Systemic inflammation markers and the prevalence of hypertension: A NHANES cross-sectional study.

Systemic inflammation markers have been highlighted recently as related to cardiac and non-cardiac disorders. However, few studies have estimated pre-diagnostic associations between these markers and hypertension. In the National Health and Nutritional Examination Survey from 1999 to 2010, 22,290 adult participants were included for analysis. We assessed associations between four systemic inflammation markers based on blood cell counts: systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and hypertension prevalence in multivariate logistic regression analysis with odds ratio (OR) and 95% confidence interval (CI). To further explore their associations, subgroup and sensitivity analyses were performed. In continuous analyses, the ORs for hypertension prevalence per ln-transformed increment in SII and NLR were estimated at 1.115 and 1.087 (95% CI: 1.045-1.188; 1.008-1.173; respectively). Compared to those in the lowest tertiles, the hypertension risks for subjects in the highest SII and NLR tertiles were 1.20 and 1.11 times, respectively. Conversely, we found that PLR and LMR were negatively associated with hypertension prevalence in continuous analyses (1.060, 0.972-1.157; 0.926, 0.845-1.014; respectively), and the highest PLR and LMR tertiles (1.041, 0.959-1.129; 0.943, 0.866-1.028; respectively). Also, subgroup and sensitivity analyses indicated that SII had a greater correlation to hypertension. In conclusion, we find positive associations between SII and NLR and the prevalence of hypertension in this cross-sectional study. Our findings highlight that SII may be a superior systemic inflammation warning marker for hypertension.

U-Shaped Relationship of Non-HDL Cholesterol With All-Cause and Cardiovascular Mortality in Men Without Statin Therapy.

Background: Non-HDL-C is well established causal risk factor for the progression of atherosclerotic cardiovascular disease. However, there remains a controversial pattern of how non-HDL-C relates to all-cause and cardiovascular mortality, and the concentration of non-HDL-C where the risk of mortality is lowest is not defined. Methods: A population-based cohort study using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014. Male participants without statin therapy were divided into the six groups according to non-HDL-C levels (<100, 100-129, 130-159, 160-189, 190-219, ≥220 mg/dl). Multivariable Cox proportional hazards models were conducted with a hazard ratio (HR) and corresponding 95% confidence interval (CI). To further explore the relationship between non-HDL-C and mortality, Kaplan-Meier survival curves, restricted cubic spline curves, and subgroup analysis were performed. Results: Among 12,574 individuals (average age 44.29 ± 16.37 years), 1,174(9.34%) deaths during a median follow-up 98.38 months. Both low and high non-HDL-C levels were significantly associated with increased risk of all-cause and cardiovascular mortality, indicating a U-shaped association. Threshold values were detected at 144 mg/dl for all-cause mortality and 142 mg/dl for cardiovascular mortality. Below the threshold, per 30 mg/dl increase in non-HDL-C reduced a 28 and 40% increased risk of all-cause (p < 0.0001) and cardiovascular mortality (p = 0.0037), respectively. Inversely, above the threshold, per 30 mg/dl increase in non-HDL-C accelerated risk of both all-cause mortality (HR 1.11, 95% CI 1.03-1.20, p = 0.0057) and cardiovascular mortality (HR 1.30, 95% CI 1.09-1.54, p = 0.0028). Conclusions: Non-HDL-C was U-shaped related to all-cause and cardiovascular mortality among men without statin therapy.

Associations Between Serum Soluble α-Klotho and the Prevalence of Specific Cardiovascular Disease.

Objective: Accumulating experimental evidence has identified the beneficial effects of the anti-aging protein, serum soluble α-Klotho, on longevity, and the cardiovascular system. Although a previous study has revealed the predictive value of α-Klotho on total cardiovascular disease (CVD), the associations between α-Klotho and specific CVDs, including congestive heart failure (CHF), coronary heart disease (CHD), myocardial infarction (MI), and stroke, remains to be fully elucidated in humans. Methods: For 8,615 adults in the 2007 to 2016 National Health and Nutrition Examination Survey, stratified multivariable logistic regression models, restricted cubic spline curves, and subgroup analyses were used to evaluate the associations between α-Klotho and the four specific CVDs. Results: In the quartile analyses, compared to those in the highest quartile, participants in the lowest level of α-Klotho were significantly associated with CHF [odds ratio (OR) = 1.46, 95% CI: 1.09-1.97] and MI (1.33, 1.02-1.74), which was not the case for CHD (1.12, 0.91-1.38) or stroke (0.96, 0.73-1.25). Each unit increment in the ln-transformed α-Klotho concentrations was only positively associated with a 38 and 24% reduction in the prevalence of CHF and MI, respectively. Restricted cubic spline curves indicated that the α-Klotho was correlated with CHF and MI in linear-inverse relationships. Conclusion: The present findings suggested that the serum soluble α-Klotho is significantly associated with the prevalence of CHF and MI. To better determine whether α-Klotho is a specific biomarker of CVD, particularly for CHD and stroke, further research in humans is needed.

Astragaloside IV Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway.

OBJECTIVE: To evaluate the protective effects of Astragaloside IV (AST) in a rat model of myocardial injury induced by cecal ligation and puncture (CLP). METHODS: The model of sepsis-induced cardiac dysfunction was induced by CLP. Using a random number table, 50 specific pathogen free grade of Sprague Dawley rats were randomized into 5 groups: the sham group (sham), the model group (CLP, 18 h/72 h) and AST group (18 h/72 h). Except the sham group, the rats in other groups received CLP surgery to induce sepsis. CLP groups received intragastric administration with normal saline after CLP. AST groups received intragastric administration with AST solution (40 mg/kg) once a day. The levels of inflammatory mediators and oxidative stress markers in the serum of the septic rats were determined via enzyme-linked immunosorbent assay (ELISA) at different time point, such as interleukin 6 (IL-6), IL-10, high mobility group box-1 protein B1 (HMGB-1), superoxide dismutase (SOD), and malondialdehyde (MDA). Cardiac function was determined by echocardiography. Moreover, changes in myocardial pathology were evaluated using hematoxylin and eosin staining. The levels of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were analysed to determine the status of CLP-induced myocardium. In addition, the apotosis of myocardial cells was analysed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). The protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), IκB kinase α (IKKα), nuclear factor kappa B p65 (NF-κB p65) were detected by Western blot analysis. Moreover, survival rate was investigated. RESULTS: AST improved the survival rate of CLP-induced rats by up to 33.3% (P<0.05). The cardioprotective effect of AST was observed by increased ejection fraction, fractional shortening and left ventricular internal diameter in diastole respectively (P<0.01 or P<0.05). Subsequently, AST attenuated CLP-induced myocardial apoptosis and the ratio of Bcl-2/Bax in the myocardium, as well as the histological alterations of myocardium (P<0.01 or P<0.05); the generation of inflammatory cytokines (IL-6, IL-10, HMGB-1) and oxidative stress markers (SOD, MDA) in the serum was significantly alleviated (P<0.01 or P<0.05). On the other hand, AST markedly suppressed CLP-induced accumulation of IKK-α and NF-κB p65 subunit phosphorylation (P<0.01 or P<0.05). CONCLUSIONS: AST plays a significant protective role in sepsis-induced cardiac dysfunction and survival outcome. The possible mechanism of cardioprotection is dependent on the activation of the IKK/NF-κB pathway in cardiomyocytes.

Effect of Tongguan Capsules () on Restenosis after Coronary Stent Implantation: Study Protocol for A Randomized Controlled Trial.

BACKGROUND: Although percutaneous coronary intervention (PCI) had become widely employed therapeutic procedure for coronary artery disease, stent restenosis limited the benefits of this revascularization and the question how to prevent such events remained unresolved. While numerous empirical observations suggested Tongguan Capsules (), a patented Chinese Medicine, could decrease frequency and duration of angina pectoris attacks, evidence supporting its efficacy on restenosis remained inadequate. OBJECTIVE: This trial was designed to determine whether Tongguan Capsules would reduce restenosis rate in patients after successful stent implantation. METHODS: Approximately 400 patients undergoing percutaneous coronary stent deployment were enrolled and randomized to control group or Tongguan Capsules (4.5 g/d) for 3 months. All patients received standard anti-platelet, anti-coagulation and lipid-decreasing treatments, concurrently. The primary clinical endpoint was the 12-month incidence of the major adverse cardiovascular events (defined as cardiac death, myocardial infarction, and recurrence of symptoms requiring additional revascularization). The angiographic end point was restenosis rate at 6 months. CONCLUSION: This study would provide important evidence for the use of Tongguan Capsules in patients after stent implantation in combination with routine therapies, which may significantly reduce incidence of the restenosis so as to potentially improve the clinical outcomes. (registration number: ChiCTR-TRC- ChiCTR-IIR-17011407).

Protective Effects of Danlou Tablet () against Murine Myocardial Ischemia and Reperfusion Injury In Vivo.

OBJECTIVE: To observe the in vivo effect of Danlou Tablet (, DLT) on myocardial ischemia and reperfusion (I/R) injury. METHODS: DLT effects were evaluated in mouse heart preparation using 30-min coronary occlusion followed by 24-h reperfusion and compared among sham group (n=6), I/R group (n=8), IPC group (ischemia preconditioning, n=6) and DLT group (I/R with DLT pretreatment for 3 days, 750 mg•kg-1•day-1, n=8). The effects of DLT were characterized in infarction size (IS) compared with risk region (RR) and left ventricle using the Evans blue/triphenyltetrazolium chloride double dye staining method in vivo. Furthermore, the dose-dependent effect of DLT on I/R injury was evaluated by double staining method. Five different concentrations of DLT (0.625, 1.25, 2.5, 5 and 10 g•kg-1•day-1) were chosen in this study, and dose-response curve of DLT was obtained on these data. RESULTS: The ratio of IS to left ventricle was significantly smaller in the DLT and IPC groups than the I/R group (P<0.05 or P<0.01), the ratio of IS to RR was also reduced in the DLT and IPC groups (P<0.01), while there were no differences in RR among the four groups (P>0.05). Experiments showed incidence of arrhythmias was reduced in the DLT group (P<0.01). Furthermore, DLT produced a dose-dependent inhibitory effect with a half maximal inhibitory concentration of 1.225 g•kg-1•day-1. CONCLUSIONS: Our research concluded that DLT was effective in reducing I/R injury in mice, and provided experimental supports for the clinical use of DLT.

Association between fibrinogen level and the severity of coronary stenosis in 418 male patients with myocardial infarction younger than 35 years old.

Fibrinogen (Fib) is a useful marker for predicting the severity of coronary artery disease (CAD) in adult population. However, whether Fib can be a predictor for the presence and severity of CAD in very young MI patients (≤35 years old) remains to be determined. A total of 418 males from 61,863 patients with MI who were under 35 years old were sequentially recruited in our study. The patients were divided into two main groups and three subgroups according to coronary angiograph and Gensini score (GS) system: no coronary artery stenosis (group A), the results of the coronary artery stenosis (group B); low GS, intermediate GS and high GS. Data indicated that Fib, body mass index, current smoking, white blood cell count (WBCC) and GS were significantly higher in group B than those in group A (all P < 0.01). Moreover, there were significant differences in Fib, mean age, diabetes mellitus, family history of CAD, WBCC, left ventricular ejection fraction, and GS between high GS and low GS subgroups (all P < 0.01). A positive correlation between Fib levels and GS was found (r = 0.242, p < 0.001). Receiver operating characteristics curve analysis demonstrated that the best cut-off level of Fib predicting the severity of coronary stenosis was 3.475g/L (sensitivity 64%; specificity 70%) and the area under the curve was 0.656. Fib was also independently associated with high GS (OR=2.173, 95%CI 1.011-4.670, P = 0.047) after adjusting for potential confounders. In conclusion, Fib is significantly related to the presence and severity of coronary stenosis in male patients with MI under 35 years old.

Salvianolate reduces murine myocardial ischemia and reperfusion injury via ERK1/2 signaling pathways in vivo.

OBJECTIVE: To analyze the effects of salvianolate on myocardial infarction in a murine in vivo model of ischemia and reperfusion (I/R) injury. METHODS: Myocardial I/R injury model was constructed in mice by 30 min of coronary occlusion followed by 24 h of reperfusion and pretreated with salvianolate 30 min before I/R (SAL group). The SAL group was compared with SHAM (no I/R and no salvianolate), I/R (no salvianolate), and ischemia preconditioning (IPC) groups. Furthermore, an ERK1/2 inhibitor PD98059 (1 mg/kg), and a phosphatidylinositol-3-kinase (PI3-K) inhibitor, LY294002 (7.5 mg/kg), were administered intraperitoneal injection (i.p) for 30 min prior to salvianolate, followed by I/R surgery in LY and PD groups. By using a double staining method, the ratio of the infarct size (IS) to left ventricle (LV) and of risk region (RR) to LV were compared among the groups. Correlations between IS and RR were analyzed. Western-blot was used to detect the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (AKT) phosphorylation changes. RESULTS: There were no significant differences between RR to LV ratio among the SHAM, I/R, IPC and SAL groups (P>0.05). The SAL and IPC groups had IS of 26.1%±1.4% and 22.3%±2.9% of RR, respectively, both of which were significantly smaller than the I/R group (38.5%±2.9% of RR, P<0.05, P<0.01, respectively). Moreover, the phosphorylation of ERK1/2 was increased in SAL group (P<0.05), while AKT had no significant change. LY294002 further reduced IS, whereas the protective role of salvianolate could be attenuated by PD98059, which increased the IS. Additionally, the IS was not linearly related to the RR (r=0.23, 0.45, 0.62, 0.17, and 0.52 in the SHAM, I/R, SAL, LY and PD groups, respectively). CONCLUSION: Salvianolate could reduce myocardial I/R injury in mice in vivo, which involves an ERK1/2 pathway, but not a PI3-K signaling pathway.

[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.

[Effect of Modified Huanglian Jiedu Decoction Purgation Combined Electroacupuncture in Intervening Gastrointestinal Dysfunction of Critically Ill Patients Undergoing Abdominal Surgery].

OBJECTIVE: To observe the effect of purgation and detoxification therapy on gastrointestinal dysfunction of critically ill patients undergoing abdominal surgery. METHODS: Totally 56 inpatients with severe gastrointestinal dysfunction after abdominal surgery at ICU of Guangdong Provincial Hospital of Traditional Chinese Medicine were assigned to the treatment group and the control group, 28 in each group. All patients received routine Western medical treatment. Patients in the treatment group additionally took Modified Huanglian Jiedu Decoction (MHJD) and received electroacupuncture (EA) for 7 days. The first exhaust time, defecation time, scores for gastrointestinal dysfunction, mechanical ventilation time, ICU hospitalization time, and 28-day fatality rate were observed. Furthermore, serum levels of diamine oxidase (DAO) and D-lactic acid were detected at day 1, 3, and 7 after treatment. RESULTS: The first exhaust time and the first defecation time in the treatment group were ahead of schedule, when compared with those of the control group (P <0. 05). Scores for gastrointestinal dysfunction, mechanical ventilation time, serum levels of DAO obviously decreased in the treatment group (P <0. 05). There was no statistical difference in serum levels of D-lactic acid, ICU stay time, the incidence of pulmonary infection, and 28-day mortality between the two groups (P >0. 05). Results of Logistic analysis showed that scores for gastrointestinal dysfunction were related with the incidence of pulmonary infection (P <0. 05). CONCLUSION: MHJD combined EA could promote the recovery of gastrointestinal function in critically ill patients after abdominal surgery via improving intestinal barrier function, which was benefit for shortening mechanical ventilation time.

[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.

Non-HDL cholesterol is a better target for predicting periprocedural myocardial injury following percutaneous coronary intervention in type 2 diabetes.

OBJECTIVE: Non-HDL cholesterol (non-HDL-C) has recently been recommended as a first target for dyslipidemia management. We previously reported that LDL cholesterol (LDL-C) and non-HDL-C levels were similarly associated with periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI) in patients with coronary artery disease. Here we investigated the comparative prognostic value of non-HDL-C and LDL-C for PMI following PCI in type 2 diabetes (T2D). METHODS: We prospectively enrolled 1194 consecutive T2D patients with normal preprocedural cTnI undergoing PCI. Patients were divided into the two groups: group A [glycated hemoglobin (HbA1c) < 7%, n = 567] and group B (HbA1c ≥ 7%, n = 627). PMI was evaluated by cTnI analysis within 24 h. The relationship of preprocedural non-HDL-C and LDL-C levels with peak cTnI values after PCI was examined. RESULTS: Patients in group B, with higher preprocedural non-HDL-C levels, had higher postprocedural cTnI levels (ß = 0.102, P = 0.011). In the multivariable model, a 1-SD increase in non-HDL-C produced a 30% and 33% increased risk of postprocedural cTnI >3 × upper limit of normal (ULN) and >5 × ULN in group B, respectively. However, neither LDL-C nor group A patients were affected. Furthermore, patients with non-HDL-C levels ≥ 130 mg/dl compared with non-HDL-C levels ≤ 100 mg/dl were associated with a 83.3% and 71.7% increased risk of postprocedural cTnI >3 × ULN and >5 × ULN in group B, respectively. CONCLUSIONS: In poorly-controlled diabetic patients (HbA1c ≥ 7%) undergoing PCI, non-HDL-C but not LDL-C was independently associated with and increased risk of PMI, and non-HDL-C levels ≥ 130 mg/dl had a worse PMI risk profile compared with non-HDL-C levels <100 mg/dl.

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.

[A study protocol for clinical pathways based on integrative medicine for patients with acute myocardial infarction].

BACKGROUND: Acute myocardial infarction (AMI) is one of the most common cardiovascular diseases. The clinical pathway is the therapeutic program for disease-specific treatment and its implementation may reduce both the duration and cost of the hospital stay. This study aims to construct and evaluate the efficacy of clinical pathways (CPs) based on integrated traditional Chinese and Western medicine for patients with AMI. METHODS AND DESIGN: The clinical pathway of integrative medicine for AMI was constructed on the basis of syndrome evolvement surveys, literature research and expert consultation. Then, a non-randomized controlled, multicenter trial was designed to evaluate the efficacy and safety of the clinical pathway around the length of hospital stay, hospital expenses and the incidence of major cardiovascular events. This also allowed further exploration into the efficacy and safety of the clinical pathway for AMI based on traditional Chinese and Western medicine. DISCUSSION: The study firstly researched CPs based on the integrative medicine in hospitals of Chinese medicine and set up the key methods and skills for the construction of CPs of integrative medicine. This study will provide a powerful reference and direction for single-disease management reform under the healthcare system and set a good example for the improvement of integrative treatments. TRIAL REGISTRATION NUMBER: ChiCTR-TNRC-10000753.

Arg124Cys mutation of the TGFBI gene in a Chinese pedigree of Reis-Bücklers corneal dystrophy.

AIM: To analyze mutations in transforming growth factor beta-induced (TGFBI) gene in a Chinese pedigree with Reis-Bücklers corneal dystrophy (RBCD, also known as GCD3). METHODS: In a five-generation Chinese family, eight members were identified with RBCD and the rest were unaffected. All members of the family underwent complete ophthalmologic examinations. Exons of TGFBI were amplified by polymerase chain reaction, sequenced, and compared with a reference database. RESULTS: A single heterozygous C>T (R124C) point mutation was found in exon 4 of TGFBI in all the affected members of the pedigree, but not in the unaffected members. CONCLUSION: R124C which was a known mutation for lattice corneal dystrophy type I, segregated with the RBCD in this pedigree. This elucidated the correlation between genotype and phenotype in a Chinese family of RBCD.