Antibiotic prophylaxis for surgical wound infections in clean and clean-contaminated surgery: an updated systematic review and meta-analysis.

BACKGROUND: The efficacy and necessity of prophylactic antibiotics in clean and clean-contaminated surgery remains controversial. METHODS: The studies were screened and extracted using databases including PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials.gov according to predefined eligibility criteria. Randomized controlled trials (RCTs) comparing the effect of preoperative and postoperative prophylactic antibiotic use on the incidence of surgical site infections (SSIs) in patients undergoing any clean or clean-contaminated surgery. RESULTS: A total of 16,189 participants in 48 RCTs were included in the primary meta-analysis following the eligibility criteria. The pooled odds ratio (OR) for SSI with antibiotic prophylaxis versus placebo was 0.60 (95% CI: 0.53-0.68). The pooled OR among gastrointestinal, oncology, orthopedics, neurosurgery, oral, and urology surgery was 3.06 (95% CI: 1.05-8.91), 1.16 (95% CI: 0.89-1.50), 2.04 (95% CI: 1.09-3.81), 3.05 (95% CI: 1.25-7.47), 3.55 (95% CI: 1.78-7.06), and 2.26 (95% CI: 1.12-4.55), respectively. Furthermore, the summary mean difference (MD) for patients' length of hospitalization was -0.91 (95% CI: -1.61, -0.16). The results of sensitivity analyses for all combined effect sizes showed good stability. CONCLUSION: Antibiotics are both effective, safe, and necessary in preventing surgical wound infections in clean and clean-contaminated procedures, attributed to their reduction in the incidence of surgical site infections as well as the length of patient hospitalization.

Initial experience with an electron FLASH research extension (FLEX) for the Clinac system.

PURPOSE: Radiotherapy delivered at ultra-high-dose-rates (≥40 Gy/s), that is, FLASH, has the potential to effectively widen the therapeutic window and considerably improve the care of cancer patients. The underlying mechanism of the FLASH effect is not well understood, and commercial systems capable of delivering such dose rates are scarce. The purpose of this study was to perform the initial acceptance and commissioning tests of an electron FLASH research product for preclinical studies. METHODS: A linear accelerator (Clinac 23EX) was modified to include a non-clinical FLASH research extension (the Clinac-FLEX system) by Varian, a Siemens Healthineers company (Palo Alto, CA) capable of delivering a 16 MeV electron beam with FLASH and conventional dose rates. The acceptance, commissioning, and dosimetric characterization of the FLEX system was performed using radiochromic film, optically stimulated luminescent dosimeters, and a plane-parallel ionization chamber. A radiation survey was conducted for which the shielding of the pre-existing vault was deemed sufficient. RESULTS: The Clinac-FLEX system is capable of delivering a 16 MeV electron FLASH beam of approximately 1 Gy/pulse at isocenter and reached a maximum dose rate >3.8 Gy/pulse near the upper accessory mount on the linac gantry. The percent depth dose curves of the 16 MeV FLASH and conventional modes for the 10 × 10 cm2 applicator agreed within 0.5 mm at a range of 50% of the maximum dose. Their respective profiles agreed well in terms of flatness but deviated for field sizes >10 × 10 cm2 . The output stability of the FLASH system exhibited a dose deviation of <1%. Preliminary cell studies showed that the FLASH dose rate (180 Gy/s) had much less impact on the cell morphology of 76N breast normal cells compared to the non-FLASH dose rate (18 Gy/s), which induced large-size cells. CONCLUSION: Our studies characterized the non-clinical Clinac-FLEX system as a viable solution to conduct FLASH research that could substantially increase access to ultra-high-dose-rate capabilities for scientists.

Plasma-induced oxygen defects in titanium dioxide to address the long-term stability of pseudocapacitive MnO2 anode for lithium ion batteries.

In this work, we developed Manganese and Titanium based oxide composites with oxygen defects (MnOx@aTiOy) via plasma processing as anodes of lithium ion batteries. By appropriately adjusting the defect concentration, the ion transport kinetics and electrical conductivity of the electrodes are significantly improved, showing stable capacity retention. Furthermore, the incremental capacity is further activated and long-term stable cycling performance is achieved, with a specific capacity of 829.5 mAh/g at 1 A/g after 2000 cycles. To scrutinize the lithium migration paths and energy barriers in MnO2 and Mn2O3, the density functional theory (DFT) calculations is performed to explore the lithium migration paths and energy barriers. Although the transformation of MnO2 into Mn2O3 through oxygen defects was initially surmised to inhibit Li ions along their standard routes, our results indicate quite the contrary. In fact, the composite's lithium diffusion rate saw a substantial increase. This can be accredited to the pronounced enhancement of conductivity and ion transport efficiency in the amorphous and porous TiOy.

Rapid detection of Heterobasidion annosum using a loop-mediated isothermal amplification assay.

Heterobasidion annosum is one of the most aggressive pathogens of Pinus forests in Europe, causing considerable economic losses. To detect H. annosum for disease diagnosis and control, we developed a loop-mediated isothermal amplification (LAMP) reaction with a primer set designed from the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) DNA sequences of H. annosum. In our study, this LAMP assay was found to be capable of efficiently amplifying the target gene within 60 min at 63°C. In specificity tests, H. annosum was positively detected, and other species were negative. The detection limit of this assay was found to be 100 pg·µL-1, and the assay was also successfully tested for use with basidiospore suspensions and wood samples. This study provides a rapid method for diagnosing root and butt rot caused by H. annosum, which will be of use in port surveillance of logs imported from Europe.

Expressing IL-15/IL-18 and CXCR2 improve infiltration and survival of EGFRvIII-targeting CAR-T cells in breast cancer.

Previously, we have generated EGFRvIII-targeting CAR-T cells and brought hope for treating advanced breast cancer. However, EGFRvIII-targeting CAR-T cells were defined limited anti-tumor efficacy, which might be due to reduced accumulation, persistence of therapeutic T cells in tumor site of breast cancer. CXCLs were highly expressed in tumor environment of breast cancer and CXCR2 is the main receptor for CXCLs. Here, CXCR2 could significantly improve the trafficking and tumor specific accumulation of CAR-T cells both in vivo and in vitro. However, the anti-tumor effect of CXCR2 CAR-T cells were weaken which might be results of the apoptosis of T cells. Cytokines could stimulate Tcell proliferation, such as interleukin (IL)-15 and IL-18. Then, we generated CXCR2 CAR with synthetic IL-15 or IL-18 production. Co-expressing IL-15 or IL-18 could significantly suppress the exhaustion and apoptosis of T cells and enhanced the anti-tumor activity of CXCR2 CAR-T cells in vivo. Further, coexpression IL-15 or IL-18 in CXCR2 CAR-T cells did not cause toxicity. These findings provide a potential therapy strategy of co-expression IL-15 or IL-18 in CXCR2 CAR-T cells for the treatment of advancing breast cancer in the future.

Shexiang Tongxin Dropping Pill Allieviates Heart Failure via Extracellula Matrix-Receptor Interaction Pathways Based on RNA-Seq Transcriptomics and Experimental Studies.

OBJECTIVE: To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills (STDP) on heart failure (HF). METHODS: Isoproterenol (ISO)-induced HF rat model and angiotensin II (Ang II)-induced neonatal rat cardiac fibroblast (CFs) model were used in the present study. HF rats were treated with and without STDP (3 g/kg). RNA-seq was performed to identify differentially expressed genes (DEGs). Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson's stainings were taken to assess cardiac fibrosis. The levels of collagen I (Col I) and collagen III (Col III) were detected by immunohistochemical staining. CCK8 kit and transwell assay were implemented to test the CFs' proliferative and migratory activity, respectively. The protein expressions of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9, Col I, and Col III were detected by Western blotting. RESULTS: The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways, such as the extracellular matrix (ECM)-receptor interaction, cell cycle, and B cell receptor interaction. Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function, inhibiting myocardial fibrosis, and reversing increases in Col I and Col III expression levels in the hearts of HF rats. Moreover, STDP (6, 9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang II in vitro (P<0.05). The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP, also the synthesis of MMP-2 and MMP-9, as well as ECM components Col I, Col III, and α-SMA were decreased in Ang II-induced neonatal rats' CFs. CONCLUSIONS: STDP had anti-fibrotic effects in HF, which might be caused by the modulation of ECM-receptor interaction pathways. Through the management of cardiac fibrosis, STDP may be a compelling candidate for improving prognosis of HF.

How does HbA1c predict mortality and readmission in patients with heart failure? A protocol for systematic review and meta-analysis.

BACKGROUND: Accumulating evidence suggests that HbA1c levels, a common clinical indicator of chronic glucose metabolism over the preceding 2-3 months, are independent risk factors for cardiovascular disease, including heart failure. However, conflicting evidence obscures clear cutoffs of HbA1c levels in various heart failure populations. The aim of this review is to assess the possible predictive value and optimal range of HbA1c on mortality and readmission in patients with heart failure. METHODS: A systematic and comprehensive search will be performed using PubMed, Embase, CINAHL, Scopus, and the Cochrane Library databases before December 2022 to identify relevant studies. All-cause mortality is the prespecified primary endpoint. Cardiovascular death and heart failure readmission are secondary endpoints of interest. We will only include prospective and retrospective cohort studies and place no restrictions on the language, race, region, or publication period. The ROBINS-I tool will be used to assess the quality of each included research. If there were sufficient studies, we will conduct a meta-analysis with pooled relative risks and corresponding 95% confidence intervals to evaluate the possible predictive value of HbA1c for mortality and readmission. Otherwise, we will undertake a narrative synthesis. Heterogeneity and publication bias will be assessed. If heterogeneity was significant among included studies, a sensitivity analysis or subgroup analysis will be used to explore the source of heterogeneity, such as diverse types of heart failure or patients with diabetes and non-diabetes. Additionally, we will conduct meta-regression to examine the time-effect and treatment-effect modifiers on all-cause mortality compared between different quantile of HbA1c levels. Finally, a restricted cubic spline model may be used to explore the dose-response relationship between HbA1c and adverse outcomes. DISCUSSION: This planned analysis is anticipated to identify the predictive value of HbA1c for mortality and readmission in patients with heart failure. Improved understanding of different HbA1c levels and their specific effect on diverse types of heart failure or patients with diabetes and non-diabetes is expected to be figured out. Importantly, a dose-response relationship or optimal range of HbA1c will be determined to instruct clinicians and patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration details: CRD42021276067.

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.

Suxiao Jiuxin Pills Prevent Ventricular Fibrillation from Inhibiting L-type Calcium Currents CaV1.2 in vivo and in vitro.

OBJECTIVE: To investigate whether Suxiao Jiuxin Pills (SJP), a Chinese herbal remedy, is an anti-ventricular fibrillation (VF) agent. METHODS: VF was induced by isoproterenolol (ISO) intraperitoneal injection followed by electrical pacing in mice and rabbits. The effects of SJP on the L-type calcium channel current (CaV1.2), voltage-dependent sodium channel current (INa), rapid and slow delayed rectifier potassium channel current (IKr and IKs, respectively) were studied by whole-cell patch-clamp method. Computer simulation was implemented to incorporate the experimental data of SJP effects on the CaV1.2 current into the action potential (AP) and pseudo-electrocardiography (pseudo-ECG) models. RESULTS: SJP prevented VF induction and reduced VF durations significantly in mice and rabbits. Patch-clamp experiments revealed that SJP decreased the peak amplitude of the CaV1.2 current with a half maximal concentration (IC50) value of 16.9 mg/L (SJP-30 mg/L, -32.8 ± 6.1 pA; Verapamil, -16.2 ±1.8 pA; vs. control, -234.5 ±16.7 pA, P<0.01, respectively). The steady-state activation curve, inactivation curve, and the recovery from inactivation of the CaV1.2 current were not shifted significantly. Specifically, SJP did not altered INa, IKr, and IKs currents significantly (SJP vs. control, P>0.05). Computer simulation showed that SJP-reduced CaV1.2 current shortened the AP duration, transiting VF into sinus rhythm in pseudo-ECG. CONCLUSION: SJP reduced VF via inhibiting the CaV1.2 current with in vivo, in vitro, and in silico studies, which provide experimental basis for SJP anti-VF clinical application.

Prospective comparison of acupuncture with sham acupuncture to determine impact on sedation and analgesia in mechanically ventilated critically ill patients (PASSION study): protocol for a randomised controlled trial.

INTRODUCTION: Sedation and analgesia are recommended to be employed in the intensive care unit (ICU) to enhance patient comfort and safety, facilitate mechanical ventilation and reduce oxygen demands. However, the increasing evidence demonstrates that excessive sedation and analgesia might prolong mechanical ventilation and increase costs and mortality. Acupuncture is known to be able to attenuate pain, anxiety and agitation symptoms while avoiding excessive sedation and analgesia caused by drugs. Therefore, we present a protocol to investigate whether acupuncture, used for sedation and analgesia, can reduce the duration of mechanical ventilation, save medical resources and reduce the mortality of critically ill patients receiving mechanical ventilation. METHODS AND ANALYSIS: Prospective, randomised controlled trial is conducted on 180 adult medical/surgical ICU patients with mechanical ventilation needing sedation at 3 ICUs between 03 November 2021 and 16 August 2023. Patients will be treated with analgesia and sedation to achieve desired target sedation levels (Richmond Agitation Sedation Score of -2 to 1). Enrolled patients will be randomly assigned in a ratio of 1:1:1 to receive deep needle insertion with combined manual and alternating-mode electrical stimulation on acupoints (AC group), superficial needle insertion without manual stimulation and electrical stimulation on non-acupoints (SAC group), or no acupuncture intervention (NAC group). The primary outcome is the duration of mechanical ventilation from randomisation until patients are free of mechanical ventilation (including non-invasive) without reinstitution for the following 48 hours. Secondary endpoints include the dose of administered sedatives and analgesic at comparable sedation levels throughout the study, ICU length of stay, hospital length of stay. Additional outcomes include the prevalence and days of delirium in ICU, mortality in ICU and within 28 days after randomisation, and the number of ventilator free days in 28 days. ETHICS AND DISSEMINATION: This trial was approved by the ethics committee at Guangdong Provincial Hospital of Chinese Medicine. We will publish the study results. TRIAL REGISTRATION NUMBER: ChiCTR2100052650.

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.

Analysis of the Dose-Response Effects of Physical Activity on Cardiocerebrovascular and All-Cause Mortality in Hypertension.

Background: Leisure-time moderate-to-vigorous physical activity (MV-PA) has been consistently regarded as a protective factor to prevent and treat hypertension. However, the effect of different levels of MV-PA against cardiocerebrovascular and all-cause mortality in hypertension is still unclear. The aim of this study was to explore the dose relationships of MV-PA on these adverse outcomes in hypertension. Methods: In the National Health and Nutritional Examination Survey (NHANES) from 1999 to 2006, participants with hypertension were enrolled and classified into inactive (0 MET-h/week), low-active (0 < to < 7.5 MET-h/week), and high-active (≥ 7.5 MET-h/week) groups. A multivariate Cox regression analysis was conducted with a hazard ratio (HR) and corresponding 95% confidence interval (CI). To further explore the association between different levels of MV-PA and adverse outcomes, Kaplan-Meier survival curves, subgroup analysis, and restricted cubic spline curves were performed. Results: During a median 10.93-year follow-up, 1,510 and 347 patients had died from any causes and cardiocerebrovascular, respectively. The high-active group had the highest event-free survivals of all outcomes compared with low-active and inactive groups. A multivariate Cox regression analysis demonstrated that the high-active and low-active groups were associated with reduced risks of all-cause [HR: 0.70, 95% CI: 0.60-0.82; 0.76 (0.68-0.86), respectively] and cardiocerebrovascular mortality [0.56 (0.41-0.77); 0.63 (0.50-0.81), respectively] compared with the inactive group. Subgroup analysis and restricted cubic spline curves showed that MV-PA surpassing 15 MET-h/week could decrease the risks of cardiovascular and all-cause mortality with inverse relationships, which was not the case for cerebrovascular mortality, indicating a U-shaped association. Conclusion: Our study suggests that highly active MV-PA of 7.5 to < 15 MET-h/week was associated with the lowest risks of cardiocerebrovascular and all-cause mortality in hypertension.

Effect of lanthanum carbonate on the progression of coronary artery calcification in hemodialysis patients: A meta-analysis of randomized controlled trials.

INTRODUCTION: Coronary artery calcification and cardiac abnormalities are common in hemodialysis patients. The value of lanthanum carbonate over calcium-based phosphate binders in managing the progression of coronary artery calcification is debated. We reviewed all randomized controlled trials (RCTs) comparing the two strategies in these patients. METHODS: RCTs comparing lanthanum carbonate with calcium-based phosphate binders used in adult hemodialysis patients were identified in the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal, and Wanfang databases. FINDINGS: Ten RCTs involving 687 patients were suitable for inclusion. Compared with calcium-based phosphate binders, lanthanum carbonate yielded lower coronary artery calcium scores (weighted mean difference, WMD: -74.28, 95% CI: -149.89, 1.33), change in coronary artery calcium scores (WMD: -105.18, 95% CI: -113.83, -96.53), and left ventricular mass index (WMD: -29.95, 95% CI: -54.25, -7.45). Lanthanum carbonate was significantly associated with lower levels of serum phosphate (WMD: -0.18, 95% CI: -0.26, -0.10), calcium (WMD: -0.22, 95% CI: -0.25, -0.20), and fibroblast growth factor 23 (FGF23) (standard mean difference: -3.78, 95% CI: -5.60, -1.96) but not intact parathyroid hormone (WMD: -4.23, 95% CI: -64.12, 55.65). Moreover, a reduced risk of nonfatal cardiovascular events (OR: 0.31, 95% CI: 0.10-0.97) but not all-cause mortality (OR: 1.08, 95% CI: 0.39-3.01) in lanthanum carbonate therapy was observed. DISCUSSION: In hemodialysis patients, lanthanum carbonate therapy may impede the progression of coronary artery calcification and left ventricular mass index and lead to reduced serum phosphate, calcium, FGF23, and nonfatal cardiovascular events compared with calcium-based phosphate binders. However, more well-designed RCTs are required for confirmation.

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.

Kuanxiong Aerosol () in Treatment of Angina Pectoris: A Literature Review and Network Pharmacology.

Angina pectoris (AP) is the most common symptom of cardiovascular diseases, which seriously affects the quality of life in cardiovascular patients. Kuanxiong (KX) Aerosol (), a compound preparation that consists of 5 traditional Chinese medicines: Herba Asari , Rhizoma Alpiniae Officinarum, Lignum Santali Albi, Fructus Piperis Longi, and Borneolum, has been used in the treatment of AP for many years, exhibiting a significant curative effect and less side-effect. For the convenience and comprehensive understanding of KX Aerosol, this review systematically summarizes evidence on KX Aerosol in the treatment of AP including the pharmacological effects of its composition, clinical research, animal experiments, and network pharmacology prediction. Meanwhile, we highlight the research limitation of KX Aerosol at present. This review may guide the clinical application of KX Aerosol and further provide a reference for the research of AP.

Effects of dissolved oxygen on the sludge dewaterability and extracellular polymeric substances distribution by bioleaching.

Bioleaching is a biological conditioning technology for sludge, which not only improves sludge dewatering performance but also removes heavy metals from sludge. As the bioleaching process is a comprehensive biological and chemical process, it is necessary to explore the effects of dissolved oxygen (DO) concentrations on bioleaching efficiency. Three bioleaching experiments with different DO concentrations (T1: 0.8-3.1 mg/L, T2: 3.1-5.5 mg/L, T3: 5.5-7.5 mg/L) were conducted for five days. The sludge dewatering efficiency was evaluated using capillary suction time (CST) and specific resistance to filtration (SRF). The relationship between sludge dewaterability and extracellular polymeric substance (EPS) fraction distribution was investigated. In the treatment with the highest DO concentration, the minimum values of SRF and CST were 4.31 × 1011 m/kg and 13.5 s, which occurred earlier than the treatment with the lower DO concentrations by approximately 24-48 h. A significant decrease (83.4-93.2%) in tightly bound EPS (TB-EPS) protein (PN) was observed in all treatments, while a positive correlation (r = 0.924, P < 0.01) was observed between SRF and PN content in TB-EPS. A relatively higher abundance of Acidithiobacillus was found with the increase in DO concentration. Additionally, other genera including Metallibacterium, Alicyclobacillus, Acidibacter, Acidocella, and Luteococcus also played important roles in EPS biodegradation. These results revealed that increasing the DO concentration could improve sludge dewatering performance and heavy metal removal by enhancing bioleaching microbial activity, the degradation of PN in TB-EPS, and sludge floc fragmentation, but only if sufficient energy sources were provided.

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).

[Molecular mechanism of Puerariae Lobatae Radix in treatment of hepatocellular carcinoma based on network pharmacology].

To investigate the potential mechanism of Puerariae Lobatae Radix in the treatment of hepatocellular carcinoma by network pharmacology and in vitro cell experiment. The main active components of Puerariae Lobatae Radix and their predicted targets were obtained from TCMSP, and the disease targets were obtained from GeneCards database. The disease and drug prediction targets were intersected to select the common potential therapeutic targets. The "compound-target-disease" network diagram was constructed in Cytoscape 3.7.1, and the common targets were input into the STRING database to build the PPI network of proteins interaction. GO function and KEGG pathway enrichment analysis on effective targets were performed by using R software. Autodock vina 1.1.2 was used for molecular docking. Finally, the core targets and pathways were preliminarily verified by in vitro experiments. The proliferation of human hepatocellular carcinoma cells was detected by CCK-8 and EDU enzyme staining, and the expressions of PTEN, PDK1, Akt and GSK3 were detected by Western blot. In this study, 10 components of Puerariae Lobatae Radix(9 components involved in hepatocellular carcinoma-related targets and signaling pathways), and 149 hepatocellular carcinoma-related targets and 156 signaling pathways were screened out. The results of network analysis indicated that Puerariae Lobatae Radix may play an anti-hepatocellular carcinoma effect on key targets, such as Akt, IL6, MAPK3, EGFR, and key pathways, such as PI3 K-Akt. The results of molecular docking indicated that puerarin, genistein and daidzein had a good binding ability with the key targets such as AKT1, MAPK3, MAPK1 and CASP3, and puerarin had the lowest Vina score with AKT1 and MAPK3 and also similar to them. In vitro cell experiments confirmed that puerarin has a significantly inhibitory effect on the proliferation of human hepatocellular carcinoma cells. Western blot results showed that puerarin could increase the phosphorylation of PTEN in human hepatocellular carcinoma cells through the PTEN/Akt/GSK3ß signaling pathway, and the phosphorylation level of its downstream Akt decreased. This series of studies confirm that puerarin can treat hepatocellular carcinoma by blocking PTEN/Akt/GSK3ß cellular signaling pathway, so as to provide ideas for subsequent studies for the molecular mechanism of puerarin in the treatment of liver cancer.