Endophilin A2 protects against renal fibrosis by targeting TGF-ß/Smad signaling.

Renal fibrosis underlies all forms of end-stage kidney disease. Endophilin A2 (EndoA2) plays a role in nephrotic syndrome; however, its effect on renal fibrosis remains unknown. Here, we demonstrate that EndoA2 protects against kidney interstitial fibrosis via the transforming growth factor-ß (TGF-ß)/Smad signaling pathway. Mouse kidneys with fibrosis or kidney biopsy specimens from patients with fibrotic nephropathy had lower levels of EndoA2 protein expression than that in kidneys without fibrosis. In vivo overexpression of EndoA2 with the endophilin A2 transgene (EndoA2Tg ) notably prevented renal fibrosis, decreased the protein expression of profibrotic molecules, suppressed tubular injury, and reduced apoptotic tubular cells in the obstructed kidney cortex of mice with unilateral ureteral obstruction (UUO). In vivo and in vitro overexpression of EndoA2 markedly inhibited UUO- or TGF-ß1-induced phosphorylation of Smad2/3 and tubular epithelial cells dedifferentiation. Furthermore, EndoA2 was co-immunoprecipitated with the type II TGF-ß receptor (TßRII), thus inhibiting the binding of the type I TGF-ß receptor (TßRI) to TßRII. These findings indicate that EndoA2 mitigates renal fibrosis, at least partially, via modulating the TGF-ß/Smad signaling. Targeting EndoA2 may be a new potential therapeutic strategy for treatment of renal fibrosis.

Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction: The CTS-AMI Randomized Clinical Trial.

Importance: Tongxinluo, a traditional Chinese medicine compound, has shown promise in in vitro, animal, and small human studies for myocardial infarction, but has not been rigorously evaluated in large randomized clinical trials. Objective: To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled clinical trial was conducted among patients with STEMI within 24 hours of symptom onset from 124 hospitals in China. Patients were enrolled from May 2019 to December 2020; the last date of follow-up was December 15, 2021. Interventions: Patients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months (a loading dose of 2.08 g after randomization, followed by the maintenance dose of 1.04 g, 3 times a day), in addition to STEMI guideline-directed treatments. Main Outcomes and Measures: The primary end point was 30-day major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke. Follow-up for MACCEs occurred every 3 months to 1 year. Results: Among 3797 patients who were randomized, 3777 (Tongxinluo: 1889 and placebo: 1888; mean age, 61 years; 76.9% male) were included in the primary analysis. Thirty-day MACCEs occurred in 64 patients (3.4%) in the Tongxinluo group vs 99 patients (5.2%) in the control group (relative risk [RR], 0.64 [95% CI, 0.47 to 0.88]; risk difference [RD], -1.8% [95% CI, -3.2% to -0.6%]). Individual components of 30-day MACCEs, including cardiac death (56 [3.0%] vs 80 [4.2%]; RR, 0.70 [95% CI, 0.50 to 0.99]; RD, -1.2% [95% CI, -2.5% to -0.1%]), were also significantly lower in the Tongxinluo group than the placebo group. By 1 year, the Tongxinluo group continued to have lower rates of MACCEs (100 [5.3%] vs 157 [8.3%]; HR, 0.64 [95% CI, 0.49 to 0.82]; RD, -3.0% [95% CI, -4.6% to -1.4%]) and cardiac death (85 [4.5%] vs 116 [6.1%]; HR, 0.73 [95% CI, 0.55 to 0.97]; RD, -1.6% [95% CI, -3.1% to -0.2%]). There were no significant differences in other secondary end points including 30-day stroke; major bleeding at 30 days and 1 year; 1-year all-cause mortality; and in-stent thrombosis (<24 hours; 1-30 days; 1-12 months). More adverse drug reactions occurred in the Tongxinluo group than the placebo group (40 [2.1%] vs 21 [1.1%]; P = .02), mainly driven by gastrointestinal symptoms. Conclusions and Relevance: In patients with STEMI, the Chinese patent medicine Tongxinluo, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly improved both 30-day and 1-year clinical outcomes. Further research is needed to determine the mechanism of action of Tongxinluo in STEMI. Trial Registration: ClinicalTrials.gov Identifier: NCT03792035.

Beneficial Effects of Baduanjin Exercise on Left Ventricular Remodelling in Patients after Acute Myocardial Infarction: an Exploratory Clinical Trial and Proteomic Analysis.

BACKGROUND: The beneficial effects of physical exercise on cardiac remodelling improvement after myocardial infarction have already been suggested. However, the results of previous clinical trials have not been consistent. Moreover, the putative molecular mechanisms leading to the clinically observed effects of physical exercise still remain elusive. AIM: We aimed to evaluate whether the well-defined and strictly controlled traditional Chinese Qigong Baduanjin exercise (BE) would attenuate the adverse left ventricular (LV) remodelling in patients with ST-elevation myocardial infarction (STEMI). METHODS: A total of 110 clinically stable STEMI patients, following successful revascularization of their infarcted coronary arteries, were randomized and enrolled in two groups: 56 were subjected to a 12-week BE-based cardiac rehabilitation programme (BE group), and the remaining 54 were exposed to the usual physical exercise (control group) for the same time period. The primary outcome was the change from baseline to 6 months in the echocardiographic LV end-diastolic volume index (ΔLVEDVi). Proteomic analysis was also performed to uncover associated mechanisms. RESULTS: Compared with the control group, the BE group showed significantly lower ΔLVEDVi (-5.1 ± 1.1 vs. 0.3 ± 1.2 mL/m2, P < 0.01). Proteomic analysis revealed BE-induced variations in the expression of 80 proteins linked to regulation the of metabolic process, immune process, and extracellular matrix reorganization. Furthermore, correlation analyses between the validated serum proteomes and primary endpoint demonstrated a positive association between ΔLVEDVi and MMP-9 expression, but a negative correlation between ΔLVEDVi and CXCL1 expression. CONCLUSION: This is the first study indicating that BE in STEMI patients can alleviate adverse LV remodelling associated with beneficial energy metabolism adaptation, inflammation curbing, and extracellular matrix organization adjustment.

Efficacy of Sodium Tanshinone IIA Sulfonate in Patients with Non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Results from a Multicentre, Controlled, Randomized Trial.

BACKGROUND: Sodium tanshinone IIA sulfonate (STS) has been widely used by Chinese medicine practitioners for chronic cardiovascular diseases. However, its direct clinical efficacy in patients with acute coronary syndrome following percutaneous coronary intervention (PCI) has not been reported yet. The present trial aimed to investigate potential cardioprotection of STS in patients undergoing PCI for non-ST elevation acute coronary syndrome (NSTE-ACS). METHODS: In a randomized, double-blind, placebo-controlled trial, 372 patients with NSTE-ACS were randomly assigned to receive STS (n = 192) or saline (n = 180) for 2 days before and 3 days after PCI along with standard therapy. The primary endpoint was the composite incidence of major adverse cardiac events (MACEs), including death, non-fatal myocardial infarction, repeated revascularization of the target vessel, and stent thrombosis, within 30 days after PCI. RESULTS: The 30-day MACEs occurred in 18.8% of the patients in the STS group and in 27.2% of the patients in the control group (P = 0.038); this difference was mostly driven by reduction of myocardial infarction incidence (17.2% vs. 26.7%, P = 0.027). Post-procedural elevation of troponin-I was also significantly lower in the STS group (26.56% vs. 47.78%, P < 0.001). Multivariable analysis identified STS as a predictor of decreased risk of MACE occurrence (odds ratio: 0.60, 95% confidence interval: 0.36 to 0.99; P = 0.045). CONCLUSION: Addition of STS to the standard treatments recommended by the current practice guidelines in patients with NSTE-ACS undergoing PCI could reduce myocardial injury and the occurrence of short-term cardiovascular events, primarily driven by non-fatal myocardial infarction. TRIAL REGISTRATION: ChiCTR-TRC-14005182.

In-depth proteomics approach reveals novel biomarkers of cardiac remodelling after myocardial infarction: An exploratory analysis.

Cardiac remodelling following myocardial infarction (MI) is a maladaptive change associated with progressive heart failure and compromises long-term clinical outcome. A substantial proportion of patients afflicted by MI still develop adverse outcomes associated with cardiac remodelling. Therefore, it is crucial to identify biomarkers for the early prediction of cardiac remodelling. An in-depth proteomics approach, including both semi-quantitative and quantitative antibody arrays, was used to identify circulating biomarkers that may be associated with detrimental cardiac remodelling. Furthermore, statistical correlation analysis was performed between the candidate biomarkers and clinical cardiac remodelling data to demonstrate their clinical utility. A systematic proteomics approach revealed that sclerostin (SOST), growth differentiation factor-15 (GDF-15), urokinase-type plasminogen activator (uPA), and midkine (MK) were increased, while monocyte chemotactic protein-3 (MCP-3) was uniquely decreased in MI patients who developed cardiac remodelling, compared to MI patients who did not develop cardiac remodelling and healthy humen. Moreover, correlation analyses between serum proteomes and cardiac remodelling echocardiographic parameters demonstrated a moderate positive association between left ventricular end-diastolic volume index (LVEDVi) and the three serum proteins, uPA, MK and GDF-15 (P < .05, respectively), and a moderate negative correlation between LV ejection fraction (LVEF) and these serum proteins (P < .05, respectively). Importantly, uPA and MK were firstly identified to be associated with the development of cardiac remodelling. The present study contributes to a better understanding of the various cytokines expressed during adverse cardiac remodelling. The identified biomarkers may facilitate early identification of patients at high risk of ischaemic heart failure pending further confirmation through larger clinical trials.

Sodium tanshinone IIA sulfonate prevents the adverse left ventricular remodelling: Focus on polymorphonuclear neutrophil-derived granule components.

AIMS: The aims of this study were to evaluate the effects of sodium tanshinone IIA sulfonate (STS) on left ventricular (LV) remodelling after for ST-elevated myocardial infarction (STEMI). METHODS AND RESULTS: In this prospective, randomized clinical trial, 101 patients with the ST-elevated MI (STEMI) and a successful reperfusion were immediately randomized to receive STS (80 mg qd for 7 days) or saline control, along with standard therapy. The primary effectiveness endpoint is the % change in LV end diastolic volumes index (%∆ LVEDVi) as measured by echocardiography from baseline to 6 months. Secondary effectiveness endpoints include 6-month period for major adverse cardiac events (MACE), including the occurrence of recurrent myocardial infarction, death, hospitalization for heart failure and malignant arrhythmia. The 6-month changes in %∆ LVEDVi were significantly smaller in the STS group than in the control group [-5.05% vs 3.32%; P < 0.001]. With respect to MACE, there was a significant difference between those who received STS (8.16%) and those patients on control (26.00%) (P = 0.019). Meaningfully, results of parallel tests aimed at mechanistic explanation of the reported clinical effects, revealed a significantly reduced levels of neutrophils-derived granule components in the blood of STS treated patients. CONCLUSION: We found that short-term treatment with STS reduced progressive left ventricular remodelling and subsequent better clinical outcome that could be mechanistically linked to the inhibition of the ultimate damage of infarcted myocardium by infiltrating neutrophils.

Tongguan capsule-derived herb reduces susceptibility to atrial fibrillation by inhibiting left atrial fibrosis via modulating cardiac fibroblasts.

Tongguan capsule is a compound Chinese medicine used to treat ischaemic heart diseases. This study aimed to investigate whether Tongguan capsule-derived herb (TGD) has a preventive effect on atrial fibrillation (AF) in post-myocardial infarction (MI) rats and to determine the underlying mechanisms. MI was induced by ligation of the left anterior descending coronary artery. TGD was administered to the post-MI rats over a 4-week period. The TGD-treated rats had lower rates of AF inducibility and shorter AF durations than the MI rats. TGD improved the left atrial (LA) conduction velocity and homogeneity. It reduced the fibrosis-positive areas and the protein levels of collagen types I and III in the left atrium. In vitro, it inhibited the expression of collagen types I and III by inhibiting the proliferation, migration, differentiation and cytokine secretion of cardiac fibroblasts (CFs). In conclusion, the current study demonstrated that TGD reduces susceptibility to AF and improves LA conduction function in rats with post-MI by inhibiting left atrial fibrosis and modulating CFs. Targeting the CF population may be a novel antiarrhythmic therapeutic approach.

Danqi soft capsule prevents infarct border zone remodelling and reduces susceptibility to ventricular arrhythmias in post-myocardial infarction rats.

Danqi soft capsule (DQ) is a traditional Chinese medicine containing Salvia miltiorrhiza and Panax notoginseng; it is safe and efficient in treating ischaemic heart diseases. The purpose of the present study was to assess whether DQ could prevent infarct border zone (IBZ) remodelling and decrease ventricular arrhythmias occurrence in post-myocardial infarction (MI) stage. MI was induced by a ligation of the left anterior descending coronary artery. DQ was administered to the post-MI rats started from 1 week after MI surgery for 4 weeks. The results showed that DQ treatment significantly attenuated tachyarrhythmia induction rates and arrhythmia score in post-MI rats. In echocardiography, DQ improved left ventricular (LV) systolic and diastolic function. Histological assessment revealed that DQ significantly reduced fibrotic areas and myocyte areas, and increased connexin (Cx) 43 positive areas in IBZ. Western blot revealed that DQ treatment significantly reduced the protein expression levels of type I and III collagens, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and Smad3 phosphorylation, while increasing Cx43 amounts. Overall, these findings mainly indicated that DQ intervention regulates interstitial fibrosis, Cx43 expression and myocyte hypertrophy by TGF-ß1/Smad3 pathway in IBZ, inhibits LV remodelling and reduces vulnerability to tachyarrhythmias after MI. This study presents a proof of concept for novel antiarrhythmic strategies in preventing IBZ remodelling, modifying the healed arrhythmogenic substrate and thus reducing susceptibility to ventricular arrhythmias in the late post-MI period.

XueBiJing Injection Versus Placebo for Critically Ill Patients With Severe Community-Acquired Pneumonia: A Randomized Controlled Trial.

OBJECTIVES: To investigate whether XueBiJing injection improves clinical outcomes in critically ill patients with severe community-acquired pneumonia. DESIGN: Prospective, randomized, controlled study. SETTING: Thirty-three hospitals in China. PATIENTS: A total of 710 adults 18-75 years old with severe community-acquired pneumonia. INTERVENTIONS: Participants in the XueBiJing group received XueBiJing, 100 mL, q12 hours, and the control group received a visually indistinguishable placebo. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 8-day improvement in the pneumonia severity index risk rating. Secondary outcomes were 28-day mortality rate, duration of mechanical ventilation and total duration of ICU stay. Improvement in the pneumonia severity index risk rating, from a previously defined endpoint, occurred in 203 (60.78%) participants receiving XueBiJing and in 158 (46.33%) participants receiving placebo (between-group difference [95% CI], 14.4% [6.9-21.8%]; p < 0.001). Fifty-three (15.87%) XueBiJing recipients and 84 (24.63%) placebo recipients (8.8% [2.4-15.2%]; p = 0.006) died within 28 days. XueBiJing administration also decreased the mechanical ventilation time and the total ICU stay duration. The median mechanical ventilation time was 11.0 versus 16.5 days for the XueBiJing and placebo groups, respectively (p = 0.012). The total duration of ICU stay was 12 days for XueBiJing recipients versus 16 days for placebo recipients (p = 0.004). A total of 256 patients experienced adverse events (119 [35.63%] vs 137 [40.18%] in the XueBiJing and placebo groups, respectively [p = 0.235]). CONCLUSIONS: In critically ill patients with severe community-acquired pneumonia, XueBiJing injection led to a statistically significant improvement in the primary endpoint of the pneumonia severity index as well a significant improvement in the secondary clinical outcomes of mortality, duration of mechanical ventilation and duration of ICU stay.

Prognostic value of HbA1c for in-hospital and short-term mortality in patients with acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: HbA1c, the most commonly used indicator of chronic glucose metabolism, is closely associated with cardiovascular disease. However, the relationship between HbA1c and the mortality of acute coronary syndrome (ACS) patients has not been elucidated yet. Here, we aim to conduct a systematic review assessing the effect of HbA1c on in-hospital and short-term mortality in ACS patients. METHODS: Relevant studies reported before July 2019 were retrieved from databases including PubMed, Embase, and Central. Pooled relative risks (RRs) and the corresponding 95% confidence interval (CI) were calculated to evaluate the predictive value of HbA1c for the in-hospital mortality and short-term mortality. RESULTS: Data from 25 studies involving 304,253 ACS patients was included in systematic review. The pooled RR of in-hospital mortality was 1.246 (95% CI 1.113-1.396, p: 0.000, I2 = 48.6%, n = 14) after sensitivity analysis in studies reporting HbA1c as categorial valuable. The pooled RR was 1.042 (95% CI 0.904-1.202, p: 0.57, I2 = 82.7%, n = 4) in random-effects model for studies reporting it as continuous valuable. Subgroup analysis by diabetic status showed that elevated HbA1c is associated increased short-term mortality in ACS patients without diabetes mellitus (DM) history and without DM (RR: 2.31, 95% CI (1.81-2.94), p = 0.000, I2 = 0.0%, n = 5; RR: 2.56, 95% CI 1.38-4.74, p = 0.003, I2 = 0.0%, n = 2, respectively), which was not the case for patients with DM and patients from studies incorporating DM and non-DM individuals (RR: 1.16, 95% CI 0.79-1.69, p = 0.451, I2 = 31.9%, n = 3; RR: 1.10, 95% CI 0.51-2.38), p = 0.809, I2 = 47.4%, n = 4, respectively). CONCLUSIONS: Higher HbA1c is a potential indicator for in-hospital death in ACS patients as well as a predictor for short-term mortality in ACS patients without known DM and without DM.

Baduanjin Exercise Prevents post-Myocardial Infarction Left Ventricular Remodeling (BE-PREMIER trial): Design and Rationale of a Pragmatic Randomized Controlled Trial.

BACKGROUND: Left ventricular (LV) remodeling following myocardial infarction (MI) is an established prognostic factor for adverse cardiovascular events and the leading cause of heart failure. Empirical observations have suggested that Baduanjin exercise, an important component of traditional Chinese Qigong, may exert potential benefits on cardiopulmonary function. However, the impact of a Baduanjin exercise-based cardiac rehabilitation program for patients recovering from a recent MI has yet to be assessed. The aim of this trial is to evaluate the potential role of Baduanjin exercise in preventing the maladaptive progression to adverse LV remodeling in patients post-MI. METHODS: A total of 110 clinically stable patients following an MI after undergoing successful infarct-related artery reperfusion will be randomly assigned to the Baduanjin exercise group or usual exercise control group. In addition to usual physical activity, participants in the Baduanjin exercise group will participate in a 45 min Baduanjin exercise training session twice a week, for a total of 12 weeks. The primary endpoint will be the percentage change in LV end-diastolic volume index (LVEDVi) assessed using echocardiography from baseline to 6 months. CONCLUSION: The results of this study may provide novel evidence on the efficacy of Baduanjin exercise therapy in post-MI patients in reversing adverse LV remodeling and improving clinical outcome. TRIAL REGISTRATION: Clinical Trials.gov: NCT02693795.

Relation of N-terminal pro-brain natriuretic peptide and new-onset atrial fibrillation in patients with acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: Several observational studies evaluated the associations of baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) and new-onset atrial fibrillation (AF) in patients with acute coronary syndrome (ACS), but the results were contradictory. METHODS: Electronic bibliographic databases were searched from inception to May 2015, and the results reviewed by two independent reviewers. Pooled standardized mean difference (SMD) and 95% confidence interval (CI) were calculated to assess associations between NT-proBNP levels and new-onset AF in patients with ACS. We performed sensitivity analyses to explore the potential sources of heterogeneity and estimated publication biases. RESULTS: Six papers, including 5861 patients (438 with AF and 5423 without AF) with ACS were analyzed. Overall, the NT-proBNP levels were higher in patients with new-onset AF than controls without AF. The SMD of the NT-proBNP levels between the patients with and those without AF was 0.53 units (95% CI 0.37-0.70), test for overall effect z-score =6.30 (p < 0.00001). The heterogeneity test showed that there were moderate differences between individual studies (p = 0.02; I(2) =( )62%). Further analysis revealed that differences of ethnic groups and the sample size of studies possibly account for this heterogeneity. CONCLUSIONS: In spite of moderate heterogeneity across the enrolled studies, our meta-analysis suggests that increased NT-proBNP levels are associated with greater risk of new-onset AF with ACS, which indicates that NT-proBNP levels may be a useful biomarker in predicting new-onset AF in patients with ACS.

Traditional Chinese medicine, Danlou tablets alleviate adverse left ventricular remodeling after myocardial infarction: results of a double-blind, randomized, placebo-controlled, pilot study.

BACKGROUND: Danlou tablets, a patented Chinese Medicine, have been long approved for the treatment of ischemic heart disease in China. While numerous empirical observations suggested Danlou tablets could decrease frequency and duration of angina pectoris attacks, evidence supporting its efficacy on cardiac remodeling remains inadequate. Therefore, this pilot trial was designed to determine whether Danlou tablets would reduce adverse left ventricular (LV) remodeling in patients with myocardial infarction (MI). METHODS AND RESULTS: Eligible patients with acute MI were enrolled and randomly assigned to Danlou tablets or placebo groups, superimposed on standard treatment for MI. Then, in addition to assessment of the clinical outcome, the changes in LV volumes were evaluated by a serial echocardiography. In total, 83 patients (Danlou tablets 42 and placebo 41) completed 90 days of treatment and had complete baseline and outcome data. Standard echocardiographic evaluations revealed significant differences in the change of LV end-diastolic volume index (LVEDVi) between group of patients treated with Danlou tablets and the placebo group (-4.49 ± 7.29 vs. -0.34 ± 9.01 mL/m2, P < 0.001). The reduction in LVEDVi was independent of beta-blocker, ACE inhibitors/ARBs use. Furthermore, treatment with Danlou tablets significantly reduced LV end-systolic volume index (-4.09 ± 5.85 vs. -0.54 ± 5.72 mL/m2, P < 0.001) and improved the LV ejection fraction (4.83 ± 9.23 vs. 0.23 ± 8.15 %, P < 0.001), as compared to placebo. Meaningfully, the incidence of the major adverse cardiovascular events was also lower in patients receiving Danlou tablets (P < 0.05). CONCLUSION: Superimposed on the standard pharmacologic treatment, Danlou tablets significantly reversed post-MI adverse LV remodeling, thereby contributed to the overall positive clinical outcome. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT02675322 (February 1, 2016).

[Construction of Research-Oriented State Key Clinical Department by Highlighting the Characteris- tics and Advantages of Chinese Medicine].

As the largest research-oriented specialty department in national traditional Chinese medicine hospitals, the Department of Critical Care Medicine in Guangdong Provincial Hospital of Chinese Medicine insists on the development mode combined with clinical medicine and scientific research. By taking clinical and basic researches for integrative medicine preventing and treating acute myocardial in-farction and sepsis as a breakthrough, authors explored key problems of Chinese medicine in improving the prognosis related diseases and patients' quality of life. In recent 3 years our department has successively become the principal unit of the national key specialties cooperative group of critical care medicine (awarded by State Administration of Traditional Chinese Medicine), the key clinical specialties (awarded by National Health and Family Planning Commission), and Guangzhou key laboratory construction unit, and achieved overall lap in clinical medical treatment, personnel training, scientific research, and social service.

[Cluster Analysis of Medication Laws for Treating Coronary Heart Disease by Distinguished Veteran Doctors of Traditional Chinese Medicine].

OBJECTIVE: To provide inspiration and ideas for clinical treatment of coronary heart disease (CHD) by data mining technology based frequency analysis and cluster analysis of medical records, prescriptions and herbs in treating CHD by distinguished veteran doctors of traditional Chinese Dedicine (TCM). METHODS: Totally 386 medical cases were retrieved from Wanfang Data, Chinese Scientific Journals Database (VIP medical information resources system, China National Knowledge Infrastructure (CNKI), and Typical Collections of Medical Cases by Contemporary Distinguished Veteran Doctors of Traditional Chinese Medicine. They input into database trimmed after unified standard. Medication laws of CHD by distinguished veteran doctors of TCM were analyzed using frequency analysis and cluster analysis, and so on. RESULTS: Distinguished veteran doctors of TCM frequently used top ten herbs in treatment of C D as Salvia miltiorrhiz , Ligusticum wallichii, Trichosanthes kirilowi, Pinellia ternat, Angelica sinensis, Poria coco stragalu , Panax ginseng, Allium macrostemon, and Radix Ophiopogonis. Cluster analysis summarized that there were 16 herb pairs commonly used, 7drug assemblies consisting of 3 herbs and 5 drug assemblies consisting of multiple herbs. CONCLUSIONS: Distinguished veteran doctors of TCM mainly used herbs assemblies capable for invigorating Pi to resolve phlegm, and promoting qi and activating blood circulation in treating CHD. Meanwhile, they concurrently used herbs combination of nourishing Xin and tranquilization, and regulating yin and yang.

Rationale and Design of Sodium Tanshinone IIA Sulfonate in Left Ventricular Remodeling Secondary to Acute Myocardial Infarction (STAMP-REMODELING) Trial: A Randomized Controlled Study.

BACKGROUND: Left ventricular (LV) remodeling in ischemic cardiomyopathy is the leading cause of heart failure and is an established prognostic factor for adverse cardiovascular events. Experimental studies suggest that sodium tanshinone IIA sulfonate attenuates cardiac remodeling in animal models of acute myocardial infarction (AMI). However, the effects of this drug in the clinical setting remain unclear. Therefore, the STAMP-REMODELING trial is set up to investigate whether treatment with sodium tanshinone IIA sulfonate would prevent the maladaptive progression to adverse LV remodeling in patients following ST-segment elevation myocardial infarction (STEMI). METHODS: Approximately 80 patients with STEMI successfully treated with primary percutaneous coronary intervention (PCI) will be enrolled and randomized to receive sodium tanshinone IIA sulfonate (80 mg q.d. for 7 days) in addition to standard therapy or the same volume of hydration per day. The primary endpoint is the variation in LV end-diastolic volume index (LVEDVi) assessed with cardiac magnetic resonance imaging (CMR) at baseline and 6 months. CONCLUSION: This study will provide important clinical evidence on the efficacy of sodium tanshinone IIA sulfonate treatment in patients with STEMI when used in combination with current therapies that may significantly reduce adverse LV remodeling and potentially improve clinical outcomes. TRIAL REGISTRATION: Clinical Trials.gov: NCT02524964.

Phytoestrogen, tanshinone IIA diminishes collagen deposition and stimulates new elastogenesis in cultures of human cardiac fibroblasts.

It has been previously reported that oral or intra-peritoneal administration of tanshinone IIA can alleviate the ventricular hypertrophy and fibrosis that develops in rats after experimental cardiac infarction. Our present studies, performed on cultures of human cardiac fibroblasts, investigated the mechanism by which tanshinone IIA produces these beneficial effects. We found that treatment of cardiac fibroblasts with 0.1-10µM tanshinone IIA significantly inhibited their deposition of collagen I, while enhancing production of new elastic fibers. Moreover, both anti-collagenogenic and pro-elastogenic effects of tanshinone IIA occurred only after selective activation of the G protein-coupled estrogen receptor (GPER). This subsequently leads to initiation of the PKA/CREB phosphorylation pathway that inversely modulated transcription of collagen I and elastin genes. Interestingly, treatment of human cardiac fibroblasts with tanshinone IIA additionally up-regulated the production of the 67-kDa elastin binding protein, which facilitates tropoelastin secretion, and increased synthesis of lysyl oxidase, catalyzing cross-linkings of tropoelastin. Moreover, tanshinone IIA also caused up-regulation in the synthesis of collagenolytic MMP-1, but down-regulated levels of elastolytic MMP-2 and MMP-9. In summary, our data validate a novel mechanism in which tanshinone IIA, interacting with a non-classic estrogen receptor, maintains the proper balance between the net deposition of collagen and elastin, allowing for optimal durability and resiliency of the newly deposited matrix.

Preprocedural N-terminal pro-B-type natriuretic peptide as a useful marker for predicting periprocedural myocardial injury following percutaneous coronary intervention in diabetic patients without cardiac dysfunction.

BACKGROUND: Elevated preprocedural N-term pro-B-type natriuretic peptide (NT-pro-BNP) and postprocedural cardiac troponin I (cTnI) are related to a poor cardiac outcome in the non-diabetic population. We hypothesized that preprocedural NT-pro-BNP might be a useful marker in predicting periprocedural myocardial injury (PMI) following elective percutaneous coronary intervention (PCI) in type 2 diabetes (T2D). METHODS: We prospectively enrolled 1194 consecutive diabetic patients with normal cardiac function and preprocedural cTnI who were successfully undergoing elective PCI. Preprocedural NT-pro-BNP levels were assessed at admission, and PMI was evaluated by analysis of cTnI within 24 hours. The relationship between preprocedural NT-pro-BNP levels and the peak values of cTnI after PCI was examined. RESULTS: Patients with high baseline NT-pro-BNP levels had higher postprocedural cTnI levels (ß = 0.123, p < 0.001). In the multivariable model, NT-pro-BNP was associated with higher risk of postprocedural cTnI elevation above 1 × upper limit of normal (ULN, OR, 3.13; 95% CI, 1.51-6.50; p = 0.002), 3 × ULN (OR, 2.44; 95% CI, 1.17-5.08; p = 0.018), 5 × ULN (OR, 3.18; 95% CI, 1.44-7.0; p = 0.004), respectively. Moreover, the incidence of cTnI elevation was higher in patients with the upper tertile of NT-pro-BNP levels than that in ones with the lower tertile of NT-pro-BNP levels (> 1 × ULN: 63.1% vs. 50.0%, p < 0.001; > 3 × ULN: 39.2% vs. 31.9%, p = 0.032; > 5 × ULN: 30.4% vs. 21.9%, p < 0.006; respectively). CONCLUSIONS: Our data, for the first time, demonstrated that increased preprocedural NT-pro-BNP levels were strongly and independently associated with a higher risk of PMI, suggesting that baseline NT-pro-BNP level might be a useful marker for predicting PMI following PCI in diabetic patients without cardiac dysfunction.

Lung ultrasound is a reliable method for evaluating extravascular lung water volume in rodents.

BACKGROUND: Lung ultrasound (LUS) can diagnose extravacular lung water (EVLW) through the visualization of B lines in both humans and large animals. However, there are no published data on the use of ultrasound to detect EVLW in rats, the gold standard to evaluate of EVLW in rats is post-mortem gravimetric analysis. The present study was designed to determine the similarity between lung sonography and gravimetric measurements of EVLW in rats in an acute lung injury (ALI) model. METHODS: Thirty male Sprague-Dawley rats were randomized into control and experimental groups. The B lines were measured byLUS at baseline. ALI was induced by the intravenous administration of oleic acid (OA) at a dose of 9 ul/100 mg, and controls were injected the same amount of isotonic saline. After 1 h, B-lines were measured by LUS in each rat following the induction of ALI. At the end of each experiment, both lungs were dissected, weighed and dried to determine wet/dry weight ratio according to the standard gravimetric methodology. Lung samples from three rats in each group were examined histologically. RESULTS: B-lines were present in all rats from experimental group at 1 h point after OA injection. The statistical correlation between the two methods of assessing EVLW provided an r = 0.834 (p < 0.001). Repeatability studies of the LUS technique (Bland-Altman plots) showed good intra-observer and inter-observer reproducibility. CONCLUSION: The data suggest that, in an experimental rat model of ALI, B lines score as assessed by LUS can provide an easy, semi-quantitative, noninvasive. Real-time index of EVLW which is strongly correlated to experimental gravimetric assessments.

[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.