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.

A Multiple Remotely Controlled Platform from Recyclable Polyurethane Composite Network with Shape-Memory Effect and Self-Healing Ability.

Stimuli-responsive materials can transform from temporary to permanent shapes by specific external triggers. However, the damage might inevitably occur to them when exposed to complex environments, causing a significant reduction in their lifetime and quality. In this study, recyclable remotely controlled shape-changing polyurethane composite with self-healing compacity is developed from polyethylene glycol, polytetrahydrofuran diol using isophorone diisocyanate as crosslinker. After the incorporation of magnetite nanoparticles (MNPs), remote heating could be generated by near-infrared irradiation and alternating magnetic fields. The results show that MNPs are uniformly distributed in the smart networks, resulting in tunable temperature changes of the polymer composite material under various direct/indirect triggering in bending experiments, presenting different shape recovery rates. Moreover, to enhance the self-healing capability, a disulfide bond is introduced into the polymer networks, and the results show that highly efficient and rapid healing could be achieved from tensile tests, scanning electron microscopy as well as optical microscopy. Additionally, the synergistic effect of transesterification and the dynamic exchange of disulfide bonds brin the networks reproducibility for recycling use. The obtained material is promising to be an alternative material for soft robots and smart sensors.

[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.

In-vivo 3D imaging of Zebrafish's intersegmental vessel development by a bi-directional light-sheet illumination microscope.

Precise quantification of vascular developments in Zebrafish requires continuous in-vivo 3D imaging. Here we employed a bi-directional light-sheet illumination microscope to characterize the development process of Zebrafish's intersegmental vessels. A Virtual Reality-based method was used to measure the lengths of intersegmental vessels (ISVs). The quantified growth rates of typical ISVs can be plotted, and unusual growth of some specific vessels was also observed.

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.

Frequency-spatial domain joint optimization for improving super-resolution images of nonlinear structured illumination microscopy.

Introducing nonlinear fluorophore excitation into structured illumination microscopy (SIM) can further extend its spatial resolution without theoretical limitation. However, it is a great challenge to recover the weak higher-order harmonic signal and reconstruct high-fidelity super-resolution (SR) images. Here, we proposed a joint optimization strategy in both the frequency and spatial domains to reconstruct high-quality nonlinear SIM (NL-SIM) images. We demonstrate that our method can reconstruct SR images with fewer artifacts and higher fidelity on the BioSR dataset with patterned-activation NL-SIM. This method could robustly overcome one of the long-lived obstacles on NL-SIM imaging, thereby promoting its wide application in biology.

[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.

The circular RNA hsa_circ_0007623 acts as a sponge of microRNA-297 and promotes cardiac repair.

Circular RNAs (circRNAs) are a kind of closed loop endogenous non-coding RNAs have attracted increasing interest in recent years. However, the mechanism of circRNAs in the pathogenesis of multiple cardiovascular diseases, particularly myocardial ischemia, is rarely reported. In the present study, we examined a circular RNA, hsa_circ_0007623, which is highly expressed in hypoxia-induced human umbilical vein endothelial cells (HUVECs) and can act as a sponge for miR-297, which is involved in cardiac repair after acute myocardial ischemia. In hypoxia-stimulated HUVECs, the inhibition of hsa_circ_0007623 expression was found to reduce cell proliferation, migration, and angiogenesis. Further in vivo experiments confirmed the cardioprotective effect of hsa_circ_0007623 expression in isoproterenol-induced acute ischemia mice. Bioinformatics analysis predicted hsa_circ_0007623, sponge miR-297 and miR-297 directly target VEGFA, which was validated by dual-luciferase assay. Subsequently, functional experiments revealed hsa_circ_0007623 silencing could up-regulate miR-297 and down-regulate VEGFA expression, and reduce cell proliferation, migration, and angiogenesis. We concluded that hsa_circ_0007623 can bind to miR-297, promote cardiac repair after acute myocardial ischemia, and protect cardiac function.

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.

Total flavone of Abelmoschl manihot L. medic exhibits protective effect against hind-limb ischemia in rat model.

Total flavones of Abelmoschus manihot L. Medic (TFA) is the major active component isolated from Chinese herb Abelmoschus manihot L. Medic. TFA has shown neuroprotective effect against cerebral ischemia injury in rats and rabbits. However, the effects of TFA on hind-limb ischemia and the underlying mechanisms remain unclear. Therefore, in the present study, we used a rat hind-limb ischemia model to investigate protective effect of TFA against limb ischemia injury. The rat model of hind-limb ischemia was established. Treatment groups received TFA at two different doses (160 and 40mg/kg) daily for 10 days. Sham operated control group and model group received saline. At the end the rats were sacrificed, hindlimb tissues were stained with Haematoxylin-Eosin and Masson's trichrome. RNA and protein were extracted from tissues for PCR and Western blot analysis. The results showed that TFA reduced lower limb ischemic injury, recovered tissue volume and diminished fibrosis and muscle degeneration. Mechanistically, we showed that TFA increased the expression of anti-apoptotic factor such as Bcl-2 and survivin, decreased the expression of pro-apoptotic factor such as Caspase 3, Bax and Bak and inhibited the activation of caspase 3 and 9. In summary, this study proves new evidence that TFA protects hind-limb against ischemia injury by inhibiting apoptosis and could be a promising therapeutic agent for acute lower extremity ischemia.

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.

Identification of Chemical Composition of Leaves and Flowers from Paeonia rockii by UHPLC-Q-Exactive Orbitrap HRMS.

The Paeonia genus, an important source of crude drugs, has been extensively used in traditional Chinese medicine (TCM) to treat cardiovascular and female-related diseases. Although many peony species have been investigated, the study of Paeonia rockii is still quite limited, especially its chemical composition. Here, an advanced ultra-high-performance liquid chromatography (UHPLC) analytical technique combined with Q-Exactive Orbitrap hybrid quadrupole-Orbitrap mass spectrometry utilizing high-resolution full MS and MS/MS scan modes was applied to screen and identify the chemical constituents of this species. As a result, a total of 46 compounds were characterized, including 11 monoterpene glycosides, five phenolic acids, six tannins and 24 flavonoids. Among them, 16 compounds were reported for the first time in Paeonia rockii.

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.

Promotion of Astragaloside IV for EA-hy926 Cell Proliferation and Angiogenic Activity via ERK1/2 Pathway.

The aim of this study was to determine the pro-angiogenic effects of Astragaloside IV (AS-IV) in vitro and reveal the potential mechanisms. A kind of human umbilical vein endothelial cells (HUVECs), named EA-hy926 cells, were treated with various dosages of AS-IV. We then utilized Cell Counting Kit-8 (CCK-8), real-time PCR and Western blot to detect EA-hy926 cells' proliferation and proangiogenic effect from AS-IV. Data showed that AS-IV promoted EA-hy926 cells proliferation, as assessed by CCK-8. The AS-IV was also associated with an increased tube formation and upregulation of vascular endothelial growth factor (VEGF) mRNA and protein in a dose-dependent manner. Interestingly, the influence of AS-IV on cell proliferation and angiogenisis could be abolished by inhibitor PD98059 through suppressed extracellular signal regulated protein kinases1/2 (ERK1/2) phosphorylation. These data demonstrated that the AS-IV activated the ERK1/2 pathway to control VEGF synthesis. Our findings conclude that the AS-IV promotes EA-hy926 cells proliferation and angiogenesis through ERK1/2 pathway, and it is also a regulator of VEGF.

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.