Synthesis and evaluation of febrifugine derivatives as anticoccidial agents.

A series of new febrifugine derivatives with a 4(3H)-quinazolinone scaffold were synthesized and evaluated for their anticoccidial activity both in vitro and in vivo. The targets' in vitro activity against Eimeria tenella was studied using quantitative real-time reverse transcription polymerase chain reaction and Madin-Darby bovine kidney cells. Most of these compounds demonstrated anticoccidial efficacy, with inhibition ratios ranging from 3.3% to 85.7%. Specifically, compounds 33 and 34 showed significant inhibitory effects on the proliferation of E. tenella and exhibited lower cytotoxicity compared to febrifugine. The IC50 values of compounds 33 and 34 were 3.48 and 1.79 µM, respectively, while the CC50 values were >100 µM for both compounds. Furthermore, in a study involving 14-day-old chickens infected with 5 × 104 sporulated oocysts, treatment with five selected compounds (22, 24, 28, 33, and 34), which exhibited in vitro inhibition rate of over 50% at 100 µM, at a dose of 40 mg/kg in daily feed for 8 consecutive days showed that compound 34 possessed moderate in vivo activity against coccidiosis, with an anticoccidial index of 164. Structure-activity relationship studies suggested that spirocyclic piperidine may be a preferable substructure to maintain high effectiveness in inhibiting Eimeria spp., when the side chain 1-(3-hydroxypiperidin-2-yl)propan-2-one was replaced.

Spontaneous Dislocation of the Lens Nucleus Into the Anterior Chamber Observed in a Patient With Overmature Senile Cataract.

Overmature cataract refers to the advanced stage of cataract where timely surgical intervention is not performed, leading to further progression characterized by decreased water content in the lens, degradation of fibers, and liquefaction within its structure, which can cause a reduction in volume, wrinkling of the capsule, as well as calcification or cholesterol crystallization on its surface. In addition, it may result in deepening of the anterior chamber. If left promptly untreated, these complications may result in visual impairment or even blindness. The occurrence of spontaneous complete dislocation of the lens nucleus into the anterior chamber in overmature cataracts is extremely uncommon. The authors present a case study involving a 74-year-old female patient who was diagnosed with complete dislocation of the lens nucleus in an overmature senile cataract without any apparent ocular injury or any relevant medical records. After undergoing cataract removal combined with anterior vitrectomy, the patient experienced relief from eye discomfort and expressed satisfaction with the surgical outcome; however, her visual acuity did not show significant improvement.

ECG criteria to distinguish hypertrophic cardiomyopathy featured with "Pseudo-STEMI" from acute ST-elevation myocardial infarction.

BACKGROUD: The ECG profile of Hypertrophic Cardiomyopathy (HCM) includes ST-segment elevation (STE) that may lead to misdiagnosis of acute ST-segment elevation myocardial infarction (STEMI). This pseudo-STEMI may bring non-essential treatment. We aimed to confirm the ECG differences between HCM featured with pseudo-STEMI and acute STEMI. MATERIAL AND METHODS: We retrospectively enrolled 59 HCM cases (Group A) and 56 acute STEMI cases (Group B). Based on the locations of STE, all the patients were divided into four subgroups, including HCM with STE in anterior leads (Group A1), anterior STEMI (Group B1), HCM with STE in inferior leads (Group A2) and inferior STEMI (Group B2). Several ECG parameters were compared between these subgroups. RESULTS: ECG parameters significantly differed between these groups, especially the number of leads with TWI. We evaluated the diagnostic value of ECG profiles for those groups. ROC analysis showed that for Group A vs. Group B, number of leads with TWI showed the highest AUC value of 0.805 and its cutoff of 2.5, with 76.3% sensitivity and 76.8% specificity. For Group A1 vs. Group B1, it showed the highest AUC value of 0.801 and its cut-off point was 2.5, with 77.1% sensitivity and 79.1% specificity. For Group A2 vs. Group B2, it showed the highest AUC value of 0.822 and the cut-off value was 4.5, with 54.5% sensitivity and 92.3% specificity. CONCLUSION: ECG plays a valid tool to distinguish "Pseudo-STEMI" HCM from acute STEMI, especially number of leads with TWI.

Orbital Apex Syndrome Caused by Intraorbital Aspergillus Infection.

Orbital apex syndrome, a clinical disease that is uncommon and has a high fatality rate. Tumor, endocrine, and inflammatory variables are frequently responsible for its occurrence. The authors describe a 53-year-old Chinese man who was diagnosed with orbital apex syndrome and coupled type 2 diabetes mellitus and a fungus infestation. Treatment included nasal endoscopic orbital apical decompression, anti-infection, and adequate debridement. Except for inevitable optic nerve damage, postoperative proptosis and headache manifestations improved, and systemic infection was timely contained with no signs of recurrence or serious complications occurred. The orbital apex syndrome is difficult to treat, and soon as possible biopsy of the lesion, aggressive surgical decompression, and antifungal treatment seem to be effective ways to improve survival rates.

[Expert consensus on clinical application of GBE50 Dispersible Tablets for ischemic cardiovascular and cerebrovascular diseases].

Ginkgo biloba Extract( GBE50) Dispersible Tablets is a new standardized prescription,which is widely used in the treatment of ischemic cardiovascular and cerebrovascular diseases. However,there are still many problems in its clinical application.Rational and safe use of GBE50 Dispersible Tablets is pivotal to the medication safety and clinical prognosis of patients. This consensus has been jointly formulated by clinical experts of traditional Chinese medicine and western medicine in cardiovascular and cerebrovascular diseases and followed the Manual for the Clinical Experts Consensus of Chinese Patent Medicine published by the China Association of Chinese Medicine. The present study identified clinical problems based on clinical investigation,searched the research papers according to PICO clinical problems,carried out evidence evaluation,classification,and recommendation by GRADE system,and reached the expert consensus with nominal group technique. The consensus combines evidence with expert experience. Sufficient evidence of clinical problems corresponds to " recommendations",while insufficient evidence to " suggestions". Safety issues of GBE50 Dispersible Tablets,such as indications,usage and dosage,and medication for special populations,are defined to improve clinical efficacy,promote rational medication,and reduce drug risks. This consensus needs to be revised based on emerging clinical issues and evidencebased updates in practical applications in the future.

Animal model of coronary microembolization under transthoracic echocardiographic guidance in rats.

The aim of the study was to develop a model of coronary microembolization (CME) in rats at a lower cost. We developed a novel rat model without thoracotomy and ventilation under the guidance of echocardiography. Rats were sacrificed at 3 h, 24 h and 1 month postoperatively in both the Echo-CME and Open-chest CME groups for the comparison of the modeling accuracy, mortality, cardiopulmonary circulation, pleural adhesion and ventilation-induced lung injury (VILI). Results showed that the coronary microthrombus formed at 3 h and reached its peak at 24 h postoperatively, which included platelet aggregation and fibrin web. The Echo-group increases success rates, decreased mortality, postoperative complications including pleural adhesion, cardiopulmonary dysfunction and VILI postoperatively than the Open-chest group at 1month postoperatively. The ejection fraction of the CME group decreased to 50% and obvious cardiac fibrosis formed at 3 months postoperatively. Our unique surgical method provided a platform to study molecular mechanisms and potential new pathways for CME treatment.

[Meta-analysis for clinical efficacy of traditional Chinese medicine in treating resistant hypertension].

To systematically evaluate the efficacy and safety of traditional Chinese medicine in treating patients with resistant hypertension. CNKI, Wanfang, VIP, CBM, PubMed, Web of Science, Cochrane Library, EMbase and other databases were retrieved by computers to screen out the randomized controlled trial of traditional Chinese medicine in treating resistant hypertension. Cochrane Handbook was used to evaluate the quality of the included literature, RevMan 5.3 and Stata 12.0 was used for Meta-analysis. Finally, 11 literatures meeting the criteria were included, involving 1 023 patients. The results of Meta-analysis showed that the combined therapy of standard triple antihypertensive regimen with traditional Chinese medicine could further reduce systolic blood pressure of patients with resistant hypertension(MD=-16.69, 95%CI[-22.21,-11.16], P<0.000 01), reduce diastolic blood pressure(MD=-7.51, 95%CI[-8.26,-6.76], P<0.000 01), improve the effective rate of anti-hypertension(OR=5.16, 95%CI[3.01, 8.84], P<0.000 01), improve the up-to-standard rate of blood pressure(OR=3.01, 95%CI[1.49, 6.09], P=0.002), and improve the effectiveness of clinical symptoms(OR=4.48, 95%CI[2.31, 8.68], P<0.000 01), with no significant effect on creatinine level(MD=-2.51, 95%CI[-6.91, 1.89], P=0.26). The results of this study indicated that the combined therapy of standard triple antihypertensive regimen with traditional Chinese medicine could further improve the clinical efficacy in patients with resistant hypertension with a good safety, but more high-quality clinical studies are still needed to verify this conclusion.

Platelet-derived microparticles promote endothelial cell proliferation in hypertension via miR-142-3p.

Endothelial cells (ECs) are located at the interface between flowing blood and the vessel wall, and abnormal EC proliferation induced by pathologic environments plays an important role in vascular remodeling in hypertensive conditions. Exchanges of information between blood components and ECs are important for EC function. Hence, the present study sought to determine how platelets induce EC dysfunction under hypertensive conditions. EC proliferation was increased in renal hypertensive rats established by abdominal aortic coarctation compared with control rats and that elevated thrombin in plasma promoted platelet activation, which may induce the release of platelet-derived microparticles (PMPs). MicroRNA (MiR) array and qPCR revealed a higher level of miR-142-3p in platelets and PMPs. In vitro, PMPs delivered miR-142-3p into ECs and enhanced their proliferation via Bcl-2-associated transcription factor (BCLAF)1 and its downstream genes. These results indicate that PMPs deliver miR-142-3p from activated platelets into ECs and that miR-142-3p may play important roles in EC dysfunction in hypertensive conditions and may be a novel therapeutic target for maintaining EC homeostasis in hypertension.-Bao, H., Chen, Y.-X., Huang, K., Zhuang, F., Bao, M., Han, Y., Chen, X.-H., Shi, Q., Yao, Q.-P., Qi, Y.-X. Platelet-derived microparticles promote endothelial cell proliferation in hypertension via miR-142-3p.

Construction of tissue-engineered lymphatic vessel using human adipose derived stem cells differentiated lymphatic endothelial like cells and decellularized arterial scaffold: A preliminary study.

We have previously demonstrated that human adipose-derived stem cells (hADSCs) can be differentiated into lymphatic endothelial like cells. The purpose of this study was to investigate the feasibility of utilizing the induced lymphatic endothelial like cells and decellularized arterial scaffold to construct the tissue-engineered lymphatic vessel. The hADSCs were isolated from adipose tissue in healthy adults and were characterized the multilineage differentiation potential. Decellularized arterial scaffold was prepared using the Triton x-100 method. ADSCs were differentiated into lymphatic-like endothelial cells, and the induced cells were then seeded onto the decellularized arterial scaffold to engineer the lymphatic vessel. The histological analyses were performed to examine the endothelialized construct. The decellularized arterial scaffold was successfully obtained and was able to maintain its vessel morphology. The isolated ADSCs can be differentiated into osteocytes and adipocytes. After seeding onto the scaffold, the seeded cells attached and grew well on the decellularized arterial scaffold. Our preliminary results demonstrated that the induced lymphatic endothelial like cells combined with decellularized arterial scaffold could be utilized to successfully engineer the lymphatic vessel. Our findings may be helpful for the development of tissue-engineering of the lymphatic graft.

The Relationship between Interleukin-6 Promotor Polymorphisms and Slow Coronary Flow Phenomenon.

BACKGROUND: Several lines of evidence suggest that slow coronary flow (SCF) phenomenon seems to be an early form of atherosclerosis and low-grade inflammation plays a role in the development of SCF. Interleukin-6 (IL-6) is a pleiotropic cytokine, functions as a mediator of inflammatory response, and has both pro-inflammatory and anti-inflammatory properties. The aim of the present study is to investigate the relationship between IL-6 -634C/G polymorphism and SCF in Han Chinese. METHODS: 250 subjects who underwent coronary angiography and had normal coronary arteries of varying coronary flow rates without any atherosclerotic lesion were enrolled in this study. 41 patients who had thrombolysis in myocardial infarction frame counts (TFC) above the normal cutoffs were considered to have SCF and 209 subjects within normal limits served as normal coronary flow (NCF) group. The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique was used to assess the genotypes. RESULTS: The distribution of the IL-6 -634C/G genotypes (CC, CG, and GG) was 56.94%, 37.80%, and 5.26% in the NCF subjects, and 36.59%, 48.78%, and 14.63% in the SCF group, respectively (p = 0.0173). The frequency of the G allele in the SCF (39.02%) group was significantly higher than that in the NCF (24.16%) group (p = 0.0054). Compared with the CC genotype, the G allele carriers (CG + GG genotypes) had increased risk of SCF in both unadjusted and adjusted analyses. In SCF patients, the average serum IL-6 levels (pg/mL) in CG + GG genotype (4.78 ± 0.42) were statistically higher than in CC genotype (3.93 ± 0.36) (p = 0.0000). CONCLUSIONS: Our data support that IL-6 -634C/G polymorphism is associated with SCF and the G allele has increased risk for SCF in Han Chinese.

Effect of Angiotensin receptor blockers on flow-mediated vasodilation: a meta-analysis of randomized controlled trials.

BACKGROUND: In a meta-analysis, we investigated the effects of angiotensin receptor blockers (ARBs) in comparison to placebo or other classes of antihypertensive drugs on endothelial function, which was measured by brachial flow-mediated vasodilation (FMD). METHODS: We searched for randomized controlled trials that compared ARBs with placebo or other classes of antihypertensive drugs in improving FMD. A random-effect model was used to compute pooled estimates. RESULTS: In 13 trials (n = 529), ARBs were more efficacious in improving brachial FMD than placebo [pooled weighted mean change difference (WMD) 1.34%, 95% CI, 0.93-1.75%, p<0.001]. In 15 trials (n = 918), treatment with ARBs had a significant effect on brachial FMD when compared with other antihypertensive drugs (pooled WMD 0.59%, 95% CI, 0.20-0.98%, p = 0.003 with significant heterogeneity). ARBs were also more efficacious in improving brachial FMD than calcium channel blockers (CCBs; pooled WMD 1.61%, 95% CI, 0.72-2.49%, p < 0.001) but not the other classes of drugs (p ≥ 0.072). CONCLUSIONS: This meta-analysis shows that ARBs improve brachial FMD, a marker of endothelial function, and that they are superior to placebo and CCBs. There was no significant difference in the effect on brachial FMD between ARBs and the other antihypertensive drugs.

A Meta-Analysis for Postoperative Complications in Tibial Plafond Fracture: Open Reduction and Internal Fixation Versus Limited Internal Fixation Combined With External Fixator.

The treatment of tibial plafond fractures is challenging to foot and ankle surgeons. Open reduction and internal fixation and limited internal fixation combined with an external fixator are 2 of the most commonly used methods of tibial plafond fracture repair. However, conclusions regarding the superior choice remain controversial. The present meta-analysis aimed to quantitatively compare the postoperative complications between open reduction and internal fixation and limited internal fixation combined with an external fixator for tibial plafond fractures. Nine studies with 498 fractures in 494 patients were included in the present study. The meta-analysis found no significant differences in bone healing complications (risk ratio [RR] 1.17, 95% confidence interval [CI] 0.68 to 2.01, p = .58], nonunion (RR 1.09, 95% CI 0.51 to 2.36, p = .82), malunion or delayed union (RR 1.24, 95% CI 0.57 to 2.69, p = .59), superficial (RR 1.56, 95% CI 0.43 to 5.61, p = .50) and deep (RR 1.89, 95% CI 0.62 to 5.80) infections, arthritis symptoms (RR 1.20, 95% CI 0.92 to 1.58, p = .18), or chronic osteomyelitis (RR 0.31, 95% CI 0.05 to 1.84, p = .20) between the 2 groups.

[Content determination of twelve major components in Tibetan medicine Zuozhu Daxi by UPLC].

A quantitative analytical method of ultra-high performance liquid chromatography (UPLC) was developed for simultaneously determining twelve components in Tibetan medicine Zuozhu Daxi. SIMPCA 12.0 software was used a principal component analysis PCA) and partial small squares analysis (PLSD-DA) on the twelve components in 10 batches from four pharmaceutical factories. Acquity UPLC BEH C15 column (2.1 mm x 100 mm, 1.7 µm) was adopted at the column temperature of 35 °C and eluted with acetonitrile (A) -0.05% phosphate acid solution (B) as the mobile phase with a flow rate of 0. 3 mL · min(-1). The injection volume was 1 µL. The detection wavelengths were set at 210 nm for alantolactone, isoalantolactone and oleanolic; 260 nm for trychnine and brucine; 288 nm for protopine; 306 nm for protopine, resveratrol and piperine; 370 nm for quercetin and isorhamnetin. The results showed a good separation among index components, with a good linearity relationship (R2 = 0.999 6) within the selected concentration range. The average sample recovery rates ranged between 99.44%-101.8%, with RSD between 0.37%-1.7%, indicating the method is rapid and accurate with a good repeatability and stability. The PCA and PLSD-DA analysis on the sample determination results revealed a great difference among samples from different pharmaceutical factories. The twelve components included in this study contributed significantly to the quantitative determination of intrinsic quality of Zuozhu Daxi. The UPLC established for to the quantitative determination of the twelve components can provide scientific basis for the comprehensive quality evaluation of Zuozhu Daxi.

Development of a GA-fuzzy-immune PID controller with incomplete derivation for robot dexterous hand.

In order to improve the performance of robot dexterous hand, a controller based on GA-fuzzy-immune PID was designed. The control system of a robot dexterous hand and mathematical model of an index finger were presented. Moreover, immune mechanism was applied to the controller design and an improved approach through integration of GA and fuzzy inference was proposed to realize parameters' optimization. Finally, a simulation example was provided and the designed controller was proved ideal.

Bulk anda single-cell transcriptome profiling reveals the molecular characteristics of T cell-mediated tumor killing in pancreatic cancer.

Background: Despite the potential of immune checkpoint blockade (ICB) as a promising treatment for Pancreatic adenocarcinoma (PAAD), there is still a need to identify specific subgroups of PAAD patients who may benefit more from ICB. T cell-mediated tumor killing (TTK) is the primary concept behind ICB. We explored subtypes according to genes correlated with the sensitivity to TKK and unraveled their underlying associations for PAAD immunotherapies. Methods: Genes that control the responsiveness of T cell-induced tumor destruction (GSTTK) were examined in PAAD, focusing on their varying expression levels and association with survival results. Moreover, samples with PAAD were separated into two subsets using unsupervised clustering based on GSTTK. Variability was evident in the tumor immune microenvironment, genetic mutation, and response to immunotherapy among different groups. In the end, we developed TRGscore, an innovative scoring system, and investigated its clinical and predictive significance in determining sensitivity to immunotherapy. Results: Patients with PAAD were categorized into 2 clusters based on the expression of 52 GSTTKs, which showed varying levels and prognostic relevance, revealing unique TTK patterns. Survival outcome, immune cell infiltration, immunotherapy responses, and functional enrichment are also distinguished among the two clusters. Moreover, we found the CATSPER1 gene promotes the progression of PAAD through experiments. In addition, the TRGscore effectively predicted the responses to chemotherapeutics or immunotherapy in patients with PAAD and overall survival. Conclusions: TTK exerted a vital influence on the tumor immune environment in PAAD. A greater understanding of TIME characteristics was gained through the evaluation of the variations in TTK modes across different tumor types. It highlights variations in the performance of T cells in PAAD and provides direction for improved treatment approaches.

Astragaloside IV stimulates angiogenesis and increases nitric oxide accumulation via JAK2/STAT3 and ERK1/2 pathway.

Astragaloside IV (AS-IV), one of the major active constituents of Astragalus membranaceus in Traditional Chinese Medicine, has been widely used to treat ischemic diseases. However, the potential mechanism is this action is unclear. In this study, we tested the hypothesis that AS-IV might promote angiogenesis through multiple signaling pathways. Our data indicate that AS-IV treatment promotes umbilical vein endothelial cells (HUVEC) proliferation, migration, and tube formation. AS-IV treatment also activates JAK2/STAT3 and ERK1/2 signaling pathways, and up-regulates endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) production. AS-IV-induced angiogenesis in HUVECs is significantly blocked by specific kinase inhibitors. Our study indicated that AS-IV is a key regulator of NO and angiogenesis through the JAK2/STAT3 and ERK1/2 pathways, which provides a mechanistic basis for the potential use of this compound in the treatment of clinical ischemic diseases.

[Effect of clinical pathways based on integrative medicine for patients with chronic heart failure: a multi-center research].

OBJECTIVE: To assess a multi-center study effectiveness of clinical pathways based on integrative medicine (IM) for chronic heart failure (CHF) patients. METHODS: A combined method of historical control study and clinical study on concurrent control was used. After the standard management for clinical pathways was carried out in four hospitals at home, the effects on hospitalization days, medical expenses, clinical efficacy, patient satisfaction, and quality of life were assessed. RESULTS: Results of non-concurrent historical control study showed that: the hospital stay was significantly shorter in the pathways group than in the retrospective group (12.59 days vs 18.44 days), and the total cost of hospitalization was significantly reduced in the pathways group (yen 9 051.90 vs yen 11 978.40), showing statistical difference (P < 0.01). Moreover, the effect on the heart function was better in the pathways group than in the retrospective group (the markedly effective rate: 45.60% vs 21.90%; the total effective rate: 96.80% vs 86.10%), showing statistical difference (P < 0.01). Results of clinical study on concurrent control showed that the hospital stay was significantly shorter in the pathways group than in the control group (11.19 days vs 13.21 days), showing statistical difference (P < 0.05). The average total cost of hospitalization was significantly lower in the pathways group than in the control group (yen 8 656.80 vs yen 11 609.70), showing statistical difference (P < 0.01). As for clinical efficacy of Chinese medical syndrome, the total effective rate was higher in the pathways group than in the control group (97.10% vs 93.62%), showing statistical difference (P < 0.05). The markedly effective rate of heart function was better in the pathways group than in the control group, showing statistical difference (49.30% vs 38.30%, P < 0.05). The overall satisfaction was higher in the pathways group than in the conventional group (P < 0.01). There was no statistical difference in the mortality within 3 months after discharge from hospital, and the readmission rate due to heart failure between the two groups (P > 0.05). But there was statistical difference in the quality of life (P < 0.05). CONCLUSION: The pathway could shorten the hospitalization time, decrease the cost of hospitalization, improve the clinical efficacy, improve patients' quality of life and satisfaction, therefore, it could be spread nationwide.

Antibacterial activity evaluation of pleuromutilin derivatives with 4(3H)-quinazolinone scaffold against methicillin-resistant Staphylococcusaureus.

Growing antibiotic resistance is causing a health care crisis, leading to an urgent need for new antibiotics to tackle serious hospital and community infections. Pleuromutilin, a naturally occurring product with moderate antibacterial activity, has a unique structure that has attracted great efforts to modify its scaffold to obtain lead compounds. Herein, we report the synthesis of a series of novel pleuromutilin derivatives with a scaffold of 4(3H)-quinazolinone or its analogues at the C-14 side chain and investigated their in vitro activity against Staphylococcus aureus and Staphylococcus epidermidis as well as Gram-negative bacteria (Escherichia coli and Salmonella enterica subsp. enterica serovar pullorum). Structure-activity relationship (SAR) studies showed that the substituents on the benzene ring of 4(3H)-quinazolinone was not as important as the substituted position to improve antibacterial activity while the substituted groups on the N-3 position of 4(3H)-quinazolinone had strong impact on the efficacy. The replacement of the benzene moiety of 4(3H)-quinazolinone with other rings (pyridine, pyrrole, thiophene, or cyclopentyl) also showed high antibacterial efficacy, meaning the benzene ring was dispensable for exerting powerful antibacterial properties. In vitro pharmacokinetics investigations and cytotoxicity assays indicated that 2-mercapto-4(3H)-quinazolinone scaffold was superior to 2-(piperazin-1-yl)quinazolin-4(3H)-one. Among this series of pleuromutilin analogues, compound 23 with a structure of 2-mercapto-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one displayed the best in vitro antibacterial activity against MRSA (MIC = 0.063 µg/mL) and low cytotoxicity to RAW 264.7 cells (IC50＞100 µM) and was demonstrated to inhibit MRSA effectively in a mouse thigh infection model, outperforming the comparator, tiamulin.

Dioscin ameliorates doxorubicin-induced heart failure via inhibiting autophagy and apoptosis by controlling the PDK1-mediated Akt/mTOR signaling pathway.

Heart failure (HF) is a disease with high mortality and morbidity rate. Autophagy is critically implicated in HF progression. The current research was designed to investigate the function of Dioscin on oxidative stress, autophagy, and apoptosis in HF. In this study, doxorubicin (Dox) was employed to induce HF model and HL-1 cell damage model. Echocardiography implied that Dioscin could dramatically relieve heart function in vivo. Western blotting determined that Dioscin treatment reversed the promotive effect of autophagy caused by Dox through modulating levels of key autophagy-associated molecules, including Atg5 and Beclin1. Dioscin also impaired apoptosis by regulating apoptosis-related protein, including Bcl-2 and cleaved caspase-3 following Dox treatment in vivo and in vitro. Furthermore, the impacts of Dioscin were mediated by upregulation of PDK1-mediated Akt/mTOR signaling. The mTOR inhibitor (rapamycin) could counteract the therapeutic impact of Dioscin in vitro. Taken together, Dioscin could relieve cardiac function through blocking apoptosis and autophagy by activating the PDK1-elicited Akt/mTOR pathway.

Cytomegalovirus infection and coronary heart disease risk: a meta-analysis.

The chronic inflammatory process including cytomegalovirus (CMV) infection has been hypothesized to induce the progression of atherosclerosis in coronary heart disease (CHD). Numbers studies were conducted to analyze the association between CMV infection and risk of CHD, but no clear consensus had been reached. To assess this relationship more precisely, a meta-analysis was performed. The electronic databases PubMed, Embase, and CNKI were searched; data were extracted and analyzed independently by two investigators. Ultimately, 55 studies, involving 9,000 cases and 8,608 controls from six prospective studies (all with a nested case-control design) and 49 retrospective case-control studies were included. Overall, people exposed to CMV infection had an odds ratio (OR) of 1.67 (95% CI, 1.56-1.79) for CHD risk, relative to those not exposed. CMV infection was clearly identified as a risk factor for CHD in both prospective studies (OR, 1.31; 95% CI, 1.132-1.517) and retrospective studies (OR, 1.79; 95% CI, 1.659-1.939), and in both Asian group (OR, 2.69; 95% CI, 2.304-3.144) and non-Asian group (OR, 1.48; 95% CI, 1.371-1.600). Interestingly, in the subgroup analyses by detection methods of CMV, the increased risk (OR, 8.121) was greater among studies using polymerase chain reaction than the risk (OR, 1.561) among studies using enzyme-linked immunosorbent assay. In conclusion, this meta-analysis suggested that CMV infection is associated with an increased risk for CHD, especially among Asian populations.