it prompts that the rebound of snail situation can be considered one of the important indicators of early warning of the rebound of human infection situation in those places where schistosomiasis transmission was controlled or interrupted. Implementing comprehensive control of the snail habitat, as well as eliminating the potential infectious source is an important measure to consolidate the achievement of schistosomiasis control.